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Effectiveness of nonpharmacological interventions to prevent adverse events in the intensive care unit: A review of systematic reviews

Open AccessPublished:December 24, 2022DOI:https://doi.org/10.1016/j.aucc.2022.11.003

      Abstract

      Background

      Different types of interventions have been assessed for the prevention of adverse events. However, determining which patient-safety practice is most effective can be challenging when there is no systematised evidence synthesis. An overview following the best methodological standards can provide the best reliable integrative evidence.

      Objectives

      The objective of this study was to provide an overview of effectiveness nonpharmacological interventions aimed at preventing adverse events in the intensive care unit.

      Methods

      A review of systematic reviews (SRs) was conducted according to the Cochrane Handbook and PRISMA recommendations. PubMed, CINAHL, and Cochrane Library were searched for SRs published until March 2022. Two reviewers independently assessed the study’s quality, using AMSTAR-2, and extracted data on intervention characteristics and effect on prevention of adverse events.

      Results

      Thirty-seven SRs were included, and 27 nonpharmacological interventions were identified to prevent 11 adverse events. Most of the reviews had critically low methodological quality. Among all the identified interventions, subglottic secretion drainage, semirecumbent position, and kinetic bed therapy were effective in preventing ventilator-associated pneumonia; the use of earplugs, early mobilisation, family participation, and music in reducing delirium; physical rehabilitation in improving muscle strength; use of respiratory support in preventing reintubation; the use of a computerised physician order entry system in reducing risk of medication errors; and the use of heated water humidifier was effective in reducing artificial airway occlusion.

      Conclusions

      Some nonpharmacological interventions reduced adverse events in the intensive care setting. These findings should be interpreted carefully due to the low methodological quality. SRs on preventing adverse events in the intensive care unit should adhere to quality assessment tools so that best evidence can be used in decision-making.

      Keywords

      1. Introduction

      Adverse events (AEs) are undesirable or unintended patient outcomes associated with healthcare management resulting in prolonged hospitalisation, disability at the time of hospital discharge, or death.
      World Health Organization
      The occurrence of AEs due to unsafe care is approximately one in every 10 patients, and half of them are judged to be preventable. Most of these incidents are related to invasive clinical procedures and therapeutic management.
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      Developing preventive interventions to reduce patient harm has become an international policy priority.
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      Moreover, the recognition that many AEs are not preventable has increased awareness to focus on preventable AEs.
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      The occurrence of adverse events is associated with increased morbidity and mortality in children admitted to a single pediatric intensive care unit.
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      Chapter V: Overviews of Reviews | Cochrane Training.
      Due to the increasing number of SRs and the multiple preventive interventions being published, it is important to evaluate the current status and provide a summary of effective interventions to prevent them.
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      Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis.
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      Adverse events among hospitalized critically ill patients: a retrospective cohort study.
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      In this way, a review of SRs (overview) can provide the best reliable integrative evidence.
      Hence, the objective of this article is to provide an overview of SRs assessing nonpharmacological interventions (NPIs) to prevent AEs in the ICU.

      2. Method

      2.1 Design

      We conducted a review of SRs following a protocol registered in PROSPERO (CRD42019147956). Amendments to information provided in the protocol are described in Supplementary material 1.
      Reviews of SRs use explicit and systematic methods to collate and appraise the methodological quality and to summarise and analyse their results across our research question identifying specific areas of available or limited evidence. A comprehensive overview can provide an accurate description of the current state of research and thus guide future research.
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      • Fernandes R.M.
      • Newton A.S.
      • Scott S.D.
      • Hartling L.
      A decision tool to help researchers make decisions about including systematic reviews in overviews of reviews of healthcare interventions.
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      • Brunton G.
      An introduction to overviews of reviews: planning a relevant research question and objective for an overview.
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      • Scott S.D.
      • Hartling L.
      The impact of different inclusion decisions on the comprehensiveness and complexity of overviews of reviews of healthcare interventions.
      The overview was performed according to the Cochrane Handbook on methods for overviews,
      and we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) checklist
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      The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
      (Supplementary material 2).

      2.2 Search methods

      We developed a systematic search strategy for MEDLINE, CINAHL, and the Cochrane Library to identify studies published from inception until March 2022. English and Spanish language studies were included. The reference list of included SRs was screened to identify potentially relevant studies.
      The keywords were selected according to the main components of our clinical question, after a discussion between the research team and tested by an experienced systematic search reviewer before publishing the final version of the protocol. The full search strategy is available in Supplementary material 3.
      A pair of trained reviewers independently assessed the inclusion eligibility of the SRs. The first screening was based on the SR title and abstract. We identified papers of peer-reviewed SRs. A full-text assessment was conducted to determine the definitive inclusion of the selected SR. Disagreements in the selection of reviews were resolved by a third reviewer.

      2.3 Inclusion and exclusion criteria

      2.3.1 Type of studies

      SRs of primary studies, including randomised controlled trials (RCTs), quasi-RCTs and controlled observational studies, investigating the effect of NPIs on AEs were included. We considered as an SR any evidence synthesis with a clear systematic methodological approach, a detailed search strategy using at least two database sources, eligible criteria relevant to our research objective, and a narrative synthesis and/or meta-analysis.

      2.3.2 Type of patients

      Adult ICU patients aged 18 years and above in medical and surgical ICUs were included.

      2.3.3 Type of interventions

      Any NPIs to prevent AEs focused on patient safety was included, described as new strategies, practices, behaviour, actions, procedures, or environment.
      We considered control interventions to be usual care or standard ICU care defined as not providing any therapy specifically aimed at preventing AEs.

      2.3.4 Types of outcome measures

      Primary outcomes were incidence and ICU mortality related to AEs such as infections (mechanical ventilation–associated pneumonia, bloodstream infection (BSI), central catheter infection, peripheral catheter infection), delirium, reintubation, airway occlusion, pressure ulcers, physical function deterioration, and medication errors. Secondary outcomes were hospital mortality, length of mechanical ventilation, and stay in the ICU or in hospital. Outcomes that reported consequences of AEs in terms of extra treatment(s) or readmission were not the focus of this overview.

      2.4 Data extraction

      Data from studies such as trial design, the number of included studies, type of intervention, type of AEs, comparator, and outcomes were extracted by one reviewer and checked for accuracy by a second reviewer. Disagreement was resolved through discussion, and a third reviewer was consulted if needed.

      2.5 Quality appraisal

      Methodological quality of the reviews was assessed using AMSTAR-2,
      • Shea B.J.
      • Reeves B.C.
      • Wells G.
      • Thuku M.
      • Hamel C.
      • Moran J.
      • et al.
      Amstar 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both.
      which provides overall ratings (high, moderate, low, critically low) based on weaknesses in critical domains. A pair of reviewers independently assessed the quality of each study. Disagreements were resolved by a third reviewer. Moreover, we described the confidence in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for the primary outcomes when the SRs reported them.

      2.6 Data analysis and synthesis

      The study characteristics and patient outcomes for all the SRs that met our inclusion criteria were grouped by types of AEs in a tabular form. To assess the overlap of primary studies among included SRs, we created a matrix of evidence as a grid, placing all the included SRs in the columns and their respective primary studies in the rows. We calculated the corrected covered area (CCA) for the whole matrix and for each pair of SRs,
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      • Meza N.
      • Bangdiwala S.
      • Guzmán N. de
      • Urrutia G.
      • Bonfill X.
      • et al.
      Graphical representation of overlap for OVErviews: GROOVE tool.
      according to previously defined methods.
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      • Antoine S.L.
      • Mathes T.
      • Neugebauer E.A.M.
      • Eikermann M.
      Systematic review finds overlapping reviews were not mentioned in every other overview.
      We considered overlap to be low if the CCA was below 5%, moderate if the CCA was between 5% and 10%, high if the CCA was between 10% and 15%, and very high if the CCA was above 15%. We repeated this process for each outcome, creating custom matrices including only the SRs and primary studies providing data for each specific comparison. We reported overlap for this custom matrix using the same thresholds mentioned above.
      We compiled the pooled effect sizes of meta-analyses reported in the SRs and analysed the intervention components. Most of the effect sizes were expressed in odds ratio (OR); however, when risk ratio (RR) was reported, these were converted to OR if the number of events per group was provided.
      Statistical analyses were performed using Review Manager V5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014). Analysis of forest plots was descriptive, and metanalysis was not performed due to the clinical diversity of intervention by outcomes and overlap among primary studies included in the SRs.

