title: Exercise rehabilitation following intensive care unit discharge for recovery from critical illness.
abstract: BACKGROUND
  Skeletal muscle wasting and weakness are significant complications of critical illness, associated with degree of illness severity and periods of reduced mobility during mechanical ventilation. They contribute to the profound physical and functional deficits observed in survivors. These impairments may persist for many years following discharge from the intensive care unit (ICU) and can markedly influence health-related quality of life. Rehabilitation is a key strategy in the recovery of patients after critical illness. Exercise-based interventions are aimed at targeting this muscle wasting and weakness. Physical rehabilitation delivered during ICU admission has been systematically evaluated and shown to be beneficial. However, its effectiveness when initiated after ICU discharge has yet to be established.
  
  
  OBJECTIVE
  To assess the effectiveness of exercise rehabilitation programmes, initiated after ICU discharge, for functional exercise capacity and health-related quality of life in adult ICU survivors who have been mechanically ventilated longer than 24 hours.
  
  
  METHODS
  We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP MEDLINE, Ovid SP EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host to 15 May 2014. We used a specific search strategy for each database. This included synonyms for ICU and critical illness, exercise training and rehabilitation. We searched the reference lists of included studies and contacted primary authors to obtain further information regarding potentially eligible studies. We also searched major clinical trials registries (Clinical Trials and Current Controlled Trials) and the personal libraries of the review authors. We applied no language or publication restriction. We reran the search in February 2015 and will deal with the three studies of interest when we update the review.
  
  
  METHODS
  We included randomized controlled trials (RCTs), quasi-RCTs and controlled clinical trials (CCTs) that compared an exercise intervention initiated after ICU discharge versus any other intervention or a control or 'usual care' programme in adult (≥ 18 years) survivors of critical illness.
  
  
  METHODS
  We used standard methodological procedures as expected by the Cochrane Collaboration.
  
  
  RESULTS
  We included six trials (483 adult ICU participants). Exercise-based interventions were delivered on the ward in two studies; both on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay following ICU discharge (up to a fixed duration of 12 weeks).Risk of bias was variable for all domains across all trials. High risk of bias was evident in all studies for performance bias, although blinding of participants and personnel in therapeutic rehabilitation trials can be pragmatically challenging. For other domains, at least half of the studies were at low risk of bias. One study was at high risk of selection bias, attrition bias and other sources of bias. Risk of bias was unclear for the remaining studies across domains. We decided not to undertake a meta-analysis because of variation in study design, types of interventions and outcome measurements. We present a narrative description of individual studies for each outcome.All six studies assessed functional exercise capacity, although we noted wide variability in the nature of interventions, outcome measures and associated metrics and data reporting. Overall quality of the evidence was very low. Individually, three studies reported positive results in favour of the intervention. One study found a small short-term benefit in anaerobic threshold (mean difference (MD) 1.8 mL O2/kg/min, 95% confidence interval (CI) 0.4 to 3.2; P value = 0.02). In a second study, both incremental (MD 4.7, 95% CI 1.69 to 7.75 watts; P value = 0.003) and endurance (MD 4.12, 95% CI 0.68 to 7.56 minutes; P value = 0.021) exercise testing results were improved with intervention. Finally self reported physical function increased significantly following use of a rehabilitation manual (P value = 0.006). Remaining studies found no effect of the intervention.Similar variability was evident with regard to findings for the primary outcome of health-related quality of life. Only two studies evaluated this outcome. Individually, neither study reported differences between intervention and control groups for health-related quality of life due to the intervention. Overall quality of the evidence was very low.Four studies reported rates of withdrawal, which ranged from 0% to 26.5% in control groups, and from 8.2% to 27.6% in intervention groups. The quality of evidence for the effect of the intervention on withdrawal was low. Very low-quality evidence showed rates of adherence with the intervention. Mortality ranging from 0% to 18.8% was reported by all studies. The quality of evidence for the effect of the intervention on mortality was low. Loss to follow-up, as reported in all studies, ranged from 0% to 14% in control groups, and from 0% to 12.5% in intervention groups, with low quality of evidence. Only one non-mortality adverse event was reported across all participants in all studies (a minor musculoskeletal injury), and the quality of the evidence was low.
  
  
  CONCLUSIONS
  At this time, we are unable to determine an overall effect on functional exercise capacity, or on health-related quality of life, of an exercise-based intervention initiated after ICU discharge for survivors of critical illness. Meta-analysis of findings was not appropriate because the number of studies and the quantity of data were insufficient. Individual study findings were inconsistent. Some studies reported a beneficial effect of the intervention on functional exercise capacity, and others did not. No effect on health-related quality of life was reported. Methodological rigour was lacking across several domains, influencing the quality of the evidence. Wide variability was noted in the characteristics of interventions, outcome measures and associated metrics and data reporting.If further trials are identified, we may be able to determine the effects of exercise-based intervention following ICU discharge on functional exercise capacity and health-related quality of life among survivors of critical illness.
authors.affiliation: Lane Fox Clinical Respiratory Physiology Research Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Connolly
authors.forename: Lisa
authors.initials: L
authors.lastname: Salisbury
authors.forename: Brenda
authors.initials: B
authors.lastname: O'Neill
authors.forename: Louise
authors.initials: L
authors.lastname: Geneen
authors.forename: Abdel
authors.initials: A
authors.lastname: Douiri
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Grocott
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hart
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
authors.forename: Bronagh
authors.initials: B
authors.lastname: Blackwood
mesh_terms: D000328:Adult; D018849:Controlled Clinical Trials as Topic; D003422:Critical Care; D016638:Critical Illness / Q000534:rehabilitation*; D005081:Exercise Therapy; D006304:Health Status; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D018908:Muscle Weakness / Q000209:etiology / Q000534:rehabilitation*; D020966:Muscular Disorders, Atrophic / Q000209:etiology / Q000534:rehabilitation*; D010351:Patient Discharge; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial; D015983:Selection Bias