California Poison Control System – San Francisco Division Seizures and Hyperthermia Associated...

California Poison Control System – San Francisco Division

Seizures and Hyperthermia Seizures and Hyperthermia Associated with Poisoning or Associated with Poisoning or

Drug OverdoseDrug Overdose

Seizures and Hyperthermia Seizures and Hyperthermia Associated with Poisoning or Associated with Poisoning or

Drug OverdoseDrug Overdose

Kent R. Olson, MD, FACEP, FACMTMedical Director, San Francisco Division

California Poison Control System

University of California, San Francisco


Causes of Status Epilepticus in the EDCauses of Status Epilepticus in the EDCauses of Status Epilepticus in the EDCauses of Status Epilepticus in the ED

1980-1989 Urban SF Hospital – 154 pts

- Anticonvulsant drug withdrawal: 39

- Alcohol-related: 39

- Drug Toxicity: 14 (9%)

- CNS infection: 12

Lowenstein DH & Alldredge BK et al: Neurol 1993; 43


OutlineOutlineOutlineOutline

• Causes of drug-induced seizures (“drug” = drug or poison)

• Consequences and complications of drug-induced seizures

• Anticonvulsants for drug-induced seizures

• Management of drug-induced hyperthermia


CaseCaseCaseCase

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:


Case (continued)Case (continued)Case (continued)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.


Case (continued)Case (continued)Case (continued)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.


Complications of Drug-Induced SeizuresComplications of Drug-Induced SeizuresComplications of Drug-Induced SeizuresComplications of Drug-Induced Seizures

• Hypoxemia

• Shock Brain Damage

• Hyperthermia

• Rhabdomyolysis

• Metabolic acidosis

• Other drug-specific complications


Common Causes of Drug-Induced SeizuresCommon Causes of Drug-Induced Seizures Common Causes of Drug-Induced SeizuresCommon Causes of Drug-Induced Seizures

• Cocaine, amphetamines, other stimulants

• Tricyclic antidepressants

• Other antidepressants & antipsychotics

• Diphenhydramine

• Isoniazid

• Many others Olson KR et al: Am J Emerg Med 1993; 11:565-568


Calls to the SF Poison Center about drug-related seizures

0%

5%

10%

15%

20%

25%

30%

35%

1981

1989

2006


Treatment of Drug-Induced SeizuresTreatment of Drug-Induced SeizuresTreatment of Drug-Induced SeizuresTreatment of Drug-Induced Seizures

• ABCD’s: Airway Breathing Circulation Dextrose

• Anticonvulsants Specific antidote, if available

• Cooling measures


Antiepileptic-Drug Therapy for Status Epilepticus.

From: Lowenstein DH & Alldredge BK: NEJM 1998; 338:970


Anticonvulsants for Drug-Induced SeizuresAnticonvulsants for Drug-Induced SeizuresAnticonvulsants for Drug-Induced SeizuresAnticonvulsants for Drug-Induced Seizures

Benzodiazepine

Phenobarbital

Phenytoin?

Pentobarbital, Propofol, or Midazolam

Specific antidote,if available


Tricyclic and Related AntidepressantsTricyclic and Related AntidepressantsTricyclic and Related AntidepressantsTricyclic and Related Antidepressants

• Cardiotoxicity often worsened by seizures

Use bicarb to restore/maintain pH > 7.4

• Muscle twitching, absent sweating increase risk of hyperthermia

Consider neuromuscular paralysis

• No specific antidote for seizures Do not use physostigmine, phenytoin


Cocaine & AmphetaminesCocaine & AmphetaminesCocaine & AmphetaminesCocaine & Amphetamines

• Seizures are usually brief, self-limited Prolonged or multiple seizures suggests

complications such as intracranial hemorrhage, head injury, hyperthermia, etc

• Treatment: Sedation Anticonvulsants if needed Cooling measures


CaseCaseCaseCase

16 year old took 200 Benadryl™ tablets

Agitation, somnolence, seizure

Wide complex QRS


AntihistaminesAntihistaminesAntihistaminesAntihistamines

• 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


Isoniazid (INH)Isoniazid (INH)Isoniazid (INH)Isoniazid (INH)

