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DESCRIPTION
Insulin is an endogenous peptide that regulates blood glucose.
FORMS AND USES
- Insulin is available in many forms and preparations.
- Among the many trademarked preparations are Iletin, Lente insulin, NPH insulin, Humulin, Novalin, and Velosulin.
- Treatment of hyperglycemia. The dose varies by individual; the usual route is subcutaneous.
- Diabetic ketoacidosis. 0.1 U/kg regular insulin intravenously, then infusion of 0.1 U/kg/h.
- Hyperkalemia. Concurrent intravenous administration of 0.1 U/kg regular insulin and glucose can be used to treat hyperkalemia in normoglycemic patients.
TOXIC DOSE
- Toxic dose is relative to the patient's underlying glucose level.
- When insulin-dependent patients take their usual dose of insulin and either do not eat regularly or undergo an unusual amount of activity, they may experience hypoglycemic episodes.
- Deliberate insulin overdose can result in profound and prolonged hypoglycemia because the injected insulin can serve as a depot that results in a sustained release of insulin over several days.
- Orally administered insulin is broken down in the stomach and is nontoxic.
PATHOPHYSIOLOGY
Insulin lowers blood glucose by increasing uptake of glucose by skeletal muscle, increasing the formation of fat in adipose tissue and increasing hepatic formation of glycogen.
EPIDEMIOLOGY
- Hypoglycemia from insulin is very common, but insulin overdose is uncommon.
- Toxic effects following exposure are typically moderate.
- Death occurs rarely, usually following deliberate overdose and before medical care is reached.
CAUSES
- Insulin toxicity is usually an accidental incident.
- Child abuse should be considered if the patient is under 1 year of age; suicide if the patient is over 6 years of age.
RISK FACTORS
- Infants and children have small glycogen stores and are especially prone to develop hypoglycemia.
- Elderly patients may have decreased glycogen stores and thus are predisposed to hypoglycemia.
DRUG AND DISEASE INTERACTIONS
- Concurrent sulfonylurea ingestion increases the risk of hypoglycemia.
- Beta-blockers may mask symptoms of hypoglycemia, allowing hypoglycemia to develop unnoticed.
PREGNANCY AND LACTATION
- US FDA Pregnancy Category B. Animal studies do not indicate a risk to the fetus, and there are no controlled human studies, or animal studies do show an adverse effect on the fetus but well-controlled studies in pregnant women do not.
- Insulin does not cross the placenta; maternal hypoglycemia, however, may lead to fetal hypoglycemia and injury.
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DIFFERENTIAL DIAGNOSIS
- Other toxic agents that cause hypoglycemia include sulfonylurea overdose, akee fruit, ethanol, salicylate, propranolol, or any substance that causes massive hepatic necrosis.
- Nontoxic causes of hypoglycemia include insulinoma, sepsis, rapidly growing tumors, and hepatic failure from other causes.
- Hypoglycemia also may be triggered by infection, myocardial infarction, or other systemic processes.
SIGNS AND SYMPTOMS
- Insulin toxicity results in hypoglycemia, which may be delayed, prolonged, or recurrent.
- With severe hypoglycemia, anxiety, diaphoresis, tremor, tachycardia, lethargy, slurred speech, coma, and seizures may develop.
- Neurologic effects may be focal or nonfocal.
Vital Signs
Hypoglycemia initially causes tachycardia, tachypnea, and hypertension, followed by hypotension, hypothermia, and respiratory depression in severe and prolonged cases.
HEENT
Pupils may be dilated.
Dermatologic
Diaphoresis is common.
Cardiovascular
Tachycardia and hypertension occur.
Pulmonary
- Tachypnea can occur.
- Acute respiratory distress syndrome has been reported but may be related to prolonged hypoglycemia or aspiration during coma.
Gastrointestinal
Hunger, nausea, and vomiting may occur.
Fluids and Electrolytes
- Hypoglycemia is universal in significant overdose unless preexisting chronic hyperglycemia was present.
- Hypokalemia can occur due to a shift of potassium from outside to inside cells.
Musculoskeletal
- Muscle weakness may result from a lack of substrate.
- Rhabdomyolysis can occur because of prolonged immobility.
Neurologic
- Disorientation, agitation, lethargy, slurred speech, paresthesia, anxiety, headache, tremors, weakness, and ataxia may occur early, followed by coma and seizures.
- Focal neurologic signs such as paraplegia are uncommon, but may occur.
- Permanent neurologic impairment may follow prolonged hypoglycemia.
