Myles. NEJM 2018. June 14 2018. Vol 374. No. 24

Aim of study

To determine whether, in adult patients undergoing major elective abdominal surgery, a restrictive fluid regimen compared with a liberal fluid regimen reduces complications and improves disability-free survival at 1 year.

Design (And Location)

International, randomised controlled trial

47 centres in 7 countries

(Australia, Canada, UK, China, USA, New Zealand and Italy)

Methodology

They randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery.

Random assignment in a 1:1 ratio

Prior to surgery, enrolled patients were asked to complete the 12 item World Health Organisation Disability Assessment Schedule (WHODAS). This was repeated at 3,6 and 12 months.

Restrictive group: 5ml/kg bolus at induction followed by 5ml/kg/hour until the end of surgery and then 0.8ml/kg/hour until 24 hours.

Liberal fluid group: 10ml/kg CSL bolus at induction followed by 8ml/kg/hour until the end of surgery and then 1.5ml/kg/hour until 24 hours.

Primary Outcome

The primary outcome was disability-free survival at 1 year.

Secondary Outcomes

Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

Statistics

All analyses were performed in a modified intention-to-treat population.

Kaplan–Meier method was used to calculate the probability of the primary outcome.

Hazard ratios calculated using Cox proportional-hazards model

Risk ratios

Outcomes regarding the duration and length of hospital stay in the two groups were compared with the use of the Wilcoxon–Breslow–Gehan test,

secondary outcomes with the use of the Holm–Bonferroni method,³

Results

Primary outcome: No difference in disability-free survival up to 1 year after surgery.

Acute kidney injury at 30 days occurred more commonly in the restrictive fluid group. Risk Ratio (RR): 1.71 (95% CI 1.29 to 2.27; P < 0.001)

Absolute Risk Increase (ARI): 3.59% (95% CI 1.76% to 5.42%; P < 0.001)

Renal-replacement therapy at 90 days occurred more frequently in the restrictive fluid therapy group. Risk Ratio: 3.27 (95% CI 1.01 to 13.8; P = 0.048)

Surgical site infection occurred more frequently in the restrictive fluid group, but this was not statistically significant.

No difference in composite 30 day mortality or major septic complications (sepsis, surgical-site infection, anastomotic leak, or pneumonia)

Risk Ratio: 1.22 (95% CI 1.03 to 1.45; P = 0.02)

Conclusions/ Discussion

In patients at increased risk for complications while undergoing elective major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen 1 year after surgery

However, the restrictive regimen was associated with a higher rate of acute kidney injury.

A modestly liberal fluid regimen is preferred.

Stated limitations from study

Clinicians could not administer intravenous fluids in a blinded manner.

This lack of blinding may have introduced bias in documentation.

Administration of fluid therapy after 24 hours was not controlled.

Fluid therapy and management of complications such as sepsis was not controlled.

Discussion from journal club meeting (? Change of practice)

Strange primary outcome to measure

Interesting that they included open, laparoscopic and lap assisted surgery all together

No patients requiring emergency abdominal surgery were included in the study.

This study is a bit old, newer studies suggest goal directed therapy is the way forward.

PPV monitoring might be the easiest way to monitor fluid responsiveness intra-operatively and may be a useful guide for goal directed therapy.

Fluid is good!

Summary by Dr D Walsh. Journal Club Meeting 7 March 2024