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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
- Anticonvulsant drug withdrawal: 39
- Alcohol-related: 39
- Drug Toxicity: 14 (9%)
- CNS infection: 12
Lowenstein DH & Alldredge BK et al: Neurol 1993; 43
California Poison Control System – San Francisco Division
Outline
• 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
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
• Hypoxemia
• Shock
Brain Damage
• Hyperthermia
• Rhabdomyolysis
• Metabolic acidosis
• Other drug-specific complications
California Poison Control System – San Francisco Division
Common 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
California Poison Control System – San Francisco Division
35%
30%
25%
Calls to the
20%
SF Poison
Center
about drug- 15%
related
10%
seizures
1981
1989
2006
5%
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SS
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0%
California Poison Control System – San Francisco Division
Treatment of Drug-Induced Seizures
• ABCD’s:
Airway
 Breathing
 Circulation
 Dextrose

• Anticonvulsants

Specific antidote, if available
• 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
• 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
California Poison Control System – San Francisco Division
Cocaine & 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

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
• 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)
• 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

California Poison Control System – San Francisco Division
Pyridoxine for INH overdose
INH
( -)
Pyridoxal-5phosphate
(+)
Pyridoxine (Vit B-6)
+
Glutamic Acid
Decarboxylase
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
• Lamotrigine
• Topiramate
• 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
Heat Dissipation
Basal metabolism
Vasodilation
Muscle activity
Ambient temperature
CORE
TEMP
Conduction/Radiation
Evaporation
California Poison Control System – San Francisco Division
Drug-Induced Hyperthermia - Mechanisms
• Muscle hyperactivity:
Cocaine, Amphetamines
 Seizures

• Reduced sweating:

Anticholinergics
• Increased cellular metabolism:
Salicylates
 Dintrophenol

California Poison Control System – San Francisco Division
Complications 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
California Poison Control System – San Francisco Division
Malignant 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

California Poison Control System – San Francisco Division
Neuroleptic 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

California Poison Control System – San Francisco Division
Serotonin 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
California Poison Control System – San Francisco Division
Anticholinergic 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

California Poison Control System – San Francisco Division
Management of Hyperthermia
Act quickly to prevent brain damage/death
ABC’s
• 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 • Strip clothing
T > 106 F or
persistent sz or
muscle rigidity
• Tepid sponging + fanning
• Do not use ice packs
Neuromuscular paralysis • 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)
• 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
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.
California Poison Control System – San Francisco Division