      3. Results

      3.1 Search results

      The initial search of all databases yielded 3812 articles (Fig. 1). After the removal of duplicates, 3225 articles remained and were screened via review of their titles and abstracts. The screening resulted in 261 articles that underwent full-text review. A total of 224 articles were excluded because they did not meet our selection criteria. Fifty-six articles were excluded because the intervention was pharmacological, bundles, or educational interventions. A list of excluded studies with the reason for exclusion can be found in Supplementary material 4. Finally, 37 systematic reviews were included in this review.
      Fig. 1
      Fig. 1Summary of search and selection – PRISMA 2020. ICU, intensive care unit; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

      3.2 Characteristics of the included systematic reviews

      The characteristics of the included NPI SRs are summarised in Table 1. More than half (n = 21) of the included SRs were published after 2016. These reviews incorporated a range of study designs; however, most of them (n = 30) included only randomised controlled trials (RCTs). Thirty-two SRs performed a meta-analysis (86.4%).
      Table 1Characteristics of the included studies.
      Adverse eventAuthorYearN studies includedIntervention(s)Comparison(s)Outcome(s)ROB assessmentMeta-analysis
      Ventilator-associated pneumonia (VAP)Alexiou20097 RCTSemirecumbent position; prone positionSupine positionIncidence of VAP; hospital mortality; duration of mechanical ventilation; ICU length of stayYesYes
      Caroff201617 RCTSSDUsual care (standard endotracheal tubes)Incidence of VAP; ICU mortality; hospital mortality; duration of mechanical ventilation; ICU length of stayYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Delaney200615 RCTKinetic or rotating bed therapyUsual care (kinetic or rotating bed therapy)Incidence of VAP; ICU mortality; duration of mechanical ventilation; ICU length of stayYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Faradita20185 RCTClosed endotracheal suctioning systemOpen endotracheal suctioning systemIncidence of VAP; hospital mortalityYesYes
      Frost20139 RCTSSDUsual care (no drainage)Incidence of VAP; ICU mortality; hospital mortalityNoYes
      Muscedere201113 RCTSSDUsual care (standard endotracheal tubes)Incidence of VAP; ICU mortality; hospital mortality; ICU length of stay; duration of mechanical ventilationNoYes
      Pozuelo20185 RCTRespiratory physiotherapy interventionsUsual care, not receiving physiotherapy, any co-interventionsIncidence of VAP; ICU mortality; ICU length of stayYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Siempos20089 RCTClosed endotracheal suctioning systemOpen endotracheal suctioning systemIncidence of VAP; ICU mortality; duration of mechanical ventilationYesYes
      Wang, Li201610 RCTSemirecumbent positionSupine positionIncidence of VAP; ICU mortality; hospital mortality; ICU length of stay; duration of mechanical ventilationYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Wang201210 RCTSSDUsual care (no drainage)Incidence of VAP; hospital mortality; ICU length of stay; duration of mechanical ventilationYesYes
      Wen20178 RCTContinuous subglottic secretion drainageIntermittent subglottic secretion drainageIncidence of VAP; hospital mortality; duration of mechanical ventilationYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      DeliriumBurry202112 RCTEnviromental interventionUsual care∗Incidence of delirium, hospital mortality; duration of mechanical ventilation; ICU length of stayYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Deng Lu-Xi20209 RCTEnviromental interventionUsual care∗Incidence of delirium, duration of ICU deliriumYesYes
      Herling201812 RCTEnviromental interventionUsual care∗Incidence of deliriumYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Kang201815 RCTNPhIsUsual care∗Incidence of delirium; ICU mortality; duration of ICU delirium; ICU length of stayYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Litton20165 RCT;

