Chapter
35
Guidelines on Inpatient
Management of Hyperglycemia
Sukhminderjit Singh Bajwa, Manash P Baruah, Sanjay Kalra, Mukul Chandra Kapoor
ABSTRACT
Hospitalized diabetic patients pose numerous clinical challenges.
Sociobehavioral, economic, nutritional, racial, ethnic and other factors
make it difficult for application of hitherto published western guidelines
in India. The present chapter is an effort to bring forth the various
clinical challenges encountered during management of different
diabetic hospitalized populations and to formulate a set of patient and
physician friendly guidelines to control hyperglycemia in such patients.
Keywords: Diabetes; hyperglycemia; inpatients; insulin therapy; insulin
analogs
INTRODUCTION
Prolonged hospitalization and poorer outcome is a common
phenomenon amongst patients with diabetes mellitus (DM).1-3
There are inconsistent data regarding outcome of intensive control of
hyperglycemia amongst hospitalized patients.4,5 Such inconsistencies
create doubts regarding the adoption of precise therapeutic
interventions in indoor patients with hyperglycemia.
A large number of DM cases are diagnosed for the first time when
they get admitted for various indications, which may or may not be
related to DM. Although Indian data reveal that every sixth patient
admitted to hospital has diabetes, in reality the number may be
higher.6
NEED FOR INDIAN/ASIAN GUIDELINES
Although a number of guidelines on inpatient hyperglycemia
management have been published, they are not without
confounding biases involving nutritional status, level of awareness,
sociobehavioral, cultural and economic factors. Moreover, racial,
ethnic and genetic differences in insulin resistance and glucose and
lipid metabolism may limit the extrapolation of western guidelines
to an Indian population.7 There is an acute need for formulation
of user-friendly guidelines relevant in India and other developing
nations as well.
The guidelines delineated in this chapter are based upon
evidences derived from available literature. Initial core writing
group consisted of the authors of this article. Review of the draft
and grading of recommendations were done by a panel of experts
consisting of four endocrinologists, one internist, one pediatrician
and one obstetrician, each having at least a decade of experience.
Grading was based on a method suggested by Frid et al. (2010),8
which includes an ABC scale of recommendation and 123 scale for
supporting scientific evidence (Table 1). For each recommendation,
the postfixed capital letter in bold indicates how much weight a
recommendation should carry in daily practice, while the number
defines its degree of support in medical literature.
GUIDELINES FOR GLYCEMIC CONTROL
Hyperglycemia can have detrimental effects in both medical
and surgical hospitalized patients.9 So far as the management
of hyperglycemia is concerned, the hospitalized patients can be
categorized into two broad categories: (1) non-critically ill, and (2)
critically ill.
Non-critically Ill Patients
Compared to ICU patients, non-critical patients are less likely to
receive adequate attention for hyperglycemia per se. Physicians’
concerns for the management of primary pathology, lack of proper
monitoring facility and dedicated paramedical staff in general wards,
unsupervised dietary intake and fear of inducing hypoglycemia are
amongst the factors responsible. These factors are also responsible
for avoidance/delay in usage of insulin even in inpatients.
Hyperglycemia may lead to longer hospitalization, impaired wound
healing, and occasional risk of polyneuropathy, higher incidence of
systemic infections, urinary tract infections, acute renal failure and
increased cardiac morbidity.10,11
The targets proposed by American Diabetic Association (ADA)
for premeal blood glucose (BG) (< 140 mg/dL) and casual (random)
BG (< 180 mg/dL) are generally acceptable. Target can be lower than
this threshold in the following situations: (1) stable patients with
optimal glycemic control prior to admission, (2) postoperative ward
and gestational DM patients in a background of available adequately
trained staff for monitoring and treating hypoglycemia.12,13 Patients
who are able to eat adequately at regular intervals are right candidates
for subcutaneous (SC) insulin, because intravenous (IV) insulin
regimen is less flexible.
