Patrick Meybohm, Hugo Van Aken, Andrea De Gasperi, Stefan De Hert, Giorgio Della Rocca, Armand RJ Girbes, Hans Gombotz, Bertrand Guidet, Walter Hasibeder, Markus W Hollmann, Can Ince, Matthias Jacob, Peter Kranke, Sibylle Kozek-Langenecker, Stephan Alexander Loer, Claude Martin, Martin Siegemund, Christian Wunder and Kai Zacharowski
We are grateful to Haase and colleagues for their interest in our paper . We appreciate their amendment to the original paper that ‘lack of fluid data after day 3 is thus due to early death or discharge from the ICU’ because this very important issue was not previously mentioned . Further, we fully agree with the authors that ‘such algorithms for HES use must undergo testing in trials with low risk of bias’.
Regarding the subgroup analysis, however, we disagree with the data analysis. Regarding 30-day mortality in the trial by Siegemund and colleagues, 36 out of 125 patients in the control group and 34 out of 119 patients in the HES group died (M Siegemund, personal communication), resulting in a risk ratio of 0.99 (0.67 to 1.47 95% CI). Taking these data into account would yield a combined risk ratio of 1.12 (0.88 to 1.42 95% CI) in the subgroup of trials with ‘high probability of correct fluid indication’ (Figure 1). This combined point estimate for mortality does not indicate an increased risk of mortality in the subgroup of probably correct indication. The estimate rather suggests that, assuming the applied principles of fluid administration are adhered to, the tested interventions are associated with a similar risk for the outcome mortality.
Most importantly, rather than empirically splitting the trials into two groups according to a cutoff value of three points on the scale, we highly recommend performing meta-regression to investigate more appropriately how the different components of the scale did influence treatment effects .
In conclusion, algorithms for HES use must undergo testing in trials with low risk of bias, and identification of patients with correct indication is recommended.