Opioid free anesthesia protocol on early quality of recovery after major surgery (SOFA trial)
Summary by Mitchell Best, MD 6.08.24
https://pubs.asahq.org/anesthesiology/article/doi/10.1097/ALN.0000000000004840/139425/Opioid-free-Anesthesia-Protocol-on-the-Early?searchresult=1
Clinical Hypothesis: An opioid free anesthesia protocol (OFA) would improve quality of recovery (QoR) at 24h postop compared to standard anesthesia protocol based on opioid administration during major elective surgeries in adults.
Take Home Message:
· An OFA protocol yielded statistically significant but not clinically significant improvements in early postoperative recovery at 24, 48, and 72 hours for patients undergoing major surgery when compared to standard anesthesia protocol involving opioids.
· There was no significant difference in quality of life at 3 months postoperative between groups
· Median length of stay in-hospital as well as hospital morphine-equivalent consumption of opioids were similar between groups
Summary:
Background: This superiority, randomized, controlled, patient-blinded, single-center trial was conducted to determine differences in quality or recovery with opioid free anesthesia vs standard anesthesia protocol in adult patients scheduled for elective major surgery.
Study Design: 136 patients were randomized into either opioid free anesthesia or standard anesthesia protocol. Following 2 surgical cancellations and 1 withdrawal of consent, there were 65 in the OFA group, and 68 in the standard anesthesia group. Only 55 of 65 OFA and only 57 of 68 standard received allocated protocol and were included in study. In the OFA group, they utilized at least 2 nonopioid agents including: clonidine infusion (initial 50μg/h titrated up to 150μg’h max as hemodynamically tolerated), magnesium sulfate infusion (40mg/kg), lidocaine infusion (1.5mg/kg bolus in 10mins followed by 1.5mg/kg/h), and ketamine infusion (0.5mg/kg bolus followed by 0.2 mg/kg/h). In the standard anesthetic arm, opioids (sufentanil or remifentanil) were utilized; this arm was also allowed to utilize a low dose ketamine bolus (0.15mg/kg) at induction with possible repeated boluses as per the facility’s standard practice. No preoperative medications were allowed; use of regional/local anesthesia was allowed (without opioid adjuvant in OFA).
Methods:
Inclusion criteria: Male and female adults aged 18 or older undergoing scheduled, major surgery estimated to last at least 90 minutes and anticipated to result in pain. Eligible surgical specialties included plastics, GI, urologic, gynecologic, and ENT.
Exclusion criteria: Surgeries involving bones, need for rapid sequence induction, pregnancy/lactation, severe psychiatric/cognitive disorders, extremes of BMI (< 18 or > 39), and contraindications to any study drugs.
Primary outcome: Early postoperative QoR at 24h as measured by French version of the QoR-15 score (a certified 15 item questionnaire yielding a total score ranging from 0 [poor recovery] to 150 [excellent recovery]).
Secondary outcomes: QoR-15 score at 48h and 72h, pain during effort (mobilization, cough, physiotherapy sessions), number of postoperative complications, postoperative consumption of morphine-equivalent opioids, length of stay in PACU and hospital, patient/anesthesiologist/surgeon satisfaction scores, and chronic postsurgery pain evaluated with the Brief Pain Inventory questionnaire as assessed by phone call 3 months postop.
Results:
QoR-15 score at 24h postop:
OFA group 114.9 +/- 15.2
Standard group 108.7 +/- 18.1
Difference 6.2; 95% CI .04 – 12; P 0.026 (assuming a difference of at least 8 to assume clinical significance)
QoR-15 score at 48h postop:
OFA group 123 +/- 13.4
Standard group 114.3 +/- 19.1
Difference 8.7; 95% CI 2.9-14.5; P 0.004
QoR-15 score at 72h postop:
OFA group 129.2 +/- 11.8
Standard group 121.9 +/- 19.4
Difference 7.3; 95% CI 1.6-13; P 0.013
Chronic pain affliction at 3months postop:
OFA group 21%
Standard group 30.8%
Difference 9.8%; 95% CI -25.2 – 5.6%; P = 0.164
No significant difference
Discussion/conclusion: Opioids are a routine and effective agent utilized in standard anesthetic management for achieving both pain relief and hemodynamic stability during and after surgery. They are also associated with a range of adverse effects that can compromise surgical recovery including delirium, drowsiness, nausea/vomiting, ileus, addiction, and apnea. Due to these effects, there has been growing adoption of opioid free anesthesia (OFA) protocols involving multimodal regimen of NMDA antagonists, anti-inflammatory meds, local anesthetics, and alpha-2 agonists. This study found that employment of these agents yielded a statistically, but not clinically, significant improvement in quality of recovery for patients undergoing major noncardiac elective procedures at 24, 48, and 72 hours postop.
Critiques:
- Low generalizability: single French center, 87.2% of participants women, 63.9% of cases plastics, most patients ASA I and II
- Despite being labeled “intention-to-treat,” this study omitted those patients initially randomized but who didn’t adhere to their treatment regimen
- Ketamine as permitted in both treatment groups and could be seen as a confounding variable
- Inappropriate power to identify prevalence of chronic pain and longer-term quality of life