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[NEJM述评]:寻找正确的平衡
2018年06月22日 研究点评, 进展交流 暂无评论

EDITORIAL

Finding the Right Balance

Birgitte Brandstrup

N Engl J Med 2018; 378:2335-2336

DOI: 10.1056/NEJMe1805615

When I was a young resident in the 1990s, surgical patients received so much intravenous saline on the day of surgery that they often gained 4 to 6 kg, and by postoperative day 2 or 3, pulmonary congestion and cardiac arrhythmias were commonplace. That was the basis for a 2003 trial of restrictive versus standard fluid therapy,1 which aimed to answer a simple question: Was so much fluid (and the ensuing tissue edema) beneficial for wound healing and cardiopulmonary function? That study, which enrolled 172 patients undergoing colorectal resection, showed that fluid overload and fluid retention were not beneficial; the numbers of complications that were reported after open colorectal surgery were nearly halved by keeping patients at a near-zero fluid balance. Subsequently, many other investigators reported a similar downside to the strategy of fluid overload.2-8

Myles et al.9 now report in the Journal the results of a randomized, controlled trial comparing a restrictive intravenous-fluid strategy with a relatively liberal fluid strategy during the perioperative period in 3000 patients at increased risk for complications during major abdominal surgery. The primary outcome was disability-free survival at 1 year. The investigators found that the restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen but was associated with a higher rate of acute kidney injury. The result may surprise many surgeons and anesthesiologists, who no doubt expected that the outcome would favor the restrictive fluid group. Indeed, the results may appear to contradict the findings of previously published trials and recommendations.

In the current trial, patients in the liberal fluid group received a perioperative median of 6 liters, and those in the restrictive fluid group received a median of 3.7 liters. However, the resulting increase in body weight (along with fluid retention) was modest — 1.6 kg in the liberal fluid group and 0.3 kg in the restrictive fluid group, which represent increases that are far lower than those in the early trials.1,3 One reason for less fluid retention in this trial may be that many surgical procedures performed today are minimally invasive, which reduces the metabolic stress that leads to fluid retention. Another reason may be the hypotonic or balanced intravenous fluids that were administered in the current study, which were associated with a lower osmotic load than isotonic fluids.6,8

There were other substantial differences between the 2003 trial and the trial by Myles et al. In the earlier trial, on the day of surgery, patients were allowed to drink freely (median intake, 413 ml) and to be fed (median intake, 500 ml by nasoduodenal tube). In the current trial, even though the authors intended to adhere to an enhanced recovery after surgery (ERAS) protocol10 that included an early return to oral intake, on postoperative day 2, one third of the patients were not drinking, and half were not eating. Furthermore, in the earlier trials, the assigned fluid treatment was continued on the ward,1-5,8postoperative diuresis was maintained above 0.5 ml per kilogram per hour,1-6 and patients were monitored for hypovolemia, which was treated with additional intravenous fluid if it occurred.1-6,8 In the trial by Myles et al., the intervention did not continue on the ward, postoperative oliguria per se was not linked to a specific action in the protocol, and hypovolemia was treated with fluid if the patients in the restrictive fluid group had evidence of bleeding. If the systolic blood pressure was below 90 mm Hg, treatment with vasopressors or fluid was optional.

Insufficient access to adequate fluid intake will ultimately lead to kidney injury; indeed, such injury occurred in more patients in the restrictive fluid group than in the liberal fluid group (8.6% vs. 5.0%, P<0.001). Furthermore, fluid therapy that was administered on postoperative day 1 or afterward may very well have influenced the negative primary outcome.

The strengths of the trial by Myles et al. include the large number of patients, along with the international, multicenter, randomized design and the relatively long follow-up. A weakness is that effective blinding was not possible. Differences in fluid volumes may create signs and symptoms (e.g., diuresis, edema, and thirst) that often identify the randomization group. More important, adequate fluid intake is vital, and for safety reasons, medical personnel must be aware of fluid balance and therapy received.

Given the intrinsic limitations, what do we learn from the trial by Myles et al.? In a modern surgical service, which includes minimally invasive surgery, 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, although patients for whom an ERAS protocol is used might not need it. In addition, we learn that physiologic principles remain valid: both hypovolemia and oliguria must be recognized and treated with fluid. Finally, I agree with the authors’ statement that their findings should not be used to support excessive administration of intravenous fluid during surgery. Rather, they show that a modestly liberal fluid regimen is safer than a truly restrictive regimen.

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