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

Pregnancy Considerations

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

Pediatric Considerations

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

[Outline]

• DESCRIPTION
• RISK FACTORS
• ETIOLOGY

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

ALERT

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

Pediatric Considerations

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

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

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

Geriatric Considerations

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

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

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.

FOLLOW-UP RECOMMENDATIONS

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

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• 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

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

[Outline]

• ICD9
• ICD10

• 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.

See Also (Topic, Algorithm, Electronic Media Element)

• Altered
• Mental
• Status

Chadi I. Kahwaji

Matthew N. Graber