Abstract Background Thoracic epidural analgesia has been the mainstay for pain control in esophageal cancer patients undergoing minimally invasive esophagectomy (MIE). Although effective epidural analgesia potentially contributes to achieving enhanced recovery after surgery (ERAS) goals in patients undergoing MIE, it can have counterproductive side effects such as hypotension, urinary retention and reduced mobility. Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery. Methods This open randomized controlled superiority trial was conducted across four Dutch centers. A total of 192 patients with esophageal cancer, scheduled for elective transthoracic MIE with intrathoracic anastomosis, were included and randomized to receive either epidural analgesia or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included the quality of life, postoperative pain, opioid consumption, need for inotropic/vasopressor medication, duration of admission, mobilization, complications, readmission, and mortality. Results From December 2019 to February 2023, 94 patients were assigned to epidural and 98 to paravertebral analgesia. QoR-40 score on POD3 did not differ between groups (mean difference 3.7; P=.268). The epidural group had higher QoR-40 scores on POD1 and 2 (mean difference 7.7; P=.018, mean difference 7.3; P=.020) and lower pain scores (1 versus 2; P=<.001, 1 versus 2; P=.033). More patients in the epidural group required vasopressor-medication on POD1 (38.3% versus 13.3%; P<.001). In the paravertebral group, the urinary catheter was removed one day earlier (P=<.001). No significant differences in complications or length of stay were observed. Conclusion This multicenter randomized controlled clinical trial did not show superiority of paravertebral analgesia over epidural analgesia in quality of recovery on the third day after minimally invasive esophagectomy. These results, however, support the safety of paravertebral analgesia as a viable alternative to epidural analgesia, enabling the provision of both techniques to patients in clinical practice.
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