Continuous Subcutaneous Insulin Infusion Pumps: Exploration of Its Presence in the
Perioperative Setting
Heather M. Montgomery, CRNA MSNA
. Susan McMullan, CRNA MSN
Major Peter Strube CRNA MSNA—Faculty Mentor
Acknowledgements
CSII Therapy in the Perioperative Period
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I would like to acknowledge individuals that were essential in my professional and
educational development. Without them, this thesis would not have been possible. First, I would
like to recognize my mentor for this project, Major Peter Strube, CRNA, MSNA APNP ARNP. I
thank you sir for your support and guidance in the development of my project. There were many
instances when I wanted to bang my head up against a wall, but then you were there to keep me
focused and on track.
Second, Ms. Susan McMullan, CRNA, MSN is my mentor both professionally and
personally. You have given me the courage to stand up to my fears and reach my professional
goals. I will never be able to repay my gratitude, but please know that I thank you from the
bottom of my soul for all that you have done.
Finally I would like to acknowledge my family, especially my mother Maureen L.
Brayman and my brother Cody M. Brayman. These two individuals were diagnosed with type I
Diabetes early in childhood and continue to fight their disease several years later. I dedicate this
thesis to them, so that they may continue the fight so that I can selfishly have a family for as long
as possible. I love you both very much and please don’t ever give up.
Table of Contents
CSII Therapy in the Perioperative Period
1. List of Abbreviations
2. List of Definitions
3. Abstract
4. Introduction
5. The Pathophysiology of Type 1 Insulin Dependent Diabetes Mellitus
6. Insulin Pump Therapy Background
7. Optimizing Diabetes Treatment via Continuous Subcutaneous Insulin Infusion Therapy
8. Continuous Subcutaneous Insulin Infusion Therapy and Anesthesia Practice
9. Attempts at Research and CSII During the Perioperative Period
10. Published Opinions and Recommendations for CSII Therapy During the Perioperative
Period
11. From the Source: Insulin Pump Manufacturer Guidelines
12. Conclusions and Recommendations
13. References
Chapter 1: List of Abbreviations
3
CSII Therapy in the Perioperative Period
BG
blood glucose
BUN
blood urea nitrogen
CHF
congestive heart failure
CMV
cytomegalovirus
CSII
continuous subcutaneous insulin infusion
DCCT
Diabetes Control and Complications Trial
DKA
diabetic ketoacidosis
ECG
electrocardiogram
HbA1c
hemoglobin A1c
HHNKS
hyperosmolar hyperglycemic nonketotic syndrome
ISBGM
intensive
ISF
insulin sensitivity factor
IV
intravenous
L
liter(s)
MDI
multiple daily insulin injection
ACTH
adrenal corticotrophic hormone
mEq/L
milliequivalent(s) per liter
mg
milligram(s)
mg/dL
milligram(s) per deciliter
MI
myocardial infarction
MRI
magnetic resonance imaging
NADPH
nicotinamide adenine dinucleotide phosphate
NPO
nothing by mouth
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CSII Therapy in the Perioperative Period
PKC
protein kinase C
AGE
advanced glycoslyation end product
PVD
peripheral vascular disease
RAGE
advanced glycoslyation end product receptor
ROS
reactive oxygen species
SBGM
self-blood glucose monitoring
SDIS
Stockholm Diabetes Interventional Study
T1DM
Type 1 diabetes mellitus
T2DM
Type 2 diabetes mellitus
U
unit(s)
U/hr
unit(s) per hour
Chapter 2: List of Definitions
5
CSII Therapy in the Perioperative Period
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Basal rate: a continuous supply of a drug or other compound
Closed-loop device: Device that provides input with automatic output
Conventional insulin therapy: Receiving no more than 2 insulin injections daily
Glycoslyated: Glucose affixed to a surface (proteins, lipids, etc.)
Hyperglycemia: Blood glucose level > 110 mg/dL
Hyperketonia: Elevated ketones
Hypoglycemia: Blood glucose level < 70 mg/dL
Insulin sensitivity factor: Amount in decrease of blood glucose per 1 unit of insulin administered
Intensive insulin therapy: Receiving > 3 injections of insulin per day
Intraoperative period: Time from patient into the operating room to the recovery unit
Open-loop device: Device provides output with manual input
Perioperative period: Time frame from initial admission to entering the operating room
Postoperative period: Time from admission to recovery unit to discharge
Postprandial: Period of time after a meal
Prandial: Period of time during a meal
PubMed: an electronic search engine for health-related research articles
Chapter 3: Abstract
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Recent improved technology and supporting research for continuous subcutaneous
insulin infusion (CSII) therapy has allowed great expansion of its use in the treatment of type 1
diabetes (T1DM). It is estimated that 35% of the United State's type 1 diabetics use CSII therapy
and this number is expected to grow. In addition, more recent research looks to expand its use in
the treatment of type 2 diabetes (T2DM). So what is an anesthesia provider to do when their
patient presents with such a device?
The following paper helps to explain what CSII therapy is and how its use in the
perioperative period can be managed. Research on the benefits of normoglycemia and CSII
therapy will be discussed. Although little research has focused on outcomes related to CSII use
in the perioperative period, a few recent case studies involving CSII perioperative use have been
published. Initial research has looked into CSII presence in the perioperative period and
analyzed anesthesia provider’s documentation related to the device.
Many hospitals have policies developed for such circumstances but not all. The
following paper demonstrates that CSII therapy can be maintained in the perioperative period
and is a potential tool in the perioperative management of T1DM. There are contraindications
for its use, but the end result for CSII therapy management should be based on the anesthesia
provider’s clinical judgment.
Chapter 4: Introduction
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The thought that the diagnosis of Type 1 insulin dependent diabetes mellitus (T1DM)
was untreatable less than 100 years ago is rather baffling considering the advanced treatments
available today. Treatments that are of considerable use transform T1DM from a death sentence
to a manageable disease that can coincide with a high quality of life. Affecting over 1 million
Americans and growing, T1DM accounts for approximately 10% of all diabetics in the United
States.1(p2) These 1 million people require optimal continuous therapy not only to survive, but
also to avoid the devastating complications seen in poorly treated diabetics.
Proper diet and exercise are important in T1DM therapy, but the ultimate result is that
patients require insulin replacement. Conventional treatment includes delivery of insulin either
by subcutaneous injections or delivery of insulin via a continuous subcutaneous insulin infusion
(CSII) pump. More experimental treatments are pancreas transplants, islet cell transplants and
stem cell transplants.1(p10) These more unconventional treatments may provide a cure for T1DM
in the future, but since they remain in juvenile stages, the risk of such transplant procedures often
outweigh the benefit of conventional T1DM therapy.
Because T1DM therapy is most often limited to subcutaneous delivery of insulin, strides
have been made to minimize interruptions in life that T1DM often requires. Interferences in an
T1DM patient include but are not limited to frequent blood glucose (BG) monitoring and the
administration of insulin. The relatively new medications glargine and insulin detemir allow 24hour coverage of controlling BG levels with one injection daily. Besides improvements in
pharmaceutical treatments, the improvement of technology in CSII pumps has widely expanded
its use in the United States. It is estimated that 35% of T1DM patients in the US receive insulin
via a CSII pump.2(p6) The number of patients receiving CSII therapy is expected to grow not
CSII Therapy in the Perioperative Period
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only because of increasing numbers of T1DM cases, but additionally, CSII ay be helpful in the
treatment of insulin dependent diabetes mellitus type 2 (T2DM).3(2297)
Due to its increased presence, there is a high likelihood that a patient with T1DM with
CSII therapy will present in the clinical setting. Approximately 50% of T1DM patients will
require surgery in their lifetime and of these patients, there is increased probability that there will
be a percentage that receives CSII therapy.19 When a T1DM patient presents for surgery and it is
noted that they receive CSII therapy, what is the anesthesia provider to do? Do they leave the
CSII pump on or do they simply tell the patient to turn off their device prior to entering the
operating room? The following paper aims to close this gap and identify what clinically is best
for the patient under such circumstances and identify the significance of CSII therapy.
In order to close this knowledge gap, several references were obtained by several
methods. Pathophysiology texts were consulted and noted to give meaning to treating the
underlying disease process. A handbook was obtained outlining CSII therapy and it’s
recommendations for its use. A Pub Med search was completed over several hours using
keywords such as “continuous subcutaneous insulin infusion therapy + general anesthesia”,
“insulin pump therapy + perioperative period”, “CSII + surgery” among several other search
engine keywords. Also, the three US CSII pump manufacturers were contacted regarding
manufacture’s guidelines for use (Medtronic, Roche and Animas).