      2 NRCT
      Use of earplugs as a sleep hygiene strategy (physical environment)Usual care∗, other interventionsIncidence of delirium; hospital mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Liang Surui202115 RCTEarly mobilisation, family participation, music, patient education, physical environmentUsual care∗Incidence of deliriumYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Physical function deteriorationAdler20127 NRCT; 3 RCTEarly mobilisation and physical therapyUsual care∗Muscle strength; physical function: mobilityNoNo
      Doiron20184 RCTEarly mobilisationUsual care (no mobilisation/active exercise, or mobilisation/active exercise given later than the intervention group)Muscle strength; physical function: mobilityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      No
      Menges20214 RCTSystematic early mobilisation standardEarly mobilisation (mobilisation initiated within 7 days but less systematically)Muscle strength; physical function: mobilityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      No
      Tipping201614 RCTActive mobilisation and rehabilitationUsual care (standard physical therapy)Muscle strength, ICU mortality; hospital mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Waldauf202018 RCTPhysical rehabilitationUsual Care∗Hospital mortalityYesYes
      ReintubationGranton20206 RCTHFNCUsual care (COT; NIV)Incidence of reintubation; hospital mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Hua-Wei20187 RCTHFNCUsual care (COT; NIV)Incidence of reintubationYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Liang Sujuan202112 RCTHFNCUsual care (COT; NIV)Incidence of reintubation; ICU mortality; hospital mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Xiaoyang Zhou202015 RCTHFNC; NIVUsual care (COT; NIV)Incidence of reintubationYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Medication errorManias20122 RCT and 22 QESCPOE systemsPaper-based orderingRate of medication errorNoNo
      Prgomet201716 RCT and NRCTCPOE systemsPaper-based orderingIncidence of medication error; ICU mortality; ICU length of stayYesYes
      Wang20158 NRCTPharmaceutical intervention (deliver pharmaceutical care in the ICU and not those solely involved in drug dispensing)Usual serviceRisk of general MEsYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Hospital-acquired pneumonia or artificial airway occlusionVargas201718 RCTHMEHWHIncidence of artificial airway occlusion; incidence of hospital-acquired pneumonia; hospital mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Maertens20186 RCTUse of endotracheal tapered cuffsUse of endotracheal nontapered cuffs (standard cuffed ET)Incidence of hospital-acquired pneumonia; ICU mortalityYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      Yes
      Healthcare-associated infections (VAP excluded)Frampton20145 RCTImplementation of checklistsUsual care∗Hospital mortality related to catheter BSIYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      No
      Chang20194 RCT and BAUniversal glovingNonglovingIncidence of healthcare-associated infectionsYesYes
      Pressure injuryLovegrove20222 RCTReactive bed surfaceStandard mattressIncidence of pressure injuryYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      No
      Nieto-García20215 RCTPre-early mobility programmePost-early mobility programmeIncidence of pressure injuryYes
      Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      No
      Tube displacement or tube occlusionGardner20051RCT; 6 NRCTETT stabilisation (twill or cotton tape, adhesive tape, gauze, or a manufactured device)Other ETT stabilisationIncidence of endotracheal tube displacementNoYes
      Bench20032 RCTHMEHWHIncidence of tracheal tube occlusion; incidence of VAPYesNo
      BA = before-and-after study; QES = quasi-experimental study; NRCT = nonrandomised controlled trial; RCT = randomised controlled trial; COT = conventional oxygen therapy; CPOE = computerised physician order entry; ETT = endotracheal tube; HFNC = high-flow nasal cannula; HME = heat moisture exchange; HWH = heated water humidifier; ICU = intensive care unit; NIV = noninvasive ventilation; NPhI = nonpharmacological intervention; SSD = subglottic secretion drainage.
      Usual Care∗: Receiving standard care as determined by the treating centre during the ICU admission and standard medical and nursing care.
      a Assessment using Cochrane risk-of-bias tool (RoB: Risk of Bias).
      The total number of eligible primary studies in the SRs ranged from 227−30 to 2431 studies. The number of patients in the eligible studies ranged from 454
      • Doiron K.
      • Hoffmann T.
      • Beller E.
      Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit.
      to 3369
      • Caroff D.A.
      • Li L.
      • Muscedere J.
      • Klompas M.
      Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis.
      and was not reported or unknown in nine (24.3%) reviews.
      The included reviews covered 11 different AEs: ventilator-associated pneumonia (VAP) (11 SRs),
      • Caroff D.A.
      • Li L.
      • Muscedere J.
      • Klompas M.
      Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis.
      • Alexiou V.G.
      • Ierodiakonou V.
      • Dimopoulos G.
      • Falagas M.E.
      Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.
      • Delaney A.
      • Gray H.
      • Laupland K.B.
      • Zuege D.J.
      Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis.
      • Faradita Aryani D.
      • Tanner J.
      Does open or closed endotracheal suction affect the incidence of ventilator associated pneumonia in the intensive care unit? A systematic review.
      • Frost S.A.
      • Azeem A.
      • Alexandrou E.
      • Tam V.
      • Murphy J.K.
      • Hunt L.
      • et al.
      Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis.
      • Pozuelo-Carrascosa D.P.
      • Torres-Costoso A.
      • Alvarez-Bueno C.
      • Cavero-Redondo I.
      • López Muñoz P.
      • Martínez-Vizcaíno V.
      Multimodality respiratory physiotherapy reduces mortality but may not prevent ventilator-associated pneumonia or reduce length of stay in the intensive care unit: a systematic review.
      • Siempos II,
      • Vardakas K.Z.
      • Falagas M.E.
      Closed tracheal suction systems for prevention of ventilator-associated pneumonia.
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      • Wang F.
      • Bo L.
      • Tang L.
      • Lou J.
      • Wu Y.
      • Chen F.
      • et al.
      Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials.
      • Wen Z.
      • Zhang H.
      • Ding J.
      • Wang Z.
      • Shen M.
      Continuous versus intermittent subglottic secretion drainage to prevent ventilator-associated pneumonia: a systematic review.
      • Muscedere J.
      • Rewa O.
      • McKechnie K.
      • Jiang X.
      • Laporta D.
      • Heyland D.
      Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis.
      delirium (six SRs),
      • Herling S.
      • Greve I.
      • Vasilevskis E.
      • Egerod I.
      • Bekker Mortensen C.
      • Møller A.
      • et al.
      Interventions for preventing intensive care unit delirium in adults.
      ,
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      • et al.
      Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: a systematic review and meta-analysis.
      • Litton E.
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      • Webb S.
      The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis.
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      S.,et al. Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis.
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      Non-pharmacological interventions to reduce the incidence and duration of delirium in critically ill patients: a systematic review and network meta-analysis.
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      Effects of nonpharmacological delirium-prevention interventions on critically ill patients' clinical, psychological, and family outcomes: a systematic review and meta-analysis.
      physical function deterioration (five SRs),
      • Doiron K.
      • Hoffmann T.
      • Beller E.
      Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit.
      ,
      • Adler J.
      • Malone D.
      Early mobilization in the intensive care unit: a systematic review.
      • Tipping C.J.
      • Harrold M.
      • Holland A.
      • Romero L.
      • Nisbet T.
      • Hodgson C.L.
      The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review.
      • Menges D.
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      Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.
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      Effects of rehabilitation interventions on clinical outcomes in critically ill patients: systematic review and meta-analysis of randomized controlled trials.
      reintubation (four SRs),
      • Granton D.
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      • Wang D.
      • Einav S.
      • Helviz Y.
      • Mauri T.
      • et al.
      High-flow nasal cannula compared with conventional oxygen therapy or noninvasive ventilation immediately postextubation: a systematic review and meta-analysis.
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      • Liang S.
      • Liu Z.
      • Qin Y.
      • Wu Y.
      The effect of high flow nasal oxygen therapy in intensive care units: a systematic review and meta-analysis.
      • Zhou X.
      • Zhou X.
      • Yao S.
      • Dong P.
      • Chen B.
      • et al.
      Preventive use of respiratory support after scheduled extubation in critically ill medical patients-a network meta-analysis of randomized controlled trials.
      medication error (three SRs),
      • Manias E.
      • Williams A.
      • Liew D.
      Interventions to reduce medication errors in adult intensive care: a systematic review.
      ,
      • Prgomet M.
      • Li L.
      • Niazkhani Z.
      • Georgiou A.
      • Westbrook J.I.
      Impact of commercial computerized provider order entry (CPOE) and clinical decision support systems (CDSSs) on medication errors, length of stay, and mortality in intensive care units: a systematic review and meta-analysis.
      ,
      • Wang T.
      • Benedict N.
      • Olsen K.M.
      • Luan R.
      • Zhu X.
      • Zhou N.
      • et al.
      Effect of critical care pharmacist’s intervention on medication errors: a systematic review and meta-analysis of observational studies.
      artificial airway occlusion or hospital-acquired pneumonia (two SRs),
      • Maertens B.
      • Blot K.
      • Blot S.
      Prevention of ventilator-associated and early postoperative pneumonia through tapered endotracheal tube cuffs: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Vargas M.
      • Chiumello D.
      • Sutherasan Y.
      • Ball L.
      • Esquinas A.M.
      • Pelosi P.
      • et al.
      Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) in adult critically ill patients: a systematic review, meta-analysis and meta-regression of randomized controlled trials.
      healthcare-associated infections (HAIs; two SRs),
      • Frampton G.K.
      • Harris P.
      • Cooper K.
      • Cooper T.
      • Cleland J.
      • Jones J.
      • et al.
      Educational interventions for preventing vascular catheter bloodstream infections in critical care: evidence map, systematic review and economic evaluation.
      ,
      • Chang N.C.N.
      • Kates A.E.
      • Ward M.A.
      • Kiscaden E.J.
      • Reisinger H.S.
      • Perencevich E.N.
      • et al.
      Association between universal gloving and healthcare-associated infections: a systematic literature review and meta-analysis.
      pressure injury (two SRs),
      • Lovegrove J.
      • Fulbrook P.
      • Miles S.
      • Steele M.
      Effectiveness of interventions to prevent pressure injury in adults admitted to intensive care settings: a systematic review and meta-analysis of randomised controlled trials.
      ,
      • Nieto-García L.
      • Carpio-Pérez A.
      • Moreiro-Barroso M.T.
      • Alonso-Sardón M.
      Can an early mobilisation programme prevent hospital-acquired pressure injures in an intensive care unit?: a systematic review and meta-analysis.
      and tube displacement or tube occlusion (two SRs).
      • Bench S.
      Humidification in the long-term ventilated patient; a systematic review.
      ,
      • Gardner A.
      • Hughes D.
      • Cook R.
      • Henson R.
      • Osborne S.
      • Gardner G.
      Best practice in stabilisation of oral endotracheal tubes: a systematic review.
      ,
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      The total number of interventions evaluated was 27, and VAP was the most frequent AE studied with seven NPIs. Usual care, defined as the standard care received by patients and determined by the treating centre during ICU admission, standard medical, and nursing care, was the most common control group.

