%0 Journal Article %T Hypernatremia and intracranial pressure: more questions than answers %A Donald EG Griesdale %A Mypinder S Sekhon %A William R Henderson %J Critical Care %D 2013 %I BioMed Central %R 10.1186/cc11888 %X In a previous issue of Critical Care, Wells and colleagues [1] report on their retrospective cohort study examining the relationship between serum sodium and intracranial pressure (ICP) with severe traumatic brain injury (TBI). This is an ongoing topic of interest to neurointensivists as hyperosmolar therapy remains a treatment option for elevated ICP [2]. We commend the authors for their contribution to a fundamentally important issue in neurocritical care; however, several issues deserve further discussion.A critical limitation of observational methodology is confounding by indication, which exists when variables associated with exposure are also associated with outcomes in the study base [3]. Clinicians administer hyperosmolar therapy and induce hypernatremia on the basis of measured and unmeasured characteristics of patients. Lack of a formalized TBI protocol, including indications for hypertonic saline (HTS), can exacerbate this bias. For example, clinicians in the study by Wells and colleagues used both boluses and infusions of HTS with a range of administered concentrations (3% versus 7.5%). No attempt was made to adjust for differences in baseline characteristics of patients. Furthermore, although regression is an important method to help reduce bias, several assumptions must be met for the analysis to be valid. Linear regression is predicated upon independence of data. With 1,230 paired sodium and ICP measurements in 81 patients, there is likely to be marked within-subject correlation of data that is not taken into account by this analysis. Consequently, a linear mixed model or other analysis is warranted to specifically model and account for this correlation [4]. Failing to do so limits the interpretability of their results.Diana L Wells, Joseph M Swanson, G Christopher Wood, Louis J Magnotti, Bradley A Boucher, Martin A Croce, Charles G Harrison, Michael S Muhlbauer and Timothy C FabianWe thank Griesdale and colleagues for their thoughtful letter describi %U http://ccforum.com/content/17/1/401