Participants were recruited as of December 2014 until December 2018. Loss to follow-up, due to exclusion or missing questionnaires, was greater than expected. The Regional Ethical Review Board granted our request to randomize another 47 patients to each group (2018/2-32). Consequently, 260 participants were included and randomized, 130 to PRM and 130 to control (Fig. 1).
Of 39 excluded participants, 21 had an ERCP, 14 had an extra surgical intervention (5 closures of mesenteric defects after previous bariatric surgery, 2 umbilical hernia repairs, 3 had extra ports because of intra-abdominal adhesions obstructing the view, and 4 received tube drainage (3 because of subtotal cholecystectomy)). Two had a complication; both postoperative infections: one requiring IV antibiotics and percutaneous drainage (CD III), and one with concomitant pancreatitis (CD II). Two participants should not have been enrolled, due to acute cholecystitis and pancreatitis, respectively.
Finally, 147 questionnaires were available for analysis, 76 in the intervention group (64 completed, 12 partially completed), and 71 in the control group (63 completed, 8 partially completed). A non-response analysis was performed on all available data, see Appendix. Apart for a shorter duration of surgery in the “loss to follow-up” group (85.5 (69.0–109.3) minutes compared to 95.0 (81.0–114.0) minutes), the analysis did not show any significant differences between the “loss to follow-up” group and the group with questionnaires.
Baseline characteristics were similar between the groups (Table 1). Clinical data are presented in Table 2. The only parameter with a significant difference between the groups was a somewhat longer duration of surgery in the PRM group. No pulmonary complication was observed.
Incidence of overall pain did not differ significantly between the groups on any occasion. For the postoperative 48-h period, the incidence of overall pain (NRS 1–10) was 98.7% in the PRM group and 94.4% in the control group (P=0.149). Overall pain intensity did not differ over time (P=0.739), nor at a certain hour (Fig. 2).
There was a significant difference in shoulder pain incidence favorable for the PRM group. During the 48 h after surgery, 44.7% suffered from shoulder pain in the PRM group, versus 63.4% in the control group (P=0.023). The Number Needed to Treat, NNT, to benefit from PRM was 6 (95% Confidence Interval, CI, 2.9–35.5). The incidence in shoulder pain was specifically lower in the PRM group 12 and 36 h after surgery (PRM 27.0% vs. control 46.4% at 12 h [P=0.016] and PRM 21.1% vs. control 38.2% at 36 h [P=0.027]) (Fig. 3). NNT was 6 (95% CI 2.9–26.1) at 12 h and 6 (95% CI 3.1–46.4) at 36 h after surgery.
Incidence of wound pain differed at 4 and 24 h postoperatively, in favor of the control group (25.7% vs. 41.3% [P=0.047] and 41.8% vs. 60.3% [P=0.029]). The difference was not significant when analyzing the occurrence of wound pain during the whole 48-h period after surgery; 67.1% experienced wound pain in the PRM group, versus 54.9% in the control group (P=0.130).
Incidence of nausea (NRS 1–10) during the 48-h period after surgery was 51.3% in the PRM group and 70.4% in the control group (P=0.018). The incidence of nausea was specifically lower in the PRM group 4 and 12 h after surgery (PRM 33.8% vs. control 55.7% at 4 h [P=0.011] and PRM 24.7% vs. control 43.5% at 12 h [P=0.018]). The NNT to benefit from reduced nausea incidence was 6 (95% CI 2.9–27.4) during the 48-h period, 5 (95% CI 2.6–16.5) 4 h after surgery, and 6 (95% CI 2.9–28.5) 12 h after surgery.
Nausea intensity was low in both groups, though differed significantly between them during the 48 postoperative hours (P=0.025) (Fig. 4). At 4 h, after surgery NRS values were 0 (0.0–2.0) in the PRM group and 1 (0.0–4.0) in the control group (P=0.006), and at 12 h, 0 (0.0–0.5) in the PRM group and 0 (0.0–2.5) in the control group (P=0.015).
No one in the PRM group had vomited 4 h after surgery, while 13.0% had vomited in the control group (P=0.001). At 12 h, 9.6% had vomited in the PRM group and 16.4% in the control group (P=0.228). Vomiting later was rare. At 4 h, after surgery 94.5% of the participants in the PRM group were up on their feet, while only 82.6% in the control group (P=0.025).
Opioid consumption during hospital stay postoperatively did not differ significantly (Table 3).
The percentage of patients receiving IV opioids postoperatively was somewhat larger in the intervention group. Although not part of the study protocol, nonsteroidal anti-inflammatory drugs (NSAID) were sometimes administered. In the PRM group 1.3% of the participants received NSAID, versus 9.9% in the control group (P=0.023). After discharge from hospital, there was no difference in analgesic consumption between the groups.
Antiemetics were more frequently needed in the control group postoperatively (P=0.027). The dose required was also higher in the control group (P=0.015). When adjusted for ondansetron given preoperatively, the difference between the groups was reinforced (P=0.003).