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Dear Sir: Rozendaal et al. [1] should not have concluded that the shortened ventilator weaning time associated with remifentanil use was because of the characteristics of this medication, without considering at least one other possible cause. Cortisol deficiency is present in 30–50% of patients receiving mechanical ventilation in some series [2, 3], and in them has been associated with more than a doubling of weaning time [2] and striking increases in mortality [3]. Acute and prolonged administration of benzodiazepines strongly inhibits cortisol production [4], with a single injection of midazolam at a dose of 0.07 mg/kg sometimes prominently inhibiting cortisol formation for more than a week [5]. Multiple studies suggest that benzodiazepine-induced lowering of cortisol levels may be enhanced by concurrent use of opioids and propofol, but cortisol levels during the use of remifentanil and propofol have not been investigated.
In order to examine the possible effect of medications in each of their study arms on the duration of required mechanical ventilation, any cortisol levels measured in their patients, any administration of corticosteroid therapy to them, relationships between these values and the duration of mechanical ventilation, and withdrawal of patients from the study for any reason, including death, would help to clarify any contributions by remifentanil to the duration of ventilator support and other aspects of patient care.
References
Rozendaal FW, Spronk PE, Snellen FF, Schoen A, van Zanten ARH, Foudraine NA (2009) Remifentanil-propofol analog-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: a centre randomized, cross-over, open-label study in the Netherlands. Intensive Care Med 35:291–298
Huang CH, Lin HC (2006) Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 173:276–280
Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Levy B, Bollaert PE (2005) Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 31:388–392
Arvat E, Maccagno B, Ramunni J, DiVito L, Giordano R, Gianotti L, Broglio F, Camanni F, Ghigo E (1999) The inhibitory effect of alprazolam, a benzodiazepine, overrides the stimulatory effect of metyrapone-induced lack of negative cortisol feedback on corticotroph secretion in humans. J Clin Endocrinol Metab 84:2611–2615
Kay J, Findling JW, Raff H (1994) Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects. Anesth Analg 79:501–505
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Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License (https://creativecommons.org/licenses/by-nc/2.0), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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Daniell, H.W. Does remifentanil shorten ventilator maintenance, midozolam prolong it, or both alter its duration?. Intensive Care Med 35, 1649 (2009). https://doi.org/10.1007/s00134-009-1539-8
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DOI: https://doi.org/10.1007/s00134-009-1539-8