FATAL CIRCULATORY COLLAPSE IN PREMATURE INFANTS RECEIVING CHLORAMPHENICOL
FATAL CIRCULATORY COLLAPSE IN PREMATURE INFANTS RECEIVING CHLORAMPHENICOL
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DOI：
10.1056/nejm195912242612604
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发表时间：
1959-01-01
影响因子：
158.5
通讯作者：
CASS, AB
中科院分区：
文献类型：
--
作者：
BURNS, LE;HODGMAN, JE;CASS, AB
在胎膜破裂24小时或更长时间后分娩的早产儿被分配到4个治疗组之一。1组不使用抗生素，2组单独使用氯霉素，3组同时使用青霉素和链霉素，4组同时使用3种抗生素。接受青霉素和链霉素治疗组的死亡率与未接受治疗组相同，但接受治疗的婴儿出现胃肠道症状的比例更高。两组患者的死亡率均显著高于其他两组。接受氯霉素治疗的婴儿遵循典型的临床过程。首先出现胃肠道症状，接着是循环衰竭和死亡。氯霉素的血药浓度持续上升。停药使症状停止恶化。康复没有留下后遗症。由于使用氯霉素是两组高死亡率的唯一共同因素，而不使用氯霉素是两组低死亡率的唯一共同因素，因此使用氯霉素的剂量可能是观察到的死亡率增加的原因。肝功能不佳，尤其是在葡萄糖醛酸缀合系统，以及肾功能下降，允许正常安全剂量累积到毒性水平。这种毒性表现为循环衰竭的特征性表现。如果毒性部分是由于葡萄糖醛酸盐结合失败，则应评估使用该代谢途径的其他药物是否适用于早产儿。没有证据表明青霉素或链霉素对婴儿有益。由于青霉素和链霉素治疗组的症状比未治疗组多，这些药物可能不是无害的。
Premature babies delivered after rupture of the fetal membranes for 24 hours or longer were assigned to one of 4 treatment groups. Group 1 received no antibiotic, Group 2 received chloramphenicol alone, Group 3 received penicillin and streptomycin, and Group 4 received all 3. The mortality of the group treated with penicillin and streptomycin was the same as that of the untreated group, but a higher number of the treated babies had gastrointestinal symptoms. The mortality rates of the 2 groups given chloramphenicol were significantly higher than those of the other 2 groups. The babies receiving chloramphenicol followed a typical clinical course. Gastrointestinal symptoms appeared first, followed by circulatory collapse and death. Blood levels of chloramphenicol showed a continuous rise. Removal of the drug stopped the progression of symptoms. Recovery left no sequelae. Since the administration of chloramphenicol was the only factor common to the 2 groups having the high mortality, and the absence of chloramphenicol the only factor common to the 2 groups with the low mortality, chloramphenicol in the dosage used must have been responsible for the increase in mortality observed. Poor liver function, especially in the glucuronide conjugation system, as well as decreased kidney function, allowed normally safe doses to accumulate to toxic levels. This toxicity manifested itself by a characteristic picture of circulatory collapse. If toxicity is partially due to failure of glucuronide conjugation, other drugs using this pathway of metabolism should be evaluated for use in the premature infant. No benefit to the infants from administration of penicillin or streptomycin could be demonstrated. Since there were more symptoms in the group treated with penicillin and streptomycin than in the nontreated group, these drugs may not be harmless.