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巴比妥类药物昏迷疗法可能会促使重度单纯性创伤性脑损伤患者出现可逆性骨髓抑制。

Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury.

作者信息

Stover J F, Stocker R

机构信息

Division of Trauma Surgery, Zürich University Hospital, Switzerland.

出版信息

Eur J Clin Pharmacol. 1998 Sep;54(7):529-34. doi: 10.1007/s002280050508.

Abstract

OBJECTIVES

Barbiturate coma is employed in brain-injured patients whenever increases in intracranial pressure remain unresponsive to less aggressive therapeutic regimens. Barbiturate-mediated neuroprotection, however, is weakened by an increased infection rate related to barbiturate-induced immunosuppression. Co-administration of barbiturates with antibiotics known to induce bone marrow suppression could, in turn, potentiate barbiturate-mediated immunosuppression. Adverse drug reactions and interactions of thiopental with antibiotics in terms of leukopenia, infection rate, and bone marrow suppression were investigated.

METHODS

White blood cells were measured daily, tracheobronchial secretion and urine were examined for bacterial growth twice a week or if an infection was suspected.

RESULTS

A total of 52 patients with severe isolated head injury were consecutively investigated. Due to increased intracranial pressure (ICP), which did not respond to analgosedation, barbiturate coma was performed in 23 cases. The other 29 patients remained analgosedated. Leukocytes and neutrophils were reversibly and significantly decreased in all patients, mostly sustained under thiopental. The pulmonary infection rate due to gram-negative organisms was nearly doubled during barbiturate coma. Reversible agranulocytosis and bone marrow suppression attributed to antibiotics developed in six patients after thiopental administration. Mortality rate, however, was not increased by these adverse effects.

CONCLUSIONS

Barbiturate coma may cause reversible leukopenia and an increased infection rate. Long-term administration of thiopental may also promote reversible antibiotic-induced bone marrow suppression. The mechanisms and site of interaction between thiopental and antibiotics cannot be assessed by the present study and remain to be clarified. However, during and after barbiturate coma, close monitoring of leukocytes and infections and careful selection of antibiotics is required.

摘要

目的

每当颅内压升高对较温和的治疗方案无反应时,巴比妥类药物昏迷疗法就会应用于脑损伤患者。然而,由于巴比妥类药物诱导的免疫抑制导致感染率增加,巴比妥类药物介导的神经保护作用会被削弱。巴比妥类药物与已知会诱导骨髓抑制的抗生素联合使用,反过来可能会增强巴比妥类药物介导的免疫抑制作用。研究了硫喷妥钠与抗生素在白细胞减少、感染率和骨髓抑制方面的药物不良反应及相互作用。

方法

每天测量白细胞,每周两次检查气管支气管分泌物和尿液中的细菌生长情况,或者在怀疑有感染时进行检查。

结果

共连续研究了52例严重孤立性头部损伤患者。由于颅内压(ICP)升高且对镇痛镇静无反应,23例患者进行了巴比妥类药物昏迷疗法。其他29例患者保持镇痛镇静状态。所有患者的白细胞和中性粒细胞均出现可逆性显著下降,在硫喷妥钠治疗期间大多持续存在。巴比妥类药物昏迷期间,革兰氏阴性菌引起的肺部感染率几乎翻倍。6例患者在使用硫喷妥钠后出现了归因于抗生素的可逆性粒细胞缺乏和骨髓抑制。然而,这些不良反应并未增加死亡率。

结论

巴比妥类药物昏迷可能导致可逆性白细胞减少和感染率增加。长期使用硫喷妥钠也可能促进抗生素诱导的可逆性骨髓抑制。本研究无法评估硫喷妥钠与抗生素之间相互作用的机制和部位,仍有待阐明。然而,在巴比妥类药物昏迷期间及之后,需要密切监测白细胞和感染情况,并谨慎选择抗生素。

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