Opioid-free Versus Opioid-based Anesthesia in Pancreatic Surgery

Stephane Hublet; Marianne Galland; Julie Navez; Patrizia Loi; Jean Closset; Patrice Forget; Pierre Lafere


BMC Anesthesiol. 2022;22(9) 

In This Article

Abstract and Introduction


Background: Opioid-free anesthesia (OFA) is associated with significantly reduced cumulative postoperative morphine consumption in comparison with opioid-based anesthesia (OBA). Whether OFA is feasible and may improve outcomes in pancreatic surgery remains unclear.

Methods: Perioperative data from 77 consecutive patients who underwent pancreatic resection were included and retrospectively reviewed. Patients received either an OBA with intraoperative remifentanil (n = 42) or an OFA (n = 35). OFA included a combination of continuous infusions of dexmedetomidine, lidocaine, and esketamine. In OBA, patients also received a single bolus of intrathecal morphine. All patients received intraoperative propofol, sevoflurane, dexamethasone, diclofenac, neuromuscular blockade. Postoperative pain management was achieved by continuous wound infiltration and patient-controlled morphine. The primary outcome was postoperative pain (Numerical Rating Scale, NRS). Opioid consumption within 48 h after extubation, length of stay, adverse events within 90 days, and 30-day mortality were included as secondary outcomes. Episodes of bradycardia and hypotension requiring rescue medication were considered as safety outcomes.

Results: Compared to OBA, NRS (3 [2–4] vs 0 [0–2], P < 0.001) and opioid consumption (36 [24–52] vs 10 [2–24], P = 0.005) were both less in the OFA group. Length of stay was shorter by 4 days with OFA (14 [7–46] vs 10 [6–16], P < 0.001). OFA (P = 0.03), with postoperative pancreatic fistula (P = 0.0002) and delayed gastric emptying (P < 0.0001) were identified as only independent factors for length of stay. The comprehensive complication index (CCI) was the lowest with OFA (24.9 ± 25.5 vs 14.1 ± 23.4, P = 0.03). There were no differences in demographics, operative time, blood loss, bradycardia, vasopressors administration or time to extubation among groups.

Conclusions: In this series, OFA during pancreatic resection is feasible and independently associated with a better outcome, in particular pain outcomes. The lower rate of postoperative complications may justify future randomized trials to test the hypothesis that OFA may improve outcomes and shorten length of stay.


Pancreas cancer is currently the seventh leading cause of cancer death worldwide. A major concern is that the incidence of pancreatic cancer is increasing in the Western world. It is anticipated to become the second leading cause of cancer-related mortality by 2030.[1] The only potentially curative treatment is surgical excision. However, by the time of diagnosis, due to advanced local progression or distant metastasis, pancreas cancer is frequently considered unresectable. Therefore, surgery is proposed as a viable option in only 10% to 20% of patients. Pancreatic resection is also the most complex abdominal operation, whose morbidity remains high with rates between 30 and 60%.[2] Postoperative complications such as surgical site infection, delayed gastric emptying (DGE), pancreatic fistula (POPF), post-pancreatectomy hemorrhage (PPH) and poor pain control are proved to be the main reasons for prolonged length of stay.[3] Even after successful pancreatic resection, the prognosis remains very poor. Early relapse and metastasis are not uncommon with a rate of recurrence between 65% to 95% of patients. Therefore, the 5-year survival rate of pancreatic cancer is approaching 20% after successful resection and chemotherapy. The median survival is between 18 and 29 months, ranking firmly last amongst all cancer sites outcomes for patients.[2]

Recent reviews have emphasized the importance of the perioperative period on oncologic outcome after cancer surgery.[4] Indeed, the biological perturbations that accompany the surgical stress response and the pharmacological effects of anesthetic drugs, paradoxically, can promote disease recurrence or the progression of metastatic disease. This is possibly linked to the suppression of natural killer cell activity, which may be particularly important after pancreatectomy.[5–7] Many perioperative risk factors that can modulate surgery-induced immunosuppression have been suggested such as anesthetic technique, analgesic agents, blood transfusion, hypothermia, and pain. Adequate postoperative pain relief during the early postoperative period seems to carry the greatest clinical implications for oncologic outcomes after pancreatic resection.[4,5] On the other hand, concerns have grown about unnecessary opioid use.[8] Nonetheless, opioids have been the mainstay of pain control after pancreas surgery. However, this approach is known to result in excess opioid consumption, potential narcotic dependence, respiratory depression, nausea, and vomiting, DGE and postoperative ileus. The latter two being known as the main drivers of length of stay after pancreatic surgery.[9] Therefore, every effort to minimize opioid use have been at the forefront with the implementation of opioid sparing strategies tailored to each institutional expertise as strongly recommended by the ERAS society.[10] Opioid-free anesthesia (OFA) is described but its feasibility and possible benefits when compared with opioid-based anesthesia (OBA) remain largely unexplored.[11] This study reviews the outcomes in a single-center cohort of patient who underwent pancreatic resections under OBA versus OFA.