Lewis R. Goldfrank, MDProfessor and Chairman of Emergency Medicine

New York University Medical Center Bellevue Hospital Center

New York University School of MedicineMedical Director, New York City Poison Center

Hypoglycemia

Track D

September 17, 2003

Barcelona

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.

Patient 2

An 18 year old male at a rock concert

History of drug use

Initially wildly agitated then becomes comatose

Pupils: “large”, - diaphoretic

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?

Causes of Hypoglycemia

A. Toxins B. Other Insulin Sepsis

Sulfonylureas Hypo- and hyperthermia

Ethanol Hepatic failure

Aspirin Myxedema

Pentamidine Insulinoma

Ackee fruit

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).

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).

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

Empiric Use of Hypertonic Dextrose in Patients With Altered Mental Status

%

All Complete Responders

(N = 25)

%

Complete Hypoglycemic

Responders

(N = 20)

Tachycardia 40 45

Diaphoresis 40 50

History of DM 52 65

Any one of above 64 75

Hoffman JR, et al: Ann Emerg Med 1992;21:20.

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.

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.

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.

Concern Over Glucose Administration

The routine use of D50W for the majority of patients with AMS is unnecessary , costly and wasteful.

Considerations for D50W

• 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

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.

How accurate should glucose reagent sticks be for the detection of hypoglycemia?

orCan we tolerate missing the diagnosis of hypoglycemia in patients who have falsely elevated results or have clinical hypoglycemia with numerically elevated glucoses?

No

Who Does Delay in Delivery of 50% D/W Place at Risk?

Anyone who is hypoglycemic

Management Errors In Hypoglycemia Patient

Assumption of psychosis, epilepsy, CVA

With presence of ethanol assuming ethanol is cause of symptoms

Single bolus dextrose therapy

Initial Treatment

In adults, reverse the hypoglycemia with boluses of dextrose D50W followed by

D5W or D10W solutions as maintenance.

Frequent bedside glucose checks until equilibrium established.

Higher concentrations of dextrose (D20W)require central venous access.

Treatment Use D25W 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).

Type Preparation Onset (hours)

Peak (hours)

Duration (hours)

Rapid-acting Regular ½ – 1 2 ½ – 5 6 – 8

Semi-lente 1 – 1 ½ 5 – 10 12 – 16

Intermediate-acting

NPH 1 – 1 ½ 4 – 12 24

Lente 1 – 2 ½ 7 – 15 24

Long-acting PZI 4 – 8 14 – 24 36

Ultralente 4 – 8 10 – 30 >36

Insulin Kinetics

Sulfonylureas Trade Names Cmax

(hours)

Half-life

(hours)

Active Metabolite

Duration of Action (hours)

First Generation:

Tolbutamide Oramide, Orinase

3 – 5 3 – 28 no 6 – 12

Tolazamide Tolamide, Tolinase

4 – 8 4 – 7 yes 10 – 14

Acetohexamide Dymelor 1 – 2 1 – 2 yes 12 – 24

Chlorpropamide Diabinese 1 – 7 25 – 60 yes Up to 72

Second Generation:

Glyburide DiaBeta, Micronase, Glynase

2 – 8 0.7 – 3 no 10 – 24

Glipizide Glucotrol 1 – 3 2 – 7.3 no 10 – 24

Gliclazide Diamicron 10 – 12 no

Sulfonylurea Kinetics

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.

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