Hypoglycemia, Emergency Medicine

Basics

Description

Deficiency in counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone) or excessive insulin response
Serum glucose < 70 mg/dL

Risk Factors

Strict glycemic control with insulin
Prior hypoglycemia episodes
Hypoglycemia unawareness
Decreased counterregulation
<5 years of age or elderly
Comorbid conditions:
- Renal disease
- Malnutrition
- Coronary artery disease
- Liver disease

Genetics

Congenital metabolic and endocrine disorders that decrease gluconeogenic ability (e.g., hereditary fructose intolerance)
Congenital hyperinsulinism
Neonatal diabetes mellitus (often a mutation effecting an ATP-dependent potassium channel)

Etiology

Increased insulin levels:
- Overdose of oral hypoglycemic agent or insulin
- Oral antihyperglycemics (i.e., α-glucosidase inhibitors, biguanides, and thiazolidinediones) do not cause hypoglycemia alone, but may enhance the risk when used with insulin or sulfonylureas.
- Sepsis
- Insulinoma
- Autoimmune hypoglycemia
- Alimentary hyperinsulinism
- Renal failure (partially responsible for insulin metabolism)
- Liver cirrhosis (responsible for significant insulin metabolism)
Underproduction of glucose:
- Alcohol (inhibitory effect on glycogen storage and gluconeogenesis)
- Drugs
- Salicylates
- β-blockers (including eye drops)
- SSRIs
- Some antibiotics (e.g., sulfonylureas, pentamidine)
- Adrenal insufficiency
- Malnutrition
- Dehydration
Cerebral edema
Extremes of age
Congestive heart failure
Counterregulatory hormone deficiency
Hypothyroidism or hyperthyroidism

3rd-trimester pregnant patients risk relative substrate deficiency-induced hypoglycemia.
The fetus is less likely to become hypoglycemic during mothers hypoglycemic episode secondary to active glucose transport across placenta:
- Oral hypoglycemic use in pregnancy may lead to profound and prolonged neonatal hypoglycemia.

Most common cause of hypoglycemia in the 1st 3 mo of life is persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in mothers with diabetes. �

Diagnosis

Signs and Symptoms

Adrenergic caused by excessive counter-regulatory hormones (i.e., epinephrine):
- Diaphoresis
- Anxiety
- Tachycardia/palpitations
- Hunger
- Paresthesias
- Chest pain
- Ischemic ECG changes
Neuroglycopenic:
- CVA mimic
- Any focal or general neurologic change
- Dizziness
- Confusion
- Mood changes
- Hyperactive or psychotic behavior
- Slurred speech
- Cranial nerve palsies
- Seizures
- Hemiplegia
- Decerebrate posturing
Neonatal presentation:
- Asymptomatic
- Limp
- Bradycardia
- Irritable
- Tremulous
- Seizures
- Poor feeding

Patients with "hypoglycemia unawareness"� have reduced warning signals, do not recognize that their blood sugar is low, and instead may present with only late findings such as seizure, focal neurologic findings, altered mental status, and coma. �
History

Underlying diseases or conditions: Diabetes, renal failure, liver failure, alcohol use.
Certain medications-long-acting insulin and oral hypoglycemic agents-are more concerning.
Possible insulin or oral hypoglycemic overdose.

Physical Exam
See Signs and Symptoms �

Essential Workup

Diagnosis requires:
- Demonstration of neuroglycopenic signs and symptoms as defined above
- Lab evidence of hypoglycemia
- Clearing of symptoms following glucose administration

Diagnosis Tests & Interpretation

Lab

Blood glucose (initial and post-treatment)
Electrolytes, BUN, creatinine
Prothrombin time
Urinalysis for possible infection
Urine and other cultures as appropriate in evaluation for infection
C-peptide if concern for exogenous insulin overdose

Imaging
CXR for: �

Possible aspiration during hypoglycemic episode
Pneumonia as source of sepsis

Diagnostic Procedures/Surgery

ECG if MI/ischemia owing to hypoglycemia or as cause of hypoglycemia suspected.
Hypoglycemia may affect cardiac electrical conduction.

