DESCRIPTION

• Ergot alkaloids are used for acute and short-term therapy for migraine or cluster headache and for treatment of uterine bleeding.
• Ergot alkaloids include ergotamine (Ergomar, Bellergal, Cafergot, Wigraine, Ergostat), ergonovine (Ergotrate), methylergonovine (Methergine), dihydroergotamine (D.H.E. 45), and methysergide (Sansert), a semisynthetic ergot alkaloid.
• Ergot alkaloids can also be found in cereal grains contaminated with the fungus Claviceps purpurea.

FORMS AND USES

• Migraine or cluster headache (acute and short-term therapy)
  • Ergotamine is administered sublingually, 2 mg every 30 minutes. The dosage must not exceed 6 mg in 24 hours or 10 mg in 7 days.
  • Dihydroergotamine is administered intravenously, 1 mg every 60 minutes. The dose must not exceed 3 mg.
  • Methysergide is administered orally, 4 to 8 mg daily for prophylaxis only.
• Uterine bleeding
  • Methylergonovine or ergonovine is administered intramuscularly or intravenously, 0.2 mg (1 ml), for control of uterine hemorrhage. For bleeding, 0.2 or 0.4 mg is given orally every 6 to 12 hours for 48 hours.

TOXIC DOSE

• Toxicity has occurred with 0.5 mg of parenteral ergotamine, 0.2 mg of ergonovine or methylergonovine, and less than 5 mg of sublingual or rectal ergotamine.
• A therapeutic dose can be toxic because some individuals are exquisitely sensitive.

PATHOPHYSIOLOGY

• The ergot alkaloids are direct vascular constrictors of both venous and arterial beds, decreasing blood flow to organs and tissues.
• Ergot alkaloids increase uterine contractions.

EPIDEMIOLOGY

• Poisoning is uncommon and usually associated with intermittent or chronic daily use.
• Rarely, ergot-producing fungus on grain has produced mass epidemics of ergotism (St. Anthony's Fire).
• Toxic effects after exposure are variable, with peripheral ischemic events most common and death occurring rarely.

CAUSES

• Poisoning is usually the result of accidental ingestion or drug interaction.
• Child neglect should be considered if the patient is under 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

• Underlying hypertension, vascular disease, coronary disease, and sepsis predispose to toxicity.
• Underlying hepatic, renal, or biliary disease increases serum level of ergot alkaloids.
• In the setting of pregnancy, hypertension, preeclampsia, and toxemia are risk factors.

DRUG AND DISEASE INTERACTIONS

• Nicotine can provoke vasoconstriction, thereby increasing the potential for ischemic sequelae.
• Macrolide antibiotics (erythromycin-type) inhibit metabolism of ergot alkaloids.
• beta-blockers potentiate the vasoconstrictive effects of ergot alkaloids.
• Sympathomimetics exacerbate the hypertensive effect of ergot alkaloids.
• Halothane antagonizes the effects of ergonovine and relaxes uterine smooth muscle, thereby increasing the risk of uterine bleeding.
• Use with heparin for deep venous thrombosis prophylaxis is associated with more frequent adverse effects.

PREGNANCY AND LACTATION

• Methylergonovine. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Ergotamine and methysergide. US FDA Pregnancy Category X. Studies have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk clearly outweighs any possible benefit.
• Fetal death has occurred following overdose.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxic causes of peripheral ischemia include sympathomimetic drugs (e.g., ephedrine, amphetamine, cocaine).
• Nontoxic causes include unrecognized compartment syndrome, direct vascular injury, and deep venous thrombosis.

SIGNS AND SYMPTOMS

Primary effect is tissue ischemia which may include myocardial ischemia and be associated with altered mental status.

Vital Signs

Tachycardia, bradycardia in the face of hypotension (centrally mediated), or hypertension may occur.

HEENT

Facial, lingual, or retinal artery ischemia with transient blindness may develop.

Dermatologic

Localized cyanosis and edema, pruritus, flushing, and nonspecific purpuric rash may occur.

Pulmonary

• Bronchospasm may develop acutely.
• Pleuritis, effusion, and fibrosis have developed during chronic use.

Cardiovascular

• Vasoconstriction may result in coronary, peripheral, CNS, mesenteric, or renal ischemia.
• There have been rare reports of heart valve fibrosis.
• Renal and mesenteric aneurysm formation has developed with chronic ergotism.

Gastrointestinal

• Nausea, vomiting, diarrhea, and abdominal pain are common at therapeutic doses and in overdose.
• Anorectal ulcers have occurred from one suppository.

Hepatic

Ischemic hepatitis and pancreatitis may occur.

Renal

• Hematuria may occur.
• Renal ischemia or renal failure may result from prolonged arterial spasm.
• Retroperitoneal fibrosis has developed rarely during chronic use.

Musculoskeletal

Pain and cyanosis of extremities and intermittent claudication may occur.