The following paper is meant to be a guideline for clinical judgment in terms of a T1DM
patient presenting for surgery who also happens to wear a CSII pump. The etiology of type 1
diabetes, T1DM’s potential effects on the human body, history of the CSII pump and benefits of
use will be explored. Recent literature will also be presented in terms of CSII pumps and the
perioperative period. In addition, two case studies that involve general anesthesia and CSII
CSII Therapy in the Perioperative Period
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pump therapy will be discussed. The goals of this thesis are of two: Anesthesia providers may
become aware more comfortable with CSII therapy and are not intimidated by it’s presence on
their patient presenting for surgery.
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Chapter 5: Pathophysiology of IDDM 1
Etiology
Recent literature suggests that the etiology of T1DM is not completely
understood, however there is a general consensus in the scientific community that there are two
factors that play a role in the cause of T1DM: A genetic predisposition and environmental
influences.5 It is widely accepted that T1DM is an autoimmune response that ultimately results
in the loss of insulin secondary to destruction of beta cells in the islets of Langerhans.5(p745) This
autoimmune destruction is T-cell mediated and the pathophysiology is described in a two-stage
process.
The immune response that leads to beta cell death in the Islets of Langerhans is complex,
with multiple pathways identified. Stage 1 begins with an initial insult, with autoantigens found
on the surface of beta islet cells begin to circulate throughout the intravascular and lymphatic
system.5(p745) These autoantigens are consumed by antigen-presenting cells, which then lead to
activation of CD4+ T helper cell lymphocytes. These lymphocytes secrete interleukin 2 that
leads to activation of beta cell autoantigen-specific T cytotoxic lymphocytes. T cytotoxic
lymphocytes infiltrate and destroy beta cells by their use of secreting granzymes and
perforins.5(p746) In addition, interferon is released from T helper lymphocytes and thus causes
additional destruction of beta cells. This release of interferon continues the destructive cycle, as
this process activates macrophages that secrete destructive cytokines and tumor necrosis factor
adding insult to the already assailed beta cell. In summary, the destruction of beta cells result
from the infiltration of lymphocytes and macrophages that lead to chronic islet inflammation
(also known as “insulitits”) and eventual beta cell death.5(p746)
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Stage 2 can be described as the increased production of beta cell autoantibodies, glutamic
acid, acid decarboxylase and other cytoplasmic proteins as well.5(p747) In addition of secretion of
interluekin 2, T helper cells secrete interleukin 4, which is responsible for the increased presence
of B-lymphocytes. B-lymphocytes are responsible for the creation of autoantibodies.
Interestingly, these antibodies can be detected in blood years before symptoms of diabetes occur.
Insulin is not immune from this response, as autoantibodies against insulin have been discovered
as well.5(p748)
Other mechanisms that contribute to the development of IDDM 1 include the reduced
presence of autoimmune mediators, such as T regulatory cells. These mediators help control the
immune response. This theory is supported by evidence of a mutation in T regulatory cells
found in a rare form of diabetes known as neonatal diabetes.5(p748)
Over the course of time, this autoimmune response leads to a large loss of beta cells and
hence insulin. C-peptide is a protein required for insulin synthesis and its presence will decrease
during the destruction of beta cells. It is thought that C-peptide plays a protective role and the
diminished presence of this protein contributes to additional beta cell loss.5(p748)
Although it is thought that the over-reactive immune response is genetically related, there
must be an initial trigger for the autoimmune response to occur. This trigger is believed to be
environmental, as in an external source that is exposed to the body. The source can either be
pharmaceutically sourced, nutritionally related, or pathogen sourced. Pharmaceutically, IDDM 1
has been linked to the drugs alloxan, streptozotocin, pentamidine, and Vacor. Cows milk and
high levels of nitrosaminde (a food preservative) in the diet have been linked to IDDM 1 as
well.5(p748) The mumps virus and coxsackivirus have been linked to IDDM 1. It is noted that
CSII Therapy in the Perioperative Period
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40% of those with congenital Rubella will eventually develop IDDM 1 . Persistent infections of
cytomegalovirus (CMV) have a small link to the development of IDDM.5(p748)
Disease Process of IDDM 1
Approximately 80-90% of beta cell loss must occur before hyperglycemia is manifested.
Alpha cells (which are responsible for glucagon production) and beta cells are affected. There is
a hormonal imbalance as glucagon is in excess of insulin. Hepatic glucose and fat metabolism is
regulated by the ratio of glucagon to insulin in the portal vein. High levels of glucagon and low
levels of insulin cause hyperglycemia and hyperketonemia.5(p748-749)
The role of insulin includes stimulation of fat synthesis and inhibition of fat metabolism.
When insulin is absent, fat metabolism is increased and as a result, there is an increase in
nonesterfied fats in the liver. This leads to increased glyconeogenesis and therefore
hyperglycemia and increased levels of ketone bodies via mitochondria in hepatic tissue.5(p748)
Because the peripheral tissue cannot utilize these excess ketones as fast as they are produced, a
drop in physiological pH occurs. The body attempts to compensate this metabolic acidosis by
creating a buffer system.5(p749) This is known as diabetic ketoacidosis (DKA) and is considered
an acute complication of IDDM 1.
With little to no insulin, chronic hyperglycemia can lead to serious complications
affecting almost every organ system. Chronic hyperglycemia can be evaluated by obtaining a
serum hemoglobin A1C level (HbA1c). HbA1c is a measurement of glycoslyated
hemoglobin.5(p749) As in the external environment, glucose is adhesive in nature, so it is expected
that glucose molecules have a tendency to “stick” to other components physiologically, also
known as glycoslyation. Glucose can attach itself to red blood cells in the blood, which is
known as glycoslyated hemoglobin. In states of excess glucose, there will be an increase in the
CSII Therapy in the Perioperative Period
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three glycoslyated hemoglobins: HbA1a, HbA1b, and HbA1c. HbA1c is used as a more longterm assessment of therapy excess. Since the average lifespan of a red blood cell is 120 days,
HbA1c gives a picture of average glycemic control over the past 3 months. Goal is to keep
HbA1c levels as close to normal as possible, with normal values described as between 4-6%,
which suggest an average BG level of 65-135 mg/dl. Elevated HbA1c levels are considered
between 8 and 10% (average BG level of 205-275 mg/dl). Seriously elevated levels are deemed
those 11-14% and correspond to an average BG level of 310-415 mg/dl. Studies have concluded
that diabetics with HbA1c levels less than 7% (a BG average of 170 mg/dl) are 50-75% less
likely to develop diabetes-related complications.
Long-Term Consequences of Poor Glycemic Control in T1DM
Chronic elevated BG levels can lead to damage at both the microvascular and
macrovascular levels. Examples of microvascular complications include retinopathy,
nephropathy and neuropathy. Examples of macrovascular damage are coronary artery disease,
cerebral vascular accident and peripheral vascular disease. How this physiological damage
occurs is complex and can result from multiple alterations in homeostatis. These mechanisms
include alterations in the polyol pathway, the hexosamine pathyway, protein kinase C levels,
nonenzymatic glycoslytion and oxidative stress.
