• Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, et al.

• N Engl J Med. 2018;378:2263–74.

An estimated 310 million patients undergo major surgery each year (Weiser et al., 2015). In order to prevent and correct fluid deficits and further complications, intravenous fluids are commonly administered peri- and postoperatively. However, the practice of how clinicians administer these fluids is changing. With guidelines now recommending a restrictive intravenous fluid strategy rather than the more traditional liberal approach (Gustafsson et al., 2012; Feldheiser et al., 2016). However, limited data has raised questions about these guideline recommendations. In this study Myles et al. uncover what effect the two approaches have on disability-free survival, and a range of secondary outcomes, in patients undergoing major abdominal surgery.

Liberal intravenous-fluid therapy is often thought of as the more traditional approach to fluid management during surgery, where generous amounts of fluids are administered peri- and postoperatively. This approach can pose risks though, with up to 7 litres of fluid administered on the day of surgery, tissue oedema and weight gain of 3–6 kg can occur (Lobo et al., 2002; Brandstrup et al., 2003; Tambyraja et al., 2004; Gustafsson et al., 2012; Boland et al., 2013). It is also thought that excessive fluid administration may lead to increased risk of acute kidney injury (AKI), sepsis, pulmonary complications, and poor wound healing (Arieff, 1999; Lang et al., 2001; Ratner et al., 2005; Prowle et al., 2010).

One strategy to avoid these risks is through restrictive fluid therapy. Some smaller studies have shown that this restrictive approach led to fewer complications and shorter length of hospital stay (Lobo et al., 2002; Brandstrup et al., 2003; Nisanevichet al., 2005). Consensus statements have backed the findings of these studies with restricting fluid to achieve zero balance being a key component in the enhanced recovery after surgery (ERAS) pathways – a perioperative care guideline (Gustafsson et al., 2012; Feldheiser et al., 2016; National Institute for Health and Care Excellence, 2017).

However, fluid restriction may increase the risk of hypotension and decrease perfusion of vital organs including the kidneys leading to organ dysfunction (Arieff, 1999). As such, there is still some uncertainty over which approach is most effective, especially in patients undergoing major abdominal surgery where results have been inconclusive (Corcoran et al., 2012; Gustafsson et al., 2012; Ljungqvist et al., 2017; National Institute for Health and Care Excellence, 2017).

Does intravenous-fluid strategy affect disability?

Hoping to discover the answer to this ongoing debate, the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted. This international study of 3000 patients with an increased risk of complications while undergoing major abdominal surgery, across 7 countries, randomly assigned patients to receive either liberal or restrictive fluid therapy. 

Increased risk of complications included age of at least 70 years, or the presence of heart disease, diabetes, renal impairment, or morbid obesity. Fluid therapies were designed to reflect traditional practice for the liberal group and to achieve net zero fluid balance in the restrictive group. During surgery the median rate of fluid infusion was 6.5 mL/kg/hour for the restrictive group, followed by 0.9 mL/kg/hour on postoperative day 1. Compared to a median infusion rate of 10.9 mL/kg/hour for the liberal group, followed by 1.5 mL/kg/hour on postoperative day 1.

The primary endpoint of this study was disability-free survival, which was measured by the 12-item World Health Organization Disability Assessment Schedule (WHODAS) prior to surgery and 1 year after surgery. Interestingly, a significant difference wasn’t observed between the two groups, with a disability-free survival rate of 81.9% in the restrictive group vs. 82.3% in the liberal group (HR=1.05, 95% CI 0.88–1.24; p=0.61). Death or persistent disability was also analysed for the two groups, reflecting similar results for the two therapies.

The impact of fluid management strategy on AKI

A number of secondary endpoints were also measured including AKI, septic complications and renal replacement therapy (figure 1). Of these secondary endpoints, AKI was more frequently reported in the restrictive group than the liberal group (8.6% vs. 5%; p=<0.001).  Each method of fluid management runs a risk of AKI as inadequate administration of fluid may result in renal hypoperfusion whereas excessive administration may result in renal interstitial oedema (Prowle et al., 2010; Kellum & Lameire, 2013). Therefore, it’s interesting to note that the risk of these outcomes was observed to be higher in the restrictive group in this patient population.

In addition, another believed risk of excessive fluid administration is impaired wound healing. However, although not statistically significant after adjustment for multiple comparisons, this study found the restrictive group to have a higher rate of surgical site infections than the liberal group (16.5% vs. 13.6%). This is possibly a result of wound or anastomotic hypoperfusion, as fluid restriction therapy increases the need for vasopressor therapy.

Although these results shed some light on the liberal versus restrictive argument, this evidence shouldn’t be used to support excessive fluid administration. In this study a modest liberal fluid regimen was found to safer than restrictive fluid therapy in preventing AKI, but no difference was seen for disability-free survival.

Further research is still required to build a stronger body of evidence for future guidelines.

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