1. Impact of postoperative non-steroidal anti-inflammatory
drugs on adverse events after
gastrointestinal surgery
Dmitri Nepogodiev
Department of Colorectal Surgery

2. Paper
STARSurg Collaborative. Impact of postoperative non-steroidal
anti-inflammatory drugs on adverse events
after gastrointestinal surgery. Br J Surg. 2014
Oct;101(11):1413-23.

3. Journal
 British Journal of Surgery.
 Top-5 general surgery journal.
 Impact factor 5.21.

4. Authors
 Student Audit and Research in Surgery (STARSurg).
National, student-led research collaborative.
 Founded in 2013.
 Core aim: To engage medical students in high quality
research, enthusing them and equipping them with
the skills to become research-active consultants in
the future.

5. Steering Committee
• Chetan Khatri
• Michael Kelly
• Stephen Chapman
• James Glasbey
• Dmitri Nepogodiev
• Edward Fitzgerald
• Aneel Bhangu

6. Primary aim
 To determine the safety profile of post-operative
NSAIDs following gastro-intestinal resection.

7. NSAIDs
Non-steroidal anti-inflammatory drugs.
 Cyclooxygenase-1 & cyclooxygenase-2 inhibitors
 Inhibit prostaglandin and thromboxane synthesis.
 Adverse effects include:
Gastrointestinal bleeding.
Myocardial infarction.

8. WHO pain ladder

9. NSAIDs and GI surgery
 Safety concerns – anastomotic leak.
 Klein (BMJ, 2012)
Multi-centre database study.
 2,766 patients.
 Diclofenac and ibuprofen associated with
increased risk of leak versus controls: 12.8% and
8.2% v 5.1% (P<0.001)

10. Risk of anastomotic leak

11. Risk of anastomotic leak

12. Risk of anastomotic leak

13. Risk of anastomotic leak

14. Hypothesis
 The 30-day adverse event rate, following risk
adjustment, should be equivalent in patients taking
and not taking NSAIDs post-operatively following
gastrointestinal resection.

15. Hypothesis
 Population: patients undergoing bowel resection.
 Intervention: post-op NSAID administration.
 Control: patients not administered NSAIDs post-op.
Outcome: 30-day adverse event rate.

16. Study design
Multi-centre study.
 Prospective cohort.

17. STARSurg Network

18. Inclusion criteria
 Adults.
Gastrointestinal resection.
 Complete transection and removal of a segment of rectum, colon,
small bowel, stomach or oesophagus.
 Elective or emergency procedures.
Open or laparoscopic procedures.

19. Primary outcome
Major morbidity rate at 30-days.
 Clavien-Dindo complication grades III-V.

20. Clavien-Dindo
I – deviation from standard post-op course within
‘allowed therapeutic regimes’
II – complication requiring pharmacological intervention
III – complication requiring surgical, endoscopic or
radiological intervention
IV – complication requiring ICU admission
V – death
Major Minor

21. Follow-up
 30-day follow-up based on hospital records.

22. Power calculation
 Detect increase in 30-day major complications from
15 to 25%.
 1:2 ratio experimental to control patients.
 300 patients on NSAIDs, 600 controls.
 Power = 80%, alpha = 0.05.

23. Statistics
 Propensity score matching.
 Estimates the effect of an intervention by
accounting for co-variables that predict receipt of
the treatment.
 Variables selected a priori:
 Age, gender, ASA grade, RCRI, timing of surgery,
indication, type of surgery, use of laparoscopy.

24. Quality assurance
Mandatory e-learning module.

25. Quality assurance
 Compulsory to have a doctor in data collection
team.

26. Quality assurance
 External data validation:
 5% data points validated.
 >98% accuracy.

27. Methods summary

28. Results
 1513 patients.
 76% colorectal.
 60% anastomosis.
 109 centres.
Mean age 64.7 years
 35% ASA III-V.

29. Results: NSAID use
 Days 1-3 post-op, 19% of patients received NSAIDs.
 Ibuprofen most commonly prescribed NSAID
(70%).

30. Results: complications
Overall, 62% of patients experienced complications.
 45% experienced minor (Clavien-Dindo I-II).
 17% experienced major (Clavien-Dindo III-V).
 Anastomotic leak rate was 4.9%.

31. Results

32. Results: NSAIDS
 Post-op NSAID administration associated with 28%
reduction in overall complications.
 36% reduction in patients receiving high dose
NSAIDs.
 Results persistent after propensity score matching.

33. Conclusions
 Early NSAID associated with reduction in total
complications following GI resection.
No evidence of increase in anastomotic leaks.
 Underlying mechanism for reduction in
complications unclear.
 Reduction in opiate consumption.
 Anti-inflammatory properties.

34. Limitations
Narrow data-collection window.
High level of data completeness.
 Heterogenity.
 Pragmatic, real-world population.
 Addressed by matching.

35. Limitations
 Selection bias.
 Propensity score matching (RCRI, ASA).
 Other analgesics used not evaluated.
 Including pre-operative NSAIDs.

36. Limitations
 Analysis of leak rate under-powered.
 Difficult to power a 5% event rate.
 Quality assurance.
 Prospective, but case ascertainment unknown.

37.  Study aims:
 To establish compliance with NICE guidelines
requiring early identification of obese patients.
 To determine the role of obesity as a risk factor
for major post-operative complications in current
UK and Irish practice.

38.  Inclusion criteria:
 All consecutive adult patients with an overnight stay
in hospital, undergoing gastrointestinal surgery or
hepatobiliary surgery.
 Powered to detect increase in adverse event rate in
obese (BMI > 30) patients versus normal weight
patients (NMI 18.5-25) from 8% to 10%.

39. Highlights
 Representation across all UK & Irish medical
schools.
More detailed outcome data collection.
More thorough quality assurance.
 REDCap.
 £12,000 awarded by INSPIRE.
 Integrated research skills course & buddy scheme.

40. Scope for RCT?
 Population?
 Bowel resection versus all major GI surgery
 Intervention?
 Pre-operative NSAID?
 Peri-operative ketorolac?
 Post-operative NSAID? (High dose? Early?)

41. Scope for RCT?
 Comparison
 Protocolised analgesia or pragmatic?
Outcome
Morbidity?
 Return to bowel function? LOS?
 PROMS?