OBJECTIVE To identify, appraise, and synthesise the best available evidence on the efficacy of perioperative interventions to reduce postoperative pulmonary complications (PPCs) in adult patients undergoing non-cardiac surgery. DESIGNSystematic review and meta-analysis of randomised controlled trials. DATA SOURCESMedline, Embase, CINHAL, and CENTRAL from January 1990 to December 2017. ELIGIBILITY CRITERIARandomised controlled trials investigating short term, protocolised medical interventions conducted before, during, or after non-cardiac surgery were included. Trials with clinical diagnostic criteria for PPC outcomes were included. Studies of surgical technique or physiological or biochemical outcomes were excluded. DATA EXTRACTION AND SYNTHESISReviewers independently identified studies, extracted data, and assessed the quality of evidence. Metaanalyses were conducted to calculate risk ratios with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. The primary outcome was the incidence of PPCs. Secondary outcomes were respiratory infection, atelectasis, length of hospital stay, and mortality. Trial sequential analysis was used to investigate the reliability and conclusiveness of available evidence. Adverse effects of interventions were not measured or compared. RESULTS117 trials enrolled 21 940 participants, investigating 11 categories of intervention. 95 randomised controlled trials enrolling 18 062 participants were included in meta-analysis; 22 trials were excluded from meta-analysis because the interventions were not sufficiently similar to be pooled. No high quality evidence was found for interventions to reduce the primary outcome (incidence of PPCs). Seven interventions had low or moderate quality evidence with confidence intervals indicating a probable reduction in PPCs: enhanced recovery pathways (risk ratio 0.35, 95% confidence interval 0.21 to 0.58), prophylactic mucolytics (0.40, 0.23 to 0.67), postoperative continuous positive airway pressure ventilation (0.49, 0.24 to 0.99), lung protective intraoperative ventilation (0.52, 0.30 to 0.88), prophylactic respiratory physiotherapy (0.55, 0.32 to 0.93), epidural analgesia (0.77, 0.65 to 0.92), and goal directed haemodynamic therapy (0.87, 0.77 to 0.98). Moderate quality evidence showed no benefit for incentive spirometry in preventing PPCs. Trial sequential analysis adjustment confidently supported a relative risk reduction of 25% in PPCs for prophylactic respiratory physiotherapy, epidural analgesia, enhanced recovery pathways, and goal directed haemodynamic therapies. Insufficient data were available to support or refute equivalent relative risk reductions for other interventions. CONCLUSIONSPredominantly low quality evidence favours multiple perioperative PPC reduction strategies. Clinicians may choose to reassess their perioperative care pathways, but the results indicate that new trials with a low risk of bias are needed to obtain conclusive evidence of efficacy for many of these interventions. STUDY REGIS...

Background Care bundles are small sets of evidence-based recommendations, designed to support the implementation of evidence-based best clinical practice. However, there is variation in the design and implementation of care bundles, which may impact on the fidelity of delivery and subsequently their clinical effectiveness. Methods A scoping review was carried out using the Arksey and O’Malley framework to identify the literature reporting on the design, implementation and evaluation of care bundles. The Embase, CINAHL, Cochrane and Ovid MEDLINE databases were searched for manuscripts published between 2001 and November 2017; hand-searching of references and citations was also undertaken. Data were initially assessed using a quality assessment tool, the Downs and Black checklist, prior to further analysis and narrative synthesis. Implementation strategies were classified using the Expert Recommendations for Implementing Change (ERIC) criteria. Results Twenty-eight thousand six hundred ninety-two publications were screened and 348 articles retrieved in full text. Ninety-nine peer-reviewed quantitative publications were included for data extraction. These consisted of one randomised crossover trial, one randomised cluster trial, one case-control study, 20 prospective cohort studies and 76 non-parallel cohort studies. Twenty-three percent of studies were classified as poor based on Downs and Black checklist, and reporting of implementation strategies lacked structure. Negative associations were found between the number of elements in a bundle and compliance (Spearman’s rho = − 0.47, non-parallel cohort and − 0.65, prospective cohort studies), and between the complexity of elements and compliance ( p < 0.001, chi-squared = 23.05). Implementation strategies associated with improved compliance included evaluative and iterative approaches, development of stakeholder relationships and education and training strategies. Conclusion Care bundles with a small number of simple elements have better compliance rates. Standardised reporting of implementation strategies may help to implement care bundles into clinical practice with high fidelity. Trial Registration This review was registered on the PROSPERO database: CRD 42015029963 in December 2015. Electronic supplementary material The online version of this article (10.1186/s13012-019-0894-2) contains supplementary material, which is available to authorized users.

ALH and HVC (Grant number: L-023032) is registered at ClinicalTrials.gov (ID: NCT02649231).We would furthermore like to thank Dr. Evgeny Krupitsky for his pioneering research into ketamine as a treatment and his input into the design of the study. This paper is dedicated to the memory of our colleague Dr. David Gilhooly.

CRD4201501277.