By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: The higher dose, very early (within 24 hours) mobilization protocol was associated with a reduction in the odds of a favorable outcome at 3 months after stroke occurrence.
SOURCE: Bernhardt J and the AVERT trial collaboration group. Efficacy and safety of very early mobilization within 24 hours of stroke onset (AVERT): A randomized controlled trial. Lancet 2015;386:46-55.
Very early (i.e., within 24 hours) mobilization after stroke onset comprised of out-of-bed sitting, standing, and walking is thought to contribute to the positive effects of stroke-unit care and is therefore recommended in many guidelines.1,2 However, positive evidence for recommending early mobilization has been quite limited.3 The biological rationale for early mobilization has centered around the clinical conclusions that bedrest negatively affects the musculoskeletal, cardiovascular, respiratory, and immune systems4 and might slow recovery, since immobility-related complications are common after stroke in patients who remain inactive.5 Finally, it has been argued that there is a narrow window for opportunity for brain plasticity to repair itself, and the optimum time for positive change is thought by many clinicians to occur soon after the stroke occurs.7,8
The AVERT Trial Collaboration group was formed to perform a study investigating the relative efficacy of a protocol intended to compare earlier-than-usual mobilization after a stroke with the usual care, which traditionally has begun 24 or more hours after the stroke.10 The researchers performed a parallel-group, single-blind, multicenter, international, randomized, controlled trial at 56 stroke units in five countries (Australia, New Zealand, Malaysia, Singapore, and the United Kingdom)9 to determine if early mobilization would improve functional outcomes, reduce immobility-related complications, and accelerate walking recovery at 3 months post-stroke occurrence with no increase in neurological complications. A total of 2104 patients were enrolled and randomized to an early mobilization group and to a usual care group. The results demonstrated that very early mobilization after a stroke was associated with a significant reduction in the odds of a favorable outcome at 3 months after the stroke; however, the number of patients who died or had serious adverse events at 3 months after the stroke did not differ significantly between groups.
The results of this very large and complex clinical trial comparing a high-dose, frequent mobilization protocol starting within 24 hours after a stroke appeared to be no better than “usual” care. However, careful analysis of the usual care protocols in the stroke care units will be required before drawing final conclusions, since components of early care intervention were already part of routine clinical care in many locations. The AVERT researchers indicated that they were going to further analyze the data and do a dose-response analysis to establish the effect of dose of rehabilitation on efficacy and safety outcomes. It should be noted that 26% of all patients were > 80 years of age and 24% of patients had received recombinant tissue plasminogen activator. Early mobilization did not reduce the incidence of immobility-related complications or significantly accelerate walking recovery. In fact, it reduced the odds of a favorable outcome at 3 months after the stroke occurred.
The results of the AVERT trial are incomplete since the authors indicated that they are now undertaking a dose-response analysis to establish the effect of dose of rehabilitation on efficacy and safety outcomes and to establish a better understanding of exactly which patients best respond to rehabilitative treatments, be they early or later, and which do not. It would appear that, for the time being, early mobilization would be appropriate and useful in carefully selected but not in all stroke patients. Until a deeper understanding evolves regarding which patients best respond to rehabilitative treatment and which patients do not is firmly established, clinicians would be advised to be cautious about early mobilization post-stroke.
- Indredavic B, et al. Treatment in a combined acute and rehabilitation stroke unit: Which aspects are most important? Stroke 1999;30:917-923.
- Govan L, et al. Does the prevention of complications explain the survival benefit of organized inpatient (stroke unit) care?: Further analysis of a systematic review. Stroke 2007;38:2536-2540.
- Bernhardt J, et al. Early mobilization after stroke: Early adoption but limited evidence. Stroke 2015;46:1141-1146.
- Allen C, et al. Bedrest: A potentially harmful treatment needing more careful evaluation. Lancet 1999;354:1229-1233.
- Langhorne P, et al. Medical complications after stroke: A multicenter study. Stroke 2000;31:1223-1229.
- Bernhardt J, et al. Inactive and alone: Physical activity within the first 14 days of acute stroke unit care. Stroke 2004;35:1005-1009.
- Murphy TH, et al. Plasticity during stroke recovery: From synapse to behavior. Nat Rev Neurosci 2009;10:861-872.
- Krakauer JW, et al. Getting neurorehabilitation right: What can be learned from animal models? Neurorehabil Neural Repair 2012;26:923-931.
- Bernhard J, et al. Statistical analysis plan (SAP) for A Very Early Rehabilitation Trial (AVERT): An international trial to determine the efficacy and safety of commencing out of bed standing and walking training (very early mobilization) within 24 hours of stroke onset versus usual stroke unit care. Int J Stroke 2015;10:23-24.
- Bernhardt J, and the AVERT trial collaboration group. Efficacy and safety of very early mobilization within 24 hours of stroke onset (AVERT): A randomized controlled trial. Lancet 2015;386:46-55.