Transcript Seizures and Hyperthermia Associated with Poisoning or Drug Overdose
Seizures and Hyperthermia Associated with Poisoning or Drug Overdose
Kent R. Olson, MD, FACEP, FACMT Medical Director, San Francisco Division California Poison Control System University of California, San Francisco California Poison Control System – San Francisco Division
Causes of Status Epilepticus in the ED
1980-1989 Urban SF Hospital – 154 pts
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Anticonvulsant drug withdrawal: 39
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Alcohol-related: 39
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Drug Toxicity: 14 (9%)
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CNS infection: 12
Lowenstein DH & Alldredge BK et al: Neurol 1993; 43
California Poison Control System – San Francisco Division
Outline
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Causes of drug-induced seizures (“drug” = drug or poison)
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Consequences and complications of drug-induced seizures
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Anticonvulsants for drug-induced seizures
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Management of drug-induced hyperthermia California Poison Control System – San Francisco Division
Case
A 27 yo man was admitted with an unknown drug overdose, unresponsive but breathing. Pupils 5 mm. Absent bowel sounds. Frequent jerking movements.
BP 120/80, HR 100/min ECG: California Poison Control System – San Francisco Division
California Poison Control System – San Francisco Division
Case (continued)
Shortly after admission he developed recurrent generalized seizures. With the onset of seizures, the QRS interval increased to 0.20 sec. The BP fell to 70 mm systolic, and dopamine and norepinephrine were given. California Poison Control System – San Francisco Division
California Poison Control System – San Francisco Division
Case (continued)
Three hours after admission, the rectal temperature was noted to be 107 F.
Despite intensive supportive care, he developed multi-organ failure and died.
California Poison Control System – San Francisco Division
Complications of Drug-Induced Seizures
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Hypoxemia
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Shock
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Hyperthermia
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Rhabdomyolysis Brain Damage
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Metabolic acidosis
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Other drug-specific complications California Poison Control System – San Francisco Division
Common Causes of Drug-Induced Seizures
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Cocaine, amphetamines, other stimulants
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Tricyclic antidepressants
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Other antidepressants & antipsychotics
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Diphenhydramine
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Isoniazid
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Many others
Olson KR et al: Am J Emerg Med 1993; 11:565-568
California Poison Control System – San Francisco Division
35% 30% 25%
Calls to the SF Poison Center about drug related seizures
20% 15% 10% 5% 1981 1989 2006 0% TC A s Is on ia zi d Th eo ph yl lin e D ip he nh yd ra m in e S tim ul an ts B up ro pi on N S ew SR a Is nt ic on vu ls an ts
California Poison Control System – San Francisco Division
Treatment of Drug-Induced Seizures
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ABCD’s:
Airway
Breathing
Circulation
Dextrose
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Anticonvulsants
Specific antidote, if available
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Cooling measures California Poison Control System – San Francisco Division
Antiepileptic-Drug Therapy for Status Epilepticus.
From: Lowenstein DH & Alldredge BK: NEJM 1998; 338:970 California Poison Control System – San Francisco Division
Anticonvulsants for Drug-Induced Seizures Benzodiazepine Specific antidote, if available Phenytoin?
