CARDIAC AND RESPIRATORY CARE
PERTINENT CONCEPTS AND PRACTICES FOR THE GENERAL SURGEON
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Introduction
Cardiac and respiratory complications are the two most frequent and most lethal
groups of complications that occur after general surgery operations. Using modern understandings of cardiac and pulmonary pathophysiology, surgeons can now prevent or
manage these events with frequent patient salvage and full recovery. This issue of Selected Readings in General Surgery (SRGS) reviews current information pertinent to the
successful management of cardiac and respiratory diseases and complications in general surgery patients.
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Perioperative cardiac complications
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Risk factors for postoperative cardiac complications
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Evidence of atherosclerotic cardiovascular disease is found at autopsy on nearly all
patients dying after the age of 40 years. Symptoms of atherosclerotic cardiovascular
disease have become increasingly common as the population of the United States ages
and cardiovascular disease is the leading cause of death among older adults in North
America. Increasingly, older patients with moderate-to-severe comorbid cardiovascular
diseases are presenting for surgical care. Current data estimate that 60%-80% of postoperative deaths after elective operation are traceable to cardiovascular complications
of surgical procedures. In the first section of the overview for this issue of SRGS, we review pertinent data on the topic of perioperative cardiac complications. Important issues relevant to risk recognition, risk modification, and prevention are discussed. Data
pertinent to the diagnosis and management of myocardial infarction, cardiac failure, arrhythmias, and cardiac arrest will be reviewed. Fundamental aspects of the diagnosis
and management of cardiac conduction system disorders and management of pacemakers and implantable defibrillators are included.
Effective prevention of perioperative cardiac complications is possible only if patients at risk can be identified. Identification of high-risk patients can lead to development and use of preventive strategies. These approaches obviously will be most useful
for patients who are scheduled to undergo elective operations. In this patient group,
there is time for a detailed history and physical examination, laboratory studies, electrocardiogram, and imaging. The articles reviewed in this section of the overview detail
the fundamental features of perioperative cardiac risk assessment and risk modification.
The first article reviewed is by Davenport and coauthors1 entitled, “Multivariable
predictors of postoperative cardiac adverse events after general and vascular surgery:
results from the patient safety in surgery study.” This article is supplied as a full-text
reprint with this issue of SRGS. The authors begin noting that cardiac complications oc2
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cur after 1%-5% of surgical procedures. Given an annual number of operations currently exceeding 30 million, this estimate would result in as many as 1.5 million adverse
cardiac events annually. The estimated mortality for adverse cardiac events exceeds
50%. Thus, as many as 750,000 deaths could be expected annually.
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The authors cite data that have identified age > 75years, diabetes mellitus, hypertension, and baseline electrocardiographic findings indicative of ischemia as risk factors
for perioperative adverse cardiac events. The current means of estimating the risk of
perioperative cardiac events are summarized in three available scoring systems focusing on factors pertinent to the operation (elective versus emergency; simple versus
complex), and on cardiac-specific risk factors such as a history of hypertension, symptomatic ischemic heart disease, diabetes, and cardiac failure. The authors stress that
popular risk scoring systems, introduced in the late 1980s, award one point for each of
several risk factors; clinical reviews of these systems have noted increased risk of adverse cardiac events with increasing risk scores. Nonetheless, there remains controversy over the ability of the available scoring systems to identify accurately patients for
whom the procedure should be delayed in order to conduct further evaluation. Furthermore, assigning a specific risk to an individual patient is difficult using existing
scoring systems.
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In an attempt to clarify and improve cardiac risk scoring for surgical patients, Davenport and coauthors used the Patient Safety in Surgery database that contains a standard dataset for patients from 128 Veterans Administration hospitals and from 14 academic medical centers. This database contains multiple demographic, preoperative,
perioperative, and outcomes variables obtained from medical record reviews conducted in a standard fashion by experienced nurse reviewers using standardized definitions.
Data on more than 180,000 patients were subjected to multivariate logistic regression
analysis. Adverse cardiac events were defined as cardiac arrest or acute myocardial infarction within 30 days of operation. Adverse cardiac events were recorded in 2362 patients and the mortality rate for these events was 60%. The authors tested a predictive
model on a sample of patients drawn from the database after logistic regression modelling of risk factors from the entire database.
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Prediction of adverse events was accurate using a model that included ASA score,
operation complexity (as reflected in procedure relative value work units), age, and
type of operation. Interestingly, none of the conventional cardiac specific risk factors
such as hypertension, prior history of myocardial infarction, or prior history of a cardiac surgical procedure was valuable as a predictor of perioperative adverse cardiac
events. When the subgroup of patients from non-VA medical facilities was considered,
the authors found that these patients, as a group, were younger and contained more
women than the VA cohort. The frequency of adverse cardiac events was less in this
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subgroup but cardiac-specific risk factors failed to predict outcomes in this subgroup
also. The authors provide a table of risk point assignments for the factors they identified as most influential in determining outcomes. A graph in their report indicates that
significant cardiac risk (>1% risk of adverse event) is recognized beginning with a total
risk score of 12-15 points.
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Davenport and colleagues emphasize the diminished predictive power of conventional cardiac specific risk factors and report that these factors become less predictive
when considered together with more global risk indicators such as ASA score. They also
note that, in the current era, patients with known conventional risk factors are often
treated preoperatively with medications and, occasionally, interventions that serve to
reduce risk. This would also work to reduce the influence of cardiac-specific risk factors.
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They further emphasize the lethality of adverse cardiac events. The mortality risk
for patients who sustain these events is large, and recognition of this serves as a stimulus to improve perioperative management. Use of measures such as avoiding emergency operation, preoperative stabilization of cardiac failure and rhythm disturbances, optimization of intraoperative monitoring, use of regional anesthesia, and use of drugs to
control heart rate and stabilize atherosclerotic plaque, are potentially useful measures.
These are discussed in more detail in the following sections of the overview. If emergency operation can be avoided, preoperative approaches to optimize coagulation, renal
function, and nutrition might assist in minimizing the risk of cardiac adverse events.
The authors conclude that their approach to outcomes prediction is well suited for inclusion in efforts to identify high and low performing hospitals as is done in the National Surgical Quality Improvement Program (NSQIP) sponsored by the American College
of Surgeons. Furthermore, their risk scoring system is designed for easy incorporation
into electronic medical records. The risk prediction model could be made available at
the bedside on a hand-held computer.
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Risk assessment
Additional detailed data relevant to cardiac risk assessment is in an article by Poldermans and coauthors2 in the Journal of the American College of Cardiology, 2008.
These authors report European experience with adverse cardiac events in the perioperative period. An annual rate of 400,000 perioperative cardiac events has been recorded in the European Union. One hundred thirty-three thousand deaths occurred because
of these complications. They agree with Davenport and colleagues that the type of operation is a major driver of risk. They cite data showing that patients older than 40
years of age have a 2.5% risk of adverse cardiac events after operation. The risk rises to
more than 6% in patients undergoing vascular surgical procedures. They stress that the
incidence of perioperative cardiac events varies because of the means used to make the
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diagnosis. When the diagnosis was made with Troponin T or I assays, the frequency of
events rose to 25% in high-risk patients. They further agree that advancing age is a
driver of cardiac risk.
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Postoperative myocardial infarction is the most important adverse cardiac event.
The pathophysiology of this complication is complex. Patients whose preoperative images show discrete areas of impaired myocardial perfusion are thought to be at increased risk for perioperative myocardial infarction. It is now clear, however, that "culprit" coronary lesions are not the predominant cause of perioperative myocardial infarction. Plaque rupture and thrombosis in coronary arteries at sites of noncritical coronary artery stenosis are frequent causes of perioperative myocardial infarction. This
understanding helps to explain the lack of benefit of preoperative myocardial revascularization of culprit lesions. Emphasis has shifted away from identification of culprit
coronary lesions and toward global pharmacologic measures for reducing cardiac risk.
The topic of preoperative interventions is discussed in a later section of the overview.
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Poldermans and associates note that features of the metabolic response to operation contribute to imbalances in myocardial oxygen demand and availability. The increased secretion of catecholamines results in tachycardia, which can create unfavorable myocardial oxygen demand/supply situations. This topic is addressed in more detail
in a report by Sander and coauthors3 in Critical Care Medicine, 2005. These authors
identified 69 patients deemed at high risk for adverse cardiac events. In a subgroup of
39 patients with sustained (>12 hours) tachycardia (heart rate > 95 bpm), the risk of a
major adverse cardiac event was 49%. In the 30 high-risk patients who did not have
tachycardia, the risk of an adverse cardiac event was 13%. The majority of the tachycardic rhythms were sinus tachycardia, although there were 16 patients with newonset atrial fibrillation.
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The authors cite data that document an association of tachycardia with prolonged
ST-segment depression, a finding known to predict perioperative myocardial infarction.
Poldermans and coauthors2 agree, noting that prolonged ST-segment depression is a
known precursor of perioperative myocardial infarction in patients undergoing vascular surgical procedures. In Sander’s report, tachycardia occurred during the 24-hour
period in which the myocardial infarction occurred in 90% of patients. Sander and associates conclude with the observation that the subgroup of their patients where no
tachycardia occurred were more likely to be receiving β-blocking drugs and epidural
analgesia. They suggest that these factors might be protective against tachycardia and
the adverse cardiac events that accompany this change in cardiac rhythm.
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Poldermans and colleagues point out that the inflammatory response that sometimes follows major surgery procedures creates an environment that contributes to hy5
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percoagulability because of activation of the coagulation mechanism and reduced fibrinolytic activity. As noted in the discussion of atherosclerotic vascular disease in a previous three-issue series of SRGS (Volume 35, Numbers 1-3), inflammatory cytokines are
potent forces that produce plaque instability and rupture. Inflammation might also contribute to the onset of postoperative tachyarrhythmias. This topic is discussed in an article by Anselmi and coauthors4 in Annals of Thoracic Surgery, 2009, focusing on causes
of new-onset atrial fibrillation after cardiac operations.
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These authors note that cardiopulmonary bypass is a potent stimulus of the inflammatory response. Inflammation, as evidenced by elevated levels of C-reactive protein, is
associated with increased risk of atrial fibrillation in surgery and nonsurgery patients.
Lower C-reactive protein levels have also been associated with improved responses to
cardioversion for new-onset atrial fibrillation. They cite one study where reduction of
risk for recurrent atrial fibrillation occurred with specific anti-inflammatory therapy
with the antioxidant Vitamin C. Anselmi and associates point out that reductions of
perioperative inflammation observed with off-pump coronary artery bypass, use of
perioperative corticosteroids, and use of preoperative statin drugs are all associated
with lowered risk of atrial fibrillation. These observations support an association between perioperative inflammation and perioperative atrial fibrillation.
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Because new-onset atrial fibrillation is associated with perioperative cardiac events,
as noted by Sander and associates3, efforts to control the inflammatory response seem
warranted. Available pharmacologic therapies that reduce inflammation such as βblockers and statins are discussed in a subsequent section of the overview.
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Poldermans and coauthors2 go on to note that existing cardiac risk scoring systems
are imprecise. Improved risk assessment would result with the inclusion of global risk
factors such as age and operation characteristics. This assertion is in agreement with
the findings of Davenport and coauthors1, noted above. The difficulty encountered by
clinicians attempting to quantify cardiac risk preoperatively using the available scoring
systems has stimulated researchers to investigate alternative means of assessing risk
for perioperative cardiac events. Two of these approaches are discussed here.
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Normal cardiac function depends, in large measure, on an appropriate balance between the influences of the sympathetic and parasympathetic nervous systems. This
balance is assessable clinically by use of special ambulatory electrocardiographic monitoring with assessment of heart rate variability. Heart rate variability is a sign of healthy
cardiac function, while loss of variability signals an imbalance in the relative influences
of the sympathetic and parasympathetic nervous systems on the heart. Loss of heart
rate variability has been associated with an increased risk of sudden cardiac death, an
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increased risk of death in multiple trauma patients, and adrenal insufficiency in the critically ill surgical patient.
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The fundamental physiology of heart rate variability and the potential application of
this assessment to the preoperative evaluation are discussed in an article by Laitio and
coauthors5 in Anesthesia and Analgesia in 2007. These authors begin by noting that
heart rate variability is an indicator of the integrated function of the parasympathetic
nervous system (especially vagus nerve activity), the sympathetic nervous system, and
the baroreceptor system. They describe the various measures used in analyses of heart
rate variability, including time domain analyses that express variability in terms of instantaneous heart rate and intervals between normal QRS complexes. Frequency domain analyses commonly express variability in terms of “power-law” spectral analyses
of RR-interval variability.
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These methods of assessing heart rate variability are time-tested and accepted but
they do not adequately describe the complex, fractal system that is heart rate variability. Because of this, dynamic assessments of heart rate variability have been developed
to analyze correlations of multiple time series of RR intervals. These analyses can be
graphed and patterns typical of normal patients, patients with heart failure, and patients prone to ischemic events can be displayed. Similar graphic displays are obtained
using Poincare plots. These show typical compact “comet shaped” patterns in normal
patients and patients analyzed after myocardial revascularization. These graphs show
diurnal variation. Heart rate variability changes during ischemic episodes are characterized by irregular widely spread graphic patterns with loss of diurnal variation.
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The actions of anesthetic drugs to down-regulate vagal activity result in changes in
heart rate variability. Changes in heart rate variability accurately predict hypotensive
episodes after induction of spinal anesthesia especially when the block reaches the thoracic spinal levels. Loss of heart rate variability in elderly patients and in diabetic patients with dysfunction of the autonomic nervous system accurately predicts episodes
of hemodynamic instability. The authors cite several studies that have related loss of
heart rate variability to short- and long-term operative mortality from myocardial ischemia and prolonged ICU stays.
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The presence of heart rate variability abnormalities improves the predictive capability of the available cardiac risk scales, especially for predicting long-term cardiac
mortality. In the cited studies, the combination of abnormal heart rate variability and
high-risk scores accurately predicted perioperative cardiac morbidity for patients undergoing cardiac and noncardiac procedures. Laitio and colleagues speculate that loss
of heart rate variability indicates unopposed sympathetic influence on the heart that
might increase myocardial oxygen demand by augmenting ventricular contractility.
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This situation favors the development of ischemia in susceptible patients. The need for
24-hour electrocardiographic monitoring and manual assessment of the tracings are
significant disincentives that have reduced the utility of heart rate variability measurements for preoperative patients. With improved, computer-assisted methodologies,
these disadvantages might be overcome.
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Additional data on the use of heart rate variability assessments as a means of predicting perioperative cardiac morbidity risk are found in an article by Hanss and coauthors6 in Anaesthesia, 2008. These authors report an initial analysis of 50 patients who
underwent heart rate variability analysis preoperatively and, during the postoperative
period, had 24-hour electrocardiographic monitoring and sequential measurements of
creatine kinase MB band in blood samples. Cardiac events were detected by a combination of electrocardiographic changes and elevations of the CPK-MB level. Seventeen of
the initial patients had cardiac events and the authors established that a heart rate variability power value <400 ms2 Hz-1 was a useful cut-off value for prediction of cardiac
events. This cut-off value was then assessed prospectively in 50 additional patients.
Cardiac events and hospital length of stay were both increased in the 26 patients with
low power scores in the prospective group. The authors conclude that heart rate variability power analysis is a useful predictor of postoperative cardiac events and the additional information might improve the predictive power of cardiac risk scoring systems.
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Additional predictive power can be obtained using serum markers that reflect vulnerability of the myocardium to ischemia. Two of these, B-type natriuretic peptide
(BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), are discussed. The
first of these is by Cuthbertson and coauthors7 in the British Journal of Anaesthesia,
2007, who analyzed outcomes data on 204 patients undergoing major noncardiac surgery procedures. Preoperative BNP levels were obtained in each patient. Perioperative
cardiac events were defined as an elevation of the troponin level or death within three
days of operation. The authors found that a preoperative elevation of BNP >40 pg/mL
was predictive of perioperative cardiac events. They performed rigorous multivariate
statistical analysis and found that the preoperative BNP level was more accurate for
risk prediction than findings on history, physical examination, or electrocardiogram.
BNP was more predictive than the revised cardiac risk score. Nonetheless, five patients
with significant postoperative cardiac events were not identified by the preoperative
BNP elevation. This observation suggests that BNP cannot be used alone to establish
risk for perioperative adverse cardiac events.
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An article analyzing the potential usefulness of NT-proBNP levels assessed preoperatively and with a single postoperative sample by Mahla and coauthors8 appeared in
Anesthesiology, 2007. These authors analyzed results in 218 patients who underwent
major vascular reconstructive procedures. Patients were followed for 30 months post8
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operatively. Twenty percent sustained a significant cardiac event during the followup
interval. The authors found that a preoperative value for NT-proBNP equal to 280
pg/mL coupled with a postoperative increase to 557 pg/mL accurately predicted shortand long-term cardiac morbidity. The authors state that NT-proBNP is released from
cardiac myocytes in response to ischemia and stretch and, therefore, this hormone
might be a good candidate for prediction of perioperative myocardial ischemia. The accuracy of the preoperative and postoperative levels combined was good, with an area
under the receiver-operating-characteristic curve of 0.8 that is as good as or better than
all available risk-scoring systems. The authors conclude that this test might offer improved prediction of cardiac events in high-risk patients undergoing major vascular operations.
Preoperative evaluation for coronary artery disease and preoperative interventions
Once a high-risk patient is identified, the next decision concerns the need for additional preoperative cardiac testing. Exercise testing, dobutamine stress echocardiography, and myocardial scintigraphy with vasodilator stress are tests commonly contemplated. Recommendations by the American Heart Association state that testing is
indicated in patients who have symptoms suggesting unstable cardiac syndromes (decompensated cardiac failure or unstable angina), patients who have poor functional capacity where a high-risk operation is contemplated (major vascular reconstruction),
and patients with known valvular heart disease. Poldermans and colleagues stress the
lack of a positive contribution of preoperative cardiac testing in cardiac stable patients,
especially those who are already using β-blocking drugs and statins with good control
of heart rate. They further emphasize that coronary artery bypass in cardiac stable patients has not resulted in improved surgical outcomes and the intervention delays the
planned noncardiac procedure. Percutaneous coronary interventions similarly delay
the planned procedure because the risk of stent thrombosis is substantial in the first
weeks following stent placement when multiple drug antiplatelet therapy is used. With
drug-eluting stents, this interval might be as long as one year.
Additional data on the use of extensive preoperative cardiac testing and preoperative cardiac interventions to prevent perioperative adverse cardiac events are reported
by Jaroszewski and coauthors9 in the Journal of Thoracic and Cardiovascular Surgery,
2008, who performed a retrospective review of 294 patients who underwent thoracotomy for a noncardiac operation in a single institution. One hundred eighty-four patients
underwent extensive preoperative assessment including, in addition to history and
physical examination with 12-lead electrocardiogram, stress testing, stress echocardiography, and/or myocardial scintigraphy. Based on preoperative test findings, 40 patients were selected to undergo coronary angiography and four of these had preoperative coronary revascularization by either operation or stenting. There was no difference
in the frequency of perioperative myocardial infarction in patients who had testing and
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intervention compared with those who did not have testing. In fact, of the four patients
who underwent revascularization, two had perioperative myocardial infarction. One of
these was from perioperative coronary stent thrombosis. These authors concluded that
there was no benefit to testing and intervention in cardiac stable patients.
Medications for reducing cardiac risk
Poldermans and coauthors2 stress the importance of general medical approaches to
cardiac risk modification in patients undergoing major elective operations. These approaches have generally consisted of careful risk stratification, and use of pharmacologic approaches designed to alter, favorably, myocardial oxygen consumption/oxygen
demand relationships as well as stabilize plaque through control of perioperative inflammatory responses. The authors note that the high catecholamine release states created by the stress of operation alter both myocardial energetics and inflammation. Initial approaches to balancing myocardial energetics included the use of β-blocking
drugs. Initially, drugs used were combined β-1 and β-2 agents, such as propranolol.
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As additional human trial data have become available, important lessons have been
learned. Poldermans and associates describe these progressive steps. For example, they
stress the observation that trials of beta blockade have generally shown reductions in
the frequency of perioperative cardiac events but some trials have disclosed risks of
hypotension and stroke, especially in older patients not judged at high risk for cardiac
events. Two prospective, randomized trials cited by these authors (references 40 and
45 in their bibliography) showed effective reduction in cardiac events but at the cost of
a significantly increased risk of stroke and overall mortality. These trials disclosed the
potential danger of pharmacologically lowering blood pressure to 100 mmHg or lower
in elderly patients. The type of beta-blocking drug used, timing of drug therapy, and
dosing are also important features of approaches that achieve maximum success. Drugs
that are β-1 selective agents (such as bisoprolol) are more effective than drugs that target both the β-1 and β-2 receptors. Blockade of both receptor types results in a state of
predominant α receptor stimulation that results in hypertension and increased myocardial stress.
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Prospective, randomized trials have shown no impact of beta blockade on the risk of
perioperative cardiac events if the drug is started on the day before or the day of the
operation. This finding implies that maximum stabilization of cardiac energetics and
plaque requires time. In fact, the DECREASE trial (reference 37 in Poldermans’ bibliography) started treatment, on average, 37 days before operation and with incremental
adjustment of the dose upward based on blood pressure and heart rate. This study disclosed a 10-fold reduction in the risk of perioperative cardiac events and death.
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All of the data cited by Poldermans and associates support the use of β-1 selective
drugs with a long half-life. The drug should be started at least one month before operation and adjusted to obtain optimum heart rate (current American Heart Association
recommendations are resting heart rates in the 60-66 bpm range) without episodes of
hypotension. Patients at low risk for cardiac events should not take beta-blocking drugs
unless they are using these drugs chronically. Moderate risk patients undergoing major
vascular operations are acceptable candidates for beta-blocking therapy and high-risk
patients undergoing any type of major operation are excellent candidates for this approach. Drugs should not be withdrawn in the perioperative period because benefit has
been shown for protection against both short-term and long-term cardiac morbidity.
Downsides of beta-blocking drug usage include a range of contraindications (asthma,
for example) and consistent observations that up to 25% of patients have episodes of
tachycardia in the perioperative period despite seemingly adequate beta blockade.
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Further analysis of the use of beta blockade for prevention of perioperative cardiac
events comes from a review by Chopra and coauthors10 entitled “Perioperative betablockers for major noncardiac surgery: Primum non nocere.” This article appeared in
The American Journal of Medicine in 2009 and a full-text reprint of the article is provided with this issue of SRGS. These authors review the actions of beta-blocking drugs.