The polyol pathway is an alternative metabolic pathway that is utilized by tissues that do
not require insulin for glucose uptake. These tissues include the lens of the eye, red blood cells,
blood vessels and nerves. When high levels of glucose are circulating in the blood, glucose is
shifted toward this pathway. Glucose is then metabolized to sorbitol via the enzyme aldose
reductase. Slowly, sorbitol is then changed to fructose per sorbitol reductase. This increase in
sorbitol and fructose attract water molecules to the site, thus resulting in an increased osmotic
CSII Therapy in the Perioperative Period
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pressure. This increase in osmotic pressure leads to cellular injury. In the nerves, sorbitol
affects ion pumps, causes injury to Schwaan cells and interferes with nerve conduction. Red
blood cells are stiffened and then become more difficult to circulate throughout the body at the
microvascular level. Aldose reductase inhibitors such as epalrestat and ranirestat may help delay
the onset of complications that are linked to the polyol pathway.5(p758)
Protein Kinase C (PKC) is an enzyme that is activated by increased glucose levels
inappropriately. Outcomes of this activation have lead to increased thickening of vascular
structures, increased production of extracellular cytokines, increased permeability and increased
contractility. These observations may contribute to both the micro and macrovascular
complications of diabetes.5(p758-759)
Nonenzymiatic glycoslyation is the non-covalent binding of gluose to proteins, lipids,
and nucleic acids without the assistance of enzymes. In a chronic hyperglycemic state, glucose
binds to collagen, vasculature, interstitial tissues and red blood cells thus becoming more
permanent. The product of this process is known as advanced glycoslyation end product (AGE)
and it’s receptor (RAGE). Both AGE and RAGE have several characteristics that cause tissue
injury. These products can lead to the trapping and cross-linking of proteins such as albumin,
low density lipoprotein, immunoglobulin and complement. This results in an increased
thickening and permeability in blood vessels and nerves. They can also bind to cellular receptors
that then release growth factors and cytokines. Increases in growth factors and cytokines result
in cell proliferation in glomueruli, smooth muscle of blood vessels and exhibits a fibrous effect
on collagen production. Additionally, AGE and RAGE can inactivate nitric oxide and hence a
loss of vasodilatation and decreased endothelium function. AGE and RAGE have been linked to
the induction of inflammation and destructive oxidative stress. The final detrimental component
CSII Therapy in the Perioperative Period
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of AGE and RAGE end products have been found to enhance coagulation with promotion of
platelet adhesion and decreased fibrinolysis.5(p759)
Another source of damage from hyperglycemia is the increased presence of reactive
oxygen species (ROS) and oxidative stress. This increased oxidative stress leads to damage in
both small and larger blood vessels. ROS is an end-product of alterations in the polyol pathway,
AGE’s, decreased nitric oxide synthesis, xanthine oxidase and nicotinamide adenine dinucleotide
phosphate (NADPH).5(p579)
Chronic hyperglycemia cause a redirection of glucose into the hexosamine pathway.
This pathway leads to the glycoslyation of many enzymes and proteins with changes in signal
transduction pathways and additional oxidative stress. A source of insulin resistance and
cardiovascular damage is thought to be from the attachement of N-actetylglucosamine on the
residues of nuclear and cytoplasmic proteins, a direct result of activation of this pathway.5(p759)
Acute Consequences of T1DM
In addition to DKA mentioned previously, there are other acute complications associated
with T1DM. These include hypoglycemia, Dawn Phenomenon and the Somogyi Effect.
Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS) is an acute complication of
T2DM and therefore will not be explored in this paper. Acute complications of T1DM can be
immediately threatening to life and if not identified and treated accordingly, can result in severe
comorbidities and mortality.
Hypoglycemia is defined as a blood glucose level less than or equal to 70 mg/dL.7 In the
neonate, hypoglycemia is defined at a lower level: Less than 35 mg/dL. Approximately 90% of
patients with IDDM 1 experience hypoglycemia and is a result of a mismatch between insulin
and carbohydrate intake, with favor towards insulin intake.5(p754) Hypoglycemia initiates a
CSII Therapy in the Perioperative Period
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sympathetic response secondary to loss of glucose to brain tissue. Although symptoms vary
between patients, general consensus states that tachycardia, palpitations, tremors, pallor, acute
anxiety and diaphoresis are symptoms of hypoglycemia. It is thought that the hypothalamus
plays a role in initiating this response. Continued loss of glucose to the brain causes an
alteration in brain kinase activity and neuron firing rates which lead to additional symptoms:
Irritability, hunger, headache, seizure activity, fatigue, lack of judgment, confusion, disruption in
vision, and coma. It is important to note that beta-blockers and general anesthesia can mask
early symptoms of hypoglycemia since these drugs alter the sympathetic response.6(p) Treatment
includes immediate restoration of blood glucose. In the awake patient, 15-20 grams of glucose
be administered and to the unconscious patient 0.5-1 mg of glucagon is administered
intramuscularly.7 Hypoglycemia is best avoided when the patient is properly educated about the
disease process of T1DM. Frequent blood glucose monitoring and customizing BG levels for the
patient being treated helps to additionally lower the risk of hypoglycemia.5,7
The Somogyi effect is an acute complication of T1DM that is associated with
hypoglycemia and then rebound hyperglycemia.5(p758) This is commonly found in the pediatric
population of IDDM 1 patients. This fluctuation of blood glucose levels can be dramatic and
warrants a change in therapy. The Somogyi effect is best described as when hypoglycemia
attempts to correct itself by initiating gluconeogenesis and glycogenolysis, thus triggering
growth hormone, epinephrine, cortisol, and glucagon release. These hormones also cause an
inhibition of peripheral glucose uptake, but breakdown fatty acids and proteins to produce
glucose. Insulin resistance has been linked to the aforementioned hormones, which this
resistance can last up to 48 hours. Factors that are linked to hyperglycemia within the Somogyi
effect include excessive carbohydrate intake. It is seen after the peak of insulin injection in
CSII Therapy in the Perioperative Period
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which hypoglycemia can result and hence cause a release of the hormones that lead to rebound
hyperglycemia. Ketones in the urine are often seen in Somogyi effect due to the breakdown of
fatty acids and proteins. Treatment includes continuous glucose monitoring and decreasing
dosages of insulin.5(p758)
The dawn phenomenon is a rise in blood glucose levels without hypoglycemia. Its cause
is thought to be from nocturnal release of growth hormone, which leads to the counter-regulation
of glucose. An increase in the clearance of insulin may also be linked. Changing the dose of
insulin and the time of its administration can help minimize dawn phenomenon. It is important
to note that treating dawn phenomenon can lead to the Somogyi effect and treatment of the
Somogyi effect can lead to dawn phenomenon.5(p758)
Long Term Consequences of T1DM
The long-term complications of T1DM greatly decrease the quality of life for these
patients and can lead to premature death. As explained previously, there are numerous
mechanisms how the pathophysiology of diabetes leads to these complications. Diabetic
complications are divided into two categories: Microvascular and macrovascular.
Endothelial thickening, thrombosis, and capillary hyperplasia lead to the microvascular
complications of retinopathy, neuropathy, and nephropathy.5(p759) Chronic hyperglycemia
(elevated HgbA1c) is associated with developments of these complications. Numerous studies
are linked with lower HgbA1c levels and lower occurrences of these complications and vice
versa.8
Macrovascular complications include coronary artery disease, cerebral vascular accident,
and peripheral vascular disease. Increased inflammation and the deposit of lipoproteins on an
already proliferated blood vessel contribute to these macrovascular comorbidities.5(p763)
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Premature atherosclerosis is linked to consequences of AGE and RAGE end products and the
increased presence of oxidation. As mentioned previously, several mechanisms at the cellular
level are involved in the development of diabetic macrovascular complications. An interesting
observation is the combination of microvascular and macrovascular complications contribute to
mortality and morbidity in this population. For example, the microvascular complication of
neuropathy affects the autonomic system so that the sympathetic nervous system does not
respond appropriately to changes in cardiac demand. This in grouping with coronary artery
disease can lead to potential for poor outcomes such as myocardial infarction and stroke.
Intensive Insulin Therapy and the Decreased Prevalence of Diabetic Complications
Several studies involving strict insulin therapy and conventional insulin therapy have
observed patient outcomes in terms of HgbA1c levels and the development of both
macrovascular and microvascular complications.8,9 “Strict” or “intensive” insulin therapy is
generally defined as receiving more than three insulin injections per day or receiving CSII
therapy. Intensive self-blood glucose monitoring (ISBGM) was also a part of the intensive
insulin therapy, which is defined as blood glucose checks greater than four times per day.
“Conventional” treatment of diabetes is viewed as patients receiving no more than two injections
of insulin with no or infrequent self-blood glucose monitoring. Most of the studies reviewed
involved both T1DM and T2DM especially when meta-analyses were performed. It is noted that
within the meta-analysis explored that IDDM 1 and IDDM 2 are analyzed separately in terms of
outcome.
In 2006, a meta-analysis, performed by Stettler et al., involved studies linking a reduction
in the development of macrovascular complications and intensive insulin therapy.9 The review
included 8 studies of IDDM 1 patients (N=1800, with a total of 5,578 person-years of intensive
CSII Therapy in the Perioperative Period
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insulin therapy and 5,717 person-years of conventional insulin therapy) and observed the
incidence of a “macrovascular event” as a measured outcome. The term “macrovascular event”
was defined as any incident that included a fatal or non-fatal myocardial infarction (MI), the
need for either cardiac bypass vessel graphing or angioplasty, the development of congested
heart failure (CHF), incidence of stroke, or the development of peripheral vascular disease
(PVD) as evidence by the diagnosis of claudication in the extremities or amputation of a lower
extremity. After analysis of the 8 studies, it was found that in the intensified group there were a
total of 33 macrovascular events within the person-years of follow-up compared to 99
macrovascular events within the conventional insulin therapy group. It was found that the
incidence of macrovascular complications was less in trials where there was a greater reduction
in HgbA1C (p= 0.050).