Sliding scale insulin (SSI), although quite popular, has been found
to be inferior to basal bolus (BB) regimen using rapid-acting analog
to fulfill prandial requirement and once daily long-acting analog to
fulfill the basal and supplemental need. Apart from achieving better
TABLE 1 │ Criteria for grading and rating recommendations8
Strength of
recommendation
Scale of scientific
support
A
Strongly recommended
B
Recommended
C
Unresolved issue
1
At least one randomized controlled study
2
At least one nonrandomized or
noncontrolled or epidemiologic study
3
Consensus expert opinion based on
extensive patient experience
Chapter 35 Guidelines on Inpatient Management of Hyperglycemia
Section 5
BG control, the incidence of various infections, respiratory failure
and acute renal failure is much lower in patients treated with insulin
analogs.14 Similarly, basal insulin analogs imparts better glycemic
control in diabetic patients receiving enteral nutrition as compared
to SSI.15
Recommendations
• Premeal BG target should be 110–130 mg/dL, and postmeal target
should be 140–180 mg/dL. Targets should be less stringent for the
elderly and patients with significant medical comorbidity. Noncritically ill inpatients on enteral nutrition should be preferably
managed with insulin [A1].
• Basal insulin to cover the basal and correctional need, and
prandial rapid-acting insulin to cover the nutritional need are
preferred choice. SSI is not recommended [A1].
• Insulin analogs should be preferred in indoor patients as they are
associated with less hypoglycemia, better therapeutic outcomes,
and are more flexible to use [A2].
TABLE 3 │ Suggested protocol for insulin infusion in ICU
A.
Preparation
50 units of regular insulin dissolved in 50 mL
normal saline (NS) in a 50 mL disposable
syringe
B.
Mode of
administration
IV infusion with an electronic syringe pump/
infusion pumps
C.
Primary target
To maintain blood sugar level within a
predefined target 140 mg/dL
D.
Control
methodology
Blood sugar to be controlled gradually in case
of severe hyperglycemia by titrating the dose
of IV insulin
E.
Pre-requisites
Initially 15–20 mL of solution should be
flushed through plastic tubing to saturate the
insulin binding sites in the tubing
F.
Targets
Dose should be adjusted as per the levels of
blood sugar
G.
Monitoring
Either by capillary blood glucose or from the
venous site/central line
Critically Ill Patients
Glycemic control in critically ill patients is a unique challenge for
both intensivist and endocrinologist, as these patients invariably
have multiorgan dysfunction. In spite of extensive data indicating
a relation between uncontrolled hyperglycemia and poor outcome
in critically ill, optimal glycemic targets are not precisely defined.
While evidence favors a tighter control in the range of 110–140 mg/
dL in surgical patients, a less aggressive target may suit medically ill
patients.3,16 Such stringent targets can lead to severe hypoglycemia (<
40 mg/dL), which is a cause of increase mortality in the critically ill.
A goal range of 140–180 mg/dL has been recently recommended and
has been approved by most, if not all.9,16
The only acceptable modality of treatment is continuous IV
insulin infusion, which should be initiated when BG levels are
greater than 180 mg/dL (Tables 2 to 4). There are many IV insulin
infusion regimens available, but those regimens are preferred, which
contain orders that take into account both current BG values and rate
of change of BG.5,17,18
For basal, mealtime and correction doses, insulin analogs are
preferred over regular and neutral protamine hagedorn (NPH)
TABLE 2 │ Estimated initial dose of insulin in non-critically ill
hospitalized patients
Total daily dose of
insulin (units/kg
body wt)
Patient characteristics
0.25
• Geriatric patients
• Renal or hepatic impairment
• On hemodialysis
0.5
• Ordinary patients
1.0
• Obesity and other insulin resistance state
• Glucocorticoid treatment
• Severe infections
• Coronary artery bypass graft (CABG)
• Total parenteral nutrition (TPN)
Calculation of subcutaneous dose of insulin in a 60 kg adult male with body mass
index (BMI) of 25 having moderate hyperglycemia:
• Total daily dose (TDD) = 0.5 units/kg body wt × 60 = 30 units
• Basal insulin dose = 50% of TDD = 50% of 30 units = 15 units basal insulin
• Bolus insulin dose per meal = (50% of TDD)/3 = (50% of 30 units)/3 = 15/3
= 5 units of rapid-acting insulin before each meal
• Assessment of correctional scale insulin is based on TDD. For a patient
with a TDD of 40 units, the low correctional scale should be ordered.
