CONVULSIONS DEFINITIONS 1. Acute generalized convulsion: paroxysmal discharge of cerebral neurons resulting in a brief clinical phenomenon characterized by loss of consciousness and generalized involuntary tonic and clonic contractions of the skeletal muscles. 2. Acute focal convulsion: paroxysmal discharge of localized central neurons (e.g. petit mal, temporal, focal motor). 3. Status epilepticus: continued unremitting convulsions or several consecutive episodes without intervening restoration of consciousness. TOXIC CAUSES Pharmaceuticals Antihistamines Camphor Carbamazepine Carbon monoxide Chlorambucil Cyclic antidepressants Cyclosporine Ergot alkaloids Hypoglycaemic agents Isoniazid Lithium salts Local anaesthetics Mefenamic acid Metronidazole Nicotine Penicillin Pentazocine Pethidine (meperidine) Phenothiazines Physostigmine Propoxyphene Salicylates Xanthine derivatives (theophylline, caffeine) Drugs of abuse Amphetamines and derivatives (e.g. MDMA/"ecstasy") Cocaine PCP (phencyclidine) Pesticides Carbamates Organochlorines Organophosphorus compounds Strychnine Others Hyperbaric oxygen Ethanol and sedative-hypnotic drug withdrawal syndrome Heavy metals (e.g., lead in children) NON-TOXIC CAUSES Structural Haemorrhage Tumour Trauma Non-structural Cardiac arrhythmia Fever Hypoxia Hypoglycaemia Infection Metabolic CLINICAL FEATURES Toxic convulsions are characterized by generalized involuntary tonic and clonic contractions of skeletal muscles. There may be evidence of physical injury (e.g.: tongue biting) and/or incontinence. The post-convulsive state may be associated with coma or altered CNS function ("Todd's paralysis"). Acute complications may include pulmonary aspiration of gastric contents, hypoventilation, hypoxia, metabolic acidosis, cardiac arrhythmias, rhabdomyolysis, and sudden death. DIFFERENTIAL DIAGNOSIS Abnormal movements (dyskinesia, myoclonic jerking, dystonic reactions) Muscular hyperactivity and/or rigidity Malingering, hysteria (pseudoseizures) Tetany or tetanus Fasciculations due to organophosphorus or carbamate poisoning RELEVANT INVESTIGATIONS The following investigations should be performed routinely: Blood glucose Serum electrolytes including calcium Additional tests that may be clinically relevant include: Arterial blood gases Cerebrospinal fluid analysis Creatine phosphokinase CT Scan head EEG Serum magnesium Serum anticonvulsant concentrations Toxicological screening. TREATMENT Most toxic convulsions are brief, lasting from a few seconds to a few minutes, and usually do not require pharmacological intervention. However, if the seizure is prolonged, or if status epilepticus supervenes, urgent medical intervention is required. Status epilepticus is an acute medical emergency. Suggested treatment protocols for adults and children are as follows: Initial Management Protect patient from self-inflicted injury; remove false teeth if present; establish a clear airway and give high flow oxygen by mask. Place the patient in lateral semiprone position. Establish intravenous access. Glucose. If rapid bedside glucose measurement indicates low blood sugar, administer intravenous glucose (adults: 25 g IV; children: 0.5 to 1 g/kg IV, as 25% dextrose). Benzodiazepines: (Note - patients should be carefully monitored for evidence of respiratory depression and hypotension during administration.) 1. Give Diazepam 10 mg intravenously (0.15 to 0.25 mg/kg) over 1 minute. If convulsions continue, give a further 10 mg over 1 minute. This may be repeated if necessary. Diazepam may be given IM, but absorption is erratic and this route is not recommended. Rectal administration has been used in children (0.5 mg/kg) when IV access is not readily available. 2. Lorazepam (0.1 mg/kg IV at 1 to 2 mg/minute up to a maximum of 10 mg) or Clonazepam (0.5 to 1mg IV) may be used instead of diazepam. Also consider midazolam, which is rapidly absorbed after intramuscular administration (IM dose: 0.1-0.2 mg/kg). If convulsions are difficult to control with large doses of benzodiazapines, the following drugs may be considered: Phenobarbitone (Phenobarbital) 15 mg/kg intravenously slowly (e.g. 2 mg/kg/min). Repeat doses may be given, up to a total dose of 30 mg/kg. Monitor blood pressure and heart rate during infusion. Hypotension may occur. Observation of respiratory state is mandatory and assisted ventilation may be required. Phenytoin. As an alternative to phenobarbitone, administer phenytoin 15 to 20 mg/kg body weight IV in 0.9% normal saline (1 g in 250 mL), to be given no faster than 50 mg/kg/minute. Monitor cardiac rhythm and blood pressure. Rapid infusion of intravenous phenytoin may cause acute hypotension, AV block, or asystole. (Note: phenytoin is not effective for patients with seizures caused by theophylline and may be dangerous in patients with tricyclic antidepressant overdose). Thiopentone. If control of convulsions is not achieved with the preceding drugs, general anaesthesia with thiopentone should be instituted (adult dose: 500mg diluted in 20 mL administered intravenously over 2 to 3 minutes or until the convulsion stops. Consider maintenance infusion at 2 to 4g/24hrs). Mechanical ventilation is required, and heart rate and blood pressure should be monitored. Note: If neuromuscular relaxants are given to control muscular hyperactivity, EEG monitoring must be instituted because CNS seizures may continue without external manifestations. Pyridoxine. If isoniazid overdose is suspected, administer Pyridoxine, 1g IV for each gram of isoniazid ingested (or 4 to 5g IV empirically). Thiamine. In alcoholic or malnourished patients, consider Thiamine 100 mg IV or IM. CLINICAL COURSE AND MONITORING Toxic seizures are usually self-limited. Monitoring of vital signs and neurological status is required until the patient is fully conscious and convulsion-free. LONG-TERM COMPLICATIONS Permanent neurologic deficit may result from prolonged convulsions or acute respiratory failure and hypoxia. AUTHOR(S)/REVIEWERS Authors: Poisons Unit, London, United Kingdom. Reviewers: Sao Paulo 9/94, Cardiff 3/95, Berlin 10/95; Cardiff 9/96: V. Afanasiev, M. Burger, T. Della Puppa, L. Fruchtengarten, K. Olsen, J. Szajewski).