Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF)

Myles PS, Bellomo R, Corcoran T et al.

New England Journal of Medicine 2018; 378 (24): 2263-74.

DOI: 10.1056/NEJMoa1801601

Hypothesis

A restrictive fluid regimen in the first 24 hours of major abdominal surgery would lead to a lower rate of complications and a higher rate of disability-free survival than a liberal fluid regimen.

Design and Location

Large randomised controlled trial conducted in seven different countries between 2013-2016.

Methodology

Inclusion criteria:

• Major elective abdominal surgery with expected operative duration over 2hrs and expected hospital stay over 3 days
• Those at increased risk of postoperative complications defined by at least one of the following:
  • Age 70 or over
  • IHD
  • Heart failure
  • Diabetes
  • Creatinine >200
  • BMI>35
  • Albumin <30
  • Anaerobic threshold< 12ml/kg/min if CPET performed

• Or two or more of the following:
  • ASA 3 or 4
  • Chronic respiratory disease
  • BMI 30-35
  • Aortic or PVD
  • Preop Hb<100
  • Creatinine 150-199
  • AT between 12-14ml/kg/min

Exclusion criteria:

• Urgent/time-critical surgery
• ASA 5
• ESRF on RRT
• Liver resection, cardiac/pulmonary surgery

All patients enrolled were asked to complete the WHODAS (WHO Disability Assessment Schedule) 12-item questionnaire on the day of the surgery, asking about difficulties due to health conditions. Random assignment of patients in 1:1 ratio to either liberal or restrictive arm in permuted blocks and stratified according to site and post-operative destination.

Anaesthetists, medical and nursing staff aware of group assignment. Research staff who were responsible for primary outcome were blinded.

All patients were followed in hospital and up to a 1yr post-op. WHODAS questionnaire was repeated at day 30, 3 months, 6 months and 12 months to look for new onset disability. All patients’ notes were reviewed at day 30 post-op.

Interventions

	Liberal Regimen	Restrictive Regimen
Induction	Bolus of CSL 10mg/kg	Bolus of CSL max dose of 5mg/kg
Peri-operative	8ml/kg/hr until the end of surgery	5ml/kg/hr until the end of surgery
Post-operative	1.5ml/kg/hr for at least 24hrs	0.8ml/kg/hr
•       Bolus colloid or blood could be used intra-operatively in both groups to replace blood loss •       Oliguria was accepted in first 24-48hr post-op and was not used as an indication for additional IVF •       Total fluid administered in first 24hr period in restrictive group is estimated to be half of the liberal group (3L vs. 6L) •       Goal-directed fluid therapy can be used in either group at clinician’s discretion. •       Early introduction of vasopressors in restrictive group in absence of hypovolaemia.

 

Primary Outcome

Disability-free survival up to a 1 year after surgery

Secondary Outcomes

Incidence of AKI, pulmonary oedema, blood transfusion and 30-day mortality or major septic complications.

Serum lactate at 6 and 24hrs; peak CRP; duration of ICU and hospital stay; unplanned admissions to ICU and quality of recovery.

Statistics

Intention to treat principle

Cox proportional hazards regression model for primary outcome.

Secondary outcomes are measured on binary scale and analysed using log-binomial regression.

Results

3000 patients were randomly assigned to either treatment arms (over 50% patients located in Australia). No difference in disability-free survival up to a year in restrictive or liberal fluid management group.

Restrictive regimen was associated with higher incidence of AKI. None of the other secondary outcomes were statistically significant between both groups.

Conclusions

In patients at increased risk of complications undergoing major abdominal surgery, restrictive fluid regimen was not associated with a higher rate of disability-free survival than liberal fluid regimen 1yr after the surgery. Restrictive regimen was associated with a higher rate of AKI.

Stated Limitations from the Study

• Lack of blinding in clinicians could have introduced bias in documentation and outcome monitoring.
• Only first 24hrs fluid therapy was dictated in the trial, no control of later fluid therapy.

Discussion from Journal Club Meeting

• Our current practice especially in elective colorectal surgery is leaning more towards liberal fluid regimen than restrictive fluid regimen. We did not feel this study would change our current practice.
• Primary outcome measures disability up to a 1yr post op based on 3L of fluid difference given in the first 24hr period- whether this could be an over-representation of the significance of the study as many other factors would be contributing to disability post major abdominal surgeries.
• Study stated that some patients received enhance recovery after surgery (ERAS) but no clear or unifying management in administration of pre-op fluids/carbohydrate drinks which are commonly adopted in current practice.
• There are some ASA 1 patients in both treatment arms, questions raised around whether they should be recruited according to inclusion criteria.
• Goal-directed fluid therapy were adopted by some clinicians at their own discretion in this study, although there were no clear criteria set out in the study to measure hypovolaemia.
•  Although not statistically significant, there seemed to be more heart failure patients recruited to the restrictive arm than liberal arm.

Summary by Dr M Zou. Journal Club 23rd August 2018.