Impact of postoperative non-steroidal anti-inflammatory drugs on adverse events after gastrointestinal surgery

Dmitri Nepogodiev

Department of Colorectal Surgery

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.

Journal British Journal of Surgery.

Top-5 general surgery journal.

Impact factor 5.21.

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.

Steering Committee

• Chetan Khatri

• Michael Kelly

• Stephen Chapman

• James Glasbey

• Dmitri Nepogodiev

• Edward Fitzgerald

• Aneel Bhangu

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

NSAIDs Non-steroidal anti-inflammatory drugs.

Cyclooxygenase-1 & cyclooxygenase-2 inhibitors

Inhibit prostaglandin and thromboxane synthesis.

Adverse effects include:

Gastrointestinal bleeding.

Myocardial infarction.

WHO pain ladder

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)

Risk of anastomotic leak

Risk of anastomotic leak

Risk of anastomotic leak

Risk of anastomotic leak

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.

Hypothesis Population: patients undergoing bowel resection.

Intervention: post-op NSAID administration.

Control: patients not administered NSAIDs post-op.

Outcome: 30-day adverse event rate.

Study design Multi-centre study.

Prospective cohort.

STARSurg Network

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.

Primary outcome Major morbidity rate at 30-days.

Clavien-Dindo complication grades III-V.

Clavien-DindoI – 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

Min

or

Majo

r

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

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.

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.

Quality assurance Mandatory e-learning module.

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

Quality assurance External data validation:

5% data points validated.

>98% accuracy.

Methods summary

Results 1513 patients.

76% colorectal.

60% anastomosis.

109 centres.

Mean age 64.7 years

35% ASA III-V.

Results: NSAID use Days 1-3 post-op, 19% of patients received NSAIDs.

Ibuprofen most commonly prescribed NSAID (70%).

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%.

Results

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.

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.

Limitations Narrow data-collection window.

High level of data completeness.

Heterogenity.

Pragmatic, real-world population.

Addressed by matching.

Limitations Selection bias.

Propensity score matching (RCRI, ASA).

Other analgesics used not evaluated.

Including pre-operative NSAIDs.

Limitations Analysis of leak rate under-powered.

Difficult to power a 5% event rate.

Quality assurance.

Prospective, but case ascertainment unknown.

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.

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%.

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.

Scope for RCT? Population?

Bowel resection versus all major GI surgery

Intervention?

Pre-operative NSAID?

Peri-operative ketorolac?

Post-operative NSAID? (High dose? Early?)

Scope for RCT? Comparison

Protocolised analgesia or pragmatic?

Outcome

Morbidity?

Return to bowel function? LOS?

PROMS?