ERGOT ALKALOIDS

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

1) More than 350 ergot alkaloids have been identified, but only a few agents are used therapeutically. The primary clinical uses have been to relieve the pain of migraine headache and to prevent and treat postpartum and postabortal hemorrhage.

Specific Substances

1) Dihydroergotamina
2) Dihydroergotamiini
3) Dihydroergotamin
4) Dihydroergotaminum
5) CAS 511-12-6

1) Codergocrine mesilate
2) Codergocrina, mesilato de
3) Co-dergocrine mesilate
4) Co-dergocrine methanesulphonate
5) Dihydroergotoxine methanesulphonate
6) Ergoloid mesylate
7) CAS 11032-41-0 (Ergoloid)
8) CAS 8067-24-1 (Ergoloid mesylate)

1) Ergobasine
2) Ergobasine maleate
3) Ergometrine
4) Ergometrine maleate
5) Erogometrine maleatas
6) Ergonovine maleate
7) Ergonovine bimaleate
8) Ergostetrine
9) Ergostetrine maleate
10) CAS 60-79-7 (Ergonovine)
11) CAS 129-51-1 (Ergonovine maleate)

1) Ergotamin tartarat
2) Ergotamina, tartrato de
3) Ergotamini tartras
4) Ergotamino tartratas
5) Ergotamintartrat
6) CAS 113-15-5 (Ergotamine)
7) CAS 379-79-3 (Ergotamine tartrate)

1) Methylergobasine
2) Methylergobasinemaleate
3) Methylergometrine
4) Methylergometrine maleate
5) Methylergonovine maleate
6) Methylergometrini
7) CAS 113-42-8 (Methylergonovine)
8) CAS 57432-61-8 (Methylergonovine maleate)

1) 1-Methyl-D-lysergic acid butanolamide
2) Methysergidum
3) CAS 361-37-5

1) Claviceps
2) Claviceps purpura
3) Ergotism

Available Forms Sources

1) DIHYDROERGOTAMINE is available as a 1 mg/mL solution for injection and 4 mg/mL nasal spray (Prod Info dihydroergotamine mesylate nasal spray, 2013; Prod Info D.H.E. 45(R) intravenous injection, intramuscular injection, subcutaneous injection, 2012).
2) ERGOLOID MESYLATES is available as 1 mg oral tablets (Prod Info ergoloid mesylates oral tablets, 2009).
3) ERGONOVINE MALEATE is available as 0.2 mg/mL solution for injection and 0.2 mg oral tablets (Prod Info ERGOTRATE(R) injection, 2006).
4) ERGOTAMINE is available as 2 mg sublingual tablets (Prod Info Ergomar(R) sublingual tablets, 2008). Ergotamine in combination with caffeine are also available as 2 mg/100 mg suppositories and 1 mg/100 mg oral tablets (Prod Info Ergotamine Tartrate and Caffeine rectal suppository, 2003; Prod Info Ergotamine Tartrate and Caffeine oral tablets, 2005).
5) METHYLERGONOVINE is available as 0.2 mg/mL solution for injection and 0.2 mg oral tablets (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun).
6) METHYSERGIDE is available as 2 mg tablets (Prod Info SANSERT(R) oral tablets, 2000).

1) DIHYDROERGOTAMINE is used for the treatment of migraine and cluster headaches (Prod Info dihydroergotamine mesylate nasal spray, 2013; Prod Info D.H.E. 45(R) intravenous injection, intramuscular injection, subcutaneous injection, 2012).
2) ERGOLOID MESYLATES is used to treat patients with dementia and Alzheimer's disease (Prod Info ergoloid mesylates oral tablets, 2009).
3) ERGONOVINE is used to prevent and treat postpartum and postabortal hemorrhage due to uterine atony (Prod Info ERGOTRATE(R) injection, 2006).
4) ERGOTAMINE is used for the treatment of migraine and vascular headaches (Prod Info Ergomar(R) sublingual tablets, 2008).
5) METHYLERGONOVINE is used in the treatment of postpartum hemorrhage, associated with uterine atony or subinvolution (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun).
6) METHYSERGIDE is used to prevent vascular headaches (Prod Info SANSERT(R) oral tablets, 2000).

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Ergot alkaloids are most commonly used to treat migraine headaches and to enhance uterine contractions postpartum. In addition, some ergot derivatives have been used for the treatment of dementia, Parkinson disease, and hyperprolactinemic states. Another source of ergots is grains contaminated by the fungus Claviceps purpurea. Ergot preparations are available in oral, intravenous, and intranasal forms.
B) PHARMACOLOGY: Ergot derivatives directly stimulate vasoconstriction and uterine contraction, antagonize alpha-adrenergic and serotonin receptors, and dilate some blood vessels via a CNS sympatholytic action. The relative contribution of each of these mechanisms varies with the specific ergot alkaloid.
C) TOXICOLOGY: Most serious toxicity results from sustained vasoconstriction, which can result in local tissue hypoxia and ischemic injury. Vasospasm may progress to irreversible vascular insufficiency and resulting gangrene.
D) EPIDEMIOLOGY: Exposures are relatively uncommon.
E) WITH THERAPEUTIC USE

1) Adverse effects include rhinitis, dizziness, hot flashes, nausea/vomiting/diarrhea, taste disturbances, local site reaction, weakness and stiffness, and pharyngitis. Severe adverse effects occur rarely (less than 1%) at therapeutic dosing and include cerebral hemorrhage, coronary artery vasospasm, hypertension, myocardial infarction, paresthesia, peripheral cyanosis, peripheral ischemia, rash, stroke, subarachnoid hemorrhage, ventricular fibrillation, ventricular tachycardia, pleural and retroperitoneal fibrosis, and cardiac valvular fibrosis. Methysergide can cause retroperitoneal fibrosis.
2) DRUG INTERACTION: Concomitant use with potent inhibitors of CYP3A4 (eg, protease inhibitors, azole antifungals, some macrolide antibiotics) has been associated with acute ergot toxicity (ergotism).

F) WITH POISONING/EXPOSURE

1) OVERDOSE: Overdose can be divided into acute and chronic categories. Most severe poisoning cases are due to chronic supratherapeutic dosing (greater than 10 mg) for migraine headaches. However, there are case reports of vasospastic incidents following normal therapeutic dosing.
2) MILD TO MODERATE POISONING: Mild intoxication results in gastrointestinal (nausea and vomiting) symptoms.
3) SEVERE POISONING: More serious poisonings cause vasoconstriction that can involve multiple parts of the body. Since ergot alkaloids may persist, vasospasm can continue up to 2 weeks. Pain, pallor, hypothermia, and loss of peripheral pulses may occur in the distal extremities, leading to gangrene. Other vasospastic complications include acute coronary syndrome, bowel infarction, renal infarction, visual disturbances, and stroke. Psychosis, seizures, and coma are rare but may also occur.

0.2.20)

A) Fetal mortality and several deformities, possibly related to ischemia in utero, have been observed in humans and experimental animals.
B) Fetal distress, stillbirth and spontaneous abortion may occur.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive, including treatment of gastrointestinal symptoms, warming of peripheral extremities, and treatment of pain.

B) MANAGEMENT OF SEVERE TOXICITY

1) Peripheral ischemia requires immediate vasodilator and anticoagulant therapy. First-line vasodilating agents include intravenous infusions of nitroprusside (starting dose 1 to 2 mcg/kg/minute) and/or phentolamine (starting dose 0.5 mg/minute). These medications should be titrated until ischemia is improved or as tolerated by the patient’s blood pressure. Rarely, intra-arterial infusion may be required. Vasodilating calcium channel blockers such as nifedipine (or other dihydropyridines) may augment collateral peripheral blood flow and thus may be beneficial. Anticoagulation therapy with heparin (sufficient to maintain the activated partial thromboplastin time (aPTT) at approximately twice normal values), or low molecular weight heparin derivatives are used to inhibit thrombosis secondary to vasospasm. If patients experience coronary spasm, administer nitroglycerin 0.15 to 0.6 mg sublingually and then start intravenous administration at 5 to 20 mcg/minute. Intracoronary artery nitroglycerin may be necessary if intravenous administration proves futile. Adding calcium channel blocker therapy may also be useful. Treat seizures with benzodiazepines and barbiturates.

C) DECONTAMINATION

1) PREHOSPITAL: Ipecac-induced vomiting is potentially useful if given immediately (within a few minutes of ingestion); however, it is not generally recommended because of the possibility of CNS depression and subsequent aspiration. Consider activated charcoal in a patient with a recent, substantial overdose who is alert or in whom airway is protected. For dermal or eye exposures, immediate decontamination by washing off the medication is recommended.
2) HOSPITAL: Most toxicity is from chronic excessive dosing, and decontamination is not generally useful in these cases. Consider activated charcoal in a patient with a recent, substantial overdose who is alert or in whom airway is protected.

D) AIRWAY MANAGEMENT

1) Respiratory depression has been reported in neonates, and might develop in adults with complications from ergot alkaloid toxicity (e.g. stroke); intubation may be necessary.

E) ANTIDOTE

1) None

F) ENHANCED ELIMINATION

1) As ergot alkaloids have extensive tissue distribution, dialysis and hemoperfusion are not effective treatments.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Most patients may be observed at home if they are not having any symptoms.
2) OBSERVATION CRITERIA: Any patient who is experiencing symptoms or had a self-harm attempt should be sent to a healthcare facility for observation. Observe asymptomatic patients for 4 to 6 hours. Admit patients with severe symptoms or patients who are still symptomatic at the end of observation.
3) ADMISSION CRITERIA: Patients exhibiting cardiovascular effects should be admitted to an intensive care setting.
4) CONSULT CRITERIA: Other consultants that may need to be involved include cardiologists (for acute coronary syndrome), neurologists (for strokes), vascular surgeons (for peripheral vascular ischemia). Consult a medical toxicologist for patients with severe poisoning or in whom the diagnosis is unclear.

H) PITFALLS

1) Signs and symptoms of ischemia may be delayed.

I) PHARMACOKINETICS

1) Depends on specific product. In general, most have quick onset of action (15 to 30 minutes) with duration of several hours (3 to 4 hours) and have a large volume of distribution. Ergot alkaloids are extensively protein bound (greater than 90%) and are mostly metabolized hepatically. Half-life is in the range of a few hours, and time to peak in serum depends on route of exposure, but is usually fairly quick (minutes to an hour). Excretion is primarily through feces, though some is excreted through the urine (mostly as metabolites).

