Background
There is increasing focus on earlier rehabilitation in patients with traumatic or hypoxic brain injury or stroke. This systematic review evaluates the benefits and harms of early head-up mobilisation versus standard care in patients with severe acquired brain injury.

Methods
We searched Medline, CENTRAL, EMBASE, four other databases and 13 selected clinical trial registries until April 2020. Eligible randomised clinical trials compared early head-up mobilisation versus standard care in patients with severe acquired brain injury and were analysed conducting random- and fixed-effects meta-analyses and Trial Sequential Analysis (TSA). Certainty of evidence was assessed by GRADE.

Main results
We identified four randomised clinical trials (total n = 385 patients) with severe acquired brain injury (stroke 86% and traumatic brain injury 13%). Two trials were at low risk and two at high risk of bias. We found no evidence of a difference between early mobilisation vs. standard care on mortality or poor functional outcome at end of the intervention (relative risk (RR) 1.19, 95% CI 0.93 to 1.53; I2 0%; very low certainty) or at maximal follow-up (RR 1.03, 95% CI 0.89 to 1.21; I2 0%; very low certainty). We found evidence against an effect on quality of life at maximal follow-up. The proportion of patients with at least one serious adverse event did not differ at end of intervention or at maximal follow-up. For most comparisons, TSA suggested that further trials are needed.

Conclusions
We found no evidence of a difference between early mobilisation versus standard care for patients with severe acquired brain injury. Early mobilisation appeared not to exert a major impact on quality of life. This systematic review highlights the insufficient evidence in patients with severe brain injury, and no firm conclusions can be drawn from these data.