麻醉

异氟醚用于ICU镇静- 死了还是活着?

作者:陈亚云 编译 来源:医学论坛网 日期:2015-12-21
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         Isoflurane for ICU sedation dead or alive? Sackey, Peter In this issue ofEuropean Journal of Anaesthesiology, Bellgardtet al.(pp. 613) present a study comparing hospital mortality and 1-year mortali

Isoflurane for ICU sedation – dead or alive?

Sackey, Peter

In this issue of European Journal of Anaesthesiology, Bellgardt et al.(pp. 6–13) present a study comparing hospital mortality and 1-year mortality in postoperative ICU patients, sedated with either isoflurane or a propofol/midazolam combination.

The original 369 consecutive surgical patients were restricted to a group of 200 in order to make groups similar. This included only patients aged 40–79 years and those who required more than 96 hours of sedation, and excluded those who received both types of sedation. The authors found that those receiving isoflurane had a lower risk of death in hospital [odds ratio (OR) 0.39, 95% confidence interval (CI) 0.22–0.71, P = 0.002] and within the first 365 days (OR 0.45, 95% CI 0.25–0.82, P = 0.009) than those who received propofol/midazolam. After adjusting for potential confounders, patients given isoflurane still had a lower risk of death in hospital (OR 0.35; 95% CI 0.18–0.68, P = 0.002) and within the first 365 days (OR 0.41; 95% CI 0.21–0.81, P = 0.01). They had more ventilator-free days at 60 days (32.5 ± 29.2 vs 23.2 ± 28.2 days, P = 0.03) and more hospital-free days at 180 days (62.1 ± 59.5 vs 44.1 ± 64.8 days, P = 0.04). Interestingly, long-term mortality differences remained significant in an additional analysis of the full cohorts, including all age groups, and also in sensitivity analyses.

This study is not without limitations. The decision to initiate isoflurane sedation was at the discretion of the physician on call and there were only two sets of equipment available. The authors further state that German Health Insurance requirements were such that only patients continuously ventilated for more than 96 h had detailed medical data in the hospital information system database, making it impossible to include patients with shorter ventilation and sedation times. Despite the limitations, this study is of special note because no other has investigated long-term mortality after prolonged volatile anaesthetic sedation. Although the study is retrospective, nonrandomised and single centre, the results remain highly provocative.

The authors report mortality from all causes only, without subdivision. How mortality might be affected by the choice of ICU sedative remains speculative. One such speculation might be that isoflurane induced some form of organ protection, and there is a body of preclinical evidence suggesting that volatile anaesthetics can do this. Several intracellular preconditioning and postconditioning mechanisms have been described.1,21,2 Apart from preclinical data, clinical studies indicate that volatile anaesthetics have organ-specific benefits for the liver,3 kidney,4 heart5–75–75–7 and brain.8,98,9 A major difference between these studies and that of Bellgardt et al. (pp. 6–13) is that they describe several days of low-dose treatment, in contrast to that administered in most studies of volatile anaesthetic-induced organ protection. Is there a general or specific organ-protective effect of isoflurane sedation, mediated via one or several postulated preconditioning or postconditioning mechanisms? Or does such long-term exposure pose toxicity risks?

There is a paucity of data on the potential positive or negative effects of long-term low-dose exposure in critically ill patients arising from this expanding off-label method of sedation (pp. 6–13). Bellgardt et al. (pp. 6–13) do not tell us the mechanisms for improved survival but their contribution is stimulating and hopefully will provoke larger randomised, controlled trials to shed more light on possible short or long-term effects of long-term isoflurane sedation in addition to possible mediators of improved survival.

This Invited Commentary accompanies the following original article:

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. Eur J Anaesthesiol 2016; 33:6–13.

European Journal of Anaesthesiology:

January 2016 - Volume 33 - Issue 1 - p 4–5

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