It is with great interest that we read the article ‘A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy’ by Citerio et al.1 The authors are to be congratulated on completing a randomised study of such magnitude. Our neuroanaesthesia practice at the University of Texas M.D. Anderson Cancer Center averages 888 craniotomies annually, the majority of which are for tumour resection. As such, this article was of particular interest to our group. However, in our discussion, we identified several issues that might strengthen the study or perhaps contribute to future studies. First, all patients received midazolam 5 mg intravenously preoperatively. In our practice, standard premedication is midazolam 1 to 2 mg, and in some instances, premedication is not administered to craniotomy patients because of its potential to contribute to delayed emergence from anaesthesia or contribute to postoperative sedation. Because the primary endpoint of this study was the time to achieve an Aldrete postanaesthesia score (of which one component is consciousness) of 9 after tracheal extubation, what was the rationale for the use of midazolam, and particularly at the relatively high dose of 5 mg? Second, we would also like to inquire about the rationale for both urine and serum biomarkers. In the authors’ opinion, how clinically relevant are urinary markers? Specifically, how is one certain that the urine captured at a specific time point, such as during dural opening, accurately reflects biological stress markers at that time, given that markers have to get filtered through the kidneys and urine may pool in the bladder as a function of patient position? Also, diurnal fluctuations of cortisol and catecholamines are known to occur.2,3 Was this accounted for in the study? Finally, the authors do not comment on the administration of corticosteroids. In our practice, dexamethasone is routinely administered to help control perioperative cerebral oedema.4 If corticosteroids were administered, as is done commonly, could this not have impacted biomarker levels? Third, our final thought was why a fourth arm in the study was not included? We would anticipate that an arm consisting of patients randomised to propofol and fentanyl would allow a more complete comparison between the interplay of inhalational and intravenous anaesthetics and narcotics. We suspect that for the primary outcome, equivalence would be found. However, more importantly, we would expect to further delineate differences in the secondary endpoints such as postoperative opioid requirements and nausea/vomiting.
Again, we applaud the authors for conducting a study of this size and importance. As the accompanying Commentary suggested,5 we as anaesthesiologists need to look beyond the operating room and examine further how our patient care in the perioperative period can contribute to outcomes.
Assistance with the letter: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none declared.
1. Citerio G, Pesenti A, Latini R, et al NeuroMorfeo Study GroupA multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy. Eur J Anaesthesiol
2. Turton MB, Deegan T. Circadian variations of plasma catecholamine, cortisol and immunoreactive insulin concentrations in supine subjects. Clin Chim Acta
3. Linsell CR, Lightman SL, Mullen PE, et al Circadian rhythms of epinephrine and norepinephrine in man. J Clin Endocrinol Metab
4. McClelland S 3rd, Long DM. Genesis of the use of corticosteroids in the treatment and prevention of brain edema. Neurosurgery
2008; 62:965–967.discussion 967–968.
5. Nathanson M, Columb M. Research on neuroanaesthesia and real outcomes. Eur J Anaesthesiol