1. Lewis R. Goldfrank, MD Professor and Chairman of Emergency Medicine New York University Medical Center Bellevue Hospital Center New York University School of Medicine Medical Director, New York City Poison Center Hypoglycemia Track D September 17, 2003 Barcelona

2. Patient 1 An elderly woman is found at the bottom of her stairs with a BP 190/110 mm Hg, pulse 110 beats/min; T: 97  F (36.1°C) and RR 20. She is hemiparetic with a large gash over her right eye. Her purse is missing.

3. Patient 2 An 18 year old male at a rock concert History of drug use Initially wildly agitated then becomes comatose Pupils: “large”, - diaphoretic

4. Patient 3 A forty five year old woman is brought to the ED in a coma. He has garbled speech but moves all extremities. Her vital signs are RR 20 HR 120 BP 140/90, T 89.6 ° F (32 ° C). What should be done?

5. Causes of Hypoglycemia A.Toxins B. Other Insulin Sepsis Sulfonylureas Hypo- and hyperthermia Ethanol Hepatic failure Aspirin Myxedema Pentamidine Insulinoma Ackee fruit

6. Incidence of Hypoglycemia 125 visits for symptomic hypoglycemia in one 12 month period 65 with obtundation, stupor or coma 38 with confusion or bizarre behavior 9 with seizures 3 with hemiparesis (2.4%) Harlem Hospital (Ann Neurol 1985;17:421).

7. Incidence of Hypoglycemia (outcome) Diabetes, ethanol, and sepsis, alone or in combination accounted for 90% of patients. Overall mortality was 11%. Only one death from hypoglycemia alone. 4 survivors and residual focal neurologic deficits (2 had no focality on presentation) Harlem Hospital (Ann Neurol 1985;17:421).

8. What Findings are Associated With Hypoglycemia? Common findings tachycardia diaphoresis change in consciousness agitation, somnolence, coma A.Catecholamine release  neurogenic, autonomic B.Cerebral glucose deprivation  neuroglycopenic

9. Empiric Use of Hypertonic Dextrose in Patients With Altered Mental Status % All Complete Responders (N = 25) % Complete Hypoglycemic Responders (N = 20) Tachycardia4045 Diaphoresis4050 History of DM5265 Any one of above6475 Hoffman JR, et al: Ann Emerg Med 1992;21:20.

10. Plasma Glucose Concentration at the Onset of Symptomatic Hypoglycemia Poorly controlled diabetics 78 mg/dl [4.3 mmol/L] Well controlled diabetics 53 mg/dl [2.9 mmol/L] (p < 0.001) Boyle PJ, et al: N Engl J Med 1988;318:1487.

11. The empiric use of hypertonic dextrose in patients with altered mental status Can the presence of “typical” clinical findings (tachycardia, diaphoresis, and/or available history of DM) accurately predict the recognition of hypoglycemia? No Hoffman, JR. Ann Emerg Med 1992;21:20.

12. Hypoglycemia and Focality Two patients with reversible decerebrate posturing from hypoglycemia (glucose were 35 mg/dL [1.9 mmol/L] and unspecified). Am J Med 1985;78:1036. Hemiplegia in 16 patients (15 with no brain disease) misdiagnosed as having had a stroke. Ann Neurol 1985;18:510.

13. Concern Over Glucose Administration The routine use of D 50 W for the majority of patients with AMS is unnecessary, costly and wasteful. Considerations for D 50 W hyperosmolar load to patients that might already be in hyperosmolar coma hypertonic dextrose can cause hypo or hyperkalemia hypertonic dextrose may damage ischemic CNS tissue

14. Effects of Hypoglycemia on Rat Ischemic Brain Injury After a 2 gm/kg glucose load ischemia is induced in rats. Animals that receive either high or low dose insulin, or another 2 gm/kg of glucose Insulin was protective, while 2 gm/kg control group had a 60% increase in infarct size. Voll Cl: Ann Neurol1988;24:638.

15. How accurate should glucose reagent sticks be for the detection of hypoglycemia? or Can we tolerate missing the diagnosis of hypoglycemia in patients who have falsely elevated results or have clinical hypoglycemia with numerically elevated glucoses? No

16. Who Does Delay in Delivery of 50% D/W Place at Risk? Anyone who is hypoglycemic

17. Management Errors In Hypoglycemia Patient Assumption of psychosis, epilepsy, CVA With presence of ethanol assuming ethanol is cause of symptoms Single bolus dextrose therapy

18. Initial Treatment n In adults, reverse the hypoglycemia with boluses of dextrose D 50 W followed by D 5 W or D 10 W solutions as maintenance. n Frequent bedside glucose checks until equilibrium established. n Higher concentrations of dextrose (D 20 W) require central venous access.

19. Treatment Use D 25 W peripherally in a child (0.5- 1gm/kg or 2-4 ml/kg IV) or 12.5% glucose (neonates). Dextrose provides only a small amount of calories in comparison to food substances. When the patient is taking food, supplemental dextrose may be discontinued, provided serum glucose remains normal (frequent checks are necessary).

20. TypePreparationOnset (hours) Peak (hours) Duration (hours) Rapid-actingRegular½ – 12 ½ – 56 – 8 Semi-lente1 – 1 ½5 – 1012 – 16 Intermediate- acting NPH1 – 1 ½4 – 1224 Lente1 – 2 ½7 – 1524 Long-actingPZI4 – 814 – 2436 Ultralente4 – 810 – 30>36 Insulin Kinetics

21. SulfonylureasTrade NamesCmax (hours) Half-life (hours) Active Metabolite Duration of Action (hours) First Generation: TolbutamideOramide, Orinase 3 – 53 – 28no6 – 12 TolazamideTolamide, Tolinase 4 – 84 – 7yes10 – 14 AcetohexamideDymelor1 – 2 yes12 – 24 ChlorpropamideDiabinese1 – 725 – 60yesUp to 72 Second Generation: GlyburideDiaBeta, Micronase, Glynase 2 – 80.7 – 3no10 – 24 GlipizideGlucotrol1 – 32 – 7.3no10 – 24 GliclazideDiamicron10 – 12no Sulfonylurea Kinetics

22. Octreotide An octapeptide analogue of somatostatin used for patients with refractory hypoglycemia Potent inhibitor of insulin release via a G protein in the beta islet cell Patients may still require dextrose/food More effective than diazoxide 50µg sc q 6 hours no significant side-effects Boyle PJ. J Clin End Metab 1993;76:752.

23. Hypoglycemia: Hospital Admission Required: Ethanol Starvation Hepatic failure Renal failure Unknown etiology Sulfonylureas (any dose in children) Intentional overdoses Insulin: if recurrent on unexplained if persistent > 4 – 6hr