J) PREDISPOSING CONDITIONS

1) Due to the vasoconstrictive and cardiovascular effects, these medications should not be administered to patients with a history of, or significant risk factors for coronary artery disease, or in the elderly. Contraindicated in pregnancy (Class X) as ergots are oxytocic. Contraindicated in breast-feeding mothers as it may be excreted in breast milk. Vomiting, diarrhea, weak pulse and unstable blood pressures have been reported in nursing infants. In addition, these medications are contraindicated in those with severe renal or hepatic dysfunction.

K) DIFFERENTIAL DIAGNOSIS

1) Can mimic other medications that can cause vasoconstriction and/or hypertension. End organ effects may be caused by many other non-toxicological related events as well (e.g. strokes, myocardial infarctions).

0.4.3)

A) Treat adverse effects from intranasal administration similarly to oral ingestions.

0.4.4)

A) Irrigation of eyes, and treat symptoms as needed.

0.4.5)

A) OVERVIEW

1) Local decontamination, and treat symptoms as needed.

0.4.6)

A) Treat as above for symptoms as needed.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.2)

A) WITH POISONING/EXPOSURE

1) Respiratory depression or arrest may develop following overdose.
2) METHYLERGONOVINE: Respiratory depression developed in a newborn following the unintentional injection of 0.2 mg of methylergonovine (Prod Info methylergonovine maleate IM, IV Injection, 2008)

3.3.3)

A) WITH POISONING/EXPOSURE

1) METHYLERGONOVINE: Hypothermia developed in a newborn following the unintentional injection of 0.2 mg of methylergonovine (Prod Info methylergonovine maleate IM, IV Injection, 2008)

3.3.4)

A) Blood pressure may be increased or decreased. It may also be normal despite the presence of peripheral or organ ischemia.

3.3.5)

A) Bradycardia is more common than tachycardia, and may occur in the presence of hypotension.

Heent

3.4.3)

A) TRANSIENT BLINDNESS: Transient monocular blindness, presumably related to retinal arterial spasm, developed abruptly in one patient after use of 8 to 10 ergotamine tartrate suppositories per week for 2 years. Ophthalmic exam was normal within 24 hours of discontinuation of the suppositories (Merhoff & Porter, 1974).

1) CASE REPORT: A 31-year-old man presented with bilateral ischemic optic neuropathy associated with severe headaches and hypertension. Symptoms appeared after administration of ergotamine tartrate and macrolides (Sommer et al, 1998).

B) NONREACTIVE PUPILS: One unconscious patient had symmetrical, nonreactive pupils following ingestion of 40 mg ergotamine tartrate and 100 mg caffeine (Deviere et al, 1987).
C) BILATERAL PAPILLITIS: Reversible bilateral papillitis with ring scotomata developed in a patient who received 5 times the recommended daily adult dose of ergotamine over a period of 14 days (Prod Info ERGOMAR(R) sublingual oral tablets, 2003).
D) DILATED PUPILS: A child developed euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness after ingesting 20 to 24 mg of methysergide (Prod Info SANSERT(R) oral tablets, 2000).

Cardiovascular

3.5.2)

A) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypertension may result from vasoconstriction (Gulbranson et al, 2002; Horowitz et al, 1996; Dua, 1994) .

1) INCIDENCE: In a retrospective study of 34 infants and children with methylergonovine poisoning, 3 (9%) developed hypertension (Aeby et al, 2003).

B) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension may result from central sympatholytic effects (Pardo Rey et al, 2003).(McGuigan, 1984).

C) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) Bradycardia may occur associated with either hypertension or hypotension (Gilman et al, 1990).

D) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) Tachycardia may occur (McGuigan, 1984).

1) INCIDENCE: In a retrospective study of 34 infants and children with methylergonovine poisoning, 6 (18%) developed tachycardia (Aeby et al, 2003).

b) METHYSERGIDE: A child developed euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness after ingesting 20 to 24 mg of methysergide (Prod Info SANSERT(R) oral tablets, 2000).

E) MYOCARDIAL ISCHEMIA

1) WITH THERAPEUTIC USE

a) Angina, myocardial infarction, ventricular dysrhythmias, and cardiac arrest have occurred following therapeutic doses as well as overdoses of a variety of ergot preparations (Nall & Feldman, 1998; Koh et al, 1994; Paz & Carmeli, 1994; Fujiwara et al, 1993; Roithinger et al, 1993; Taylor & Cohen, 1985; Szlachcic et al, 1984; Carr, 1981; Browning, 1974) Baillie, 1969; (Goldfischer, 1960; Carter, 1940) .
b) The use of heparin-dihydroergotamine has been associated with myocardial infarction, presumably due to vasospasm in patients with underlying coronary artery disease or atypical chest pain (Bachner et al, 1990; Shackford & Davis, 1988; Rem et al, 1987; Gatterer, 1986) .
c) Ergonovine provocation tests for myocardial ischemia have induced arterial spasm, thrombus formation, myocardial infarction, and ventricular dysrhythmias (Hays et al, 1993; Bedogni et al, 1992; Harding et al, 1992; Serota et al, 1991; Szlachcic et al, 1984) .
d) CASE REPORTS

1) Acute chest pain and ECG changes suggestive of myocardial ischemia occurred in a healthy 31-year-old man after he ingested a combination of ergotamine tartrate and methysergide for headaches. Chest pain was relieved with a sublingual nitroglycerine tablet (0.6 mg). No further symptoms were reported after the discontinuation of ergotamine tartrate (Galer et al, 1991).
2) A 35-year-old with no history of ischemic heart disease presented with acute chest pain after taking dihydroergotamine for 3 years. ECG showed inverted T waves on leads V4 and V6. Chest pain resolved and ECG was normal after discontinuation of dihydroergotamine (Paz & Carmeli, 1994).
3) A 43-year-old premenopausal woman developed an acute anterior myocardial infarction after the use of sumatriptan succinate injectable and methysergide maleate (Liston et al, 1999).
4) POSTPARTUM: A 28-year-old healthy woman developed acute chest pain and acute non-ST-segment elevation myocardial infarction 9 hours after receiving 0.2 mg of methergine (total dose 1.2 mg over 2 days) for severe vaginal bleeding secondary to a spontaneous second trimester abortion(Nall & Feldman, 1998).

a) Cardiac catheterization revealed coronary artery dilatation in 3 vessels with acute thrombosis in 2, and coronary artery bypass grafting was performed subsequently.

5) POSTPARTUM: A 27-year-old female smoker with a familial history of hypercholesterolemia had an anterior myocardial infarction after receiving 0.5 mg ergometrine following spontaneous vaginal delivery at home. The patient underwent successful angioplasty for 3 vessel occlusion (Mousa et al, 2000).

2) WITH POISONING/EXPOSURE

a) CASE REPORTS

1) A 51-year-old woman developed widespread ST depression, most marked in the inferolateral ECG leads, without associated chest pain or other symptoms and without elevation of CK levels 3 hours after ingesting 60 mg of methysergide. She was treated with aspirin, enoxaparin, oxygen, and intravenous hydration, and her ECG normalized 20 hours after ingestion (Fisher & LeCouteur, 2000).
2) Atrial fibrillation, ventricular fibrillation, and asystole were reported in a 29-year-old man following the ingestion of 60 tablets containing 2 mg ergotamine, 50 mg cyclizine, and 100 mg caffeine per tablet (Carr, 1981).

F) VASOSPASM

1) WITH THERAPEUTIC USE

a) Cerebral, coronary, mesenteric, ophthalmic, and renal artery vasospasm may produce ischemia or infarction in the corresponding end organ (Pardo Rey et al, 2003).
b) Severe arterial spasms of the hands and feet are well-documented complications of ergotamine misuse and can occur during therapeutic use (Pardo Rey et al, 2003; Tay & Chee, 1998; Paraskevopoulos et al, 1995; Magee, 1991; Palombo et al, 1991; Harrison, 1978) . Prolonged vasospasm and vasoconstriction may lead to pain, pallor, coolness, paresthesias, absence of pulses, and gangrene in the extremities (Safar et al, 2002; Zavaleta et al, 2001; Wells et al, 1986; Merhoff & Porter, 1974) .

1) The lower extremities are more frequently affected (McKiernan et al, 1994). An 18-year-old woman presented with lower limb pain at rest and mild cyanosis of both legs. The patient had a 3 year history of chronic ergotamine use for migraines and a 3 day history of use of clarithromycin for an upper respiratory infection. The patient stated her leg pain started 1 day after starting the clarithromycin. Angiograms of the iliac, popiteal, and crural arteries revealed no thrombus but a very thin appearance consistent with vasospasm. The patient was diagnosed with ergotamine-induced lower limb vasospasm. The patient's symptoms resolved within 4 days after discontinuing both the ergotamine and clarithromycin (Demir et al, 2010).
2) INCIDENCE: In a retrospective study of 34 infants and children with methylergonovine poisoning, 8 (24%) developed vasoconstriction (Aeby et al, 2003).
3) Claudication is common (Magee, 1991; Schulman & Rosenberg, 1991) and has occurred following chronic ergot toxicity (Garcia et al, 2000).

c) METHYSERGIDE: Adults have experienced peripheral vasospasm, with diminished or absent pulses, coldness, mottling, and cyanosis after ingesting methysergide 200 mg (Prod Info SANSERT(R) oral tablets, 2000).
d) CASE REPORTS

1) LIMB ISCHEMIA

a) A 32-year-old man treated with antiretroviral therapy (tenofovir, abacavir, and lopinavir/ritonavir) for HIV infection presented to the emergency department with upper and lower bilateral extremity pain, decreased circulation, and paresthesias hands and feet approximately 4 days after ingesting a 1 mg dose of ergotamine to treat a migraine. Examination revealed vasospasms and severe ischemia to all extremities. Symptoms did not improve after withdrawal of antiretroviral drugs and treatment with IV heparin, morphine, and sodium nitroprusside; however, restoration of all pulses occurred within 24 hours with treatment of IV iloprost and oral sildenafil. He was discharged in good condition 5 days after admission (Marine et al, 2011).
b) A 49-year-old woman with a history of smoking, Raynaud disease and migraine headaches developed peripheral arterial vasoconstriction in association with periods of ergotamine use (Weaver et al, 1989).
c) A 48-year-old woman taking ergotamine for headaches presented with hypertension, claudication, and cool, pale lower extremities with absent pulses. There was evidence of severe stenosis of the femoral arteries on arteriography. Intraarterial nitroglycerin ameliorated the stenosis and she was treated with heparin, nifedipine, prazosin, and nitroprusside, with resolution of her symptoms (Zavaleta et al, 2001).
d) A 63-year-old woman with a 20 year history of ergotamine use presented with pain and numbness of her right arm, which was noted to be cool, pale, and weak on examination. Angiography revealed diffuse narrowing of the brachial artery and bilateral occlusion of the external carotids. She was treated with heparin and prazosin and improved (Safar et al, 2002).
e) A 28-year-old man developed lower extremity vascular insufficiency requiring foot amputation for ischemia causing gangrene after 5 days of ergotamine therapy for headache. The vascular insufficiency was refractory to multiple treatment modalities, including sodium nitroprusside, nifedipine, and beraprost (Musikatavorn & Suteparuk, 2008).
f) A 72-year-old woman with Parkinson disease was taking pergolide 8 mg/day to prevent medication-induced dyskinesias. She complained of tingling and blue discoloration of her digits for 2 months. Within 1 week of discontinuing pergolide, the digit discoloration improved, and complete resolution of symptoms was seen by 3 months (Morgan & Sethi, 2006).