Differential Diagnosis

The differential diagnosis is extensive; see Altered Mental Status for a complete list. Major concerns include: �

Neurologic:
- Cerebral vascular accident/transient ischemic attack (CVA/TIA)
- Seizure disorder
Drug or alcohol intoxication
Hypoxia
Sepsis
Metabolic derangements
Endocrine derangements
Environmental stressors
Psychosis, depression, or anxiety

Growth hormone deficiency
Inborn errors of metabolism
Ketotic hypoglycemia
Reye syndrome
Salicylate ingestion

Treatment

Pre-Hospital

Diagnosis with finger stick glucose
IV dextrose preferred
Oral glucose-containing fluids in awake patient if unable to obtain IV
Glucagon if unable to give IV glucose or oral glucose

Initial Stabilization/Therapy

ABCs with aspiration and seizure precautions
Glucose:
- Dextrose IV push (IVP)-this should always be given if possible.
- Oral glucose in awake patient (with no IV) without risk of aspiration
- Glucagon IM if unable to establish IV access

Ed Treatment/Procedures

Administer D50W 50 mL for decreased level of consciousness:
- 2nd or 3rd amp may be necessary.
- Complications include volume overload and hypokalemia.
Administer octreotide:
- If hypoglycemia refractory to glucose administration
- If hypoglycemia secondary to sulfonylureas
- Initiate continuous IV infusion of 5-20% glucose solution for persistent mild hypoglycemia or if patient cannot eat.
Administer glucagon:
- If hypoglycemia refractory to glucose
- If IV access delayed
- Ineffective in alcohol-induced hypoglycemia and significant liver disease
- May repeat twice q20-30min
- Administer hydrocortisone with glucagon for adrenal insufficiency.
- Effective in 10-20 min

Elderly patients often have less hypoglycemic awareness and require significant time for resolution of symptoms, even after appropriate treatment of hypoglycemia. �

Medication

First Line

D50W: 1-2 amps (25 g) of 50% dextrose IVP
- Zimmerman rule of 50: Adult 1 mL/kg of D50W; child: 2 mL/kg D25W; infants: 5 mL/kg D10W)

Second Line

Octreotide: 50 μg IV bolus then 50 μg IV/hr drip or 50 μg q12hSC/IV
Glucagon: 0.5-2 mg IV/IM/SC:
- Child: 0.03-0.1 mg/kg IV/IM/SC
- Infant: 0.3 mg/kg IV/IM/SC
- May repeat in 4 hr
Hydrocortisone: 100 mg (peds: 1-2 mg/kg) IV
Oral glucose: 20 g orally equals ~12 oz nondiet fruit juice, 14 oz nondiet cola
- Carbohydrate without fat or protein preferred

Follow-Up

Disposition

Admission Criteria

Overdose of long-acting oral hypoglycemic agent (e.g., sulfonylureas) or long-acting insulin mandate observation for at least 24 hr.
Failure of neuroglycopenic symptoms to improve with glucose administration suggests neurologic injury, pre-existing neurologic condition, or another cause for these symptoms.
Recurrent hypoglycemic state in ED
Patients unable to tolerate oral fluids or food
Suicidal intentions
Older patients may require several days for complete recovery from severe or prolonged hypoglycemia.

Discharge Criteria

Discharge mild unintentional insulin overusage or failure to take oral calories if blood glucose normal, symptoms resolved, tolerating oral intake, and can be observed.
Families of patient with recurrent hypoglycemia should be instructed in IM glucagon administration.
Monitor blood glucose for at least 3 hr prior to discharge.

Issues for Referral
Refer to primary physician for consideration of medication or diet changes if recurrent hypoglycemic episodes. �

Followup Recommendations

PMD follow-up for medication re-evaluation within 48 hr �

Pearls and Pitfalls

Administration of PO glucose or food may initially further decrease glucose level; therefore, IV dextrose always preferred if possible
Multiple amps of D50W commonly required
Do not over rely on D10/D20 as even these concentrations contain relatively small amounts of glucose.
Hypoglycemia should be in the differential for all neurologic and psychiatric presentations.
Recurrent hypoglycemia patients often require hours to days for full neurologic recovery

Additional Reading

McCall �AL. Insulin therapy and hypoglycemia. Endocniol Metab Clin North Am. 2012;41(1):57-87.
Service �FJ. Hypoglycemia. Med Clin North Am. 1995;79(1):1-8.
Stanley �CA, Baker �L. The causes of neonatal hypoglycemia. N Engl J Med. 1999;340:1200-1201.

Codes

ICD9

251.1 Other specified hypoglycemia
251.2 Hypoglycemia, unspecified
775.1 Neonatal diabetes mellitus

ICD10

E16.1 Other hypoglycemia
E16.2 Hypoglycemia, unspecified
P70.2 Neonatal diabetes mellitus

SNOMED

302866003 Hypoglycemia (disorder)
49817004 neonatal diabetes mellitus (disorder)
71858003 Autoimmune hypoglycemia (disorder)
52767006 Neonatal hypoglycemia (disorder)
360337007 PHHI - Persistent hyperinsulinemic hypoglycemia of infancy (disorder)

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