We appreciate Li's and Wang's1 comments on our recently published article in which we compared survival after long-term isoflurane sedation with intravenous (i.v.) sedation in critically ill surgical patients.2 We strongly agree with several of the important points they outlined, especially that deep sedation may increase long-term mortality.3 In the years the study was performed, we generally targeted Ramsay Scores between 2 and 4 in both groups. Unfortunately, because of poor documentation, we cannot present actual scores. However, patients sedated with isoflurane usually did not react to verbal stimuli, hence reached higher scores. We recently analysed Richmond Agitation and Sedation Scores of patients sedated i.v. or by inhalation. We found significantly deeper degrees of sedation in patients sedated by inhalation. Hence, patients in the isoflurane group appear to have been sedated more deeply, which cannot explain their lower mortality rate. However, deep i.v. sedation may have provoked a high mortality in that group, whereas with volatile anaesthetics, depth of sedation may not play a role. In our article,2 we discussed that perhaps isoflurane use per se is not the reason for an improved survival rate, but rather the avoidance of deleterious adverse effects of i.v. sedatives. Further analyses are needed to find the best sedation depth for isoflurane.
We also agree that tracheostomy and the long time span for patient recruitment could be a confounder in our mortality analysis.4–6 Based on these suggestions, we looked at the data again; 30 of 128 (23%) patients in the propofol/midazolam group and 23 of 72 (32%) patients in the isoflurane group were tracheotomised during their ventilation period. The slightly higher tracheostomy rate in isoflurane patients may be explained by their higher survival rate. The years the patients were included were distributed as follows (propofol/midazolam versus isoflurane): 2005, 22 versus 6; 2006, 23 versus 9; 2007, 24 versus 15; 2008, 21 versus 17; 2009, 24 versus 14 and 2010, 14 versus 11. Neither the tracheotomy rate nor the year of inclusion showed statistically significant differences (P = 0.19 and P = 0.36, respectively). We further adjusted for tracheostomy and the year of sedation, as well as all previously adjusted confounders in our final study population. After adjustment, following isoflurane sedation, patients still had a lower risk of in-hospital death (odds ratio 0.36; 95% confidence interval 0.19 to 0.71, P = 0.003) and of death within 365 days (odds ratio 0.42; 95% confidence interval 0.21 to 0.84, P = 0.014). These results underline the proposed benefit of isoflurane sedation as opposed to i.v. sedation in critically ill surgical patients.
However, as this is a retrospective study performed in one hospital only, we cannot completely rule out provider bias and agree with Li and Wang that further multicentre randomised controlled trials are needed to examine outcome parameters after inhalational versus i.v. sedation.
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1. Li X, Wang R. Survival after long-term isoflurane sedation in critically ill surgical patients. Eur J Anaesthesiol
2. Bellgardt M, Bomberg H, Herzog-Niescery J, et al. Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: retrospective analysis. Eur J Anaesthesiol
3. Shehabi Y, Chan L, Kadiman S, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med
4. Griffiths J, Barber VS, Morgan L, et al. Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation. BMJ
5. Koch T, Hecker B, Hecker A, et al. Early tracheostomy decreases ventilation time but has no impact on mortality of intensive care patients: a randomized study. Langenbecks Arch Surg
6. Dunham CM, Cutrona AF, Gruber BS, et al. Early tracheostomy in severe traumatic brain injury: evidence for decreased mechanical ventilation and increased hospital mortality. Int J Burns Trauma