2) LINGUAL ISCHEMIA

a) A 72-year-old woman developed lingual arterial stenosis with tongue necrosis following a single rectal dose of ergotamine tartrate 2 mg (Vazquez-Doval et al, 1994).
b) A patient developed hypertension, peripheral cyanosis, and lingual ischemia 2 hours after administration of a 2 mg dose of ergotamine tartrate on the fifth day of clarithromycin therapy(Horowitz et al, 1996).

3) ANORECTAL ISCHEMIA

a) ANORECTAL ERGOTISM: Fifteen cases of anorectal ergotism occurred following use of suppositories containing ergotamine. Eight patients developed fistulas, while 7 reported ulceration as the only effect (Jost et al, 1991).

4) NEONATES

a) CASE SERIES: In a retrospective review of 7 cases of improper administration of ergot alkaloids (dose range 0.125 mg to 0.5 mg ergometrine) to neonates, all experienced peripheral circulatory disturbances (low volume peripheral pulses, poor perfusion, and acral cyanosis) with paradoxical evidence of vasodilatation of peripheral skin vasculature. Despite circulatory impairment, none of the infants had peripheral necrosis (digital ischemia) or gangrene. Most symptoms resolved in 4 days (Dargaville & Campbell, 1998).
b) CASE REPORT: Following the unintentional administration of methylergonovine maleate (0.1 mg) in a newborn, symptomatic alterations in splanchnic arterial flow were recorded by Doppler. Blood flow normalized within 96 hours with supportive care (Baum et al, 1996).

5) CEREBRAL ISCHEMIA

a) A 37-year-old woman on ritonavir developed right-sided weakness and aphasia after taking 5 ergotamine suppositories over 4 days (10 mg ergotamine total). Angiography showed multiple stenoses of the distal portions of the extracranial arteries and circle of Willis, and the patient had watershed infarcts of both left and right hemispheres. Ritonavir likely contributed to toxicity by interfering with ergotamine metabolism via cytochrome P450 3A4 interactions (Spiegel et al, 2001).
b) A 34-year-old woman with HIV infection treated with ritonavir, lamivudine, and stavudine developed visual loss, headache, disorientation, and decreased level of consciousness after taking 3 ergotamine tartrate1 mg tablets over 4 days. Arteriography revealed stenosis and vasospasm of the mesenteric, renal, femoral, humeral, and internal carotid arteries. CT revealed multiple subcortical infarcts and she remained in a persistent vegetative state (Pardo Rey et al, 2003).
c) FACIAL ISCHEMIA has occurred from spasm of both carotid arteries during therapy with ergotamine (Lazarides et al, 1992).

G) CONDUCTION DISORDER OF THE HEART

1) WITH THERAPEUTIC USE

a) In a study of 95 patients with variant angina who underwent ergonovine testing, 24 (25%) developed significant ventricular dysrhythmias, including ventricular tachycardia (8), bigeminy (7), premature ventricular contractions in couplets (5), and frequent premature ventricular extrasystoles (4) (Szlachcic et al, 1984).

2) WITH POISONING/EXPOSURE

a) CASE REPORT: Atrial fibrillation, ventricular fibrillation, and asystole were reported in a 29-year-old man following the ingestion of 60 tablets containing 2 mg ergotamine, 50 mg cyclizine, and 100 mg caffeine per tablet (Carr, 1981).

H) CARDIOVASCULAR FINDING

1) WITH THERAPEUTIC USE

a) Long-term ingestion of ergot alkaloids has been associated with the development of valvular heart disease including mitral regurgitation and stenosis, aortic regurgitation, pulmonic and tricuspid regurgitation (Hauck et al, 1990; Redfield et al, 1992).

2) WITH POISONING/EXPOSURE

a) A retrospective, nested case-control study found overuse of ergotamine (greater than or equal to 90 daily doses/year) to be a significant risk factor for ischemic complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients using cardiovascular drugs concurrently with ergotamine were at greatest risk (OR 8.52; 95% CI: 2.57 to 28.2) (Wammes-vanderHeijden et al, 2006).

I) FIBROSIS

1) WITH THERAPEUTIC USE

a) A rare complication of methysergide use is endocardial or pericardial fibrosis, which resolves when the drug is discontinued (Orlando et al, 1978).
b) Pleural and pericardial fibrosis has also been associated with long-term ergotamine therapy (Allen et al, 1994; Robert et al, 1984) .

J) INJURY OF ILIAC ARTERY

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 38-year-old woman with a 5 year history of progressive bilateral lower extremity claudication presented with a 2 week history of bilateral lower extremity rest pain. She had been taking gabapentin for her leg symptoms and oral cafergot (an unknown dose) for migraine headache. Arteriography revealed extensive pruning of the distal arterial tree along with bilateral external iliac artery dissections. Following the discontinuation of cafergot and endovascular stenting of the dissections, her symptoms improved. A follow-up lower extremity angiogram 6 weeks later showed resolution of the iliac artery dissections along with restoration of nearly normal lower extremity runoff vessels (Molkara et al, 2006).

K) CLAUDICATION

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 32-year-old man treated with antiretroviral therapy (tenofovir, abacavir, and lopinavir/ritonavir) for HIV infection experienced claudication 24 hours after ingesting a 1 mg dose of ergotamine to treat a migraine. Initially he developed claudication after walking 200 m but this progressed to pain at rest by the time he presented to the emergency department 3 days later. At admission his leg pain was more severe on the right side compared with the left and his hands and feet were cold, cyanotic, and pulseless (femoral pulses were weakly palpable). CT of upper and lower extremities showed bilateral multilevel ischemia and diffuse arterial narrowing consistent with severe spasms. Symptoms were unresponsive to withdrawal of antiretroviral drugs and treatment with IV heparin, morphine, and sodium nitroprusside. After treatment with IV iloprost and oral sildenafil, restoration of all pulses occurred within 24 hours. CT angiography findings were normal after 3 days of treatment. He was discharged in good condition 5 days after admission (Marine et al, 2011).

Respiratory

3.6.2)

A) RESPIRATORY FAILURE

1) WITH POISONING/EXPOSURE

a) ERGONOVINE: Neonates have developed respiratory depression following unintentional administration of ergonovine maleate (Mitchell et al, 1983; Pandey & Haines, 1982; Kenna, 1972) .
b) METHYLERGONOVINE: Respiratory depression developed in a newborn following the unintentional injection of 0.2 mg of methylergonovine (Prod Info methylergonovine maleate IM, IV Injection, 2008)
c) INCIDENCE: In a retrospective study of 34 infants and children with methylergonovine poisoning, 2 (6%) developed apnea (Aeby et al, 2003).
d) CASE REPORT: A full-term male infant, with respiratory depression (Apgar scores were 3 at 1 minute and 8 at 5 minutes), was unintentionally given 0.18 mg of methylergonovine intramuscularly 10 minutes after birth instead of naloxone. Initially, there was a slight decrease in oxygen saturation and a delay in capillary refill (3 seconds); however, within 3.5 hours following methylergonovine administration, he developed hypercarbia (PCO2 94 mmHg), necessitating mechanical ventilation. He was also pale to slightly gray in color. Within 2 hours after beginning nitroprusside infusion, the patient's peripheral perfusion (capillary refill) and respiratory status improved, and he was extubated 51 hours later (Bangh et al, 2005).

B) BRONCHOSPASM

1) WITH THERAPEUTIC USE

a) ERGOTAMINE: Severe and sometimes fatal bronchospasm may occur following therapeutic doses of ergotamine in patients with a history of asthma (Talwar et al, 1985).

C) PLEURAL EFFUSION

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 68-year-old woman developed bilateral pleural effusions after taking lisuride 4 mg/day for approximately 1 year. Her chest x-ray had been normal at the initiation of lisuride therapy. Respiratory symptoms and chest film improved upon discontinuation of the drug (Bhatt et al, 1991).
b) CASE REPORT: A 62-year-old smoker developed bilateral pleural thickening with a small left pleural effusion and bilateral atelectasis with fibrosis after taking cabergoline 10 mg/day for one year. Symptoms and x-ray findings improved after discontinuation of the drug (Bhatt et al, 1991).

D) FIBROSIS OF LUNG

1) WITH THERAPEUTIC USE

a) A rare complication of methysergide use is pleuropulmonary fibrosis, which resolves when the drug is discontinued (Orlando et al, 1978).
b) Pleural and pericardial fibrosis has also been associated with ergotamine therapy (Allen et al, 1994; Robert et al, 1984) .

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) ERGOTAMINE: Lethargy and coma have been reported after ergotamine overdose (Harrison, 1978).
b) Anxiety, dizziness, depression, slurring of speech, euphoria, akathisia, and insomnia have also been reported (Richter & Banker, 1973).
c) METHYLERGONOVINE: Hypertonicity with jerking movements have been reported following unintentional injection of 0.2 mg of methylergonovine to newborns (Prod Info methylergonovine maleate IM, IV Injection, 2008)
d) METHYSERGIDE: A child developed euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness after ingesting 20 to 24 mg of methysergide (Prod Info SANSERT(R) oral tablets, 2000).

B) SEIZURE

1) WITH POISONING/EXPOSURE

a) Seizures have occurred within a few hours of administration of ergot alkaloid uterotonics to neonates (Harrison, 1978).

