From Pages to Practice
Intravenous fluid therapy in major abdominal surgery is a classic Goldilocks dilemma: Too little fluid can result in low blood pressure and consequent organ damage, but too much fluid can cause tissue edema, potentially delaying recovery of bowel function and precipitating cardiopulmonary complications. What is the right balance?
The international Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial randomized 3000 patients who were at increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal perioperative intravenous-fluid regimen. Risk factors for complications included patient characteristics (age ≥70 years, presence of heart or kidney disease, morbid obesity) and surgical attributes (large skin incision, anticipated operative duration of at least 2 hours, anticipated hospital stay of at least 3 days).
The restrictive-fluid regimen aimed to achieve a net zero body fluid balance. Before surgery, a bolus of no more than 5 ml per kilogram was administered; during surgery, fluids were given at 5 ml per kilogram per hour; and for the 24-hour period after surgery, fluids were continued at 0.8 ml per kilogram per hour. (e.g., a patient weighing 80 kg might receive 400 ml before surgery, 400 ml per hour during surgery, and 1.5 liters during the next 24 hours). The liberal-fluid regimen involved administration of twice as much fluid during the same period (an 80-kg patient might receive 800 ml before surgery, 640 ml per hour during surgery, and 2.9 liters during the next 24 hours). The amount of fluid could be decreased or increased if there was evidence of fluid overload or concern for under-resuscitation.
The primary outcome was disability-free survival at one year. Disability was defined as persistent impairment in health status lasting 6 months or longer. Disability-free survival did not differ between the two groups (81.9% vs. 82.3% in the restrictive- and liberal- fluid groups, respectively; P=0.61). However, the restrictive-fluid regimen was associated with significant differences in key secondary outcomes, including higher rates of acute kidney injury at 30 days (8.6% vs. 5% in the liberal-fluid group; P<0.001), renal-replacement therapy at 90 days (13 vs. 4 patients; P=0.004), and surgical-site infections (16.5% vs. 13.6% patients; P=0.003). No differences between groups were detected for many other secondary outcomes, including a composite of septic complications or 30-day mortality (P=0.19), death at 90 days or 1 year, rates of pneumonia and pulmonary edema, median time spent on mechanical ventilation. median duration of hospital stays (6.4 days vs. 5.6 days; P=0.26), median duration in the intensive care unit (ICU), and the rate of unplanned ICU admissions.
These observed differences — and lack of differences — are striking. The authors had hypothesized that a restrictive-fluid management strategy would prove favorable, but the results suggest no clear benefit and identify areas of potentially increased risk. In this intention-to-treat analysis, the observed difference in median fluid volume between groups was smaller than expected and the median cumulative fluid volume at 24 hours after surgery was higher than expected in both groups, likely making it harder to detect any potential benefit associated with a restrictive strategy.
Restricted use of fluids is a prominent tenet of the Enhanced Recovery After Surgery (ERAS) pathway, which is now employed widely for many forms of major abdominal surgery. In my specialty, urologic surgery, ERAS is often used to manage patients undergoing cystectomy, a major operation associated with high morbidity that involves removing the bladder and using segments of bowel to build a new system for evacuating urine from the body. As surgeons, we have been trained to regard bowel edema as the enemy — an invitation for ileus, which can cause a delayed return to oral intake, poor nutrition, poor wound healing, and protracted hospital stays.
The results of the RELIEF trial suggest that a more nuanced, moderated fluid-management strategy may be prudent. In an accompanying editorial, Birgitte Brandstrup, Ph.D. of Holbaek Hospital in Denmark states, “A modestly liberal administration of balanced salt solutions does not create substantial fluid retention, and it appears to be safe to administer a fluid volume that slightly exceeds zero fluid balance.” By design, a trial such as RELIEF that compares two approaches on opposite ends of a spectrum cannot prescribe the optimal fluid balance for individual patients or specific types of surgery. But the sweet spot, as with any Goldilocks dilemma, likely falls somewhere between extremes.