Seizures

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DESCRIPTION

Seizure is an abrupt onset of involuntary muscle activity associated with loss of consciousness, possibly associated with a toxic exposure.
See also the chapter on movement disorders.

PATHOPHYSIOLOGY

Most seizures associated with toxic causes are generalized, tonic-clonic seizures.
Typically, a seizure of toxic origin is caused by metabolic changes or alteration in the neurotransmitter levels within the brain (e.g., inhibition of gamma aminobutyric acid activity).

EPIDEMIOLOGY

Seizures are a common toxic effect of drugs.
Permanent sequelae or death may occur if prolonged, repeated seizures occur.

RISK FACTORS

Patients with an underlying seizure disorder are more likely to develop seizures as a toxic effect.

PREGNANCY AND LACTATION

Seizure in a pregnant patient should always suggest eclampsia.

Section Outline:

DESCRIPTION
PATHOPHYSIOLOGY
EPIDEMIOLOGY
RISK FACTORS
PREGNANCY AND LACTATION

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DIFFERENTIAL DIAGNOSIS

Common Toxicologic Causes

Antihistamines/anticholinergic agents. Associated with dry mouth, tachycardia, decreased bowel activity, and delirium
Buproprion. Self-limited seizures and, often, tachycardia
Camphor. Usually occurring in children and associated with a "mothball" odor
Carbon monoxide. Headache and nausea; often, simultaneous multiple victims
Cocaine/amphetamines. Agitation, tachycardia, hypertension, and hyperthermia
Ergotamine. Peripheral vasospasm, cyanosis, and vomiting
Hydrocarbons. Strong "solvent" odor; pulmonary edema if toxin is aspirated
Isoniazid. Seizures refractory to standard therapy; often involving patient under treatment for tuberculosis
Lithium. Vomiting, altered mental status, fasciculations, hyperactive reflexes, and clonus
Meperidine or propoxyphene. CNS depression, miosis, and respiratory depression
Oral hypoglycemic agents or insulin. Hypoglycemia, delirium, and diaphoresis
Organophosphate or carbamate insecticide. Salivation, vomiting, diarrhea, diaphoresis, and pulmonary edema
Phencyclidine. Nystagmus, marked agitation, and delirium
Phenothiazines. Dry mouth, tachycardia, decreased bowel activity, and history of psychiatric illness
Salicylate. Tachypnea and, prior to seizure, anion gap acidosis
Theophylline. Tachycardia (often marked), vomiting, hypokalemia, and tremors
Tricyclic antidepressants (TCAs). Tachycardia, QRS widening, coma, and hypotension

Uncommon Toxicologic Causes

Butyrophenones. Somnolence and history of psychiatric illness
DEET. Usually a small child treated with mosquito repellent
Chloroquine. Cardiovascular collapse and wide complex tachycardia
Lindane. History of recent treatment for scabies
Lead. Anemia, encephalopathy, or abdominal pain
Local anesthetics. Seizures often preceded by tingling and flushing
Monoamine oxidase (MAO) inhibitors. Hyperthermia, autonomic instability, coma, and muscular rigidity
Strychnine. Intermittent severe muscular spasms with normal mental status (not true seizures)
Water hemlock. History of ingestion of a plant root found near water

Nontoxicologic Causes

CNS infections, including meningitis, encephalitis, and abscess
Structural abnormalities, including subdural hematoma, epidural hematoma, intracerebral bleed, cerebral contusion, CNS tumors, stroke, subarachnoid hemorrhage, and cerebral edema
Metabolic, including hypoxia, hypoglycemia, and electrolyte abnormalities
Idiopathic, including epilepsy
Withdrawal from ethanol or sedative-hypnotic agents, which may also present with tremor, hypertension, tachycardia, low-grade fever, and hallucinosis
Pseudoseizures should be suspected in patients with a psychiatric history, atypical seizures, asynchronous extremity movement, eyes rolled back into the head or a lack of postictal period; however, this diagnosis can rarely be made in the emergency department.

SYMPTOMS AND SIGNS

Associated physical signs may help reveal the poison involved when they are associated with a seizure.

Vital Signs

Tachycardia, hypertension, and hyperthermia suggest cocaine, amphetamines, other stimulants, MAO inhibitor, neuroleptic malignant syndrome, serotonin syndrome, or withdrawal from benzodiazepines, ethanol, or barbiturates.
Tachycardia and hypotension suggest TCAs, theophylline, quinidine, or chloroquine.
Bradycardia and hypotension suggest propranolol, organophosphate, or carbamate insecticides.

HEENT

Dry mucous membranes and large pupils suggest anticholinergic drugs, antihistamines, or TCAs.
Small pupils suggests meperidine, propoxyphene, organophosphate, or carbamate insecticide.
Nystagmus suggests PCP, carbamazepine, or other anticonvulsants.

Dermatologic

Diaphoresis suggests cocaine, amphetamines, organophosphate, or carbamate insecticide, or withdrawal from agents such as benzodiazepines, ethanol, or barbiturates.
Dermatitis and excoriations may suggest that the patient received lindane therapy for scabies.