1) CASE REPORTS

a) Ergonovine maleate (0.1 mg) was unintentionally given to a neonate who developed status epilepticus within 10 minutes of exposure. Long-term follow-up at 22 months indicated normal developmental scores (Anderson et al, 1994).
b) Seizures occurred 2 hours postinjection and lasted approximately 48 hours in a newborn given 0.5 mg of ergometrine intramuscularly (Pandey & Haines, 1982).
c) A neonate developed seizures at 2 hours after unintentional administration of 0.5 mg ergonovine (Pandey & Haines, 1982).
d) Seizure developed in one neonate after the unintentional injection of 0.2 mg of methylergonovine (Prod Info methylergonovine maleate IM, IV Injection, 2008)

2) CASE SERIES

a) Among 24 cases of unintentional administration of ergot alkaloids to neonates, 15 developed seizures, 7 within the first hour of administration (Donatini et al, 1993).
b) LONG-TERM OUTCOME: In a retrospective review of 7 cases of unintentional ergot alkaloid (dose range 0.125 mg to 0.5 mg ergometrine) exposure to neonates, most developed seizures, encephalopathy, peripheral vascular disturbances, and oliguria acutely, but long-term neurological developmental appeared normal (Dargaville & Campbell, 1998).

C) CEREBROVASCULAR DISEASE

1) WITH THERAPEUTIC USE

a) CEREBRAL INFARCTION has been reported after acute and chronic use. Chronic poisoning may result in confusion or focal neurological deficits, depending on whether cerebral vasospasm is diffuse or localized. In many cases, neurological deficits are reversible but may require days or weeks for resolution (Pardo Rey et al, 2003; Spiegel et al, 2001; Senter et al, 1976; Ludolph et al, 1988; Barinagarrementeria et al, 1992; Lindboe et al, 1989).
b) CORTICAL ATROPHY: Focal cortical atrophy has been associated with chronic ergotamine use (Fincham et al, 1985).

D) HEADACHE

1) WITH POISONING/EXPOSURE

a) Headaches may occur after overdose with ergot alkaloids, and may also be seen on cessation of chronic therapy with high-dose ergotamine (Pardo Rey et al, 2003; Harrison, 1978).

E) HYPERACTIVE BEHAVIOR

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 35-year-old man developed akathisia characterized by incessant pacing and movement following administration of 2 mg methysergide twice a day. Symptoms resolved upon discontinuation of methysergide and reappeared upon rechallenge (Bernick, 1988).

F) DYSTONIA

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 59-year-old smoker chronically using 5 to 15 mg ergotamine daily developed intermittent claudication followed by left foot dystonia. This was characterized by involuntary plantar flexion, big toe extension, and left foot inversion (Merello et al, 1991).

1) Dystonia and pain resolved with treatment including calcitonin, methylprednisolone, physical therapy, nifedipine, and aspirin.
2) The diagnosis of reflex sympathetic dystonia was disputed by other authors (Olson, 1992).

G) NEUROPATHY

1) WITH THERAPEUTIC USE

a) Facial and peripheral nerve palsies have been reported (Mitchell et al, 1983; Merhoff & Porter, 1974).

H) PARALYSIS

1) WITH POISONING/EXPOSURE

a) BULBAR PALSY: A 59-year-old man developed bilateral peripheral facial palsy, ptosis, anisocoria, and external strabismus on the right secondary to bilateral external carotid spasm after using 3 suppositories containing ergotamine tartrate 2 mg and caffeine 100 mg in 12 hours (Lazarides et al, 1992).

I) DELIRIUM

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 75-year-old woman developed complex auditory hallucinations followed by confusion, irritability, and hypertension after chronically taking more than 2 tablets a day of an analgesic containing ergotamine 1 mg and caffeine 100 mg. Hallucinations and confusion resolved 48 hours after the ergotamine was discontinued (Gulbranson et al, 2002).

J) PARESTHESIA

1) WITH POISONING/EXPOSURE

a) METHYLERGONOVINE: Ingestion of 4 tablets (2 mg) resulted in paresthesias and clamminess in an adult (Prod Info methylergonovine maleate IM, IV Injection, 2008).

Gastrointestinal

3.8.2)

A) GASTROENTERITIS

1) WITH POISONING/EXPOSURE

a) Vomiting occurs frequently, accompanied by abdominal cramps, and diarrhea (Harrison, 1972).
b) INCIDENCE: In a retrospective study of 34 infants and children with methylergonovine poisoning, 12 (34%) developed vomiting and 7 (20%) developed diarrhea (Aeby et al, 2003).

B) PANCREATITIS

1) WITH POISONING/EXPOSURE

a) Ischemic pancreatitis and hepatitis have been reported following acute ergotamine poisoning (Deviere et al, 1987).

C) DISORDER OF RECTUM

1) WITH THERAPEUTIC USE

a) RECTAL STENOSIS: Two patients developed rectal stenosis after using ergotamine-containing suppositories for 20 years (Ontyd et al, 1989).

D) VASCULAR INSUFFICIENCY OF INTESTINE

1) WITH THERAPEUTIC USE

a) INTESTINAL INFARCTION: A 43-year-old woman with longstanding migraines treated with ergotamine caffeine suppositories (2 to 6 mg/attack; 1 to 3 times/week) developed recurrent abdominal pain and vomiting. Abdominal CT angiogram showed narrowing of the celiac and superior mesenteric arteries. Ergotamine was discontinued, but the patient developed peritonitis. Laparotomy revealed extensive small bowel ischemia and spasm of all intraabdominal arteries and resection of 30 cm of small bowel was required (Christopoulos et al, 2001).

2) WITH POISONING/EXPOSURE

a) MESENTERIC ISCHEMIA: A case of mesenteric ischemia without peripheral vasoconstriction was reported in a 68-year-old man who abused ergotamine-caffeine suppositories (Rogers & Mansberger, 1989).

E) ULCERATION OF INTESTINE

1) WITH THERAPEUTIC USE

a) CASE SERIES: Among 15 cases of anorectal ergotism, 8 developed fistulas, while 7 reported ulceration as the only effect (Jost et al, 1991).

Hepatic

3.9.2)

A) PORTAL HYPERTENSION

1) WITH THERAPEUTIC USE

a) CASE REPORT: Chronic use of high-dose ergotamine tartrate and caffeine was associated with the development of extrahepatic portal hypertension in a 48-year-old woman taking 6 mg/day of ergotamine tartrate with caffeine for 3 months (Fisher et al, 1985).

B) TOXIC HEPATITIS

1) WITH POISONING/EXPOSURE

a) Ischemic pancreatitis and hepatitis have been reported following acute ergotamine poisoning (Deviere et al, 1987).

Genitourinary

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 40-year-old woman developed aortic, femoral, and iliac arterial spasm with renal artery stenosis and a transient decrease in creatinine clearance after using 10 mg of ergotamine as suppositories over 60 hours (Fedotin & Hartman, 1970).
b) CASE SERIES (NEONATES): In a retrospective review of 7 cases of unintentional ergot alkaloid (dose range 0.125 mg to 0.5 mg ergometrine) administration to neonates, 3 infants developed transient oliguria or anuria. Renal function recovered within a week (Dargaville & Campbell, 1998).

2) WITH POISONING/EXPOSURE

a) CASE REPORT: A 29-year-old man sustained several cardiac arrests (ventricular fibrillation and asystole), followed by several hours of sustained hypotension after ingesting 60 tablets containing 2 mg of ergotamine, 50 mg of cyclizine, and 100 mg of caffeine. He subsequently developed popliteal artery spasm which was treated with intravenous nitroprusside for 5 days. He had transient oliguria and azotemia but recovered complete renal function (Carr, 1981).
b) CASE REPORT (PEDIATRIC): A full-term male infant unintentionally given 0.18 mg of methylergonovine instead of naloxone for treatment of respiratory depression became anuric for 16 hours. Urine output normalized (1.8 cm(3)/kg/hr) within 24 hours (Bangh et al, 2005).

Dermatologic

3.14.2)

A) CYANOSIS

1) WITH THERAPEUTIC USE

a) Cyanosis and mottled skin may occur secondary to peripheral ischemia.
b) CASE REPORT: A 32-year-old man treated with antiretroviral therapy (tenofovir, abacavir, and lopinavir/ritonavir) for HIV infection presented to the emergency department with cyanosis to bilateral hands and feet approximately 4 days after ingesting a 1 mg dose of ergotamine to treat a migraine. Examination revealed vasospasms and severe ischemia to all extremities. After treatment with IV iloprost and oral sildenafil, restoration of all pulses occurred within 24 hours. He was discharged in good condition 5 days after admission (Marine et al, 2011).

B) PURPURIC RASH

1) WITH THERAPEUTIC USE

a) Five infants injected with ergonovine maleate 0.2 mg IM developed cyanosis and purpuric lesions with hemorrhagic blebs on the extremities, groin, and genitalia (Edwards, 1971).

C) ECZEMA

1) WITH POISONING/EXPOSURE

a) TOPICAL EXPOSURE: Occupational exposure to nebulized nicergoline and its synthetic intermediates resulted in facial eczema and oculorhinitis in a pharmaceutical industry technician (Fumagalli et al, 1992).

D) INJECTION SITE PAIN

1) WITH THERAPEUTIC USE

a) Patients complain of local burning and pain with subcutaneous administration of dihydroergotamine. Dilution with normal saline has been suggested to minimize discomfort (Wheeler, 1993).

Musculoskeletal

3.15.2)

A) PAIN

1) WITH THERAPEUTIC USE

a) Muscle pain and weakness may be a symptom of extremity ischemia. Claudication and generalized cramping are reported.
b) CASE REPORT: A 32-year-old man treated with antiretroviral therapy (tenofovir, abacavir, and lopinavir/ritonavir) for HIV infection experienced claudication 24 hours after ingesting a 1 mg dose of ergotamine to treat a migraine. Initially he developed claudication after walking 200 m but this progressed to pain at rest by the time he presented to the emergency department 3 days later. At admission his leg pain was more severe on the right side compared with the left and his hands and feet were cold, cyanotic, and pulseless (femoral pulses were weakly palpable). CT of upper and lower extremities showed bilateral multilevel ischemia and diffuse arterial narrowing consistent with severe spasms. Symptoms were unresponsive to withdrawal of antiretroviral drugs and treatment with IV heparin, morphine, and sodium nitroprusside. After treatment with IV iloprost and oral sildenafil, restoration of all pulses occurred within 24 hours. CT angiography findings were normal after 3 days of treatment. He was discharged in good condition 5 days after admission (Marine et al, 2011).

