Transcript here

Hypoglycemia in the
Hospital
Sara Alexanian, MD
Director, Inpatient Diabetes
Program
Department of Endocrinology,
Diabetes and Nutrition
Agenda
 Glycemic
goals
 Physiology
 Epidemiology and risks of
hypoglycemia
 Preventing and avoiding
hypoglycemia
Hyperglycemia in the Hospital:
the Facts
Hyperglycemia is noted in 20-40% of
hospitalized patients.
 Hyperglycemia, irrespective of it’s cause,
is unequivocally associated with adverse
clinical outcomes.
 Intervention studies directed at BG control
have resulted in improved outcomes in
some, but not all studies.
 Insulin therapy, in particular (“intensive
glycemic control”) carries a risk of
hypoglycemia.

What are the recommendations
for glucose control in the
hospital?
AACE/ADA Target Glucose Levels
in Non–ICU Patients
 Non–ICU
setting:
– Premeal glucose targets <140 mg/dL
– Random BG <180 mg/dL
– To avoid hypoglycemia, reassess insulin
regimen if BG levels fall below 100 mg/dL
– Occasional patients may be maintained
with a glucose range below and/or above
these cut-points
AACE/ADA Target Glucose Level
in ICU Patients
 ICU
setting:
– Starting threshold of no higher than 180 mg/dL
– Once IV insulin is started, the glucose level should
be maintained between 140 and 180 mg/dL
– Lower glucose targets (110-140 mg/dL) may be
appropriate in selected patients
– Targets <110 mg/dL or >180 mg/dL are not
recommended
Not recommended
<110
Acceptable
110-140
Recommended Not recommended
140-180
>180
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).
http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.
Case #1


60 year-old female with a history of COPD
admitted with respiratory failure, intubated, and
started on tube feeds in the ICU.
The patient is started on an insulin drip to control
glucose. After returning from a CT during which
tube feeds were discontinued, her glucose is
noted to be 55 mg/dL. The patient is
asymptomatic, she is treated with dextrose and
tube feeds are restarted.
Question: What, if anything, does
this low glucose mean for the patients’ prognosis?
Hypoglycemia: what and what
is happening
Background
insulin
Glucose
60-120 mg/dL
“post-absorptive”
state
glucagon
“fed” state
G G
G
G
G
G
G G
Defining Hypoglycemia
<80
<70
 Symptomatic
<60
<50
<40
hypoglycemia:
symptoms and BG <70 mg/dL
 Severe hypoglycemia: event requiring
assistance from another person to
administer treatment
 Relative hypoglycemia: symptoms and
BG >70 mg/dL in patient with
chronically poorly controlled DM
 Limited utility in studies
Hypoglycemia Symptoms
normal
90
70
Counterregulatory hormone release
60
Adrenergic symptoms
50
Neuroglycopenic symptoms
40
30
20
lethargy
coma
seizure
Chronic and Recurrent
hypoglycemia
Hypoglycemia in Diabetes
Proposed mechanism of
increased mortality
 Prolonged,
profound hypoglycemia
can cause brain death.
 Most deaths are presumed to be due
to arrhythmia:
– Hypokalemia
– Sympathoadrenal activation
– Prolonged QT
Potential mechanism of iatrogenic hypoglycemiainduced hypoglycemia-associated autonomic
failure (HAAF) mediated sudden death in diabetes
Cryer. Am J Med 24: 993-996, 2011
Inpatient Hypoglycemia: Frequency
Hospital Location
SICU <40 mg/dL
Frequency
1
5.1%
1
18.9%
MICU <40 mg/dL
SICU/MICU <40 mg/dL
3
ICU <40 mg/dL
4
ICU <45 mg/dL
5
ICU <81 mg/dL
6
Wards ≤50 mg/dL
2
0.34%
16%
6.8%
13.8%
7.7%
1. Van den Berge G et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11):3151-9. 2.
Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic
Proc 2004;79(992-1000). 3. Arabi YM et al, Hypoglycemia with intensive insulin therapy in critically ill patients. Crit Care Med
2009;37(9):2536-44. 4. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med
2006;34(11)2714-8. 5. Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical
illness. Crit Care Med 2009;13(3):R91. 6. Turchin A et al, Hypoglycemia and clinical outcomes in patients with diabetes hospitalized
in the general ward. Diabetes Care 2009;32(7):1153-7.
Inpatient Hypoglycemia: Mortality
Hospital Location
No hypos
Hypos
ICU (<81 mg/dL)
1
19.7%
36.6%
ICU (<81 mg/dL)
2
15.5%
25.6%
ICU (≤40 mg/dL)
3
23%
52%
4
9.6%
12.7%
0.82%
2.96%
AMI (<60 mg/dl)
Wards (≤50 mg/dL)
5
1. Egi M et al, Hypoglycemia and outcomes in critically ill patients. Mayo Clin Proc 2010;85(3):217-24. 2. Bagshaw SM et
al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med
2009;13(3):R91 3. Van den Berge et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes
2006;55(11):3151-9. 4. Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality
in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64. 5. Turchin A et al, Hypoglycemia
and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32(7):1153-7.
<36 mg/dL
38-44
45-52
53-62
63-70
71-80
≥80
Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in
critical illness. Crit Care Med 2009;13(3):R91
We hold these truths to be selfevident…
is all hypoglycemia equal?
“Spontaneous” Hypoglycemia
Hypoglycemia occurring without prior
insulin or anti-hyperglycemic therapy.
 Increased in critical illness: mechanical
ventilation, sepsis, renal insufficiency,
higher APACHE II score.
 Frequency:

