Hyperosmolar Agents for TBI: All Are Equal, But Some Are More Equal Than Others?

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LETTERS TO THE EDITOR

Hyperosmolar Agents for TBI: All Are Equal, But Some Are More Equal Than Others? H. Quintard1*  , G. Meyfroidt2,3 and G. Citerio4 © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society

We read with interest the guidelines for the acute treatment of cerebral edema in neurocritical care patients published by Cook et al. [1] and congratulate the authors for their work. Brain edema is a major complication after brain injury, which has a strong association with poor prognosis, and may lead to death if left untreated. We agree with the authors that hyperosmolar agents (hypertonic saline (HTS), mannitol) are cornerstones in its management. However, we do not think the recommendation to suggest a preference for HTS over mannitol to treat cerebral edema in TBI patients is justified. This recommendation is based on very low level evidence, summarized in two meta-analyses [2, 3], where no significant mortality or outcome benefit could be demonstrated in favor of HTS or any other osmotic agent. On the other hand, it is acknowledged that ‘the literature suggested HTS was at least as safe and effective as mannitol,’ and mannitol is presented as ‘also a safe and effective option.’ We believe these statements present an inherent contradiction. To support the preference for HTS in their recommendations, the authors refer to ‘consistency across the numerous lower-quality studies that HTS was more effective than mannitol for reducing ICP or cerebral edema,’ suggesting a potential quicker onset of action, and a more robust and durable ICP reduction for HTS treatment. However, we believe such consistency cannot be claimed, as the (small) study quoted to support this claim [4] has actually compared a HTS/starch combination to mannitol and found that both effectively reduced ICP. While the HTS/starch combination had a statistically *Correspondence: [email protected] 1 Intensive Care Unit, CHU Nice, Nice, France Full list of author information is available at the end of the article This article refers to the response: https​://doi.org/10.1007/s1202​8-02001064​-5; https​://doi.org/10.1007/s1202​8-020-00959​-7.

significant higher maximum ICP decrease and lower ICP values at 60 min compared to mannitol, it is highly questionable whether these statistical differences have any clinical relevance [4]. The same applies to other solutions such as hypertonic lactate [5]. A European Society of Intensive Care Medicine (ESICM) consensus on fluid therapy in brain injured patients has addressed this question as well [6]. Nine randomized controlled trials (RCTs) were selected comparing mannitol with HTS, representing only low-quality evidence in favor or against specific hypertonic agents [5, 7–11]. The one multicenter observational study that reported potential superiority of HTS (a significantly lower mean daily and cumulative ICP burden in the HTS group compared with mannitol) was graded as very low evidence [12]. The final conclusion of the consensus was that the studies com