Exercise therapy for the treatment of delirium in the intensive care unit.

Rationale: Exercise therapy in critical illness is a safe, feasible, and cost-effective approach that may improve cognitive function and reduce delirium as part of multicomponent nonpharmacologic approaches. However, there is still uncertainty regarding the effectiveness of each individual component.

Objectives: To assess the benefits and harms of exercise therapy for the treatment of delirium in critically ill adults in the intensive care unit, compared to no intervention, usual care or any pharmacological treatment.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and major trial registers as well as citation searching up to 12 July 2024.

Eligibility criteria: We included randomised controlled trials (RCTs) and cluster-RCTs assessing the effects of exercise therapy in adults with a diagnosis of delirium after admission to the intensive care unit (ICU), with or without mechanical ventilation, compared to no intervention, usual care or any other pharmacological treatment. We excluded cross-over RCTs and quasi-RCTs.

Outcomes: Outcomes of interest were duration of delirium, health-related quality of life, delirium severity, cognitive function, mortality in the ICU, ICU length of stay, hospital length of stay and adverse events.

Risk of bias: We used Cochrane's risk of bias 2 tool (RoB 2) for assessing RCTs.

Synthesis methods: We conducted meta-analyses using random-effects models to calculate risk ratios (RR) or mean differences (MD) and their 95% confidence intervals (95% CI) for all outcomes reported in the included trials. We summarised the certainty of the evidence using GRADE methods.

Included studies: We included four parallel RCTs with a total of 491 participants. Three studies were conducted in mixed ICUs and one in a medical ICU. The studies were published between 2016 and 2023 and were conducted in China, Germany, the UK, and Turkey.

Synthesis of results: Exercise therapy compared to no intervention or usual care In adults with a diagnosis of delirium after admission to the ICU, exercise therapy may reduce the duration of delirium (MD -1.07 days, 95% CI -1.75 to -0.39; 4 studies, 121 participants; low-certainty evidence). Additionally, exercise therapy may result in no adverse events in adults with a diagnosis of delirium after admission to the ICU, as no adverse events were reported in either group (2 studies, 90 participants; low-certainty evidence). Exercise therapy probably reduces the ICU length of stay in adults with a diagnosis of delirium after admission to the ICU (MD -2.24 days, 95% CI -3.63 to -0.85; 3 studies, 107 participants; moderate-certainty evidence). None of the included studies assessed health-related quality of life or delirium severity for this comparison. The included studies had an overall high risk of bias, or we had some concerns about the risk of bias, for the different evaluated outcomes. Imprecision in the effect estimates was also a concern due to small sample sizes and limited numbers of events. Exercise therapy compared to pharmacological treatment None of the included studies evaluated a comparison between exercise therapy and pharmacological treatment.

Authors' conclusions: In adults with a diagnosis of delirium after admission to the ICU, exercise therapy may reduce the duration of delirium, probably reduces the ICU length of stay, and may result in no adverse events. None of the included studies reported health-related quality of life or delirium severity, and no studies compared exercise therapy to any pharmacological treatment. The certainty of the evidence was low to moderate. We need further studies assessing the effects of exercise therapy on treating delirium in the ICU. These new studies must address the limitations found in the studies included in this review, especially considering larger sample sizes. Future studies should also focus on health-related quality of life, delirium severity, and cognitive function. They must also compare exercise therapy with additional treatment available in the clinical setting, such as highly disseminated pharmacological treatments, and focus on different population ages, delirium subtypes and pre-existing dementia status.

Funding: This Cochrane review had no dedicated funding.

Registration: Protocol (2024): doi.org/10.1002/14651858.CD015830.