澳大利亚乔治全球健康研究所John A. Myburgh团队研究了消化道选择性去污染对危重病人机械通气住院死亡率的影响。2022年10月26日出版的《美国医学会杂志》发表了这项成果。

消化道选择性去污染（SDD）能否降低危重病人的死亡率仍不确定。为了确定SDD是否能降低危重患者的住院死亡率，研究组进行了一项群集、交叉、随机临床试验，于2018年4月至2021年5月从澳大利亚19个重症监护病房（ICU）招募了5982名机械通气成年患者（最终随访至2021年8月）。同期生态评估在2017年5月至2021年8月从参与ICU中招募了8599名患者。

ICU被随机分配为采用或不采用SDD策略，交替进行两个12个月的周期，间隔3个月。SDD组患者（n = 2791）在机械通气期间，每6小时接受一次口服糊剂，并施用含有大肠杆菌素、妥布霉素和制霉菌素的胃悬浮液，同时连续4天静脉注射合适抗菌谱的抗生素。对照组患者（n = 3191）接受标准护理。主要结局是90天内的住院死亡率。共有8个次要结局，包括新阳性血培养、抗生素耐药菌（ARO）和艰难梭菌感染患者的比例。在生态评估中，包括ARO的新培养物在内的3种结果的非劣效性界限为2%。

在19个ICU登记的5982名患者（平均年龄58.3岁；女性占36.8%）中，所有患者均完成了试验。SDD组和标准护理组的住院死亡率分别为753/2791（27.0%）和928/3191（29.1%）（平均差异为−1.7%；优势比为0.91）。在8个预先指定的次要结局中，6个没有显示出显著差异。

SDD组与标准护理组中分别有23.1%与34.6%患者有新的ARO培养物，5.6%与8.1%有新的阳性血培养，0.5%与0.9%有新的艰难梭菌感染。在参与生态评估的8599名患者中，SDD的使用并未显示出对新ARO患者比例变化的非劣效性，在第一阶段分别为−3.3%与−1.59%；在第二阶段分别为0.88%与0.55%。

研究结果表明，在接受机械通气的危重病人中，与没有SDD的标准护理相比，SDD并没有显著降低住院死亡率。然而，效果估计的置信区间包括临床上重要的益处。

附：英文原文

Title: Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial

Author: The SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Catherine Boschert, Emma Broadfield, Timothy Chimunda, Jason Fletcher, Cameron Knott, Sanjay Porwal, Julie Smith, Deepak Bhonagiri, Monique Leijten, Sandhya Narayan, David Sanchez, Peta Saunders, Carli Sherriff, Jonathan Barrett, Gabrielle Hanlon, Sarah Jelly-Butterworth, Julie ODonnell, Judith Watson, Shailesh Bihari, Julia Brown, Sharon Comerford, Russell Laver, JoAnne McIntyre, Tapaswi Shrestha, Jin Xia, Samantha Bates, Gerard Fennessy, Craig French, Sathyajith Kootayi, Fiona Marshall, Rebecca McEldrew, Forbes McGain, Rebecca Morgan, John Mulder, Anna Tippett, Miriam Towns, Ellie Barker, Shelley Donovan, Katrina Ellis, Atul Gaur, Hannah Gibbons, Rebecca Gregory, Eloise Hair, Mary Keehan, Jess Naumoff, Elisha Turner, Gail Brinkerhoff, Dustin Bush, Federica Cazzola, Ken Havill, Paul Healey, Amber Poulter, Krishna Sunkara, Anders Aneman, Rachel Choit, Kelsey Dobell-Brown, Kairui Guo, Jillian Lee, Lien Lombardo, Zachariah Manalil, Jennene Miller, Jordan Rogers, Antony Stewart, Jana Yanga, Rebecca Gresham, Julie Lowrey, Kristy Masters, Christina Whitehead, Beverly Zaratan, Matthew Grigg, Meg Harward, Cassie Jones, Josephine Mackay, Jason Meyer, Emma Saylor

Issue&Volume: 2022-10-26

Abstract:

Importance  Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.

Objective  To determine whether SDD reduces in-hospital mortality in critically ill adults.

Design, Setting, and Participants  A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.

Interventions  ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n=2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n=3191) received standard care.

Main Outcomes and Measures  The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs.

Results  Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, 1.7% [95% CI, 4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P=.12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, 11.0%; 95% CI, 14.7% to 7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, 1.95%; 95% CI, 3.5% to 0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, 0.24%; 95% CI, 0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (3.3% vs 1.59%; mean difference, 1.71% [1-sided 97.5% CI, ∞ to 4.31%] and 0.88% vs 0.55%; mean difference, 0.32% [1-sided 97.5% CI, ∞ to 5.47%]) in the first and second periods, respectively.

Conclusions and Relevance  Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit.

DOI: 10.1001/jama.2022.17927

Source: https://jamanetwork.com/journals/jama/fullarticle/2798011