They note that there are three subtypes of beta-receptors and these receptors are presented on the cell surface of many types of human tissue. Beta one receptors are found
in the myocardium, the kidney, and the eye. Beta two receptors are found in adipose tissue, liver, pancreas, smooth muscle, and skeletal muscle. Beta three receptors are primarily involved with metabolic regulation and lipolytic pathways. The receptors are Gcoupled proteins that activate intracellular adenyl cyclase and produce intracellular effects via adenosine monophosphate production and opening of excitatory channels.
Chopra and associates confirm the observations of Poldermans and coauthors2 and
suggest that beta blockade use be targeted toward patients at high risk for perioperative cardiac events. Beta-blocking drug therapy should be started at least one month before operation, and tight heart rate control should be sought with maximum protection
against hypotensive events. Drug therapy should be continued during the postoperative
period, and that use of statins and/or aspirin should be considered.
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Supporting data on the value of tight heart rate control is in a meta-analysis authored by Beattie and coauthors11 in Anesthesia and Analgesia, 2008. These authors
provide an analysis that specifically focuses on reasons for inadequate heart rate control in trials of beta-blocking drugs. They emphasize that early implementation of beta
blockade with progressive upward adjustment of dose to obtain consistent resting
heart rates in the 60-65 bpm range is associated with maximum reductions of risk of
perioperative cardiac events. Several recent trials have shown that fixed dose ap11
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proaches do not produce maximum protection against perioperative cardiac events.
They stress that the available trial data strongly indicate that variation in achieving optimum heart rate control accounts for 60% of the variability in trial results. They also
document that the type of drug used and the concomitant use of calcium channel blockers might alter the heart rate response.
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Based on their analysis they recommend that beta-blocking drugs other than
metoprolol be chosen, especially in patients concomitantly using calcium channel
blockers. Most of the available trials disclose failure to achieve heart rate goals in 20%35% of patients. Suboptimum heart rate control might be the result, according to Beattie and colleagues, of the presence of the AA variant of the beta-receptor resistant to the
beta-blocking drugs. In the setting where optimum heart rate is not achieved, combination therapy with calcium channel blockers might be necessary.
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Beattie and colleagues point out that available data does not adequately address the
risk of exacerbation of congestive heart failure from tight heart rate control with betablockers. Nor does the data adequately evaluate the use of other approaches to stabilization of myocardial energetics such as the use of regional anesthesia/analgesia and α2 receptor agonists, which have both been shown to reduce the frequency of perioperative cardiac events. The authors recommend therapy to obtain optimum heart rate control but caution that the best approach to achieve this goal might not be available yet.
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An alternative approach to achieving optimum balance between control of heart
rate and maintenance of cardiac output is described in an article by Suttner and coauthors12 in the British Journal of Anesthesia, 2009. These authors note that concerns
about the effect of beta-blocking drugs on blood pressure and cardiac output have led to
reluctance on the part of some clinicians to use beta blockade for high-risk patients, especially those who might need urgent or emergent intervention. In the current study, an
analysis is presented of results in 75 high-risk (as defined by three or more risk factors)
vascular surgery patients randomized to receive continuous perioperative beta blockade with intravenous esmolol alone, esmolol plus enoximone (a phosphodiesterase type
III inhibitor), and standard therapy.
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Perioperative cardiac events were documented by elevations of troponin or BNP.
The authors explain that phosphodiesterase inhibitors such as enoximone and milrinone have the potential to maintain cardiac contractile function when catecholamine
pathways are pharmacologically blocked. In this study, they noted no abnormalities of
troponin in either group receiving esmolol. BNP was lowest in the esmolol + enoximone
group and this group had the best maintenance of cardiac index. They suggest that
enoximone support of cardiac index occurred because of its action that promotes influx
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of calcium into myocytes, thereby favoring increased contractility. In vascular smooth
muscle, enoximone promotes calcium efflux, favoring vasodilation.
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These authors rightly caution that dosing of esmolol and enoximone should be managed carefully because higher doses might predispose to new-onset arrhythmias. While
these salutary effects were obtained in high-risk vascular surgery patients, the numbers
of patients are small. Furthermore, even though these patients were said to be at high
risk for perioperative cardiac events, fewer than 20% of each group received preoperative beta-blocker and/or statin therapy. The results of this study suggest, but do not
prove, that an approach such as described might have protective effects in high-risk patients who are not using beta-blocking drugs and who require urgent or emergent operation.
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Additional plaque stability effects accrue to patients from the use of drugs such as
statins and aspirin. Several trials have shown protection against perioperative cardiac
events, and both short- and long-term mortality with the use of statins. Sustained release preparations are preferred because intravenous statin preparations are not available. As with beta-blocking drugs, therapy should not be withdrawn postoperatively,
and patients who are chronically using statins should have these continued in the postoperative period. Low-dose aspirin has also been shown to be protective against both
short- and long-term cardiac events and death.
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Because of data suggesting benefit in terms of reduction of perioperative cardiac
events for high-risk patients from statins and from beta-blocking drugs, it is useful to
determine whether using the drugs in combination would be helpful. This issue is addressed in a study by Dunkelgrun and coauthors13 in Annals of Surgery, 2009. This article concerns a randomized prospective trial of beta blockade using bisoprolol compared
with the use of a statin drug (fluvastatin) alone, a combination of the two drugs, or neither drug. The patients were deemed intermediate risk (cardiac event risk of up to 6%).
The authors noted that cardiac event rates were significantly reduced in patients receiving beta blockade with or without the statin drug. A lesser reduction (nonsignificant) was seen with the statin drug alone. Although this study does not support the addition of statin drugs to beta blockade as a means of gaining additional control of cardiac event risk, the study is limited because of the small number of enrolled patients.
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From the perspective of the editor, there is convincing evidence to support careful
preoperative cardiac risk assessment. Furthermore, it is expected that an increasing
number of patients will present for operation already taking beta-blocking drugs,
statins, or both. In this case, drug therapy with both drugs should be continued during
and after the perioperative period with dose and type of drug adjusted to make certain
that full effects of both drugs are maintained. For intermediate-risk patients undergoing
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high-risk operations (abdominal or thoracic vascular procedures) and for high-risk patients, beta-blocking drug therapy, at least, should be implemented and dosage adjusted
progressively during the preoperative interval to obtain a resting heart rate in the 5565 bpm range. Therapy should continue into the postoperative recovery period. Other
adjuncts, such as regional anesthesia/analgesia, aspirin therapy, and statin therapy
might be useful.
Perioperative myocardial infarction
In the foregoing discussion, emphasis was placed on the vulnerability of coronary
artery plaque and the hazard of plaque rupture with thrombosis of the coronary artery
as the proximate cause of perioperative myocardial infarction. The significant, and increasing, prevalence of coronary artery disease in surgery patients is a reminder to surgeons that this problem is a continuing challenge. Increased resource consumption
from postoperative myocardial infarction is significant. In a 2006 report by Mackey and
coauthors,14 results from a prospective analysis of 236 patients deemed at high risk
showed significant incremental increases in both hospital and ICU lengths of stay when
vascular surgery patients developed a perioperative myocardial infarction. Perioperative myocardial infarction was a marker for long-term use of healthcare resources as
well.
Nearly one-quarter of the study patients discharged alive returned to the emergency
department for care during the year after discharge. Frequently, postoperative myocardial infarction occurs without chest pain. Nonspecific signs such as hypotension, dyspnea, arrhythmia, onset of new cardiac murmur, and alterations in the level of consciousness might be the only clinical symptoms. Electrocardiographic diagnosis and laboratory diagnosis using serum markers such as troponin might yield nonspecific results. The typical electrocardiographic findings of spontaneous myocardial infarction
include the appearance of Q waves, ST-segment elevation, and T-wave inversion. In contrast, postoperative myocardial infarction is associated with intervals, occasionally prolonged, of ST-segment depression indicating subendocardial ischemia. Increasingly,
echocardiographic cardiac imaging is used to obtain diagnostic information. Features of
the pathophysiology, diagnosis, and management of perioperative myocardial infarction will be discussed.
Pathophysiology of myocardial infarction
The first article discussed is by Burke and Virmani15 entitled “Pathophysiology of
myocardial infarction.” The review appeared in Medical Clinics of North America in
2007. The authors begin by noting that 80% of spontaneous myocardial infarctions are
caused by thrombosis of coronary arteries critically narrowed by atherosclerotic
plaque. Unusual causes of myocardial infarction are coronary embolization, coronary
spasm, and thromboses of nondiseased coronary arteries. Concentric subendocardial
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necrosis that might result from prolonged global ischemia from cardiac arrest can also
lead to coronary artery thrombosis. Myocardial ischemia results in acute pallor of the
myocardium, visible grossly within 12 hours of the onset of ischemia. Tetrazolium salt
staining of the myocardium can detect myocardial necrosis within 2-3 hours of the onset of ischemia. After 5-7 days, the infarcted area is soft with a hyperemic border. If
reperfusion occurs, the infarcted area might be reddened from trapped red blood cells.
Healing of a myocardial infarction takes from 4 weeks to 3 months and the lesion
evolves into a white scar, which might be the source of rhythm disturbances. Histologic
findings begin with the development of tissue eosinophilia followed by typical inflammatory changes, followed by fibrosis and scarring. Infarctions that involve more than
50% of the myocardial wall thickness are termed transmural and these produce Q-wave
changes in the electrocardiogram.
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In humans, reperfusion of ischemic myocardium within 4-6 hours of the onset of ischemia results in myocardial salvage. In this circumstance, the ischemic area remains
subendocardial and transmural extension does not occur.
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Myocardial energy metabolism depends upon the oxidation of free fatty acids to
produce ATP. Ischemia causes an immediate shift to anaerobic glycolysis. Exhaustion of
ATP supply leads to inhibition of Na/K ATPase with breakdown of cell membrane defenses and influx of sodium and chloride into the myocardial cell. Increases in cytosolic
calcium and cellular acidosis lead to myocyte contractile dysfunction. Cell death can result from necrosis, oncosis, apoptosis, or autophagy. Because apoptosis is an energy
consuming function, this occurs in perfused myocardium surrounding the necrotic area.
Autophagic cell death also requires energy and occurs in a manner that is independent
of the caspase-mediated pathway leading to apoptosis.
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Infarct size is determined by the extent and efficiency of coronary collateral circulation. Well-developed coronary collaterals are present in approximately 40% of adult
men and these individuals are resistant to the development of transmural infarctions.
Rather, coronary atherosclerosis in these patients produces anginal pain. In patients
with well-developed collateral circulation, another means of myocardial protection is
ischemic preconditioning. Ischemic preconditioning is the term applied to the phenomenon of preservation of myocyte energy-producing capability after an ischemic event
preceded by a short interval (10 minutes) of ischemia followed by reperfusion. Potassium-ATP channels play a central role in ischemic preconditioning. Blockage of these
channels prevents the protective effect of ischemic preconditioning. Interestingly, cardiac myocyte protection can be induced by ischemic events in distant tissue sites. This
phenomenon is known as remote ischemic preconditioning.
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A review of the potential for remote ischemic preconditioning to produce cardiac
myocyte protection comes from an article by Walsh and coauthors16 in the Journal of
Vascular Surgery, 2009. These authors report that myocyte protection has been produced after the production of ischemia to kidney, intestine, and skeletal muscle. Preoperative tourniquet ischemia of an upper extremity was associated with reduced risk
for postoperative cardiac events in patients undergoing coronary artery bypass grafting. These authors report results of ischemic preconditioning in randomized analysis
involving 82 patients undergoing open abdominal aortic aneurysm repair. Ten minutes
of ischemia to each leg was produced by clamping the iliac arteries individually. Thirteen of the 42 control patients developed clinically significant perioperative myocardial
ischemia. Only two of the 40 patients who had ischemic preconditioning developed myocardial ischemic events. Because this study was conducted in patients who had undergone maximum preoperative preparation with beta-blocking drugs, the results suggest
there might be incremental protection because of ischemic preconditioning; this technique should be further evaluated.
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Burke and Virmani15 assert that plaque instability universally preceded coronary
thrombosis. Seventy-five percent of coronary thromboses are the result of plaque rupture and the remaining 25% result from plaque erosion. The left anterior descending
coronary artery is the most frequent site of thrombosis, followed by the right coronary
artery and the left circumflex coronary artery. Arrhythmias and contractile dysfunction
in myocardium distal to a thrombosis might be aggravated by post-thrombosis microembolization. Complications of myocardial infarction include cardiac rupture, ventricular aneurysm, mural thrombus with embolization, mitral valve insufficiency from papillary muscle rupture, and pericardial effusion.
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Additional information on complications of myocardial infarction is in a review by
Wilansky and coauthors17 in Critical Care Medicine in 2007. These authors provide short
descriptions of clinical characteristics of the most important complications of myocardial infarction. Left ventricular free wall rupture, a frequently lethal complication of
myocardial infarction, traditionally has afflicted up to 6% of patients sustaining myocardial infarction. With the onset of rapid reperfusion protocols and angioplasty, the
frequency of this complication has dropped to 1%. Nonetheless, up to 17% of the deaths
from myocardial infarction result from ventricular free wall rupture. This complication
occurs within the first week after infarction with nearly half occurring during the first
24 hours. Older age, male gender, first infarction, single vessel disease, lack of ventricular hypertrophy, transmural infarction and anterior location of the infarction are all risk
factors for left ventricular free wall rupture. This condition can result in acute
hemopericardium and pericardial tamponade.
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Approximately one-third of patients with free wall rupture present with a more
subacute clinical picture characterized by persistent chest pain, right heart failure, and
hemodynamic deterioration. Electrocardiogram findings are nonspecific. Echocardiography might show pericardial effusion. As noted in the article by Burke and Vimani,15
approximately 25% of myocardial infarction patients will have nonspecific pericardial
effusion, and this will make diagnosis of cardiac rupture difficult. Doppler imaging or
contrast echocardiography might be needed to show pericardial blood clot or the rupture site. Surgical repair of the rupture will be required. Some patients might be amenable to stabilization with fluids, pressors, and/or intraaortic balloon pump.
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A variant of cardiac rupture is ventricular septal rupture. Older age, female gender,
hypertension, absence of a smoking history, and anterior infarction location are risk
factors for septal rupture. Clinically, this complication presents with hemodynamic collapse in the presence of a new systolic murmur. Diagnosis is established with echocardiography. Surgical revascularization and septal repair are therapies of choice.
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Left ventricular outflow tract obstruction from severe systolic anterior motion of
the mitral valve is an unusual complication of myocardial infarction. The clinical
presentation is one of a new systolic murmur and refractory hypotension in the setting
of an apical infarction. Echocardiography can confirm the diagnosis. Therapy includes
volume expansion, beta-blocking drugs to reduce hyperdynamic contraction of the
heart, and alpha agonists to support blood pressure.
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Mitral regurgitation might complicate myocardial infarction because of ischemia of
the valve or from papillary muscle rupture. Ischemic mitral regurgitation might be clinically silent and evidenced only by the presence of a cardiac murmur. Transesophageal
echocardiography is the mainstay of diagnosis. Management varies according to the
clinical status of the patient and the hemodynamic effects of the valvular dysfunction.
Papillary muscle rupture is a critical care emergency with acute pulmonary edema and
cardiogenic shock commonly present. A loud systolic murmur is present. Immediate
management includes support of cardiac function with afterload reduction and the use
of an intraaortic balloon pump. Transesophageal echocardiography provides accurate
delineation of the valvular anatomy and the extent of dysfunction. Surgical management
of the mitral regurgitation and critical coronary stenoses is associated with significant
operative mortality (25%-40%), but survivors have good quality of life in long-term followup.
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Diagnosis and management of postoperative myocardial infarction
Traditionally, the diagnosis of myocardial infarction is made based on the presence
of typical chest pain, electrocardiographic evidence of ischemia (ST-segment elevation,
presence of Q waves), and elevation of biomarkers such as troponin. As noted previous17
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ly, perioperative myocardial infarction might be clinically silent. Chest pain might be
absent because patients are receiving analgesics, are sedated for mechanical ventilation, or are emerging from general anesthesia. Troponin levels might be elevated in
surgery patients in the absence of myocardial infarction, but persistent elevations of
troponin > 3, especially combined with ST segment depression intervals of > 60 min on
electrocardiographic monitoring, predict an increased risk of myocardial infarction and
mortality.
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An article evaluating diagnostic accuracy of the electrocardiogram in critically ill patients by Lim and coauthors appeared 18 in Critical Care Medicine, 2006. These authors
determined intra- and inter-rater reliability for electrocardiogram interpretation in patients at high risk for myocardial infarction in a single ICU. The authors reaffirm the difficulties in detecting clinical symptoms of myocardial ischemia. Interpreting troponin
levels in patients recovering from noncardiac operations and in patients who are critically ill is also challenging. Lim and colleagues state that the lack of reliability of troponin measurements has led to increased emphasis on electrocardiographic changes as
a means of confirming the diagnosis of myocardial infarction. This study was an analysis by two observers of all electrocardiograms obtained on patients at risk for myocardial infarction in a single ICU during two months.
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The changes sought as evidence of myocardial infarction were those recommended
by the European Society of Cardiology/American College of Cardiology diagnostic criteria. The findings included pathologic Q waves, ST-segment elevation in at least two contiguous leads, ST-segment depression in at least two contiguous leads, symmetric inversion of T-waves (> 1mm) in at least two contiguous leads, T-wave flattening, and
new onset left bundle branch block. The last criterion was chosen because left bundle
branch block could obscure ST-segment elevation. The analysis of rater performance
indicated that intra-rater and inter-rater reliability was poor when the raters had no
knowledge of the serum troponin level. The raters were more likely to diagnose accurately electrocardiographic signs of myocardial infarction if they knew that there was a
significant elevation of the serum troponin level. Electrocardiographic abnormalities
most often identified accurately were T-wave inversion, Q-waves, and left bundle
branch block. These authors conclude that accurate diagnosis of myocardial infarction
in critically ill patients (who have physiologic similarities to postoperative patients) are
facilitated using a synthesis of clinical information that includes the electrocardiogram,
troponin levels, and, possibly, echocardiographic imaging.
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In an editorial by Engel19 that accompanies Lim’s article, the difficulty in arriving at
an accurate diagnosis of myocardial infarction is reemphasized. Engel agrees that use of
the electrocardiogram as the principle means of diagnosis of myocardial infarction in
postoperative or critically ill patients is hazardous. Furthermore, choosing interven18
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tional therapy in this patient subgroup is challenging because thrombolysis, coronary
angiography, and percutaneous coronary interventions requiring antiplatelet therapy
might not be safe.
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Management of the patient who has had a perioperative myocardial infarction is
based on providing support for the patient’s heart function while planning for appropriate means of revascularization. Support from cardiologists and cardiothoracic surgeons will be needed to facilitate these decisions. Cardiogenic shock is the most common lethal complication of perioperative myocardial infarction. Management of this
condition is discussed in detail in the next issue of SRGS.
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Perioperative cardiac arrhythmia
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Management of supraventricular tachycardia and atrial fibrillation
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In an earlier portion of this overview, we noted the association of postoperative inflammation, postoperative tachycardia, and postoperative atrial fibrillation with cardiac
morbidity. In patients at high risk for perioperative cardiac events, control of heart rate
and rapid diagnosis and therapy for treatable tachycardias are important for prevention of cardiac complications. The most common treatable tachycardias encountered in
postoperative patients are supraventricular tachycardias and atrial flutter/fibrillation.
In this section of the overview, we review pertinent features of the diagnosis and management of these cardiac rhythm disorders.
Supraventricular tachycardia is the subject of a review by Fox and coauthors20 in
Mayo Clinic Proceedings, 2008. A full-text reprint of this article is included with this issue of SRGS. The authors provide a working definition of supraventricular tachycardia
that includes all tachycardias arising cephalad to the bifurcation of the His bundle and
all tachycardias dependent on the His bundle for impulse transmission. These tachycardias usually have rates exceeding 100 bpm (unless atrioventricular conduction block is
present), and QRS morphology is usually normal. In the presence of bundle branch
block, however, QRS complexes might be widened or otherwise abnormal in shape. Data from long-term ambulatory electrocardiographic monitoring have permitted estimates of the incidence of supraventricular tachycardia. The authors cite data that disclose an incidence of 76% in a group of elderly patients with a 20% incidence of symptomatic coronary artery disease. In studies of asymptomatic healthy patients aged 1865 years, the incidence ranged from 12-18%.
Supraventricular tachycardia is usually of sudden onset and might spontaneously
terminate. The patient might complain of chest pain, and syncope occasionally occurs
(usually in very rapid tachycardias associated with reductions in cardiac output). Although no clear association between chest pain during a tachycardia episode and coronary artery disease has been established, the diagnosis might be suspected in elderly
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patients with tachycardia and chest pain. Patients usually complain of palpitations; patients with chronic heart failure might not sense the palpitations but, instead, present
with cardiac decompensation. The catecholamine response stimulated by tachycardia
and hypotension serves to perpetuate the rhythm disturbance.
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These authors note that atrioventricular nodal re-entry, atypical atrioventricular
nodal re-entry, or atrial tachycardias are the usual mechanisms of these rhythm disturbances. Atrioventricular node dependent tachycardias are usually terminated by inducing atrioventricular nodal block with a vagal stimulating maneuver (Valsalva, carotid sinus massage, or immersion of the face in cold water), or pharmacologically. Atrioventricular node independent rhythms include atrial flutter and atrial fibrillation.
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Diagnosis of tachycardia is usually possible using a 12 lead electrocardiogram,
which is preferred over a rhythm strip. QRS morphology is usually normal with QRS duration of 90 milliseconds or less. QRS complexes might be abnormal if there is intermittent or permanent bundle branch block. Other factors to be considered in interpreting
the electrocardiogram are the heart rate, mode of onset and termination of the tachycardia, relative position of the P-wave within the RR interval, and morphology of the P
wave. The tachycardia rate is usually higher than 100 bpm and can be variable. A steady
rate of 150 bpm suggests atrial flutter with a 2:1 atrioventricular block, according to
Fox and associates.
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Another means of determining the type of tachycardia is by examining the relationship of the P wave to the preceding and subsequent R wave. When the distance between
the R wave and the next P wave is longer than the subsequent PR interval, the tachycardia is a “long RP” rhythm. If the distance between the R wave and the subsequent P
wave is shorter than the subsequent PR interval, the rhythm is termed “short RP.” Long
RP tachycardias are atrial and might progress to flutter or fibrillation. Supraventricular
tachycardias, according to these authors, are mainly short RP rhythms. At very rapid
heart rates, RP and PR intervals become very short and might be difficult to interpret.
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Management of supraventricular tachycardia is usually straightforward because the
patients are usually hemodynamically stable. If there is instability, the patient is managed according to the typical ABC approach emphasizing airway, breathing, and circulation. Vagal maneuvers such as carotid sinus massage might terminate the rhythm
promptly and these maneuvers are ineffective in atrial flutter/fibrillation. Carotid sinus
massage should not be done if there is a carotid bruit present. Pharmacologic management of supraventricular tachycardia is accomplished using adenosine, calcium channel
blockers, or β-blocking drugs. Adenosine is the first-line drug and is given in 6 mg or 12
mg boluses. Smaller doses are used in patients taking dipyridamole.
