What ICU Evidence Applies
to the OR?
Ross Blank, MD
Assistant Professor
Division of Critical Care
Director, Thoracic Anesthesia
What We Do
Anesthesia providers practice intensive care.
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Airway Management
Mechanical Ventilation
Fluid Resuscitation
Vasopressor Support
Antibiotic Management
What Works in ARDS?
VENTILATOR MANAGEMENT
What is ARDS?
Definition formalized
in 1992 American
European Consensus
Conference
1. Acute onset, bilateral
infiltrates on CXR
2. PCWP ≤ 18 mmHg or
no clinical evidence of
left atrial hypertension
3. PaO2/FiO2 (P/F) Ratio
≤ 300 for ALI
≤ 200 for ARDS
Bernard et al. AJRCCM 1994;149:818-824
What is ARDS? – Berlin Definition
The ARDS Definition Task Force. JAMA 2012;307:2526-2533
Treatments of ARDS
Non-pharmacologic
Pharmacologic
Low tidal volumes
High PEEP
Recruitment maneuvers
Prone positioning
High Frequency Oscillatory Ventilation
(HFOV)
Airway Pressure Release Ventilation
(APRV)
Conservative fluids
Renal Replacement Therapy
Early enteral feeding
PA Catheter
ECMO
Corticosteroids
Nitric oxide
Alkali Therapy
Neuromuscular blockade
Ketoconazole
Lisofylline
Oxepa
Antioxidants
Neutrophil elastase inhibition
Exogenous surfactant
Liquid ventilation
Inhaled β-agonists
Statins
Treatments of ARDS with Mortality
Benefit
Non-pharmacologic
Pharmacologic
Low tidal volumes (ARMA, NEJM 2000)
High PEEP (meta-analysis, JAMA 2010)
Recruitment maneuvers
Prone positioning (NEJM 2013)
High Frequency Oscillatory Ventilation
(HFOV)
Airway Pressure Release Ventilation
(APRV)
Conservative fluids
Renal Replacement Therapy
Early enteral feeding
PA catheter
ECMO?
Corticosteroids?
Nitric oxide
Alkali Therapy
Neuromuscular blockade (NEJM 2010)
Ketoconazole
Lisofylline
Oxepa?
Antioxidants
Neutrophil elastase inhibition
Exogenous surfactant
Liquid ventilation
Inhaled β-agonists
Statins
ARDSNet ARMA Trial
RCT of 6 mL/kg vs. 12 mL/kg PBW Tidal
Volume
Further TV adjustments to maintain PPLAT < 30
cm H2O vs. < 50 cm H2O
Ventilator Mode – Volume Control A/C
PEEP/FiO2 per table in both groups
861 patients
Mortality 31.0% vs. 39.8% (p = 0.007)
NEJM 2000;342:1301-1308
Transpulmonary Pressure (PTP)
Slutsky and Ranieri. NEJM 2013;369:2126-2136
PTP – Talmor Trial
PTP – Talmor Trial
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Calculated as difference
between airway pressure
and pleural pressure from
esophageal balloon
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Measured after endexpiratory and endinspiratory occlusions
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After RM, adjust PEEP for
goal PTP,exp 0-10 cm H2O,
decrease TV to keep PTP,insp
< 25 cm H2O
Talmor et al. NEJM 2008;359:2095-2104
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On average, increased
PEEP in experimental
group (17 vs. 10 cm H2O)
associated with increased
PO2, improved compliance,
lower FiO2, and modest
increases in peak, plateau,
and mean airway pressures
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Control group generally
had negative PTP,exp
PTP – Talmor Trial
Static Compliance =
TV/(PPLAT - PEEP)
The observation that
PEEP increases were
associated with more
modest PPLAT increases
demonstrates the
improvement in
compliance
Talmor et al. NEJM 2008;359:2095-2104
Compliance Curve
Best Compliance
Compliance low:
Atelectasis, Shunt
Blanch et al. Curr Opin Crit Care 2007;13:332-337
Compliance low:
Overinflation
High VD/VT
PTP – Talmor Trial
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Small trial (n = 61)
Single center
Unexpected signal of
decreased 28-day mortality
in experimental group
Interestingly, 3/30
experimental group
patients actually had their
PEEP lowered based on
initial PTP measurements . . .
one size does not fit all
Talmor et al. NEJM 2008;359:2095-2104
• Follow-up, large,
multi-center trial
ongoing
Why is PTP relevant to the OR?
