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HYPOGLYCEMIA MANAGEMENT IN THE EMERGENCY DEPARTMENT Silu Zuo, Pharm.D. PGY1 Pharmacy Resident UW Medicine Patient Case 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 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 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 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 Critical illness Hormone deficiency 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 Oral carbohydrate replacement IV glucose/dextrose Glucagon Octreotide Diazoxide UWMC Hypoglycemia Protocol UWMC Hypoglycemia Protocol UWMC Hypoglycemia Protocol Oral Carbohydrates 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 After treatment, eat snack with protein/fat to prevent recurrence Clinical Diabetes 2012 Jan;30(1):38 IV Glucose/Dextrose “IV glucose” = IV dextrose 50% (50g/100mL) Dose = 12.5-25 g (25 g/50 mL = 1 amp) IV push Dextrose 5%, 10%, 20%, 30%, 40%, 50%, 70% 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 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 Somatostatin analogue Provides more potent inhibition of growth hormone, glucagon, and insulin as compared to endogenous somatostatin 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 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 Adverse effects: bradycardia, dizziness, hyperglycemia, diarrhea, constipation Sandostatin [prescribing information]. Diazoxide 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 No randomized, controlled studies Few case reports Pentamidine-induced hypoglycemia Sulfonylurea-induced hypoglycemia Pharmacol Rev. 2003 Mar;55(1):105-31. Diazoxide 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 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 Sent to Harborview for surgical management References 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. UptoDate. Instant glucose and intravenous dextrose: Drug information. LexiComp. GlucaGen HypoKit (glucagon) [prescribing information]. Princeton, NJ: Novo Nordisk Inc; December 2011. Glucagon Emergency Kit [prescribing information]. Indianapolis, IN: Eli Lilly and Company; February 18, 2005. Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacol Rev. 2003 Mar;55(1):105-31. 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. Diazoxide [prescribing information]. Baker Norton Pharmaceuticals, Miami, FL, 1997.