Reproductive

3.20.1)

3.20.2)

A) HYPOXIA

1) Fetal mortality and malformations have been observed in experimental animals and may be associated with hypoxia in utero from maternal vascular insufficiency or from vasoconstriction in the fetus (Griffith et al, 1978).

B) CONGENITAL ANOMALY

1) A woman who took ergotamine, propranolol, and caffeine for the first 14 to 20 weeks of gestation gave birth to an infant with multiple deformities (Hughes & Golstein, 1988).
2) An infant with multiple birth defects was born after mother received a single dose of 2 mg ergotamine, 100 mg caffeine, 0.25 mg belladonna alkaloid and 100 mg butalbital administered at 4 and 1/2 months gestation (Verloes et al, 1990).

3.20.3)

A) SPONTANEOUS ABORTION

1) Spontaneous abortion may occur secondary to uterine stimulation (Zimran et al, 1984; Au et al, 1985). Inhibition of implantation has also been noted in animal studies (Griffith et al, 1978).

B) STILLBIRTH

1) Intrauterine fetal death at the thirty-fifth week of gestation and myocardial ischemia were reported in a 17-year-old primigravida 13 hours after ingestion of a single dose of 20 mg of ergotamine (Au et al, 1985).

C) FETAL DISTRESS

1) Administration of 2 mg ergotamine tartrate with 100 mg caffeine at 39 weeks gestation was associated with the development of fetal distress, including reduced fetal activity and respiration (de Groot et al, 1993).

D) UTERINE SPASM

1) A patient developed uterine hypertonicity following erroneous administration of 0.2 mg methylergonovine maleate. A healthy child was delivered by cesarean section (Moise & Carpenter, 1988).

E) CEREBROVASCULAR DISORDER

1) POSTPARTUM EFFECTS - Intravenous ergonovine 0.2 mg given to mother after cesarean section resulted in cerebral vasospasm and infarction (Barinagarrementeria et al, 1992).
2) Postpartum eclampsia was associated with the administration of intravenous ergonovine maleate 500 mcg followed by 5 units of syntocinon. Blood pressure was 150/95 mmHg and pulse 72 bpm within 30 minutes of administration. The patient developed eclamptic seizures after 9 hours that were treated successfully with diazepam. Blood pressure was controlled with intravenous hydralazine, and the patient recovered (Dua, 1994).

F) PREGNANCY CATEGORY

1) ERGOTAMINE has been classified as FDA pregnancy category X (Prod Info Ergomar(R) sublingual tablets, 2007).
2) METHYLERGONOVINE has been classified as FDA pregnancy category C; however, it is contraindicated during pregnancy due to its uterotonic effects (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun)

3.20.4)

A) EFFECTS ON LACTATION

1) SUMMARY - Prolonged administration can inhibit lactation (Prod Info Ergomar(R) sublingual tablests, ergotamine tartrate, 2000).
2) Inhibition of prolactin by ergotamine, ergonovine and methylergonovine secretion may suppress lactation (Rall & Schleifer, 1985) Lawrence 1994.
3) A study of 1429 healthy women about to give birth showed no difference in postpartum prolactin levels between those who received ergonovine and those who did not. However, women who received ergonovine were more likely to discontinue breastfeeding before 4 weeks than those who did not due to the perception that milk production was too low to adequately feed the baby (Begley, 1990).

B) BREASTFEEDING

1) Ergotamine, ergonovine and methylergonovine are excreted into breast milk.
2) It is recommended that women not breastfeed during methylergonovine therapy and for at least 12 hours after the last dose. It is also recommended that milk secreted during this period be discarded. Adverse effects in the breastfeeding infant may occur if the mother is receiving methylergonovine (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun). IM or IV methylergonovine (intended for the mother) inadvertently administered to newborns has resulted in serious adverse events, including respiratory depression, cyanosis, oliguria, and seizures (Novartis Pharmaceuticals Corporation, 2012)
3) The American Academy of Pediatrics considers the use of ergotamine during breast feeding to be contraindicated based on a study in which vomiting, diarrhea, and convulsions were observed in most nursing infants (Briggs et al, 1998).

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor basic blood work (e.g. complete blood count, metabolic panel) in all symptomatic patients.
B) Patients showing signs of cardiac toxicity should have cardiac biomarkers ordered along with continuous cardiac monitoring and serial ECGs.
C) Patients exhibiting neurological deficits, or in whom intestinal or renal ischemia is suspected, should undergo CT scan.

4.1.2)

A) TOXICITY

1) Serum or plasma concentrations are not clinically useful.
2) Toxic effects may persist despite undetectable concentrations in the blood (Tfelt-Hansen & Manniche, 1984).
3) The diagnosis and treatment of ergot poisoning should be based on clinical findings (Graham et al, 1984).
4) Monitor basic blood work (e.g. complete blood count, metabolic panel) in all symptomatic patients.

4.1.4)

A) OTHER

1) ECG

a) Patients showing signs of cardiac toxicity should have cardiac biomarkers ordered along with continuous cardiac monitoring and serial ECGs.

2) ULTRASOUND

a) Doppler ultrasound studies and plethysmography should be obtained if there is any question of peripheral vascular insufficiency, and may be used to diagnose and to assess the efficacy of treatment for vasoconstriction.

Radiographic Studies

1) ANGIOGRAPHY is often used when the history and clinical features are inadequate to confirm diagnosis of vascular insufficiency (Hirsh & Eger, 1972). It will also differentiate vascular spasm from thrombosis.

a) Angiographic findings include rat-tail or thread-like arterial narrowing (more severe distally), total occlusion, collateral formation (especially in chronic cases), and rarely concomitant thrombus formation (Bagby & Cooper, 1972).

1) Computerized tomography may support diagnosis of cerebral infarction.
2) Computerized tomography and intravenous pyelography may support a diagnosis of renal infarction.
3) Abdominal radiographs and computerized tomography may support a diagnosis of intestinal infarction.

Methods

1) HPLC has been used to identify and measure ergot alkaloids and their dihydrogenated methanesulphonate salts in human plasma (Zorz et al, 1985).
2) However, ergot plasma concentrations are not clinically useful.

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients exhibiting cardiovascular effects should be admitted to an intensive care setting.

6.3.1.2) HOME CRITERIA/ORAL

A) Most patients may be observed at home if they are not having any symptoms.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Other consultants that may need to be involved include cardiologists (for acute coronary syndrome), neurologists (for strokes), vascular surgeons (for peripheral vascular ischemia). Consult a medical toxicologist for patients with severe poisoning or in whom the diagnosis is unclear.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Any patient who is experiencing symptoms or had a self-harm attempt should be sent to a healthcare facility for observation. Observe asymptomatic patients for 4 to 6 hours. Admit patients with severe symptoms or patients who are still symptomatic at the end of observation.

Monitoring

Oral Exposure

6.5.1)

A) Ipecac-induced vomiting is potentially useful if given immediately (within a few minutes of ingestion); however, it is not generally recommended because of the possibility of CNS depression and subsequent aspiration. Consider activated charcoal in a patient with a recent, substantial overdose who is alert or in whom airway is protected.
B) ACTIVATED CHARCOAL

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.2)

A) Most toxicity is from chronic excessive dosing, and decontamination is not generally useful in these cases. Consider activated charcoal in a patient with a recent, substantial overdose who is alert or in whom airway is protected.
B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

b) ADVERSE EFFECTS/CONTRAINDICATIONS

6.5.3)

A) MONITORING OF PATIENT

1) Monitor basic blood work (e.g. complete blood count, metabolic panel) in all symptomatic patients.
2) Patients showing signs of cardiac toxicity should have cardiac biomarkers ordered along with continuous cardiac monitoring and serial ECGs.
3) Patients exhibiting neurological deficits, or in whom intestinal or renal ischemia is suspected, should undergo CT scan.

B) PAIN

1) Treat pain with analgesics and/or opioids as necessary to achieve control.

C) SODIUM NITROPRUSSIDE

1) Sodium nitroprusside is recommended for the treatment of hypertensive emergencies associated with ergot alkaloid exposure.
2) Sodium nitroprusside has been effective in the reversal of ergotamine-associated vasoconstriction and peripheral ischemia (Carliner et al, 1974; Lewis et al, 1986; Dierckx et al, 1986).
3) Intravenous administration of sodium nitroprusside in doses of 1 to 5 mcg/kg/min has been shown to reduce systemic vascular resistance with accompanying improvement of ischemia (Eurin et al, 1978; Andersen et al, 1977).
4) Sodium nitroprusside administered by local continuous arterial infusion successfully treated peripheral arterial occlusive disease exacerbated by ergotamine-induced severe vasospasm in a patient that was unresponsive to 200 mcg/min intravenous sodium nitroprusside (Dierckx et al, 1986).
5) INFANTS - Vasodilator therapy has not been reported in infants who have received ergonovine. If necessary, sodium nitroprusside has been safely administered to infants 2 days old (Davies, 1975).

a) A dose of 0.5 to 1 mcg/kg/min may be administered and the infants monitored closely for metabolic acidosis and tachyphylaxis.

D) NITROGLYCERIN

1) Nitroglycerin has been effective in adults in reversing ergonovine-induced coronary artery spasm and ergotamine-induced peripheral ischemia (Husum et al, 1979; Tfelt-Hansen et al, 1982; Hanpler et al, 1978).
2) NITROGLYCERIN/INDICATIONS

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

3) NITROGLYCERIN/ADULT DOSE

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

4) NITROGLYCERIN/PEDIATRIC DOSE

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

E) PHENTOLAMINE

1) Phentolamine has also been suggested for treatment of severe hypertension or cerebral, myocardial or mesenteric ischemia (Chu & Lewin, 2002).
2) PHENTOLAMINE/INDICATIONS

a) Useful for severe hypertension, particularly if caused by agents with alpha adrenergic agonist effects usually induced by catecholamine excess (Rhoney & Peacock, 2009).

3) PHENTOLAMINE/ADULT DOSE

a) BOLUS DOSE: 5 to 15 mg IV bolus repeated as needed (U.S. Departement of Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, 2004). Onset of action is 1 to 2 minutes with a duration of 10 to 30 minutes (Rhoney & Peacock, 2009).
b) CONTINUOUS INFUSION: 1 mg/hr, adjusted hourly to stabilize blood pressure. Prepared by adding 60 mg of phentolamine mesylate to 100 mL of 0.9% sodium chloride injection; continuous infusion ranging from 12 to 52 mg/hr over 4 days has been used in case reports (McMillian et al, 2011).

