Inpatient Management of Hyperglycemia: The Northwestern Experience

Article (PDF Available)inEndocrine Practice 12(5):491-505 · September 2006with67 Reads
DOI: 10.4158/EP.12.5.491 · Source: PubMed
Abstract
To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.
ABSTRACT
Objective: To describe a novel method of safe and
effective intensive management of inpatient hyper-
glycemia with use of cost-effective protocols directed by a
glucose management service (GMS).
Methods: An intravenous insulin protocol was
designed to achieve a glycemic target of 80 to 110 mg/dL.
When stable inpatients were transferred from the intra-
venous protocol to a subcutaneous insulin protocol, which
consisted of basal long-acting and prandial and supple-
mental rapid-acting insulins, the blood glucose target was
80 to 150 mg/dL. Glucose levels were reviewed by the
GMS at least daily for protocol adjustments, when neces-
sary.
Results: The intravenous insulin protocol was used in
276 patients, and 4,058 capillary blood glucose levels
were recorded. Glycemic target levels (80 to 110 mg/dL)
were achieved, on average, 10.6 ± 5.2 hours after initiation
of insulin drip therapy. The mean capillary blood glucose
level during the study interval was 135.3 ± 49.9 mg/dL.
Hypoglycemia (60 mg/dL) was recorded in 1.5% of glu-
cose values, and hyperglycemia (400 mg/dL) was
recorded in only 0.06%. The subcutaneous insulin proto-
col was used in 922 patients, and 18,067 capillary glucose
levels were documented. The mean blood glucose level
was 145.6 ± 55.8 mg/dL during the study period. The
blood glucose target of 80 to 150 mg/dL was achieved in
58.6%, whereas 74.3% of glycemic values were in the
clinically acceptable range (80 to 180 mg/dL).
Hypoglycemia (60 mg/dL) occurred in 1.3% of capillary
blood glucose values, and hyperglycemia (400 mg/dL)
occurred in 0.4% of values.
Conclusion: Validated protocols dedicated to the
achievement of strict glycemic goals were implemented
by a GMS and resulted in substantial improvements in
glycemic control on the surgical inpatient services, with a
reduced frequency of hypoglycemia. The protocols and
the GMS have been well received by the inpatient nursing
and surgical staff members, and all of this has been done
in a cost-effective manner.
(Endocr Pract. 2006;12:491-
505)
INTRODUCTION
Guidelines for the diagnosis and management of dia-
betes mellitus (DM), supported by evidence from random-
ized clinical trials, are well established in the outpatient
setting. In contrast, corresponding guidelines for the man-
agement of DM in the inpatient arena are haphazard at
best, and practice patterns differ considerably. This dis-
crepancy is due, in part, to a lack of evidence to support
the control of hyperglycemia in some inpatient popula-
tions and the belief by most health-care providers that
hyperglycemia is a normal physiologic response to illness
or hospital-induced stress. Recent evidence belies this
belief. Hyperglycemia is common in hospitalized patients,
with a prevalence of approximately 25%, and is an inde-
pendent risk factor for poor clinical outcome in multiple
patient populations (1,2). In addition to stress-induced
hyperglycemia, contributing factors to inpatient hyper-
glycemia include pharmacologic agents (3), enteral and
parenteral nutrition (4,5), and glucocorticoid therapy (6).
Recent clinical trials have shown clear benefits rela-
tive to morbidity and mortality from intensive manage-
ment of inpatient hyperglycemia, even in patients without
a prior history of DM (7-10). The medical community is
INPATIENT MANAGEMENT OF HYPERGLYCEMIA:
THE NORTHWESTERN EXPERIENCE
Anthony J. DeSantis, MD,
1
Lowell R. Schmeltz, MD,
1
Kathleen Schmidt, MSN, APRN-BC,
1
Eileen O’Shea-Mahler, MSN, APRN-BC,
1
Connie Rhee, MD,
2
Angela Wells, PA-C, MMS,
1
Stephen Brandt, MD,
1
Sara Peterson, BA,
1
and Mark E. Molitch, MD
1
Submitted for publication November 9, 2005
Accepted for publication February 22, 2006
From the
1
Division of Endocrinology, Metabolism and Molecular
Medicine, Northwestern University Feinberg School of Medicine, Chicago,
Illinois, and
2
Department of General Internal Medicine, Oregon Health and
Sciences University, Portland, Oregon.
Address correspondence and reprint requests to Dr. Mark E. Molitch,
Division of Endocrinology, Metabolism and Molecular Medicine,
Northwestern University Feinberg School of Medicine, 676 North St. Clair,
303 E. Chicago Ave., Terry 15-731, Chicago, IL 60611.
© 2006 AACE.
ENDOCRINE PRACTICE Vol 12 No. 5 September/October 2006 491
Original Article
Abbreviations:
BMI = body mass index; CVICU = cardiovascular
intensive care unit; DM = diabetes mellitus; GMS =
glucose management service; ICU = intensive care unit;
SICU = surgical intensive care unit; TPN = total par-
enteral nutrition
obligated to respond to this growing literature supporting
intensive treatment of inpatient hyperglycemia. The devel-
opment of easy-to-follow, effective, and safe management
strategies must become a priority for inpatient providers.
In this report, we describe our experience at Northwestern
Memorial Hospital, a 776-bed tertiary care center in
Chicago, Illinois, with the development and promulgation
of protocols directed by an inpatient glucose management
service (GMS) to provide safe inpatient glycemic control.