The incidence rate ratio was 0.36 for all studies analyzed, in favor of
intensive insulin therapy. Limitations of this meta-analysis include noting that all of these
studies in did not set out to observe macrovascular complications directly. For example, the
Diabetes Control and Complications Trial (DCCT) study used the development of retinopathy (a
microvascular complication) as a measured end-point for observation of intensive versus
conventional insulin therapy. The incidence of macrovascular complications was not a targeted
measurement, but however was an indirect observation. Many of these observations were
subclinical in nature without patient complaint, meaning that a routine ECG that indicated a past
MI was included as a macrovascular event (i.e. a “silent MI”). In addition, there were six
studies included in this meta-analysis that were measurements of relatively small sample
populations (average N= 59) as compared to two other studies that were very large in sample size
(average N= 719.5). It is possible that the two larger studies could have caused skewing of the
overall data observed.
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A meta-analysis of the incidence development of microvascular complications in terms
of conventional versus intensive insulin therapy could not be retrieved. However, it is noted that
there are studies have been conducted that favor an intensive insulin therapy regimen for a
reduction in the incidence of microvascular comorbidities. The largest of these studies (which
was included in the aforementioned meta-analysis) was the DCCT, which was performed in
1993.8(p2232) The sample size included 711 patients who were assigned intensive glucose control
and 730 who were assigned conservative glucose control. The sample population was followed
for an average of 6.5 years. In the DCCT trial, “intensive glucose control” involved treating
T1DM with either multiple daily insulin injection (MDI) or CSII therapy. Both intensive
management therapies included ISBGM. Conventional glucose control was managed by no
more than two injections of insulin daily with infrequent self-blood glucose monitoring (SBGM).
This study shows it’s significance by observing a 76% decrease in the development of
retinopathy in those with intensive glucose control (p= <0.001) and a 69% reduction in the
development of neuropathy with intensive glucose control (p=0.006).8(p2233) It is important to
note that this study was partially blinded and that if serious complications developed, both the
patient and the clinical researcher were allowed access to outcome data. Otherwise, data was
inaccessible to both parties.
The Stockholm Diabetes Intervention Study (SDIS) was also conducted in 1993 and
observed both HgbA1c levels and the development of serious retinopathy as measurable
outcomes.8(p2233) In comparison to the DCCT study, the SDIS study looked at a smaller
population size (N= 102) with 48 patients receiving intensive glucose control therapies and 54
utilizing conventional treatments. The SDIS “intensive” therapy differed from the DCCT trial by
omitting CSII as a treatment option. Instead, at least three daily subcutaneous injections of
CSII Therapy in the Perioperative Period
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insulin were administered within this group, along with continuous education about the
importance of maintaining blood glucose control. The conventional group received insulin in no
more than two subcutaneous injections per day and routine diabetes management. The first 5
years of the study included both the intensive and conventional therapy groups, however at the
end of the 5 years, the conventional group was switched to the intensive therapy group. The
study was conducted over 7.5 years. The development of severe retinopathy in the intensive
control group was 27% as compared to 52% incidence in the conventional therapy group. This
was calculated to be significant with a p value of 0.04. The development of nephropathy in the
intensive control group was statically lower in the intensive glucose therapy group (p= 0.04).
However, there was no significance in the development of peripheral neuropathy when
comparing the two groups (p= 0.1). Limitations to this study include a small sample size and the
incidence of up to 60% of conventional therapy individuals being switched to intensive treatment
during the last 2.5 years of the study.8(p2233-2234)
Despite the limitations of the previous studies, it is fair to state that optimal glucose
control has benefits to reducing the long-term complications of T1DM. Intensive glucose
control therapy more closely resembles how the pancreas functions under normal circumstances.
As the pancreas continuously secretes insulin to control blood glucose levels, so does frequent
administration of insulin for the diabetic patient aids in achieving normoglycemia and thus the
prevention of complications associated with T1DM.
CSII Therapy in the Perioperative Period
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Chapter 6: Insulin Pump Therapy Background
Initial Conception and Early Designs
The idea of an external device used to continuously deliver insulin was first
conceptualized in the early 1960’s. In 1963 Arnold Kadish introduced a closed-loop device,
meaning that while delivering insulin, blood glucose levels were constantly monitored.2(p2) This
closed-loop machine would administer additional insulin when blood glucose levels were
detected outside an acceptable range using a pump with an autoanalyzer and pump function was
controlled via an on-off servomechanism.10 The device resembled more of a jetpack and it’s
large and bulky structure left little to practical use.
Advances in computer technology lead to development of the first machine run by a
computer. In 1974, the Biostator was introduced which used computer algorithms to calculate
insulin and dextrose delivery based blood glucose levels. The pump itself was computer
controlled, and blood glucose levels could be plotted and printed in minute intervals on a graph.
Like Kadish’s device, the Biostator was a closed-loop system, allowing continuous monitoring of
blood glucose levels and an allowing an appropriate response from the machine. Again, the
Biostator was large and bulky, requiring it’s placement on a desktop for use. Because of this
limitation, it was mainly used for clinical trials, thus providing primary research for more
practical approaches to CSII therapy.10(p128)
The late 1970’s saw improvements in computer technology and the introduction of the
microprocessor. The Mill-Hill insulin infusion pump took advantage of this technology: It was
portable and weighed at a relatively light 159 grams, it allowed two means of insulin delivery
with a basal infusion rate and an increased prandial rate, and it was powered with a battery.2(p3)
The user pushed a button initiated the prandial rate before a meal was consumed and allowed an
CSII Therapy in the Perioperative Period
24
eight times higher than basal rate infusion. This pump was an open-loop system meaning that
the administration of insulin was not immediately adjusted to blood glucose levels. The MillHill infusion pump was a first in that delivery of insulin was via the subcutaneous route. An
intravenous (IV) route connected previous devices, which lead to complications such as
phlebitis, infection, and thrombosis.
Studies such as the 1978 Pickup and Keen study demonstrated that portable CSII could
be a practical approach in the management of T1DM.11 Additional support from additional
research lead to the first commercially available CSII pump. One of the first marketed pumps,
the Autosyringe, became available in 1978. The same team that developed the Mill-Hill infuser
developed a pump that utilized a microprocessor-controlled pump known as the Nordisk
infuser.10(p129) Because of the continuous improvements to technology, pharmaceutical
companies began to develop more CSII pumps during the early 1980’s.
Early Limitations of Its Use and Improvements in Technology
These early insulin pumps did have their limitations that eventually lead to reservation of
its use and a sense of caution in healthcare providers. For example, in the 1980’s, the pumps
were relatively large, awkward (average weight was around 400 grams) and their batteries had to
be recharged often.16 Several instances of tube occlusion and needle dislodgement lead to
several cases of DKA and hyperglycemia. Infection at the site of infusion was common, not to
mention that needles used to deliver the insulin were metal and very uncomfortable. There were
no safety alarms so careful observation of the insulin reservoir had to be maintained so that there
wasn’t a sudden loss of insulin. The basal rates were limited in customization and some pumps
required a screwdriver to alter the basal rate. Because of these limitations, CSII was often
reserved to difficult-to-manage diabetes, and even then outcomes were less than optimal.10(p130)
CSII Therapy in the Perioperative Period
25
The 1990s gave way to vast improvements in CSII therapy. Improvements in technology
lead to resolution of previous issues such as tube occlusion, the accidental delivery of too much
insulin, leaking of insulin, and a decrease of the pump size.10 Also, alarms became available to
notify the patient of low battery status and low insulin levels in the pump. These many
improvements in insulin pump technology lead to greater use among T1DM patients and allowed
adequate sample populations to be studied.
Today CSII therapy involves pumps that are comparable in size and weight to a pager.
