8/18/2019 Isoflurane for ICU Sedation Dead or Alive .2

1/2 Copyright © 2015 Wolters Kluwer Health Inc. All rights reserved.

INVITED COMMENTARY

Isoflurane for ICU sedation – dead or alive?Peter Sackey

European Journal of Anaesthesiology   2016,  33:4–5

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 ¼ 0.002] and within

the first 365 days (OR 0.45, 95% CI 0.25–0.82,  P ¼ 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 ¼ 0.002) and within the

first 365 days (OR 0.41; 95% CI 0.21–0.81,   P ¼ 0.01).

They had more ventilator-free days at 60 days

(32.5 29.2 vs 23.2 28.2 days,  P ¼ 0.03) and more hos-pital-free days at 180 days (62.1 59.5 vs 44.1 64.8 days,

 P ¼ 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 anaestheticsedation. Although the study is retrospective, nonrando-

mised and single centre, the results remain highly provo-

cative.

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 postcondition-

ing mechanisms have been described.1,2 Apart from pre-

clinical data, clinical studies indicate that volatileanaesthetics have   organ-specific  benefits for the liver,3

kidney,4 heart5– 7 and brain.8,9 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 postu-

lated 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 incritically 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 pro-

voke 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.

Eur J Anaesthesiol  2016;  33:4–5

This Invited Commentary accompanies the follow-

ing 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 sur-gical patients.  Eur J Anaesthesiol  2016;  33:6–13.

From the Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Correspondence to Peter Sackey, Karolinska University Hospital/Karolinska Institutet, Stockholm, SwedenE-mail: peter.sackey@karolinska.se

0265-0215 Copyright    2015 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000000351

mailto:peter.sackey@karolinska.sehttp://dx.doi.org/10.1097/EJA.0000000000000351http://dx.doi.org/10.1097/EJA.0000000000000351mailto:peter.sackey@karolinska.se

8/18/2019 Isoflurane for ICU Sedation Dead or Alive .2

2/2 Copyright © 2015 Wolters Kluwer Health Inc. All rights reserved.

Acknowledgements relating to this articleAssistance with the Invited Commentary: none.

Financial support and sponsorship: none.

Conflicts of interest: the author has received honoraria from

Abbvie AB in respect of lectures given and has been a consultant

for Baxter Global and for Scandinavian Development Services,

Stockholm.

Comment from the Editor: this Invited Commentary was checked

andaccepted by theeditorsbut wasnot sent for external peer review.

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pharmacological postconditioning in liver surgery: results of a prospectiverandomized controlled trial.  Ann Surg  2012;  256:837-844.

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Eur J Anaesthesiol  2016;  33:4–5