      3.3 Methodological quality of SRs

      The AMSTAR-2 quality scores of the included reviews are described in Table 2. Twenty-eight (75.6%) SRs scored critically low on methodological quality, six (16.2%) SRs scored low, three (8.1%) scored moderate, and only one (2.7%) scored high. The main deficiencies noted in critical domains were failure to report a prior registered protocol, adequacy of the literature search, and justification for excluding studies, while in noncritical domains, the main deficiencies were reasons for study design selection and describing the included studies in adequate detail. None of the included SRs fulfilled all the AMSTAR-2 criteria. Regarding the certainty of the evidence, only six (16.2%) SRs reported the certainty of evidence for the primary outcomes.
      Table 2AMSTAR-2 assessment.
      ReferenceAMSTAR-2 domains
      12345678910111213141516Overall quality
      Adler 2012YesNoNoPYNoNoNoPYNoNoNMANMANoNoNMANoCritically low
      Alexiou 2009YesNoNoPYYesYesNoPYPYNoYesNoNoYesNoNoCritically low
      Bench 2003YesNoNoPYNoNoYesYesPYNoNMANMANoNoNMANoCritically low
      Burry 2021YesYesNoPYYesYesNoPYYesYesYesNoYesNoNoYesCritically low
      Caroff 2016YesNoYesPYNoYesNoPYYesNoNoYesYesYesYesYesCritically low
      Chang 2019YesNoNoPYYesYesNoYesPYYesNoNoYesYesYesYesCritically low
      Delaney 2006YesPYNoYesYesYesNoYesYesNoYesYesYesYesYesYesLow
      Deng Lu-Xi 2020YesPYNoPYYesYesNoPYPYNoYesNoNoYesYesYesCritically low
      Doiron 2018YesYesNoYesYesYesYesYesYesYesNMANMAYesYesNMAYesHigh
      Faradita 2018YesNoYesNoYesYesNoNoYesNoNoNoNoNoNoNoCritically low
      Frampton 2014YesPYNoPYYesYesYesYesYesYesNMANMAYesYesNMAYesModerate
      Frost 2013YesNoNoPYNoNoNoNoNoNoYesNoNoYesYesNoCritically low
      Gardner 2005YesNoNoPYYesNoNoPYNoNoYesNoYesYesNoNoCritically low
      Granton 2020YesYesNoNoYesYesNoYesYesYesYesYesYesYesNoYesCritically low
      Herling 2018YesYesNoYesYesYesYesYesYesYesYesYesYesYesNoYesLow
      Hua-Wei Huang 2018YesPYNoPYYesYesYesYesYesYesYesYesYesYesYesYesModerate
      Kang Lee 2018YesNoNoPYYesYesNoPYPYYesNoYesYesNoYesYesCritically low
      Lian Sujuan 2021YesNoNoNoNoYesNoPYYesNoYesNoNoYesYesYesCritically low
      Liang Surui 2021YesYesNoNoYesYesNoPYYesYesYesYesYesYesYesYesCritically low
      Litton 2016YesNoNoPYYesYesNoPYPYNoNoNoYesYesYesYesCritically low
      Lovegrove 2022YesYesNoNoYesYesNoYesYesYesYesYesNoYesNoYesCritically low
      Maertens 2018YesNoYesYesNoNoYesPYYesNoYesYesYesYesYesYesLow
      Manias 2012YesNoNoNoYesYesNoPYPYYesNMANMANoNoNMAYesCritically low
      Menges 2021YesYesYesPYYesYesYesYesYesYesYesYesYesYesNoYesLow
      Muscedere 2011YesNoYesPYYesYesNoPYNoNoYesNoNoYesNoYesCritically low
      Nieto Garcia 2020YesNoNoNoYesYesNoPYYesNoYesNoNoNoNoNoCritically low
      Pozuelo 2018YesNoYesPYYesYesNoPYYesNoYesYesYesYesNoYesCritically low
      Prgomet 2017YesPYNoPYYesNoNoPYYesNoNoNoNoNoNoYesCritically low
      Siempos 2008YesNoYesNoYesYesNoPYPYYesNoNoNoYesYesNoCritically low
      Tipping 2017YesPYYesYesYesYesNoPYPYNoNoYesYesYesNoYesCritically low
      Vargas 2017YesNoYesPYYesYesNoPYYesNoYesYesYesNoYesYesCritically low
      Waldauf 2020YesYesNoPYYesYesNoPYPYYesYesNoNoNoYesYesCritically low
      Wang F. 2012YesNoYesPYNoYesNoNoYesNoYesYesNoNoYesYesCritically low
      Wang L. 2016YesYesYesPYYesYesYesYesYesNoYesYesYesYesYesYesModerate
      Wang T. 2015YesNoYesPYYesNoNoPYPYNoNoNoYesNoNoNoCritically low
      Wen 2017YesNoYesPYYesYesNoPYYesNoNoNoNoNoNoNoCritically low
      Zhou Xiaoyang 2020YesYesNoPYYesYesYesPYYesYesYesYesYesYesNoYesLow
      PY = partial yes; NMA = no meta-analysis.

      3.4 Methodological quality of the primary studies included in the SRs

      The Cochrane Risk of Bias tool (RoB) was the most-used tool to determine methodological quality of the primary studies (62.2%), while 10 (24.3%) SRs only provided a narrative discussion of quality, and five (13.5%) SRs did not assess RoB. Most review authors noted that results should be interpreted with caution due to methodological study limitations.

      3.5 Overlap assessment

      The 37 included SRs comprised a total of 246 individual primary studies. The overall CCA, considering all SRs and all primary studies included in the reviews, was 1.0% (slight overlap). Supplementary material 5 provides a detailed assessment of the overall overlap among SRs.
      Six of 17 comparisons regarding VAP outcomes included at least two SRs. Considering only SRs and primary studies providing data for each specific comparison, the overall CCA and detailed CCA by pair of reviews were very high for all the comparisons. For example, comparison 1.1.1 includes four SRs, comprising a total of 17 individual primary studies. Of these, seven were included in all SRs. This is reflected in the detailed overlap assessment, which shows that all SRs have a CCA of at least 47.1% (very high overlap).
      One comparison regarding the incidence of delirium included four SRs and the overlap assessment was high (10.3%). Two comparisons regarding reintubation outcomes included at least two SRs, and the overlap assessment was high for the comparison of high flow nasal cannula (HFNC) versus conventional oxygen therapy (COT) and very high for the comparison noninvasive ventilation (NIV) versus conventional oxygen therapy (Supplementary material 6).
      For other AEs studied, comparisons included only one SR; therefore, no overlap assessment was possible.

      3.6 Effects of patient-safety interventions

      3.6.1 Ventilator-associated pneumonia

      3.6.1.1 Incidence of VAP

      VAP definition varied among the studies depending on the diagnosis criteria used. Eight SRs considered VAP according to clinical, laboratory, and imaging findings, and three SRs did not provide this information.
      Eleven SRs
      • Caroff D.A.
      • Li L.
      • Muscedere J.
      • Klompas M.
      Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis.
      • Alexiou V.G.
      • Ierodiakonou V.
      • Dimopoulos G.
      • Falagas M.E.
      Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.
      • Delaney A.
      • Gray H.
      • Laupland K.B.
      • Zuege D.J.
      Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis.
      • Faradita Aryani D.
      • Tanner J.
      Does open or closed endotracheal suction affect the incidence of ventilator associated pneumonia in the intensive care unit? A systematic review.
      • Frost S.A.
      • Azeem A.
      • Alexandrou E.
      • Tam V.
      • Murphy J.K.
      • Hunt L.
      • et al.
      Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis.
      • Pozuelo-Carrascosa D.P.
      • Torres-Costoso A.
      • Alvarez-Bueno C.
      • Cavero-Redondo I.
      • López Muñoz P.
      • Martínez-Vizcaíno V.
      Multimodality respiratory physiotherapy reduces mortality but may not prevent ventilator-associated pneumonia or reduce length of stay in the intensive care unit: a systematic review.
      • Siempos II,
      • Vardakas K.Z.
      • Falagas M.E.
      Closed tracheal suction systems for prevention of ventilator-associated pneumonia.
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      • Wang F.
      • Bo L.
      • Tang L.
      • Lou J.
      • Wu Y.
      • Chen F.
      • et al.
      Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials.
      • Wen Z.
      • Zhang H.
      • Ding J.
      • Wang Z.
      • Shen M.
      Continuous versus intermittent subglottic secretion drainage to prevent ventilator-associated pneumonia: a systematic review.
      • Muscedere J.
      • Rewa O.
      • McKechnie K.
      • Jiang X.
      • Laporta D.
      • Heyland D.
      Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis.
      assessed seven different NPIs for preventing VAP. Subglottic secretion drainage (SSD) compared with no drainage was assessed in four SRs, with a total of 44 RCTs and 10,193 patients. Results showed a statistically significant effect ranging from an OR of 0.48 (95% confidence interval [CI]: 0.38, 0.60) to an OR of 0.55 (95% CI: 0.46, 0.66).
      Semirecumbent position compared with supine position was evaluated in two SRs
      • Alexiou V.G.
      • Ierodiakonou V.
      • Dimopoulos G.
      • Falagas M.E.
      Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.
      ,
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      with 11 RCTs and 1096 patients. Results showed a statistically significant effect ranging from an OR of 0.42 (95% CI: 0.29, 0.59) to an OR of 0.47 (95% CI: 0.27, 0.82). Only one of them
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      assessed the certainty of the evidence, and it was graded as moderate.
      Use of kinetic bed compared with usual bed was analysed in a single SR
      • Delaney A.
      • Gray H.
      • Laupland K.B.
      • Zuege D.J.
      Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis.
      and showed a statistically significant reduction in the incidence of VAP: (OR: 0.38; 95% CI: 0.28, 0.52). This effect was based on a total of 10 RCTs and 967 patients. The other comparison showed no differences between the experimental and control group for this outcome (Fig. 2a) .
      Fig. 2
      Fig. 2Forest plot of the influence of non-pharmacological interventions to reduce ventilator-associated pneumonia (VAP). (a) Incidence of VAP. (b) ICU mortality related to VAP. (c) Hospital mortality related to VAP. CI = confidence interval; ICU, intensive care unit; SSD = subglottic secretion drainage.

