Risk of NSAIDs on Anastomotic Leak for Rectal Surgery

Early Postoperative Non-steroidal Anti-inflammatory Drugs and Anastomotic Leakage for Rectal Cancer

Conflicting reports of the association between early postoperative non-steroidal anti-inflammatory drugs (NSAIDs) administration and anastomotic leak (AL) after rectal surgery have continued. The definition of AL and the exposure of NSAIDs differ from each other among studies, which may result in the different conclusions.

The aim of this retrospective study was to clarify the effect of NSAIDs on anastomotic leak from new angels.

Study Overview

• Status: Completed
• Conditions: Anastomotic Leak; Anti-Inflammatory Agents, Non-Steroidal
• Intervention / Treatment: Drug: NSAIDs

Detailed Description

Concerning about the side effects induced by opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) have gained its popularity in ERAS protocols. NSAIDs competitively inhibits the activity of cyclooxygenases (COXs), which are involved in migration of epithelial cell and mucosal restitution, angiogenesis and collagen synthesis during healing. Conflicting reports of the association between early postoperative non-steroidal anti-inflammatory drugs (NSAIDs) administration and anastomotic leak (AL) after rectal surgery have continued.

Notably, the definition of AL and the exposure of NSAIDs (i.e. NSAIDs administration) differ from each other among the studies, which may result in the different conclusions. In concrete terms, the definition of NSAIDs administration timing varies from the first day to the first week after surgery, while the AL was also defined in multiple ways (timing varies from 14 to 90 days postoperatively, or only leaks with operative intervention included). Most previous studies suggested that early and late AL are different entities with different risk factors. These interesting evidences indicate reconsidering the effect of NSAIDs on AL is needed.

Hence, investigators defined the NSAIDs administration as at least once in the early postoperative period--the day of and the day after surgery (NSAID group), to avoid the inclusion of patients started on NSAIDs secondary to a complication. At the same time, investigators also classified AL into early AL (confirmed within 6 days) and late AL (over 6 days). Moreover, concerning the higher rate of AL in rectal surgery than colonic surgery and the trend of minimally invasive surgery, investigators performed the current study, aiming to clarify the association between early postoperative NSAIDs and anastomotic leak in rectal surgery.

• Study Type: Observational
• Enrollment (Actual): 1969

Contacts and Locations

Study Locations

• China
  • None Selected
    • Chongqing, None Selected, China
      • Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients who underwent elective rectal resection surgery

Description

Inclusion Criteria:

• Biopsy-proven adenocarcinoma of the rectum
• Age over 18 years old
• Patients underwent non-emergency minimally invasive surgery with a primary anastomosis

Exclusion Criteria:

• Incomplete medical records
• Patients with distant metastasis before surgery
• Patients with multiple primary colorectal carcinomas

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NSAIDs; patients were treated with NSAIDs postoperatively	Drug: NSAIDs; The exposure to NSAIDs: NSAIDs was used at least once within the first day after surgery
No-NSAIDs; patients were not treated with NSAIDs postoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of postoperative anastomotic leak	The primary outcome was anastomotic leak within 30 days after surgery. AL was defined as observing clinical signs of leak (such as high fever, abdominal pain, increasing of inflammatory factors in blood, purulent or fecal drainage from the drain, wound or vagina), and was confirmed by digital imaging or reoperation. Early AL was defined as being confirmed within 6 days postoperatively while late AL was defined as being confirmed after 6 days postoperatively	within 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of postoperative compolications	Secondary outcomes include wound infection, anastomotic bleeding and obstruction.	within 30 days

Collaborators and Investigators

• Sponsor: Third Military Medical University
• Investigators: Study Director: WeiDong Tong, MD, Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): February 25, 2024

Study Registration Dates

• First Submitted: November 24, 2023
• First Submitted That Met QC Criteria: November 24, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Anastomotic Leak
• Other Study ID Numbers: 20230804

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No