Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial

• Published in: British journal of surgery Vol. 111; no. 5
• Main Authors: Traeger, Luke, Bedrikovetski, Sergei, Fitzsimmons, Tracy, Nguyen, Thuy-My, Moore, James W, Lewis, Mark, Sammour, Tarik
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 03.05.2024
• Subjects: Adult; Aged; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - adverse effects; Cholinesterase Inhibitors - therapeutic use; Double-Blind Method; Female; Humans; Ileus - etiology; Ileus - prevention & control; Length of Stay; Male; Middle Aged; Postoperative Complications - prevention & control; Pyridostigmine Bromide - administration & dosage; Pyridostigmine Bromide - therapeutic use; Treatment Outcome
• ISSN: 0007-1323; 1365-2168; 1365-2168
• DOI: 10.1093/bjs/znae121

Abstract Background Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. Methods This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. Results Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1–3) versus 3 (2–4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4–8.75) versus 5 (4–7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. Conclusion Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au). In this 130-patient RCT, administration of pyridostigmine after colorectal surgery improved GI-2 by 1 day compared with placebo. There was no increase in complications or patient-reported side effects. This study demonstrated that pyridostigmine is effective and potentially safe in improving gastrointestinal recovery after colorectal surgery.