Kopolovic R, Thraikill K M, Martin D T, Carey L C, Cloutier C T
Surgery. 1986 Oct;100(4):679-90.
Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial. Recently research has been directed toward manipulation of the arachidonic acid cascade. Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS. The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa. Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2. Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P. aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis. Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P. aeruginosa infusion. In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema. Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed. The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS. On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis.
据报道，接受大剂量类固醇疗法的脓毒症和成人呼吸窘迫综合征（ARDS）患者生存率有所提高，但这种疗法及其益处仍存在争议。最近的研究已转向对花生四烯酸级联反应的调控。在脓毒症和ARDS的动物模型中，已报道使用非甾体抗炎药（NSAID）可提高生存率并改善血流动力学。本研究的目的是在持续输注活的铜绿假单胞菌诱导的脓毒症ARDS猪模型中比较类固醇（甲泼尼龙）和NSAID（布洛芬）的效果。对插管、麻痹并以250 ml潮气量和0.5 FiO₂进行通气的动物监测心肺参数。猪被随机分为五组：第一组和第二组在基线后20分钟和210分钟分别接受12.5 mg/kg布洛芬和30 mg/kg甲泼尼龙；第三组仅接受铜绿假单胞菌；第四组和第五组在脓毒症20分钟和210分钟分别接受布洛芬和甲泼尼龙。输注铜绿假单胞菌后出现明显肺水肿、肺内分流增加、低氧血症、血液浓缩和全身性低血压。在用布洛芬治疗的脓毒症动物中，维持了正常的体循环动脉压，血液浓缩减轻，氧合改善，分流和肺水肿显著减少。给予甲泼尼龙可改善血液浓缩和心脏指数，但未观察到对肺水肿、肺内分流或氧合有显著影响。本研究结果表明布洛芬有显著有益作用，我们鼓励对该药物在脓毒症和ARDS治疗中的应用进行对照临床试验。另一方面，发现甲泼尼龙在治疗与脓毒症相关的循环衰竭和ARDS方面相对无效。