Neurologic

• Peripheral paresthesia, hallucinations, dysphoria, confusion, depression, and seizures may occur.
• Cerebral infarction, cranial nerve palsies, tinnitus, and vertigo have occurred.

Reproductive

• Hypertonic uterine contractions can occur.
• Spontaneous abortion may occur.
• The suppression of prolactin may inhibit lactation.

Hematologic

Neutropenia and eosinophilia can occur.

Psychological

• Dependence can develop.
• Psychosis may follow acute overdose.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests are usually needed in asymptomatic patients.

Recommended Tests

• Serum electrolytes, BUN, creatinine to evaluate renal function
• ECG if there is evidence of cardiac ischemia
• ECG, serum acetaminophen, and aspirin levels in an overdose setting to detect occult ingestion
• Head CT, lumbar puncture, and other tests as needed to evaluate other causes of altered mental status or seizures
• Angiography to evaluate peripheral vasospasm
• Intravenous pyelogram in the setting of suspected retroperitoneal fibrosis

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Pulmonary
  • Cardiovascular
  • Gastrointestinal
  • Hepatic
  • Renal
  • Musculoskeletal
  • Neurologic
  • Reproductive
  • Hematologic
  • Psychological
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on withdrawal of the offending agent and therapy of vasoconstriction.
• Dose and time of exposure need to be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Evidence of peripheral ischemia, cerebrovascular accident, myocardial infarction, or other severe effects are present.
• Toxic effects are not consistent with ergotamine poisoning.
• 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.
• Patient or caregiver seems unreliable.
• Any toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for patients with systemic effects or evidence of tissue ischemia.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of ingestion for alert pediatric or adult patients if health-care evaluation will be delayed.

In Hospital

• Ipecac should be administered to induce emesis within 1 hour of ingestion for the alert patient who is too small to have effective gastric lavage.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTE

There is no specific antidote for ergotamine poisoning.

ADJUNCTIVE TREATMENT

Hypertension

If end-organ damage develops (aortic dissection, CNS bleed, myocardial infarction), administer a short-acting titratable agent (see vascular spasm below).

Vascular Spasm

Multiple Modalities Have Been Used for Spasm

• Sodium nitroprusside is used most commonly.
  • Adult and pediatric dose is 0.5 µg/kg/min by intravenous infusion. Infusion is increased by 0.25 to 0.5 µg/kg/min every 5 minutes, titrating dose to desired effect.
  • Infusion rate over 10 µg/kg/min is rarely required and may produce cyanide toxicity.
  • Nitroprusside should be tapered gradually in order to avoid rebound hypertension.
• In mild to moderate cases, captopril, nifedipine, or prazosin have been used successfully.
• Peripheral ischemia may require treatment with intraarterial phentolamine (for vasospasm) or thrombolytics (for thrombus).

Coronary Artery Spasm

• Standard techniques are used, such as sublingual or intravenous nitroglycerin.
• Heparin and aspirin are provided as indicated.
• beta-blockers should be avoided to prevent unopposed alpha-adrenergic receptor stimulation.

Control of Agitation or Seizure

• The airway must be secured and monitored throughout.
• A benzodiazepine familiar to the provider should be administered, for example, diazepam (adult dose 5-10 mg intravenously, pediatric dose 0.2-0.5 mg/kg intravenously, repeated at 10-minute intervals, titrating to effect) or lorazepam: (adult dose 1-2 mg intravenously, pediatric dose 0.05 mg/kg, repeated every 10 minutes, titrating to effect).

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTE
• ADJUNCTIVE TREATMENT
  • Hypertension
  • Vascular Spasm
  • Coronary Artery Spasm
  • Control of Agitation or Seizure

PATIENT MONITORING

Cardiac, hemodynamic, and pulmonary status should be monitored continuously in symptomatic patients.

EXPECTED COURSE AND PROGNOSIS

• Possible complications include loss of extremity or other appendage, myocardial infarction, or cerebrovascular accident.
• Arterial spasm may linger for 72 hours and may end with infarction or other permanent tissue injury.

DISCHARGE CRITERIA AND INSTRUCTIONS

• From the emergency department. Asymptomatic patients with normal vital signs may be discharged after decontamination and 6 hours of observation.
• From the hospital. Patients may be discharged after vascular effects have resolved for 12 to 24 hours.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA AND INSTRUCTIONS

It is often necessary to try more than one vasodilator before vasospasm resolves.

Poisoning by drugs primarily affecting the autonomic nervous system.

See Also: SECTION II, Hypertension chapter; SECTION III, Nitroprusside chapter.

RECOMMENDED READING

de Groot ANJA, van Dongen PWJ, van Roosmalen J, et al. Ergotamine-induced fetal stress: review of side effects of ergot alkaloids during pregnancy. Eur J Obstet Gynecol Reprod Biol 1993;51:73-77.

Author: Michael Stackpool

Reviewer: Katherine M. Hurlbut