To the Editor:
Carisoprodol is a centrally acting skeletal muscle relaxant, structurally and pharmacologically related to meprobamate Citation1. It was first introduced in the 1950s for the relief of back pain and muscle spasms. Carisoprodol is metabolized to meprobamate, a potent and addictive sedative. Carisoprodol also has weak anticholinergic, antipyretic, and analgesic properties Citation2&3. Poisoning with carisoprodol is reported infrequently. Following ingestion of a large dose, death is attributed to CNS depression with respiratory failure. Ingestion of 3.5 g of carisoprodol has resulted in the death of a 4‐year‐old Citation4. Seizures and coma persisting for 33h Citation5 followed ingestion of up to 14.7 g of carisoprodol in an adult, whereas ingestion of 9.45 g has resulted in milder CNS effects Citation2.
We report a 40‐year‐old white male who ingested 21 g (60 tablets) of carisoprodol along with an unknown quantity of chlordiazepoxide and temazepam. This case is worth reporting because it illustrates one of the highest‐reported blood levels of carisoprodol. The patient was found unresponsive by the paramedics at a video store, where he underwent emergent endotracheal intubation and received artificial ventilation. On arrival to the Emergency Department, he was unresponsive to painful stimuli. He had a HR of 130bpm, BP 220/118 mm HG, a temperature of 100.5°F, and was manually ventilated. The patient also demonstrated anticholinergic signs. Pupils were symmetric, dilated, and sluggishly reactive to light. Breath sounds were coarse with rales on the right side. Abdominal exam revealed absent bowel sounds as often seen in an anticholinergic toxidrome. He was deeply comatose, with absent tendon and plantar reflexes. His skin was warm and dry. The patient had a past medical history significant for psychiatric illness, substance abuse, chronic back pain, and hypertension. Initial blood gas analysis revealed a mild respiratory acidosis with a ph of 7.31 and a pCO2 of 50.1 mmHg (partially compensated with artificial ventilation). Other baseline labs were normal. The toxicology urine immunoassay was positive for cocaine metabolites and benzodiazepines. Chest radiographs showed a right upper lobe infiltrate. EKG revealed sinus tachycardia with a prolonged QT interval (exact measurements no longer available) mimicking a possible tricyclic overdose. In view of the possibility of multiple‐drug ingestion and since he presented to the ER within an hour after his ingestion, the treatment in the emergency department consisted of gastric lavage and activated charcoal with sorbitol. Naloxone was used as part of the coma cocktail, and sodium bicarbonate was used to reverse cardiac toxicity from a tricyclic antidepressant. The use of flumazenil to reverse the possible benzodiazepine component of his presentation was considered ill‐advised as the patient was on chronic benzodiazepine therapy, thus increasing the risk of withdrawal seizures. Intravenous clindamycin was initiated for aspiration pneumonia. After 36h in the intensive care unit the patient was extubated. He was hemodynamically stable and returned to his baseline mental status. Blood concentrations of carisoprodol measured by gas chromatography were 107 mg/L (therapeutic range: 10–40 mg/L and fell to 47.6 and 2.2 mg/L on the second and third days, respectively. The chlorodiazepoxide level was 2.3 mg/L (therapeutic range: 0.4–1.5 mg/L). The concentration of the active metabolite, meprobamate, was not measured.
Although its mechanism of action is not completely understood, carisoprodol and its active sedative hypnotic metabolite, meprobamate, are indirect agonists at the gamma aminobutyric acid receptor complex Citation6. Their central nervous system chloride ion channel conduction effects are similar to the benzodiazepines. Carisoprodol has a pka of 4.2 Citation7. More than 95% of the drug is metabolized by dealkylation to meprobamate Citation4Citation8&9. The two other products formed during liver biotransformation of carisoprodol are hydroxycarisoprodol and hydroxymeprobamate. Its half life is 8h Citation10. Metabolites are either conjugated or directly eliminated in the urine. Due to the rapid gastrointestinal absorption of carisoprodol, the peak plasma concentrations of 4 to 7 mg/L are achieved within 2 to 4h, and its onset of action is within 30 min Citation11.
The recommended treatment for carisoprodol overdose is to institute supportive measures. For those presenting soon after ingestion, gastric lavage is a reasonable approach; however, 1–2h postingestion, administration of activated charcoal should suffice Citation10. The shared receptor affinity with benzodiazepines raises the possibility of use of flumazenil as an antidote. A 51‐year‐old woman who ingested carisoprodol returned to her baseline neurologic status after IV administration of flumazenil Citation11. Flumazenil was not utilized in our case as intubation had already been performed Citation12. Elimination of the drug may be enhanced in several ways, including multiple doses of activated charcoal and intravenous fluids, in quantities sufficient to produce good urine flow. Although there is a theoretical benefit of hemoperfusion Citation10, supportive care in an intensive care setting is often sufficient, as with our patient.
This case is interesting because it illustrates one of the highest‐reported blood levels of 107 mg/L, and despite an ingestion of 21 g of carisoprodol the patient made full recovery with supportive care and mechanical ventilation. The practice of prescribing large quantities of carisoprodol or its use for chronic musculoskeletal pain should be discouraged as the potential toxicity outweighs the small alleged therapeutic benefit.
Acknowledgment
Acknowlegement of editorial help to Charles McKay M.D. Division of Medical Toxicology, Department of Emergency Medicine Hartford Hospital Connecticut.
Munawar Siddiqi, M.D.
Department of Anesthesiology
Cleveland Clinic Foundation
Marymount Hospital, Garfield Heights
Ohio, USA
Constance A. Jennings, M.D.
Department of Pulmonary and Critical Care Medicine
Cleveland Clinic Foundation
Marymount Hospital, Garfield Heights
Ohio, USA
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