      3.6.1.2 ICU mortality related to VAP

      Five different NPIs for preventing ICU mortality related to VAP were assessed in six SRs.
      • Delaney A.
      • Gray H.
      • Laupland K.B.
      • Zuege D.J.
      Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis.
      ,
      • Frost S.A.
      • Azeem A.
      • Alexandrou E.
      • Tam V.
      • Murphy J.K.
      • Hunt L.
      • et al.
      Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis.
      • Pozuelo-Carrascosa D.P.
      • Torres-Costoso A.
      • Alvarez-Bueno C.
      • Cavero-Redondo I.
      • López Muñoz P.
      • Martínez-Vizcaíno V.
      Multimodality respiratory physiotherapy reduces mortality but may not prevent ventilator-associated pneumonia or reduce length of stay in the intensive care unit: a systematic review.
      • Siempos II,
      • Vardakas K.Z.
      • Falagas M.E.
      Closed tracheal suction systems for prevention of ventilator-associated pneumonia.
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      ,
      • Muscedere J.
      • Rewa O.
      • McKechnie K.
      • Jiang X.
      • Laporta D.
      • Heyland D.
      Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis.
      Respiratory physiotherapy compared with usual care was analysed in a single SR
      • Pozuelo-Carrascosa D.P.
      • Torres-Costoso A.
      • Alvarez-Bueno C.
      • Cavero-Redondo I.
      • López Muñoz P.
      • Martínez-Vizcaíno V.
      Multimodality respiratory physiotherapy reduces mortality but may not prevent ventilator-associated pneumonia or reduce length of stay in the intensive care unit: a systematic review.
      and showed a statistically significant reduction in the ICU mortality related to VAP (OR: 0.67; 95% CI: 0.47, 0.96). This effect was based on five RCTs and 603 patients. The other comparison showed no differences between the experimental and control group for this outcome (Fig. 2b).

      3.6.1.3 Hospital mortality related to VAP

      Five experimental interventions for preventing hospital mortality related to VAP were assessed in eight SRs;
      • Caroff D.A.
      • Li L.
      • Muscedere J.
      • Klompas M.
      Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis.
      ,
      • Alexiou V.G.
      • Ierodiakonou V.
      • Dimopoulos G.
      • Falagas M.E.
      Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.
      ,
      • Faradita Aryani D.
      • Tanner J.
      Does open or closed endotracheal suction affect the incidence of ventilator associated pneumonia in the intensive care unit? A systematic review.
      ,
      • Frost S.A.
      • Azeem A.
      • Alexandrou E.
      • Tam V.
      • Murphy J.K.
      • Hunt L.
      • et al.
      Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis.
      ,
      • Wang L.
      • Li X.
      • Yang Z.
      • Tang X.
      • Yuan Q.
      • Deng L.
      • et al.
      Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
      • Wang F.
      • Bo L.
      • Tang L.
      • Lou J.
      • Wu Y.
      • Chen F.
      • et al.
      Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials.
      • Wen Z.
      • Zhang H.
      • Ding J.
      • Wang Z.
      • Shen M.
      Continuous versus intermittent subglottic secretion drainage to prevent ventilator-associated pneumonia: a systematic review.
      • Muscedere J.
      • Rewa O.
      • McKechnie K.
      • Jiang X.
      • Laporta D.
      • Heyland D.
      Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis.
      however, none of them showed significant results.
      The comparison that drew most SRs (four)
      • Caroff D.A.
      • Li L.
      • Muscedere J.
      • Klompas M.
      Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis.
      ,
      • Frost S.A.
      • Azeem A.
      • Alexandrou E.
      • Tam V.
      • Murphy J.K.
      • Hunt L.
      • et al.
      Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis.
      ,
      • Wang F.
      • Bo L.
      • Tang L.
      • Lou J.
      • Wu Y.
      • Chen F.
      • et al.
      Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials.
      ,
      • Muscedere J.
      • Rewa O.
      • McKechnie K.
      • Jiang X.
      • Laporta D.
      • Heyland D.
      Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis.
      was SSD compared with no drainage, with a total of 35 RCTs and 8520 patients. Measures of effect ranged from an OR of 0.91 (95% CI: 0.73, 1.13) to an OR of 1.03 (95% CI: 0.80, 1.32) (Fig. 2c).

      3.6.2 Delirium

      3.6.2.1 Incidence of delirium

      Six SRs
      • Herling S.
      • Greve I.
      • Vasilevskis E.
      • Egerod I.
      • Bekker Mortensen C.
      • Møller A.
      • et al.
      Interventions for preventing intensive care unit delirium in adults.
      ,
      • Kang J.
      • Lee M.
      • Ko H.
      • Kim S.
      • Yun S.
      • Jeong Y.
      • et al.
      Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: a systematic review and meta-analysis.
      • Litton E.
      • Carnegie V.
      • Elliott R.
      • Webb S.
      The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis.
      • Burry L.D.
      • Cheng W.
      • Williamson D.R.
      • Adhikari N.K.
      • Egerod I.
      • Kanji
      S.,et al. Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis.
      • Deng L.X.
      • Cao L.
      • Zhang L.N.
      • Peng X.B.
      • Zhang L.
      Non-pharmacological interventions to reduce the incidence and duration of delirium in critically ill patients: a systematic review and network meta-analysis.
      • Liang S.
      • Chau J.P.C.
      • Lo S.H.S.
      • Zhao J.
      • Choi K.C.
      Effects of nonpharmacological delirium-prevention interventions on critically ill patients' clinical, psychological, and family outcomes: a systematic review and meta-analysis.
      assessed interventions to prevent delirium. Some authors compared environmental intervention (changes in light or sound/hearing) vs usual care in 26 RCTs. Results were not significant, ranging from an OR of 0.83 (95% CI: 0.49, 1,41) to an OR of 1.22 (95% CI: 0.92, 1.62). Only one of them
      • Liang S.
      • Chau J.P.C.
      • Lo S.H.S.
      • Zhao J.
      • Choi K.C.
      Effects of nonpharmacological delirium-prevention interventions on critically ill patients' clinical, psychological, and family outcomes: a systematic review and meta-analysis.
      assessed the certainty of the evidence, and it was graded as low (Fig. 3).
      Fig. 3
      Fig. 3Forest plot of the influence of nonpharmacological interventions to reduce incidence of delirium. CI = confidence interval.
      Litton et al.
      • Litton E.
      • Carnegie V.
      • Elliott R.
      • Webb S.
      The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis.
      found that earplug use was associated with a lower incidence of delirium than usual care: an OR of 0.59 (95% CI: 0.44, 0.79). This effect was based on five RCTs and 832 patients.
      Kang et al.
      • Kang J.
      • Lee M.
      • Ko H.
      • Kim S.
      • Yun S.
      • Jeong Y.
      • et al.
      Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: a systematic review and meta-analysis.
      grouped different NPIs and found these were effective in reducing incidence of delirium with an OR of 0.66 (95% CI: 0.50, 0.87). This effect was based on 14 studies (cohort and RCTs) and 3372 patients.
      Liang Surui et al.
      • Liang S.
      • Chau J.P.C.
      • Lo S.H.S.
      • Zhao J.
      • Choi K.C.
      Effects of nonpharmacological delirium-prevention interventions on critically ill patients' clinical, psychological, and family outcomes: a systematic review and meta-analysis.
      found that early mobilisation (moderate-certainty evidence), family participation (moderate-certainty evidence), and music (low-certainty evidence) have a statistically significant effect on decreasing delirium incidence.

      3.6.2.2 Mortality related to delirium

      Only Kang et al.
      • Kang J.
      • Lee M.
      • Ko H.
      • Kim S.
      • Yun S.
      • Jeong Y.
      • et al.
      Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: a systematic review and meta-analysis.
      assessed ICU mortality, including three studies (cohort and RCTs), and results were not statistically significant (OR: 0.81; 95% CI: 0.61, 1.07).
      Concerning the outcome hospital mortality related to delirium, this was reported in two SRs,
      • Litton E.
      • Carnegie V.
      • Elliott R.
      • Webb S.
      The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis.
      ,
      • Burry L.D.
      • Cheng W.
      • Williamson D.R.
      • Adhikari N.K.
      • Egerod I.
      • Kanji
      S.,et al. Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis.
      and results were not statistically significant ranging from an OR of 0.77 (95% CI: 0.54, 1.10) to an OR of 0.91 (95% CI: 0.63, 1.31).

