Transcript Hypoglycemia Management in the Emergency Department

HYPOGLYCEMIA MANAGEMENT IN
THE EMERGENCY DEPARTMENT
Silu Zuo, Pharm.D.
PGY1 Pharmacy Resident
UW Medicine
Patient Case
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CC: JT is a 53 y/o female presenting to ED with
profound hypoglycemia and unresponsiveness
during nuclear medicine study
HPI:
 Progressive
hypoglycemia over past several years, at
times resulting in loss of consciousness
 Recent CT scan showed possible neuroendocrine tumor
on pancreas  nuclear medicine study to further assess
 At nuclear medicine, was unresponsive with BG of 20
Patient Case
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PMH:
 Epilepsy,
complex partial
 Turner's syndrome
 Hypoglycemia
 Osteoporosis
 Macrocytic anemia
Patient Case

Medications:
Alendronate 70 mg PO Q7 days
 Benztropine 0.5 mg PO BID
 Carbamazepine 400 mg PO BID
 Depakote 500 mg PO EC BID
 Glucagon 1mg Injection PRN hypoglycemia
 Glucose 40% oral gel 15 gram tube PO PRN hypoglycemia
 Olanzapine 15 mg PO QHS
 Potassium chloride ER 20 MEQ PO daily
 Sertraline Hcl 100mg PO daily
 Topiramate 25 mg PO BID

Patient Case
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Vitals
 BP
102/53 HR 88 RR 18 SpO2 100% RA
To be continued….
Glucose Homeostasis
Glucose Homeostasis
↓ blood
glucose
↑ blood
glucose
Glucose Homeostasis

The pancreas is a major player
 Alpha
cells: secrete glucagon
 Beta cells: secrete insulin
 Delta cells: secrete somatostatin
 Important
role in maintaining balance of both insulin and
glucagon

Other counter-regulatory hormones
 Adrenaline
 Cortistol
(epinephrine)
Glucose Homeostasis
Hypoglycemia
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Normal blood glucose (fasting): 70-110 mg/dL
Small excursions above range post-prandially
Hypoglycemia – “Whipple’s triad”
 1)
Symptoms consistent with hypoglycemia
 2) Low plasma glucose concentration (<70 mg/dL)
 3) Relief of those symptoms after the plasma glucose
level is raised
Harper's Illustrated Biochemistry, 29e. New York, NY: McGraw-Hill; 2012.
Hypoglycemia
Hypoglycemia

Hypoglycemia can be very dangerous if untreated
 Brain
cannot make glucose or store very much glycogen
 requires a continuous supply of glucose from blood
circulation

Serious hypoglycemia
 Seizure,
loss of consciousness, coma, death
Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
Hypoglycemia
Causes
 Drugs
Insulin or insulin secretagogue, alcohol
 Gatifloxacin (removed from market), pentamidine, quinine,
indomethacin, others
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Critical illness

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Hormone deficiency

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Hepatic, renal or cardiac failure, sepsis
Cortisol, glucagon, epinephrine (in insulin-deficient diabetes)
Non–islet cell tumor
J Clin Endocrinol Metab 94:709, 2009.
Hypoglycemia
Causes
 Endogenous hyperinsulinism
 Insulinoma
 Functional
beta-cell disorder (noninsulinoma
pancreatogenous hypoglycemia, post gastric bypass)
 Insulin or insulin receptor antibody
 Insulin autoimmune hypoglycemia

Accidental, surreptitious, or malicious hypoglycemia
J Clin Endocrinol Metab 94:709, 2009.
Treatment
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Oral carbohydrate replacement
IV glucose/dextrose
Glucagon
Octreotide
Diazoxide
UWMC Hypoglycemia Protocol
UWMC Hypoglycemia Protocol
UWMC Hypoglycemia Protocol
Oral Carbohydrates
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Glucose 15-20 g orally – preferred initial
treatment in conscious individual with hypoglycemia
Examples of 15 g of carbohydrates:
4
ounces of juice
 4 ounces of nondiet soda
 8 ounces of skim milk
 3-4 glucose tablets
 5-6 Life Savers candies
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After treatment, eat snack with protein/fat to
prevent recurrence
Clinical Diabetes 2012 Jan;30(1):38
IV Glucose/Dextrose
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“IV glucose” = IV dextrose 50% (50g/100mL)
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Dose = 12.5-25 g (25 g/50 mL = 1 amp) IV push
Dextrose 5%, 10%, 20%, 30%, 40%, 50%, 70%
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5-10% can give via peripheral IV

10% at fast rate may cause irritation and ↑ risk of
extravasation
Concentrations >10% (hypertonic) may cause
thrombosis if infused via peripheral veins 
administer via central line
 AVOID extravasation (vesicant)

