In this episode, I’ll discuss the use of volatile anesthetic agents for ICU sedation.
Background
The concept of using volatile agents for ICU sedation is something that has been studied and marketed for over a decade internationally. With the focus on preventing the development of ICU delirium, volatile anesthetic agents are being investigated as an alternative to standard ICU sedatives.
Agents
The most commonly used volatile anesthetic agents are desflurane, sevoflurane, and isoflurane. Each of these agents produces a state of sedation due to effects on GABA, nicotinic acetylcholine, and glutamate receptors. The complete mechanism of action of these agents is unknown.
The onset of action of each of these agents is within minutes. The duration of action is context sensitive, with longer periods of use corresponding to longer durations of action.
Excretion for these agents occurs primarily in the lungs, therefore hepatic and renal dysfunction should not affect elimination or duration of action.
Safety & Efficacy
Because the volatile anesthetic agents act primarily in the cerebral cortex, cardiovascular and respiratory effects are much less frequent than with standard ICU sedatives.
The safety of prolonged use of volatile agents for ICU sedation is much less studied compared with traditional sedatives.
I discussed a recent meta-analysis of the use of volatile anesthetic agents for ICU sedation in episode 141. The authors reviewed randomized controlled trials comparing inhaled volatile agents (desflurane, sevoflurane, and isoflurane) for sedation to intravenous midazolam or propofol. Eight trials with 523 patients were included in the analysis. The reduction in extubation time using volatile agents was a mean of 292 minutes with midazolam and 29 minutes with propofol. There was no significant difference in time to obey verbal commands, the proportion of time spent in target sedation, adverse events, death, or length of hospital stay.
The external validity of this data is limited by publication bias. In addition, extubation time is a soft endpoint. Hard endpoints like reductions in morbidity and mortality will need to be demonstrated before the use of volatile agents in the ICU becomes more widespread.
A long-term randomized trial comparing intravenous propofol/midazolam to inhaled isoflurane is due to be completed September 2017. This study is intended as a pilot study to explore the feasibility of providing ICU sedation with isoflurane to adult ICU patients requiring mechanical ventilation and sedation for more than 48 hours.
A study of sevoflurane for ICU sedation in patients who are agitated despite maximal doses of propofol or midazolam is due to be completed October 2017. This study is primarily looking at the time to sedation with sevoflurane, although safety data will also be collected.
German guidelines for the management of delirium, analgesia, and sedation in intensive care medicine list volatile agents as a second-line option for sedation of patients in the ICU.
Practical considerations
There are several practical considerations for the use of volatile anesthetic agents for ICU sedation:
- Staff will need to be fully trained on equipment and the unique properties of these agents.
- Steps need to be taken to minimize the amount of these gasses which escape into the air that staff, visitors, and other patients will breathe in.
- The rare risk of malignant hyperthermia with these agents means that staff will need to be able to promptly recognize and treat malignant hyperthermia should it occur.
- Close interdisciplinary communication must occur. Dosing for these agents changes as the minute ventilation changes. While a physician or respiratory therapist may typically adjust an ICU patient’s minute volume, the nurse is typically responsible for titration of sedative doses.
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