• Elevated pleural pressure is an indicator of
decreased chest wall compliance
• We deal with decreased chest wall compliance every
day – thoracic/abdominal operations, thoracoscopy,
laparoscopy, head-down position, obesity,
pregnancy, ascites, effusions, skeletal deformities,
etc. etc.
Why is PTP relevant to the OR?
• In general, high airway pressures measured on the
ventilator suggest that we may have to lower PEEP
and tidal volume to prevent barotrauma and/or lung
injury
• In situations of decreased chest wall compliance,
higher pressures (both PEEP and PIP) may be
necessary to overcome the elevated pleural pressure
A simpler way to set PEEP?
1. Perform RM
2. Decremental PEEP trial while measuring dynamic compliance
3. Identify PEEP associated with highest compliance
4. Repeat RM and set PEEP at or just above PEEP determined
above
This PEEP corresponds to CT scan findings just before atelectasis
appears . . . in pigs after lung lavage.
Suarez-Sipmann et al. Crit Care Med 2007;35:214-221
A simpler way to set PEEP?
Maisch et al. Anesth Analg 2008;106:175-181
How Much? To What End? Which One?
FLUID RESUSCITATION
Septic Shock - Early Goal-Directed
Therapy
Over 6 hours:
More Fluid (5.0 L vs 3.5 L)
More Blood (64% vs. 19%)
More Dobutamine (14% vs. 1%)
Less Death (30.5% vs 46.5%)
Rivers et al. NEJM 2001;345:1368-1377
Septic Shock – Lactate Clearnace
Jones et al. JAMA 2010;303:739-746
Septic Shock – Lactate Clearnace
Control group – Rivers Protocol
Intervention group – Replace
ScvO2 goal with ≥ 10% lactate
clearance every 1-2 hours
No differences in ScvO2 levels,
length of stay, or mortality
Jones et al. JAMA 2010;303:739-746
Alternatives to Crystalloid - SAFE
NEJM 2004;350:2247-2256
Alternatives to Crystalloid
Albumin
Hydroxyethyl Starch
•Human-derived
•Expensive
•Established indications
•Synthetic
•Relatively inexpensive
•Widely used
•Safe
•Safe?
Alternatives to Crystalloid - CHEST
6% HES 130/0.4
Increased rate of renal replacement therapy, no difference in mortality
in HES group (n = 6651)
Myburgh et al. NEJM 2012;367:1901-1911
Alternatives to Crystalloid
NEJM 2012;367:124-134
NEJM 2008;358:125-139
Control = LR
Crit Care 2012;16:R94
Alternatives to Crystalloid
NEJM 2012;367:124-134
NEJM 2008;358:125-139
Control = LR
↑ RRT
n = 537
↑ RRT
↑ Death
n = 698
Crit Care 2012;16:R94
No differences
n = 196
Alternatives to Crystalloid CRISTAL
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Multi-center trial conducted in 57 ICUs from 2003-2012
Patients received either all crystalloid or all colloid for resuscitation
needs but specific fluid not specified
No difference in 28-day mortality or need for RRT, decreased 90-day
mortality in colloid group
More ventilator- and vasopressor-free days in colloid group
Annane et al. JAMA 2013;310:1809-1817
What about the control group?
• Retrospective study of 22,851 surgical patients
• 22% incidence of postoperative Cl- > 110 mmol/L
• Hyperchloremic patients developed more renal dysfunction,
had longer hospital stays, and demonstrated increased 30-day
mortality compared to propensity-matched controls
• “Normal” saline is the only common fluid likely to cause
hyperchloremia
McCluskey et al. Anesth Analg 2013;117:412-421
Alternatives to Crystalloid
JAMA 2012;308:1566-1572
Ann Surg 2012;
255:821-829
Ann Surg 2014;
259:255-262
Crystalloid Solutions
NS
LR
Plasma-Lyte/
Normosol
Plasma
154
130
140
136-146
K+
4
5
3.5-5.0
Ca2+
3
Na+
Mg2+
Cl-
154
109
2.1-2.6
3
0.6-1.0
98
98-108
HCO3-
22-34
Lactate
28
Acetate
27
Gluconate
23
Osm
308
273
294
280-300
What is Tangible Bias?
