Author:
Japheth J.Baker
Matthew N.Graber
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 yr 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 Prophylaxis |
- Third-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 first 3 mo of life is persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in mothers with diabetes |
Signs and Symptoms
- Adrenergic caused by excessive counterregulatory 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 |
| 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
Essential Workup
- Diagnosis requires:
- Demonstration of neuroglycopenic signs and symptoms as defined above
- Lab evidence of hypoglycemia
- Clearing of symptoms following glucose administration
Diagnostic 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:
- Drug or alcohol intoxication
- Cardiac ischemia/ACS
- 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
|
Prehospital
- 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:
- Second or third 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 mcg IV bolus then 50 mcg IV/hr drip or 50 mcg q12h SC/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, max dose 1 mg
- 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
- Other possible treatments:
- SSRI medications
- Selective adrenergic antagonists
- Opiate antagonists
- Fructose
- Selective ATP-sensitive K-channel agonists
Disposition
Admission Criteria
- Overdose of long-acting oral hypoglycemic agent (e.g., sulfonylureas) or long-acting insulin (e.g., glargine, detemir) or ultra-long acting insulin (e.g., degludec) mand ate 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
- CryerPEC. Mechanisms of hypoglycemia-associated autonomic failure in diabetes . N Engl J Med. 2013;369(4):362-372.
- McCallAL. Insulin therapy and hypoglycemia . Endocniol Metab Clin North Am. 2012;41(1):57-87.
- ShafieeG, Mohajeri-TehraniM, PajouhiM, et al. The importance of hypoglycemia in diabetic patients . J. Diabetes Metab Disord. 2012;11(1):17.
See Also (Topic, Algorithm, Electronic Media Element)
Altered Mental Status