TABLE 4 │ Titration of insulin dose according to blood glucose
(BG) levels
Blood glucose
levels (mg/dL)
Dosage of insulin infusion
< 100
No insulin to be given
100–149
1–1.5 units/hour
150–199
2 units/hour
200–249
2.5 units/hour
250–299
3 units/hour
300–349
3.5 units/hour
350–399
4 units/hour
For any further increase in BG, consulting endocrinologist/physician/
intensivist needs to decide the rate subjectively. If BG does not fall
more than 10%, insulin can be increased to 1.5 times the normal dose.
If BG is < 50 mg/dL
Administer 50 mL of dextrose (25 g), check
blood sugar at 15 minutes and if blood glucose
increases to more than 100 mg/dL, start insulin
infusion after 1 hour
BG between 50 mg/
dL and 75 mg/dL
Infuse 50 mL dextrose (25 g) if hypoglycemia
manifests clinically. If asymptomatic, give half
dose of the above solution. Check blood sugar
after 15 minutes and start insulin 1 hour after BG
reaches > 100 mg/dL.
insulin as they have a predictable absorption mechanism and exhibit
minimal pharmacokinetic variability. The incidence of hypoglycemia
is significantly minimized if pre- and postprandial regular insulin is
replaced by rapid-acting insulin analogs. Predictable duration of
action with minimal stacking effect enables the analogs to achieve
euglycemia with minimal hypoglycemia.19
Recommendations
• Maintain BG level at a range of 140–180 mg/dL for majority of
patients with medical morbidity, and 110–140 mg/dL for those
with surgical morbidity [A1].
• Only IV insulin is recommended. Subcutaneous regimens with
premixed insulin, intermediate-acting or long-acting insulin and
SSI are not recommended [A1].
• Regular insulin or rapid-acting insulin analogs (aspart, lispro,
glulisine) can be used as IV infusion. Glulisine should be used
only with normal saline [A2].
165
Diabetology
• Transition to subcutaneous insulin from IV insulin should have
an overlapping period of 1–2 hour. The overlap can be reduced to
15–30 min if rapid analogs are used [A2].
Section 5
Flow chart 1: A simple algorithm of point of care monitoring of blood
glucose in critically ill inpatients
MONITORING OF BLOOD GLUCOSE
Technologies enabling bedside capillary blood glucose monitoring
with agility, rapidity and reasonable safety have revolutionized
inpatient management of hyperglycemia.20
Different approaches, such as venous, capillary blood and/or
plasma or whole blood have been used for precise measurement
of blood glucose.21 The question of accuracy of capillary vis-ä-vis
venous measurement has become redundant with the advent of
newer glucometer, which allows samples from either source to be
measured. The resulting advantages are minimal needle pricks (less
injury, less contamination, cost cutting) and elimination of factitious
reporting.22,23 However, to minimize errors, the glucometer readings
should always be tested and compared intermittently with laboratory
glucose values (internal quality control). A structured protocolbased approach is of utmost importance (Flow chart 1). Continuous
glucose monitoring system (CGMS), which can monitor glucose
levels continuously up to 72 hours, may be useful in emergency
and intensive care units as it exhibits various glycemic trends and
patterns, help in timely detection of hypoglycemia and assesses
efficacy of ongoing therapy. However, the high cost, delay in obtaining
the results (after 72 hours) and limitation of real time display are a few
disadvantages.24
Recommendations
• Mandatory BG testing for every patient on admission and at least
two readings in the next 24 hours to rule out hyperglycemia [A2]
.• Glycated hemoglobin should be obtained in patient with
hyperglycemia without prior history of DM and with persistent
hyperglycemia of uncertain etiology. This test is unreliable in
patients receiving massive blood transfusions [B2].