Phenobarbital Pentobarbital, Propofol, or Midazolam California Poison Control System – San Francisco Division
Tricyclic and Related Antidepressants
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Cardiotoxicity often worsened by seizures
Use bicarb to restore/maintain pH > 7.4
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Muscle twitching, absent sweating increase risk of hyperthermia
Consider neuromuscular paralysis
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No specific antidote for seizures
Do not use physostigmine, phenytoin California Poison Control System – San Francisco Division
Cocaine & Amphetamines
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Seizures are usually brief, self-limited
Prolonged or multiple seizures suggests complications such as intracranial hemorrhage, head injury, hyperthermia, etc
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Treatment:
Sedation
Anticonvulsants if needed
Cooling measures California Poison Control System – San Francisco Division
Case
16 year old took 200 Benadryl ™ tablets Agitation, somnolence, seizure Wide complex QRS California Poison Control System – San Francisco Division
Antihistamines
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Diphenhydramine is most common
Seizures usually brief, self-limited
Accompanied by mild-moderate anticholinergic findings
Massive diphenhydramine OD may cause TCA-like cardiotoxicity Treatment:
Anticonvulsants if needed
Bicarbonate for TCA-like QRS prolongation California Poison Control System – San Francisco Division
Isoniazid (INH)
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Common TB drug
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Marked lactic acidosis
pH 6.8-6.9 common after even 1-2 brief seizures
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Treatment of seizures:
Diazepam often effective
Pyridoxine is specific antidote - give 1 gm for each gm OD; 5 gm if dose unknown California Poison Control System – San Francisco Division
Pyridoxine for INH overdose
INH ( ) Pyridoxal-5 phosphate + Glutamic Acid Decarboxylase (+) Pyridoxine (Vit B-6) Glutamate GABA California Poison Control System – San Francisco Division
Case
28 year old man had a seizure and was brought to the ER by a friend Tox screen (+) for amphetamines But, he denied amphetamine use
He had borrowed one of his friend’s pills, which had been obtained from…
California Poison Control System – San Francisco Division
California Poison Control System – San Francisco Division
Zyban ™
Bupropion
Antidepressant = Wellbutrin ™
Well-known cause of seizures
Can occur even at therapeutic antidepressant doses
Can give false-positive result for amphetamines on tox screening California Poison Control System – San Francisco Division
Other antidepressants & etc
All the SSRI’s have been associated with seizures in OD - Venlafaxine - Fluoxetine - Citalopram Newer and older antipsychotics also California Poison Control System – San Francisco Division
New Anticonvulsants Causing Seizures
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Lamotrigine
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Topiramate
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Tiagabine
One case report of status epilepticus resistant to benzos, controlled with propofol Haney ST et al: Internet J Toxicol 2004, 1(2) California Poison Control System – San Francisco Division
Case of the hot taquitos
5 people with new onset seizures None had prior sz Utox negative All had eaten taquitos purchased from a convenience store California Poison Control System – San Francisco Division
Case (cont.)
Leftover taquitos were found to contain the pesticide endrin Organochlorine pesticides
DDT
Endrin
Aldrin
Lindane California Poison Control System – San Francisco Division
Another case
36 year old man ingested some Elston Gopher Getter ™ Bait Developed “seizures” (diffuse tonic spasms) but remained awake during and between events California Poison Control System – San Francisco Division
Strychnine
Popular poison for thousands of years
Strychnos nux vomica
Not true “seizures” as CNS is minimally affected (until victim is hypoxic) Spinal cord glycine receptor action
Inhibits inhibitory action of glycine on spinal cord reflex motor response
Similar to tetanus California Poison Control System – San Francisco Division
Final “hot” case
21 yo released from a drug rehab facility for a home visit Became agitated, combative, shoving his brother, talking nonsense
GM seizure HR 160/min, T 105.7 F Skin red, dry Incontinent California Poison Control System – San Francisco Division
Hot dude, cont.
Utox negative LP: meningitis!!
California Poison Control System – San Francisco Division
“Rule outs”
“A T O M I C” A: alcohol withdrawal T: trauma/tomography O: overdose M: metabolic I: infection C: carbon monoxide California Poison Control System – San Francisco Division
Hyperthermia (Temp > 40 C)
Heat Production Basal metabolism Heat Dissipation Vasodilation Muscle activity CORE TEMP Conduction/Radiation Ambient temperature Evaporation California Poison Control System – San Francisco Division
Drug-Induced Hyperthermia - Mechanisms
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Muscle hyperactivity:
Cocaine, Amphetamines
Seizures
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Reduced sweating:
Anticholinergics
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Increased cellular metabolism:
Salicylates
Dintrophenol California Poison Control System – San Francisco Division
Complications of Hyperthermia
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Hypotension due to vasodilation, sweating, MI
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Brain injury from hypotension, hyperthermia, prolonged seizures, hypoxemia
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Coagulopathy due to reduced production of clotting factors, and endothelial wall damage
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Rhabdomyolysis caused by muscle hyperactivity, hyperthermia, and reduced muscle blood flow
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Renal failure from myoglobinuria, hyperthermia California Poison Control System – San Francisco Division
Malignant Hyperthermia
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Specific disorder of muscle cell
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Most commonly associated with general anesthetics (succinylcholine, halothane)
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Rigidity, acidosis, hyperthermia
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Specific treatment:
Dantrolene
NM paralysis is not effective California Poison Control System – San Francisco Division
Neuroleptic Malignant Syndrome
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Associated with chronic antipsychotic use (haloperidol, etc.)
