NEJM: 积极与适度液体复苏治疗急性胰腺炎的比较

Abstract

Background: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.

早期积极液体复苏被广泛推荐用于急性胰腺炎的治疗，但这一做法的证据有限。

Methods: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer’s solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient’s clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients.

在18家研究中心，我们将急性胰腺炎患者随机分组，分别接受目标指导下的乳酸盐林格液积极或适度复苏。积极液体复苏包括快速输注20 mL/kg，随后给予3 mL/（kg·h）。适度液体复苏包括向血容量不足的患者快速输注10 mL/kg，对于血容量正常的患者不进行快速输注，随后对于这一组的所有患者，给予1.5 mL/（kg·h）。患者在12、24、48和72小时接受评估，液体复苏根据患者的临床状态进行调整。主要结局是住院期间中度重症或重症胰腺炎的发生。主要安全性结局是液体过多。计划样本量为744，第一次计划的期中分析在纳入248例患者后进行。

Results: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group.

共计249例患者被纳入期中分析。由于安全性结局存在组间差异，而中度重症或重症胰腺炎发生率（积极复苏组22.1%和适度复苏组17.3%；经校正的相对危险度，1.30；95%置信区间[CI]，0.78～2.18；P=0.32）无显著差异，本试验终止。积极复苏组20.5%的患者和适度复苏组6.3%的患者发生了液体过多（经校正的相对危险度，2.85；95% CI，1.36～5.94，P=0.004）。在积极复苏组和适度复苏组中，中位住院持续时间分别为6天（四分位距，4～8）和5天（四分位距，3～7）。

Conclusions: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.)

在这项在急性胰腺炎患者中进行的随机试验中，早期积极液体复苏导致液体过多的发生率较高，并且临床结局无改善（由萨洛德卡洛斯三世研究所[Instituto de Salud CarlosⅢ]等资助，WATERFALL在ClinicalTrials.gov注册号为NCT04381169）。