Heard Kennon, Dart Richard C, Bogdan Gregory, O'Malley Gerald F, Burkhart Keith K, Donovan J Ward, Ward Suzanne B
University of Colorado Health Sciences Center Section of Medical Toxicology, Division of Emergency Medicine, Department of Surgery, Denver 80231, USA.
Clin Toxicol (Phila). 2006;44(3):275-81. doi: 10.1080/15563650600584428.
Animal studies suggest that tricyclic antidepressant antibody fragments (TCA Fab) may be a useful therapy for tricyclic antidepressant poisoning. The objective of this study is to determine if TCA Fab increases total serum TCA levels without raising free serum TCA levels in human overdose patients, indicating that TCA Fab effectively binds TCA.
This was a prospective, dose escalation study of patients with mild to moderate TCA poisoning. Patients were treated with an escalating intravenous infusion totaling 7 or 14 gm of TCA Fab. The outcomes of interest were serum TCA levels (total and free), worsening of TCA toxicity, and adverse effects.
Seven patients were treated with Fab. Infusion of TCA Fab was associated with a dramatic increase in total serum TCA levels, while free TCA levels fell in both dosing groups. There were no significant changes in QRS duration, heart rate or mean arterial pressure associated with the Fab Infusion. Worsening of TCA toxicity did not occur despite marked elevation of total serum TCA concentrations. The two patients with the greatest prolongation of QRS showed a prompt shortening in their QRS duration temporally associated with the Fab infusion. Mild wheezing was observed in one asthmatic patient.
动物研究表明,三环类抗抑郁药抗体片段(TCA Fab)可能是治疗三环类抗抑郁药中毒的有效疗法。本研究的目的是确定TCA Fab在人类过量用药患者中是否会提高血清总三环类抗抑郁药水平而不提高血清游离三环类抗抑郁药水平,这表明TCA Fab能有效结合三环类抗抑郁药。
这是一项针对轻度至中度三环类抗抑郁药中毒患者的前瞻性剂量递增研究。患者接受了总量为7克或14克的TCA Fab静脉输注,剂量逐渐增加。感兴趣的结果包括血清三环类抗抑郁药水平(总水平和游离水平)、三环类抗抑郁药毒性恶化情况及不良反应。
7例患者接受了Fab治疗。输注TCA Fab与血清总三环类抗抑郁药水平显著升高相关,而两个给药组的游离三环类抗抑郁药水平均下降。与Fab输注相关的QRS时限、心率或平均动脉压无显著变化。尽管血清总三环类抗抑郁药浓度显著升高,但三环类抗抑郁药毒性并未恶化。QRS时限延长最明显的两名患者在输注Fab后,QRS时限迅速缩短。1例哮喘患者出现轻度喘息。
1)TCA Fab可提高三环类抗抑郁药中毒患者的血清总三环类抗抑郁药水平,同时降低游离水平;2)三环类抗抑郁药水平升高未产生毒性作用,且在输注Fab后的住院过程中未观察到严重不良反应。