4) PHENTOLAMINE/PEDIATRIC DOSE

a) 0.05 to 0.1 mg/kg/dose (maximum of 5 mg per dose) intravenously every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Singh et al, 2012; Koch-Weser, 1974).

5) PHENTOLAMINE/ADVERSE EFFECTS

a) Adverse events can include orthostatic or prolonged hypotension, tachycardia, dysrhythmias, angina, flushing, headache, nasal congestion, nausea, vomiting, abdominal pain and diarrhea (Rhoney & Peacock, 2009; Prod Info Phentolamine Mesylate IM, IV injection Sandoz Standard, 2005).

6) CAUTION

a) Phentolamine should be used with caution in patients with coronary artery disease because it may induce angina or myocardial infarction (Rhoney & Peacock, 2009).

F) PRAZOSIN

1) In less severe cases, oral prazosin may be used as an alternative to parenteral agents.
2) Prazosin has been effective in reversing peripheral ischemia caused by chronic ergotamine therapy (Safar et al, 2002; Zavaleta et al, 2001). Doses of 1 to 3 mg/day have been used.

G) CAPTOPRIL

1) In less severe cases, oral captopril may be used as an alternative to parenteral agents.
2) Captopril 50 mg orally three times a day, was effective in restoring peripheral pulses and relieving pain within 3 hours in a patient receiving chronic excessive ergotamine therapy (Zimran et al, 1984).

H) NIFEDIPINE

1) In less severe cases, oral nifedipine may be used as an alternative to parenteral agents.
2) Nifedipine (10 mg orally three times a day) was effective in reversing vascular insufficiency due to chronic ergotamine abuse (Kemerer et al, 1984).

I) PROSTAGLANDIN

1) Prostaglandin E1: A potent vasodilator, has been given by direct arterial infusion to treat arterial spasm.
2) A case of severe acute peripheral arterial insufficiency secondary to ergotamine toxicity was treated with an intravenous infusion of prostacyclin (epoprostenol and prostaglandin I2).

a) The dose of prostacyclin was 20 nanograms/kg/min. Improvement was seen in 5 hours, but a fasciotomy was still required for decompression of one leg.
b) The prostacyclin infusion was replaced by a prostaglandin E1 infusion which ran for 6 days. Circulation improved.
c) Heparin, nifedipine (20 mg twice daily), aspirin, morphine, and topical glyceryl trinitrate were also used (Edwards et al, 1991).

3) PROSTAGLANDIN I2 CASE REPORT: A 32-year-old man treated with antiretroviral therapy (tenofovir, abacavir, and lopinavir/ritonavir) for HIV infection experienced claudication 24 hours after ingesting a 1 mg dose of ergotamine to treat a migraine. Initially he developed claudication after walking 200 m but this progressed to pain at rest by the time he presented to the emergency department 3 days later. At admission his leg pain was more severe on the right side compared with the left and his hands and feet were cold, cyanotic, and pulseless (femoral pulses were weakly palpable). CT of upper and lower extremities showed bilateral multilevel ischemia and diffuse arterial narrowing consistent with severe spasms. Symptoms were unresponsive to withdrawal of antiretroviral drugs and treatment with IV heparin, morphine, and sodium nitroprusside. There was some improvement in plethysmography after intra-arterial prostaglandin E1 (Prostin) injection. He was treated with IV iloprost (up to 2 ng/kg/min) and oral sildenafil (25 mg every 8 hours) , and restoration of all pulses occurred within 24 hours. CT angiography findings were normal after 3 days of treatment. He was discharged in good condition 5 days after admission (Marine et al, 2011).

J) CYPROHEPTADINE

1) CASE REPORT - Cyproheptadine (4 mg orally three times daily) was given to a 41-year-old female with ergotism who developed hypotension during vasodilator therapy with intravenous sodium nitroprusside (SNP). The SNP dose was decreased despite worsening symptoms, but within 2 hours of the patient's first dose of cyproheptadine her symptoms of pallor and pain markedly improved (Carlton et al, 1995).
2) The authors suggested that the vasoconstrictive effects of ergots may be due to interaction with both adrenergic and serotoninergic (cyproheptadine is a serotonin antagonist) receptors on vasculature.

K) CONTRAINDICATED TREATMENT

1) Diazoxide, niacin, papaverine, phenoxybenzamine, reserpine, and tolazoline have been used in the past but are NO longer recommended (Fedotin & Hartman, 1970; Carliner et al, 1974; Enge & Sivertssen, 1965; Levy et al, 1984; Thomson et al, 1950; Greene et al, 1977; Harrison, 1978).
2) Similarly, spinal anesthesia and surgical sympathectomy are no longer recommended (Harrison, 1978; Levy et al, 1984).

L) HYPERBARIC OXYGEN THERAPY

1) Hyperbaric oxygen treatment has been successful in reversing ergotamine-induced peripheral ischemia when attempts to reverse vasoconstriction (including nitroprusside in one patient) fail (Merrick et al, 1978).
2) CASE REPORT - Hyperbaric oxygen therapy was successful in treating a 26-year-old female with peripheral ischemia following ergotamine poisoning. Various pharmacologic treatment modalities (eg, anticoagulants, thrombolytics, vasodilators and prostaglandin inhibitors) were attempted without success. Therapy at 2.4 ATA for 90 minutes with 32 treatments over 21 days resulted in marked improvement with restoration of distal lower extremity pulses.

a) No complications occurred and 9 months after presentation. The patient was ambulatory with crutches using an ankle brace on the left and a cast on the right foot (Bilden & Adkinson, 1998).

M) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

N) BRADYCARDIA

1) ATROPINE/DOSE

a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

1) There is no minimum dose (de Caen et al, 2015).
2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

O) VENTRICULAR ARRHYTHMIA

1) Lidocaine is the drug of choice for management of ventricular tachycardia and ventricular fibrillation that is resistant to defibrillation.

a) LIDOCAINE/DOSE

1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.

a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

b) LIDOCAINE/MAJOR ADVERSE REACTIONS

1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

c) LIDOCAINE/MONITORING PARAMETERS

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

P) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

Q) ANTICOAGULANT

1) Anticoagulant (heparin in combination with sodium nitroprusside or nitroglycerin) therapy should be instituted in all patients with evidence of vascular insufficiency (Harrison, 1977; Skowronski, 1979).

R) THROMBOLYTIC

1) Since the incidence of thrombosis is low in patients with arterial insufficiency from ergot, thrombolytic therapy should generally be reserved for those with angiographic evidence of thrombosis.

S) VASOSPASM

1) Fogarty balloon dilatation, angioplasty, atherectomy and other interventions have been used in cases of severe vasospasm. Because aggressive medical treatment is usually effective, interventional procedures should be reserved unless gangrene is imminent (McKiernan et al, 1994).

T) SEROTONIN SYNDROME

1) SUMMARY

a) Benzodiazepines are the mainstay of therapy. Cyproheptadine, a 5-HT antagonist, is also commonly used. Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with non-depolarizing agents(Claassen & Gelissen, 2005).

2) HYPERTHERMIA

a) Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans.
b) MUSCLE ACTIVITY: Benzodiazepines are the drug of choice to control agitation and muscle activity. DIAZEPAM: ADULT: 5 to 10 mg IV every 5 to 10 minutes as needed, monitor for respiratory depression and need for intubation. CHILD: 0.25 mg/kg IV every 5 to 10 minutes; monitor for respiratory depression and need for intubation.
c) Non-depolarizing paralytics may be used in severe cases.

3) CYPROHEPTADINE

a) Cyproheptadine is a non-specific 5-HT antagonist that has been shown to block development of serotonin syndrome in animals (Sternbach, 1991). Cyproheptadine has been used in the treatment of serotonin syndrome (Mills, 1997; Goldberg & Huk, 1992). There are no controlled human trials substantiating its efficacy.
b) ADULT: 12 mg initially followed by 2 mg every 2 hours if symptoms persist, up to a maximum of 32 mg in 24 hours. Maintenance dose 8 mg orally repeated every 6 hours (Boyer & Shannon, 2005).
c) CHILD: 0.25 mg/kg/day divided every 6 hours, maximum dose 12 mg/day (Mills, 1997).

4) HYPERTENSION

a) Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic intervention is usually not necessary.

5) HYPOTENSION

a) Administer 10 to 20 mL/kg 0.9% saline bolus and place patient supine. Further fluid therapy should be guided by central venous pressure or right heart catheterization to avoid volume overload.
b) Pressor agents with dopaminergic effects may theoretically worsen serotonin syndrome and should be used with caution. Direct acting agents (norepinephrine, epinephrine, phentolamine) are theoretically preferred.
c) NOREPINEPHRINE

1) PREPARATION: Add 4 mL of 0.1% solution to 1000 mL of dextrose 5% in water to produce 4 mcg/mL.
2) INITIAL DOSE

a) ADULT: 2 to 3 mL (8 to 12 mcg)/minute.
b) ADULT or CHILD: 0.1 to 0.2 mcg/kg/min. Titrate to maintain adequate blood pressure.

3) MAINTENANCE DOSE

a) 0.5 to 1 mL (2 to 4 mcg)/minute.

6) SEIZURES

a) DIAZEPAM

1) MAXIMUM RATE: Administer diazepam IV over 2 to 3 minutes (maximum rate: 5 mg/min).
2) ADULT DIAZEPAM DOSE: 5 to 10 mg initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
3) PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 mg/kg, repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
4) RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (not FDA approved), or lorazepam may be given intramuscularly.

b) LORAZEPAM

1) MAXIMUM RATE: The rate of IV administration of lorazepam should not exceed 2 mg/min (Prod Info Ativan(R), 1991).
2) ADULT LORAZEPAM DOSE: 2 to 4 mg IV. Initial doses may be repeated in 10 to 15 minutes, if seizures persist (Prod Info ATIVAN(R) injection, 2003).
3) PEDIATRIC LORAZEPAM DOSE: 0.1 mg/kg IV push (range: 0.05 to 0.1 mg/kg; maximum dose 4 mg); may repeat dose in 5 to 10 minutes if seizures continue. It has also been given rectally at the same dose in children with no IV access (Sreenath et al, 2009; Chin et al, 2008; Wheless, 2004; Qureshi et al, 2002; De Negri & Baglietto, 2001; Mitchell, 1996; Appleton, 1995; Giang & McBride, 1988).

c) RECURRING SEIZURES

1) If seizures cannot be controlled with diazepam or recur, give phenobarbital or propofol.

d) PHENOBARBITAL

1) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (15 to 25 mcg/mL).
2) ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 mg of phenobarbital IV initially (10 to 20 mg/kg) diluted in 60 mL of 0.9% saline given at 25 to 50 mg/minute.
3) ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 mg may be given every 20 minutes.
4) MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 mg/min until seizure control was achieved or a total dose of 10 mg/kg.
5) PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 mg/kg of phenobarbital intravenously at a rate of 25 to 50 mg/min.
6) PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 mg/kg may be given every 20 minutes.
7) MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 mg/kg within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
8) NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 mg/kg IV at a rate of no more than 1 mg/kg/min in patients with no preexisting phenobarbital serum levels.
9) NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 mg/kg every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 mcg/mL.
10) MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 mg/kg/min up to a total of 30 mg/kg have been tolerated in neonates.
11) CAUTION: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.