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Broadening of the QRS complex might occur in supraventricular tachycardia if there
is bundle branch block. Fox and colleagues caution that if the patient is older than 70
years or there is a history of symptomatic coronary artery disease, a broad QRS tachycardia should be considered a ventricular tachycardia until proved otherwise. An article
discussing the use of response to adenosine bolus therapy as a means of differentiating
supraventricular from ventricular tachycardia when wide QRS tachycardia comes from
Critical Care Medicine, 2009, by Marill and coauthors.21 The authors note that differentiation of atrial from ventricular tachycardia when the heart rate is steady and the QRS
complex is widened is important, but current algorithms are neither sensitive nor specific in identifying the type of rhythm present. Drug therapy using procainamide or
amiodarone might effectively treat the rhythm but side effects such as hypotension limit the usefulness of these agents. Electrical cardioversion is effective but is painful, does
not protect against recurrence of the rhythm, and offers little diagnostic information.
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These authors hypothesize that adenosine will safely terminate most supraventricular tachycardias, will slow heart rate enough to allow detection of atrial flutter or fibrillation, and will be not predictably alter ventricular tachycardia. In a 15-year interval,
these authors treated 197 patients with steady-rate wide QRS complex tachycardia with
a 12 mg bolus of adenosine. Patients determined to have ventricular tachycardia were
older, more often had a history of myocardial infarction and prior episodes of ventricular tachycardia. Two of 81 patients with ventricular tachycardia responded to adenosine while 104 of 116 patients with nonventricular tachycardia responded to adenosine. There were no serious adverse events (defined as emergent drug therapy or electrical shock) observed in either subgroup. These authors concluded that nonresponse
to adenosine was the only factor that diagnosed ventricular tachycardia with a high
sensitivity and specificity.
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The nondihydropyridine group of calcium channel blockers (verapamil and diltiazem) are alternative drugs used to terminate supraventricular tachycardia. A summary of the data supporting these drugs in comparison to adenosine, by Anugwom and
coauthors22 appeared in American Family Physician, 2007. These authors reviewed data
from eight studies involving nearly 600 patients. The data disclose that adenosine and
calcium channel blockers are equivalently effective in terminating paroxysmal supraventricular tachycardias. Transient, minor side effects such as flushing, nausea, and
headache are common with adenosine. Severe side effects (cardiac arrest and hypotension) were observed only in patients treated with calcium channel blockers. These authors note that the American Heart Association guidelines recommend adenosine as
first-line therapy for paroxysmal supraventricular tachycardia because of the low risk
of severe side effects, the rapid onset of action, and the short half-life of the drug. The
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advanced cardiac life support course also recommends adenosine for the management
of supraventricular tachycardia.
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Of the atrial arrhythmias, atrial fibrillation is the most commonly encountered. A
discussion of the management of acute atrial fibrillation is in an article by Siu and coauthors23 in Critical Care Medicine, 2009. These authors report a randomized, nonblinded
trial comparing the effectiveness of diltiazem, digoxin, and amiodarone for rate control
and symptom improvement in patients presenting acutely with symptomatic, newonset atrial fibrillation. The authors note that atrial fibrillation is a common arrhythmia
and the frequency of this condition is increasing. Traditionally, two approaches have
been used to manage atrial fibrillation, rhythm control and rate control. Rhythm control
approaches use direct current cardioversion; this modality might not be available on a
24/7 basis.
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Guidelines published from the American Heart Association recommend emergency
direct current cardioversion only for patients with acute atrial fibrillation who are hemodynamically unstable. Direct current cardioversion might require that the patient be
anticoagulated, especially if there is atrial enlargement. This fact limits application of
this modality to postoperative patients. The authors analyzed results in 166 patients.
Patients were excluded from the study if they were unstable, had evidence of symptomatic coronary artery disease, were hypotensive, had an implanted defibrillator, had a
history of recent myocardial infarction, had a history of heart failure, or had angina pectoris. Drug therapies used were diltiazem, digoxin, and amiodarone. The endpoints examined were control of heart rate (heart rate < 90 bpm, sustained, at 24 hours after initiation of therapy) and improvement of symptoms. In this study, rate control and symptom improvement was best achieved with diltiazem. There was only one adverse event
recorded, an episode of phlebitis at the injection site, in one of the patients receiving
amiodarone.
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In an editorial by Karth24 that accompanies Siu’s article, the editorialist stresses that
these data, though valuable and convincing, were obtained in relatively healthy patients
and, because of this, the data might not be directly applicable to typical postoperative
patients since surgical patients are increasingly presenting with significant comorbid
conditions. Nonetheless, there is sufficient reason, based on the data reported by Siu, to
consider diltiazem as initial therapy in patients with acute, new-onset atrial fibrillation
when rhythm control strategies are not appropriate.
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In surgery patients, prevention of postoperative atrial fibrillation would be desirable if risk for the development of this arrhythmia could be quantified, and if safe, pharmacologic prevention strategies were available. A prevention strategy is discussed in a
report by Zebis and coauthors25 in Annals of Thoracic Surgery, 2007. These authors re22
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port a randomized, placebo controlled, double blind trial comparing amiodarone with
placebo in a group of patients undergoing coronary artery bypass (a known high-risk
group for the development of postoperative atrial fibrillation). These authors noted a
14% absolute risk reduction for patients treated prophylactically with amiodarone. Of
the patients in the placebo group who developed atrial fibrillation, more than 80% were
symptomatic; just over 40% of the patients in the amiodarone group who developed
atrial fibrillation were symptomatic. While these data have limited application to typical
general surgery patients, a preventive strategy might be considered in patients who
have previously undergone cardioversion for atrial fibrillation if antiarrhythmia drugs
are not already being used.
Management of surgical patients with disorders of the cardiac conduction system
A single review article is discussed in this section of the overview by Allen26 from
Anaesthesia in 2006. The article is entitled “Pacemakers and implantable cardioverter
defibrillators” and a full-text reprint of this article is provided with this issue of SRGS.
The author opens the discussion noting that pacemaker implantation is increasing with
increasing age of the surgery patient population. Likewise, the number of implanted
cardioverter defibrillators is increasing. Patients who have these devices are elderly
with histories of significant symptomatic heart disease.
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The author notes that modern pacemakers work by delivering, via an intracardiac
electrode, a low-voltage impulse to cardiac muscle. Devices in current use are capable of
detecting the intrinsic electrical signals within the heart so that the devices deliver pacing impulses only when they are needed. Improvement in pacing lead design has led to
“active fixation” leads that ensure optimum contact with the endocardial surface of the
heart. These leads also are designed to elute steroid medications to minimize inflammation at the contact site.
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Battery life has improved so that battery replacement is only necessary once in each
10-year interval. Furthermore, the titanium casing of modern pacemakers is light and
protects the device from outside electromagnetic interference so that patients can safely use microwave ovens, electric shavers, and mobile telephones. In addition, modern
devices carry electromagnetic interference detection software that offers additional
protection. For patients who undergo surgical procedures, the most common form of
electromagnetic interference comes from use of electrical coagulation devices. Bipolar
diathermy is preferred when the patient has an implanted cardiac device. If monopolar
diathermy use is unavoidable, the contact plate should be placed as far away from the
pacemaker as possible. Advice from the clinician who implanted the pacemaker can be
sought to reprogram the device if necessary. Reprogramming ideally occurs just before
beginning the procedure. Ideally, the physician who inserted the pacemaker would remain in the area until the procedure is completed.
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While earlier devices paced the ventricle alone, current devices offer dual-channel
pacing which improves cardiac output by taking advantage of atrial systolic contraction.
Allen emphasizes data that have documented reductions in risk for mitral and tricuspid
regurgitation and reductions in frequency of heart failure and chronic atrial fibrillation
with dual-chamber pacing.
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Allen goes on to provide information on the various pacing modes of current pacemaker devices. More than three-quarters of currently used pacemakers are rate-sensing
so that pacing current is supplied only when heart rates fall below a preselected level.
More than half of currently implanted devices are dual-chamber pacing devices. Currently, rate-sensing pacemakers adjust current output based on surrogates for increased physical activity such as body movement and respiratory excursion. Ideally,
rate-sensing devices would assess catecholamine levels or autonomic activity. Such
sensors are under development but, as of 2006, were not available. Pacemaker rate
sensors can sometimes interpret signals from intraoperative monitoring devices (such
as respiratory rate monitors that determine thoracic impedance) as body movement.
This results in rapid pacing.
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In patients with chronic heart failure, multiple sites within the cardiac chambers are
paced; this is termed cardiac resynchronization therapy. In these devices, impulse delivery to both ventricles in multiple sites can be timed to maximize cardiac output. Implanted cardioverter defibrillators are equipped with complex algorithm software that
tailors a response to a detected dangerous ventricular rhythm. Rate, beat-to-beat variation, atrial activity, and QRS morphology can be detected by the software and electrical
shocks are delivered based on the rhythm detected. All implantable cardiac convertor
defibrillators have pacemaker capability. These devices are not generally sensitive to
external electromagnetic interference, but it will be wise to obtain advice from the clinician who implanted the device about any precautions anticipated during anesthesia and
surgery.
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Cardiac failure in the surgical patient
Cardiac failure is an extremely common medical problem. More than 1 million hospitalizations annually in the United States are for cardiac failure; there is a 50% likelihood of death or recurrence of cardiac failure during the six months subsequent to a
hospital admission. Cardiac failure will develop in up to one-third of patients with
symptomatic ischemic cardiac disease; this condition will develop in 15% of diabetics
and 10% of patients with hypertension. While it is unlikely that surgeons will be involved in the first-line management of patients with acutely decompensated cardiac
failure, surgeons will be called to assist in the care of patients with heart failure who
develop conditions requiring elective or urgent surgical conditions. It is important that
surgeons understand the fundamentals of disordered cardiac function characteristic of
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the various forms of heart failure, and the pharmacology and side effects of the various
therapies employed in these patients. This set of topics is reviewed in this section of the
overview.
Systolic cardiac failure
The first article reviewed by Chatterjee and Rame27 appears in Critical Care Medicine, 2008, entitled “Systolic heart failure: chronic and acute syndromes.” The authors
define systolic cardiac failure as inadequate function of the heart as a pump manifest by
reduced ejection fraction. The condition most often emerges in patients with diabetes,
hypertension, or ischemic heart disease. Systolic heart failure might also be encountered in patients with dilated cardiomyopathy from other conditions such as myocarditis. Systolic cardiac failure results from a process termed “ventricular remodelling.” The
ventricles take on a more globular shape and chamber size increases. Although ventricular muscle mass increases, chamber size increases results in an increased chamber/ventricular wall ratio. The alteration in the chamber/ventricular wall ratio results
in increased ventricular wall stress; the result of these changes is an increase in end diastolic and end systolic chamber volumes, resulting in diminished ejection fraction.
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Chatterjee and Rame emphasize the importance or neurohumoral activation as the
process required for progression of systolic cardiac failure. Adrenergic, reninangiotensin, and aldosterone systems are all activated and the degree of activation is
linearly related to severity of symptoms and outcome. In the cardiac myocyte, results of
neurohumoral activation are hypertrophy, apoptosis, necrosis, and fibrosis. There is evidence of increased oxidative stress that produces additional cytotoxicity. Increases in
peripheral vascular resistance, ventricular filling pressures, and arterial stiffness are also results of neurohumoral activation, and these features contribute to cardiac failure
progression.
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Additional insight into the complex metabolic processes that influence the severity
and progression of heart failure is from an article by Ashrafian and coauthors28 in Circulation, 2007. These authors open their discussion with a description of myocardial energy metabolism and the balances necessary for efficient energy use. They point out
that daily myocardial ATP turnover is much greater than the myocardial ATP pool, and
normal myocardial energy metabolism extracts only 25% of available substrate. Because of these facts, subtle changes in the efficiency of myocardial energy metabolism
have far-reaching implications for cellular energy levels. One of the most important areas of study has been altered myocardial carbohydrate metabolism and the related
state of myocardial insulin resistance. At the cellular level, as insulin concentrations
vary, an attenuated glucose response results. These authors cite research data that
demonstrate a steadily increasing risk of heart failure with age in diabetic patients.
There is also an increasing risk of heart failure as hemoglobin A1c levels increase. Per25
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sistent hyperglycemia predicts increased risk for the development of heart failure and
for heart-failure-related hospitalizations. They refer to additional evidence supporting a
linkage between myocardial insulin resistance and the subsequent development of cardiac failure. Neurohumoral disorders characteristic of cardiac failure also facilitate the
development of hyperglycemia. Persistent inflammation, demonstrable in patients with
cardiac failure, contributes to hyperglycemia and myocardial insulin resistance.
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The aggregate result of the metabolic dysfunctions noted in cardiac failure is a heart
that is energy deficient. Because the heart must produce ATP in amounts many times
the weight of the heart, energy deficiency becomes a major factor in the onset and progression of heart failure. In addition, heart failure is associated with major reductions
(approximating 70%) in phosphocreatine, the “energy reserve” of the heart.
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Implications for management of cardiac failure emphasize control of the neurohumoral dysfunction concurrently with optimization of glucose levels as a means of combating insulin resistance. Ashrafian and associates discuss several new pharmacologic
agents that have the potential to improve myocardial energetics in cardiac failure patients.
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Patients with Type 2 diabetes and the metabolic syndrome are at increased risk for
the development of cardiac failure. Management of this patient group is challenging because the two mainstays of diabetic therapy for Type 2 diabetes, the biguanides (metformin) and the thiazolidinediones (rosiglitazone) are currently contraindicated in patients with clinical evidence of cardiac failure. Several classes of diabetic drugs are
available as adjuncts to conventional neurohumoral modulating agents in this patient
group. This topic is reviewed in detail in an article by Masoudi and Inzucchi.29 Interested readers are encouraged to review this article.
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Anemia is an additional condition frequently observed in patients with cardiac failure. A discussion of this topic comes from an article by Mitchell30 in the American Journal of Cardiology, 2007. The author notes that anemia is present, overall, in 33% of
heart failure patients and the proportion of patients who are judged to be anemic (hemoglobin level < 12 gm/dL) increases with increasing severity of heart failure. New
York Heart Association Class IV patients have a 76% prevalence of anemia. The causes
of anemia are complex, with contributions from impaired erythropoietin synthesis and
utilization, hemodilution, impaired iron and vitamin B12 absorption, and persistent gastrointestinal bleeding in patients who take aspirin.
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Anemia, like other disease features, is associated with increased levels of proinflammatory mediators and oxidative stress factors. Anemia is known to be an independent driver for increased rates of heart failure hospitalization and death. Mitchell
cites several confirming data sources. Mortality risk is particularly high when anemia
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and renal insufficiency coexist. Because ischemic cardiac disease is an important precursor of cardiac failure, assessment of this patient group for anemia has been carried
out by several investigators cited by Mitchell. Data disclose an association of anemia
with the onset and progression of ischemic cardiac disease. Anemia might lead to increased cardiac output that contributes to imbalances of myocardial energy availability/utilization that contribute to progression of cardiac failure.
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Mitchell notes that elevation of hemoglobin levels is associated with improved left
ventricular ejection fraction and improved quality of life indices. Elevation of hemoglobin levels with erythropoietin analogues and iron is desirable. Red blood cell transfusion has lowered short-term mortality in a small group of elderly patients but it is not
clear, according to this author, whether the benefit of transfusion outweighs the risks.
Additional information on this topic is in an article by Gerber31 in Critical Care Medicine,
2008. The focus of this article is the use of transfusion in patients with ischemic cardiac
disease. It is likely, however, that many of the basic findings pertinent to the ischemic
cardiac disease patient will also be appropriately applied to patients with cardiac failure.
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The author begins by reviewing the complications of transfusion with acute complications such as transfusion reaction and transfusion-related lung injury (this topic is
discussed in more detail later in the overview), and the medium term complication of
blood-borne disease transmission. Because there are significant risks to transfusion, the
decision to use transfusion must depend on an assessment of the extent to which oxygen availability to cells will be increased by raising the number of red blood cells with
transfused cells and documentation of improved outcomes in anemic heart disease patients who receive transfusions. Gerber notes that the average storage age of transfused
red blood cells is 17 days. Currently, stored red cells have lost 2,3 diphosphoglycerate
and the p50 of the cells has changed so that cellular affinity for oxygen is increased and
the ability to offload oxygen from transfused red cells to tissue is reduced. Structural
changes in red cells have also occurred and the cells have become stiff so that passage
into and through the microcirculation is impaired. Although measured oxygen content
of blood might increase following transfusion of stored red cells, increased cellular oxygen availability is by no means assured.
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Data from studies of septic patients and patients in septic shock, cited by Gerber,
suggest that cellular oxygen delivery is not increased by red blood cell transfusion. Gerber then reviews several studies where outcomes have been analyzed in anemic heart
disease patients who have been transfused. Only one study has shown improved outcomes, and the improvement was observed only in elderly patients with admission
hematocrits < 33%. In all the other studies there was no improvement, with several
studies suggesting worse outcomes in transfused patients. He concludes by stressing
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that there is no convincing evidence to support the routine use of transfusion to improve outcomes in anemic patients with cardiac disease.
Diastolic cardiac failure
Approximately 50% of patients with acute symptoms of cardiac failure, manifest as
dyspnea with radiologic signs of pulmonary edema, have preserved left ventricular
ejection fraction, according to data presented in an article by Kumar and coauthors32 in
Critical Care Medicine, 2008. Patients with this form of cardiac failure are often elderly,
female, and less likely to be African American than are patients with other forms of cardiac failure. The clinical presentation in many patients consists of signs of acute pulmonary edema associated with elevated systolic blood pressure. Because echocardiographic imaging that documents maintenance of left ventricular ejection fraction is performed, in many patients, after treatment for heart failure has begun, the suggestion has
been made that ejection fractions were depressed at the time of symptom onset and
improved with treatment. Kumar and associates cite a report of echocardiographic
analyses performed in patients acutely and after 24 hours of treatment. There was
maintenance of left ventricular ejection fraction at both time points, suggesting that
heart failure occurred in the presence of normal left ventricular ejection fraction.
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These authors note that diastolic cardiac failure and pulmonary edema are likely
caused when venous return to the right ventricle acutely increases and an increased
volume of blood is delivered to the pulmonary circulation. Left ventricular dysfunction
creates a situation in which the left ventricle cannot accept the increased blood flow
without elevating left atrial pressure. In the setting of elevated left ventricular pressure
(especially with a peak late in systole), left ventricular relaxation is impaired. Pulmonary blood volume increases and this overcomes the ability of the pulmonary lymphatics to remove fluid from the pulmonary interstitium. Pulmonary edema is the result.
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Additional data on diastolic cardiac function are found in an article entitled “Left
ventricular diastolic function” by Hoit33 in Critical Care Medicine, 2007. Hoit notes that
cardiac diastole is the result of processes whereby the heart loses ability to generate
contractile force produced by myocyte shortening. The heart returns to a precontractile
state in preparation for filling and the subsequent systole. Responsible for this series of
events are myocardial relaxation and the pressure/volume properties of the ventricle.
Relaxation is an energy-consuming process. Calcium is released from troponin C and actin-myosin cross bridges detach. Calcium is sequestered in the sarcoplasmic reticulum
and, simultaneously, calcium is extruded from myocyte cytoplasm by active sodiumcalcium exchange. Multiple factors influence the left ventricular end diastolic pressurevolume relationship including left ventricular physical properties (stiffness), the efficiency of relaxation, and extrinsic factors such as pericardial restraint and intrapleural
pressure. Echocardiography is a valuable means for quantifying left ventricular diastolic
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function. Ventricular compliance and left atrial volume can be assessed with echocardiographic imaging. Using Doppler imaging, flow velocities across the mitral valve and in
the pulmonary veins can be measured and the relaxation dynamics of the left ventricle
can be determined.
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Acute echocardiographic imaging is emerging as an important tool permitting quantification of cardiac function and intravascular volume status in patients with suspected
myocardial infarction, hypovolemia, or cardiac failure. Features of acute echocardiographic evaluation are reviewed in detail in an article by Glassberg and coauthors34 in
Critical Care Medicine, 2008. These authors describe the use of Doppler echocardiographic imaging to assess preload and afterload. They note that recent data disclose an
increased rate of cardiac adverse events in patients with acute cardiac decompensation
monitored using pulmonary artery catheters. They further note that Doppler echocardiography has the capability of providing accurate estimates of cardiac output, right
atrial pressure, pulmonary artery mean, systolic, and diastolic pressures as well as left
ventricular filling pressure. Echocardiographic imaging might produce clinical information that is equivalent to the information gained from the pulmonary artery catheter
without the risk of central venous catheterization. They conclude that acute echocardiographic imaging is an important component of the evaluation of patients with acute
hemodynamic instability where cardiac failure is an important part of the differential
diagnosis.
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Management of heart failure in the surgical patient
Where systolic or diastolic cardiac failure is suspected, the history, physical examination, and acute echocardiographic imaging are used to establish a diagnosis. Laboratory studies, including serum assays of brain natriuretic peptide (BNP) or N-terminal
pro-brain natriuretic peptide (NT-proBNP) might be helpful in providing additional diagnostic information. The use of these serum markers is discussed in an article by Omland35 in Critical Care Medicine, 2008. Omland stresses the value of diagnostic information that can be gained from serum levels of BNP or NT-proBNP obtained in the
emergency department or in the ICU when patients present with acute dyspnea. Abnormal BNP or NT-proBNP was 84%-90% accurate diagnosing diastolic cardiac failure
as the cause of acute dyspnea in several studies cited by this author. Omland stresses
that BNP levels are frequently normal in patients with chronic heart failure. Furthermore, BNP and NT-proBNP levels were not consistently useful as means of assessing
progression or improvement of cardiac failure. Data discussed earlier describe the limitations of serum tests in postoperative patients.
Therapy for systolic cardiac failure depends on the clinical presentation. The presence of echocardiographic evidence of increased filling pressures suggests the use of
loop diuretics (furosemide) to improve pulmonary congestion, dyspnea, and hypoxia.
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Significant low cardiac output states in patients with systolic cardiac failure can be
treated with afterload reduction using vasodilators. Sublingual nitroglycerin is the firstline approach in this regard. With very low cardiac output, short duration inotropic
therapy can be considered.
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The use of inotropic drugs for systolic cardiac failure is the topic of an article by Petersen and Felker36 in Critical Care Medicine, 2008. These authors emphasize data,
which they review in this article, indicating a lack of clinical value of inotropic drugs in
patients without clearly documented end-organ hypoperfusion. They further report the
clinical challenges in documenting end-organ hypoperfusion. Traditionally, this diagnosis has been made by documenting worsening renal function. Petersen and Felker note
that increases in serum creatinine after the institution of loop diuretic therapy might
indicate presence of cardiorenal syndrome and not end-organ hypoperfusion. These authors note that some patients with very low cardiac output states will maintain normal
levels of serum creatinine.
