Anesthesia in the News
  • Benefits and Risks of One Opioid-free Anesthetic Regimen

    Concerns that perioperative intravenous (IV) opioids may contribute to persistent postoperative opioid use have led to attempts to avoid or limit their use in this setting. Smaller studies have already shown that opioid-free anesthesia (OFA) allows postoperative opioid sparing. After bariatric surgery (Feld et al, 2006), and spine surgery (Hwang et al, 2015), OFA protocols allowed better postoperative analgesia with less morphine consumption, and less risk of postoperative nausea and vomiting occurred with OFA during bariatric surgery (Ziemann-Gimmel et al, 2014).

    A team of French anesthesia researchers sought to test their premise that the reduced opioid consumption allowed by OFA compared with standard of care would be associated with a reduction of postoperative opioid-related adverse events (AEs).

    Their prospective, multicenter, parallel-group, single-blind randomized, and controlled trial was published earlier this year in journal Anesthesiology. It compared postoperative outcomes in patients undergoing elective intermediate or major noncardiac surgery receiving balanced general anesthetic using desflurane plus IV infusions of nonopioids (ketamine, lidocaine, dexmedetomidine) versus those receiving desflurane plus ketamine, lidocaine, and opioids (remifentanil plus a morphine bolus at the end of surgery).

    Protocols and outcomes

    The trial conducted in 10 centers across France, began participant recruitment in November 2017. 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 hours after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting.

    Stopped for safety

    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 in 110 of 152 (72%) of dexmedetomidine group and in 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-hour 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.

    ‘Converse’ results

    In summary, among study patients undergoing elective intermediate or major noncardiac surgery, more of those having OFA with dexmedetomidine had serious AEs compared with those receiving remifentanil. Despite less postoperative opioid consumption and nausea and vomiting, patients receiving OFA with dexmedetomidine had more intraoperative severe bradycardia and hypoxemia in the Post-Anesthesia Care Unit (PACU), longer time to extubation, and longer PACU stay.

    Notwithstanding the study’s limitations — including its premature interruption due to safety concerns —the authors write that their results “suggest that opioid-free balanced anesthesia is not as outstanding when compared with intraoperative opioids and raises questions about the benefit of eliminating intraoperative opioids and using dexmedetomidine when lidocaine and ketamine are already used.”

    Find the full study, “Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery”. Anesthesiology. 2021 Apr 1;134(4):541-551. and read it at no cost at: https://pubs.asahq.org/anesthesiology/article/134/4/541/115422/Balanced-Opioid-free-Anesthesia-with