VASOPRESSOR THERAPY
Vasopressor Choice - Phenylephrine
Thiele et al. Anesth Analg 2011;113:284-296
Thiele et al. Anesth Analg 2011;113:297-304
Vasopressor Choice - Phenylephrine
“Favoring less important but immediately measurable
variables, such as mean arterial blood pressure (MAP),
over more important but less measurable variables, such
as tissue oxygen delivery (DO2), is the result of “tangible
bias,” our tendency to favor what we can see and
understand over what we cannot. Despite the
practicalities that preclude the routine measurement of
regional blood flow, changes in global and regional blood
flow should be anticipated any time hemodynamics are
manipulated, with the goal being adequate DO2 and
nutrients to organs of interest.”
Thiele et al. Anesth Analg 2011;113:284-296
Vasopressor Choice - Phenylephrine
• Arterial vasoconstriction increases MAP/SVR/afterload and thus
increases myocardial oxygen demand – most relevant in cases of
pre-existing myocardial failure
• Venoconstriction may decrease venous capacitance and initially
increase venous return/RV preload but the resulting increase in
venous resistance limits sustained increase in venous return/cardiac
output
• Likely decreased myocardial, renal, and mesenteric blood flow
• Net effect is an increase in MAP associated with a decrease in
cardiac output
Thiele et al. Anesth Analg 2011;113:284-296
Vasopressor Choice – Surviving
Sepsis
Dellinger et al. Crit Care Med 2013;41:580-637
Vasopressor Choice – NE vs. Dopa
SOAP II Investigators’ multicenter RCT of
norepinephrine vs.
dopamine in treatment of
shock
No mortality difference but
more arrhythmias in
dopamine group
De Backer et al. NEJM 2010;362:779-789
Vasopressor Choice – NE vs. Epi
CATS trial of
norepinephrine/ dobutamine
vs. epinephrine for septic
shock pts
No significant mortality
difference or increase in
adverse advents with
epinephrine
Annane et al. Lancet 2007;370:676-684
Vasopressor Choice – NE vs. AVP
VASST trial of
norepinephrine vs. low-dose
vasopressin for septic shock
pts
No significant mortality
difference or increase in
adverse advents with
vasopressin
Russell et al. NEJM 2008;358:877-887
Why not phenylephrine for septic
shock?
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No large trial comparing it to first-line therapy i.e.
norepinephrine
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Pharmacologic concerns regarding decreased cardiac
output
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Only literature reference is a small trial of 32 patients
that documented no measurable differences between
phenylephrine and norepinephrine in terms of cardiac
function and global/regional perfusion
Morelli et al. Crit Care 2008;12:R143
Where are the RCTs?
ANTIBIOTIC MANAGEMENT
Rapid Treatment
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There is already an evidence-based push for early
intervention in acute coronary syndromes and strokes
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We have seen that early fluid resuscitation saves lives
in septic shock
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Where are the trials of early antibiotics?
Early, Effective Antibiotics
Kumar et al. Crit Care Med 2006;34:1589-1596
Combination Therapy
Possible Benefits:
– More likely to cover
resistant pathogens
– Synergy?
– Prevent development
of resistance?
Often advocated for
suspected Pseudomonas
infections and for
neutropenic patients
Kumar et al. Crit Care Med 2010;38:1773-1785
All SEPTIC SHOCK pts
Classes of Antibiotics
Penicillins (i.e. peni-, ampi-, piperacillin)
β-lactam/β-lactamase inhibitors (i.e. ampsulbactam, pip-tazobactam)
Cephalosporins (i.e. ceftriaxone, cefepime)
Carbapenems (i.e. imi-, meropenem)
Aminoglycosides (i.e. genta-, tobramycin)
Fluoroquinolones (i.e. levo-, ciprofloxacin)
Macrolides (i.e. azithromycin)
CELL WALL
ACTIVE
AGENTS
PROTEIN
SYNTHESIS
INHIBITORS
Conclusions
• We take care of critically ill patients in the
OR
• There is significant overlap between
“healthy” outpatients and sick inpatients
Conclusions
• Lung-protective ventilation, alveolar
recruitment, goal-directed fluid
resuscitation, the dangers of certain fluids,
vasopressor/inotrope selection, rational yet
aggressive use of antibiotics – these are
concepts that we can and should apply in
the OR every day