      3.6.3 Physical function deterioration

      Five SRs reported results on physical function deterioration. Three of them
      • Doiron K.
      • Hoffmann T.
      • Beller E.
      Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit.
      ,
      • Adler J.
      • Malone D.
      Early mobilization in the intensive care unit: a systematic review.
      ,
      • Menges D.
      • Seiler B.
      • Tomonaga Y.
      • Schwenkglenks M.
      • Puhan M.A.
      • Yebyo H.G.
      Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.
      assessed muscle strength at ICU discharge using the Medical Research Council scale and physical function using the Barthel Index or Short Form (SF-36) questionnaire to measure mobility–disability. We could not pool results from those SRs because the interventions assessed were different.
      Tipping et al.
      • Tipping C.J.
      • Harrold M.
      • Holland A.
      • Romero L.
      • Nisbet T.
      • Hodgson C.L.
      The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review.
      assessed physical functional status and muscle strength using the WHO International Classification of Functioning, Disability and Health. Physical rehabilitation in the ICU was assessed in comparison to usual care, and the experimental group demonstrated an improvement in muscle strength (mean difference (MD): 8.62; 95% CI: 1.39, 15.86).
      For early or systematic mobilisation compared with late or standard care, authors
      • Doiron K.
      • Hoffmann T.
      • Beller E.
      Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit.
      ,
      • Adler J.
      • Malone D.
      Early mobilization in the intensive care unit: a systematic review.
      ,
      • Menges D.
      • Seiler B.
      • Tomonaga Y.
      • Schwenkglenks M.
      • Puhan M.A.
      • Yebyo H.G.
      Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.
      found no statistically significant benefit on muscle strength. Tipping et al.
      • Tipping C.J.
      • Harrold M.
      • Holland A.
      • Romero L.
      • Nisbet T.
      • Hodgson C.L.
      The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review.
      and Waldauf et al.
      • Waldauf P.
      • Jiroutková K.
      • Krajčová A.
      • Puthucheary Z.
      • Duška F.
      Effects of rehabilitation interventions on clinical outcomes in critically ill patients: systematic review and meta-analysis of randomized controlled trials.
      showed that active mobilisation and physical rehabilitation compared with usual care did not impact mortality related to physical deterioration.

      3.6.4 Reintubation

      3.6.4.1 Rate of reintubation

      Four SRs
      • Granton D.
      • Chaudhuri D.
      • Wang D.
      • Einav S.
      • Helviz Y.
      • Mauri T.
      • et al.
      High-flow nasal cannula compared with conventional oxygen therapy or noninvasive ventilation immediately postextubation: a systematic review and meta-analysis.
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      • Liang S.
      • Liu Z.
      • Qin Y.
      • Wu Y.
      The effect of high flow nasal oxygen therapy in intensive care units: a systematic review and meta-analysis.
      • Zhou X.
      • Zhou X.
      • Yao S.
      • Dong P.
      • Chen B.
      • et al.
      Preventive use of respiratory support after scheduled extubation in critically ill medical patients-a network meta-analysis of randomized controlled trials.
      assessed two different NPIs for preventing reintubation. HFNC compared with conventional oxygen therapy was assessed in six RCTs and 1558 patients. Results showed a statistically significant effect ranging from an OR of 0.35 (95% CI: 0.19, 0.64) to an OR of 0.78 (95% CI: 0.62, 0.98). The certainty of the evidence was moderate for two reviews
      • Granton D.
      • Chaudhuri D.
      • Wang D.
      • Einav S.
      • Helviz Y.
      • Mauri T.
      • et al.
      High-flow nasal cannula compared with conventional oxygen therapy or noninvasive ventilation immediately postextubation: a systematic review and meta-analysis.
      ,
      • Zhou X.
      • Zhou X.
      • Yao S.
      • Dong P.
      • Chen B.
      • et al.
      Preventive use of respiratory support after scheduled extubation in critically ill medical patients-a network meta-analysis of randomized controlled trials.
      and low for one of them.
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      HFNC-compared NIVs included seven RCTs and 1839 patients. Results did not demonstrate statistically significant effects on decreasing intubation rate, ranging from an OR of 0.82 (95% CI: 0.61, 1.10) to an OR of 1.19 (95% CI: 0.87, 1.63). NIV compared with conventional oxygen therapy was assessed in nine trials, and results did not show a statistically significant effect (OR: 0.62; 95% CI: 0.46, 0.84, moderate-certainty evidence) (Fig. 4a).
      Fig. 4
      Fig. 4Forest plot of the influence of non-pharmacological interventions to reduce reintubation. (a) Rate of reintubation. (b) ICU mortality related to reintubation. (c) Hospital mortality related to reintubation. CI = confidence interval; NPI = nonpharmacological interventions; ICU = intensive care unit; SSD = subglottic secretion drainage; HFNC = high flow nasal cannula; COT = conventional oxygen therapy; NIV = noninvasive ventilation.

      3.6.4.2 Mortality related to reintubation

      Two SRs
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Liang S.
      • Liu Z.
      • Qin Y.
      • Wu Y.
      The effect of high flow nasal oxygen therapy in intensive care units: a systematic review and meta-analysis.
      compared HFNC with conventional oxygen therapy (OR: 0.97; 95% CI: 0.79, 1.18 to OR: 1.11; 95% CI: 0.44, 2.80; 6RCTs, 1749 participants) and HFNC with NIV (OR: 0.67; 95% CI: 0.44, 1.03 to OR: 1.14; 95% CI: 0.61, 2.13; 5RCTs, 1434 participants). Results had no statistically significant effects on the ICU mortality outcome (Fig. 4b).
      Concerning the outcome of hospital mortality related to reintubation, this was reported in three SRs
      • Granton D.
      • Chaudhuri D.
      • Wang D.
      • Einav S.
      • Helviz Y.
      • Mauri T.
      • et al.
      High-flow nasal cannula compared with conventional oxygen therapy or noninvasive ventilation immediately postextubation: a systematic review and meta-analysis.
      • Huang H.
      • Sun X.
      • Shi Z.
      • Chen G.
      • Chen L.
      • Friedrich J.
      • et al.
      Effect of high-flow nasal cannula oxygen therapy versus conventional oxygen therapy and noninvasive ventilation on reintubation rate in adult patients after extubation: a systematic review and meta-analysis of randomized controlled trials.
      • Liang S.
      • Liu Z.
      • Qin Y.
      • Wu Y.
      The effect of high flow nasal oxygen therapy in intensive care units: a systematic review and meta-analysis.
      that compared HFNC with conventional oxygen therapy (OR: 0.89; 95% CI: 0.46, 1.72 to OR: 0.93; 95% CI: 0.57, 1.52; 6RCTs, 1321 participants) and HFNC with NIV (OR: 1.09; 95% CI: 0.79, 1.50 to OR: 1.14; 95% CI: 0.82, 1.58; 5 RCTs, 1284 participants). Results had no statistically significant effects. Only one SR, for each comparison, reported certainty evidence, and it was graded as moderate (Fig. 4c).

      3.6.5 Medication error

      All SRs examining medication error (ME) included RCTs and NRCTs. We found that pharmaceutical intervention vs usual care did not show significant effects.
      • Wang T.
      • Benedict N.
      • Olsen K.M.
      • Luan R.
      • Zhu X.
      • Zhou N.
      • et al.
      Effect of critical care pharmacist’s intervention on medication errors: a systematic review and meta-analysis of observational studies.
      However, computerised physician order entry system vs paper-based ordering was associated with a significant reduction in MEs, with an RR of 0.71 (95% CI: 0.68–0.75).
      • Prgomet M.
      • Li L.
      • Niazkhani Z.
      • Georgiou A.
      • Westbrook J.I.
      Impact of commercial computerized provider order entry (CPOE) and clinical decision support systems (CDSSs) on medication errors, length of stay, and mortality in intensive care units: a systematic review and meta-analysis.
      This result was based on 16 studies.

