Volatile agents for ICU sedation?

Abstract

Sedation is a standard part of critical care and was unchallenged from 1960 to 2000. Classical sedation approaches are associated with significant post-traumatic stress traits [1]. Because of poor pharmacokinetics/pharmacodynamics and planning problems, patients in the intensive care unit (ICU) spend one-third of their duration of stay being ventilated after the resolution of the problem mandating intubation [2, 3]. The aim of sedation in the ICU is to make the patient calm and tolerant to the critical care therapies, in particular mechanical ventilation. Recently several approaches have proven beneficial for patient care and the healthcare system: prospective trials have shown that daily interruptions of sedation are associated with a decrease in length of ventilation and decrease in ICU stay [4]. If a spontaneous breathing trial is used in addition to daily sedation interruption, the 1-year survival is improved [5] without an increase in psychological consequences [6]. Recent data suggest that no sedation at all may be better [7]. This move has been made possible by the improvement in ventilator algorithms, which are increasingly flexible in dealing with variable patient efforts. Over the last 10 years, the pendulum has moved toward a decrease in sedation with proactive strategies [8]. In this frame, the quest for the ideal sedation agent is continuing. The ideal sedative agent should be fast acting, have a rapid onset, not be organ dependent in terms of degradation, not have metabolically active or toxic by-products, have little cardiovascular effects, and be cheap. Over the last 30 years, midazolam, propofol [9], and dexmedetomidine [10,11] have been rolled out with the promise of being better than the previous generation of drugs.Sedation management in the ICU is a complex process involving sedation level assessment, medication administration, and an overall strategy. These three components are essential for correct ICU sedation. No one will give norepinephrine in the ICU without measuring blood pressure and having a strategy and objectives for vasopressor use, i.e., norepinephrine up to 20 lg/min for a mean arterial pressure (MAP) of 65 mmHg. Why are we tolerating this ''art'' of sedation and analgesia in the ICU? There is confusion in the literature between sedation/ hypnosis, analgesia, delirium management, and relaxation. This is shown by a recent meta-analysis regarding dexmedetomidine [12] pooling studies on dexmedetomidine used with sedation end points, morphine-sparing end points, and delirium end points. A hypnotic is a hypnotic, an analgesic is an analgesic, an antipsychotic is a drug used to treat delirium episodes [13], and a neuromuscular blocker is a relaxant medication. Although these classes of drugs have synergistic effects they cannot be used interchangeably.Volatile anesthesia agents have been in use for 50 years in anesthesia but only marginally in the ICU [14,15]. The first volatile agents were hepatotoxic and induced significant arrhythmias, which make then unsuitable for longterm ICU...

Propofol increases morbidity and mortality in a rat model of sepsis

“…We are aware that performing sedation with volatile anesthetics is an off-label use in many countries and is not considered a standard regimen [ 24 ]. However, these drugs may provide benefits such as no organ-dependent degradation, minimal metabolism and short titration and awakening times [ 64 ].…”

Sedation for Critically Ill or Injured Adults in the Intensive Care Unit

“…desflurane, isoflurane and sevoflurane) for ICU sedation. [300][301][302] At low alveolar concentrations, volatile anaesthetics produce amnesia, euphoria, analgesia and hypnosis. [50] At higher concentrations, they lead to deep sedation, muscle relaxation and diminished motor and autonomic responses to painful stimuli.…”

“…[306] Although the AnaConDa Ò has been introduced for use in the ICU setting [300,302] (table IV), its widespread uptake is likely limited secondary to various device-and non-device-related concerns. [301,306] First, changing the respiratory rate or tidal volume altered the expired volatile anaesthetic fraction in one bench study, and the standard luer lock on the liquid volatile-filled syringe allowed it to be inadvertently connected to an intravenous infusion line. [306] Second, there may be issues surrounding environmental pollution and adequate scavenging of waste gas.…”

Intensive care sedation: the past, present and the future

“…To avoid repeating the etomidate story, safety assessment according to current drug development standards is mandatory before introducing new drugs for ICU sedation [29]. At the moment, even the most basic experimental safety data on the long-term effects of prolonged administration of inhalational anesthetics are lacking.…”