Hyperosmolar therapy for acute brain injury: study protocol for an umbrella review of meta-analyses and an evidence mapping

Abstract

IntroductionAcute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care.Methods and analysisWe will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observational studies or both) that evaluate one or more hyperosmolar solutions (including hypertonic saline and/or mannitol) for the treatment of adult patients with acute brain injury of any severity. Two researchers will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion with a third researcher. Primary outcomes will be mortality and neurological outcomes at discharge. Secondary outcomes will include control of intracranial pressure, cerebral perfusion pressure, length of stay (in hospital an intensive care unit) and any adverse event. Quality of the included meta-analyses will be assessed using the AMSTAR-2 tool. An overall summary of methods and results will be performed using tabular and graphical approaches and will be supplemented by narrative description. We will analyse whether published meta-analyses present an outline of available evidence (eg, cited, described and discussed any previous meta-analysis). Where objectives from two or more meta-analyses overlap, we will assess the causes of any noted discrepancies between meta-analyses.Ethics and disseminationNo ethical approval will be required. Findings from this study will be published in a peer-reviewed journal. All data will be deposited in a cross-disciplinary public repository.PROSPERO registration numberCRD42019148152.

Mannitol or Hypertonic Saline in Traumatic Brain Injury patients: a CENTER-TBI study

“…Our ndings therefore are in line with previous research and consolidates the notion of lack of superiority of one agent over the other. To summarize the current ndings of several systematic reviews and meta-analyses, an umbrella trial is set-up [29]. This will make interpretation of current results more easy until the time more data comes available from a new RCT.…”

AMSTAR 2 Appraisal of Systematic Reviews and Meta-analyses in the Field of Heart Failure from High-impact Journals

“…The same is true for MOOSE and QUORUM. Apparently, preregistration or publishing a pre-established protocol is not yet a common practice for SRs, but more studies have been following this step in recent years [40][41][42][43]. Q7 is based on the same content as in Cochrane Handbook Chapter 4, with the further instruction that "the list of excluded studies should be as brief as possible.…”

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

“…Its reflection coefficient is 1 [ 13 , 14 ]. It seems to reduce ICH and improve cerebral perfusion pressure more effectively than mannitol [ 15 , 16 , 17 ]. Some studies also documented better outcomes in patients treated with HTS compared to mannitol, however the osmotherapy-related electrolyte disequilibrium appears to be an independent predictor of poor outcome, regardless of the type of osmotically active medication [ 18 , 19 , 20 ].…”

“…There is a dose–response relationship between the use of mannitol and the incidence and severity of AKI, with a cut-off of the daily dose at 1.34 g/kg body weight [ 73 ]. Interestingly, the combined therapy of ICH with mannitol and HTS did not increase the risk of AKI more than HTS alone, however several authors suggested to use HTS, demonstrating its superiority over mannitol [ 13 , 14 , 16 , 18 , 74 ]. In conclusion, it can be postulated that an increase in plasma hyperosmolality per se, as well as the use of osmotically active medications, may impair renal function, and that maintaining adequate renal perfusion may reduce the risk of AKI.…”