• Point of care monitoring of blood glucose is to be done preferably
with capillary method. In cases of hypotension, hypothermia,
shock, use of vasoconstrictors and vasopressors, use venous
sampling instead [A2].
• Initial monitoring should be done on an hourly basis. Interval
of testing can be increased when three consecutive readings are
consistently around the target [B2].
• If logistics permit, CGMS should be used while monitoring
glycemic status in critically ill patients [B2].
• Postprandial testing should be included while monitoring
glycemia in patients on oral feed [C3].
SPECIAL POPULATIONS
Perioperative Management
Insulin is the preferred therapy in majority of surgical patients. The
most commonly used insulin regimens in India are GIK (glucose,
insulin and potassium) and variable insulin infusion regimens. The
cost associated with the pump infusion system prohibits the use
of such regimens in low resource settings. Alternatively, the use of
micro-drip set attached to dextrose solution containing therapeutic
insulin and potassium is cost effective, and can be used in any setting
where monitoring of BG is possible as and when required. Adequate
control of hyperglycemia has shown to improve outcome in general
as well as special surgery wards.25-27
Transplant surgery in diabetes is challenging as uncontrolled
hyperglycemia is associated with increased cardiac morbidity, risk
of organ failure, acute graft versus host disease (grade II–IV) and
increased risk of non-relapse-related mortality.28 Each 10 mg/dL
166
Capillary blood sample can be used except in situations like hypotension,
hypothermia, shock, use of vasoconstrictors and vasopressors where venous
samples are preferred
increase of BG is associated with 1–1.5 fold increase in odds ratio
of bacteremia in neutropenic patients not on glucocorticoids.29
Administration of immunosuppressants in post-transplant period is
associated with hyperglycemia. As such, insulin requirement is much
higher in these patients. On the other hand, patient’s dietary changes
may lead to sudden hypoglycemia. These factors warrant the use of
insulin analogs due to their flexibility.30
Recommendations
• Tight glycemic control with insulin is advocated for a better
surgical outcome, with targets of BG between 110 mg/dL and 140
mg/dL [A1].
• Glucose and insulin should be given through separate IV routes.
Serum potassium should be monitored and maintained through
supplementation [B2].
• Relatively minor procedure such as cataract surgery where
patients need not remain nil per orally for prolonged periods may
continue on oral hypoglycemic agents if they are well controlled
[A2].
• The blood glucose target in post-transplant patients should be
similar to that of surgical inpatients. Analogs should be preferred
[A2].
Patients with Acute Myocardial Infarction
Hyperglycemia has been found to be associated with poor clinical
outcome in acute myocardial infarction (AMI) patients.31 Whether
hyperglycemia is an indicator of the severity of AMI or it acts as a
mediator in causation of various complications associated with AMI
remains controversial. These controversies are further heightened by
the fact that patients with hypoglycemia who suffer from acute MI
also have an adverse outcome.32,33 Tight glycemic control may not
contribute toward any increased mortality but it definitely reduces
the risk of complications associated with MI such as congestive
Section 5
Chapter 35 Guidelines on Inpatient Management of Hyperglycemia
cardiac failure and reinfarction.34 The efficacy of GIK regimen in
patients with acute AMI has remained inconclusive.35
Peripartum Control of Hyperglycemia
• Hyperglycemia and hypoglycemia both should be avoided in
patients with AMI to decrease morbidity and mortality [A1].
• Optimal glycemic control insulin, preferably analogs during and
after the episode, decreases the risk of complications associated
with AMI [A2].