Subcutaneous insulin delivery infusion sets that are plastic thus making the wearing of the device
more comfortable. Proper education and development of improved insertion techniques have
lead to a decrease in the incidence of infection at the infusion site.3(p2296) Batteries can be used
for extensive periods of time before recharging or replacing is required. Prandial boluses can be
calculated from integrated programs within the pump. Depending on the brand, basal rates can
be adjusted within 0.025 U/hr.10(p131) A unique feature of the Medtronic MiniMed Paradigm
CSII pump is the availability of a separate continuous glucose monitor that transmits data to the
pump so that trends can be established and warn of any potential fluctuations in BG.12 These
several improvements in CSII therapy have eliminated many past fears associated with it’s use
and has greatly expanded CSII therapy.
Advantages to CSII Use
The obvious benefit to CSII therapy in T1DM patients is better glycemic control as
compared to conventional diabetes management. There is evidence that gives CSII an advantage
over blood glucose control as compared to MDI therapy.13,15 A meta-analysis exploring this
topic will be reviewed in the next chapter. This benefit of controlled BG levels results in a
CSII Therapy in the Perioperative Period
26
decrease of HgbA1c level and can be concluded that the risk of developing T1DM complications
is lowered as well.
Studies have shown that hypoglycemic events have a decreased incidence among patients
who utilize CSII therapy. In fact, recurring hypoglycemia is an indication for CSII use. This
minimization of hypoglycemia may be contributed to the patient’s commitment to check BG
levels frequently. Also, with CSII therapy, there is no depot of insulin that is created at the site
of infusion, unlike with regular subcutaneous injection sites. Exercise, exposure to heat, and
manual manipulation can cause increased availability of insulin to the blood stream from the
development of these depots. As mentioned previously, some CSII pumps come with a
continuous BG monitor that alarms when hypoglycemic events are about to occur.
Perhaps the greatest advantage to CSII therapy is the flexibility it allows the T1DM
patient. Patients are able to adjust their insulin rates on an hourly basis and therefore it is
allowable to skip a meal without the consequence of hypoglycemia.3(p2295) Additionally, they can
sleep in late if they choose since the CSII pump continues to deliver insulin in an unconscious
state. They do not have to inject themselves on a regular basis and are able to engage in
strenuous exercise. It is thought that increased patient freedoms have lead to a spike in CSII
therapy use.2
Disadvantages to CSII Use
CSII therapy does have its fair share of drawbacks. CSII therapy does not create a depot
of insulin at the infusion site can therefore result in DKA if insulin infusion is suddenly
interrupted. This in combination that a short-acting insulin (lispro is the common insulin used in
CSII pumps) can lead to DKA more quickly than with other treatment methods. On the opposite
spectrum, in the past there have been reports of CSII pump malfunction in which too much
CSII Therapy in the Perioperative Period
27
insulin is delivered resulting in severe hypoglycemia.3(p2295) However, improved microprocessor
technologies have generally eliminated this problem and this problem has not been documented
in the past 10 years.10(p130) Frequent blood glucose monitoring can help eliminate both potential
DKA and severe hypoglycemia.
Also, there is a risk of infection at the site of infusion. This is listed as a primary reason
behind discontinuing CSII therapy. Often, a cellulitis develops because of infection. The
development of an abscess is rare in CSII site infection. The estimated occurrence rate of
infection is between 7.3 and 11.3 per 100 patient years.10(p130) Proper education and aseptic
techniques can help minimize this complication.
Weight gain is common among patients who switch from conventional T1DM therapy to
CSII therapy. In the DCCT trial, patients utilizing CSII treatment gained an average of 4.5
kilograms as compared to those within the conventional treatment group. It is important to note
the same study revealed no difference in the weight gained between CSII therapy and MDI
therapy. The weight gain is mostly due to reducing glycosuria in these patients, but exercise and
close monitoring of caloric intake can help minimize this disadvantage.10(p131)
How a CSII pump works
A CSII pump (or insulin pump) is a small electronic device that currently is about the size
of a pager and weighs less than 100 grams. There are two main parts: The infusion pump and the
infusion catheter set. The insulin used is ultrashort-acting and the most commonly found in CSII
pumps is lispro.3(p2296) Insulin is found in a syringe or reservoir within the pump. Rechargeable
or replaceable batteries are found within the pump device.
Using several calculations and making adjustments based on patient response, basal rate
and prandial insulin rates can be calculated.12(p2) CSII pumps have the ability to store several
CSII Therapy in the Perioperative Period
28
different basal rates depending on the pump manufacturer.3(p2294) In addition, some pumps allow
the capability to calculate postprandial insulin doses by entering how many carbohydrates were
consumed during the meal. As mentioned previously, those CSII pumps that have continuous
glucose monitoring capabilities allow trend in insulin delivery and blood glucose levels to be
observed.
All CSII pumps on the market today are open-loop systems and are not to be confused
with a closed-loop system. Open-loop systems require manual input from the user to adjust
insulin dosage rates whereas a closed-loop system acts more like an artificial pancreas as
described previously. Although some current CSII pumps allow continuous glucose monitoring
of interstitial fluid and the blood glucose level is calculated and transmitted to the device, insulin
rates are not adjusted per the pump. Patients must decide on their basal rate for the day and
manually press a pad on the CSII pump to activate bolus doses. Current technology does not
allow for automatic adjustments in insulin rates, as there are limitations in the continuous
glucose-monitoring device for acceptable use in a closed-loop system.2,3,10
Primary insertion sites for CSII infusion catheters include subcutaneous tissue found
around the abdomen and the upper buttocks. Upper arm and upper anterior thigh subcutaneous
tissue are additional insertion sites.12 The infusion catheter set can remain for 72 hours before
removal is required. The catheter infusion set must be rotated to a different aforementioned site
in order to prevent the development of lipohytroperphy and scar tissue. During pregnancy,
insertion of the device is best avoided in skin tissue of the abdomen where the skin is tense. The
best practice for preventing skin infection at the insertion site is to maintain aseptic technique:
Wash hands prior to inserting the catheter infusion set, keep the infusion set sterile, and cleanse
CSII Therapy in the Perioperative Period
the site with an aseptic skin wipe. If a skin infection develops, it is often caused by the
staphylococcal bacterium and is treated with oral antibiotics. 3(p2295)
29
30
CSII Therapy in the Perioperative Period
Chapter 7: Optimizing Diabetes Treatment via Continuous Subcutaneous Insulin Infusion
Therapy
Evidence in Support for CSII versus MDI treatment of T1DM
Perhaps the best support for CSII therapy came from a meta-analysis by Jeitler et al in
2008.15 This retrospective analysis reviewed data from a total of 17 studies. The goal of the
meta-analysis was to compare the effects of CSII therapy to MDI therapy, which was measured
by glycemic control. Other measured outcomes such as insulin requirements and hypoglycemic
events were reviewed, but not included in the meta-analysis. A total of 22 studies were reviewed
to include all measured outcomes, however only 17 studies were considered for the metaanalysis. For purposes of this paper, the meta-analysis regarding adult T1DM patients and
glycoslated hemoglobin will be reviewed.
Twelve of the total 17 studies were included in evaluation of glycoslated hemoglobin
levels. Six of the 12 adult T1DM studies were included in meta-analysis of HgbA1c comparison
between MDI therapy and CSII therapy. It was found that the weighted mean difference
between MDI therapy and CSII therapy was -0.04% in favor of CSII therapy and held an I2=
72% indicating heterogeneity. The remaining 6 studies measured HgbA1 with a weighted mean
difference of -0.06% in favor of CSII therapy and an I2= 84% which also indicated
heterogeneity. Additionally, there was no statistical difference when the two groups were
analyzed.15(p943-946)
Based on these results, it can be strongly suggested that CSII therapy is beneficial for
decreasing glycoslated hemoglobin levels without the increased risk of developing
hypoglycemia. According to the authors of the study, no meta-analysis of hypoglycemic events
was performed due to small numbers of patients reporting mild hypoglycemia and rare reports of
CSII Therapy in the Perioperative Period
31
severe hypoglycemia during the trials. There was also a lack of values in the studies that were
required for variance calculations.
Limitations of the analysis included the high degree of heterogeneity. It is noted that
several sensitivity tests were performed to help explain the high levels of heterogeneity but were
unable to do so.14(p946) Several of the studies included were older in nature (dating from 1982),
did not use the same CSII pump, were not the same in terms of study design, and had smaller
sample populations. Interestingly, older studies did not show a statistical difference in the
lowering of glycoslated hemoglobin between CSII therapy and MDI therapy, however all studies
newer than the year 2000 did show a statistical difference. Perhaps this is an indication of
improved technology yielding improved results.
Current use of CSII Therapy in Diabetes Mellitus
The most studied and utilization group for CSII therapy is by far the T1DM population.