METHODS
Development of Protocols to Treat Hyperglycemia
Our goal was to design a system of care for accurate
identification and treatment of hyperglycemia among hos-
pitalized patients. A retrospective review estimated that
21% of patients requiring admission to our institution in
September 2003 had documented glucose levels >200
mg/dL. For our protocols, glycemic targets were set
according to preexisting guidelines (11,12). In the critical-
ly ill population, a target glycemic range of 80 to 110
mg/dL was established, on the basis of evidence from
other studies supporting a reduction of morbidity and mor-
tality with achievement of similar glycemic levels (7). In
the non-critically ill population, a glycemic target of 80 to
150 mg/dL was established. Blood glucose levels ranging
from 80 to 150 mg/dL and from 80 to 180 mg/dL are con-
sidered clinically acceptable in the critically ill and the
non-critically ill populations, respectively, as defined by a
recent consensus conference (12).
Orally administered hypoglycemic agents are rela-
tively contraindicated in the hospital setting (13). The
extended duration of action and the potential for harmful
drug interactions, coupled with the rapidly changing clin-
ical scenario of hospitalized patients, make these agents
less desirable for achieving strict glycemic goals. Insulin
therapy can achieve strict glycemic control efficiently and
predictably with the least amount of drug interactions. A
literature search of extant inpatient hyperglycemia man-
agement protocols was performed (14-16). We adapted
elements of these protocols to fit our patient and provider
populations optimally, specifically emphasizing safety,
efficacy, and ease of application. Separate protocols were
designed for the delivery and management of intravenous
insulin therapy and subcutaneous insulin therapy.
Intravenous Insulin Protocol
The intravenous protocol was developed to achieve a
glycemic target (80 to 110 mg/dL) while minimizing the
risk of hypoglycemia (Appendix 1). The efficacy of the
protocol for the management of diabetic ketoacidosis has
not been validated and cannot be recommended.
Intravenous insulin therapy is administered as a regular
insulin solution (100 U of regular insulin in 100 mL of iso-
tonic saline). The initial insulin drip rate is determined by
the initial capillary blood glucose value (Appendix 1). A
loading bolus dose of regular insulin, equivalent to the
hourly drip rate, is also administered at the initiation of the
infusion (see Table 1 in Appendix 1). The insulin drip is
subsequently titrated on the basis of the current capillary
blood glucose value and the rate of change from the pre-
ceding capillary blood glucose value. Nurses refer to the
appropriate table for insulin drip adjustment, depending on
whether the current glucose value had increased (see Table
2 in Appendix 1) or decreased (see Table 3 in Appendix 1)
from the previous value. The degree of change from the
previous blood glucose value (with a change in capillary
blood glucose of 60 mg/dL as a cutoff value) determines
which column within each table is referenced for insulin
drip titration orders, consisting of rate changes and addi-
tional boluses as indicated (see Tables 2 and 3 in
Appendix 1).
For example, if the previous blood glucose value was
100 mg/dL and the current blood glucose value is 170
mg/dL, the nurse would reference Table 2 in Appendix 1
because the glucose level increased. Because the degree of
change in the glucose level was 70 mg/dL, the orders in
the far right column of Table 2 (“Greater than 60 mg/dL”)
would be followed, and the insulin drip rate should be
increased by 0.5 U/h with a 2-U bolus administered. The
next blood glucose assessment would be in 1 hour, and
further insulin drip titration would be performed.
The intravenous insulin protocol order set stipulates
the frequency of capillary blood glucose monitoring.
Initially, capillary blood glucose levels are monitored
every hour, and then the frequency of monitoring is
decreased to every 2 to 4 hours, depending on the stabili-
ty of blood glucose values and the clinical situation. The
protocol incorporates variables for intravenous fluid
administration, including glucose and potassium repletion
to minimize hypoglycemia and hypokalemia. Guidelines
for the treatment of hypoglycemia are explicit (Appendix
1). Orders to notify the managing service of various clini-
cal scenarios—specifically, persistent hypoglycemia or
hyperglycemia, rapid changes in glucose values (increase
or decrease >100 mg/dL), hypokalemia, or impending
dietary changes—are included.
Subcutaneous Insulin Protocol
The subcutaneous insulin protocol was designed for
effective and safe achievement of target blood glucose val-
ues of 80 to 150 mg/dL, with insulin delivery modeling
physiologic insulin secretion (Appendix 2). Similar to pre-
viously published protocols (17), insulin needs were
subdivided into basal, prandial, and supplemental require-
ments. Basal insulin controls hepatic glucose output and
gluconeogenesis in the fasting state, prandial insulin com-
pensates for blood glucose elevations from caloric intake,
and supplemental insulin is used as a corrective factor for
preprandial hyperglycemia. The GMS routinely uses the
long-acting insulin analogue, glargine (Lantus), for basal
insulin requirements because of its once-daily dosing and
relatively flat insulin profile. Guided by the hospital
formulary, the GMS generally uses the rapid-acting
492 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
insulin analogue, aspart (NovoLog), for prandial and sup-
plemental insulin requirements.
Capillary blood glucose monitoring is ordered before
every meal and at bedtime in those patients tolerating an
oral diet, every 6 hours if the patient is allowed nothing
orally or is receiving continuous enteral or parenteral
nutrition, and with greater frequency as clinically indicat-
ed. To minimize the need to call a physician for a patient
with abnormal glucose values, the nursing staff adminis-
ters supplemental insulin doses according to the ordered
supplemental insulin scale given concurrently with sched-
uled prandial insulin (if eating) or alone (if the patient is
allowed nothing by mouth or is receiving enteral or par-
enteral therapy) (see Order 4 in Appendix 2). Daily review
of bedside capillary blood glucose values is performed by
the GMS so that titration of basal, prandial, or supplemen-
tal insulin doses can achieve the aforementioned glycemic
goals. The subcutaneous insulin protocol provides guide-
lines regarding hypoglycemia management and service
notification for persistent capillary blood glucose values
outside the target range and if dietary changes are planned.