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These patients will frequently have nonspecific symptoms such as abdominal pain,
nausea, fatigue, and diminished cognitive function. Documentation of low cardiac output with echocardiography or pulmonary artery catheter monitoring will likely provide
confirmatory evidence. The authors note that documented low cardiac output in patients with systolic heart failure is a marker for increased short-term mortality. If inotropic therapy is contemplated, dobutamine and milrinone are the first-line drugs. Both
drugs produce improvements in cardiac output via augmentation of cellular cyclic AMP.
Milrinone has greater vasodilating function than dobutamine and might have lower risk
of inciting arrhythmias. Devices useful for supporting cardiac function include the intraaortic balloon pump, left ventricular assist devices, and ultrafiltration devices. These
devices reliably support cardiac function until definitive therapies using revascularization or transplantation can be organized and implemented. These devices are discussed
in a review by Kale and Fang37 in Critical Care Medicine, 2008.
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According to Kumar and coauthors,32 treatment of acute pulmonary edema, the
main clinical manifestation of diastolic cardiac failure, focuses on improving oxygenation and relieving patient symptoms. Noninvasive ventilation with continuous positive
airway pressure is valuable for reversing hypoxia. Early administration of a loop diuretic along with intravenous β-blocking drugs will improve pulmonary congestion, lower
blood pressure and heart rate, and relieve patient symptoms. These authors stress that
diuretic-naïve patients might have a very brisk diuresis and, therefore, lower diuretic
doses initially might provide a greater margin of safety. Morphine is helpful for relieving symptoms also. Afterload reduction with sublingual nitrate drugs is frequently helpful.
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Perioperative management of diastolic cardiac failure is discussed in a review by
Pirrachio and coauthors38 in the British Journal of Anesthesia, 2007, who stress that the
focus of perioperative management is to choose an anesthetic strategy that will not decrease left ventricular function. Intravenous agents such as propofol and most muscle
relaxants do not affect left ventricular function. Volatile anesthetics such as sevoflurane
and desflurane also do not change left ventricular function. These authors stress the
importance of aggressively controlling the catecholamine response that accompanies
operation and they recommend preoperative beta blockade supplemented by intravenous short-acting agents such as esmolol for management of hypertension and tachycardia.
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Cardiopulmonary resuscitation
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History of cardiopulmonary resuscitation
Data on the frequency of out-of-hospital and in-hospital cardiac arrest appear in articles by Ramsay and Maxwell,39 Ali and Zafari,40 and Ehlenbach and coauthors.41 The
articles by Ramsay and Maxwell and Ali and Zarari are supplied as full-text reprints
with this issue of SRGS. These articles confirm that there are more than 400,000 sudden
deaths annually ascribed to cardiac disease resulting in cardiac arrest. Ramsay and
Maxwell cite data indicating that there are 165,000 witnessed episodes of out-ofhospital cardiac arrest in the United States each year. In-hospital cardiac arrest occurs
at a rate of nearly three events/1000 admissions, according to data cited by Ehlenbach
and coauthors. Cardiac arrest is the cause of 5.6% of all deaths annually in the United
States, according to data cited in the article by Ali and Zafari. Despite the availability of
effective methods of cardiopulmonary resuscitation, mortality for witnessed out-ofhospital and in-hospital cardiac arrest exceeds 80%. All the authors cited note the disappointing statistics indicating that nearly three-quarters of the patients who sustain
witnessed cardiac arrest have no attempt at resuscitation made. In this section of the
overview, we review several topics pertinent to effective management of witnessed outof-hospital cardiac arrest and in-hospital cardiac arrest.
Ramsay and Maxwell describe a short history of cardiopulmonary resuscitation in
their article from The American Surgeon in 2009. The authors note that descriptions of
mouth-to-mouth rescue breathing appear in the Old Testament. In the 14th century,
rescue breaths were administered using bellows devices placed intranasally or through
a reed inserted into the trachea via an anterior neck incision. During the 18th and 19th
centuries, “humane societies” were formed in several European countries to foster the
use of artificial respiration techniques for drowning victims. In studies on animals, John
Hunter noted that cessation of breathing led to cardiac standstill and immediate resumption of breathing led to restoration of cardiac action.
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The use of electricity for defibrillation was championed by Wiggers who also supported the use of open cardiac massage. Open massage was used for resuscitation of intraoperative cardiac arrest by Beck of Johns Hopkins Medical School, and this method of
resuscitation was the focus of his research from 1920–1937. Closed chest massage was
developed at Johns Hopkins and described in a 1960 publication in the Journal of the
American Medical Association by Kouwenhoven, Knickerbocker, and surgeon James
Jude. Training in techniques of cardiopulmonary resuscitation for emergency medical
services personnel and citizen responders was made simpler and more effective by the
development of life-like mannequins for intubation and resuscitation by Safar and
Laerdal. Currently, national standards for citizen, emergency medical services, and inhospital cardiopulmonary resuscitation are promulgated by courses sponsored by the
American Heart Association (Basic Cardiac Life Support and Advanced Cardiac Life
Support).
Current practice and outcomes for cardiopulmonary resuscitation
Ali and Zafari40 note that sudden cardiac arrest is, in the main, caused by coronary
artery disease. They cite data from autopsy studies indicating that more than 80% of
nonsurvivors of cardiac arrest have severe coronary artery disease confirmed by postmortem examination. Other causes of cardiac arrest are aortic stenosis, WolfParkinson-White syndrome, cardiomyopathy, and congenital cardiac disease. The presence of a “shockable” (ventricular tachycardia or ventricular fibrillation) rhythm is associated with better outcomes of cardiopulmonary resuscitation. These authors note
that these rhythms are being documented less often during cardiopulmonary resuscitation events. Fewer than one-third of patients have a shockable rhythm on initial electrocardiographic tracing. Asystole and pulseless electrical activity rhythms are being
recorded with increasing frequency.
These authors describe a “four phase” classification of a cardiac arrest event. The
“electrical phase” extends from time 0–4 minutes after arrest. The “circulatory phase”
extends from 4-10 minutes post arrest. The “metabolic phase” begins at 10 minutes
post arrest. During the electrical phase, defibrillation is the most effective therapy if a
shockable rhythm is noted. During the circulatory phase, qood-quality cardiac compression is critical. In the metabolic phase, resuscitative efforts focus on reversing the effects of global ischemia. The importance of defibrillation during the electrical phase
supports the distribution of automatic defibrillators and the use of these devices by
trained citizen rescuers since it is unlikely that trained emergency medical services personnel will arrive on the scene before the late circulatory or metabolic phase of resuscitation.
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Data cited in Table 2 of the article by Ali and Zafari confirm the value of early defibrillation if a shockable rhythm is discovered within the first five minutes following the
arrest event.
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Adequate cardiac compressions (optimum rate with optimum excursion) given before defibrillation shock are associated with improved outcomes, according to data cited by Ali and Zafari. They also note that optimum cardiac compressions provide coronary perfusion that serves to minimize the depleting affect of ventricular fibrillation on
cardiomyocyte energy stores. Rescue breaths (two breaths administered by mouth-tomouth or mouth-to-airway respiration before instituting cardiac compression) are currently recommended by the American Heart Association, but this is controversial and
subject to change.
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Ramsay and Maxwell39 note that current recommendations urge rescuers to perform chest compressions with two hands in adults at a rate of 100 compressions/minute with a compression excursion of 4 cm. For patients who have an airway
placed, the ratio of compressions/breaths is recommended at 30:2. Mouth-to-mouth
and mouth-to-airway “rescue breaths” previously recommended to precede chest compressions are now eliminated in many regional protocols recognizing that encouragement to administer mouth-to-mouth breaths is a strong disincentive to provision of any
sort of rescue resuscitation. As noted above, in current studies, no resuscitation attempt
is made in the majority of witnessed out-of-hospital cardiac arrests. Recent data cited
by Ramsay and Maxwell (reference 9 in their bibliography) indicate that chest compressions without rescue breaths result in improved outcomes for cardiopulmonary resuscitation in witnessed out-of-hospital cardiac arrest events.
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A more favorable neurologic outcome, more frequent occurrence of shockable cardiac rhythm on initial electrocardiogram, and improved overall survival when resuscitation was begun within four minutes of cardiac arrest were all confirmed in the study
cited. These observations have lent support to the primacy of supplying effective chest
compressions. Rescue personnel are no longer encouraged to supply a “stack” of three
electrical defibrillation shocks when a shockable rhythm (ventricular tachycardia or
ventricular fibrillation) is discovered on the initial electrocardiogram. Instead, a single
shock is applied and compressions are resumed. In addition, drug administration (intravenous or endotracheal instillation) is recommended while compressions continue
rather than a “drug-breath-shock-compression” cycle. Despite dissemination of this information nationally, data cited by Ramsay and Maxwell indicate an unsatisfactory level
of compliance with these guidelines. In a study of in-hospital cardiac arrest, compression rates of less than 100/min were noted in more than 90% of resuscitations (reference 10 in their bibliography). An additional finding of this study was a disturbing fre-
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quency of “no-flow” intervals (intervals during which there are no compressions).
These exceeded 10 seconds/minute of resuscitation events.
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Research confirming the critical importance of high-quality chest compressions is
from a report by Ristagno and coauthors42 in Chest, 2007. These authors performed a
study in pigs; cardiac arrest was produced by ligation of the left anterior descending
coronary artery. Chest compressions were begun 5 minutes after onset of cardiac arrest. “Adequate” chest compression was defined as compression excursion equal to
25% of the anterior-posterior chest diameter (6 cm excursion) and “conventional” chest
compression as 4 cm excursion. A single defibrillation shock of 150 joules was delivered
before or after compressions began, according to the experimental protocol for each animal group; each group consisted of six animals. The data presented indicate that endtidal PCO2 and coronary perfusion pressures (both variables are related to adequate
myocardial and peripheral perfusion) were lower in animals receiving conventional
compressions. With optimal chest compressions, fewer shocks were required to restore
cardiac rhythm and all animals were resuscitated.
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No animals were resuscitated when defibrillation shock preceded conventional
compressions. Two of six animals were resuscitated successfully when shocks were
administered after a period of conventional chest compression. This animal study supports current clinical recommendations that stress the importance of adequate chest
compressions. Adequacy of chest compression is important whether a “shock first” or
“shock after compression” protocol is followed. These data lend support to the urgent
need to improve the quality of compressions offered to patients who sustain cardiac arrest. These authors cite data that indicate adequacy of chest compressions in less than
one-third of cardiopulmonary resuscitation events, and they stress the importance of
aggressive educational efforts to improve the quality of chest compressions in cardiopulmonary resuscitation events.
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Ramsay and Maxwell go on to discuss methods for ventilating the intubated patient
during a cardiac arrest event. The foregoing discussion has noted the recommendation
of a breath-to-compression ratio of 30:2. Hyperventilation raises intrathoracic pressures with resultant reduction in venous return and depression of compression mediated cardiac output. With increased intrathoracic pressure, coronary perfusion is reduced. If hypocarbia is induced, cerebral vasoconstriction might reduce cerebral oxygenation. Placement of an impedance threshold device in the ventilation circuit serves
to reduce intrathoracic pressure and improve venous return. This device works by reducing air entry into the lung during the chest recoil phase that follows a cardiac compression. Lowered intrathoracic pressures, improved end-tidal PCO2, and improved
coronary perfusion pressures have been documented with the use of this device during
experimental and clinical cardiopulmonary resuscitation.
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A meta-analysis of research results relevant to the use of the impedance threshold
device is reported by Cabrini and coauthors43 in Critical Care Medicine, 2008. These authors reviewed data from five high-quality studies involving more than 800 patients.
They found that use of the impedance threshold device was associated with significant
improvements in return of effective cardiac rhythm, early survival, and early favorable
neurologic outcomes with no significant effect noted on long-term survival. The authors
note that this study focused on data generated from studies of out-of-hospital cardiac
arrest. They further note that optimum results in terms of improved venous return to
the heart depend on rescuers permitting full recoil of the chest wall by lifting the palms
off the chest after each compression. They stress that data they reviewed showed improved outcomes even in patients with event-to-compression times of 10 minutes or
more. Improvements are also noted in outcomes of patients with unfavorable rhythms
such as asystole.
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The use of adjunctive drug therapy during cardiopulmonary resuscitation is reviewed by Ali and Zafari.40 The objective of initial drug therapy is to provide strong αreceptor agonist capability. Alpha stimulation works to redistribute blood flow to the
brain. Epinephrine 1mg intravenously or instilled into the endotracheal tube has been
the initial drug for a number of years. Recently, additional pressor activity has been
achieved with vasopressin in a dose of 40 international units given intravenously. These
authors cite data from studies comparing epinephrine and vasopressin; no difference in
survival-to-hospital discharge was noted in either group. A subsequent study showed
improved survival in patients receiving both epinephrine and vasopressin. Current recommendations support use of both drugs in combination.
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Although epinephrine has been used for many years to improve brain blood flow,
research data questions whether this drug results in true increases in brain cellular oxygen delivery. This issue is the topic of a research study by Ristagno and coauthors44 in
Critical Care Medicine, 2009. These authors conducted experiments on pigs and note
that the sine qua non of successful cardiopulmonary resuscitation is successful recovery
of brain function. The alpha-receptor stimulating properties of epinephrine have been
thought to facilitate redistribution of blood flow to the brain during cardiopulmonary
resuscitation. These authors cite evidence for beta-receptor stimulating activity of
norepinephrine during experimental shock. This property resulted in failure of the drug
to restore appropriate nutrient tissue blood flow.
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In these experiments, the authors assessed brain nutrient delivery by measuring
microcirculatory blood flow using orthogonal polarization spectral imaging. Tissue carbon dioxide and oxygen tensions were also measured. Ventricular fibrillation was induced and drug therapy administered after three minutes. Animals were divided into
groups that received placebo, epinephrine, and epinephrine in the presence of two dif35
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ferent forms of alpha and beta receptor blockade. The data disclosed reductions in both
brain oxygen tension and microcirculatory blood flow in animals receiving epinephrine.
This was accompanied by increased brain tissue carbon dioxide levels. The effect was
traced to the alpha stimulatory effects of epinephrine.
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Drug therapy has also been suggested to facilitate the return of effective cardiac
rhythm. This topic is also reviewed by Ali and Zafari. Drugs used for this purpose include lidocaine, atropine, and amiodarone. Studies of atropine use have not demonstrated statistically improved survival although there might be improved conversion of
slow pulseless electrical activity with atropine use. Lidocaine is currently not recommended as a means of improving conversion from ventricular tachycardia and fibrillation to an effective rhythm. Amiodarone is the current drug of choice to assist with
rhythm conversion. Concern that the diluent in which amiodarone is delivered (polysorbate 80 and benzoyl alcohol) might be a cause of hypotension has been voiced but
data, to date, do not support this as a frequent complication. There is now an aqueous
preparation of amiodarone that can be infused rapidly and this preparation has not
shown increased frequencies of hypotension. The current recommended dose of amiodarone is 300 mg. Another drug occasionally used in cardiopulmonary resuscitation is
magnesium sulfate. This drug is used in 1-2 gram doses for one specific rhythm, torsade
de pointes. This rhythm is a polymorphic ventricular tachycardia associated with a prolonged QT interval.
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Recovery of effective cardiac activity after cardiopulmonary arrest is associated
with a pro-inflammatory state characterized by elaboration of inflammatory cytokines,
changes in coagulation, and increased oxidative stress. Because of this observation and
because adrenal insufficiency has also been observed after cardiopulmonary arrest, anti-inflammatory therapy has been suggested as a means of improving outcomes. This
topic is addressed by Mentzelopoulos and coauthors45 in an article entitled “Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest.” These authors begin
by citing animal experiment data supporting the use of vasopressin, epinephrine, and
corticosteroids as a means of improving neurologic outcomes of cardiac arrest. These
authors conducted a single-center, randomized, prospective, double-blind study to assess effects of this drug combination with the use of stress dose corticosteroid replacement in patients found to have adrenal insufficiency on the outcomes of cardiopulmonary resuscitation. The authors noted improved recovery of effective cardiac rhythm
and improved survival-to-hospital discharge in patients who received the corticosteroid drug combination. Two patients in the corticosteroid group survived to hospital discharge versus none in the control group. Unfortunately, both survivors had severe neurologic deficits. Although this study is suggestive of a benefit in a very high-risk group of
patients, the small numbers and the questionable clinical significance of two neurologi36
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cally disabled survivors versus none indicates that these results should be interpreted
very cautiously.
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Optimization of recovery of effective cardiac rhythm, myocardial perfusion, and cerebral perfusion are efforts directed toward the electrical and circulatory phases of cardiac arrest. The main attempt to ameliorate the effects of the metabolic phase of cardiopulmonary resuscitation has emphasized the use of therapeutic hypothermia. Ramsay
and Maxwell39 note experimental data indicating a reduction in brain oxidative stress
and oxygen demand when post-cardiac arrest hypothermia is used. These authors review data from the Hypothermia After Cardiac Arrest Group. This group conducted a
randomized trial of hypothermia (bladder temperature 32-34°C for 24 hours) following
successful resuscitation in patients with ventricular fibrillation. There were significantly improved neurologic outcomes (55% good outcomes versus 39% in controls) when
hypothermia was used. Six-month mortality was 41% in the hypothermia patients versus 55% in controls. These data support use of post-resuscitation hypothermia in patients with witnessed out-of-hospital cardiac arrest where successful defibrillation occurs.
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The topic of hypothermia application is discussed in more detail in two additional
reviews and an editorial which accompanied one the reviews.46-48 One of these articles,
by Schneider and coauthors,48 is a detailed, yet readable comprehensive review of metabolic approaches to cardiac arrest and this article is included as a full-text reprint with
this issue of SRGS. These articles stress the importance of maximizing nutrient blood
flow by optimizing compressions, improving venous return, and protecting against hyperventilation and lung hyperinflation. They also note the utility of mild post-arrest hypothermia in patients who have witnessed arrests, prompt resuscitation, and a shockable rhythm. Hypothermia is designed to protect cerebral tissue metabolism.
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The articles and the editorial stress the cellular causes of cerebral dysfunction,
which result from massive accumulations of calcium in brain cells after cardiac arrest.
Currently, hypothermia is indicated for children remaining comatose following cardiac
arrest and adults with recovery of spontaneous circulation after out-of-hospital ventricular fibrillation. Hypothermia can potentially assist recovery of patients with other
rhythms, but data confirming this benefit are not available. Data are badly needed because ventricular fibrillation is declining as the main rhythm for out-of-hospital cardiac
arrest. For in-hospital cardiac arrest, ventricular fibrillation is not often discovered on
the initial electrocardiogram. The authors of these three articles note that the multiple
comorbid conditions found in victims of in-hospital cardiac arrest makes recovery in
these patients less likely. These reports note the potential for agents such as growth factors and apoptosis inhibitors; data about these approaches should be forthcoming in
the future.
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Another approach to applying hypothermia and circulatory support for victims of
cardiac arrest is with the use of extracorporeal membrane oxygenation. This topic is the
subject of a report by Thiagarajan and coauthors 49 in Annals of Thoracic Surgery, 2009,
of an analysis of a large extracorporeal membrane oxygenation database. Eleven percent of patients in the database had the device applied as an adjunct to management of
cardiac arrest. The most frequent diagnosis recorded was “cardiac disease.” The authors documented a 27% survival in these patients. The proportion of in-hospital versus out-of hospital cardiac arrests is not provided, and the presence of a shockable
rhythm is likewise unknown. These data suggest potential utility of the extracorporeal
membrane oxygenator in patients sustaining cardiac arrest. Improved outcomes occurred when the device was applied within two hours of arrest. A diagnosis other than
myocarditis was also associated with improved survival. Renal insufficiency requiring
dialysis was associated with increased mortality risk.
Cardiopulmonary resuscitation for in-hospital cardiac arrest: epidemiology and outcomes
As has been noted previously, outcomes for in-hospital cardiac arrest are, in general,
worse than those for out-of-hospital cardiac arrest, primarily due to the multiplicity of
unfavorable risk factors in patients who sustain in-hospital cardiac arrest. In addition,
the presenting rhythms for patients with in-hospital cardiac arrest are more often
pulseless electrical activity or asystole. The first article examining the epidemiology of
in-hospital cardiac arrest in elderly patients is by Ehlenbach and coauthors 41 in the
New England Journal of Medicine, 2009. These authors analyzed data from the Medicare
database over the interval 1992-2005. They examined data from records of 434,000 patients who underwent in-hospital cardiopulmonary resuscitation. The overall survival
of these patients was 18%, which is, interestingly, very close to the overall survival for
out-of-hospital cardiac arrest.
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Survival of nonwhite patients was worse than survival in white patients. The authors note that the data for nonwhite patients were drawn, disproportionately, from
hospitals with lower overall cardiac arrest survival and this might explain the racial
discrepancy, at least in part. The analysis indicated that results of in-hospital resuscitation did not improve during the study interval. In the discussion section of this report,
the authors make several interesting observations and speculations. They note, for example, that between-hospital comparisons suggest that hospitals that make use of more
extensive monitoring seem to have faster responses to cardiac arrest and improved
outcomes.
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One approach to shortening response time for cardiac arrest has been to institute
rapid response teams. This topic is the subject of a report by Chan and coauthors50 in
the Journal of the American Medical Association, 2008. These authors compared the
rates of cardiorespiratory arrest codes and mortality for cardiopulmonary resuscitation
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before and after implementation of a rapid response team. Nearly 25,000 patients were
available for analysis in each group. The analysis was performed prospectively in a single institution. The results of the analysis indicated that there were 376 rapid response
team activations in the 20 months of experience analyzed after team implementation.
The frequency of out-of-ICU codes declined (this is a hoped-for result of rapid response
team implementation). Unfortunately, there was no reduction in the overall mortality
when the two periods were compared.
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The authors note that there is no standard approach to rapid response team activation and no standard organization of the team. These problems make comparisons difficult. It is interesting to note recent developments in several hospitals where rapid response team activation can be accomplished by patients or patients’ families without
the need to summon nursing staff. Additional data will be interesting to document the
potential effectiveness of rapid response teams.
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Ehlenbach and coauthors note that their data indicate that the proportion of inhospital deaths preceded by formal efforts at cardiopulmonary resuscitation increased
during each year of the study they conducted. They speculate that this increase might
be because nonwhite patients tend to have lower rates of do-not-resuscitate orders
than do white patients. They further speculate that do-not-resuscitate orders might be
ignored in a significant proportion of in-hospital cardiac arrest incidents.
