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Meprobamate kinetics during and after terminated hemoperfusion in acute intoxications
D Jacobsen1, E Wiik-Larsen, E Saltvedt
1Medical Department, Ullevaal University Hospital, Oslo, Norway.
Abstract:
We report four cases of severe meprobamate intoxication. Maximal plasma levels reached 800 (176), 816 (180), 863 (190) and 923 mumol/l (203 mg/l). All patients survived without sequelae including one patient resuscitated from cardiac arrest. The clinical course was complicated by coma, hypotension, and hypothermia in all patients. Three cases were treated with charcoal hemoperfusion with mean hemoperfusion clearance ranging from 134-164 ml/min compared to 174 ml/min in one case treated with resin filter and the same blood flow of 200 ml/min. In two cases, a mean renal meprobamate clearance of 15 and 23 ml/min was calculated comprising only 9-15% of the hemoperfusion clearance. The amount of meprobamate removed by hemoperfusion ranged from 1.6-6.2 g. In one case, the half-life of plasma meprobamate during hemoperfusion was 2.6 hours compared to 8.3 hours after hemoperfusion. Thus the half-life was reduced more than 3-fold. These data show that hemoperfusion may be indicated in severe meprobamate intoxication.
Insights
Severe meprobamate intoxication can be life-threatening, but hemoperfusion offers an effective treatment. This study shows hemoperfusion significantly reduces meprobamate levels and shortens its half-life in patients.
Area of Science:
- Toxicology
- Pharmacology
- Nephrology
Background:
- Meprobamate is a sedative-hypnotic drug with a narrow therapeutic index.
- Severe meprobamate intoxication can lead to serious complications, including coma, hypotension, and cardiac arrest.
- Limited data exists on effective interventions for severe meprobamate overdose.
Observation:
- Four cases of severe meprobamate intoxication are presented, with peak plasma concentrations exceeding 800 mumol/l.
- All patients experienced coma, hypotension, and hypothermia.
- One patient required resuscitation from cardiac arrest but survived without sequelae.
Findings:
- Hemoperfusion was utilized in three cases, demonstrating significant meprobamate clearance (134-164 ml/min).
- Resin hemoperfusion showed comparable clearance (174 ml/min) at the same blood flow.
- Renal clearance was minimal (9-15% of hemoperfusion clearance), highlighting the efficacy of extracorporeal methods.
- Hemoperfusion reduced meprobamate half-life by over threefold (2.6 hours during vs. 8.3 hours post-hemoperfusion).
Implications:
- Hemoperfusion is a potentially life-saving intervention for severe meprobamate intoxication.
- Extracorporeal clearance methods are crucial for managing severe overdoses when conservative measures fail.
- Further research should explore optimal protocols for hemoperfusion in meprobamate poisoning.