Development of the Glucose Management Service
The GMS was formed with a team-oriented approach
to cover all aspects of hyperglycemia management. The
team consists of the following health-care providers: an
advanced practice nurse (or nurses) or a physician’s assis-
tant, responsible for initial patient consultation and daily
management; an endocrinology attending, responsible for
initial patient consultation, evaluation, and management;
an endocrinology fellow, responsible for night and week-
end coverage of the service; and an administrator, respon-
sible for collection and storage of pertinent data. The team
functions in coordination with ancillary health-care
providers critical to comprehensive management of DM,
including inpatient dietitians and diabetes educators.
Approval for use of the insulin protocols as directed
by the GMS was granted by the Medication Safety,
Pharmacy, and Therapeutics Subcommittee and the
Quality Assurance Subcommittee at Northwestern
Memorial Hospital. The initial strategy was to limit use of
the insulin protocols in a select inpatient group, to monitor
safety and efficacy of the protocols over a specified peri-
od and to make necessary adjustments, and then to expand
the use of the service in a stepwise fashion. Initially, the
insulin protocols were restricted to the GMS and available
as a patient care tool only after consultation with the GMS
was obtained.
The pilot groups for the GMS and insulin protocols
were the surgical intensive care unit (SICU) and cardio-
vascular intensive care unit (CVICU) because intensive
glycemic control already had been shown to provide ben-
efit in such intensive care unit (ICU) populations (7,8).
Educational sessions describing protocol rationale and use
were given to the SICU and CVICU provider staffs by a
member of the GMS. Data regarding efficacy to achieve
glycemic targets, adherence to protocol guidelines, and
safety were collected. After 1 month of protocol use on the
CVICU and SICU services, modifications were made to
improve efficacy, adherence, and safety. Once safety of
the protocols was demonstrated, use of the protocols was
expanded to additional ICUs and the general medical and
surgical hospital wards. In-service education was provid-
ed to the nursing staff of each unit before implementation
of the insulin protocols.
Capillary blood glucose monitoring allows immediate
point-of-care assessments with which to base clinical deci-
sions. The SICU and CVICU nursing staffs were instruct-
ed to perform capillary blood glucose monitoring for all
patients. The initiation and frequency of glucose monitor-
ing (preoperatively, intraoperatively, or postoperatively)
were based on the clinical discretion of the managing sur-
gical and anesthesia staffs. Most commonly, capillary
blood glucose monitoring was performed every 4 hours
and begun in the postoperative setting. Management of
hyperglycemia was considered necessary if capillary
blood glucose values exceeded 110 mg/dL on 2 separate
occasions or exceeded 200 mg/dL once. Once hyper-
glycemia was established, the GMS was consulted, and
insulin administration (intravenous or subcutaneous) was
determined on the basis of the clinical scenario. In most
patients with hyperglycemia, intravenous insulin therapy
was begun in the immediate postoperative period (24 to 72
hours), at a time when the patients had limited dietary
intake, were intubated, and/or were receiving intravenous-
ly administered pressor agents. Transition to a subcuta-
neous insulin regimen occurred once the critical illness
had resolved and dietary intake was adequate. The insulin
protocols proved to be safe and effective (see the
“Results” section). It became apparent after 1 month of
protocol use that the SICU and CVICU nursing staffs were
sufficiently qualified to use the protocols without prereq-
uisite consultation from the GMS. Members of the GMS
were available for consultation, and protocol outcomes
were continually monitored.
Eventually, approval for the use of the insulin proto-
cols was granted hospitalwide by the various hospital care
committees. Consultation with the GMS was no longer
mandatory for insulin protocol implementation. The most
common scenario for postsurgical hyperglycemia identifi-
cation, insulin protocol initiation, and GMS consultation
at our institution is schematically represented in Figure 1.
Hyperglycemia Management Strategies
Postoperative capillary blood glucose monitoring has
now become routine in the ICUs and as clinically indicat-
ed on the general surgical nursing units. In the SICU and
CVICU, a blood glucose level is determined within an
hour after transfer from the recovery room. SICU and
CVICU protocol indicates initiation of an insulin drip if
blood glucose values exceed 200 mg/dL once or 110
mg/dL on 2 occasions independent of the GMS. In the
non-ICU areas, the GMS is consulted for assistance with
glycemic control in patients with hyperglycemia at the dis-
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 493
cretion of the managing service. The initial hyperglycemia
treatment strategy is dependent on the clinical scenario
and multiple variables.
Intravenously administered insulin is most appropri-
ate, but not exclusively, for critically ill patients with
blood glucose values exceeding 110 mg/dL, those with a
history of DM unable to receive oral caloric support, and
patients with severe hyperglycemia (glucocorticoids, sep-
sis, pressor agents). In the postoperative critical care set-
ting, the patient is often intubated, and dietary intake is
restricted. Nursing personnel initiate the intravenous
insulin protocols and titrate infusion rates accordingly for
those patients identified as having hyperglycemia. The
insulin infusions are maintained while the patient is
receiving nothing orally. The GMS is consulted if the tar-
get glycemic range is not achieved within 8 hours after
insulin drip initiation or for assistance with conversion to
subcutaneous insulin therapy after the critical illness
resolves and the decision to advance diet is made by the
managing service. The GMS continues insulin manage-
ment throughout the rest of the hospitalization.