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Prearrest predictors of survival after cardiopulmonary resuscitation have been
sought. This subject is the topic of an analysis authored by Gonzalez and coauthors51 in
Circulation, 2008, who examined outcomes of cardiopulmonary resuscitation in a group
of patients who had undergone echocardiographic assessment of left ventricular function on average 11 days before the arrest event. The authors found that a left ventricular ejection fraction of less than 45% predicted a worse outcome. Mortality in the group
with diminished left ventricular function was 92% compared with 81% in patients with
normal left ventricular function.
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The analysis also produced data showing that post-cardiopulmonary resuscitation
of left ventricular function was depressed in all patients by an average of 25%. The authors concluded that the depression of ventricular function attendant to cardiopulmonary resuscitation could not be tolerated in patients with depressed ventricular function before the cardiac arrest event. This analysis is interesting. The high proportion of
echocardiographic analyses before arrest (77%) suggests that these patients were
largely patients hospitalized with cardiac disease and generalization of these data to
other patient groups might not be possible. The authors speculate that the hyperadrenergic state that follows restoration of cardiac rhythm might be especially stressful for
patients with diminished left ventricular function.
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Ehlenbach and associates also noted differences in outcomes of resuscitation depending on the day and time of cardiac arrest occurrence. This topic is the focus of a report by Peberdy and coauthors52 in the Journal of the American Medical Association,
2008. These authors analyzed data from cardiac arrest events occurring from 07002259 versus 2300-0700. They also compared mortalities from cardiac arrests occurring
from 2300 on Friday to 0659 on Monday. The database analyzed was the National Registry of Cardiopulmonary Resuscitation that contains data from more than 500 participating hospitals. They noted significant reductions in survival-to-discharge and good
neurologic outcomes in patients who sustained cardiac arrest at night or on weekends.
This difference was stable when the data were adjusted for differences in patient
comorbidity and risk. The data suggested a somewhat increased odds of death for cardiac arrest occurring in the operating room or ICU and a slight (nonsignificant) reduction of risk for cardiac arrest occurring in the emergency department. Patients admitted
after injuries were, as a group, slightly more likely to survive cardiac arrest.
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Data such as those discussed above suggest the need to improve effective cardiopulmonary resuscitation in hospitals. Educational activities such as performance debriefings and feedback might function to improve cardiopulmonary resuscitation performance and, perhaps, results. The first article that deals with this topic is by Edelson
and coauthors53 and is entitled “Improving in-hospital cardiac arrest process and outcomes with performance debriefing.” This article appeared in Archives of Internal Medicine, 2008. A debriefing conference was held for residents who participated in cardiopulmonary resuscitation events. Data from sensing defibrillators and observations
made by trained observers were used to identify areas for improvement and training.
One hundred twenty-three patient events after implementation of the debriefing session were compared with 101 historic controls. These authors found that adherence to
national recommendations about compression rate, excursion, and ventilation improved in the post-debriefing period. There was an increased rate of return of spontaneous circulation in the post-debriefing patients but there was no improvement in survival-to-discharge. Another method of performance assessment and improvement includes the use of real-time audiovisual feedback combined with debriefing. This approach is analyzed in a study by Dine and coauthors54 in Critical Care Medicine, 2008.
These authors compared debriefing alone with debriefing with real-time audiovisual
feedback in two groups of nurses undergoing training using a cardiopulmonary resuscitation simulator. The authors found that performance, evidenced by compliance with
recommendations for compression rate and excursion, improved with debriefing alone.
The addition of audiovisual feedback provided significant additional improvement.
Overall, twice as many participants provided optimum compressions after debriefing
with audiovisual feedback as with debriefing alone.
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Editorial comment
From the perspective of the editor, it seems clear that we have the capability to predict perioperative cardiac complications using global risk factors that overcome, at least
partially, the imprecision associated with the use of risk scoring systems that focus on
risk factors specific to the cardiovascular system. Once high-risk patients or patients at
moderate risk who are scheduled to undergo high-risk operations (open vascular reconstruction or thoracotomy) are identified, careful preoperative preparation using beta-blocking drugs (selective beta-1 receptor blocking drugs) will provide control of
heart rate and blood pressure in approximately 80% of this patient group. Preparation
will need to begin at least one month preoperatively. If patients have indications for
statin drugs based on lipid profiles or risk scores for cardiac disease (such as the Framingham score), statin drugs and low-dose aspirin are potentially useful additions. Ideally, these measures will have been implemented by the patient’s primary care physician.
Surgeons need to insure that there is no interruption of drug therapy during the perioperative interval.
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Perioperative myocardial infarction is a potentially lethal complication occurring as
a result of coronary artery plaque instability or rupture with coronary artery thrombosis. Prediction of which plaque will rupture is not possible currently. Because of this,
planning preoperative revascularization interventions based on identification of a “culprit” coronary stenosis does not reliably reduce risk of perioperative myocardial infarction. Indications for preoperative coronary imaging and revascularization are made
based on conventional indications, and these are undertaken in patients with “unstable”
ischemic diseases such as unstable angina, recent myocardial infarction, and cardiac
failure. The usual diagnostic clues for diagnosis of myocardial infarction (chest pain, Qwaves or ST segment elevation on electrocardiogram, and elevated troponin levels) lack
specificity in the patient who has recently undergone a surgical procedure. Clinical
signs of perioperative myocardial infarction might be vague and include intermittent
hypotension, changing mental status, new onset arrhythmia, and ST-segment depression on electrocardiographic tracings. Because of these facts, a low threshold for use of
serial troponin levels, continuous electrocardiographic monitoring, and echocardiographic imaging are necessary to make a prompt diagnosis.
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Perioperative tachycardia will occasionally require pharmacologic intervention or
even electrical cardioversion. Knowledge of the elements of diagnosis and emergency
treatment of these arrhythmias will be valuable. Even though surgeons will not normally be the lead caregiver for patients with cardiac failure, it is useful to understand the
pathophysiology of this condition so that factors that increase cardiac stress can be
minimized during the perioperative interval. Echocardiography is the most useful modality for quantification of the severity of cardiac failure.
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Finally, the features of successful resuscitation of patients who sustain out-ofhospital or in-hospital cardiac arrest are important components of the knowledge base
of surgeons. Resuscitation maneuvers such as chest compressions and ventilation maneuvers are frequently not performed in compliance with recommendations from national groups like the American Heart Association. It is important to recall that maneuvers to provide effective chest compression and optimum venous return to the heart
are critical features leading to successful resuscitation.
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Surgeons will be consulted to assist in the management of injuries sustained during
cardiopulmonary resuscitation. Injuries from cardiopulmonary resuscitation are relatively common; clinically significant injuries are discovered in 10%-15% of autopsied
patients. Injuries might be discovered in a larger proportion of survivors. Rib fracture
and/or costochondral separation are the most commonly diagnosed injuries. Pneumothorax, hemothorax, diaphragm injury, and lacerations of the liver and spleen are occasionally encountered.
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Perioperative respiratory complications
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Risk factors for respiratory complications
Respiratory complications after major surgical procedures might range from minor
complications like microatelectasis that can be cleared with coughing, deep breathing,
and early ambulation, to major, life threatening events such as postoperative respiratory failure. Risk of major respiratory failure requiring ventilatory intervention is increasing as the surgical patient population ages and the frequency of preexisting respiratory
diseases, such as obstructive sleep apnea, is increasingly recognized. The proinflammatory state stimulated by anesthesia, operation, and transfusion leads to acute
lung injury that often progresses to acute respiratory distress syndrome. In order to
minimize the negative impact of postoperative respiratory complications, surgeons require knowledge of the pathophysiology, effective preventive measures, features of diagnosis, and therapies available. These topics will be addressed in this section of the
overview.
Discussion of risk factors for development of postoperative respiratory complications and postoperative respiratory failure opens with a review of an article by Johnson
and coauthors55 entitled “Multivariable predictors of postoperative respiratory failure
after general and vascular surgery: results from the patient safety in surgery study.”
This article was published in the Journal of the American College of Surgeons in 2007
and a full-text reprint accompanies this issue of SRGS. This article is one part of a series
of reports detailing the results of the patient safety in surgery study that was the precursor of NSQIP. Another component of this series was cited previously in the overview
in the discussion of risk factors for postoperative cardiac events.
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These authors analyzed demographic and outcomes data from 128 Veterans Administration hospitals and 14 academic medical centers. Postoperative respiratory failure
was defined as the need for unplanned postoperative intubation and/or more than 48
hours of mechanical ventilation assistance postoperatively. In contrast to the previously
discussed analysis of postoperative cardiac complications where global risk factors
markedly reduced the impact of cardiac-specific risk factors, this analysis found that
postoperative respiratory failure was best predicted using a combination of global and
lung-specific risk factors. More than 180,000 patients were analyzed. Respiratory failure occurred in 3% of this group. Global risk factors such as higher ASA score, the need
for emergency operation, more complex procedures, preoperative sepsis, and signs of
renal insufficiency all predicted postoperative respiratory failure. Patients who developed postoperative respiratory failure tended to be male and older.
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Smoking, a diagnosis of chronic obstructive pulmonary disease (COPD), and a history of congestive heart failure were risk factors specific to the cardiopulmonary system
that also predicted postoperative respiratory failure. The authors developed a “respiratory risk index” by assigning points based on rounding of the calculated odds ratio for
respiratory failure determined from the risk analysis. For example, a calculated odds ratio of 1.25 would add one point to the respiratory risk index. Patients were then divided
into risk groups of low, medium, and high risk based on the calculated probability of
respiratory failure. The risk scoring system was validated in a separate sample drawn
from the database. The data disclose that respiratory risk index of eight or lower is associated with a 0.1% risk of respiratory failure. Risk index score of 8-12 is associated
with a 1% incidence of respiratory failure. For scores >12, overall risk is 7% but the risk
steadily increases with increasing risk score; a score of 25 predicts a frequency of respiratory failure of 40%.
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The authors use the discussion section of the article to confirm that respiratory failure is associated with more healthcare resource utilization than any other group of
postoperative complications. They further note that other analyses have identified similar arrays of risk factors, both global and lung specific, that predict postoperative respiratory failure. Not surprisingly, the risk of respiratory failure increases with a thoracic incision. After sternotomy or thoracotomy for cardiac procedures, the overall frequency of respiratory failure was 7% compared with 3% associated with general and
vascular procedures in the analysis presented by Johnson and colleagues.
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Obstructive sleep apnea is being diagnosed with increasing frequency. The presence
of this disorder in obese patients and patients with the “metabolic syndrome” of obesity, hypertension, and hyperglycemia is firmly established. The diagnosis of obstructive
sleep apnea is predictive of postoperative respiratory complications. The next article
reviewed investigates the possibility that preoperative testing for obstructive sleep ap43
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nea might identify patients at increased risk for episodes of postoperative hypoxemia.
The article is by Gali and coauthors56 and appeared in Anesthesiology, 2009. The authors
cite data indicating a substantial rate of underdiagnosis of obstructive sleep apnea.
They refer to 1993 reports (references 6 and 7 in their bibliography) that estimated
that 4% of men and 2% of women in the 30-60 year age group had obstructive sleep
apnea and that this condition was an independent risk factor for postoperative mortality.
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By the end of the 1990s, there had been a 12-fold increase in the diagnosis of obstructive sleep apnea. Later estimates have concluded that 82% of men and 93% of
women with obstructive sleep apnea remain undiagnosed. It is likely that many of these
individuals will require surgical care and that this group will be at increased risk for
perioperative respiratory complications. The authors describe the pathophysiology of
respiratory complications in patients with obstructive sleep apnea. The anatomic and
physiologic abnormalities of obstructive sleep apnea can be brought on by the diminished responses to hypoxia and hypercapnia as well as the diminished pharyngeal tone
produced by anesthetic and analgesic medications.
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In this report, the authors hypothesize that a preoperative risk assessment for obstructive sleep apnea applied in patients not known to have obstructive sleep apnea,
coupled with post-anesthesia monitoring for hypoxemic events, will identify patients at
risk and prevent complications. The preoperative assessment used consisted of obtaining a sleep apnea clinical score. This score assigns points based on responses to questions about the presence of hypertension and a history that patients had been told by
persons sharing their sleeping area that they snore. For this question, 1 point is assigned for snoring 3-5 times/week or for snoring every night. The patients are also
asked whether they have been told that they gasp, choke, or snort while sleeping. The
point assignments are based on frequency of symptoms.
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The final assessment is a measurement of neck circumference. Points are assigned
for various neck circumferences with hypertension, historic features, or both. A score of
>15 indicates a high likelihood of obstructive sleep apnea. Postoperative monitoring of
patients enrolled in this study included continuous oxygen saturation monitoring, and
monitoring for apnea, bradypnea, and pain level/sedation mismatch. The last assessment is accomplished when a patient indicates severe pain on a visual-analog scale but
appears too sedated to receive additional analgesia.
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In all, 673 patients were enrolled. Sleep apnea scores of > 15 predicted episodes of
desaturation and recurrent potential hypoxemic events in the post-anesthesia care area. The combination of a high sleep apnea score and post-anesthesia area hypoxemic
events predicted postoperative respiratory complications. A high sleep apnea clinical
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score was recorded in nearly 32% of this patient group. This patient group had higher
ASA scores also. Patients with high clinical scores and recurrent hypoxemic events in
the post-anesthesia care area had a frequency of diagnosed postoperative respiratory
complications of 33%. Patients with low scores and recurrent post-anesthesia events
had a frequency of postoperative respiratory complications of 11%. Patients with low
scores and no events developed postoperative respiratory complications in less than
1% of patients. The authors note that the gold standard for diagnosis of obstructive
sleep apnea is polysomnography.
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Validation of the sleep apnea clinical score with comparisons to other scores and
polysomnography are found in two articles57-58 conducted in 1994 and 2003 confirming
that the sleep apnea clinical score has a positive predictive value for an accurate diagnosis of obstructive sleep apnea of more than 80% compared with polysomnography. A
limitation of the study authored by Gali and associates is that polysomnography was not
used to validate the findings reported. Nonetheless, the data suggest that obstructive
sleep apnea might be underdiagnosed. Furthermore, sleep apnea clinical scores of > 15
are, when combined with assessments performed in the post-anesthesia care area, predictive of postoperative respiratory complications. Finally, this straightforward assessment can be used to identify patients at risk.
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Because obstructive sleep apnea is a common condition accompanying morbid obesity, identification of patients with this condition who are scheduled to undergo bariatric procedures could lead to preventive interventions, reduction of risk for postoperative pulmonary failure, and lower consumption of healthcare resources. An article dealing with this topic by Hallowell and coauthors 59 appeared in Surgery, 2007. This analysis compares the need for ICU admission for respiratory complications in a group of 318
morbidly obese patients undergoing bariatric procedures. Polysomnography for diagnosis of obstructive sleep apnea was performed in all the patients. The frequency of ICU
admission in this group was compared with a historic control group. In the control
group, obstructive sleep apnea assessment using polysomnography was used based on
clinical suspicion and/or surgeon preference.
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After implementation of routine polysomnography, ICU admission for respiratory
complications decreased from 5% to less than 1%. The authors note other changes in
their practice that occurred simultaneously. They note an increasing use of laparoscopic
gastric bypass in the second group. They also note that the rate of ICU admission for any
reason was already declining in their practice. In spite of these limitations, the analysis
does disclose a significant risk for undiagnosed obstructive sleep apnea in morbidly
obese patients. Improving the rate of diagnosis of obstructive sleep apnea in this patient
group could create an opportunity for implementing preventive measures to reduce
perioperative respiratory complications.
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In the discussion section of the article, Hallowell and colleagues review the changes
occurring because of increasing body weight that contribute to respiratory complications. These include upward displacement of the diaphragm, increased chest wall mass
leading to decreased chest wall compliance, and increased pulmonary vascular resistance resulting from chronically expanded blood volume. These authors also stress
that obstructive sleep apnea might be occult in this patient group. The use of preoperative and postoperative noninvasive ventilation with continuous positive airway pressure is one effective preventive measure. The authors note that concerns over application of continuous positive airway pressure in a patient with a newly constructed gastrojejunostomy seem unfounded. They cite data from clinical reviews documenting no
increase in anastomotic leak rates in patients who used continuous positive airway
pressure devices. They conclude by reviewing the costs of the measures they used to
prevent respiratory complications leading to ICU admission. They note that ICU admission for two days would add more than $12,000 of hospital costs in their institution.
Polysomnography and perioperative continuous positive airway pressure add less than
$3000 of additional cost.
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Editorial comment
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Prevention of respiratory complications
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Preoperative maneuvers
From the perspective of the editor, it seems that easily obtained information from
the history and physical examination could identify patients for use of polysomnography and/or preventive continuous positive airway pressure. Information on a history of
hypertension, snoring, obesity, and neck circumference > 17 inches would provide a basis for further evaluation.
Patients having the constellation of risk factors discussed above are candidates for
preventive strategies to reduce risk of respiratory complications. Multivariable risk
studies have identified systemic risk factors such as elevated ASA score, smoking, obesity, older age, and need for complex operation as significant predictors of postoperative
respiratory complications. Congestive heart failure and COPD are patient-specific factors potentially modifiable. It is well recognized that smoking cessation and measures
to stabilize cardiovascular disease require two months or more of preoperative effort
for a meaningful impact on complication risk to occur. Lung specific interventions such
as treatment of lung infection, sputum reduction measures, use of bronchodilators, and
preoperative respiratory muscle training have potential value. These topics will be discussed in the following section of the overview.
The first article reviewed here is by Gore60 in Gerontology, 2007. The article is entitled “Preoperative maneuvers to avert postoperative respiratory failure in elderly patients.” The author opens the review by emphasizing the clinical importance of abnor46
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mal postoperative ventilation, hypoxemia, and hypercarbia. These lead to the need for
intubation and mechanical ventilator support. Dysfunctional ventilation leading to intubation greatly increases the risk of ventilator-associated pneumonia associated with a
mortality risk exceeding 50% (see discussion in SRGS, Vol. 35, No. 7). Mortality rates for
ventilator-associated pneumonia have not changed in many years. This consistent observation supports the importance of preventive strategies to reduce the need for intubation in this patient group.
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Particular problems that might predispose elderly patients to perioperative respiratory complications include 1) a gradual decline in one-second forced expiratory volume
(FEV1) with advancing age; 2) increased ventilation/perfusion mismatching caused by
increased early airway closure in dependent lung units; and 3) depressed responses to
hypoxemia and hypercarbia. Gore cites data that document decreased FEV1 as an accurate predictor of postoperative respiratory complications, especially in patients with
COPD. Ventilation/perfusion mismatching causes an age-related decline in resting arterial oxygen tension. Furthermore, older patients develop blunted responses to hypoxemia and hypercarbia and are vulnerable to analgesic and sedative-induced respiratory
depression. Age-related decreases in mucociliary function reduce clearance of bacteria
from the airway and contribute to increases in risk for perioperative pneumonia. This
abnormality is particularly pronounced in smokers.
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Preoperative evaluation can include easily obtained data from the history and physical examination that can guide subsequent preventive efforts. In addition to obstructive sleep apnea screening (discussed above) a history of smoking, reactive airway disease, allergy, cough, and excessive sputum production can be obtained. The degree of
chronic cough can be ascertained using a “cough test.” The patient is asked to cough. If
the cough results in production of sputum or repeated coughing, additional testing
(such as quantification of FEV1) might be helpful. If excessive sputum production is
documented, a sputum culture is obtained. Recovery of a pathogen such as H. influenza,
S. Pneumoniae, or MRSA can prompt a short course of preemptive antibiotics. Additional
interventions that can strengthen cough and reduce sputum production include postural drainage, assisted cough, and deep breathing exercises.
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Inhaled bronchodilators are indicated preoperatively in patients with reactive airway disease and in patients with chronic bronchitis. Data cited by Gore suggest that
ipratropium bromide (Atrovent®) is a useful first-line inhalant. Aminophylline has also
been used for this purpose but data cited by Gore suggest that the association of this
drug with tachycardia limits its use in elderly surgical patients. In patients with documented COPD, preoperative corticosteroid therapy might be useful. Effectiveness of
steroid therapy is monitored with sequential assessments of FEV1. If this variable improves with steroid therapy, preoperative and postoperative therapy is valuable. Gore
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stresses that, overall, fewer than one-third of COPD patients will have significant responses to corticosteroids although degrees of improvement in some patients are substantial. Gore emphasizes the importance of continuing preoperative therapy into the
postoperative recovery period.
Postoperative maneuvers
Time-honored patient care processes for minimizing postoperative pulmonary
complications include early ambulation, encouraging cough, elevation of the head of the
bed, and judicious use of analgesics and sedatives. These interventions are valuable for
preventing atelectasis and maintaining lung inflation. One device used for maintenance
of lung inflation is the incentive spirometer. Use of this device is the topic of an article
by Westwood and coauthors61 in Surgeon, 2007. These authors analyzed data from 263
patients; the study was not randomized. One group of patients had intensive chest
physiotherapy supported by a physiotherapist visit at least once daily during the postoperative hospitalization. The other group had similar physiotherapy with the addition
of the incentive spirometer. Respiratory complications were defined as new fever >
38°C, signs of atelectasis or infiltrate on chest radiograph, and/or institution of antimicrobial therapy for suspected pulmonary infection. Both patient groups consisted of elderly patients (mean age 68 years); more than half of each group had a history of smoking and both groups underwent high-risk abdominal or noncardiac thoracic operations.
Respiratory complications, according to the authors’ definition, occurred in 17% of controls and 6% of patients using the incentive spirometer.
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The Westwood article and the article authored by Gore60 review data from other
studies relevant to the use of the incentive spirometer. Of the available studies, half
show benefit from use of the device and half show no favorable effect on postoperative
respiratory complications. The available studies vary in the application of other approaches such as intensive chest physiotherapy. The main complication of incentive
spirometer use is gastric dilatation, which has been reported several times.
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Westwood’s study reports no instances of this complication. It is difficult to ascribe
a consistent clinical benefit to incentive spirometer use as an isolated intervention. Significant benefit for the device when it is added to dedicated chest physical therapy
might be associated with the fact that a well-trained patient can use the device during
the intervals between physical therapist visits.
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A randomized trial evaluating intensive inspiratory muscle training under the supervision of a physical therapist as a means of reducing perioperative respiratory complications by Dronkers and coauthors62 appeared in Clinical Rehabilitation, 2008. In this
study, 20 patients undergoing open abdominal aortic aneurysm repair were randomized to receive intensive inspiratory muscle training (one physical therapist supervised
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session and five unsupervised sessions/week for two weeks prior to operation). This
group was compared with a control group receiving instruction in deep breathing and
incentive spirometer use. The primary endpoint of this study was detection of atelectasis on chest radiograph. The analysis disclosed a nonsignificant trend toward less atelectasis in the group that received intensive inspiratory muscle training. Maximum inspiratory force increased by 10% in the intervention group. Patient satisfaction with
the intervention was high. The authors acknowledge the need for additional studies involving larger patient groups.
