Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora.
Department of Pharmacy, University of Colorado Hospital, Aurora.
JAMA Intern Med. 2014 Apr;174(4):564-74. doi: 10.1001/jamainternmed.2013.14673.
IMPORTANCE Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are commonly used to prevent gastrointestinal tract (GI) hemorrhage in critically ill patients. The stronger acid suppression of PPIs may reduce the rate of bleeding but enhance infectious complications, specifically pneumonia and Clostridium difficile infection (CDI). OBJECTIVE To evaluate the occurrence and risk factors for GI hemorrhage, pneumonia, and CDI in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS A pharmacoepidemiological cohort study was conducted of adult patients requiring mechanical ventilation for 24 hours or more and administered either an H2RA or PPI for 48 hours or more while intubated across 71 hospitals between January 1, 2003, and December 31, 2008. Propensity score-adjusted and propensity-matched multivariate regression models were used to control for confounders. MAIN OUTCOMES AND MEASURES Primary outcomes were secondary diagnoses of International Classification of Diseases, Ninth Revision (ICD-9)-coded GI hemorrhage, pneumonia, and CDI occurring 48 hours or more after initiating invasive ventilation. RESULTS Of 35 312 patients, 13 439 (38.1%) received H2RAs and 21 873 (61.9%) received PPIs. Gastrointestinal hemorrhage (2.1% vs 5.9%; P < .001), pneumonia (27% vs 38.6%; P < .001), and CDI (2.2% vs 3.8%; P < .001) occurred less frequently in the H2RA group. After adjusting for propensity score and covariates, odds ratios of GI hemorrhage (2.24; 95% CI, 1.81-2.76), pneumonia (1.2; 95% CI, 1.03-1.41), and CDI (1.29; 95% CI, 1.04-1.64) were greater with PPIs. Similar results were obtained in the propensity-matched models of 8799 patients in each cohort. CONCLUSIONS AND RELEVANCE Proton pump inhibitors are associated with greater risks of GI hemorrhage, pneumonia, and CDI than H2RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.
重要性 组胺 2 受体拮抗剂（H2RAs）和质子泵抑制剂（PPIs）常用于预防重症患者的胃肠道（GI）出血。PPIs 的更强的抑酸作用可能会降低出血率，但会增加感染并发症，特别是肺炎和艰难梭菌感染（CDI）。 目的 评估重症患者 GI 出血、肺炎和 CDI 的发生和危险因素。 设计、地点和参与者 这是一项药物流行病学队列研究，纳入了 2003 年 1 月 1 日至 2008 年 12 月 31 日期间在 71 家医院接受机械通气 24 小时或更长时间且插管期间接受 H2RA 或 PPI 治疗 48 小时或更长时间的成年患者。采用倾向评分调整和倾向评分匹配的多变量回归模型来控制混杂因素。 主要结局和测量 主要结局是在开始侵入性通气后 48 小时或更长时间发生的国际疾病分类，第 9 版（ICD-9）编码的 GI 出血、肺炎和 CDI 的次要诊断。 结果 在 35312 名患者中，13439 名（38.1%）接受 H2RAs 治疗，21873 名（61.9%）接受 PPI 治疗。H2RA 组 GI 出血（2.1%比 5.9%；P < 0.001）、肺炎（27%比 38.6%；P < 0.001）和 CDI（2.2%比 3.8%；P < 0.001）的发生率较低。在调整倾向评分和协变量后，PPIs 组 GI 出血（2.24；95%CI，1.81-2.76）、肺炎（1.2；95%CI，1.03-1.41）和 CDI（1.29；95%CI，1.04-1.64）的比值比更大。在每个队列中匹配 8799 名患者的倾向评分匹配模型中也得到了类似的结果。 结论和相关性 质子泵抑制剂与机械通气患者的 GI 出血、肺炎和 CDI 风险高于 H2RA。还有许多其他明显的风险因素。这些数据需要在比较性前瞻性研究中得到证实。