7) CHLORPROMAZINE

a) Chlorpromazine is a 5-HT2 receptor antagonist that has been used to treat cases of serotonin syndrome (Graham, 1997; Gillman, 1996). Controlled human trial documenting its efficacy are lacking.
b) ADULT: 25 to 100 mg intramuscularly repeated in 1 hour if necessary.
c) CHILD: 0.5 to 1 mg/kg repeated as needed every 6 to 12 hours not to exceed 2 mg/kg/day.

8) NOT RECOMMENDED

a) BROMOCRIPTINE: It has been used in the treatment of neuroleptic malignant syndrome but is NOT RECOMMENDED in the treatment of serotonin syndrome as it has serotonergic effects (Gillman, 1997). In one case the use of bromocriptine was associated with a fatal outcome (Kline et al, 1989).

Enhanced Elimination

1) As ergot alkaloids have extensive tissue distribution, dialysis and hemoperfusion are not effective treatments.

1) PERITONEAL DIALYSIS was reported successful in a 13-month-old female who ingested an estimated 15 milligrams of ergotamine. Analysis of the first 200 mL of dialysate return yielded 90 mcg of ergotamine.

a) Although slow clinical improvement was noted following the procedure, kinetic data are insufficient to support the efficacy of peritoneal dialysis with respect to drug removal (Jones & Williams, 1966).

Abstracts

Case Reports

1) A 29-year-old man presented with coma, respiratory depression, unreactive pupils, tachycardia, nonpalpable pulses, unobtainable blood pressure, and lactic acidosis 1 hour after ingesting 40 tablets, each containing 1 mg ergotamine and 100 mg caffeine (Deviere et al, 1987).
2) A 32-year-old woman developed acute peripheral arterial insufficiency with leg pain and weakness following the use of a single rectal ergotamine suppository (Harrison, 1984).

1) Twelve newborns developed sepsis-like symptoms and encephalopathy within the first 6 hours of life when methylergonovine (MEV) 0.2 mg was accidently administered to each child instead of vitamin K in the delivery room. Symptoms included lethargy (41.7%), seizure (75%), feeding intolerance (66.6%), hypoventilation (58%), irritability (25%), and peripheral circulation abnormalities (58%). The error was not discovered until 3 days after the event. The hospital stay ranged from 5 to 10 days, but all 12 children recovered with supportive care and were discharged without any reported health deficits(Bas et al, 2011).
2) Unintentional intramuscular administration of ergonovine to the neonate has resulted in respiratory depression, seizures, acute renal failure, and peripheral cyanosis (Mitchell et al, 1983; Kenna, 1972)
3) Cyanosis of the extremities in 5 neonates has been reported, but unintentional administration of ergonovine was not confirmed in any case (Edwards, 1971).
4) Respiratory failure, seizures, acute renal failure, and lactose intolerance were reported in a full-term infant unintentionally administered 0.5 mg of ergonovine instead of Vitamin E immediately after birth (Pandey & Haines, 1982).
5) Eight cases of lisuride ingestion were reported by van Tittelboom & Mostin (1985). Symptoms were fatigue, nausea, vomiting and orthostatic hypotension. Of special interest was the sudden onset and short duration of symptoms (van Tittelboom & Mostin, 1985).

Range Of Toxicity

Summary

Therapeutic Dose

7.2.1)

A) DIHYDROERGOTAMINE MESYLATE

1) PARENTERAL: 1 mL IV, IM or SubQ; may be repeated as needed at 1-hour intervals to a total dose of 3 mL IM or SubQ delivery or 2 mL for IV delivery in a 24-hour period; maximum weekly dose should not exceed 6 mL (Prod Info D.H.E. 45(R) intravenous injection, intramuscular injection, subcutaneous injection, 2012).
2) NASAL: 0.5 mg (one spray) each nostril; followed by another spray (one) in each nostril 15 minutes later (4 sprays, total 2 mg) (Prod Info dihydroergotamine mesylate nasal spray, 2013).

B) ERGOLOID MESYLATES

1) ORAL: 1 mg orally 3 times a day (Prod Info ergoloid mesylates oral tablets, 2009).

C) ERGONOVINE MALEATE

1) PARENTERAL: 0.2 mg/mL IM or IV, repeat doses may be required in severe uterine bleeding no more often than once in 2 to 4 hours (Prod Info ERGOTRATE(R) injection, 2006).
2) ORAL: 0.2 to 0.4 mg orally every 6 to 12 hours until danger of uterine atony has passed (usually 48 hours) (Prod Info ERGOTRATE(R) oral tablets, 2004).

D) ERGOTAMINE TARTRATE

1) SUBLINGUAL: 2 mg in a single initial dose, then repeat another 2 mg tablet in 30 minutes; daily dose should not exceed 3 2-mg tablets in any 24 hour period. Dose should be limited to not more than 5 tablets (10 mg) in any week (Prod Info Ergomar(R) sublingual tablets, 2008).

E) ERGOTAMINE TARTRATE PLUS CAFFEINE

1) RECTAL: One suppository at the start of the attack; second suppository after 1 hour, if needed (Prod Info Ergotamine Tartrate and Caffeine rectal suppository, 2003).

F) METHYLERGONOVINE MALEATE

1) IM: 0.2 mg (1 mL) following delivery of the placenta or the anterior shoulder or during the puerperium; may repeat every 2 to 4 hours as needed (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun)
2) IV: 0.2 mg (1 mL) slowly over at least 60 seconds; routine IV administration is not recommended, use only if essential for lifesaving measures (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun).
3) ORAL: 0.2 mg 3 or 4 times daily during the puerperium; up to 1 week duration (Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun).

G) METHYSERGIDE

1) ORAL: 4 to 8 mg/day in divided doses with meals (Prod Info SANSERT(R) oral tablets, 2000).

7.2.2)

A) Safety and efficacy have not been established in pediatric patients (Prod Info dihydroergotamine mesylate nasal spray, 2013; Prod Info Methergine(R) oral tablets intramuscular, intravenous injection, Jun; Prod Info D.H.E. 45(R) intravenous injection, intramuscular injection, subcutaneous injection, 2012; Prod Info Ergomar(R) sublingual tablets, 2008; Prod Info SANSERT(R) oral tablets, 2000).

Minimum Lethal Exposure

1) ERGONOVINE

a) INFANT - A 14-month-old infant died after ingesting 12 mg of ergonovine (Prod Info ERGOTRATE(R) injection, 2006).
b) NEWBORN - Neonatal fatality has been reported following the intramuscular injection of 0.2 mg ergonovine (Edwards, 1971), however mortality was attributed to Klebsiella pneumonia and severe respiratory distress. A direct toxic effect of the drug as a cause of death was not established.
c) ADULT - A patient died after ingesting 25 mg of ergonovine over several days (Prod Info ERGOTRATE(R) injection, 2006).

2) ERGOTAMINE

a) ADULTS - Death has been reported in adults, generally those with cardiovascular disease, following 0.5 mg ergotamine given subcutaneously (Carter, 1940).

3) METHYLERGONOVINE

a) NEONATAL fatality has been reported following the intramuscular injection of 0.2 mg methylergonovine (Anon, 1961).

Maximum Tolerated Exposure

1) Due to differences in individual susceptibility to ergot alkaloids, the acute toxic dose is not well established (McGuigan, 1984).
2) Since even a small dose can lead to toxicity in hypersensitive individuals, all unintentional or intentional ingestions should be considered potentially toxic.
3) Although small doses may cause toxicity, doses of ergotamine tartrate in excess of approximately 15 mg in 24 hours or 40 mg in a few days are likely to cause poisoning (Prod Info Ergomar(R) sublingual tablests, ergotamine tartrate, 2000).

1) ERGOTAMINE

a) A 32-year-old woman developed lower back and leg pain and diminished pedal pulses after using a single ergotamine suppository (Harrison, 1984).
b) A 72-year-old woman developed tongue necrosis with stenosis of both external carotid and lingual arteries and the right ophthalmic artery after using a single 2 mg ergotamine suppository (Vazquez-Doval et al, 1994).

2) ERGONOVINE

a) NEWBORN

1) Rabe & Vicas (1989) described 3 newborns who unintentionally received 0.25 mg of ergonovine intramuscularly in the first 4 hours of life. All 3 infants developed significant symptoms requiring admission of a tertiary level NICU for supportive care. All three infants recovered fully (Rabe & Vicas, 1989).
2) Severe toxicity has occurred in newborns mistakenly given 0.2 mg ergonovine (Mitchell et al, 1983) and 0.5 mg ergonovine with 5 International Units oxytocin (Kenna, 1972; Brereton-Stiles et al, 1972).
3) Toxicity may be observed following ergonovine doses of 3 more or greater (Prod Info ERGOTRATE(R) injection, 2006).
4) NEONATES/CASE SERIES - Seizures and peripheral circulatory abnormalities have been reported in infants (n=7) exposed to ergometrine (ergonovine) doses of 0.125 mg to 0.5 mg intramuscularly either given alone or in combination with synthetic oxytocin (Dargaville & Campbell, 1998). Most symptoms resolved in 4 days with no long-term neurological deficits observed at follow-up (mean length 3.5 years).

b) ADULT

1) A 34-year-old woman suffered an acute myocardial infarction and hypotension after receiving 0.2 mg of methylergonovine intravenously after a spontaneous abortion (Liao et al, 1991).
2) A 28-year-old woman with post-partum cerebral angiopathy (exact mechanism unknown) developed cerebral infarction after receiving 0.2 mg of ergonovine IV following an uncomplicated caesarean section (Barinagarrementeria et al, 1992).

