Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP

We read with interest the prospective, double-blind, randomized study by Lee et al. [1], on comparing the sedative effect and adverse events of midazolam + meperidine + dexmedetomidine with those of midazolam + meperidine during endoscopic retrograde cholangiopancreatography (ERCP). The authors’ conclusion that the addition of dexmedetomidine to the midazolam + meperidine regimen provided better sedative efficacy during ERCP is significant to clinical practice for painless choledochoscopy procedures. However, we would like to make the following comments on the study.

First, dexmedetomidine is a relatively selective α₂ adrenergic agonist, which can induce not only sedation that is similar to physical sleep, but also produces an analgesic and anti-anxiety effect. However, in short procedures such as ERCP, the onset and duration of the effects of midazolam are too late and too prolonged to be useful in clinical practice; the same applies for meperidine.

Second, the addition of dexmedetomidine in the Lee et al. study significantly reduced the supplemental and total doses of midazolam required compared with the group without dexmedetomidine. However, according to the prescribing instructions for dexmedetomidine (Precedex; Abbott Laboratories, North Chicago, Illinois, USA), dose reduction should be considered in patients with impaired hepatic function because dexmedetomidine clearance decreases with increasing severity of hepatic impairment [2]. In the article by Lee et al., it appears that patients with hepatic impairment were not excluded from the study and this may have affected the results.

In addition, regarding the bispectral index evaluation of sedation used in the article, Haenggi et al. conducted an interventional study in healthy volunteers and found that variability of the bispectral index increased as sedation deepened [3]. This suggests that the bispectral index has not been adequately validated for monitoring sedation [3] [4].

• References

• 1 Lee BS, Ryu J, Lee SH et al. Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP: prospective, randomized, double-blinded trial. Endoscopy 2014; 46: 291-298
• 2 Abbott Laboratories. Precedex dexmedetomidine hydrochloride injection. North Chicago, Illinois: Abbott Laboratories; 2001 http://www.dexmedetomidine.com/Precedex.pdf Accessed July 2014
• 3 Haenggi M, Ypparila-Wolters H, Hauser K et al. Intra- and inter-individual variation of BIS-index^® and Entropy^® during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study. Crit Care 2009; 13: R20
• 4 Haenggi M, Ypparila-Wolters H, Buerki S et al. Auditory event-related potentials, bispectral index, and entropy for the discrimination of different levels of sedation in intensive care unit patients. Anesth Analg 2009; 109: 807-816