Comments on Albrecht etal. reviews.

Abstract

We read with great interest the two meta-analyses by Albrecht's group on opioid-free anaesthesia 1 and dexmedetomidine 2. These studies are notable for addressing a very important question in this era of increasingly widespread opioid-free anaesthesia around the world: what are the clinically meaningful benefits of opioid-free anaesthesia? The conclusions of these two meta-analyses should, however, be taken with caution. In the first, Frauenknecht et al. 1 reported moderate evidence that postoperative nausea and vomiting is reduced with opioid-free anaesthesia compared with opioid-based anaesthesia. In the second meta-analysis, Grape et al. 2 reported moderate evidence that intra-operative dexmedetomidine during general anaesthesia improves postoperative pain with fewer side-effects. As clearly specified by the authors in their introduction, this meta-analysis examined intra-operative dexmedetomidine included in opioid-free anaesthesia. Therefore, in order to compare opioid-free anaesthesia with opioid-based anaesthesia, studies in which patients received opioids in both groups should not be included in the two meta-analyses, However, in both meta-analyses, patients in four studies received opioids in both groups and some studies date back to 1991 and 1996 and therefore do not reflect today's practice. Indeed, modern opioid-free anaesthesia is not just about avoiding opioids but rather it involves multi-modal anaesthesia with differing drugs. Recent opioid-free anaesthesia studies did not appear to be included 3. In terms of methodology, the outcome in some of the included studies was the haemodynamic effect of dexmedetomidine and not pain scores or morphine consumption. Dexmedetomidine has indeed been proposed as an adjuvant during opioid-free anaesthesia due to its haemodynamic stability. The primary outcome of both meta-analyses was, however, pain at rest. The research was not exhaustive since only two identical electronic databases were searched; PubMed is an interface used to search Medline. In these circumstances, publication bias cannot be excluded. ‘Opioid-free’ was not one of the keywords used for the search in the first meta-analysis and the presence, or not, of regional/epidural anaesthesia was not assessed. Furthermore, the difference reported at 2 h in the dexmedetomidine group does not reach clinical significance because 0.7 points represents < 20% of the mean pain scores in the remifentanil group and this difference did not persist at 24 h. Finally, the authors did not downgrade the confidence in the evidence despite serious inconsistencies reported in both meta-analyses for the primary outcome (I2 > 80%). All of these elements, when combined, decrease confidence in the conclusions and the message should be moderated. We believe that opioid-free anaesthesia is a promising technique and anaesthetists are rightly enthusiastic about it; however, we also need to be cautious, as rigorous randomised controlled trials looking at modern opioid-free anaesthesia are lacking. The technique of opioid-free anaesthesia cannot be formally recommended until further evidence of its benefits is shown.