After multiple reports of supporting research in favor of CSII therapy, its use has greatly
expanded, especially in the United States. It is estimated that 35% of IDDM 1 patients in the
United States are current CSII users.2(p6) The United States is considered a “high-use” country as
compared to the United Kingdom where current CSII use is only limited “a few hundred
users”.14 Discrepancies in rates of use can be contributed to unpredictable reimbursement of
pumps and/or supplies and lack of knowledge in regards to benefits of CSII therapy. At this
point, use in T2DM patients is limited, although its expanded use in this patient population is
currently being explored.
When a patient and his or her endocrinologist explore potential implementation of CSII
therapy for the treatment of T1DM, there are several indications for CSII therapy: Recurrent
hypoglycemia, pregnancy, frequent hospitalizations, recurrent episodes of DKA, incidence of
CSII Therapy in the Perioperative Period
32
dawn phenomenon, gastroparesis, low insulin requirements, or patient preference.2,14 The patient
should meet the following characteristics as well: be highly motivated, be responsible, be
psychologically stable, be agreeing to measure food intake, and be agreeing to medical followup.
Although there are few studies evaluating CSII therapy for T2DM treatment, research in
this topic is expanding due to a potentially large market. As T2DM continues its course, insulin
resistance increases and beta cell dysfunction increases. Eventually many patients require
insulin to maintain normoglycemia. Many of the potential benefits that could be obtained from
CSII therapy in T2DM patients are extrapolated from benefits seen in CSII therapy in T1DM
patients.2(p79) The use of CSII in T2DM is controversial and is associated with additional weight
gain but nonetheless, additional research is required to determine the appropriateness of CSII
therapy in T2DM patients.15(p948)
CSII Therapy in the Perioperative Period
33
Chapter 8: Continuous Subcutaneous Insulin Infusion Therapy and Anesthesia Practice
Effects of Surgery and Anesthesia on Glucose Regulation
Perhaps the most obvious effect of surgery on the patient is stress response. Stress
response can be defined as an increased metabolic rate, increased secretion of hormones, an
impaired immune response, among other physiologic responses. The sympathetic stress
response results in increased circulating epinephrine, norepinephrine, cortisol, and growth
hormones.16,17 In regards to the diabetic patient, the key stress response to surgery is the
secretion of cortisol. Cortisol is a powerful hormone that is secreted by the zona fasiculata in the
adrenal glands. It is responsible for the induction of glycogenolysis to increase BG levels and
dampen the immune response. Neuraxial anesthesia can help minimize the sympathetic
response to surgery and therefore minimize these glucose-liberating hormones.16(p)
In addition to the sympathetic response created by surgical trauma, halogenated
anesthetics have adverse effects on metabolic homeostasis. In vitro studies have demonstrated a
dose-dependent decrease in insulin response to hyperglycemia in the following anesthetic agents:
Isoflurane, halothane, and enflurane. Although benzodiazepines decrease the presence of adrenal
corticotrophic hormone (ACTH) and thus the secretion of cortisol, they have been linked to a
paradoxical response that results in an increased secretion of growth hormone.17(p85)
Despite the negative impacts of surgery and anesthesia on glucose regulation, there are a
few examples of anesthetic technique that can help stabilize the previously mentioned alterations
in glucose homeostasis. Etomidate has been demonstrated the ability to minimize cortisol
secretion by impairing the production of adrenal steroids.16,17(85) Use of high-dose opioids block
the sympathetic response to surgical stress and therefore prevents the release of metabolic-
CSII Therapy in the Perioperative Period
34
altering hormones. In continuation of opioids-based technique, regional anesthesia is also
beneficial in glucose regulation because of its ability to block the sympathetic response.17(p86)
Normoglycemia and Improved Surgical Outcomes
Poorly controlled blood glucose levels have been linked to several postoperative
complications. Acute hyperglycemia has been shown to delay wound healing secondary to
depression of immune function. It has also been related to increased levels of inflammatorycausing cytokines. Hyperglycemia can trigger diuresis and thus lead to dehydration and
electrolyte imbalances.18 DKA is always a potentially lethal outcome, especially in T1DM
patients after surgery.
Several retrospective studies linking postoperative complications and BG control have
focused on patients undergoing cardiac surgery. These studies have produced mixed results in
terms of perioperative glucose control and improved surgical outcomes, although more current
studies suggest that there is indeed a link between glycemic control and unfavorable
outcomes.18(p484) A 2005 study by Gandhi et al suggested that within cardiac surgery patients,
there is a 30% risk increase in adverse outcomes for every BG increase of 20 mg/dL in serum
glucose greater than 100 mg/dL.19 For non-cardiac surgical patients, there are few studies that
research intraoperative BG control and a potential link to poor outcomes.
What constitutes an acceptable upper-end perioperative serum glucose level is diverse
among anesthesia providers. Generally, acceptable practice is to control BG levels and prevent
both hyperglycemia and hypoglycemia. A more definitive “high end” BG level was defined in
2009 by a joint statement from the American Association of Clinical Endocrinologists and the
American Diabetes Association. Current recommendation is to generally keep blood glucose
levels less than 180 mg/dL, depending on the patient’s status.20 For example, in the critically ill
CSII Therapy in the Perioperative Period
35
patient, a BG level of 140-180 mg/dL is more desirable. The group also cautions against
ambitious treatment of hyperglycemia, as hypoglycemia is more likely to result. A suggestion to
prevent hypoglycemia is the implementation of frequent BG checks.
Establishing the Clinical Question: What is the Role of CSII in the Perioperative Period?
It is clear that CSII therapy is beneficial in the treatment of T1DM. It provides the
continuous basal infusion rate that T1DM patients require for survival. It also provides
postprandial bolus doses so that large fluctuations in BG levels can be avoided. CSII therapy has
suggested through numerous studies that it is superior in maintaining normoglycemia and
preventing long-term complications of T1DM as compared to conventional insulin therapy or
MDI therapy. Likewise, maintaining normoglycemia, as evidence by numerous clinical studies,
can minimize the risk of perioperative complications. Is it possible to utilize a patient’s CSII
pump during a surgical procedure as an adjunct in management of T1DM? Attempts to close
this knowledge gap will be explored in the following chapters.
CSII Therapy in the Perioperative Period
36
Chapter 9: Attempts at Research and CSII during the Perioperative Period
Unfortunately, randomized studies observing the outcomes of conventional IDDM 1
management and use of CSII during the perioperative period have not been explored. Most
recommendations for its presence during this inpatient timeframe are based on expert opinion
and not evidence-based medicine. However, the need to close this knowledge gap has been
identified as case studies and preliminary studies have recently been published. The following
investigates the presence of CSII in the perioperative setting.
Case Study #1: Presence of CSII During General Anesthesia
In 2004 the AANA Journal published a case study on a 43 year-old patient, physical
status III, who had T1DM and managed his diabetes via CSII. He presented for repair of L5-S1
disc herniation, which resulted in right leg and back pain. He had no other medical problems
besides the aforementioned issues. He was of normal weight and stature. His labs were normal
except that his BG level was 64 mg/dL, therefore he was given a 4 gram glucose tablet to
ingest.21
His CSII pump was set to deliver his established basal rate at 0.3 u/hr and the insulin used
in his pump was the standard ultrashort-acting insulin lispro. According to the authors, the
patient was very knowledgeable regarding his disease and use of his CSII pump. Dependent on
time of the day, the patient’s CSII pump would infuse various basal rates, ranging from 0.2 U/hr
to 1.0 U/hr. What was not discussed in the case study was the patient’s insulin sensitivity factor
(ISF), what time of the day the patient underwent surgery, or what determined the 0.3 U/hr basal
insulin infusion rate.21(p354)
The patient had a remifentanyl infusion begun prior to his rapid sequence induction.
After successful induction, the patient was repositioned prone and care was taken not to interfere
CSII Therapy in the Perioperative Period
37
with the CSII pump’s position and operational status. The maintenance of general anesthesia
was obtained by utilizing the remifentanyl infusion at between 0.125 and 0.50 mcg/kg and
sevoflurane at 0.8%. The entire operation lasted 66 minutes. Intraoperatively, BG was found to
be 118 mg/dL and no adjustments were made to the patient’s CSII pump. A high dose
administration of dexamethasone 20 mg IV was performed at the surgeon’s request along with
ketorolac 30 mg intramuscularly.
At completion of the procedure, the patient was extubated without incident and
transferred to the postanesthesia care unit. His blood glucose was checked and was 158 mg/dL.