The effect of placental hormones, growth factors and cytokines
increases insulin resistance during pregnancy, and this significantly
enhances insulin requirements. Constant vigil for sudden onset of
metabolic complications like maternal ketoacidosis during labor
and neonatal hypoglycemia is essential and has to be managed
appropriately. Insulin dose should be titrated on an individual basis
as parturient shows wide variability in insulin resistance after 14
weeks of gestation.43
Patients on Glucocorticoid Therapy
Recommendations
Due to sustained hyperglycemia especially during post-prandial
period, susceptible glucocorticoid users can be treated with
titration of meal-time insulin dose.36,37 The variable sensitivity and
requirement of the insulin mandates monitoring of BG for 48 hours in
patients receiving high-dose glucocorticoid therapy so as to prevent
any episode of hyperglycemia or hypoglycemia.38 Basal bolus insulin
in the patient can be adjusted on the basis of correctional insulin
requirements. An increment of 20% of intermediate- or long-acting
insulin doses is considered safe to control hyperglycemia.38,39 Due
to inadequate quality evidence in medical literature, formulating
the best apprach to control hyperglycemia in patients on high-dose
glucocorticoid therapy remains a difficult task.
• Insulin is the preferred therapy in pregnancy complicated by
diabetes [A1].
• Rapid-acting insulin analogs—aspart and lispro are preferred for
use in pregnancy. Detemir is a preferred choice as basal insulin
[A2].
• Patients in active labor should be on glucose, IV insulin plus
potassium infusion to prevent hypokalemia, hypoglycemia as
well as ketosis [A1].
• Incremental insulin dose is required for pregnant ladies receiving
long-acting glucocorticoid for fetal maturity [B2].
Recommendations
Management of hyperglycemia in pediatric patients is challenging
especially among critically sick patients.44 Factors such as longer
duration of hyperglycemia and higher peak BG (> 180 mg/dL) can lead
to prolonged hospitalization, increased nosocomial infections and
3.5 fold increase in sepsis-related mortality risks.44-47 Management
of hyperglycemia in ICU with IV insulin infusion is definitely a safer
option in pediatric patients.48 The target of BG (110–150 mg/dL)
should be modest, and insulin should be used judiciously to avoid
hypoglycemia and ketosis.49 The physiological insulin resistance
during pubertal growth may be perceived as increased insulin
requirement in this age group.50 To this end, the use of insulin analogs
(both basal and rapid) looks quite promising.
Recommendations
• Regular and sustained monitoring of BG should be done in
patients on high dose of glucocorticoid therapy [A1].
• Treatment naïve patients developing hyperglycemia after
glucocorticoid initiation should be managed with insulin [A2].
• For patients already on insulin, 20% increment in total daily
insulin dose at time of high-dose glucocorticoid initiation is a
reasonable step [B2].
Patients on Enteral Nutrition
The control of hyperglycemia is challenging in patients receiving
enteral nutrition as glycemic levels show marked variability with
type and duration of enteral nutrition (i.e. Ryles tube or gastrostomy
tube). Basal insulin may exert hypoglycemic effects on sudden
discontinuation of enteral nutrition.40,41 Basal insulin analogs
control hyperglycemia, in combination with SSI, without any higher
incidence of hypoglycemia as compared to SSI alone, as the latter
regimen is associated with additional requirement of intermediateacting insulin in 48% cases.15
Recommendations
• Insulin analogs should be preferred to control hyperglycemia in
indoor patients on enteral nutrition [A2].
• Basal plus multiple SC prandial boluses are to be preferred over
SSI [A1].
Patients Receiving Parenteral Nutrition
Parenteral nutrition can be extremely detrimental to critically ill
diabetic patients as the large amount of glucose in these solutions
results in severe hyperglycemia. The uncontrolled hyperglycemia is
responsible for higher incidence of complications and mortality in
this subset of population.42
Recommendations
• Intravenous insulin is the preferred treatment for control of
hyperglycemia in patients receiving parenteral nutrition [A1].
• Glucose targets should be based on the severity of underlying
illness [A1].
Critically Ill Pediatric Patients
Recommendations
• Insulin is the preferred therapy in pediatric ICU with optimal BG
target of 110–150 mg/dL [A2].
• Insulin analogs are preferred over conventional insulin.
Recommended age limit is greater than 2 years for aspart, greater
than 3 years for lispro, greater than 4 years for glulisine, greater
than 2 years for detemir, and greater than 6 years for glargine [A2].
