摘要:
目的 探讨百草枯(PQ)解毒组方联合持续血液灌流(HP)治疗对急性百草枯中毒(APP)患者的临床疗效以及可溶性白细胞分化抗原CD14亚型(sCD14-st,又称Presepsin)的临床意义.方法 采用前瞻性随机对照研究方法,选择2013年7月至2017年6月河北医科大学哈励逊国际和平医院急救医学部收治的中度APP患者152例,按随机数字表法将患者分为3组.单纯HP组35例患者接受连续3次的HP治疗、每次2 h、8 h 1 次;PQ解毒组方联合常规HP组50例患者在单纯HP组基础上口服PQ解毒一号方、2 h 1次,粪中无PQ成分后改服PQ解毒二号方、每日3次、连续14 d;PQ解毒组方联合持续HP组67例患者在口服PQ解毒组方的基础上接受持续HP治疗,直至血中检测不到PQ成分.分别于治疗前后不同时间点检测患者各项器官功能指标、炎性因子及血中Presepsin和PQ含量,记录临床疗效及28 d病死率;采用Pearson相关法分析血中Presepsin水平与PQ含量和28 d病死率的相关性;绘制受试者工作特征曲线(ROC),分析血中Presepsin对预后的预测价值.结果 与单纯HP组和PQ解毒组方联合常规HP组比较,PQ解毒组方联合持续HP组总有效率显著升高〔70.1%(47/67)比34.3%(12/35)、54.0%(27/50)〕,28 d病死率明显降低〔29.8%(20/67)比65.7% (23/35)、46.0%(23/50),均P<0.05〕.治疗前3组患者丙氨酸转氨酶(ALT)、肌酸激酶同工酶(CK-MB)、血肌酐(SCr)、C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-6、IL-10)水平比较差异均无统计学意义;治疗5 d,3组患者各项指标均较治疗前升高,但以PQ解毒组方联合持续HP组升高幅度最小;治疗7 d, 3组患者各项指标均有下降趋势,以PQ解毒组方联合持续HP组降低最明显.3组治疗前血中Presepsin和PQ水平比较差异无统计学意义;随治疗时间延长,单纯HP组、PQ解毒组方联合常规HP组及PQ解毒组方联合持续HP组Prespsin水平均呈升高趋势,12 h达峰值(μg/L:4.28±0.20、3.87±0.25、3.53±0.23),随后逐渐降低;8 h起PQ含量即较治疗前降低(mg/L:1.76±0.12比2.12±0.17、1.57±0.08比2.24±0.16、1.25±0.10比2.14±0.18),并呈时间依赖性,以PQ解毒组方联合持续HP组降低更为显著(均P<0.05).相关分析显示,APP患者24 h内血中Presepsin水平与PQ含量和28 d病死率呈显著正相关(r1=0.917,r2=0.864,均P=0.001),提示患者血中PQ含量越高,Presepsin水平越高,病死率就越高.ROC曲线分析显示,24 h内Presepsin预测28 d病死率的ROC曲线下面积(AUC)为0.863;当截断值为1.22 μg/L时,敏感度为83.3%,特异度为81.4%,阳性预测值为77.46%,阴性预测值为86.42%.结论 早期给予PQ解毒组方联合持续HP治疗能有效降低中度APP患者Presepsin水平,从而降低病死率,改善预后.血中Presepsin水平可能成为早期判断APP患者预后的指标.%Objective To investigate the clinical effect of paraquat (PQ) detoxification recipe combined with continuous hemoperfusion (HP) in the treatment of patients with acute paraquat poisoning (APP) and clinical significance of soluble CD14 subtype (sCD14-st, Presepsin). Methods A prospective randomized controlled trial was conducted. 152 patients with moderate APP admitted to Department of Emergency Medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University from July 2013 to June 2017 were enrolled, and they were randomly divided into three groups. The patients in HP group (group A, n = 35) only received 2-hour HP for 3 times, 8 hours each time, those in PQ detoxification recipe combined with HP group (group B, n = 50) received PQ detoxification recipe 1 (once per 2 hours until no PQ component was found in faeces) and 2 (3 times a day for 14 days) beside HP. The others in PQ detoxification recipe combined with persistent HP group (group C, n = 67) received continuous HP until the PQ component in serum was not detected. The parameters of organ function and inflammatory factor, and blood Presepsin and PQ contents were determined before and after treatment. The curative effect and 28-day mortality were recorded. The correlations between serum Presepsin level and PQ content as well as 28-day mortality were analyzed with Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of Presepsin on prognosis. Results The total effective rate of group C was significantly higher than that of groups A and B [70.1% (47/67) vs. 34.3% (12/35), 54.0% (27/50)], and 28-day mortality was significantly lowered [29.8% (20/67) vs. 65.7% (23/35), 46.0% (23/50), both P < 0.05]. There was no significant difference in alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukins (IL-6 and IL-10) before treatment among the three groups. Five days after treatment, the above parameters in the three groups were increased as compared with those before treatment, but the increase degree in group C was the lowest. At 7 days after treatment, the parameters were decreased, especially in group C. There was no significant difference in serum Presepsin and PQ levels before treatment among the three groups. With the prolongation of treatment time, the Prespsin levels in groups A, B, and C were increased, and peaked at 12 hours (μg/L: 4.28±0.20, 3.87±0.25, 3.53±0.23), then gradually decreased,and the PQ contents were lower than those before treatment from 8 hours (mg/L: 1.76±0.12 vs. 2.12±0.17, 1.57±0.08 vs. 2.24±0.16, 1.25±0.10 vs. 2.14±0.18), with a time dependence pattern, especially in group C (all P < 0.05) . Correlation analysis showed that blood Presepsin level was positively correlated with PQ content and 28-day mortality (r1= 0.917, r2= 0.864, both P = 0.001), suggesting that the higher the PQ content was, the higher the Presepsin level, and the higher the 28-day mortality was. ROC curve analysis showed that the area under ROC curve (AUC) of Presepsin predicting 28-day mortality was 0.863; when the cut-off value was 1.22 μg/L, the sensitivity was 83.3%, the specificity was 81.4%, the positive predictive value was 77.46%, and the negative predictive value was 86.42%. Conclusions Early administration of PQ detoxification recipe combined with continuous HP treatment can effectively reduce Presepsin level, decrease the mortality of patients with moderate APP, improve the prognosis. Presepsin can assess the prognosis of patients with APP.