Objective: To estimate the predictive value of heart rate (HR)-blood pressure (BP) products of multiplication for compensated shock in children. Methods: The study population consisted of 99 children with shock who had lactate measured before receiving vasopressor agents in Department of Critical Care Medicine of Children's Hospital, Capital Institute of Pediatrics from October 2015 to March 2021. The clinical data including the HR, BP, HR to BP ratio, HR-BP product and lactate at admission and after the correction of shock, as well as the 28-day mortality were collected. According to the outcome at the 28th day, the patients were divided into survival group and non-survival group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test. Pearson correlation analysis was used to analyze the correlations between lactate and HR, BP, HR to BP ratio and HR-BP product, respectively. Receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive values of HR, BP, HR to BP ratio and HR-BP product for lactate greater than 2 mmol/L. Results: In these 99 children, 49 were males, and the median age was 3.8 (0.7-6.0) years. The most common type of shock was septic shock (61 cases, 62%), followed by cardiogenic shock (12 cases, 12%), hemorrhagic shock (12 cases, 12%), Kawasaki disease shock syndrome (8 cases, 8%) and anaphylactic shock (6 cases, 6%). Sixty-six patients (67%) survived, and 33 patients (33%) died. ROC curve showed that the area under curves (AUC) of lactate (optimal cutoff value 3.15 mmol/L, sensitivity 96.0%, specificity 54.4%, P<0.01) and HR to systolic blood pressure ratio (HR/SBP) (optimal cutoff value 2.0 times/(min·mmHg), sensitivity 62.5%, specificity 69.0%, P = 0.03) for predicting adverse outcome were 0.769 and 0.649, respectively. There were significant correlations between lactate and HR to diastolic blood pressure (DBP) ratio, HR to mean blood pressure (MBP) ratio, SBP, HR/SBP, MBP, DBP and HR (r= 0.476, 0.452, -0.444, 0.425,-0.410, -0.364, 0.177, all P<0.01), while no significant correlation was found between lactate and the products of HR and BP(all P>0.05). HR/SBP performed better than the other six parameters for predicting lactate>2 mmol/L, with the AUC of 0.872 and the optimal cutoff value of 1.4 bpm/mmHg (sensitivity 92.1%, specificity 70.9%, P<0.01). When MBP was greater than or equal to 65 mmHg, MBP × HR, DBP × HR, SBP × HR, HR, HR/SBP, HR/MBP and HR/DBP were significantly correlated with lactate (r= 0.706, 0.705, 0.669, 0.626, 0.555, 0.502, 0.446, all P<0.01). And MBP × HR performed better for predicting lactate>2 mmol/L than the other six parameters, with the AUC of 0.974 and the optimal cutoff value of 9446 bpm × mmHg (sensitivity 100.0%, specificity 90.9%, P<0.01). Conclusions: The product of HR and BP, especially the MBP × HR, shows higher predictive values for abnormally elevated lactate in children with compensated shock than the HR/SBP does. It is worth recommending for early identification of compensated shock in children.目的： 探讨心率血压乘积识别儿童代偿期休克的价值。 方法： 回顾性分析2015年10月至2021年3月就诊于首都儿科研究所附属儿童医院重症监护室（PICU）99例诊断休克的患儿入PICU时（未应用血管活性药物状态）及休克纠正后的心率、血压、心率血压比值、心率血压乘积、乳酸及28 d转归等临床资料。根据28 d转归分为生存组和死亡组，组间比较应用独立样本t检验、Mann-Whitney U检验、χ²检验。应用Pearson相关分析分析心率、血压、心率血压比值、心率血压乘积与乳酸的相关性，受试者工作特征（ROC）曲线分析心率、血压、心率血压比值、心率血压乘积对乳酸>2 mmol/L的预测价值。 结果： 99例患儿中男49例、女50例，年龄3.8（0.7，6.0）岁，其中脓毒性休克61例（62%），心源性休克12例（12%），失血性休克12例（12%），川崎病休克综合征8例（8%），过敏性休克6例（6%）。随访28 d生存66例（67%），死亡33例（33%）。ROC曲线显示乳酸、心率/收缩压均对28 d死亡有预测价值（均P<0.05），曲线下面积（AUC）分别为0.769、0.649，最佳临界值分别为3.15 mmol/L、2.0 次/（min·mmHg）（1 mmHg=0.133 kPa），灵敏度分别为96.0%、62.5%，特异度分别为54.4%、69.0%。Pearson相关分析显示乳酸与心率/舒张压、心率/平均压、心率/收缩压、心率均正相关（r=0.476、0.452、0.425、0.177，均P<0.01），与收缩压、平均压、舒张压均负相关（r=-0.444、-0.410、-0.364，均P<0.01），与心率血压乘积无相关性（P>0.05）；ROC曲线显示心率/收缩压预测乳酸>2 mmol/L的AUC最大为0.872［最佳临界值1.4 次/（min·mmHg），灵敏度92.1%，特异度70.9%，P<0.01］。当平均压≥65 mmHg时，乳酸与心率平均压乘积、心率舒张压乘积、心率收缩压乘积、心率、心率/收缩压、心率/平均压、心率/舒张压均正相关（r=0.706、0.705、0.669、0.626、0.555、0.502、0.446，均P<0.01）；ROC曲线显示心率平均压乘积预测乳酸>2 mmol/L的AUC最大为0.974［最佳临界值9 446（次· mmHg/min），灵敏度100.0%，特异度90.9%，P<0.01］。 结论： 心率血压乘积尤其是心率平均压乘积对儿童代偿期休克的动脉血乳酸异常升高有较高的预测价值，优于心率/收缩压，值得推荐用于儿童代偿期休克的早期识别。.
Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity.Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP.The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP.The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.
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