A subcutaneous insulin treatment strategy is optimal
for inpatients with hyperglycemia who are receiving a sta-
ble caloric source or in whom orally administered hypo-
glycemic agents are contraindicated. Many clinical
variables are taken into account by the GMS to determine
the basal, prandial, and supplemental insulin requirements
to be met by a subcutaneous insulin strategy. Patients
receiving total parenteral nutrition (TPN) will commonly
have regular insulin added to their TPN after GMS con-
sultation with the TPN nurse. Patients with hyperglycemia
receiving continuous enteral nutrition are usually treated
with a long-acting basal insulin. Supplemental insulin is
administered as needed on the basis of capillary blood glu-
cose monitoring every 6 hours.
Conversion From Intravenous Insulin Therapy
When the patient’s therapy is being converted from an
intravenous insulin drip, the drip rate is used as a guide to
determine total daily insulin requirements. The insulin
drip rate for the preceding 6 hours is averaged to obtain a
stable hourly rate. The average rate is multiplied by 24
494 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
Fig. 1. Algorithm for identification and treatment of inpatients with hyperglycemia. BG = blood glu-
cose;
CBG = capillary blood glucose; D/C = discontinue; GMS = glucose management service; IV =
intravenous;
NPO = nothing allowed by mouth; qAM = every morning; SQ = subcutaneous.
hours to calculate the total daily insulin requirement. The
basal insulin dose ordered is 80% of the total daily insulin
requirement and usually administered as a once-daily sub-
cutaneous injection of glargine insulin. Most commonly,
the prandial insulin dose for each meal is 10% of the
glargine dose, usually given as insulin aspart per hospital
formulary. The prandial insulin dose is adjusted accord-
ingly as the patient’s appetite improves postoperatively.
The proportion of insulin given for prandial dosing is sub-
stantially less than that recommended by others because
these patients are generally consuming only a clear liquid
diet initially with a reduced caloric content. The dose is
maintained the next day because the overall insulin
requirement is generally decreasing substantially as the
stress of the surgical procedure or acute illness abates. The
initial doses of basal and prandial insulin are given at sep-
arate injection sites concomitant with the discontinuation
of the intravenous insulin drip and ingestion of the first
postoperative meal (see Example 1 in Table 1). During the
first few months of using the protocols, it was mandated
that the insulin infusion be continued for at least 2 hours
after the injection of glargine to maintain adequate serum
insulin levels. Data analysis revealed inadequate glycemic
control 6 hours after the glargine injection despite the
overlap period with the insulin drip. In addition, it became
apparent that practical necessities outweighed this physio-
logic reasoning, in that transfer of the patient from intra-
venous to subcutaneous insulin therapy often coincided
with transfer of the patient out of the ICU, with the result
that the insulin infusion was simply stopped without an
overlap period. Therefore, we changed our protocol to
include a conversion dose of aspart insulin that was 10%
of the glargine dose given simultaneously to discontinuing
the intravenous infusion and the first administration of
glargine to maintain adequate glycemic control.
Initiation of Subcutaneous Insulin Protocol When No
Intravenous Insulin Therapy Has Been Given
In the non-critical care surgical population, the GMS
is consulted for management of hyperglycemia in patients
with known DM or those in whom postoperative hyper-
glycemia develops. Often these patients are receiving a
stable caloric source and have not received insulin intra-
venously during the current hospitalization. A subcuta-
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 495
Table 1
Calculation of Subcutaneous Insulin Need
Example 1. Conversion From Intravenous Insulin Therapy
Step 1. Intravenous insulin drip rate averaged 1.8 U/h with final glucose level 98 mg/dL
Step 2. Calculate average insulin infusion rate for last 6 h = 2.1 U/h and multiply
× 24 to get total daily insulin
requirement (2.1
× 24 = 50 U/24 h)
Step 3. Multiply this 24-h dose (50 U)
× 80% to obtain glargine dose = 40 U, which is given and the infusion is
stopped
Step 4. Multiply the glargine dose by 10% to give as a rapid-acting insulin (e.g., aspart, lispro, or glulisine) at
the time the glargine is given and the infusion is stopped
Step 5. Give 10% of the glargine dose as prandial doses before each meal
Example 2. Estimating Insulin Doses When No Intravenous Insulin Therapy Has Been Given
Step 1. Calculate estimated total daily dose of insulin as follows:
Type 2 diabetes (known): 0.5 to 0.7 U/kg
Type 1 diabetes (known): 0.3 to 0.5 U/kg
Unknown: 0.3 to 0.5 U/kg
Step 2. Divide total daily dose of insulin into 50% basal as glargine and 50% prandial as aspart, lispro, or
glulisine
Step 3. Divide prandial insulin into 3 equal doses to be given with meals
neous insulin strategy is developed by the GMS. The total
daily insulin requirement is influenced by multiple clinical
variables (for example, prior history of DM, type of DM,
body mass index [BMI], outpatient hypoglycemia regi-
men, surgical stress, concomitant medications, caloric
intake) that affect insulin sensitivity and secretion. Body
weight can be used as a guideline to calculate initial
insulin dosing requirements (0.5 U/kg for patients with
type 2 DM and 0.3 U/kg for those with type 1 DM or with-
out a prior history of DM). Half of the calculated daily
insulin requirement is given as a daily subcutaneous injec-
tion of glargine insulin to meet basal insulin coverage. The
remainder is divided into 3 equal doses administered as
aspart insulin with meals to fulfill prandial insulin needs
(see Example 2 in Table 1).
A supplemental insulin scale is determined on the
basis of multiple clinical factors (for example, type and
severity of hyperglycemia, BMI, insulin requirements,
medical stress, concomitant medications) and is delivered
in addition to the standing prandial insulin dose in the
form of aspart insulin to correct preprandial hyper-
glycemia. Capillary blood glucose is monitored at meals
and at bedtime. Daily adjustment of basal or bolus insulin
doses on the basis of individual glycemic results is a criti-
cal function of the GMS.