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Mechanism is central dopamine blockade
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Lead-pipe rigidity, diaphoresis, altered mental status, hyperthermia
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Specific treatment:
Bromocriptine?
NM paralysis California Poison Control System – San Francisco Division
Serotonin Syndrome
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SSRI OD or added to MAO inhibitors:
also: MAOI + Meperidine, Trazodone, Tryptophan, Dextromethorphan, others
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Confusion, agitation, increased muscle tone (especially lower extr. clonus)
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Specific Treatment:
Cyproheptadine?
NM paralysis California Poison Control System – San Francisco Division
Anticholinergic Syndrome
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Dilated pupils, tachycardia, decreased bowel sounds, urinary retention Agitation, delirium, or coma Muscular twitching common Absent sweating Treatment:
Physostigmine? (with caution)
Usual cooling measures California Poison Control System – San Francisco Division
Management of Hyperthermia
Act quickly to prevent brain damage/death
ABC’s
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Protect airway, assist ventilation Give supplemental oxygen IV fluid bolus if hypotensive Dextrose if needed based on bedside BS Anticonvulsants if seizures are present California Poison Control System – San Francisco Division
Management of Hyperthermia (cont.)
Rapid external cooling
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Strip clothing Tepid sponging + fanning Do not use ice packs
T > 106 F or persistent sz or muscle rigidity
Neuromuscular paralysis
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Most rapidly effective Rx Use non-depolarizing agent California Poison Control System – San Francisco Division
Management of Hyperthermia (cont.)
persistent muscle rigidity despite NM paralysis
Suspect muscle defect (malignant hyperthermia)
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Give Dantrolene Continue external cooling California Poison Control System – San Francisco Division
Evaporative Cooling
Weiner JS, Khogali M: A physiological body-cooling unit for treatment of heat stroke. Lancet. 1980;1(8167):507-9.
California Poison Control System – San Francisco Division
Some References
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Alvarez FG, Guntupalli KK. Isoniazid overdose: four case reports and review of the literature. Intensive Care Med. 1995 Aug;21(8):641-4.
Beaubien A et al. Antagonism of imipramine poisoning by anticonvulsants in the rat. Toxicol Appl Pharmacol 1976;38:1 –6 Blake KV et al: Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice. Ann Emerg Med. 1988 Oct;17(10):1024-8 Centers for Disease Control (CDC). Endrin poisoning associated with taquito ingestion--California. MMWR Morb Mortal Wkly Rep. 1989 May 19;38(19):345-7. Clark RF, Vance MV. Massive diphenhydramine poisoning resulting in a wide-complex tachycardia: successful treatment with sodium bicarbonate.
Haney ST et al: Tiagabine-induced status epilepticus responds to propofol. Internet J Toxicol 2004, 1(2) Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology 1993;43:483-488 Lowenstein DH & Alldredge BK: Status epilepticus. NEJM 1998; 338:970 Mayron R, Ruiz E. Phenytoin:does it reverse tricyclic antidepressant induced cardiac conduction abnormalities? Ann Emerg Med 1986;15:876 –80 Olson KR, Benowitz NL. Environmental and drug-induced hyperthermia. Pathophysiology, recognition, and management. Emerg Med Clin North Am. 1984 Aug;2(3):459-74. Olson KR et al. Seizures associated with poisoning and drug overdose. Am J Emerg Med. 1994 May;12(3):392-5. Stecker MM et al. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 1998;39:18-26 Yarbrough BE, Wood JP. Isoniazid overdose treated with high-dose pyridoxine. Ann Emerg Med. 1983 May;12(5):303-5. Wood DM et al: Case report: Survival after deliberate strychnine self-poisoning, with toxicokinetic data. it Care. 2002; 6(5): 456 –459 Ann Emerg Med. 1992 Mar;21(3):318-21.
California Poison Control System – San Francisco Division