Eyer Florian, Felgenhauer Norbert, Pfab Rudi, Thürmel Klaus, Zilker Thomas
Department of Toxicology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
Med Sci Monit. 2008 Dec;14(12):CS145-8.
Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. However, besides supportive care, specific treatment recommendations to enhance elimination of the parent compound have been discussed controversially and effectiveness of hemoperfusion is under debate.
A women with a prehistory of cerebral seizures was presented following a severe iatrogenic phenytoin overdose with a peak plasma concentration of 117 mg/L. A Phenytoin overdose could be contributed to both inadequate dosing and missed repeated drug monitoring. Native phenytoin body clearance failed to relevantly lower phenytoin concentration. Thus, three sessions of a four-hour long combination of activated charcoal hemoperfusion and high-flux hemodialysis were performed resulting in considerably reduced half-life during these measures of about 7-13 hours compared to the native half-life wavering between 40-100 hours. This resulted in a substantial clinical improvement in terms of central nervous system toxicity.
Hemodiaperfusion with activated charcoal seems to be a reasonable measure for forced lowering of highly toxic phenytoin plasma concentration and should be considered especially in circumstances following intravenous overdose (e.g. inadequate iatrogenic dosing). Its narrow therapeutic range enforces strictly adequate dosing and subsequent repeated drug monitoring of phenytoin.
苯妥英是一种广泛使用的抗惊厥药物,会导致许多有意和无意的过量用药情况。然而,除了支持性护理外,关于增强母体化合物消除的具体治疗建议一直存在争议,血液灌流的有效性也备受争议。
一名有癫痫病史的女性在发生严重医源性苯妥英过量后前来就诊,血浆峰值浓度为117mg/L。苯妥英过量可能是由于给药不足和错过重复药物监测所致。苯妥英的体内清除率未能显著降低苯妥英浓度。因此,进行了三次为期四小时的活性炭血液灌流与高通量血液透析联合治疗,与天然半衰期在40至100小时之间波动相比,这些措施期间的半衰期大幅缩短至约7至13小时。这在中枢神经系统毒性方面带来了显著的临床改善。
活性炭血液透析似乎是强制降低高毒性苯妥英血浆浓度的合理措施,尤其在静脉用药过量(如医源性给药不足)的情况下应予以考虑。其狭窄的治疗范围要求严格进行苯妥英的适当给药及随后的重复药物监测。