ANALYSES
The major efficacy end points for the intravenous
insulin protocol were the time from initiation of drip
insulin therapy to target glycemia (80 to 110 mg/dL) and
the mean blood glucose level during the infusion. The
incidences of hypoglycemia (60 mg/dL) and hyper-
glycemia (400 mg/dL) were tallied. Adherence to the
protocol was also monitored.
The efficacy of the subcutaneous insulin protocol was
determined by percentages of capillary blood glucose
measurements in the target glycemic range (80 to 150
mg/dL) and the clinically acceptable range (80 to 180
mg/dL). The incidences of hypoglycemia (60 mg/dL)
and hyperglycemia (400 mg/dL) were recorded as well.
Approval to publish data was granted by the Institutional
Review Board of the Northwestern University, Feinberg
School of Medicine.
Adherence to the protocol was defined as a function
of accuracy of insulin dosing and accuracy of service noti-
fication, as outlined by the protocol order sets. Adherence
of the nursing staff to the intravenous insulin protocol was
monitored retrospectively.
RESULTS
Intravenous Insulin Protocol
Two hundred seventy-six patients were managed with
the intravenous insulin protocol after consultation with the
GMS between June 2004 and June 2005 (excluding
September 2004, for which no data are available).
Demographic data for these patients are shown in Table 2.
Most patients were men (63%), and cardiovascular
surgery was the managing service most frequently
requesting consultation (47%). The majority of patients
were in the CVICU or SICU while receiving intravenous
insulin therapy. The mean age was 59.6 years, and the
mean BMI was 29.1 kg/m
2
. The majority of patients had
no prior history of diabetes (64%), whereas 32% had a his-
tory of type 2 DM and only 4% a history of type 1 DM
(Table 2). It bears repeating that the intravenous insulin
protocol was not intended for use in the treatment of dia-
betic ketoacidosis, and any use of the protocol outside the
postoperative setting should be done with caution.
Glycemic target levels (80 to 110 mg/dL) were
achieved, on average, 10.6 ± 5.2 hours after initiation of
insulin drip therapy. The mean capillary blood glucose
concentration for the study interval was 135.3 ± 49.9
mg/dL. In these 276 patients, 4,058 capillary blood glu-
cose levels were recorded. Hypoglycemia (60 mg/dL)
was recorded in 1.5% of capillary blood glucose values,
and hyperglycemia (400 mg/dL) was recorded in only
0.06%.
Glycemic control in the CVICU and SICU from
September 1 through September 30, 2003, before the
development of the GMS and implementation of the intra-
venous insulin protocol, was used as a historic control for
comparative purposes. The mean blood glucose level in
patients in the CVICU and SICU during that period was
169.0 ± 69.0 mg/dL, with 0.6% and 0.4% of capillary
blood glucose values (N = 526) 60 mg/dL and 400
mg/dL, respectively.
With respect to protocol adherence, insulin drip rates
were appropriately initiated in accordance with the proto-
col 84% of the time. Insulin drip rates were titrated in
496 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
Table 2
Demographic Data
for 276 Patients Managed
With the Intravenous Insulin Protocol
Factor Data
Mean age (yr) 59.6 ± 6.8
Male patients 63%
Admitting service, no. (%)
Cardiovascular surgery 129 (46.7)
Transplantation surgery 51 (18.5)
General surgery 12 (4.3)
Surgical oncology 17 (6.2)
Other 67 (24.3)
History of diabetes, no. (%)
Known type 1 diabetes 10 (3.6)
Known type 2 diabetes 88 (31.9)
No previous history of diabetes 178 (64.5)
accordance with the protocol 58% of the time, with the
most common error (22%) being underdosing of insulin.
Subcutaneous Insulin Protocol
A total of 922 patients received subcutaneous insulin
management in consultation with the GMS from June
2004 through June 2005 (excluding September 2004, for
which no data are available). Similar to those receiving the
intravenous insulin protocol, the majority were male
patients (61%), and the most frequent service requesting
GMS consultation was cardiovascular surgery (42%).
Demographic data for these patients are summarized in
Table 3. The mean age at the time of GMS consultation
was 60.5 years, and the mean BMI was 29.2 kg/m
2
. The
majority of patients with hyperglycemia had no prior his-
tory of diabetes (51.2%); 42.3% and 6.5% had a history of
type 2 DM and type 1 DM, respectively.
In these 922 patients, 18,067 capillary blood glucose
levels were obtained. The mean blood glucose concentra-
tion was 145.6 ± 55.8 mg/dL during the study period. The
majority of capillary blood glucose measurements (58.6%)
were in the target range of 80 to 150 mg/dL, and 74.3%
were in the clinically acceptable range (80 to 180 mg/dL).
Hypoglycemia (60 mg/dL) was documented in 1.3% of
capillary blood glucose values, with an incidence of 0.25
episode per patient. Hyperglycemia (400 mg/dL) was
less frequent; it was documented in 0.4% of capillary
blood glucose measurements and occurred with a frequen-
cy of 0.09 episode per patient (Fig. 2).
A historical comparison of glycemic control on the
same surgical services from September 1 through
September 30, 2003, a period before the development of
the GMS and implementation of the subcutaneous insulin
protocol, was made. During that period, 2,379 capillary
blood glucose levels were determined. The mean blood
glucose level was 163.5 ± 68.3 mg/dL, with the glycemic
target range (80 to 150 mg/dL) being achieved in 48.4% of
capillary blood glucose values and the clinically accept-
able range (80 to 180 mg/dL) being achieved in 67%.
Hypoglycemia (60 mg/dL) occurred in 1.4%, and hyper-
glycemia (400 mg/dL) occurred in 0.88% of these values.
