Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery

Abstract

Background It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. Methods Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. Results The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. Conclusions This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Opioid-Free Anesthesia Benefit–Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…After a review of the titles and abstracts, 81 studies were selected and assessed for potential inclusion into this systematic review. After reading the full-text articles, 33 RCTs (published between 1994 and 2021) including 2209 participants were finally included ( Figure 1 ) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. No unpublished trials were identified with our eligibility criteria in the clinicaltrial.gov register.…”

“…The median target sample size was 60 [ 27 , 28 , 29 , 30 , 31 ] (median (min–max)) patients. Participants were adults with American Society of Anesthesiologists physical statuses categorized as classes I to III.…”

“…Does OFA produce new side effects? The POFA trial provides crucial results to this question and offers a more reliable evaluation of the benefit–risk ratio of new strategies in anesthesia management, which is why this large multi-centric study is so precious among OFA studies [ 31 ]. In fact, under-evaluation and under-reporting of severe adverse events in the literature about new medications or strategies for OFA are clear limitations to the development of a complete understanding of the pharmacology and related side effects of OFA.…”

“…In the POFA trial, which is the largest available trial conducted on OFA, the high incidence of bradycardia led to the recommendation of a maximal dose of continuous dexmedetomidine use of 1 mcg/kg/h. Then, after severe adverse events were reported, with five cases of asystolia, patient recruitment was interrupted [ 31 ]. The emergence of severe adverse events in a significant cohort underlines that a collection of small studies is unable to offer a reliable evaluation of tolerance issues.…”

Effects of lidocaine, dexmedetomidine, and their combination infusion on postoperative nausea and vomiting following laparoscopic hysterectomy: a randomized controlled trial

“…Although dexmedetomidine possesses the hypnotic and sedative effect, bradycardia is the most common side effect of dexmedetomidine administration, especially a large dose of dexmedetomidine. Beloeil H et al reported that dexmedetomidine-based, opioid-free anesthesia had higher rates of severe bradycardia [ 28 ]. A recent study reported prolonged recovery in patients receiving dexmedetomidine, which was explained by over-sedation, hypotension, and bradycardia [ 29 ].…”