title: Permissive hypoxaemia versus normoxaemia for mechanically ventilated critically ill patients.
abstract: BACKGROUND
  Permissive hypoxaemia describes a concept in which a lower level of arterial oxygenation (PaO2) than usual is accepted to avoid the detrimental effects of high fractional inspired oxygen and invasive mechanical ventilation. Currently however, no specific threshold is known that defines permissive hypoxaemia, and its use in adults remains formally untested. The importance of this systematic review is thus to determine whether any substantial evidence is available to support the notion that permissive hypoxaemia may improve clinical outcomes in mechanically ventilated critically ill patients.
  
  
  OBJECTIVE
  We assessed whether permissive hypoxaemia (accepting a lower PaO2 than is current practice) in mechanically ventilated critically ill patients affects patient morbidity and mortality. We planned to conduct subgroup and sensitivity analyses and to examine the role of bias to determine the level of evidence provided.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 11, part of The Cochrane Library; MEDLINE (1954 to November 2013); EMBASE (1980 to November 2013); CINAHL (1982 to November 2013) and ISI Web of Science (1946 to November 2013). We combined the sensitive search strategies described in the Cochrane Handbook for Systematic Reviews of Interventions to search for randomized controlled trials (RCTs) in MEDLINE and EMBASE. For ongoing trials, we also searched the following databases: MetaRegister of ControlledTrials and the National Research Register. We applied no language restrictions.
  
  
  METHODS
  RCTs and quasi-RCTs that compared outcomes for mechanically ventilated critically ill participants, in which the intervention group was targeted to be hypoxaemic relative to the control group, and the control group was normoxaemic or was mildly hypoxaemic, were eligible for inclusion in this review. Exact values defining 'conventional' and 'permissive hypoxaemia' groupings were purposely not specified, and the manner in which these oxygenation goals were achieved also was not specified. We did state however that the intervention group required a target oxygenation level lower than that of the control group, and that the control group target levels should be in the range of normoxaemia or mild hypoxaemia (not hyperoxaemia).
  
  
  METHODS
  We used standard methodological procedures expected by The Cochrane Collaboration. Using the results of the above searches, two review authors (EG-K and KM) independently screened all titles and abstracts for eligibility and duplication. No discrepancies were encountered, nor was it necessary for review authors to contact the first author of any trial to ask for additional information.
  
  
  RESULTS
  Our search strategy yielded a total of 2419 results. After exclusion of duplications, 1651 candidate studies were identified. Screening of titles and abstracts revealed that no studies met our inclusion criteria.
  
  
  CONCLUSIONS
  This comprehensive review failed to identify any relevant studies evaluating permissive hypoxaemia versus normoxaemia in mechanically ventilated critically ill participants. Therefore we are unable to support or refute the hypothesis that this treatment strategy is of benefit to patients.Given the substantial amount of provocative evidence derived from related clinical contexts (resuscitation, myocardial infarction, stroke), we believe that this review highlights an important unanswered question within critical care.  In the presence of two competing harms (hypoxia and hyperoxia), it will be important to carefully evaluate the safety and feasibility of permissive hypoxaemia before proceeding to efficacy and effectiveness trials.
authors.affiliation: University College London Centre for Altitude Space and Extreme Environment (CASE) Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London, UK.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Gilbert-Kawai
authors.forename: Kay
authors.initials: K
authors.lastname: Mitchell
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: John
authors.initials: J
authors.lastname: Carlisle
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Grocott
mesh_terms: D000328:Adult; D016638:Critical Illness; D006801:Humans; D000860:Hypoxia; D010100:Oxygen / Q000097:blood*; D012016:Reference Values; D012121:Respiration, Artificial
chemical_list: D010100:Oxygen