Improvement With Protocol Use Over Time
A basic tenet of the GMS is to conduct periodic
review of outcomes and to adjust protocols and manage-
ment strategies as needed for improvement. A comparison
of outcomes for both the intravenous insulin protocol and
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 497
Table 3
Demographic Data
for 922 Patients Managed
With the Subcutaneous Insulin Protocol
Factor Data
Mean age (yr) 60.5 ± 13.5
Male patients 61%
Admitting service, no. (%)
Cardiovascular surgery 388 (42.1)
Transplantation surgery 161 (17.5)
General surgery 62 (6.7)
Surgical oncology 101 (11.0)
Other 210 (22.8)
History of diabetes, no. (%)
Known type 1 diabetes 60 (6.5)
Known type 2 diabetes 390 (42.3)
No previous history of diabetes 472 (51.2)
Fig. 2. Glycemic ranges in hospitalized patients treated with the subcutaneous insulin protocol
between June 2004 and June 2005 (excluding September 2004). The results consist of 18,067
capillary glucose measurements performed in 922 patients. The percentages of glucose values
in the ranges of <80 mg/dL, 80 to 150 mg/dL, 150 to 180 mg/dL, and >180 mg/dL are shown.
Overall, 74% of values were in the clinically acceptable range of 80 to 180 mg/dL. It should be
noted that only 1.3% of values were 60 mg/dL and only 0.4% of values were 400 mg/dL.
the subcutaneous insulin protocol for the first quarter
(June 1, 2004 to August 31, 2004) and the most recent
quarter (April 1, 2005 to June 30, 2005) analyzed is out-
lined in Table 4. An improvement in glycemic end points
is seen, despite an increase in the number of consultations.
DISCUSSION
The number of hospitalizations for DM or DM-relat-
ed complications in the United States was estimated at 4.6
million in 2001, with an estimated cost of $40 billion (18).
In the hospital setting, however, DM is often unrecog-
nized, and treatment is seldom standardized. A retrospec-
tive review of patients admitted to a Philadelphia hospital
revealed that 31% met the American Diabetes Association
criteria for DM, 41% of whom were unrecognized as hav-
ing DM at the time of dismissal from the hospital (19). A
retrospective analysis of blood glucose measurements (N
= 3,092) on the medicine services at Northwestern
Memorial Hospital from September 1 through September
30, 2003, revealed a mean blood glucose level of 182.6 ±
87.8 mg/dL, with only 53.1% of the capillary blood glu-
cose levels measured being in the clinically acceptable
range of 80 to 180 mg/dL.
Hyperglycemia has been shown to be an independent
risk factor for a poor clinical outcome in multiple inpatient
settings. In patients who have undergone a cardiac surgi-
cal procedure, DM is an independent predictor of pro-
longed ICU stay, sternal wound infection, postoperative
delirium, perioperative stroke, renal dysfunction, and need
for postoperative reintubation (20). Patients with a mean
blood glucose level >150 mg/dL during the 3 days after a
cardiovascular surgical procedure have double the infec-
tion rate and up to 13 times the mortality of their normo-
glycemic counterparts (8). Hyperglycemia is associated
with a 9-fold and a 2-fold increase in mortality during hos-
pitalization among those with new-onset hyperglycemia
and those with a known history of diabetes, respectively
(1). The results of these studies emphasize the importance
of recognition of hyperglycemia in all inpatients, even
those without a prior history of DM. As noted previously,
less than half of the patients with hyperglycemia treated by
us had a prior diagnosis of DM.
Treatment of hyperglycemia with insulin has been
shown to reduce mortality, sepsis, ICU stay, need for dial-
ysis, need for transfusion, and duration of ventilation in
the postoperative setting (7). Furthermore, postoperative
glycemic control has been shown to decrease postopera-
498 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
Table 4
Comparison of Glucose Values in the Initial Quarter*
and the Latest Quarter† for the
Intravenous and Subcutaneous Insulin Protocols
Initial Latest
Protocol quarter quarter
Intravenous
Total number of patients 34 114
Total number of glucose measurements 674 1,543
Time to glucose goal (h) 18.2 8.3
Mean glucose level (mg/dL) 148.4 133.2
Glucose levels (mg/dL)
80-110 (%) 24.1 27.6
80-150 (%) 57.3 65.8
60 (%) 3.1 1.0
400 (%) 0.2 0.3
Subcutaneous
Total number of patients 120 331
Total number of glucose measurements 2,337 6,524
Mean glucose level (mg/dL) 153.6 139.7
Glucose levels (mg/dL)
80-110 (%) 47.0 66.2
80-150 (%) 65.5 79.8
60 (%) 1.6 1.1
400 (%) 0.5 0.3
*June 1, 2004 to August 31, 2004.
†April 1, 2005 to June 30, 2005.
tive wound infections (8). On the basis of these studies, the
American Diabetes Association and the American
Association of Clinical Endocrinologists have put forward
recommendations for inpatient management of hyper-
glycemia (11,12).
In this report, we describe a practical approach to
identify and treat inpatient hyperglycemia. We have
shown a substantial improvement in mean blood glucose
level and percentage of blood glucose values reported in
the target glucose range (80 to 150 mg/dL) and in what has
been termed the clinically acceptable range (80 to 180
mg/dL) (12) at our institution with the use of easy-to-fol-
low insulin protocols guided by a formal management ser-
vice. This change has been accomplished safely with no
increase in hypoglycemia in comparison with historical
methods of glycemic management.
