氨基末端脑钠肽前体对儿童重症手足口病心力衰竭评估价值

Clinical significance of N-terminal pro-brain natriuretic peptide in patients with severe hand,foot and mouth disease

目的心肺功能衰竭是重症手足口病患儿的主要死亡原因。通过快速检测心力衰竭指标——血清氨基末端脑钠肽前体(NT-proBNP)水平,探讨其在评估急症手足口病患儿并发心力衰竭的临床价值。方法选择在湖南省儿童医院就诊和住院的392例手足口病患儿,根据卫生部"肠道病毒71型(EV71)感染重症病例临床救治专家共识(2011年版)",按病情进展分为5组:第一期(手足口病出疹期)组、第二期(神经系统受累期)组、第三期(心肺功能衰竭前期)组、第四期(心肺功能衰竭期)组、第五期(恢复期)组。5组患儿入院后立即检测肌酸激酶同工酶(CKMB)、血清NT-proBNP和心肌肌钙蛋白I(cTnI)水平,并进行床旁超声心动图检查。结果采用spearman相关分析血清心功能指标与超声心动图指标左室射血分数(LVEF)相关性,cTnI、CKMB与LVEF无相关(P>0.05)。NT-proBNP浓度与LVEF呈负相关(r=-1,P<0.05),NT-proBNP水平随着手足口病患儿病情加重,呈增高趋势。手足口病第三期组NT-proBNP中位数为921 pg/mL,而第二期组仅为55 pg/mL。通过ROC曲线分析,NT-proBNP水平对重症手足口病患儿心力衰竭前期的检测阈值是400 pg/mL(灵敏度94%、特异度83%),对重症手足口病患儿心肺衰竭期的检测阈值是1 500 pg/mL(灵敏度92%、特异度94%)。12例死亡患儿血清NT-proBNP水平均大于5 000 pg/mL,显著高于同期存活患儿水平。结论急诊快速检测NT-proBNP水平可反映手足口病患儿的严重程度,有效的甄别第二期和第三期。NT-proBNP是预警重症手足口病患儿心力衰竭的一项非常有用的生化指标。

Objective Cardiorespiratory failure is the main cause of death in children with severe hand, foot and mouth disease （HFMD）. This study aimed to evaluate the clinical significance of N terminal pro-brain natriuretic peptide （NT-proBNP） in HFMD children at risk of heart failure. Methods A total of 392 children with HFMD and 200 healthy controls were enrolled in this study. The patients were allocated to one of five groups based on the severity of HFMD according to the Expert Consensus on Clinical Treatment of Severe Enterovirus 71 Infection （2011 edition） issued by China Ministry of Health. Patient group corresponded to the disease stage of HFMD, i. e., rash period （stage 1 ）, nervous system involvement （stage 2）, early cardiorespiratory failure （stage 3）, cardiorespiratory failure （stage 4）, and recovery （stage 5）. Serum NT proBNP, creatine kinase-MB（CKMB）, and cTnI levels were tested and bedside echocardiography was performed for all patients immediately when they first came to hospital. Results Spearman correlation analysis revealed no correlation between cTnI, CKMB and left ventricular ejection fraction （LVEF） （ P 〉 0. 05 ）. However, negative correlation was found between NT-proBNP level and LVEF（r= - 1, P〈0. 05）. Increasing serum NT proBNP level was associated with worsening of HFMD. The median level of NT-proBNP was 921 pg/mL in the patients at the stage of nervous system involvement, 55 pg/mL in the patients at stage of early cardiorespiratory failure. Receiver operating characteristic （ROLE） curve analysis indicated that NT-proBNP testing had a sensitivity of 94% and specificity of 83% at cutoff value of 〉~400 pg/mL in detecting HFMD at third or higher stage; and a sensitivity of 92% and specificity of 94% at cutoff value of 〉 1 500 pg/mL in identifying HFMD at fourth or higher stage. Serum NT-proBNP 〉 5 000 pg/mL was highly sensitive and specific in predicting patient death. Conclusions Serum NT-proBNP level by rapid test in Emergency Room can reflect the severity of HFMD in children. NT-proBNP is a very useful biomarker for evaluating the risk of heart failure in children with severe HFMD.