Transition to Outdoor Management
Discharge and outdoor management of patients with diabetes
should be done only after prior stabilization of blood glucose levels.
Physicians should be aware of the onset, peak and the effective
duration of each type of insulin before writing out the treatment
plan (Table 5). It is prodent to follow a practival plan of switching
over to SC insulin based on the most recent IV insulin requirement,
rather than doing it arbitrarily with inconsistent results (Table 6).
The patient should be provided a simplified treatment plan including
drug regime and its appropriate use, BG monitoring schedule,
hypoglycemic symptoms and their management, and contact
number of primary care physician whom they can contact during any
major complaint or emergency. Patients should be shifted to more
convenient insulin regimes, such as premixed insulin twice daily,
if possible, before discharge from hospital, and the concordance of
meals and SC insulin should be ensured. They should be monitored
on this regime for a few days in hospital if possible, and the first
follow-up should be done within 10–14 days time period.51
167
Diabetology
Section 5
TABLE 5 │ Onset, peak and total effective duration of action of
various preparations of insulin
Insulin preparation
among various disciplines. Appropriate use of insulin and insulin
analogs using IV or SC regimes as required to target euglycemia
ensures better therapeutic outcomes. Along with this, training of
health workers, education of support staff, use of simple protocols,
auditing of mortality and morbidity statistics and a good feedback
system are essential for the successful management of hyperglycemia
in low resource health set-up.
Onset
(hour)
Peak
(hour)
Effective
duration
(hour)
Lispro
< 0.25
0.5–1.5
3–4
Aspart
< 0.25
0.5–1.5
3–4
ACKNOWLEDGMENTS
Glulisine
< 0.25
0.5–1.5
3–4
Regular
0.5–1.0
2–3
4–6
The authors are grateful to Dr Ganpathi Bantwal, Dr Mathew John,
Dr Rakesh K Sahay, Dr AG Unnikrishnan, Dr Raman Setty, Dr
Inderpreet Sohi, Dr Sukhwinder Kaur Bajwa for their critical inputs
while formulating and grading the evidences.
Neutral protamine hagedorn
(NPH)
1–4
6–10
10–16
Detemir
1–4
24
Glargine
1–4
24
Short-acting subcutaneous
Long-acting
REFERENCES
TABLE 6 │ Insulin dose calculation during transition from
intravenous to subcutaneous regimen
Example: Baseline insulin requirement while NPO = 2 units/hour
Step 1
Adjusted basal dose calculation
• Patient’s hourly insulin infusion rate while NPO =
2 units/hour
• 24-hours basal insulin dose during stress = 24 × 2 = 48 units
• Adjusted basal dose accounting for stress reduction = 2/3 ×
48 = 32 units of basal insulin/24 hour
Step 2
Total SC dose calculation
2 × Adjusted basal dose = 2 × 32 = 64 units
Step 3
Step 4
Mealtime bolus dose calculation
Patient just started to eat, so 10% of basal dose can be
started with each meal = 0.1 × 32 = 3 units with each meal
Correctional scale estimation
A moderate level correctional scale is most appropriate for an
estimated total daily dose (TDD) of 64 units
Recommendations
• Patients being discharged from the hospital may be prescribed
basal-bolus or premixed insulin regimen as required [A2].
• Education regarding insulin technique, self-monitoring of blood
glucose (SMBG), hypoglycemia, and self adjustment of doses
should be provided before discharge and on an ongoing basis.
Elaborate, clear instructions written in comprehensible language
should be provided [B2].
Supportive Treatment
Besides pharmacological therapies, management of diabetes also
requires nonpharmacological support including medical nutrition
therapy, physical activity, behavioral therapy and cessation of
smoking. Individualized, patient centered, enteral and parenteral
nutrition in diabetic inpatients is given with due consideration to
appetite, severity of underlying illness and associated comorbidities.
Coordinated teamwork can go a long way in establishing various
simple protocols to manage hyperglycemia in the hospital setting.
CONCLUSION
The management of diabetes in hospitalized patients is easier as
compared to outpatients, provided that there is good coordination
168
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