SPI Webcast Seizures and Hyperthermia Associated with Poisoning or Drug Overdose

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SPI WebcastSeizures and Hyperthermia Associated
with Poisoning or Drug Overdose

• Speaker Kent R. Olson, MD, FACEP, FACMT,
• Medical Director, San Francisco Division,
  California Poison Control System. University of
  California, San Francisco
• Moderator Kathryn Meier, PharmD, DABAT, CSPI
• San Francisco Division, California Poison Control
  System. University of California, San Francisco
• Thursday, August 31, 2006, 1200-1345 PST
• Sponsored by HRSA

2
Moderators Opening Comments

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3
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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

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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

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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

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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

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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.

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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.

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Complications of Drug-Induced Seizures

• Hypoxemia
• Shock Brain Damage
• Hyperthermia
• Rhabdomyolysis
• Metabolic acidosis
• Other drug-specific complications

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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
  11565-568

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Calls to the SF Poison Center about drug-related
seizures
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Treatment of Drug-Induced Seizures

• ABCDs
• Airway
• Breathing
• Circulation
• Dextrose
• Anticonvulsants
• Specific antidote, if available
• Cooling measures

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Antiepileptic-Drug Therapy for Status Epilepticus.
From Lowenstein DH Alldredge BK NEJM 1998
338970
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Anticonvulsants for Drug-Induced Seizures
Specific antidote, if available
Benzodiazepine
Phenytoin?
Phenobarbital
Pentobarbital, Propofol, or Midazolam
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Tricyclic and Related Antidepressants

• Cardiotoxicity often worsened by seizures
• Use bicarb to restore/maintain pH gt 7.4
• Muscle twitching, absent sweating increase risk
  of hyperthermia
• Consider neuromuscular paralysis
• No specific antidote for seizures
• Do not use physostigmine, phenytoin

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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

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Case

• 16 year old took 200 Benadryl tablets
• Agitation, somnolence, seizure
• Wide complex QRS

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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

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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

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Pyridoxine for INH overdose
(-)
()
Pyridoxal-5- phosphate
INH
Pyridoxine (Vit B-6)

Glutamic Acid Decarboxylase
GABA
Glutamate
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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 friends pills, which
  had been obtained from

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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

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Other antidepressants etc

• All the SSRIs have been associated with seizures
  in OD
• - Venlafaxine
• - Fluoxetine
• - Citalopram
• Newer and older antipsychotics also

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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)

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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

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Case (cont.)

• Leftover taquitos were found to contain the
  pesticide endrin
• Organochlorine pesticides
• DDT
• Endrin
• Aldrin
• Lindane

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Another case

• 36 year old man ingested some Elston Gopher
  Getter Bait
• Developed seizures (diffuse tonic spasms) but
  remained awake during and between events

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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

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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

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Hot dude, cont.

• Utox negative
• LP meningitis!!

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Rule outs

• A T O M I C
• A alcohol withdrawal
• T trauma/tomography
• O overdose
• M metabolic
• I infection
• C carbon monoxide

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Hyperthermia (Temp gt 40 C)
Heat Production
Heat Dissipation
Basal metabolism
Vasodilation
CORE TEMP
Muscle activity
Conduction/Radiation
Ambient temperature
Evaporation
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Drug-Induced Hyperthermia - Mechanisms

• Muscle hyperactivity
• Cocaine, Amphetamines
• Seizures
• Reduced sweating
• Anticholinergics
• Increased cellular metabolism
• Salicylates
• Dintrophenol

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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

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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

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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

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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

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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

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Management of Hyperthermia

• Act quickly to prevent brain damage/death

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

ABCs
Dextrose
if needed based on bedside BS
Anticonvulsants
if seizures are present
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Management of Hyperthermia (cont.)
Rapid external cooling

• Strip clothing
• Tepid sponging fanning
• Do not use ice packs

T gt 106 F or persistent sz or muscle rigidity
Neuromuscular paralysis

• Most rapidly effective Rx
• Use non-depolarizing agent

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Management of Hyperthermia (cont.)
persistent muscle rigidity despite NM paralysis
Suspect muscle defect (malignant hyperthermia)

• Give Dantrolene
• Continue external cooling

46
Evaporative Cooling
Weiner JS, Khogali M A physiological
body-cooling unit for treatment of heat stroke.
Lancet. 19801(8167)507-9.
47
Some References

• Alvarez FG, Guntupalli KK. Isoniazid overdose
  four case reports and review of the literature.
  Intensive Care Med. 1995 Aug21(8)641-4.
• Beaubien A et al. Antagonism of imipramine
  poisoning by anticonvulsants in the rat. Toxicol
  Appl Pharmacol 19763816
• Blake KV et al Relative efficacy of phenytoin
  and phenobarbital for the prevention of
  theophylline-induced seizures in mice. Ann Emerg
  Med. 1988 Oct17(10)1024-8
• Centers for Disease Control (CDC). Endrin
  poisoning associated with taquito
  ingestion--California. MMWR Morb Mortal Wkly Rep.
  1989 May 1938(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 199343483-488
• Lowenstein DH Alldredge BK Status epilepticus.
  NEJM 1998 338970
• Mayron R, Ruiz E. Phenytoindoes it reverse
  tricyclic antidepressant induced cardiac
  conduction abnormalities? Ann Emerg Med
  19861587680
• Olson KR, Benowitz NL. Environmental and
  drug-induced hyperthermia. Pathophysiology,
  recognition, and management. Emerg Med Clin North
  Am. 1984 Aug2(3)459-74.
• Olson KR et al. Seizures associated with
  poisoning and drug overdose. Am J Emerg Med. 1994
  May12(3)392-5.
• Stecker MM et al. Treatment of refractory status
  epilepticus with propofol clinical and
  pharmacokinetic findings. Epilepsia 19983918-26
• Yarbrough BE, Wood JP. Isoniazid overdose treated
  with high-dose pyridoxine. Ann Emerg Med. 1983
  May12(5)303-5.
• Wood DM et al Case report Survival after
  deliberate strychnine self-poisoning, with
  toxicokinetic data. it Care. 2002 6(5) 456459
  Ann Emerg Med. 1992 Mar21(3)318-21.

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Moderator Closing Comments

• Registration If there were multiple viewers from
  your computer - forward the total count of
  participants and names (esp. if those persons
  wish to receive CE Credits.)
• CE Credits
• -Complete the exam evaluation located at
• www.aapcc.org -gt More for Members -gt
  Presentations
• -Email or fax completed test by 9/15/06 to
• ann.slattery_at_chsys.org or A.Slattery,
  205-939-9245
• Include Name, Poison Center affiliation, email
  mailing address
• Indicate either Nursing or Pharmacy CE credits.
• A score gt 70 is needed to pass, One retake is
  permitted if needed.
• CE certificates will be mailed to the address
  you provided.
• 3. Please complete the evaluation even if no CE
  is requested.