The limited number of patients treated thus far has not
allowed us to evaluate the effect of this service on mor-
bidity and mortality outcomes. On the basis of the results
of other studies, however, we would expect similar clini-
cal benefits. Our results are limited to the inpatient surgi-
cal services, and extrapolation to other inpatient
populations may not be appropriate. Nevertheless, one
could argue that the complicated clinical environment
characteristic of the current inpatient experience necessi-
tates a focused specialized approach to hyperglycemia in
all such patients. Hyperglycemia has been associated with
a poor clinical outcome in a variety of other patient popu-
lations, including those admitted to the hospital with a
diagnosis of congestive heart failure (21), stroke (2), and
acute myocardial infarction (22), and improved glycemic
control has been shown to benefit the last-mentioned
group of patients.
The use of advanced practice nurses as the corner-
stone of inpatient hyperglycemia management, in con-
junction with supervision by a board-certified
endocrinologist, has proved effective and financially
viable. Revenue generated by the GMS consultation activ-
ity at the current census has been able to provide salary
support for 2 full-time advanced practice nurses, an
administrator, and 25% of a supervising physician’s
salary.
CONCLUSION
In summary, we have developed strategies to identify
inpatient hyperglycemia and validated protocols dedicated
to the achievement of strict glycemic goals. With use of
these interventions, we have made substantial improve-
ments in glycemic control on our surgical inpatient ser-
vices. These efforts have been undertaken without
jeopardizing patient safety and have, in fact, reduced the
frequency of hypoglycemia. The protocols and GMS have
been well received by the inpatient nursing and surgical
staff members, and all of this has been done in a cost-
effective manner. Analyses of long-term health outcome
data in patients managed with use of these protocols are
now in progress.
DISCLOSURE
Mark E. Molitch, MD, has received research support
from Sanofi-Aventis Pharmaceuticals, Genentech, and
Amgen. In addition, he is a consultant for Abbott
Laboratories and Sanofi-Aventis Pharmaceuticals.
Anthony J. DeSantis, MD, is a consultant for Sanofi-
Aventis Pharmaceuticals.
ACKNOWLEDGMENT
We acknowledge the support of Gerald Baumann,
MD, Herman Blomeier, MD, Allison Hahr, MD, Rekha
Ramamurthy, MD, and Joy Springer, RN, CDE.
REFERENCES
1. Umpierrez GE, Isaacs SD, Barzagan N, You X, Thaler
LM, Kitabchi AE.
Hyperglycemia: an independent mark-
er of in-hospital mortality in patients with undiagnosed dia-
betes.
J Clin Endocrinol Metab. 2002;87:978-982.
2.
Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein
HC.
Stress hyperglycemia and prognosis of stroke in non-
diabetic and diabetic patients: a systematic overview.
Stroke. 2001;32:2426-2432.
3.
Luna B, Feinglos MN. Drug-induced hyperglycemia.
JAMA. 2001;286:1945-1948.
4.
Rosmarin DK, Wardlaw GM, Mirtallo J. Hypergly-
cemia associated with high, continuous infusion rates of
total parenteral nutrition dextrose.
Nutr Clin Pract. 1996;
11:151-156.
5.
Cheung NW, Napier B, Zaccaria C, Fletcher JP. Hyper-
glycemia is associated with adverse outcomes in patients
receiving total parenteral nutrition.
Diabetes Care.
2005;28:2367-2371.
6.
Hollingdal M, Juhl CB, Dall R, et al. Glucocorticoid
induced insulin resistance impairs basal but not glucose
entrained high-frequency insulin pulsatility in humans.
Diabetologia. 2002;45:49-55.
7.
Van den Berghe G, Wouters P, Weekers F, et al.
Intensive insulin therapy in the critically ill patients. N
Engl J Med
. 2001;345:1359-1367.
8.
Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia
and continuous intravenous insulin infusions on outcomes
of cardiac surgical procedures: the Portland Diabetic
Project.
Endocr Pract. 2004;10(Suppl 2):21-33.
9.
Wahab NN, Cowden EA, Pearce NJ, Gardner MJ,
Merry H, Cox JL (ICONS Investigators).
Is blood glu-
cose an independent predictor of mortality in acute
myocardial infarction in the thrombolytic era?
J Am Coll
Cardiol
. 2002;40:1748-1754.
10.
Guvener M, Pasaoglu I, Demircin M, Oc M.
Perioperative hyperglycemia is a strong correlate of post-
operative infection in type II diabetic patients after coro-
nary artery bypass grafting.
Endocr J. 2002;49:531-537.
11.
American Diabetes Association. Standards of medical
care in diabetes [erratum in
Diabetes Care. 2005;28:990].
Diabetes Care. 2005;28(Suppl 1):S4-S36.
12.
Moghissi ES, Hirsch IB. Hospital management of dia-
betes.
Endocrinol Metab Clin North Am. 2005;34:99-116.
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 499
13. Clement S, Braithwaite SS, Magee MF, et al (American
Diabetes Association Diabetes in Hospitals Writing
Committee).
Management of diabetes and hyperglycemia
in hospitals [errata in
Diabetes Care. 2004;27:856 and
Diabetes Care. 2004;27:1255]. Diabetes Care. 2004;27:
553-591.
14.
Markovitz LJ, Wiechmann RJ, Harris N, et al.
Description and evaluation of a glycemic management pro-
tocol for patients with diabetes undergoing heart surgery.
Endocr Pract. 2002;8:10-18.
15.
Goldberg PA, Siegel MD, Sherwin RS, et al.
Implementation of a safe and effective insulin infusion pro-
tocol in a medical intensive care unit.
Diabetes Care. 2004;
27:461-467.
16. The Portland protocol. Available at: http://www.provi-
dence.org/Oregon/Programs_and_Service/Heart/
portlandprotocol/default.htm. Accessed for verification
August 27, 2006.
17.
Trence DL, Kelly JL, Hirsch IB. The rationale and man-
agement of hyperglycemia for in-patients with cardiovas-
cular disease: time for a change.
J Clin Endocrinol Metab.