      3.6.6 Artificial airway occlusion or hospital acquired pneumonia (non-VAP)

      Heat moisture exchangers compared with headted water humidifier for preventing artificial airway occlusion were assessed in one SR,
      • Vargas M.
      • Chiumello D.
      • Sutherasan Y.
      • Ball L.
      • Esquinas A.M.
      • Pelosi P.
      • et al.
      Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) in adult critically ill patients: a systematic review, meta-analysis and meta-regression of randomized controlled trials.
      including 14 RCTs and 2125 patients. Results were statistically significant, favouring headted water humidifier with an OR of 2.51 (95% CI: 1.27, 4.95), but there were no differences in the prevention of hospital-acquired pneumonia.
      Endotracheal tapered cuffs vs endotracheal nontapered cuffs were also assessed in one SR,
      • Maertens B.
      • Blot K.
      • Blot S.
      Prevention of ventilator-associated and early postoperative pneumonia through tapered endotracheal tube cuffs: a systematic review and meta-analysis of randomized controlled trials.
      which included six RCTs and 1324 patients, for prevention of ICU mortality related to hospital-acquired pneumonia, but results were not statistically significant.

      3.6.7 HAIs: catheter BSI

      Two SRs assessed the implementation of checklists
      • Frampton G.K.
      • Harris P.
      • Cooper K.
      • Cooper T.
      • Cleland J.
      • Jones J.
      • et al.
      Educational interventions for preventing vascular catheter bloodstream infections in critical care: evidence map, systematic review and economic evaluation.
      and universal gloving
      • Chang N.C.N.
      • Kates A.E.
      • Ward M.A.
      • Kiscaden E.J.
      • Reisinger H.S.
      • Perencevich E.N.
      • et al.
      Association between universal gloving and healthcare-associated infections: a systematic literature review and meta-analysis.
      compared with usual care for preventing HAI: catheter BSI. One SR
      • Frampton G.K.
      • Harris P.
      • Cooper K.
      • Cooper T.
      • Cleland J.
      • Jones J.
      • et al.
      Educational interventions for preventing vascular catheter bloodstream infections in critical care: evidence map, systematic review and economic evaluation.
      affirmed that there were insufficient data to draw conclusions, and the other SR
      • Chang N.C.N.
      • Kates A.E.
      • Ward M.A.
      • Kiscaden E.J.
      • Reisinger H.S.
      • Perencevich E.N.
      • et al.
      Association between universal gloving and healthcare-associated infections: a systematic literature review and meta-analysis.
      found that results were not statistically significant when only RCTs were pooled.

      3.6.8 Pressure injury

      Two SRs were included; one of them compared reactive bed surface with a standard mattress, and the other compared pre-early with post-early mobility programs to reduce pressure injury incidence. No one showed statistically significant results, and findings were inconclusive due to the differences in clinical characteristics and length of stay of patients.
      There were other interventions to prevent AEs (tube displacement and tube occlusion), but we found few SRs included for each one. The individual results of them are summarised in Supplementary material 7.

      4. Discussion

      To the best of our knowledge, this is the first overview to systematically summarise and assess the quality of SRs and overlap of primary studies on NPIs for preventing AEs in ICU patients. We included 37 SRs of NPIs that evaluated 27 patient-safety interventions to reduce 11 different AEs.
      We found the overall confidence of results based on the AMSTAR-2 was critically low because 73.7% of the SRs included had important methodological quality limitations. The main failures in critical domain assessment were reporting without a registered protocol, inadequacy of the literature search, and lack of justification for excluding studies, remaining the unawareness of the reason for their exclusion.
      ,
      • Shea B.J.
      • Reeves B.C.
      • Wells G.
      • Thuku M.
      • Hamel C.
      • Moran J.
      • et al.
      Amstar 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both.
      Despite a slight overall overlap for the overview as a whole, our overlap assessment at the outcome level showed a high and very high overlap for 12 comparisons. This overlapping raises awareness of redundant SRs publications in this area.
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      ,
      • Torres A.
      • Niederman M.S.
      • Chastre J.
      • et al.
      International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia.
      There were several interventions to prevent VAP, which remains among the most frequent infections in the ICU setting.
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      Most current guidelines focus on therapy and diagnosis recommendations of VAP, not prevention.
      • Torres A.
      • Niederman M.S.
      • Chastre J.
      • et al.
      International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia.
      ,
      • Campogiani L.
      • Tejada S.
      • Ferreira-Coimbra J.
      • Restrepo M.I.
      • Rello J.
      Evidence supporting recommendations from international guidelines on treatment, diagnosis, and prevention of HAP and VAP in adults.
      However, from seven types of NPIs, only three showed significant effects in reducing the incidence of VAP: subglottic secretion, elevating the head of the patient, and kinetic bed therapy. A literature review also found other pharmacological interventions but concluded that these implemented practices should be reviewed due to the low level of evidence.
      • Isac C.
      • Samson H.R.
      • John A.
      Prevention of VAP: Endless evolving evidences-systematic literature review.
      Many included SRs showed a reduction in the incidence of delirium. Early mobilisation showed a significant effect on preventing delirium; this finding is consistent with a previous clinical practice guideline that recommend performing early mobilisation of adult ICU patients whenever feasible to reduce the incidence of delirium.
      • Barr J.
      • Fraser G.L.
      • Puntillo K.
      • et al.
      Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.
      A recent review found that multicomponent (pharmacological and nonpharmacological) interventions were optimal for preventing delirium,
      • Deng L.X.
      • Cao L.
      • Zhang L.N.
      • Peng X.B.
      • Zhang L.
      Non-pharmacological interventions to reduce the incidence and duration of delirium in critically ill patients: a systematic review and network meta-analysis.
      and family participation resulted in better outcomes for reducing the incidence of delirium.
      • Deng L.X.
      • Cao L.
      • Zhang L.N.
      • Peng X.B.
      • Zhang L.
      Non-pharmacological interventions to reduce the incidence and duration of delirium in critically ill patients: a systematic review and network meta-analysis.
      ,
      • Liang S.
      • Chau J.P.C.
      • Lo S.H.S.
      • Zhao J.
      • Choi K.C.
      Effects of nonpharmacological delirium-prevention interventions on critically ill patients' clinical, psychological, and family outcomes: a systematic review and meta-analysis.
      In fact, our findings are supportive of international guidelines, suggesting the use of NPIs as part of a multimodal approach, especially in the management of delirium.
      • Devlin J.W.
      • Skrobik Y.
      • Gélinas C.
      • Needham D.M.
      • Slooter A.J.C.
      • Pandharipande P.
      • et al.
      Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU.
      ,
      • Celis-Rodríguez E.
      • Birchenall C.
      • de la Cal M.Á.
      • Castorena Arellano G.
      • Hernández A.
      • et al.
      Guía de práctica clínica basada en la evidencia para el manejo de la sedoanalgesia en el paciente adulto críticamente enfermo.
      We have not included guidelines or health technology assessments in our search; therefore, possible SRs have not been identified. We have found two guidelines, Devlin et al. (update of the Barr et al. guideline) and DAS-TASK 2015
      • Barr J.
      • Fraser G.L.
      • Puntillo K.
      • et al.
      Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.
      ,
      • Devlin J.W.
      • Skrobik Y.
      • Gélinas C.
      • Needham D.M.
      • Slooter A.J.C.
      • Pandharipande P.
      • et al.
      Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU.
      ,
      • Baron R.
      • Binder A.
      • Biniek R.
      • Braune S.
      • Buerkle H.
      • Dall P.
      • et al.
      Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-guideline 2015) – short version.
      that performed SRs to answer questions and made recommendations. The guideline of Devlin et al. addresses the management of pain, agitation/sedation, delirium, immobility, and sleep disruption, whereas the guideline of DAS-TASK 2015 tackles the management of delirium, analgesia, and sedation. Our overview agrees with these two guidelines in evaluating the nonpharmacological preventive measures to avoid delirium and the effects of immobility. We agree on the inclusion of most primary studies, except for the benefits of rehabilitation and mobilisation, of which Devlin included 16 RCTs, whereas we included 12 RCTs. However, the evidence was very similar.
      Patients’ physical rehabilitation and active mobilisation on their own combined with therapy prevents physical deterioration. However, some authors suggest that best outcomes in physical function are associated with good pain management, awakening, and breathing coordination, delirium management, and early exercise/mobility.
      • Devlin J.W.
      • Skrobik Y.
      • Gélinas C.
      • Needham D.M.
      • Slooter A.J.C.
      • Pandharipande P.
      • et al.
      Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU.
      ,
      • Costa D.K.
      • White M.R.
      • Ginier E.
      • Manojlovich M.
      • Govindan S.
      • Iwashyna T.
      • et al.
      Identifying barriers to delivering the awakening and breathing coordination, delirium, and early exercise/mobility bundle to minimize adverse outcomes for mechanically ventilated patients: a systematic review.
      HFNC or NIV compared to conventional oxygen therapy reduced the rate of reintubation, but there were no significant effects on ICU or hospital mortality. The certainty evidence varied among reviews from low to high. These findings are consistent with European Respiratory guidelines regarding the NIV in patients at high risk of reintubation as a conditional recommendation, given the low certainty of evidence.