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A meta-analysis of available data from studies evaluating prophylactic respiratory
physical therapy by Pasquina and coauthors63 from Chest, 2006, evaluated 35 trials that
provided data on the possible value of respiratory physical therapy as a means of preventing perioperative respiratory complications. Significant differences in postoperative respiratory events were reported in only four studies that included a “no intervention” control group. In some studies differences occurred in the frequency of atelectasis
(usually defined as a change on chest radiograph). Most studies did not focus on important complications such as pneumonia, need for intubation, or ventilator support.
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In the single study analyzing effects of respiratory physical therapy on the frequency
of pneumonia, a significant reduction was recorded but the frequency of pneumonia in
the control group was higher than baseline rates for this complication recorded in other
clinical series. This fact limits the external validity of this study. Unspecified respiratory
complications were reduced in one analysis. These authors concluded that routine use
of physiotherapy is not indicated in low and moderate risk patients undergoing abdominal operations. There were no reports of adverse events associated with the use of
physical therapy. Readers will recall that we noted earlier reports of gastric distention
associated with the use of the incentive spirometer but few of the studies supporting
use of this device report occurrences of gastric distention. Failure to consider potential
harm from an intervention weakens data supporting use of the intervention.
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Gore60 concludes his article with a discussion of nutritional support and cessation of
alcohol use as a means of preventing perioperative respiratory complications. He notes
that use of supplemental parenteral nutrition as a means of improving nutrition has
been limited by the known complications of this intervention (hyperglycemia, liver dysfunction), its cost, and the need for central venous access. Use of this intervention is unusual except in patients who have lost more than 5% of ideal body weight or patients
who were profoundly hypoalbuminemic from nutritional impairment. Use of preoperative enteral nutrition is also unusual because of the need for enteral access and limited
patient tolerance. Enteral access should be acquired in patients undergoing high-risk
abdominal procedures where preoperative weight loss and/or hypoalbuminemia suggest nutritional deficit. Although there are data indicating value of human growth hor49
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mone therapy in managing burn patients (especially burned children), Gore stresses
that there are no high-quality data supporting use of this agent to reduce perioperative
respiratory complications.
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Gore concludes his article by emphasizing the importance of cessation of alcohol use
by heavy drinkers before a major operation. This will require careful counseling of each
individual patient. Abstinence from alcohol use, even for short intervals before operation might be valuable. Acute cessation of alcohol use might precipitate clinical alcohol
withdrawal syndrome, which carries its own risk of mortality. This eventuality should
be avoided to the extent possible.
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Editorial comment
In the section of the overview, we have discussed preoperative and postoperative
maneuvers that might be helpful for prevention of respiratory complications. Interpretation of the available data is challenging because of the variable definitions of respiratory complications and the small patient groups that make up most of the available
studies. Most patients undergoing abdominal or thoracic operations should have early
ambulation, elevation of the head of the bed, brief training in coughing and deep breathing, and careful pain control. Interventions such as preoperative antibiotics, inhaled
bronchodilators, continuous positive airway pressure breathing, and corticosteroids
should be applied in carefully selected patients.
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The most consistent marker for postoperative respiratory complications is the need
for intubation in the postoperative period. Analyses of this event in two recent
studies64-65 indicated that intubation in the post-anesthesia care unit is closely related
to the presence of residual neuromuscular blockade. Careful tracking and recording of
the level of neuromuscular blockade effectively prevented early, unplanned intubations.
In populations of postoperative general surgery patients, unplanned intubation is an
event associated mainly with nonmodifiable events such as chronic disorders of consciousness, severe cardiovascular and/or pulmonary disease, and the development of
postoperative sepsis.
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Data indicate that the overall incidence of unplanned postoperative intubation is
low (less than 3%) but the event carries a mortality risk in excess of 40%. Current preventive interventions such as emergency response teams have had limited impact on
the frequency and mortality risk of this complication. Most unplanned postoperative intubations occur in patients who are already in the ICU. Prevention of unplanned intubation seems to be most useful for patients in the post-anesthesia care unit. Recognition of
risk factors such as severe cardiopulmonary disease and chronic depressed level of
consciousness might help identify patients at increased risk for postoperative unplanned intubation.
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Noninvasive ventilation for postoperative respiratory complications
Increasing recognition that the morbidity of postoperative respiratory failure is
driven, at least in part, by complications of intubation and mechanical ventilation (especially ventilator-associated pneumonia) has stimulated efforts to use nonintubation
interventions for early treatment of this complication. The first article reviewed that
deals with this topic is by Michelet and coauthors66 from the British Journal of Surgery,
2009. This article is supplied as a full-text reprint with this issue of SRGS. The authors
note that respiratory failure and anastomotic leak are linked complications in patients
undergoing esophagectomy. Anastomotic leak occurs when ischemia or diminished oxygen delivery to the anastomotic area occurs. Thus, hypoxia, which might accompany
the onset of postoperative respiratory failure, can contribute to the risk of anastomotic
leak.
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The reported study is a case-control design study in which a group of patients treated with postoperative noninvasive ventilation was compared with a group of patients
who did not receive this intervention. In all other aspects, the patient groups were
comparable. Thirty-six patients comprised each study group. Acute respiratory failure
was characterized by dyspnea and use of accessory muscles of ventilation, new infiltrates visible on chest radiograph, purulent sputum, fever, and hypoxemia (Pa02/FI02
ratio of < 200). Noninvasive ventilation was delivered with a face mask and a ventilator.
Continuous positive airway pressure and positive end-expiratory pressure were used
and pressures incrementally increased until tidal volume reached a level of 6 mL/kg estimated ideal body weight and arterial oxygen saturation exceeded 90%. Maximum inspiratory pressure was maintained below 25 cm H20. Episodes of noninvasive ventilation were interspersed with 45-60 minute intervals without assisted ventilation.
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Nine of 36 patients in the noninvasive ventilation group eventually required endotracheal intubation, but only one of these because of intolerance of the mask. In comparison, 19/36 patients in the control group required intubation. This very low incidence of mask intolerance contrasts with data from a report by Conti and coauthors67
that describes a comparison between a mask and a helmet interface for delivery of noninvasive ventilation. In this study, the patients treated with the helmet device were
compared with historic control patients treated with mask ventilation. Diagnostic criteria for postoperative acute respiratory failure used by Conti and colleagues were similar to the criteria used by Michelet and associates. Twenty percent of the helmet patients and 48% of the mask patients required intubation and the main reason was intolerance of the noninvasive intervention.
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Both studies indicate that noninvasive ventilation can effectively improve oxygenation and prevent the need for intubation in many patients. Overall, 20%-50% of patients in whom noninvasive ventilation is attempted will fail and failure is often times
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because the patient cannot tolerate the device. Careful patient selection and availability
of close bedside supervision of the ventilation might reduce this risk, but at significant
added cost in terms of respiratory therapist and nursing time. In general, patients selected for noninvasive ventilation should have normal sensorium and not have severe
dyspnea or difficulty managing secretions. If these criteria can be met, this intervention
is often effective as a means of supporting oxygenation and avoiding intubation.
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The use of noninvasive ventilation in patients with more severe forms of respiratory
failure is controversial. The main benefit of this approach would be to avoid intubation
with the attendant reduction in risk of ventilator-induced lung injury and ventilatorassociated pneumonia. This subject is the focus of two articles reviewed at this time.
The first is by Antonelli and coauthors68 in Critical Care Medicine, 2007. The authors cite
data from other studies indicating the possibility that intubation rates for patients with
early acute respiratory distress syndrome might be reduced by as much as 50% with
use of noninvasive ventilation. This report deals with 147 patients admitted to two
ICUs. The authors note that both units have extensive experience in the use of noninvasive ventilation. The patients were diagnosed with acute respiratory distress syndrome
using standard criteria. Noninvasive ventilation was supplied using a mask or a helmet
device. Continuous positive airway pressure and positive end-expiratory pressure were
gradually increased in increments until exhaled volumes reached 6 mL/kg, respiratory
rate was < 25 breaths/min, and oxygen saturation was consistently >90%. Failure to
achieve these goals and/or failure of the patient to tolerate noninvasive ventilation defined failure of noninvasive ventilation.
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The authors achieved success avoiding intubation in 54% of the patients enrolled in
this study. They noted predictors of failure of noninvasive ventilation as higher severity
of illness scores, older age, requirement for PEEP > 12 cm H20, and failure to improve
oxygenation after one hour of noninvasive ventilation. Patients who required intubation
were more likely to have severe sepsis or septic shock and a mortality rate of 54% was
recorded in the group requiring intubation. Only 12% of patients could not tolerate
noninvasive ventilation. It is likely that the extensive experience of these clinicians with
noninvasive ventilation contributed to this level of success.
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Contrasting data are presented in an article by Rana and coauthors69 in Critical Care,
2006, entitled “Failure of noninvasive ventilation in patients with acute lung injury: observational cohort study.” This report presents data on 54 patients who had noninvasive ventilation attempted as the first intervention for respiratory distress requiring
admission to the ICU. The patients were severely ill with sepsis diagnosed in 88% of patients. Septic shock was present in 19 of the 54 patients. Data on Pa02/Fi02 ratios disclose that this patient group met criteria for acute respiratory distress syndrome rather
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than acute lung injury in essentially all patients. This was, thus, a high-risk cohort of patients. The authors observed failure of noninvasive ventilation in 70% of patients.
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The presence of shock, acidosis, and severe hypoxemia were predictive of failure of
noninvasive ventilation. The higher failure rate in this series serves to emphasize the
importance of patient selection. Severely ill patients, especially those with severe hypoxemia and hemodynamic instability, are at increased risk for failure of noninvasive
ventilation. These findings are similar to those of Antonelli and coauthors68 discussed
above. Because concerns have been raised about possible harmful effects of delaying intubation in patients who are at high risk of progressing to severe acute respiratory distress syndrome, candidates for noninvasive ventilation should be carefully selected.
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Acute lung injury and acute respiratory distress syndrome
Acute lung injury is a term applied to a complex response of the lung to systemic
and localized inflammatory stimuli. A multitude of injuring agents, acting singly or in
combination, can produce the histologic, radiologic, and clinical manifestations of acute
lung injury. These agents might act by direct injury to the lung tissue (pulmonary contusion, pulmonary blast injury) or to the airway (aspiration, inhalation injury). In other
instances, the inflammatory process begins with a remote stimulus (peritonitis, pancreatitis, sepsis, combined traumatic injury, shock, and resuscitation) and the lung is injured because of circulating factors that act directly on the lung microcirculation and/or
lung tissue or through activation of inflammatory mediators within the lung microcirculation. Pneumonia can trigger the development of acute lung injury in adjacent noninfected lung through propagation of the inflammatory process.
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Patients can recover from acute lung injury or might progress to acute respiratory
distress syndrome, a clinical entity that is manifest by hypoxemia from ventilation/perfusion mismatching, loss of lung compliance because of alveolar flooding and
consolidation of lung tissue, and increased dead space ventilation resulting from pulmonary microvascular occlusion. There is no specific therapy for acute lung injury.
Support of ventilation and oxygenation using adjuvant ventilation therapies can assist
the lungs in the effort to maintain oxygen transfer from alveolus to blood but these
therapies have no positive effect on the severity or clinical course of acute respiratory
distress syndrome. In fact, as clinicians have learned over the past decade, adjuvant
ventilator therapy can produce additional injury in the lung through effects of pressure,
volume, cycling of ventilation, and promotion of the inflammatory process.
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In this section of the overview, we discuss important clinical features of the pathophysiology, diagnosis, and management of acute lung injury and acute respiratory distress syndrome. Entire volumes have been written on these topics and, because of the
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vastness of the information available, this review will not be comprehensive; the review
will focus on clinically valid understandings and effective interventions.
Pathophysiology
Biomarkers of inflammation, altered coagulation, fibrinolysis, and increased oxidative stress are activated, elevated, or suppressed to varying degrees and with different
trajectories in all inflammation-mediated diseases including acute lung injury. Proinflammatory cytokines can be recovered from blood and from alveolar fluid in animals
and patients with acute lung injury and adult respiratory distress syndrome. Elevations
of some biomarkers such as interleukin-6 (IL-6), interleukin-8 (IL-8), and intercellular
adhesion molecule-1 (ICAM-1) are associated with poorer clinical outcomes for acute
lung injury. This is also true for coagulation factors. Lower levels of Protein C and elevations of thrombomodulin indicate a pro-coagulant state; this pattern is associated with
poor outcomes. Finally, impaired fibrinolysis is indicated by elevations of plasminogen
activator inhibitor-1 (PAI-1) and elevated levels of this substance have been associated
with poor outcomes of acute lung injury and acute respiratory distress syndrome.
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Recent changes in clinical approaches to acute respiratory distress syndrome include the use of low tidal volume (6 mL/kg), low mean airway pressures (25 cm H20),
positive end expiratory pressure (12 cm H20), and permissive hypercapnia as clinicians
attempt to minimize inflammatory stimuli and reduce the impact of ventilatorassociated lung injury. This approach is termed “open-lung” ventilation or “lungprotective” ventilation. There are data suggesting that “open-lung” ventilation reduces
inflammatory mediators and the reduction is associated with improved clinical outcomes. The first article discussed in this section analyzes the effect of open lung ventilation on inflammatory mediators and seeks to explore the question whether patterns of
inflammatory mediator levels remain predictive of outcomes in the era of “open-lung”
ventilation. The article by McClintock and coauthors70 appeared in Critical Care, 2008.
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The authors collected ventilator data and serum levels of biomarkers in 50 patients
with acute respiratory distress syndrome. The causes of acute respiratory distress syndrome varied and included most of the common causes; no single cause predominated.
The ventilator data confirmed that patients were treated with the “open-lung” approach. Serum biomarker patterns were significantly different in survivors and nonsurvivors. After adjustment for various risk factors, elevated levels of ICAM-1 and IL-8, and
depressed levels of Protein C were predictive of mortality. The authors concluded that
patterns of biomarker activation are predictive of outcomes and this predictive value
has not been eliminated by “open-lung” ventilation strategies. In the discussion section
of this report, lower levels of Protein C were predictive of mortality even when the data
were adjusted for the frequency of sepsis as the cause of acute respiratory distress syndrome. This observation suggests that Protein C administration might favorably affect
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recovery in some patients with acute respiratory distress syndrome. It is disappointing
that recent data have not shown a benefit for administration of Protein C in patients
with acute respiratory distress syndrome.
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Burn induced lung injury combined with inhalation injury is a prototypical example
of combined lung parenchyma and airway injury. The features of combined
burn/inhalation injury are discussed in an article by Enkhbaatar and Traber71 in Clinical Science, 2004. The article is supplied as a full-text reprint accompanying this issue of
SRGS. The authors begin by noting that inflammation induced increases in microcirculatory permeability characterizes burn injuries that exceed 30% of the body surface area.
This hyperpermeability affects the microcirculation at the burn site and in tissues remote from the site of the burn injury. The result is a large flux of fluid and protein from
the intravascular to the interstitial space with edema formation in the area of the burn
and in all tissues. Inhalation injury alone and combined burn and inhalation injury
cause increased pulmonary microcirculatory permeability. Pulmonary edema occurs
not only because of flux of protein and fluid from the pulmonary circulation but also because of enormous increases in blood flow to the tracheal-bronchial tree. Anatomic
connections between the bronchial arteries and the pulmonary circulation deliver a
portion of this increased blood flow to the pulmonary circulation and this contributes to
pulmonary edema formation. In animal experiments these investigators noted that occlusion of the bronchial-pulmonary connecting channels in a smoke inhalation model
greatly reduces pulmonary edema and improves lung function after inhalation injury.
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In burn-induced acute lung injury, there is also a strong pro-inflammatory state. Nitric oxide and metabolites of this substance play major roles in the inflammationinduced lung injury caused by burn. The authors have shown in experimental preparations that there is upregulation of nitric oxide production. Stable plasma metabolites of
nitric oxide increase 2-2.5 fold after burn injury.
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Nitric oxide exists in three forms, neuronal nitric oxide (nNOS), endothelial nitric
oxide (eNOS), and inducible nitric oxide (iNOS); nNOS and eNOS are constitutive
isoforms and iNOS is induced by multiple components of the pro-inflammatory state.
These authors note that the pro-inflammatory factors IL-1 and endotoxin activate nuclear factor κ-B. This factor is a potent stimulus for production of iNOS. This same activation pathway leads to increased production of superoxide that contributes to the oxidative stress characteristic of the pro-inflammatory state. Elevated levels of iNOS also
contribute to the oxidative stress by combining with superoxide to produce peroxynitrite, which can damage the alveolar capillary membrane. When stores of arginine are
depleted, iNOS produces superoxide, which can cause tissue damage.
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The authors note that experimental studies have demonstrated arginine depletion
in combined inhalation/burn injury with pulmonary dysfunction. The vasodilating
properties of iNOS contribute to one of the most important features of acute lung injury,
ventilation/perfusion mismatching. Hypoxic vasoconstriction, the protective reaction
that redistributes blood from underventilated alveoli to ventilated alveoli, cannot function in a high iNOS environment. In acute lung injury, underventilated alveoli have sustained perfusion leading to delivery of unoxygenated blood to the pulmonary veins. The
finding of hypoxemia and an abnormal alveolar-arterial gradient in patients with acute
lung injury can be explained by the failure of the hypoxic vasoconstriction. Data from
the authors’ laboratory have shown improved lung function when animals are pretreated with an iNOS inhibitor.
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Enkhbaatar and Traber caution that iNOS is a component of the complex defense
against inflammation and a contributor to the pathophysiology of acute lung injury. Because of this, inhibition of iNOS has not produced improved outcomes in clinical studies
of pro-inflammatory states such as septic shock. Specific inhibitors of one or another of
the NOS isoforms might produce better outcomes. The authors note data from animal
experiments showing improved lung function in acute lung injury treated with a specific nNOS inhibitor or with the anti-inflammatory agent, ketorolac.
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Another factor activated by inflammation with resultant cell damage and death is
poly-(ADP-ribose)-polymerase or PARP. This substance is activated in cells in response
to DNA damage and this factor is active in DNA repair processes. Over activation results
in depletion of cellular energy stores that can lead to necrotic cell death. PARP is an important contributor to endotoxin-induced lung inflammation and inhibition of PARP can
preserve ATP levels in the lung after acute lung injury according to data cited in the report by Enkhbaatar and Traber.
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Combined inhalation and burn injury results in small airway obstruction because of
leakage of exudate rich in neutrophils and products of coagulation, such as fibrin, into
the airway lumen. Airway obstruction results in increasing dead space ventilation and
contributing to the pathophysiology of acute lung injury. Experimental data from studies completed by these authors demonstrate that this process can be reversed, partially
by using nebulized tissue plasminogen activator.
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The complex pathophysiology of acute lung injury is produced by inflammatory injury to the lung microcirculation, the alveolar capillary interface, and the airways. Each
component is present, to varying degrees, depending on the agent producing the inflammatory state and the resulting lung injury. Transfusion of banked blood is one
cause of acute lung injury. This topic is reviewed by Swanson and coauthors72 in Lung,
2006. Trauma and critical care surgeons have consistently observed an association be56
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tween massive transfusion and post-trauma acute respiratory distress syndrome. That
single transfusions of blood products (except albumin) can cause lung injury and respiratory distress acutely was first recognized in 1951. Characterization of transfusion
related lung injury as a transfusion reaction resulted from studies demonstrating antileucocyte antibodies in patients with acute lung injury closely following transfusion.
The term transfusion related lung injury (TRALI) was first coined in a 1983 report cited
by Swanson and coauthors.
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The TRALI clinical syndrome affects approximately 0.2% of patients who receive
transfusions. Eight percent of transfusion reactions result in lung injury and this entity
is the cause of 13% of transfusion-related fatalities. Overall mortality for a TRALI episode is 5%-10%. Respiratory distress usually develops within six hours of transfusion.
The clinical picture is typical of acute lung injury and consists of hypoxemia, tachypnea,
and pulmonary infiltrates on chest radiograph. Supplemental oxygen is required in all
patients and nearly three-quarters of the symptomatic patients will require intubation
and ventilator support. The typical TRALI episode will resolve with supportive care in
48-96 hours.
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A definitive clinical diagnosis requires exclusion of other causes of acute lung injury.
Most patients who require blood product transfusions are significantly injured or ill and
exclusion of other causes for acute lung injury might not be possible. Recovery of antiHLA and/or anti-leucocyte antibodies from donor blood supports a diagnosis of TRALI,
especially if the recipient is shown to have a leucocyte antigen phenotype matching the
antibody recovered from donor blood. Culprit antibodies are found in up to 90% of donor blood samples when a TRALI episode occurs. Despite this observation, TRALI episodes occur without demonstrable immune reaction. The observation that older banked
blood is more likely to cause TRALI has led to the development of nonimmune models
of TRALI. These involve factors that prime neutrophils and are present in increased
concentrations in older banked blood. The specific factor or factors responsible are not
known but plasma from recipients who develop TRALI contains increased concentrations of neutrophil-priming substances. Histopathology of the lung shows pronounced
leucocyte sequestration in the lung. It is likely that lung damage is caused by oxygen
free radicals induced by the sequestered leucocytes.
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Therapy for TRALI is mainly focused on support of oxygenation until the process resolves. Prevention of TRALI is challenging. Rejection of blood donation by donors implicated in a TRALI episode is one avenue. Probably the most effective approach will be to
adopt conservative transfusion protocols so that banked blood transfusion is reduced,
overall.
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Epidemiology and outcomes of acute lung injury and acute respiratory distress syndrome
Two older articles are discussed in this section to provide perspective about morbidity and mortality associated with acute lung injury and acute respiratory distress
syndrome. Prognostic factors will also be discussed. The first article discussed is by
Luhr and coauthors73 from the American Journal of Respiratory and Critical Care Medicine, 1999. These authors begin by citing several reports that document mortality rates
for acute respiratory failure and acute respiratory distress syndrome ranging from
40%-50%. They note, also, that several reports have suggested that mortality for acute
respiratory distress syndrome might be decreasing. Interpretation of data is challenging because of the variability of clinical definitions used in the reported studies. The aim
is this analysis was to perform a prospective cohort study involving patients aged 15
years and older admitted to ICUs in Sweden, Denmark, and Iceland during an eightweek interval.