Cardiovascular

Tachycardia, QRS greater than 100 msec (0.1 sec), and hypotension suggest TCAs, type 1 antidysrhythmic agents, quinine, or chloroquine.
Peripheral vasospasm and cyanosis suggest ergot toxicity.

Pulmonary

Increased pulmonary secretions and pulmonary edema suggest exposure to organophosphate or carbamate insecticide or nicotine, or mushroom ingestion.
Noncardiogenic pulmonary edema suggests hydrocarbon aspiration, salicylate, or camphor.

Gastrointestinal

Recurrent vomiting or diarrhea suggests organophosphates, carbamates, lithium, or mushrooms.

Hepatic

Hepatic injury suggests chlorinated hydrocarbons.

Renal

Diabetes insipidus suggests lithium.

Fluids and Electrolytes

Hypokalemia suggests theophylline.

Musculoskeletal

Rhabdomyolysis may occur with any cause of seizures.
Fasciculation and tremor suggests theophylline, lithium, organophosphates, or carbamates.
Muscular rigidity suggests MAO inhibitors, neuroleptic malignant syndrome, or serotonin syndrome.
Opisthotonos suggests strychnine.

Neurologic

Agitation and psychosis are seen with cocaine, amphetamines, hypoxia from any cause, PCP or other hallucinogens, or withdrawal from agents such as benzodiazepines, ethanol, or barbiturates.
Seizures refractory to standard therapy suggest isoniazid exposure.
Ataxia, coma, and somnolence suggest propoxyphene, meperidine, carbamazepine, chlorinated hydrocarbons, carbon monoxide, butyrophenones, or phenothiazines.

Endocrine

Hypoglycemia suggests insulin, oral hypoglycemics, or propranolol.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Serum electrolytes, BUN, creatinine, and rapid glucose test should be obtained in all patients. An increased anion gap acidosis that clears promptly over 2 to 3 hours may follow seizures.
ECG is used to evaluate QRS duration for possible ingestion of TCA, phenothiazine, or antidysrhythmic agent.
Arterial blood gases and pulse oximetry assess oxygenation and effects on respiration.

Recommended Tests

Serum acetaminophen and aspirin levels and urine toxicology screen are used to detect occult ingestion.
Serum levels of anticonvulsants are measured to assess potential noncompliance or seizure induced by anticonvulsant toxicity.
Carboxyhemoglobin level is measured if inhalation exposure to carbon monoxide was possible.
Serum drug levels are measured as indicated: salicylate, theophylline, red blood cell or plasma cholinesterase.
Head CT, lumbar puncture, bacterial cultures, and other tests are used as needed to assess altered mental status.

Section Outline:

DIFFERENTIAL DIAGNOSIS
SYMPTOMS AND SIGNS
PROCEDURES AND LABORATORY TESTS
- Essential Tests
- Recommended Tests

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Focus therapy on appropriate airway management and immediate treatment of seizures.
Dose and time of exposure should be determined for all substances involved.

DECONTAMINATION

Out of Hospital

Emesis should be avoided.

In Hospital

Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ADJUNCTIVE TREATMENT

Endotracheal intubation may prevent pulmonary aspiration.
It is vital to determine glucose and oxygen concentrations rapidly.
Supplemental oxygen should be administered.
Benzodiazepine is administered for initial control, while monitoring the airway closely.
- Diazepam. Adult, 5 to 10 mg intravenous push over 2 to 5 minutes, repeated every 10 minutes as needed; pediatric, 0.2 to 0.5 mg/kg every 10 minutes as needed.
- Lorazepam. Adult, 2 to 4 mg intravenous push over 2 to 5 minutes, repeated every 10 minutes as needed; pediatric, 0.1 mg/kg intravenous push over 2 to 5 minutes (not to exceed 4 mg/dose), repeated every 10 minutes as needed.
Seizure unresponsive to benzodiazepine
- Phenobarbital should be given (after intubation due to respiratory depression).
- Pediatric and adult dose is 18 mg/kg intravenously.
- Rate of infusion should not exceed 60 to 100 mg/min.
- Rapid infusion may cause hypotension.
Seizure unresponsive to phenobarbital
- Patient must be intubated.
- Neuromuscular blockade is performed with a nondepolarizing agent to prevent ongoing acidosis and muscle injury.
- Paralyzed patients should have continual EEG monitoring as nonconvulsive status epilepticus can result in ongoing brain injury.
- Patients with ongoing EEG evidence of seizures should receive intravenous bolus of pentobarbital, 5 to 6 mg/kg at 25 mg/min, followed by 1.0 to 3.0 mg/kg/hr infusion, titrated to EEG effect.
Phenytoin is considered less effective for seizure of toxic origin but is not contraindicated.

ANTIDOTES

Pyridoxine

Indications. Seizures of unknown etiology that are refractory to standard measures
Dosage and method of use. Pyridoxine should be administered empirically. The dose is 5 g administered intravenously. If needed, the dose is repeated once in 30 minutes. Unless the patient received a known isoniazid overdose (in which case a gram-for-gram treatment is used) the treatment should not exceed 10 g.

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