      Rochwerg B., Brochard L., Elliott M.W., Hess D., Hill N. S. Nava S., et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure TASK FORCE REPORT ERS/ATS GUIDELINES. Eur Respir J 2017;50:1602426. doi:10.1183/13993003.02426-2016.

      Furthermore, the European Society of Intensive Care Medicine made a conditional recommendation for HFNC following extubation (moderate certainty) in reducing rates of reintubation.
      • Rochwerg B.
      • Einav S.
      • Chaudhuri D.
      • Mancebo J.
      • Mauri T.
      • Helviz Y.
      • et al.
      The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.
      We found that in the ICU setting, the use of a computerised physician order entry system reduces the risk of general medication errors compared with paper-based ordering. However, computerised physician order entry systems are implemented in only about one-third of hospitals. Further research is needed to better characterise links to patient harm.

      Rodziewicz T., Houseman B., Hipskind J. Medical error reduction and prevention - StatPearls - NCBI Bookshelf.. 2021https://www.ncbi.nlm.nih.gov/books/NBK499956/#_NBK499956_pubdet_.

      ,
      • Radley D.C.
      • Wasserman M.R.
      • Olsho L.E.
      • Shoemaker S.J.
      • Spranca M.D.
      • Bradshaw B.
      Reduction in medication errors in hospitals due to adoption of computerized provider order entry systems.
      We only found one SR that indicated that headted water humidifier significantly reduced the incidence of artificial airway occlusion. However, due to the small number of studies included and the low quality of this evidence, it is difficult to be confident about this finding.
      • Mort T.C.
      • Keck J.P.
      • Meisterling L.
      Endotracheal tube and respiratory care.
      Similarl to our findings, other authors have affirmed that there is little evidence on the effects of interventions to prevent HAIs such as infection control programs.
      • Thandar M.M.
      • Matsuoka S.
      • Rahman O.
      • Ota E.
      • Baba Ta
      Infection control teams for reducing healthcare-associated infections in hospitals and other healthcare settings: a protocol for systematic review.
      For a better understanding, a more detailed analysis of the infection type and where and how this AE occurs is required.

      European Centre for Disease Prevention and Control. AER for 2017: healthcare-associated infections acquired in intensive care units.

      Even our findings on using reactive bed surfaces or implementing a pre-early mobility programme did not show benefits in reducing pressure injuries; the European guideline for prevention and treatment of pressure ulcers remarks that those can be a preventive measure. However, the strength of the recommendation is weak. Moreover, early mobilisation in critical patients is based on good practice statements that are not supported by evidence to be significant for clinical practice.
      Panel EPUA
      International guideline for prevention and treatment of pressure ulcers/injuries.
      While it is true that preventing AEs should be considered a patient safety goal, comfort is the principal consideration in supportive care, especially in critical patients.

      Norton L., Parslow N., Johnston D., Ho, C., Afalavi, A., Mark, M., et al. Best practice recommendations for the prevention and management of pressure injuries. Foundations of best practice for skin and wound management. A supplement of wound care Canada; 2017. Published online.

      4.1 Limitations

      We did not search for potential SRs included in the guidelines published; thus, information on other nonpharmacological preventive interventions may have been omitted. Furthermore, our overview is limited by the methodological quality of the SRs and its included primary studies. Results are presented descriptively using findings from SRs, but we did not conduct a meta-analysis grouping data. Participants among SRs included were heterogeneous. Even when patients were in the adult ICU, they had a wide variety of diseases, patient characteristics, reasons for ICU admission, and variation in standard intensive care practices. Furthermore, not all comparisons reported certainty of evidence, which limited drawing conclusions about NPIs.
      The main strength is that the overview was carried out rigorously following the Cochrane methodology, with an updated comprehensive literature search, prespecified criteria for searching and analysis, and the selection and quality assessment of included studies evaluated independently by two authors.
      Studies should be better conducted and reported to provide adequate information on preventive interventions focused on patient safety and outcomes. Future SRs should be properly designed and conducted using the AMSTAR-2 checklist, principally by providing a research protocol, performing study selection and data extraction in duplicate, providing a list of both included and excluded studies, and assessing the risk of bias in the primary studies. Moreover, we need to synthesise other types of interventions to prevent AEs, including pharmacological intervention, educational programs, and multicomponent interventions, as well as focus the intervention on patient outcomes. Some AEs studied in this overview are not yet included in standard documents or considered quality indicators to optimise patient care. Therefore, our findings could be considered in developing or updating clinical practice guidelines to prevent AEs.
      One major limitation to this project is that the search strategy did not include professional guidelines that were constructed using the process of systematic review where the term 'systematic review' was not in the title. Readers are cautioned to search for guidelines and review those in addition to this summary prior to making practice changes. Future authors are cautioned to filter the search strategy by 'systematic review' instead of searching for the words 'systematic review' in the title as it is now standard practice for professional guidelines to be written using the process of systematic review.

      5. Conclusions

      We found some nonpharmacological interventions reduced AEs in an intensive care setting. A significant effect was found for SSD, semirecumbent position, and kinetic bed therapy in reducing the incidence of VAP; for the use of earplugs, early mobilisation, family participation, and music in reducing delirium; for physical rehabilitation in improving muscle strength; for the use of respiratory support in preventing reintubation; for use of a computerised physician order entry system in reducing ICU mortality related to medication errors; and for the use of headted water humidifier in reducing artificial airway occlusion. However, the findings are questionable due to the variety of patient characteristics, lack of certainty of evidence reported, the very high overlap for some comparisons, and the critically low quality of SRs included, making it difficult to be confident about them. In situations where strength of the evidence to support the evidence is low, clinical leaders are advised to deploy an evidence-based practice model when translating these interventions into practice to monitor quality outcomes. SRs about preventing AEs in the ICU should adhere to quality assessment tools so that best evidence can be used with greater confidence in decision-making.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

      Credit authorship contribution statement

      Stefanie Suclupe: Conceptualisation, Writing - original draft, Formal analysis, Data curation, Writing - review & editing
      Percy Efrain Pantoja Bustillos: Formal analysis, Data curation, Writing - review & editing
      Javier Bracchiglione: Formal analysis, Data curation, Writing - review & editing
      Carolina Requeijo: Data curation, Writing - review & editing
      Karla Salas-Gama: Data curation, Writing - review & editing
      Ivan Solà: Data curation, Writing - review & editing
      Angela Merchán-Galvis: Data curation, Writing - review & editing
      Jaume Uya Muntaña: Data curation
      Gemma Robleda: Conceptualisation, Review & editing
      Maria Jose Martinez–Zapata: Conceptualisation, Supervision, Writing - original draft, Formal analysis, Data curation, Writing - review & editing.
      All authors approved the final version of the study.

      Conflict of interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Ethical statement

      Ethical statement not applicable the authors undertook a systematic review, no ethical statements to declare.

      Registration of reviews

      The protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews); number CRD42019147956; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019147956

      Acknowledgements

      Stefanie Suclupe is a doctoral candidate at the Methodology of Biomedical Research and Public Health Program, Universitat Autònoma de Barcelona, Spain. Maria José Martinez Zapata is funded by a Miguel Servet research contract (CPII20/00023), Percy Efrain Pantoja by a Rio Hortega research contract (CM19/00168), and Angela Merchan-Galvis by a predoctoral research contract (FI17/00190) from the Instituto de Salud Carlos III.

      Appendix A. Supplementary data

      The following is/are the Supplementary data to this article:

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