2003;88:2430-2437.
18.
Hogan P, Dall T, Nikolov P (American Diabetes
Association).
Economic costs of diabetes in the US in
2002.
Diabetes Care. 2003;26:917-932.
19.
Levetan CS, Passaro M, Jablonski K, Kass M, Ratner
RE.
Unrecognized diabetes among hospitalized patients.
Diabetes Care. 1998;21:246-249.
20.
Bucerius J, Gummert JF, Walther T, et al. Impact of
diabetes mellitus on cardiac surgery outcome [erratum in
Thorac Cardiovasc Surg. 2003;51:113]. Thorac
Cardiovasc Surg
. 2003;51:11-16.
21.
Bhatia V, Wilding GE, Dhindsa G, et al. Association of
poor glycemic control with prolonged hospital stay in
patients with diabetes admitted with exacerbation of con-
gestive heart failure.
Endocr Pract. 2004;10:467-471.
22.
Malmberg K, Norhammar A, Wedel H, Ryden L.
Glucometabolic state at admission: important risk marker
of mortality in conventionally treated patients with dia-
betes mellitus and acute myocardial infarction; long-term
results from the Diabetes and Insulin-Glucose Infusion in
Acute Myocardial Infarction (DIGAMI) study.
Circulation. 1999;99:2626-2632.
500 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 501
APPENDIX 1
502 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 503
504 Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5)
APPENDIX 2
Inpatient Hyperglycemia, Endocr Pract. 2006;12(No. 5) 505
    • "This retrospective cohort study used an EMR database of adult medicalsurgical inpatients with DM-2; we evaluated whether there is a direct relationship between the cost of hospitalization, LOS, excess admission days, and DC-BG levels with implementing a standardized glycemic protocol during hospital admissions. The topic is of relevance because hyperglycemia is a risk factor for less than desired clinical outcomes within the inpatient setting (DeSantis et al., 2006). This study demonstrated that the development and systematic implementation of protocol-based care for DM-2 patients is associated with improved glycemic control at the time of hospital discharge, while decreasing the LOS and excess admission days; hence, providing evidence that a standardized protocol benefits patient outcomes. "
    [Show abstract] [Hide abstract] ABSTRACT: Rising healthcare costs and the management of diabetes are financially straining to healthcare organizations. The study purpose was to examine whether a direct relationship existed between the cost of hospitalization, length of stay, excess admission days, and discharge blood glucose (DC-BG) levels and utilizing a standardized glycemic protocol. A retrospective cohort analysis was conducted of adult diabetes mellitus type 2 (DM-2) patients' pre-diabetic protocol (January 1, 2011-December 31, 2011) and post-diabetic protocol (August 1, 2012-October 31, 2012). The sample included DM-2 inpatients aged ≥18 years admitted without complications and/or with abnormal fasting blood glucose. Pre-protocol sample comprised n = 346 subjects and post-protocol sample comprised n = 149 subjects. Patients who received the diabetic protocol in 2012 experienced a decrease in the DC-BG (p < .05) and decrease in excess admission days (p < .05). Evidence supports that utilizing a standardized glycemic protocol improves glycemic control and reduces healthcare cost.
    Full-text · Article · Jun 2014
    • "Many factors are suggested to contribute to the disturbed glucose metabolism. Although insulin is infused during CPB to maintain blood glucose level, the counter regulatory hormones secreted, as a result of stress, lead to insulin resistance and hence a high blood glucose level.[1516] Non-esterified fatty acids produced as a result of high level of heparin infusion during CPB, are suggested to have a role in hyperglycemia.[17] "
    [Show abstract] [Hide abstract] ABSTRACT: Cardiopulmonary bypass (CPB) during coronary artery bypass grafting is thought to contribute significantly to increased blood glucose level and altered blood electrolytes balance during the operation. In this (CABG) study, blood electrolytes and glucose during CPB in insulin-dependent diabetic and non-diabetic patients were assessed with special emphasis on the trend of the changes. Blood glucose and electrolytes were assessed in 30 insulin-dependent diabetic and 30 non-diabetic patients, classified as class II and III American Society of Anesthesiologist, before, during, and after CPB. Repeated-measures analysis of variance (ANOVA) was used to compare the trend of the changes during CPB for the two groups. The trend in blood glucose level did not show any significant difference between two groups (P = 0.59). For other blood factors, no significant between-group difference was detected except for PaCO2 (P = 0.002). The study suggested that the changes in blood electrolytes and the increase in blood glucose level do not differ between insulin dependent diabetic and non-diabetic patients.
    Article · Apr 2013
    • "Recently, computer-based algorithms have become commercially available to assist the nursing staff in adjusting insulin infusion rates [85] [86]. Although studies have shown that computer-based algorithms have been associated with tighter glucose control, there have been no reported differences in the frequency of hypoglycemic events, length of ICU and hospital stay, or mortality with these algorithms; their use depends on physicians' preferences and cost considerations [87] [88] [89]. The following are the current recommendations of the Society of Thoracic Surgery regarding blood glucose management during adult cardiac surgery [81]. "
    [Show abstract] [Hide abstract] ABSTRACT: Hyperglycemia, which occurs in the perioperative period during cardiac surgery, has been shown to be associated with increased morbidity and mortality. The management of perioperative hyperglycemia during coronary artery bypass graft surgery and all cardiac surgical procedures has been the focus of intensive study in recent years. This report will paper the pathophysiology responsible for the detrimental effects of perioperative hyperglycemia during cardiac surgery, show how continuous insulin infusions in the perioperative period have improved outcomes, and discuss the results of trials designed to determine what level of a glycemic control is necessary to achieve optimal clinical outcomes.
    Full-text · Article · Nov 2012
Show more