• Common TB drug

• Marked lactic acidosis pH 6.8-6.9 common after even 1-2 brief

seizures

• Treatment of seizures: Diazepam often effective Pyridoxine is specific antidote - give 1 gm

for each gm OD; 5 gm if dose unknown


Pyridoxine for INH overdosePyridoxine for INH overdosePyridoxine for INH overdosePyridoxine for INH overdose

Glutamate GABA

Pyridoxal-5-phosphate

Glutamic Acid Decarboxylase

+

INH(-)

Pyridoxine (Vit B-6)(+)


CaseCaseCaseCase

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…


ZybanZyban™™ZybanZyban™™

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


Other antidepressants & etcOther antidepressants & etcOther antidepressants & etcOther antidepressants & etc

All the SSRI’s have been associated with seizures in OD

- Venlafaxine

- Fluoxetine

- Citalopram

Newer and older antipsychotics also


New Anticonvulsants Causing SeizuresNew Anticonvulsants Causing SeizuresNew Anticonvulsants Causing SeizuresNew Anticonvulsants Causing Seizures

• Lamotrigine

• Topiramate

• Tiagabine One case report of status epilepticus

resistant to benzos, controlled with propofolHaney ST et al: Internet J Toxicol 2004, 1(2)


Case of the hot taquitosCase of the hot taquitosCase of the hot taquitosCase 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


Case (cont.)Case (cont.)Case (cont.)Case (cont.)

Leftover taquitos were found to contain the pesticide endrin

Organochlorine pesticides DDT Endrin Aldrin Lindane


Another caseAnother caseAnother caseAnother case

36 year old man ingested some Elston Gopher Getter™ Bait

Developed “seizures” (diffuse tonic spasms) but remained awake during and between events


StrychnineStrychnineStrychnineStrychnine

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


Final “hot” caseFinal “hot” caseFinal “hot” caseFinal “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


Hot dude, cont.Hot dude, cont.Hot dude, cont.Hot dude, cont.

Utox negative

LP: meningitis!!


““Rule outs”Rule outs”““Rule outs”Rule outs”

“A T O M I C”

A: alcohol withdrawal

T: trauma/tomography

O: overdose

M: metabolic

I: infection

C: carbon monoxide


Hyperthermia (Temp > 40 C)Hyperthermia (Temp > 40 C)Hyperthermia (Temp > 40 C)Hyperthermia (Temp > 40 C)

Heat Production Heat Dissipation

Basal metabolism

Muscle activity

Ambient temperature

CORETEMP

Vasodilation

Conduction/Radiation

Evaporation


Drug-Induced Hyperthermia - MechanismsDrug-Induced Hyperthermia - MechanismsDrug-Induced Hyperthermia - MechanismsDrug-Induced Hyperthermia - Mechanisms

• Muscle hyperactivity: Cocaine, Amphetamines Seizures

• Reduced sweating: Anticholinergics

• Increased cellular metabolism: Salicylates Dintrophenol


Complications of HyperthermiaComplications of HyperthermiaComplications of HyperthermiaComplications of Hyperthermia

• Hypotension due to vasodilation, sweating, MI

• Brain injury from hypotension, hyperthermia, prolonged seizures, hypoxemia

• Coagulopathy due to reduced production of clotting factors, and endothelial wall damage

• Rhabdomyolysis caused by muscle hyperactivity, hyperthermia, and reduced muscle blood flow

• Renal failure from myoglobinuria, hyperthermia


Malignant HyperthermiaMalignant HyperthermiaMalignant HyperthermiaMalignant Hyperthermia

• Specific disorder of muscle cell

• Most commonly associated with general anesthetics (succinylcholine, halothane)

• Rigidity, acidosis, hyperthermia

• Specific treatment: Dantrolene NM paralysis is not effective


Neuroleptic Malignant SyndromeNeuroleptic Malignant SyndromeNeuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome

• Associated with chronic antipsychotic use (haloperidol, etc.)