PROCEDURES AND LABORATORY TESTS
Essential Tests
Blood glucose levels should be obtained hourly, whenever the patient becomes symptomatic, and following each treatment with dextrose.
Recommended Tests
- ECG, serum acetaminophen and aspirin levels should be obtained to detect occult ingestion.
- Serum electrolytes, BUN, creatinine, liver function tests, CT, and lumbar puncture should be performed as needed to rule out other causes of altered mental status.
- Serum insulin, proinsulin, and C-peptide levels should be obtained if surreptitious use of insulin is suspected.
- C-peptide is a section of the insulin peptide that is not present in exogenous insulin but is present in secreted insulin.
- Factitious hypoglycemia can be diagnosed by documentation of a low serum C-peptide level during a hypoglycemic episode.
- Patients with a potential diagnosis of factitious hypoglycemia may require admission and serial fasting glucose levels.
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- Management should focus on immediate dextrose administration, airway protection, serum glucose monitoring, and determination of cause for hypoglycemia.
- Dose and time of exposure should be determined for all substances involved.
DIRECTING PATIENT COURSE
The health-care provider should call a poison control center when:
- The patient or caregiver indicates that an insulin overdose has occurred.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Attempted suicide or homicide is possible.
- Signs and symptoms are not consistent with hypoglycemia.
- The patient or caregiver seems unreliable.
- Altered mental status, diaphoresis, or other toxic effects are present.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Inpatient management is warranted for patients who suffer possible parenteral overdose or who develop persistent or recurrent hypoglycemia.
DECONTAMINATION
- Oral decontamination is not necessary in cases of isolated insulin overdose.
- If coingestion of another toxic substance is possible, one dose of activated charcoal (1-2 g/kg) should be administered if a substantial ingestion has occurred within the previous few hours.
- After a massive subcutaneous insulin injection or injection of any amount of long-acting insulin, surgical excision of the site may be effective if it is performed soon after injection.
ANTIDOTES
Dextrose is the specific antidote for insulin poisoning.
Indications
Dextrose should be administered upon appearance of symptoms of hypoglycemia or glucose level below 60 mg/dl.
Method of Administration and Dosage
- Adults. 50 mL D50W by bolus intravenous infusion.
- Children. D25W 2 to 4 ml/kg (D10W 1-2 ml/kg for neonate).
- Dextrose dose should be repeated until blood glucose level is above 100 mg/dl.
- Blood glucose should be followed at least hourly to guide further therapy.
- Initiate infusion of D5W, D10W, or D20W dextrose as needed if recurrent hypoglycemia develops.
- Dextrose infusions of 20% or higher require a central venous line to avoid venous irritation.
ADJUNCTIVE TREATMENT
- Potassium replacement may be required and should be based on serum levels.
- Glucagon should not be used for insulin overdose.
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PATIENT MONITORING
- Cardiac and respiratory function should be monitored continuously.
- Glucose levels should be monitored hourly, or more frequently as needed initially.
EXPECTED COURSE AND PROGNOSIS
- Full recovery is expected if prolonged hypoglycemia is avoided.
- Permanent neurologic injury may result from prolonged hypoglycemia.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Patients who are asymptomatic may be discharged when they maintain serum glucose levels above 60 mg/dl (without dextrose treatment) during 6 to 8 hours of observation and following a psychiatric evaluation, if needed.
- From the hospital. Patients who are asymptomatic, are euglycemic without supplemental dextrose administration for 6 to 8 hours, and tolerate food may be discharged following psychiatric evaluation, if needed.
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DIAGNOSIS
- Early infusion of dextrose to an asymptomatic patient may maintain normal blood glucose and obscure the diagnosis of serious poisoning.
- It is important to determine whether an oral hypoglycemic is involved in addition to injected insulin.
- Multiple cases of psychiatric patients who induce hypoglycemia by injecting insulin have been reported.
TREATMENT
Patients requiring large dextrose doses should have central access established to allow infusion of D20W or greater concentrations.
FOLLOW-UP
Hypoglycemia may recur despite dextrose infusion.
Section Outline:
ICD-9-CM 962.3Poisoning by hormones and synthetic substitutes: insulins and antidiabetic agents.
See Also: SECTION III, Dextrose chapter.
RECOMMENDED READING
Arem R, Zoghbi W. Insulin overdose in eight patients: insulin pharmacokinetics and review of the literature. Medicine 1985;64:323-332.
Author: Kennon Heard
Reviewer: Richard C. Dart