Sielaff T D, Sugerman H J, Tatum J L, Blocher C R
Surgery. 1987 Aug;102(2):350-7.
Porcine Pseudomonas adult respiratory distress syndrome (ARDS) has been shown to respond to combination therapy of 150 mg of cimetidine, 12.5 mg/kg of ibuprofen, 10 mg/kg of diphenhydramine, 0.2 mg/kg of ketanserin, and 30 mg/kg of methylprednisolone (CIDKM or Poly-5) given at 20 and 120 minutes after the onset of a continuous infusion of liver Pseudomonas aeruginosa, 5 X 10(8) colony-forming units (CFU) ml at 0.3 ml/20 kg/min. The present study was designed to determine the minimal, effective therapy by selective deletion of individual agents from CIDKM. Eight groups were studied: saline control (S, n = 9), Pseudomonas control (P, n = 8), and the following Pseudomonas plus treatment groups (each n = 5): CIDKM (cimetidine, ibuprofen, diphenhydramine, and ketanserin), CID (cimetidine, ibuprofen, and diphenhydramine), IC (ibuprofen and cimetidine), ID (ibuprofen and diphenhydramine), and CD (cimetidine and diphenhydramine). Pseudomonas alone produced severe ARDS with significant (p less than .05) decreases in PAO2 cardiac index, and systemic arterial pressure and significant increases in pulmonary artery pressure, extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux measured as slope index (SI). Full therapy, CIDKM or Poly-5, showed significant improvement in all parameters. Deletion of methylprednisolone did not significantly effect any parameter measured. The deletion of ketanserin, leaving CID, did not alter treatment efficacy, except for a significant decline in cardiac index at 3 hours. Deletion of ibuprofen from CID resulted in a failure to reverse pulmonary arterial hypertension, hypoxemia, elevated EVLW, and increased SI. Removal of either cimetidine or diphenhydramine from CID resulted in significant increases in EVLW compared with control levels and SI compared with both control levels and CID. These results indicate that a combination of both histamine H1 and H2 receptor blockers and the cyclooxygenase inhibitor, ibuprofen, is effective and essential in the treatment of hypoxemia, early pulmonary hypertension, and pulmonary microvascular injury in this fulminant model of porcine Pseudomonas ARDS.
猪铜绿假单胞菌所致成人呼吸窘迫综合征（ARDS）已被证明对以下联合疗法有反应：在以0.3 ml/20 kg/min的速度持续输注5×10⁸菌落形成单位（CFU）/ml的肝脏铜绿假单胞菌开始后20分钟和120分钟，给予150 mg西咪替丁、12.5 mg/kg布洛芬、10 mg/kg苯海拉明、0.2 mg/kg酮色林和30 mg/kg甲泼尼龙（CIDKM或Poly-5）。本研究旨在通过从CIDKM中选择性去除个别药物来确定最小有效治疗方案。研究了八组：生理盐水对照组（S，n = 9）、铜绿假单胞菌对照组（P，n = 8），以及以下铜绿假单胞菌加治疗组（每组n = 5）：CIDKM（西咪替丁、布洛芬、苯海拉明和酮色林）、CID（西咪替丁、布洛芬和苯海拉明）、IC（布洛芬和西咪替丁）、ID（布洛芬和苯海拉明）和CD（西咪替丁和苯海拉明）。单独的铜绿假单胞菌可导致严重的ARDS，动脉血氧分压（PAO₂）、心脏指数和体循环动脉压显著降低（p < 0.05），肺动脉压、血管外肺水（EVLW）以及以斜率指数（SI）测量的闪烁显像法测定的肺白蛋白通量显著增加。全疗法，即CIDKM或Poly-5，在所有参数上均显示出显著改善。去除甲泼尼龙对所测任何参数均无显著影响。去除酮色林，即使用CID，除3小时时心脏指数显著下降外，不改变治疗效果。从CID中去除布洛芬导致无法逆转肺动脉高压、低氧血症、升高的EVLW和增加的SI。与对照组相比，从CID中去除西咪替丁或苯海拉明导致EVLW显著增加，与对照组和CID相比，SI显著增加。这些结果表明，组胺H1和H2受体阻滞剂以及环氧化酶抑制剂布洛芬的联合使用在治疗猪铜绿假单胞菌ARDS这种暴发性模型中的低氧血症、早期肺动脉高压和肺微血管损伤方面是有效且必不可少的。