• Mechanism is central dopamine blockade

• Lead-pipe rigidity, diaphoresis, altered mental status, hyperthermia

• Specific treatment: Bromocriptine? NM paralysis


Serotonin SyndromeSerotonin SyndromeSerotonin SyndromeSerotonin Syndrome

• SSRI OD or added to MAO inhibitors: also: MAOI + Meperidine, Trazodone,

Tryptophan, Dextromethorphan, others

• Confusion, agitation, increased muscle tone (especially lower extr. clonus)

• Specific Treatment: Cyproheptadine? NM paralysis


Anticholinergic SyndromeAnticholinergic SyndromeAnticholinergic SyndromeAnticholinergic Syndrome

• Dilated pupils, tachycardia, decreased bowel sounds, urinary retention

• Agitation, delirium, or coma

• Muscular twitching common

• Absent sweating

• Treatment: Physostigmine? (with caution) Usual cooling measures


Management of HyperthermiaManagement of HyperthermiaManagement of HyperthermiaManagement of Hyperthermia

Act quickly to prevent brain damage/deathAct quickly to prevent brain damage/death

ABC’sABC’s

DextroseDextrose

• Protect airway, assist ventilation• Give supplemental oxygen• IV fluid bolus if hypotensive

if needed based on bedside BS

AnticonvulsantsAnticonvulsants if seizures are present


Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)

Rapid external coolingRapid external cooling • Strip clothing• Tepid sponging + fanning• Do not use ice packs

Neuromuscular paralysisNeuromuscular paralysis

T > 106 F orpersistent sz ormuscle rigidity

• Most rapidly effective Rx• Use non-depolarizing agent


Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)Management of Hyperthermia (cont.)

Suspect muscle defect(malignant hyperthermia)

Suspect muscle defect(malignant hyperthermia)

persistent muscle rigiditydespite NM paralysis

• Give Dantrolene• Continue external cooling


Evaporative CoolingEvaporative CoolingEvaporative CoolingEvaporative Cooling

Weiner JS, Khogali M: A physiological body-cooling unit for treatment of heat stroke. Lancet. 1980;1(8167):507-9.


Some ReferencesSome ReferencesSome ReferencesSome References

1. Alvarez FG, Guntupalli KK. Isoniazid overdose: four case reports and review of the literature. Intensive Care Med. 1995 Aug;21(8):641-4.

2. Beaubien A et al. Antagonism of imipramine poisoning by anticonvulsants in the rat. Toxicol Appl Pharmacol 1976;38:1–6

3. 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

4. Centers for Disease Control (CDC). Endrin poisoning associated with taquito ingestion--California. MMWR Morb Mortal Wkly Rep. 1989 May

19;38(19):345-7.

5. Clark RF, Vance MV. Massive diphenhydramine poisoning resulting in a wide-complex tachycardia: successful treatment with sodium

bicarbonate.

6. Haney ST et al: Tiagabine-induced status epilepticus responds to propofol. Internet J Toxicol 2004, 1(2)

7. Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology 1993;43:483-488

8. Lowenstein DH & Alldredge BK: Status epilepticus. NEJM 1998; 338:970

9. Mayron R, Ruiz E. Phenytoin:does it reverse tricyclic antidepressant induced cardiac conduction abnormalities? Ann Emerg Med

1986;15:876–80

10. Olson KR, Benowitz NL. Environmental and drug-induced hyperthermia. Pathophysiology, recognition, and management. Emerg Med Clin

North Am. 1984 Aug;2(3):459-74.

11. Olson KR et al. Seizures associated with poisoning and drug overdose. Am J Emerg Med. 1994 May;12(3):392-5.

12. Stecker MM et al. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 1998;39:18-26

13. Yarbrough BE, Wood JP. Isoniazid overdose treated with high-dose pyridoxine. Ann Emerg Med. 1983 May;12(5):303-5.

14. 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.

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