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Acute respiratory failure was defined as endotracheal intubation followed by 24
hours or more of ventilator support. Acute lung injury and acute respiratory distress
syndrome were defined according to criteria promulgated by the American-European
Consensus Conference on ARDS. The consensus conference definition includes the following criteria 1) acute symptom onset; 2) Pa02/FI02 ratio of < 300 for acute lung injury and < 200 for acute respiratory distress syndrome; 3) bilateral infiltrates on chest
radiograph; and 4) pulmonary artery occlusion pressure < 18 mmHg or no clinical evidence of left atrial hypertension. Each patient was enrolled at the time of the first admission to the ICU and this admission was the only incident of respiratory distress
counted in the study. The study included 1231 patients who fulfilled criteria of acute
respiratory failure. Of this group 287 patients fulfilled criteria for acute lung injury and
221 fulfilled criteria for acute respiratory distress syndrome. Mortality for the total
group was 41%. Mortality rates for acute lung injury (42.2%) and acute respiratory distress syndrome (41.2%) were nearly identical to the total group mortality. The question
of whether these patients died from the respiratory disease or died with the respiratory
disease remains unanswered by these data.
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The authors note that the close agreement of death rates for all three clinical diagnoses suggests that death from refractory hypoxemia might be less common than death
from a condition associated with or, perhaps, precipitating hypoxemia. Luhr and associates were able to demonstrate significant mortality prediction from the presence of liver disease, advanced age, and a nonpulmonary cause of respiratory dysfunction. These
factors also suggest that death might not have occurred solely because of respiratory
insufficiency. Additional perspective on this issue appears in an article by Rocco and coauthors74 in Annals of Surgery, 2001. These authors conducted a retrospective, single
institution review analyzing mortality and prognostic factors in 980 consecutive patients who were intubated and who received ventilator support in the ICU. Among these
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were 111 patients who fulfilled the American-European Consensus Conference on
ARDS criteria for acute respiratory distress syndrome (see discussion above).
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Lung injury scores were calculated for each patient. The lung injury score assigns
points for assessments of the chest radiograph, degree of hypoxemia, level of PEEP, and
lung compliance. A score of 2.5 or more is indicative of acute respiratory distress syndrome. Lung injury scores were > 2.5 in all 111 patients. Patients were divided into
subgroups depending on whether the patient was a “surgical” patient or a “trauma” patient. Patients were also divided into a group of patients admitted between January 1,
1990, and December 31, 1994, and those admitted between January 1, 1995, and December 31, 1998. The data indicate that surgical patients were older and more likely to
have respiratory failure related to intraabdominal infection. Trauma patients were
more likely to have respiratory failure related to multiple injuries and/or direct thoracic injury. Mortality rates declined in both periods but the magnitude of decline was statistically significant for trauma patients only.
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In the second interval, overall mortality for acute respiratory distress syndrome declined from 72% to 38% and this decline was statistically significant. The authors emphasize that the decline in mortality occurred even though the patients in the second interval were older. One characteristic of the more recent group was that emergency operation frequency declined. A decrease in emergency operations was probably associated with a lower risk for intraabdominal infection, which was the most common cause of
fatal acute respiratory distress syndrome. The authors also point out that they used
lower tidal volumes and lower mean airway pressures as ventilator strategies in the
later group. The authors note that advanced age and comorbid illness (particularly liver
disease) were strongly predictive of mortality.
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Editorial comment
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Ventilator strategies
The data discussed above document the correlation between age, increasing illness
severity, infection, and acute respiratory distress syndrome. The role of inflammation in
the genesis of acute lung injury and as a driver of progression to acute respiratory distress syndrome is confirmed in the clinical series. Younger patients with direct lung injury (trauma patients) are more likely, as a group, to survive. Ventilator strategies
might also play a role in producing the improved outcomes observed in the article by
Rocco and colleagues.74 The current approaches to ventilator support for patients with
acute lung injury and acute respiratory distress syndrome is discussed in more detail in
the next section.
The approach to ventilator therapy for patients with acute lung injury and acute
respiratory distress syndrome has changed in one major and several minor ways over
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the past three to five years. Traditionally the approach to ventilation has been designed
to maintain oxygenation and carbon dioxide removal. An understanding of the basic
mechanisms of acute respiratory failure (many of these discussed above) has improved
understanding. Most importantly, surgeons are now aware of the potential patient
harm that might accompany ventilator therapy. The effects of ventilator pressures and
volumes on hemodynamics have been well recognized for many years.
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More recently, a group of phenomena has been recognized known as ventilatorinduced lung injury. Included in this category are barotrauma (mediastinal emphysema,
pneumothorax), which refers to lung damage from disruption of alveoli resulting from
excess alveolar pressures. Barotrauma can also result from the combination of rapid
ventilator rates with PEEP that produces “auto-PEEP,” a phenomenon that produces
successively increasing airway pressure because the rapid respiratory rate does not allow return of airway pressure to the set PEEP level before the next breath is delivered.
Volutrauma refers to alveolar damage caused by ventilation of high-compliance areas of
the lung with large inspired volumes. The large volumes are delivered to highcompliance areas because consolidated areas of the lung lose compliance and the inspired gas is “shunted” to the high-compliance alveoli. Atelectrauma is the term for alveolar injury that occurs from successive deflation and inflation of alveoli during the
ventilator cycle. Unstable alveoli might collapse at end expiration and have to be reopened with the next inspiration, which produces injury to the alveolus. The “collapsereopen” cycle also increases the intensity of the lung inflammatory response. Production of pro-inflammatory cytokines is stimulated and this phenomenon contributes to
ventilator-associated lung injury.
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The approach to minimizing ventilator-associated lung injury is based on an understanding that lung injury results from interactions of the ventilator cycle, mean airway
pressure, and tidal volume. High mean airway pressure required to deliver high tidal
volumes is the main cause of ventilator-associated lung injury. Approaches to lungprotective ventilation strategies emphasize the need to lower tidal volume and lower
mean airway pressure. In patients with acute respiratory distress syndrome, microcirculatory obstruction and small airway obstruction might increase dead space ventilation to the extent that PaC02 rises. This rise can be made tolerable for the patient so that
additional respiratory distress does not occur. The process of allowing PaC02 to increase is termed “permissive hypercapnia” and this is a component of lung-protective
ventilation strategies.
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Data from randomized trials have demonstrated a significant reduction in mortality
for acute respiratory distress syndrome with the use of lung-protective ventilation. In
this section of the overview, we will review some recent contributions to the medical
literature pertinent to ventilator therapy for patients with acute respiratory distress
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syndrome. The scientific basis and clinical effectiveness of “recruitment maneuvers” designed to reopen and maintain alveoli and alternative strategies for “weaning” the patient from ventilator therapy are reviewed.
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The first article was published in 2003 in Critical Care Medicine75 and is a randomized controlled trial of alveolar recruitment maneuvers sponsored by the ARDSNet
group of investigators. A full-text reprint of this article accompanies this issue of SRGS.
Brower and coauthors note that lung-protective ventilation has been shown to decrease
mortality. From the available data, it is not clear that lung protective ventilation contributed to alveolar recruitment, lowered risk of ventilator-associated lung injury, or
improved outcomes in terms of lung function. This study was performed to assess the
effectiveness of maneuvers designed to reopen and maintain alveolar inflation. In the
experimental group, recruitment maneuvers were administered on the first and third
or second and fourth mornings after enrollment. The recruitment maneuver consisted
of changing the ventilator mode to continuous positive airway pressure mode and increasing airway pressure in increments up to 35-40 cmH20 depending on body weight.
The recruitment maneuver was held for 30 seconds unless hemodynamic instability,
cardiac arrhythmia, decreased oxygen saturation, or tachycardia (>130 bpm) occurred.
The control patient group received sham recruitment maneuvers. PEEP was adjusted
according to the level of inspired oxygen required by the patient. An upper limit of 24
cmH20 was permitted.
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The authors noted immediate improved oxygenation after the use of recruitment
maneuvers but the effect diminished over time. The authors note that this observation
might have occurred because near maximal alveolar inflation had already been
achieved using PEEP. They note that the single recruitment maneuver might not be as
effective as repeated maneuvers. The topic of multiple recruitment maneuvers is the focus of the next article reviewed.
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The second article is by Meade and coauthors76 in the Journal of the American Medical Association, 2008. These authors report a randomized trial of patients whose acute
respiratory distress syndrome was diagnosed by standard criteria. One group of patients was treated with standard lung-protective ventilation (respiratory rate < 25, tidal
volume of 6 mL/kg, and PEEP of 8-12 cmH20). Another group had lung protective ventilation combined with recruitment maneuvers (inspiration with breath hold at a steady
pressure of 40 cm H20 for 10-15 seconds during each ventilator disconnection for suctioning or other reasons up to 4 times/day). In the experimental group, PEEP was set
dependent on the Fi02 required by the patient. PEEP pressures ranged from 5-10 cmH20
for Fi02 of 0.6 or less and ranged up to 24 cmH20 for patients requiring Fi02 of 1.0. Volume-controlled assisted breaths were used in control patients and pressure-controlled
ventilation was used in the experimental group. “Rescue therapies” (prone position,
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high frequency oscillation ventilation, extracorporeal membrane support) were permitted for patients with refractory hypoxemia and/or acidosis.
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The frequency of barotrauma (mediastinal emphysema, pneumothorax) was recorded. The data demonstrate that the experimental group had improved oxygenation
with no increase in the risk of barotrauma or rescue interventions. The mortality for the
entire group was 38% and there was no significant difference in mortality risks for the
two groups. Of interest is that attributable mortality for refractory adult respiratory
syndrome was only 6% overall. The experimental group had a significant reduction in
mortality from refractory hypoxemia. The authors concluded that addition of recruitment maneuvers and incremental increases in PEEP (based on the required inspired
oxygen concentration) resulted in improved oxygenation that was durable over time.
This strategy represents an acceptable alternative to conventional therapy.
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An abiding question regarding the effectiveness of recruitment maneuvers relates to
whether recruitment maneuvers, combined with optimum PEEP, distend already inflated alveoli or recruit previously contracted or collapsed alveoli. This issue is the topic of
an article by Schreiter and coauthors77 in Critical Care Medicine, 2004. This study analyzed helical CT images obtained before and after recruitment maneuvers and PEEP adjustment in 17 patients with direct lung trauma resulting in acute respiratory distress
syndrome. The authors observed increased lung inflation on CT images that was obtained by reducing consolidated lung area rather than expanding inflated lung. They
concluded that recruitment maneuvers combined with optimum PEEP reopens contracted or collapsed alveoli and provides sustained inflation of these lung areas.
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The next article reviewed by Mercat and coauthors78 appeared in the Journal of the
American Medical Association, 2008. This report describes a randomized controlled trial
in patients who had acute respiratory distress syndrome diagnosed by standard criteria. One group of patients was treated with lung-protective ventilation with PEEP levels
set from 5-9 cmH20 based on the level of oxygenation. The second group of patients had
PEEP adjusted upward to establish a plateau airway pressure of 28-30 cmH20. In this
study the experimental group had higher fluid requirements (probably because of the
hemodynamic effects of higher airway pressures), but experienced better oxygenation,
a lower risk of requiring “rescue” interventions, and decreased ventilator and organ
failure days. The authors caution that the patients in this study who met criteria for
acute lung injury versus acute respiratory distress syndrome had less benefit from the
higher PEEP strategy, and this patient group might actually experience lung injury from
high PEEP.
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The data about the durability of alveolar recruitment are variable, as is obvious
from the articles previously reviewed. A systematic review of available data on recruit62
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ment maneuvers by Fan and coauthors79 in the American Journal of Respiratory and
Critical Care Medicine, 2008, analyzed data from studies involving nearly 1200 patients.
Available studies all showed improved oxygenation after application of recruitment
maneuvers but most studies also disclosed that improvement was transient. Adverse
events are unusual but arterial hypotension accompanies most recruitment maneuvers.
Hypotension is noted more often in patients with less severe lung injury. They note that
PEEP elevations after a recruitment maneuver improve the durability of the improvement in oxygenation. The authors conclude with the caution that the value of transient
improved oxygenation noted after recruitment maneuvers is currently unknown. Significant impact of recruitment maneuvers on global outcomes measures such as mortality
has not been demonstrated. These authors urge that the decision to employ recruitment
maneuvers be based on the severity of respiratory distress (less severely hypoxemic
patients probably do not benefit) and the response of the individual patient to PEEP
and recruitment maneuvers. The least improvement in oxygenation was observed in
patients with low lung compliance. This might indicate that such patients have limited
capacity for alveolar recruitment.
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The fundamental concept supporting the use of PEEP and recruitment maneuvers is
that alveolar collapse is a major driver of ventilation/perfusion mismatching, hypoxemia, and loss of compliance in acute lung injury. An experimental study examining this
question is by Mertens and coauthors80 appeared in Critical Care Medicine, 2009. These
authors used darkfield intravital microscopy to view the lung parenchyma visualized
through a transthoracic window. Lung injury was induced with intratracheal hydrochloric acid.
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These authors found that alveolar distention increases with ventilation pressure in
normal lungs with a sigmoid shaped curve demonstrated when the percent increase in
alveolar volume was plotted against inflation pressure. Damage to the lung resulted in
alveolar thickening and reduced alveolar volume but alveolar collapse was not observed. In an editorial by Hubmightr accompanying Mertens’ article, the editorialist
notes that the elegant observations reported in the work of Mertens and colleagues
shows that in the normal lung alveoli are not recruited but distend and contract. The
lung damage produced in this study did not result in lung edema, and Hubmightr notes
that alveolar damage leading to alveolar collapse can result from fracture of liquid
bridges in the edematous lung with inflation and deflation. Thus, the injury in this study
might not have reproduced the pathophysiology of acute lung injury. He concludes that
additional work is required before a full understanding is achieved of alveolar inflation
in the face of lung injury.
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Another ventilation strategy for patients with severe acute respiratory distress syndrome is high-frequency oscillatory ventilation. This modality is used frequently in
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premature infants with respiratory distress. Ventilation of the lung occurs from rapid
administration of very small tidal volumes (1-3 mL/kg) delivered at high ventilatory
rates that allow mixing of gas within the lung so that oxygenation is preserved and carbon dioxide is removed. High-frequency oscillating ventilation allows maintenance of
high end-expiratory lung volume without overdistention of alveoli. The topic of highfrequency oscillatory ventilation and ventilator-induced lung injury is addressed in an
article by Imai and Slutsky81 in Critical Care Medicine, 2005. Consistent data from studies in neonates indicate the effectiveness of high-frequency oscillatory ventilation combined with maneuvers designed to maintain lung inflation volumes using recruitment
maneuvers and PEEP adjustments. Minimal frequencies of ventilator-associated lung injury were observed in these studies.
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The authors note that studies in adult patients with acute respiratory distress syndrome have not shown consistent benefit from the use of high-frequency oscillatory
ventilation. Ideal strategies for maximizing pressure in the proximal and distal airways
and optimizing lung volumes with this ventilatory strategy have not yet been developed
and this limits application of this modality. Although there are data to suggest transient
improvement in oxygenation, there is no demonstration of improved mortality outcomes and routine use of this modality is not recommended.
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The main objectives of lung-protective ventilation are to preserve adequate oxygenation, maintain lung inflation, facilitate re-inflation of contracted or collapsed alveoli,
and minimize the risk of ventilator-associated lung injury. Continuous positive airway
pressure strategies are well suited to these objectives. The limitations of continuous
positive airway approaches include that use of these approaches requires an alert; cooperative, spontaneously breathing patient and these approaches are sometimes difficult to apply in intubated patients. In addition, a relatively small proportion of ICU ventilators can deliver continuous positive airway pressure efficiently. Thus, continuous
positive airway pressure is most useful during the “liberation” or “weaning” process as
the patient is assisted through the transition from ventilator support to normal breathing. One variant of continuous positive airway pressure, airway pressure release ventilation, can be used in intubated patients. The patient must be breathing spontaneously
in order for this mode of ventilation to work properly. In suitable patients, airway pressure release ventilation can maintain lung inflation and recruit additional alveoli in the
dependent areas of the lung during spontaneous breathing intervals.
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An article describing airway pressure release ventilation is by Habashi82 in Critical
Care Medicine, 2005. This article is supplied as a full-text reprint with this issue of SRGS.
Habashi notes that airway pressure release ventilation was initially described in two articles authored by Stock and Downs in 1987. This approach to ventilation uses continuous positive airway pressure (Phigh) to maintain lung inflation for a preselected interval
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(Thigh). Elimination of carbon dioxide is facilitated by scheduling periodic releases of
airway pressure that permit airway pressure to fall to a preselected level (Plow). Low
pressure is maintained for a preselected interval (Tlow) and carbon dioxide is eliminated
by this exhalation. Spontaneous, patient-generated breaths assist in recruiting alveoli
by supplying diaphragmatic contractions. The recruited alveoli are in the dependent
lung areas adjacent to the diaphragm. The author notes that the process of alveolar recruitment proceeds along variable time courses because inflation of one group of alveoli
affects the inflation rate of neighboring alveoli. Recruitment, therefore, proceeds in a
wave or “avalanche” fashion. Maintenance of continuous positive airway pressure assists in maintaining inflation as additional alveolar units open. Recruitment occurs because of decreases in pleural pressure rather than increases in airway pressure and Habashi emphasizes that the intermittent airway pressure releases also work to prevent
lung overdistention. To minimize de-recruitment, low pressure intervals are kept as
short as possible (0.2–0.8 seconds in adults).
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Airway pressure release ventilation contrasts with pure continuous positive airway
pressure breathing in that the work of breathing increases with continuous positive
airway pressure alone because of the need for the patient to expend energy to remove
carbon dioxide. In patients with decreased lung compliance and respiratory muscle deconditioning, this increased work of breathing might not be tolerated by the patient.
Airway pressure release ventilation effectively addresses this problem. Habashi notes
that alveolar ventilation is intermittent while carbon dioxide delivery to the alveolus is
continuous. The intermittent pressure releases refreshed alveolar gas and reestablishes the gradient for diffusion of carbon dioxide from blood to alveolar gas.
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Improvement of oxygenation during airway pressure release ventilation occurs because of maintenance of high mean airway pressure that serves to increase the number
of ventilated, perfused alveoli. Spontaneous breaths during the high-pressure interval
serve to recruit additional alveoli in the dependent, perfused lung areas and this mechanism assists in supporting oxygenation as well. The author notes that resistance of the
artificial airway during the early phase of the pressure release interval provides airway
resistance that effectively produces PEEP which also assists in supporting oxygenation.
Because of the PEEP that results from airway resistance, the low pressure setting is
preferably zero.
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Initial set-up of airway pressure release ventilation is accomplished depending on
whether the patient is newly intubated or whether this modality is being used to assist
in transition to weaning. Suggested set-up strategies are presented in Table 2 of Habashi’s article. For example, an adult patient newly intubated would have a desired
plateau airway pressure selected (20-35 cmH20), and this would be the high-pressure
setting. Higher pressures might be required where combined lung and chest wall com65
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pliance are reduced (obese patients). Low pressure would be set at zero. The high time
interval would be set at 4-6 seconds and the low time interval would be 0.2-0.8 seconds.
Longer low-time intervals might be required in patients with chronic obstructive lung
disease. These settings would produce 10-12 exhalations/minute. In patients who are
transitioning from conventional ventilator support, the high pressure is set at the prior
ventilation mode plateau pressure.
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Habashi notes that airway pressure release ventilation is a useful ventilation mode
for spontaneously breathing patients who are ventilated in the prone position or in kinetic beds (see discussion in SRGS, Vol. 35, No. 6). He also notes that addition of pressure support ventilation to airway pressure release ventilation produces unfavorable
increases in transpulmonary pressure. The author notes that spontaneous breathing is
required for effective use of airway pressure release ventilation and, therefore, this approach is not indicated in patients who require aggressive sedation/analgesia or neuromuscular blockade. The modality is associated with less patient discomfort from the
use of adjuvant ventilation compared with conventional ventilation. This consistent observation suggests that intervals of heavy sedation use or neuromuscular blockade
might be shortened by applying airway pressure release ventilation. Habashi concludes
by noting that weaning from airway pressure release ventilation is a simple process involving reductions of the high pressure setting and extension of the high pressure time
interval. Decreasing the number of releases as the pressure changes are made facilitates
transition to normal patient breathing. Finally, Habashi notes that this modality can be
applied using noninvasive ventilation interfaces.
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Comparative clinical data documenting the benefit of airway pressure release ventilation are found in a review by Siau and Stewart83 in Clinics in Chest Medicine, 2008.
These authors note that clinical series evaluating airway pressure release ventilation
have been retrospective observational studies or comparative studies employing historic controls. These studies suggest a reduction of mortality with the use of this modality
in traumatic lung injury patients. There has been little control of confounding variables
in these analyses and, because of this, a definite reduction in mortality cannot be assumed. Reductions in ICU lengths of stay and ventilator intervals have been reported.
Direct comparisons of airway pressure release ventilation to lung-protective ventilation
have not been reported. Siau and Stewart conclude that airway pressure release ventilation is appropriate for carefully selected patients but a recommendation for widespread use of this approach cannot be made based on current evidence.
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One area where airway pressure release ventilation might be valuable is in patients
who need a transition between conventional ventilation and implementation of a formal “weaning” protocol. Weaning from ventilator support is clinically challenging. During full ventilator support respiratory muscle deconditioning occurs and, because of
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this, muscle weakness might limit ventilatory effort. Lung and chest wall compliance are
decreased by the primary lung disease, body habitus (obesity), pain from incisions,
chest drainage tubes, and rib fractures. Successful weaning requires that the primary
disease causing acute respiratory distress syndrome be under control. In addition, the
patient should be capable of initiating spontaneous breathing efforts. Ideally, use of sedation and analgesia are reduced to the point that the patient can cough, make deep
breathing efforts, and participate in patient care by changing position in the bed or
moving from bed to chair with assistance. Correction of nutritional deficits should be
underway. Once these conditions are met, transition to an assisted-ventilation strategy
is a first step. Spontaneous breathing trials can be scheduled three or four times daily
under nursing and/or respiratory therapist supervision, and intervals of spontaneous
breathing can be incrementally increased (“wind sprints”). When extubation is possible,
noninvasive interfaces can be used to assist patients with “graduation” to normal
breathing. These approaches are particularly useful in patients with COPD.
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A systematic review of available data on the use of noninvasive ventilation as a
weaning adjunct appears in an article by Burns and coauthors84 in British Medical Journal, 2009. These authors reviewed 12 trials involving 530 patients. They note that most
patients enrolled in weaning trials using noninvasive ventilation had COPD. COPD was
not necessarily the main contributor to the need for ventilator support in the reported
trials. The authors note that pooled data suggest a reduction in mortality and ICU length
of stay for patients with COPD weaned with noninvasive ventilation protocols. There
was no increased risk of weaning failure, pneumonia, or reintubation in the reported
trials. These authors conclude that the evidence in support of noninvasive ventilation as
a means of facilitating weaning is sufficiently strong to recommend this modality in patients with COPD.
