高渗盐水液体复苏对重症急性胰腺炎的前瞻性多中心随机对照临床试验

A prospective,multicenter,randomized controlled clinical trial of fluid resuscitation with hypertonic saline in severe acute pancreatitis

目的探讨高渗盐水(HS)液体复苏对重症急性胰腺炎(SAP)的临床价值。方法采用前瞻性、多中心、随机对照临床试验方法,纳入2018年8月至2022年2月期间3家医院重症医学科(ICU)收治的40例SAP患者,随机分为HS组(n=19)和林格液(LR)组(n=21),观察并比较两组患者液体复苏24 h后的血流动力学变化、前3 d液体复苏量、第7天脏器功能评分和炎症指标,治疗期间机械通气、血液净化治疗、血管活性药物和外科手术等治疗干预情况,胰腺坏死和继发感染发生率,以及ICU住院天数、总住院天数、住院病死率、不良反应发生率,并采用二元Logistic回归分析观察影响患者第7天脏器衰竭的相关因素。结果HS和LR液体复苏24 h后,两组心率和血乳酸水平较基线值下降(P<0.05)。HS组较LR组前3 d所需液体复苏量更少(mL:12287±3083 vs.14494±4475,P<0.05),第7天改良Marshall评分<2分比例更高(47.36%vs.9.52%),急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分(分:4.83±3.22 vs.7.91±4.84)和序贯器官衰竭评分(SOFA)[分:2(1.75,3.5)vs.4(3.5,7.5)]更低,总胆红素[mmol/L:17.40(12.10,25.25)vs.38.70(19.75,91.95)]、C-反应蛋白[mg/L:62.50(15.67,145.30)vs.164.00(68.15,204.50)]和降钙素原[ng/L:0.40(0.17,0.68)vs.0.91(0.35,1.67)]更低(均P<0.05),但血肌酐(Cr)和白细胞介素-6(IL-6)比较差异无统计学意义(P>0.05);HS组较LR组需要机械通气比例(26.32%vs.66.67%)和血管活性药物治疗干预比例(5.26%vs.38.10%)更低,ICU住院天数更短[d:6.11(4.67,10.89)vs.11.81(7.28,16.62)],且均P<0.05,但需要血液净化治疗和外科手术干预、胰腺坏死和继发感染、总住院天数和住院病死率等比较差异无统计学意义(P>0.05)。二元Logistic回归分析显示,HS是影响SAP患者第7天脏器衰竭的独立保护因素(OR=0.105,95%CI 0.19~0.591,P<0.05)。HS组液体复苏后,第2天血钠离子(Na+)水平较基线值升高[mmol/L:140(134~150)vs.136(128~158),P<0.05]。结论与LR比较,HS液体复苏能够减少SAP患者输液量、减轻炎症反应、减少血管活性药物和机械通气的使用,并且安全性良好,还改善SAP患者早期阶段脏器功能,并减少ICU住院时间等预后指标。

Objective To investigate the clinical value of fluid resuscitation with hypertonic saline in severe acute pancreatitis(SAP).Methods A prospective,multicenter,randomized controlled clinical trial included 40 patients with SAP who were admitted to the intensive care unit(ICU)of three hospitals between August 2018 and February 2022.Patients were randomly divided into hypertonic saline group(HS,n=19)and Ringer's solution group(LR,n=21).The hemodynamic changes,fluid resuscitation volume in the first 3 days,organ function scores and inflammation indexes on 7th day after fluid resuscitation were analyzed.The therapeutic interventions such as mechanical ventilation,CRRT therapy,vasoactive drugs,surgery,and the prognostic index including the incidence of pancreatic necrosis and secondary infection,the length of ICU and hospital stay,hospital morbidity and mortality rate,and adverse effects were also compared between the two groups.Binary Logistic regression was used to analyze the related factors of organ failure on the 7th day.Results After 24 h of fluid resuscitation,the heart rate and lactate levels decreased significantly in both groups(P<0.05).Comparing with the LR group,the HS group required less fluid resuscitation volume on the following 3 days after admission(mL:12287±3083 vs.14494±4475,P<0.05);a higher proportion of modified Marshall score<2(47.36%vs.9.52%),and lower APACHEⅡ(scores:4.83±3.22 vs.7.91±4.84)and SOFA[scores:2(1.75,3.5)vs.4(3.5,7.5)],total bilirubin[mmol/L:17.40(12.10,25.25)vs.38.70(19.75,91.95)],C-reactive protein[mg/L:62.50(15.67,145.30)vs.164.00(68.15,204.50)],and procalcitonin[ng/L:0.40(0.17,0.68)vs.0.91(0.35,1.67)]levels were observed on the 7th day in the HS group(all P<0.05),but there were no statistically significant differences in creatinine and interleukin-6 levels(P>0.05).The HS group had the lower rates of mechanical ventilation(26.32%vs.66.67%)and vasoactive drug therapeutic interventions(5.26%vs.38.10%),and the shorter days of ICU stay[d:6.11(4.67,10.89)vs.11.81(7.28,16.62)](all P<0.05),there were no statistically significant differences in the rate of CRRT,surgical interventions,pancreatic necrosis,secondary infection,and the length of the hospital stay and hospital mortality between the two groups(P>0.05).Binary Logistic regression analysis showed that HS was an independent protective factor for organ failure on the 7th day in the patients with SAP(OR=0.105,95%CI 0.190-0.591,P<0.05).The blood sodium levels were increased on the 2nd day after fluid resuscitation in the HS group compared to baseline values[mmol/L:140(134-150)vs.136(128-158),P<0.05].Conclusions Compared with LR,HS was not only able to reduce the amount of resuscitation fluid given to patients with SAP,but also reduce the inflammatory level,and the use of vasoactive drugs and mechanical ventilation with a good safety profile,it can improve organ function at the early stages of SAP and reduce the length of ICU stay.