I read with interest the article by Sackey et al.  1and accompanying editorial2discussing the use of volatile anesthetics for sedation in the intensive care unit. Although the points regarding tailoring sedation to individual needs are accurate, there is a developing body of literature that suggests prolonged exposure to volatile anesthetics is unsafe, and I believe that Payen understates the case in the editorial.2 

It is clear that volatile anesthetics (and all N -methyl-d-aspartate receptor antagonists) cause widespread neurodegeneration in both rodent and primate models.3,4What is unclear is the relevance of these models to humans. To quote an occasionally used phrase, “rats are funny people,” and a prolonged exposure of 10-day-old rat pups to isoflurane, while mimicking the gestational age of a 36-week premature infant, may not be applicable to the relatively brief exposure of humans to volatile agents in a typical operating room setting. Prolonged use in the intensive care unit (ICU), however, is far different and comes closer to the exposure duration of the animal models.3,4Even Sackey et al.  mention reversible symptoms of ataxia, tremor, and clonus in children in whom volatile anesthetics have been used for sedation.1Although the potential harm to patients exhibiting these symptoms is unclear, their presence is unlikely to beneficial. Similarly, the aging brain may be vulnerable to yet-to-be elucidated neurotoxic effects of volatile anesthetics. Postoperative cognitive dysfunction in the elderly is a well-known phenomenon whose precise etiology is elusive, but again, animal studies suggest a possible correlation with expressions of Alzheimer-like pathology in rodents after volatile anesthetic exposure.5As is the case in studies of the developing brain, the relevance of animal models to human clinical care is unclear, but the prolonged exposure to volatile anesthetics in a scenario of ICU sedation approaches experimental conditions in animal studies. Finally, the mutagenic effects of volatile anesthetic exposure continue to be debated in the literature with some evidence to support acceleration of cancers after anesthesia.6 

The use of benzodiazepines, narcotics, and intravenous hypnotic agents such as propofol for ICU sedation is well established with an acceptable safety profile. As with any pharmaceutical therapy, there are side effects and challenges associated with their long-term administration, especially when relying on clinical guidance for management when muscle relaxants are used and without Bispectral Index or other monitors of depth of anesthesia. In the report by Sackey et al. , it is likely that the same therapeutic goals could have been accomplished with better titration of intravenous agents and use of Bispectral Index or similar technology and without the use of volatile anesthetics. It is increasingly clear that prolonged exposure to volatile anesthetics, especially in the immature, elderly, and compromised brain (the patients most likely to be in an ICU), may be associated with significant risk that is not justified by the clinical benefit of their use for ICU sedation. Until more definitive studies are done, I believe the use of volatile anesthetics for prolonged sedation should be approached with great caution, if at all.

Drexel University School of Medicine, Philadelphia, Pennsylvania. george.mychaskiw@drexelmed.edu

Sackey PV, Eriksson LI, Martling CR, Radell PJ: Case scenario: Tailored sedation to the individual needs of the intensive care unit patient. Anesthesiology 2010; 113:1439–46
Payen J: Toward tailored sedation with halogenated anesthetics in the intensive care unit? Anesthesiology 2010; 113:268–9
Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF: Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23:876–82
Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, Dissen GA, Creeley CE, Olney JW: Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010; 112:834–41
Mena MA, Preucho J, Rubio I, de Yebenes JG: Studies in animal model of the effects of anesthetics on behavior, biochemistry and neuronal cell death. J Alzheimers Dis 2010; 22 Suppl 3:43–8
Forget P, De Kock M: Could anaesthesia, analgesia and sympathetic modulation affect neoplastic recurrence after surgery? A systematic review centred over the modulation of natural killer cells activity. Ann Fr Anesth Reanim 2009; 28:751–68