1
– 26% of all ICU pts with hypoglycemia
2
– 28% of patients admitted with acute MI
1. Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically
ill adult patients. Mayo Clinic Proc 2004;79(992-1000). 2. Kosiborod M et al, Relationship between
spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial
infarction. JAMA 2009;301(15):1556-64.
Risk of therapy or marker of
illness?
 Treated
with insulin?: AMI
– Mortality with spontaneous
hypoglycemia: 18.4%( increased from
control)
– Mortality of insulin-associated
hypoglycemia: 10.4% (NO increase
from control)
Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in
patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64.
Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in
patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64.
Risk of therapy or marker of
illness?
 Correct
for comorbid illness:
– Study #1: case control correcting for
age, sex, duration of ICU stay, APACHE
II score: no association with incidental
hypoglycemia and death (41% vs. 27%,
1
not significant) .
– Study #2: case control correcting for
diagnosis, APACHE II, age diabetes
history: Increase mortality associated
2
with hypoglycemia (55.9% vs. 39.5%) .
1. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med
2006;34(11)2714-8. 2. Krinsley JS et al, The effect of an intensive glucose management protocol on the
mortality of critically ill adult patients. Mayo Clinic Proc 2004;79(992-1000).
…but
 Time
from hypoglycemic episode to
death:
– 221 hours (54-530 hours)
1
– 152 hours (87-407 hours)
2
– 11 days (0-204 days)
1
1. Van den Berghe, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes
2006;55(11):3151-9. 2. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU.
Crit Care Med 2006;34(11)2714-8.
Case #1


60 year-old female with a history of COPD
admitted with respiratory failure, intubated, and
started on tube feeds in the ICU.
The patient is started on an insulin drip to control
glucose. After returning from a CT during which
tube feeds were discontinued, her glucose is
noted to be 55 mg/dL. The patient is
asymptomatic, she is treated with dextrose and
tube feeds are restarted.
Question: What, if anything, does
this low glucose mean for the patients’ prognosis?
?????
So…hypoglycemia is bad.
However there is confounding from
illness, and spontaneous
hypoglycema.
However, we should avoid it.
So what can I do?
Know the Risk Factors
 Advanced
age
 Slender and or longstanding diabetes
 Malnutrition
 Active cancer
 Renal disease
 Liver disease
 Congestive heart failure
 History of heavy alcohol intake
 Chronic pancreatitis
 Critical illness
Know who is at most risk to suffer
adverse consequences
 Inability
to recognize or
communicate hypoglycemic
symptoms
 Stroke patients
 Dementia
 Altered Mental Status: sedation,
intubated, previous hypoglycemia
Treating your patients’
hyperglycemia
Always use weight-based insulin
 Do not simply order a patients’ outpatient
regimen if it does not appear safe.
Beware of programs > 1 unit/kg/day.
 Review your patients glucose levels at
least twice per day
 Consider a change if a glucose is <100.
 Ask yourself, why is my patient low? Why
is my patient high?