After initial phase recovery, the patient consumed a meal and administered a 1.8 U insulin bolus
via his CSII pump. The final BG obtained was 185 mg/dL and discharged home one hour
later.21(p355) It was not mentioned in the case study that the patient received any extra insulin
from hospital staff.
This case study revealed that CSII could be utilized during the perioperative period. The
authors believe that CSII is a helpful tool in managing a patient’s T1DM and simplifies glucose
control by eliminating the need of intravenous insulin and dextrose infusions. The authors
recommend that patients are normoglycemic prior to induction so that the occurrence of
intraoperative hypoglycemia is minimized. They also recommend that the anesthesia provider
ask the patient how to turn off the CSII pump, how to adjust basal insulin rates, how to determine
proper pump function and how to attach an infusion catheter set should it become dislodged.
Support of this recommendation originates in their belief that the CSII pump user is highly
educated of their device and disease. The authors also recommend checking BG levels at a
minimum of one hour and checking CSII pump screen occasionally to assess pump function
CSII Therapy in the Perioperative Period
38
during the intraoperative period. The authors also recommend that intravenous solutions should
not contain dextrose.
Reservations raised from this case study include location of the CSII pump infusion site
and what guidelines would be utilized if adjustments in the basal rate were required during the
intraoperative period. The authors did not discuss where the infusion site was located and
whether or not the infusion site needed to be moved to a site that allowed both optimal surgical
access and anesthesia provider access to the CSII pump. These are potential issues that could
interfere with CSII therapy during a surgical procedure. Also, concern arises from adjusting
basal rates without asking the patient about their ISF. ISF is the amount a patient’s blood
glucose level decreases with one unit of ultra short-acting insulin lispro administered. As
mentioned previously, the patient’s ISF was not disclosed in this case study although a general
consensus was discussed and that for one unit of subcutaneous lispro will lower BG30 to 50
mg/dL. As patients with CSII pumps are very knowledgeable, patients are able to disclose their
personal ISF to the anesthesia provider, which can be useful in determining customizable
intraoperative basal rates.
Case Study #2: Complications After Discontinuation of CSII Therapy
In 2005 the Journal of Clinical Anesthesia published a case study about extreme
hyperkalemia after discontinuation of CSII therapy. The patient was a 35 year-old male,
physical status IV, who was undergoing surgery for renal transplant. He had the diagnoses of
T1DM, retinopathy, hypertension, gastroparesis and renal failure. His medication list included
aspirin, fexofenadine, ranitidine, valsartan, verapamil, ramipril, furosemide, and terazosin. He
received insulin via a CSII pump and his basal rate was set at 0.8 U/hr. His BG in perioperative
CSII Therapy in the Perioperative Period
39
labs was 74 mg/dL and his potassium was 5.1 mEq/L. Decreased renal function was evident as
BUN was 75 mg/dL and creatinine was 4.6 mg/dL.22
Since the CSII pump infusion site was located within the surgical field, the CSII pump
was discontinued and removed from the patient. Plan was to frequently monitor BG levels and
cover insulin requirements as needed. Induction of general anesthesia was performed without
complications. Maintenance of general anesthesia was obtained via isoflurane. Following
induction, blood glucose was 134 mg/dL and serum potassium was 5.3 mEq/L. Three hours after
start of surgery, BG was found to be 112 mg/dL however serum potassium was found to be a
critical 7.6 mEq/dL. Despite the hyperkalemia, no changes in electrocardiogram were noted per
the authors. The patient was administered 3 U of regular insulin and hyperventilated (minute
ventilation of 11 L). In 15 minutes serum potassium had decreased to 6.9 mEq/L. The patient
was then given a 2 unit regular insulin bolus and started on a regular insulin infusion of 0.8 U/hr
(note the basal rate of the CSSII pump). Serum glucose was 201 mg/dL however the serum
potassium continued to trend downward with a value of 6.1 mEq/L. Shortly after initiation of the
insulin infusion, renal blood flow was established to the newly transplanted kidney; the kidney
immediately began to produce urine. The serum potassium level was 5.2 mEq/L after 1 hour of
the intravenous insulin infusion drip. Normoglycemia was present as evidence by a blood
glucose level of 114 mg/dL. According to the authors, the remainder of the surgery was
uneventful. After transfer to the postanesthesia care unit, BG was 169 mg/dL and serum
potassium was 4.9 mEq/L.22(p631)
This article demonstrates not only the role of insulin and extracellular potassium
regulation, but also the need for frequent monitoring of these patients. Although BG and serum
potassium levels did not dramatically rise immediately, had levels been checked every hour
CSII Therapy in the Perioperative Period
40
instead of the initial 3 hours, the rise in potassium could have been trended and treated before it
reached critically high levels. Based on description of this patient, he had poorly controlled
diabetes that had resulted in several co-morbidities. This is evidence in itself for frequent serum
monitoring. Although this is only one example of complication from discontinuation of CSII
therapy, it can be extrapolated that these patients should have some sort of basal insulin infusion
either via their CSII pump or via an intravenous insulin infusion drip set at their basal infusion
rate. Upon conclusion of the case study, the authors present the same recommendation.
Observing CSII Therapy in Patients During the Perioperative Period
The purpose of a study titled “Insulin Pump Therapy in Patients Undergoing Surgery”
was to observe the perioperative management of patients who received CSII therapy. The
findings were presented during the American Association of Clinical Endocrinologists’ Annual
Meeting in 2011. The study was retrospective and used documentation review for gathering
data.23
The study reviewed 50 general anesthesia surgical cases over the course of 5 years in
which the 35 patients with T1DM utilized CSII therapy. The nature of the surgery varied: 16
orthopedic, 9 general surgical cases, 7 urologic, 7 involving renal transplant, and 11 were
classified as “other”. The review of documentation revealed discrepancies in not only CSII
pump use, but documentation of BG levels as well. During the intraoperative period,
documentation revealed that in 7 cases the patient was disconnected from the CSII pump, in
another 7 cases the CSII pump was only suspended. The status of the CSII pump in the
remaining 36 cases during the intraoperative period is unknown, as documentation of its
presence is absent. Further review showed that intraoperative glucose was recorded in 30 of the
50 cases.
CSII Therapy in the Perioperative Period
41
This study revealed inconsistency in documentation of intraoperative management of
T1DM, which happens to be a responsibility of the anesthesia provider. Because of the poor
documentation, it is difficult to draw conclusion about how anesthesia providers feel about the
presence of CSII therapy during the perioperative period or how it is managed. The sample
population was small and the outcomes of this study are a possibly a reflection of an institutions
attitude toward management of T1DM and CSII therapy. Further studies should not include a
retrospective approach, but instead a prospective approach so that outcomes may be observed.
CSII Therapy in the Perioperative Period
42
Chapter 10: Published Opinions and Recommendations for CSII Therapy During the
Perioperative Period
Specific guidelines have yet to be published for CSII therapy during the perioperative
period. The American Diabetes Association and the American Association of Clinical
Endocrinologists have yet to establish recommendations or guidelines regarding this topic.
Guidelines that were retrieved from the literature were sourced from hospital-based policy and
procedures. These guidelines were variable from institution to institution, as were professional
opinions.
In a published review from The Diabetes Educator, guidelines with outcome measures
were proposed for CSII therapy in the hospital setting. Contraindications to inpatient CSII
therapy included:
“Patient with altered states of consciousness; critically ill patient requiring intensive care;
patient at risk for suicide; patient refuses or is otherwise unable to participate in own care;
family member, friend or significant other refuses or is otherwise unable to participate in
care; radiology procedure; other circumstances identified by the physician”24
Patients would also be required to carry their own CSII pump supplies since, according to the
authors, “because hospitals typically do not keep insulin pump supplies in their formulary
(except for insulin)”.24(p852) Unfortunately, the proposed guidelines did not include CSII therapy
use during the perioperative period and the authors noted this limitation. They did state that if a
patient required general anesthesia for a surgical procedure that CSII therapy should be
discontinued since the patient would be unable to regulate their CSII pump. An argument
against this recommendation is that patients are unconscious every night as they sleep yet still
continue to receive insulin via their CSII pump.
CSII Therapy in the Perioperative Period
43
An example of an institutional perioperative glycemic control program can be found at
Yale-New Haven Hospital in Connecticut. Fortunately, the staff involved acknowledged patients
on CSII therapy and stated that those receiving therapy should have their basal rate decreased by
20% at midnight before surgery. However, guidelines at this institution state that
intraoperatively, CSII therapy should be discontinued and insulin should be administered IV.