UpToDate.
Glucagon
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Dose: 1 mg IV/IM/SQ, may repeat in 15 mins
IV dextrose should be administered as soon as it is
available; if patient fails to respond to glucagon, IV
dextrose must be given.
Role: patients without IV access (especially severe
hypoglycemia, unconscious patients
Glucagon HypoKit
GlucaGen HypoKit (glucagon) [prescribing information].
Glucagon Emergency Kit [prescribing information].
Glucagon Emergency Kit
Patient, Case Cont’d
Time
Blood Glucose Notes
1214
165
After IV glucose 12.5 g
1250
17
 D50% 12.5 g, D5/NS 100 mL/hr
1326
76
1348
33
1413
168
1428
134
1452
107
1536
99
1600
114
 D50% 12.5 g
Central line placed, D10 100 mL/hr
Octreotide
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Somatostatin analogue
 Provides
more potent inhibition of growth hormone,
glucagon, and insulin as compared to endogenous
somatostatin
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May reduce recurrent hypoglycemia as with dextrosealone therapy
Should be used with IV dextrose/oral carbohydrates
Dose: (ideal dose not well established)
 SQ:
50-100 mcg, repeat every 6 hours PRN
 IV: up to 125 mcg/hour has been used
Pharmacol Rev. 2003 Mar;55(1):105-31.
Ann Emerg Med, 2000, 36(2):133-6.
Octreotide
Design
Prospective, double-blind, placebo-controlled trial
Patients
• 40 adult patients presenting to ED with hypoglycemia
(BG≤60 mg/dL)
• Taking a sulfonylurea or a combination of insulin and
sulfonylurea
• Admitted to hospital for at least 24 hrs
• Exclusions: pregnancy, not taking insulin/SU
Intervention/ Intervention (N=22)
Comparator Standard treatment (1
ampule of 50% dextrose IV
and oral carbs) + 1 dose
of octreotide 75 mcg SQ
Ann Emerg Med 2008; 51(4):400-406.
Comparator (N=18)
Standard treatment +
placebo (1 mL of 0.9%
NS SQ)
Octreotide
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Results
 Reduced
Ann Emerg Med 2008; 51(4):400-406.
rate of recurrent hypoglycemia
Octreotide

Warnings/precautions:
 Cholelithiasis
– may inhibit gallbladder contractility
 Glucose regulation
 Hypothyroidism – may suppress TSH secretion
 Pancreatitis – may change absorption of fats
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Adverse effects: bradycardia, dizziness,
hyperglycemia, diarrhea, constipation
Sandostatin [prescribing information].
Diazoxide
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Antidote for hypoglycemia due to hyperinsulinemia;
vasodilator
Opens ATP-dependent K+ channels on pancreatic
beta cells  hyperpolarization of the beta cell 
inhibition of insulin release
Binds to a different site on the potassium channel
than the sulfonylureas
Dose: 3-8 mg/kg/day PO in divided doses Q8H
 Starting
dose 3 mg/kg/day PO divided in 2-3 doses
Diazoxide
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No randomized, controlled studies
Few case reports
 Pentamidine-induced
hypoglycemia
 Sulfonylurea-induced hypoglycemia
Pharmacol Rev. 2003 Mar;55(1):105-31.
Diazoxide
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Contraindications: hypersensitivity to diazoxide or to
other thiazides
Warnings/precautions:
failure – antidiuretic actions, may ↑ fluid retention
 Gout – may cause hyperuricemia
 Renal dysfunction
 Heart

Adverse effects: hypotension, hyperglycemia
Diazoxide [prescribing information].
Patient Case, Cont’d
Time
Blood Glucose
Notes
1633
131
Diazoxide __ mg
1817-2012
84-111
Transferred to MICU
2117-2353
61/55/78
 D50% 25 g x 3 amps
0246
74
 D50% 25 g x 1 amp, changed to D20%
1345
73
D50% 25 g x 1 amp, changed to to
D50%/0.45%NS
Patient Case, Cont’d
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Post-ED, admitted to MICU with close follow-up from
Endocrinology
Continued to IV dextrose infusion with PRN D50% and
Q3-6H BG checks
Extensive workup for neuroendocrine tumor:

Labs:
Low insulin, c-peptide, and high betahydroxybutyrate  does not
suggest insulinoma
 High pro-insulin  may mimic effects of insulin and likely cause of
low BG

Octreotide scan – negative findings
 Endoscopic US Biopsy of pancreatic mass: Positive for
neoplasia neuroendocrine tumor
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Sent to Harborview for surgical management
References
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Bender DA, Mayes PA. Chapter 20. Gluconeogenesis & the Control of Blood Glucose. In: Murray RK, Bender DA, Botham KM,
Kennelly PJ, Rodwell VW, Weil P. eds. Harper's Illustrated Biochemistry, 29e. New York, NY: McGraw-Hill; 2012.
Cryer PE, Davis SN. Chapter 345. Hypoglycemia. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo
J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society
Clinical Practice Guideline. J Clin Endocrinol Metab. 2009 Mar;94(3):709-28.

American Diabetes Association. Hypoglycemia? Low Blood Glucose? Low Blood Sugar? Clinical Diabetes 2012 Jan;30(1):38.
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UptoDate. Instant glucose and intravenous dextrose: Drug information. LexiComp.
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GlucaGen HypoKit (glucagon) [prescribing information]. Princeton, NJ: Novo Nordisk Inc; December 2011.
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Glucagon Emergency Kit [prescribing information]. Indianapolis, IN: Eli Lilly and Company; February 18, 2005.
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Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacol Rev. 2003 Mar;55(1):105-31.
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McLaughlin SA, Crandall CS, and McKinney PE, “Octreotide: An Antidote for Sulfonylurea-Induced Hypoglycemia,” Ann Emerg
Med, 2000, 36(2):133-6.
Fasano CJ, O'Malley G, Dominici P, et al: Comparison of octreotide and standard therapy versus standard therapy alone for
the treatment of sulfonylurea-induced hypoglycemia. Ann Emerg Med 2008; 51(4):400-406.

Sandostatin [prescribing information]. East Hanover, NJ: March 2012.
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Diazoxide [prescribing information]. Baker Norton Pharmaceuticals, Miami, FL, 1997.