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Editorial comment
From the perspective of the editor, weaning critically ill surgical patients from mechanical ventilation is highly dependent on the success of efforts to control the process
that led to the need for ventilation in the first place. Deconditioning is an especially
challenging problem that limits success of weaning in the elderly and in patients with
severe comorbid conditions. Failure of weaning with deterioration of oxygenation and
lung compliance leading to reinstitution of ventilation is a high price the patient pays
for suboptimal timing of weaning. Weaning failure and extubation failure resulting in
the need to reinstitute mechanical ventilation are, in my view, largely avoidable complications. Underestimation of the need for analgesia/sedation, underuse of assistive exercise physical therapy programs, inadequate patient counseling, delay or nonuse of nutritional support, and suboptimal level of consciousness are common modifiable factors
contributing to weaning failure. Education of nurses, physical therapists, and respiratory therapists in the use of weaning protocols permits weaning and extubation when cri67
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teria for acceptable patient-controlled breathing are fulfilled. Use of these multidisciplinary protocols can improve the success rates for weaning in critically ill surgical patients.
Nonventilator adjunctive measures
Several adjuncts to traditional ventilator therapy might improve outcomes of acute
lung injury and acute respiratory distress syndrome in carefully selected patient
groups. These adjuncts can be categorized as 1) measures for reducing the risk of additional lung injury (fluid therapy); 2) measures that modulate the inflammatory process
(corticosteroid therapy); 3) interventions that modify pulmonary hypertension (nitric
oxide); 4) measures designed to improve distribution of ventilation and perfusion
(prone positioning, discussed in SRGS, Vol. 35, No. 6); 5) adjuncts that replace lung
function (extracorporeal membrane oxygenation); and 6) interventions that alter the
airway (tracheostomy). In this section of the overview, we review these topics.
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The first article reviewed appeared in the New England Journal of Medicine in 200685
entitled “Comparison of two fluid-management strategies in acute lung injury.” This article is supplied as a full-text reprint with this issue of SRGS. The article by Wiedemann
and coauthors is a report of a randomized, prospective trial comparing two approaches
to fluid management in patients with acute respiratory distress syndrome. The study
was conducted by the ARDSNet group of investigators. One thousand patients were enrolled and randomly assigned to a conservative or liberal fluid management group. The
characteristics of fluid management for each enrolled patient were determined in real
time depending on the central venous pressure or pulmonary artery pressure, the presence of shock (arterial pressure < 60 mmHg), and external signs of inadequate perfusion, such as skin mottling or oliguria. Thus, a patient with effective circulation and no
oliguria who had a central venous pressure of >13 and was assigned to the conservative
fluid group would receive furosemide and intravenous fluids at a minimum rate until
central venous pressure was in the 9-13 cm H20 range.
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Patients in shock were treated with fluids and vasoactive agents as needed until appropriate hemodynamic response and venous or pulmonary artery target pressures
were achieved. All patients enrolled met standard criteria for acute respiratory distress
syndrome and all were ventilated with standard ventilator strategies. The investigators
found that there was no statistically significant difference in mortality in the two groups
of patients. There were significant improvements in oxygenation in the conservative
strategy group. Ventilator days and ICU stay were reduced in the conservative group
and there was no increase in the frequency of renal insufficiency or the diagnosis of
shock in the conservative therapy group.
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In the discussion section, data indicate that small increases in pulmonary artery occlusion pressure above the normal range can be associated with large increases in extravascular lung water. The authors also cite studies indicating that removal of excess
interstitial space fluid with furosemide is associated with improved oxygenation. Supplemental albumin infusion given to hypoalbuminemic patients to improve oncotic
pressure did not result in improved oxygenation unless furosemide was given along
with the colloid infusion. These results suggest that there is a “mobilizable” fluid space
within the lung amenable to movement of fluid along pressure gradients but that protein leakage might limit the effectiveness of efforts to improve oncotic pressure. The
lack of mortality difference in this study most likely relates to the fact that patients who
died were actually dying of an associated illness, and not from acute respiratory insufficiency.
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Recognition of the role of inflammation in the pathophysiology of acute lung injury
has stimulated evaluation of anti-inflammatory strategies for treatment of acute respiratory distress syndrome. This topic is the subject of a report by Tang and coauthors86 in
Critical Care Medicine, 2009, who report a meta-analysis of randomized controlled trials
and observational studies of low-dose corticosteroids (0.5-2.5 mg/kg/day) in patients
with acute respiratory distress syndrome. For cohort studies, analyses of data drawn
from 307 patients were included. Randomized trials included 341 patients. Both types
of studies demonstrated improved mortality risk and both types of studies demonstrated improved oxygenation and decreased ICU length of stay. Overall, there was a 38%
reduction in risk of death for patients treated with low dose methylprednisolone. There
was no increased risk of infection, neuromyopathy, or major complications in the steroid treated groups.
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The authors note that their study effectively deals with the challenges faced by other
investigators who attempted to determine whether there was a benefit to corticosteroid treatment with no increase in complications. Earlier analyses dealt with widely varying dosage ranges, differing types of steroid drugs, and heterogeneous patient groups.
This study dealt with studies using low-dose medication with standard definitions of
acute respiratory distress syndrome and standard reporting of outcomes. The authors
conducted subgroup analysis that indicated efficacy of low-dose corticosteroids even
when treatment was started several days after the onset of acute respiratory distress
syndrome. In addition, treatment effect was independent of the use of “open lung” ventilation strategies. The analysis also confirmed that the treatment effect was independent of any affect on the outcomes of sepsis. The authors conclude that low-dose steroid
treatment is effective and safe in patients with acute respiratory distress syndrome. The
data indicate that steroid therapy should be tapered and not stopped abruptly. Abrupt
cessation of steroids can be associated with rebound inflammation and worsening of
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lung function. Tang and associates acknowledge that this study is limited by the fact
that they had no knowledge of the presence or absence of dysfunction of the pituitaryadrenal axis in these studies.
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An approach to the diagnosis of adrenal insufficiency in critically ill patients is the
topic of a consensus report by Marik and coauthors87 in Critical Care Medicine, 2008.
This article is supplied as a full-text reprint with this issue of SRGS These authors recommend that the diagnosis of adrenal insufficiency in critically ill patients can be established by documenting an increase of less than 9 μg/dL of total serum cortisol after a
dose of adrenocorticotrophic hormone of 250 μg or a random total serum cortisol level
of < 10 μg/dL. Once the diagnosis is established, treatment with corticosteroid replacement is valuable especially in patients with septic shock and inadequate responses
to fluids and vasoactive drugs. Steroid therapy is useful in the treatment of early acute
respiratory distress syndrome confirming the observations of Tang and coauthors, discussed earlier. Readers should note that the treatment benefit observed by Tang and
colleagues was not limited to early acute respiratory distress syndrome.
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Inhaled nitric oxide has potent pulmonary vasodilating properties and, according to
some data, anti-inflammatory features also. Thus, this agent has been suggested as a
means of improving ventilation/perfusion matching in patients with acute respiratory
distress syndrome. A meta-analysis of data pertinent to this topic appears in an article
by Adhikari and coauthors88 in the British Medical Journal, 2007; analyzed data from 12
trials of acceptable quality that had enrolled more than 1200 patients. The data disclosed modest, transient, improvements in oxygenation but no affect on mortality from
acute respiratory distress syndrome. In addition, patients receiving nitric oxide incurred a significant increased risk of renal dysfunction. The authors concluded that
available data do not support a role for inhaled nitric oxide in the treatment of acute
respiratory distress syndrome.
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Another adjunctive therapy applied to patients with acute respiratory distress syndrome is extracorporeal membrane oxygenator support. Using this support device involves connecting a membrane oxygenation device and a heat exchanger to the patient
using a venovenous circuit or, in patients with hemodynamic instability, a venoarterial
circuit. Limited anticoagulation is required for the circuit to function. Blood is drawn
from a central venous or arterial source and returned via a second venous access after
oxygenation and warming. This device has been primarily used as “rescue” therapy for
patients who cannot be adequately ventilated. Intuitively, the best results should be obtained in patients with isolated lung damage caused by noninfectious etiologies. For
these reasons, patients with direct pulmonary injury would be a patient group where
the device would probably achieve the best results.
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A clinical series reporting results of extracorporeal membrane oxygenator usage in
patients with multiple injuries is reported in an article by Cordell-Smith and
coauthors89 in Injury, 2005. These authors report a series of 28 patients who received
extracorporeal membrane oxygenator support for severe acute respiratory distress
syndrome developing after direct pulmonary traumatic injury or after multiple trauma
(mostly pelvic and long bone fractures). Because of the need for anticoagulation, use of
this rescue approach would be limited in patients with central nervous system injuries
or intraabdominal injuries. The authors note that the duration of support in this patient
group was, on average, 141 hours. This support interval is shorter than intervals of
support used in other patient groups. Twenty of the 28 patients survived. Nonsurvival
was noted more often in patients with systemic sepsis or pulmonary infection.
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The report does not detail the characteristics of the ventilator therapy used in these
patients and it is, therefore, not completely clear whether the use of extracorporeal
membrane oxygenation was to “rescue” patients or not. This mortality rate is somewhat
lower than the mortality reported for patient groups containing both surgery and trauma patients treated with aggressive “open-lung” ventilation strategies, but the patient
numbers in this report are small and the process of selecting the patients for therapy
with the external device is not described in detail. Nonetheless, trauma patients might
represent a favorable group for use of extracorporeal membrane oxygenator support.
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Long-term results of extracorporeal membrane oxygenator support are important
because these data provide insight into the process of lung healing and offer the opportunity to assess potential chronic adverse effects of extracorporeal support. An article
providing data relevant to this topic, by Linden and coauthors,90 appeared in Acta Anaesthesiologica Scandinavica, 2009. These authors report results of high-resolution lung
CT scans, extensive pulmonary function tests, lung scintigraphy, and lung-specific quality of life questionnaire responses in a group of 21 patients who survived severe acute
respiratory distress syndrome treated with extracorporeal membrane oxygenator support. During extracorporeal membrane oxygenator support episodes, patients were
maintained on low-level continuous positive airway pressure ventilation. Clinical assessments were performed at least one year after therapy in all patients. Highresolution CT images disclosed changes consistent with lung fibrosis in all patients, but
the extent of the changes was limited and the distribution of CT changes was not the
typical anterior distribution of ventilator induced lung injury. Pulmonary function tests
showed abnormal carbon dioxide diffusing capacity in nearly two-thirds of the patients
tested. The abnormality was small, however, and functional impairment was mild.
Overall, pulmonary function tests were within the normal range. Pulmonary scintigraphy showed residual airway obstructive patterns in all patients characterized by prolonged washout intervals for the inhaled radioisotope. Exercise testing was performed;
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reduced exercise tolerance was seen in one-third of patients, but the limitation was leg
fatigue rather than pulmonary symptoms in all of these patients.
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All the patients responded to the quality of life questionnaire and all stated that
quality of life was reduced after treatment with extracorporeal membrane oxygenator
support. Importantly, none of the patients required supplemental oxygen and all were
employed full-time in the same occupations held before their illness. The authors concluded that long-term impairment after extracorporeal membrane oxygenator support
is usually mild.
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Tracheostomy is an adjunctive treatment used in patients with acute respiratory
distress syndrome. The objective of tracheostomy use is mainly to improve patient
comfort, permit speech, reduce the risk for laryngeal injury, and optimize airway access.
Available data suggest that tracheostomy facilitates discharge of patients from the ICU,
shortens ventilator intervals, and, possibly, reduces the frequency and severity of ventilator-associated pneumonia. These potential benefits are accompanied by costs and
complications.
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Tracheostomy, at a minimum, results in disfiguring scarring of the anterior neck.
Airway bleeding, tracheal ring fracture, tracheal stenosis, and esophageal injury might
occur. Tracheal-innominate artery fistula is a complication that has nearly disappeared
with reductions in post-tracheostomy local wound infection and appropriate choice of
the level of tracheostomy tube insertion (third tracheal ring). Bedside percutaneous
tracheostomy techniques have reduced the need to transfer patients to the operating
room for formal surgical procedures. Overall reductions in healthcare resource use
have been reported with the use of bedside percutaneous tracheostomy; bedside tracheostomy requires partial removal of the endotracheal tube and use of the flexible fiberoptic bronchoscope to guide tracheostomy tube insertion. Thus, additional costs are
incurred along with the risk for sudden airway loss during the procedure. In this section
of the overview, several articles dealing with the use of tracheostomy as an adjunct to
other treatments for acute respiratory distress syndrome are discussed.
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The first article discussed is by De Leyn and coauthors.91 It appeared in the European Journal of Cardio-Thoracic Surgery, 2007, and is supplied as a full-text reprint accompanying this issue of SRGS. It reports practice guidelines for the use of tracheostomy developed by a joint committee of the Belgian Society of Pneumonology and the
Belgian Association for Cardiothoracic Surgery. The process of guideline development is
described in the article. This process included collection and evaluation of peerreviewed articles, discussion in committee meetings, posting of proposed guidelines
online for comment, and final promulgation of the guidelines.
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The authors begin by listing the indications for tracheostomy, which include longterm ventilation, failure to wean, upper airway obstruction, and copious secretions.
They also list contraindications such as active soft tissue infection in the anterior neck,
and extensive scarring from earlier surgical procedures and/or radiation therapy. Current approaches to the care of patients with cervical spine injury might include early
open reduction and internal fixation of spinal fractures. The presence of a fresh surgical
incision with implanted devices is a relative contraindication to tracheostomy. The authors next discuss technique for open tracheostomy. If possible, the patient is positioned with the neck extended. The conventional approach is to make a transverse or
vertical skin incision 1 cm below the lower border of the cricoid cartilage. Soft tissues
are separated and, if necessary, the thyroid isthmus is divided and retracted. The anterior tracheal wall is identified and the second and third tracheal rings are located. The
endotracheal tube is withdrawn until the distal orifice is above the tracheostomy site.
The trachea is entered and the opening is dilated. Incision of the tracheal ring above or
below the opening is sometimes necessary to facilitate insertion of the tracheostomy
appliance.
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The authors recommend using a tracheostomy appliance with a low-pressure cuff.
Lubrication of the tracheostomy appliance facilitates insertion because the lowpressure cuff is redundant and might “hang-up” on the tracheal rings. Advance preparation should be made to connect the airway circuit to the tracheostomy appliance immediately on completion of successful insertion. Some surgeons, including the editor, prefer to perform immediate fiberoptic bronchoscopy to make certain that blood clots and
mucous plugs are cleared from the airway and that there is no residual airway bleeding.
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De Leyn and colleagues discuss percutaneous dilational tracheostomy. The two most
commonly used devices are the “Blue Rhino®” device and the “Percu-twist®” device.
Each device uses a percutaneous needle for tracheal access, and optimal patient safety
concerns have dictated the use of flexible fiberoptic bronchoscopic control of the procedure so that the point of needle entry and tracheostomy device placement is documented. The main difference between the two devices lies in the means of dilation of
the skin, subcutaneous tissue, and tracheal wall channel into the tracheal lumen. The
Blue Rhino device uses a curved, hydrophilic-coated dilator, which needs to be passed
through the channel a minimum of three passages using the previously placed guidewire. The Percu-twist device uses a hydrophilic-coated screw that is rotated in a clockwise direction to create the entry channel for the tracheostomy device.
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The authors list and discuss early and late complications of both surgical and percutaneous dilational tracheostomy. They note that conventional wound care approaches
are necessary to reduce the risk of peri-tracheostomy infection. In addition, they note
that the swallowing dysfunction that accompanies tracheostomy usually means that pa73
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tients will not be able to eat normally. Aspiration episodes are frequent and collection
of secretions above the tracheostomy balloon must be anticipated. If ventilator support
can be interrupted, patients might be able to speak if the tracheostomy tube orifice is
covered with a gloved finger. Tracheostomy appliance balloons tend to increase in volume over time with concomitant increases in balloon pressure. Pressures in excess of
25 mmHg might interrupt tracheal mucosal blood flow. Tracheostomy cuff pressure
should be monitored to keep pressures in the appropriate range.
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A comparison of surgical tracheostomy to percutaneous tracheostomy is the topic of
a report by Beltrame and coauthors92 in Minerva Anesthesiologica, 2008. These authors
report an analysis comparing surgical tracheostomy to percutaneous tracheostomy.
Three hundred sixty-seven patients undergoing percutaneous tracheostomy were compared with 161 historic control patients who had surgical tracheostomy. Procedure duration was shorter for percutaneous tracheostomy. Complications were low and equivalent for both techniques. ICU length of stay was shorter for percutaneous tracheostomy
patients; there is no report of concomitant changes in ICU patient care processes that
might have worked to shorten ICU stay in the later group. The authors cite data showing that patients with tracheostomy might require less analgesia and sedation compared to patients with endotracheal tubes. The authors note that analgesia/sedation
protocols are not standardized in most reports so it is not possible to determine whether intubated patients are simply oversedated.
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De Leyn and colleagues note there is controversy over the timing of tracheostomy
and the impact of tracheostomy on outcomes of ventilation for acute respiratory distress syndrome. Observational studies and one randomized clinical trial demonstrating
reduced mortality, intensive care length of stay, and reduced frequency of pneumonia
are cited by these authors. The numbers of patients in these studies are small and, because of this, categorical statements of benefit from early tracheostomy cannot be
made. They cite, in addition, a systematic review of early tracheostomy in trauma patients that did not demonstrate clear evidence of benefit from early tracheostomy. Much
of the debate centers on the definition of “early tracheostomy.” Studies that do not show
benefit usually report tracheostomy performed within the first 10 days of ventilation;
studies showing benefit report tracheostomy performed within the first 48 hours of
ventilation. Obviously, both approaches are subject to selection bias since prediction of
outcomes within the first 48 hours is challenging and, in the reported studies, some patients subjected to early tracheostomy are weaned from the ventilator within 3-4 days
of the tracheostomy. This subgroup of patients could possibly have been weaned to extubation without the tracheostomy. Patients who have tracheostomy at the end of the
first week of ventilation are probably patients who are going to require prolonged support regardless of the approach to airway management.
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A comparison of “early” versus “late” tracheostomy in injured patients is the focus of
a report by Arabi and coauthors93 in Critical Care, 2004. These authors queried a prospectively managed trauma ICU database and compared a group of 29 patients who had
tracheostomy performed earlier to day 7 of ventilation with 107 patients who had tracheostomy performed after 7 days. Lower ICU lengths of stay were noted in the patients
who had “early” tracheostomy. The authors noted that the patients having early tracheostomy were more likely to have severe brain injury and this raises the question
whether early tracheostomy was associated with benefit in terms of improved outcomes for respiratory failure or, rather, the tracheostomy facilitated transfer of braininjured patients to other care areas. Overall hospital outcomes was not influenced by
early tracheostomy in this study.
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A report of an analysis of the affects of early tracheostomy versus late tracheostomy
on patient outcomes from a statewide trauma database is the topic of a report by
Schauer and coauthors94 in the Journal of Trauma, 2009. These authors reviewed patient data on 685 patients who underwent tracheostomy. Early tracheostomy was defined as tracheostomy performed within the first four days after injury. The authors
calculated survival probability using standard injury severity indices. Low survival
probability was defined as a probability of survival of less than 25%. The authors noted
there was high early mortality in the patients in the low survival probability group and
this group of patients did not benefit from early tracheostomy. In patients with survival
probability of more than 25%, early tracheostomy resulted in shorter ICU lengths of
stay and shorter hospital lengths of stay.
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With the increased use of percutaneous dilational tracheostomy, patients referred
to surgeons for formal surgical tracheostomy are often patients with very obese necks,
prior neck scarring, patients who cannot be optimally positioned, and patients with difficult upper airway anatomy and/or history of difficult intubation. These changes in patient characteristics mean that surgical tracheostomy usually means a formal procedure
performed under general anesthesia in the operating room. Patients will frequently not
have optimum ventilator support during transport and in the operating room (see discussion of ventilatory associated pneumonia in SRGS, Vol. 35 No. 6). Careful coordination of the surgical and anesthesia teams is necessary because of the hazard of airway
loss. Surgical exposure is often challenging and technical measures to minimize the risk
of bleeding include positioning the patient in a slightly head-up position (to lower venous pressure in neck veins), ventilation of the patient using low airway pressures, and
the use of larger incisions.
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Editorial comment
From the perspective of the editor, it seems clear that early tracheostomy facilitates
the care of certain types of injured patients. This patient group consists mainly of pa75
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tients with moderate-to-severe brain injury who can be expected to survive and, perhaps, recover brain function over time. Tracheostomy can facilitate transfer of such patients to rehabilitation facilities or to assisted care facilities. The reductions in ICU
lengths of stay and hospital lengths of stay reported in the articles discussed above
supports this conclusion. This patient group is also at increased risk for pneumonia and
tracheostomy might improve the diagnostic process for pneumonia. By reducing aspiration of secretions, pneumonia risk might be reduced. The reasons for decreased length
of ventilator support reported by some authors in patients undergoing tracheostomy
(especially early tracheostomy) are not clear. Reductions in airway-related complications and pneumonia risk could contribute to such reductions.
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The available data, and clinical experience, have shown that provision of consistent
open-lung ventilation (discussed in the previous section) with minimal interruption of
ventilation will maximize the likelihood of weaning and recovery of lung function as
long as the process producing acute respiratory distress syndrome can be adequately
controlled and ventilator-associated pneumonia can be avoided.
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In the editor’s experience, clinical judgment can usually determine, with acceptable
accuracy, those patients who will likely require prolonged ventilator support. In this patient group, early tracheostomy is likely to have its greatest benefit. In my view, tracheostomy facilitates the diagnosis of ventilator-associated pneumonia using bronchoalveolar lavage. I have consistently observed less use of supine positioning and more frequent suctioning of patients with tracheostomies. Patients with tracheostomies are repositioned in bed more frequently and are easier to move from bed to chair compared
with patients who have endotracheal tubes. These features might contribute to lowering of pneumonia risk.
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Percutaneous tracheostomy is the most efficient procedure and this approach is, in
the experience of the editor, associated with the shortest interval of interruption of ventilator therapy. As higher risk patients have increasingly been selected for open tracheostomy under general anesthesia in the operating room, maneuvers to safely place the
tracheostomy when exposure is limited have been sought.
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One valuable maneuver, in the experience of the editor, is to use the percutaneous
dilational tracheostomy insertion equipment to assist in placing the tracheostomy appliance once the anterior tracheal wall is identified. The needle and guidewire are inserted using bronchoscopic control and the dilator is used to establish entry into the
tracheal lumen. Stay sutures are placed on each side of the trachea entry site so that the
trachea can be elevated. The tracheostomy appliance (sometimes a long appliance is
necessary and advanced planning to make certain such devices are available is helpful)
can then be placed safely.
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