Abstract: We have included 18 studies with 1087 participants of whom 545 received HS compared to 542 who received IS. All participants were over 18 years of age and all trials excluded high-risk patients (ASA IV). All trials assessed haematological parameters peri-operatively and up to three days post-operatively. There were three (< 1%) deaths reported in the IS group and four (< 1%) in the HS group, as assessed at 90 days in one study. There were no reports of serious adverse events. Most participants were in a positive fluid balance postoperatively (4.4 L IS and 2.5 L HS), with the excess significantly less in HS participants (MD -1.92 L, 95% confidence interval (CI) -2.61 to -1.22 L; P < 0.00001). IS participants received a mean volume of 2.4 L and HS participants received 1.49 L, significantly less fluid than IS-treated participants (MD -0.91 L, 95% CI -1.24 to -0.59 L; P < 0.00001). The maximum average serum sodium ranged between 138.5 and 159 in HS groups compared to between 136 and 143 meq/L in the IS groups. The maximum serum sodium was significantly higher in HS participants (MD 7.73, 95% CI 5.84 to 9.62; P < 0.00001), although the level remained within normal limits (136 to 146 meq/L). A high degree of heterogeneity appeared to be related to considerable differences in the dose of HS between studies. The quality of the evidence for the outcomes reported ranged from high to very low. The risk of bias for many of the studies could not be determined for performance and detection bias, criteria that we assess as likely to impact the study outcomes. HS reduces the volume of intravenous fluid required to maintain people undergoing surgery but transiently increases serum sodium. It is not known if HS affects survival and morbidity, but this should be examined in randomized controlled trials that are designed and powered to test these outcomes.

Plain-language summary: We included 18 trials that compared HS to IS in people undergoing surgery. The trials included 1087 participants. Five hundred and forty-five (545) participants received HS and 542 received IS during their operations. The participants were randomly assigned to their groups. The studies took place in 11 countries. Study participants were over the age of 18. All studies excluded people with serious health risks from participating. All studies monitored fluid levels during the operation and up to three days after. There were seven deaths in total, three (less than 1%) from the IS group and four (less than 1%) from the HS group. The risk of death was very low in these studies. The studies did not report the occurrence of serious adverse events. Thirteen studies reported the amount of fluid given. The IS group received a mean of 2.4 L and the HS group received 0.91 L less (1.49 L). The highest amount of sodium in the blood over the course of the study was reported by 16 studies. The IS group had a median of 139 meq/L and the HS group was 7.73 meq/L higher. The normal acceptable range is 136 to 146 meq/L. For deaths and adverse events the trials lacked sufficient size and duration to adequately assess differences. We assessed the quality of evidence for deaths to be very low, and future studies are likely to change the result reported here. The reporting of the highest amount of sodium is of moderate quality. The measuring of blood sodium during an operation is a common measurement that is unlikely to be misrepresented.