They recommend that hourly BG checks should be performed throughout the perioperative
period.25(p6)
It is recommended that CSII therapy be discontinued when the patient is to undergo
major surgery.2(p47) Instead the patient should be transitioned to a regular insulin intravenous
infusion at the basal infusion rate with blood sugars being monitored at least every hour. There
are conflicting opinions as whether or not to place the patient on a dextrose infusion as to when
an IV insulin drip is initiated.25,26 Currently there are no evidence-based studies to support these
claims, but are instead a matter of professional opinion.
If the procedure is short and non-complex, the anesthesia provider feels comfortable with
the CSII pump, the CSII pump will not interfere with the surgical field, or radiology will not be
performed intraoperatively, there are recommendations for using CSII therapy during the
perioperative period. Some recommendations for the anesthesia provider include: maintaining
the insulin infusion rate, withholding preprandial doses of insulin, measuring blood glucose
levels at least every hour, knowing the ISF, and making sure preoperative diet is resumed.27(669)
If hyperglycemia occurs during the surgical administration, regular insulin can be administered
subcutaneously. Making sure the CSII pump is secure and available to the anesthesia provider at
all times is necessary as well. Again, these recommendations are not evidence-based, but
founded on expert opinion.
CSII Therapy in the Perioperative Period
Chapter 11: From the Source: Insulin Pump Manufacturer Guidelines
44
CSII Therapy in the Perioperative Period
45
The 3 most popular insulin pumps available in the United States include Medtronic,
Insulet Corporation and Animas Corporation. Of the 3, Medtronic offers inpatient guidelines for
management of patients on their insulin pump (the Medtronic MiniMed Paradigm). They also
happen to represent approximately 85% of the United States market share.10(p133)
According to Medtronic, the company agrees that the best method to maintaining
normoglycemia during inpatient status is through use of the patient’s CSII pump. The
manufacturer also emphasizes that staff should place trust in the patient regarding management
and knowledge of his or her CSII pump. Basal rate is to continue despite NPO status. It is
strongly suggested to continue CSII therapy, as discontinuation will result in DKA. If CSII
therapy must be withheld, treatment should involve administration of fast-acting insulin.
Medtronic notes that their pumps are not MRI compatible and will require removal. The CSII
pump should not be exposed to radiation (i.e. x-ray, computerized tomography scans,
fluoroscopy).
Note: It is important that this information was received in informal, company-provided literature.
Chapter 12: Conclusions and Recommendations
CSII Therapy in the Perioperative Period
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Disease Process of IDDM 1 Results in Potentially Devastating Complications
Currently, there is no ability to prevent the autoimmune destruction of beta cells that
eventually leads to T1DM. Initial insult may have occurred before symptoms of T1DM appear
and therefore treatment does not begin until beta cell destruction is near complete. The disease
affects millions worldwide and percentage of occurrence is noted to be increasing.1
The pathophysiology of T1DM is complicated, with several derangements of metabolic
pathways. Because of chronic hyperglycemia alterations in metabolic pathways there is creation
of irreversible damage at the microcellular level that eventually results in more global injury.
These injuries are numerous and include: Blindness secondary to retinopathy, renal failure
secondary to nephropathy, painful neuropathies, and heart disease and myocardial injury
secondary to vascular damage. All of these complications result in an obvious poor quality of
life.
Fortunately, optimizing glycemic control can significantly reduce the risk of these
complications from developing. Several studies and subsequent meta-analysis reviews have
greatly supported this claim. However, optimizing glycemic control can prove to be a challenge
as it can be difficult for a patient to attempt to mimic the normal physiologic response to insulin
secretion. Conventional insulin therapy (no more than 2 insulin injections per day) does not best
obtain normoglycemia (as evidence by research) and MDI therapy offers improvement in
achieving normoglycemia. According to several studies and meta-analysis review, the ideal
form of achieving normoglycemia is through CSII therapy.
From its early conception, CSII therapy is designed to replicate pancreatic function. It
provides a basal rate, in which so does a normal functioning pancreas. Improved technology in
CSII pumps have allowed preprogrammed boluses to be administered for post meal insulin
CSII Therapy in the Perioperative Period
47
requirements. CSII pumps can be worn along with continuous glucose monitoring, which allows
trends in glucose level and insulin administration to be analyzed. Not only has research
supported improved normoglycemia in CSII therapy, but has also demonstrated a risk reduction
in: The onset of diabetic complications, a decreased risk in hypoglycemia, and decreasing insulin
requirements. Also, a link between improved psychosocial status and CSII therapy has been
identified in research.
CSII Therapy and the Perioperative Period
Because of improved technology and supporting evidence for its use, CSII therapy is
increasing in popularity as a method of treating T1DM. As more T1DM patients look to this
form of therapy, there will be an increased presence of patients who present for surgery who
receive CSII treatment. These patients will present for surgery, as an estimated 50% of all
IDDM 1 patients will require surgical intervention at some point during their lifetime. There is a
general consensus among anesthesia providers that optimized glucose control within the
perioperative period allows improved outcomes, whether these outcomes include avoidance of
DKA, avoidance of hypoglycemia, or improved wound healing.
Practice Recommendations
It should be known to all anesthesia providers that all T1DM patients do require some
form of basal insulin. That could be in the form of a long-acting agent such as glargine or a
continuous infusion of ultrashort-acting insulin lispro via a CSII pump. It is important to note
that serious complications can develop in a relatively short period of time if a patient is abruptly
discontinued from their continuous ultra short-acting insulin. Because of this, it is highly
recommended that either CSII therapy continue, or a regular insulin IV infusion is started at the
patient’s NPO basal rate immediately after discontinuation of the CSII pump. At this time, it is
CSII Therapy in the Perioperative Period
48
debatable whether or not to include a potassium-dextrose containing IV solution when an insulin
infusion drip is initiated.4,19 Argument for the dextrose solution is that hypoglycemia and
hypokalemia will be prevented and at the worst, mild hyperglycemia will result. Argument
against the supplemental solution is that if regular insulin were replacing the NPO basal rate of
the CSII pump, then no additional nutrition would be required.
Additional recommendations include checking BG levels at a minimum of every hour to
avoid hypoglycemia and hyperglycemia. This recommendation applies to providers who may
decide to continue CSII therapy during the procedure or if CSII is discontinued. As mentioned in
the previous case study discussing serious hyperkalemia after discontinuation of CSII therapy,
drastic changes in baseline labs can be at the least trended and addressed prior to critical levels if
they are being monitored frequently.
Deciding on whether or not to utilize CSII therapy during the perioperative period
depends on several factors. Initially, the anesthesia provider should investigate to locate any
potential hospital-based guidelines regarding inpatient or perioperative CSII therapy use.
However, deciding whether or not to continue CSII therapy during the perioperative period is
based on the anesthesia provider’s comfort level with the device. If the anesthesia provider feels
he or she does not have confidence in managing the patient’s CSII pump, then it should be
discontinued, and the patient is provided insulin coverage. Other factors that limit CSII therapy
in the perioperative period include: Surgical site interference, long and complex procedures, and
the use of radiology or MRI during the procedure. It should be noted that CSII pump catheter
insertion site could alternatively be inserted into the back of arms or the upper buttock and thigh.
Consideration should also be placed on whether or not the anesthesia provider has access to the
pump during the procedure. If it is decided that CSII therapy will be used intraoperatively, care
CSII Therapy in the Perioperative Period
49
should be taken as to secure the device so that the catheter set or the CSII pump becomes
dislodged. A back up for insulin administration should be considered as a precaution should the
CSII pump become inoperable.
Need for More Research
Although the previous recommendations for CSII therapy in the perioperative period
were extrapolated from expert opinions, research in this area is minimal. Studies observing
glycemic outcomes comparing CSII therapy and conventional perioperative management of
T1DM would be helpful in identifying potential benefits or complications. If more studies were
completed, specific guidelines could be establish that were evidence-based in practice. Attempts
at research and reported case studies of CSII use in the perioperative period are clues that a
knowledge gap has been identified. Fortunately, from research that is already known, critical
thinking can be applied to CSII therapy in the perioperative period. This application of
knowledge can help the anesthesia provider decide what is best for his or her patient who
receives CSII therapy. As CSII therapy for the treatment of T1DM continues to grow, more
research will be gathered to assist the decision making process.
Chapter 13: References
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