3) ERGOTAMINE

a) The manufacturer reports some cases of poisoning have occurred with ingestions of less than 5 mg of ergotamine tartrate (Prod Info Ergostat(R), ergotamine tartrate sublingual tablets, 1991).
b) ADULT - Reversible bilateral papillitis with ring scotomata developed in a patient who received 5 times the recommended daily adult dose of ergotamine over a period of 14 days (Prod Info ERGOMAR(R) sublingual oral tablets, 2003).
c) ADULT - A 29-year-old male survived an ingestion of 120 mg of ergotamine, 3 grams cyclizine, and 6 grams caffeine, despite a series of cardiac arrests (Carr, 1981).
d) INFANT - A 13-month-old child survived the ingestion of 15 mg of ergotamine (combined with phenobarbital and belladonna) (Jones & Williams, 1966).

4) METHYLERGONOVINE MALEATE

a) NEWBORN

1) NEWBORN - Unintentional injection of 0.2 mg of methylergonovine to newborns resulted in recovery in all but one case. Effects noted following injection included respiratory depression, hypothermia, and hypertonicity with jerking movements. One patient developed a single seizure (Prod Info methylergonovine maleate IM, IV Injection, 2008).

a) In newborns with methylergonovine poisoning the mean dose in those who developed symptoms after oral exposure was 0.12 mg/kg (range 0.02 to 0.35 mg/kg). All patients recovered with supportive care (Aeby et al, 2003).

2) CASE REPORT - A full-term male infant, was unintentionally given 0.18 mg methylergonovine intramuscularly instead of naloxone for treatment of respiratory depression and subsequently developed respiratory failure and oliguria. The patient recovered following administration of nitroprusside infusion and furosemide (Bangh et al, 2005).

b) CHILDREN

1) Unintentional ingestions of up to 10 tablets (2 mg) methylergonovine resulted in no apparent ill effects in several children 1 to 3 years of age (Prod Info methylergonovine maleate IM, IV Injection, 2008).
2) In children (median age 2 years, range 4 months to 15 years) with methylergonovine poisoning, the mean dose in those who developed clinical toxicity was 0.06 mg/kg (range 0.008 mg/kg to 0.19 mg/kg). All patients recovered with supportive care (Aeby et al, 2003).

c) ADULTS

1) Ingestion of 4 tablets (2 mg) resulted in paresthesias and clamminess in an adult (Prod Info methylergonovine maleate IM, IV Injection, 2008).
2) POSTPARTUM - A 28-year-old healthy female developed coronary artery thrombosis and an inferior-posterior myocardial infarct following a total of 1.2 mg of methergine for severe vaginal bleeding after a spontaneous second trimester abortion (Nall & Feldman, 1998). Emergent coronary artery bypass grafting was required.

5) METHYSERGIDE

a) CHILDREN - A child developed euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness after ingesting 20 to 24 mg of methysergide (Prod Info SANSERT(R) oral tablets, 2000).
b) ADULTS - Adults have experienced peripheral vasospasm, with diminished or absent pulses, coldness, mottling and cyanosis after ingesting methysergide 200 mg (Prod Info SANSERT(R) oral tablets, 2000).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CONCENTRATION LEVEL

a) Toxicity may not easily be correlated to the serum concentration and quantitative blood concentrations are not clinically useful.
b) In one study (Graham et al, 1984), a concentration of 1.9 nanograms (ng)/mL was associated with no side effects, but 0.07 ng/mL caused nausea, vomiting, and muscle cramps.
c) Others have found that adverse reactions occurred more frequently in patients with plasma levels of ergotamine greater than 1.8 ng/mL(Orton & Richardson, 1982).
d) Pharmacologic and toxic effects may persist for days after blood levels become undetectable (Tfelt-Hansen & Paalzow, 1985). Pharmacodynamic studies indicate marked individual variability in sensitivity to ergotamine (Tfelt-Hansen & Manniche, 1984).

Toxicity Information

7.7.1)

A) ERGOMETRINE
B) METHYLERGONOVINE

1) LD50- (ORAL)MOUSE:

a) 187 mg/kg (Prod Info methylergonovine maleate IM, IV Injection, 2008)

2) LD50- (ORAL)RAT:

a) 93 mg/kg (Prod Info methylergonovine maleate IM, IV Injection, 2008)

Pharmacology Toxicology

Pharmacologic Mechanism

1) The degree of activity of each alkaloid at these receptor sites varies greatly and determines the pharmacological activity of the different agents.
2) The major pharmacological effects include smooth muscle stimulation, resulting in vasoconstriction, hypertension, increased uterine muscle activity, peripheral adrenergic blockade, and central sympatholytic activity, resulting in hypotension (Merhoff & Porter, 1974; Griffith et al, 1978; Harrison, 1978).

Action	Constriction	Oxytocic	Alpha-Blocker	Sympatholytic
Ergotamine	Most acute	Not active/delayed	Active	Active
Dihydroergotamine	Less active	Active	Most active	Most active
Dihydroergotoxine	None	Active	Most active	Most active
Ergonovine	Slight	Most active	None	---
Methylergonovine	Slight	Most active	None	---
Methysergide	Slight	Low	Low	---
Bromocriptine	Slight	None	Moderate	Mild

Physicochemical

Animal Toxicology

Clinical Effects

11.1.2)

A) Clinical signs in cattle include diarrhea, ptyalism, edema of the hind limb phalanges, gangrene, and areas of skin necrosis (Gibbons, 1985; Bryson, 1990; (Holliman & Barnes, 1990; Hogg, 1991). Cattle are more sensitive than mice or swine (Coppock et al, 1989).

11.1.3)

A) Similar symptoms as in livestock, well as piloerection, have been noted in cats and dogs (Griffith et al, 1978).

11.1.6)

A) Similar symptoms as in livestock, as well as piloerection, have been noted in cats and dogs (Griffith et al, 1978).

11.1.13)

A) OTHER

1) Various conditions have been reported in cattle, sheep, horses, and swine feeding on grains infected with Claviceps purpurea (Burfening, 1973). These include:

a) "Nervous ergotism" (vertigo, staggering, seizures, drowsiness, paralysis, muscle spasms)
b) "Gangrenous ergotism" (necrosis of limbs, tails, and ears; temperature elevation, salivation, diarrhea, anorexia, tameness, tachycardia, tachypnea)
c) Abortion
d) Decreased milk production

Treatment

11.2.1)

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) SUMMARY -

1) REMOVE THE ANIMALS FROM THE SOURCE. Ergot commonly grows in rye, triticale, barley, oats, bromegrass, timothy, and quack grasses. Avoid pastures containing these grasses.

b) EMESIS/GASTRIC LAVAGE -

1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
3) DOGS AND CATS

a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

c) ACTIVATED CHARCOAL/CATHARTIC -

1) ACTIVATED CHARCOAL/HORSES: Administer 0.5 to 1 kilogram of activated charcoal in up to 1 gallon warm water via nasogastric tube. Neonates: administer 250 grams (one-half pound) activated charcoal in up to 2 quarts water.
2) ACTIVATED CHARCOAL/RUMINANTS: Administer 2 to 9 grams/ kilogram of activated charcoal in a slurry of 1 gram charcoal/3 to 5 milliliters warm water via stomach tube. Sheep may be given 0.5 kilogram charcoal in slurry.
3) CATHARTICS/HORSES: Mineral oil is administered 30 minutes after activated charcoal. DOSE: 4 to 6 liters in adult horses and 1 to 4 liters in neonates or foals.

a) Magnesium sulfate: 0.2 to 0.9 grams/kilogram (500 grams for adults).
b) The sulfate laxatives are especially effective when given 30 to 45 minutes after mineral oil administration.
c) Carbachol (lentin): administer 1 milligram to an adult.

4) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.

a) The sulfate laxatives are especially effective when given 30 to 45 minutes after cathartic administration.
b) Mineral oil: Do not administer within 30 minutes of activated charcoal. DOSE: small ruminants and swine, 60 to 200 milliliters; cattle, 0.5 to 1 gallon.
c) Magnesium oxide: (Milk of Magnesia) Small ruminants, up to 0.25 gram/kilogram in 1 to 3 gallons warm water; adult cattle up to 1 gram/kilogram in 1 to 3 gallons warm water or 2 to 4 boluses MgOH per os.
d) Give these solutions via stomach tube and monitor for aspiration.

11.2.5)

A) DOGS/CATS

1) MAINTAIN VITAL FUNCTIONS - as necessary.
2) ANTIBIOTICS may be indicated to control secondary bacterial infections.
3) NITROPRUSSIDE has been somewhat successful as intravenous infusion in alleviating the vasoconstriction (Beasley et al, 1989).
4) FOLLOW-UP -

a) Instruct the owner to return for a follow up appointment at which physical examination and appropriate laboratory tests will be repeated.

B) RUMINANTS/HORSES/SWINE

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
2) ANTIBIOTICS may be indicated to control secondary bacterial infections.
3) NITROPRUSSIDE has been somewhat successful as intravenous infusion in alleviating the vasoconstriction (Beasley et al, 1989).
4) KEEP THE ANIMAL WARM AND DRY. Control flies in hot weather, and prevent vasoconstriction from being exacerbated in cold weather.
5) FOLLOW-UP -

a) Instruct the owner to return for a follow up appointment at which physical examination and appropriate laboratory tests will be repeated.

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) SUMMARY -

1) REMOVE THE ANIMALS FROM THE SOURCE. Ergot commonly grows in rye, triticale, barley, oats, bromegrass, timothy, and quack grasses. Avoid pastures containing these grasses.

b) EMESIS/GASTRIC LAVAGE -

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

c) ACTIVATED CHARCOAL/CATHARTIC -

4) CATHARTICS/RUMINANTS & SWINE: Adult cattle: administer 500 grams sodium or magnesium sulfate. Other ruminants and swine: administer 1 to 2 grams/kilogram.

11.4.3)

11.4.3.5) SUPPORTIVE CARE

A) GENERAL

1) Ongoing treatment is symptomatic and supportive.

11.4.3.6) OTHER

A) OTHER

1) GENERAL

a) POSTMORTEM FINDINGS include swelling of pasterns, necrosis of the skin, multiple ulcerations of the abomasum, fibrin tags through the small and large intestines, and edema of the mesentery (Coppock et al, 1989).

References

General Bibliography

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FeedBack

ERGOT ALKALOIDS

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

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Genitourinary

Dermatologic

Musculoskeletal

Reproductive

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

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Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Toxicity Information

Pharmacologic Mechanism

Clinical Effects

Treatment

Continuing Care

General Bibliography