Case #2
 76
yo M with DM2 on admitted from
NH when found confused, BG 58
mg/dL.
 Patient with prior CVA, CKD, HTN.
 Labs on admit: BG 121, Cr 2.72
mg/dL, normal LFTs.
 Weight: 98 kg.
Case #2
 Outpatient
program: glargine 45
units at HS, novolog 35 units
prebreakfast and presupper.
 Per NH, FS run 90-180
 Most recent A1c 1 month ago 5.1%.
Case #2
 What
are the red flags here?
– High outpatient dose
– Low A1c
– Dementia
– CKD
– Advanced age
What insulin program do YOU
recommend?
Average insulin need: 0.5 u/kg/day
Advance age: -0.1 u/kg/day
Renal insufficiency: -.0 1 u/kg/day
Initial TDD : 0.3 u/kg/day
98 kg x 0.3 = apx 30 u/day
50% basal
15 units of glargine
50% nutritional
5 units lispro TID
Correction
CF 1:50, start at 200 HS
How did he do?
 Fasting
2
Bg on chemistry: 99 mg/dL
POC: 127 mg/dL, 157 mg/dL
Case #3
 23
yo M with type 1 diabetes.
 Weight: 58 kg
 Inpatient insulin program: 16 units
of glargine at HS, lispro 5 TID with
meals, lispro SS. TDD: 30 units.
Case #3
TDD 30 units/day
Meal insulin and SS
C7
287
Bedtime
257
Lispro 9
SS
lunch
313
MN
>600
Lispro 10
X1
supper
330
2:45 AM 5:40 AM
30
405
Lispro 10
X1
Truth and Consequences
Hyperglycemia is a common problem that
requires treatment.
 Insulin treatment carries a risk of
hypoglycemia (even just “sliding scale”).
 Both hyper- and hypoglycemia are
associated with an increase in hospital
mortality, hospital cost, and increase LOS.
 Frequency of hypoglycemia can be
mitigated by following current guidelines
for BG targets, tailoring insulin programs,
and being active in assessing your insulin
program.

What can you do?
Critically evaluate your patients insulin
program, on admission and daily.
 Tailor your program to your patient
 Be aware of insulin “stacking” and
appropriate correction insulin doses
 Always re-evaluate a program if the BG is
low, and reconsider if <100.
 Take the time to figure out what is
happening.
 Consult the GLUC or NP service if you
need help.

Thanks!
What do i do for an insulin
program?
Remaining Questions
 What
cutoffs should define
hypoglycemia in studies?
 How do we sort out the risk of
iatrogenic hypoglycemia from
hypoglycemia as a marker of
disease?
 How does hypoglycemia increase
mortality?
Hypoglycemia in Patients with Diabetes:
contributing factors
 Medication/iatrogenic:
insulin,
sulfonylureas, meglitinides
 Abnormal hormonal counterregulation
 Hypoglycemic unawareness
 autonomic dysregulation
 exercise
Hypoglycemia in patients with
Diabetes: contributing factors
Medications/iatrogenic: insulin,
sulfonylureas, meglitinides
 Abnormal hormonal counter-regulation
 Hypoglycemic unawareness
 Renal and hepatic dysfunction
 Autonomic dysregulation
 Age
 Exercise
 Alcohol
