He Huaiwu, Yuan Siyi, Long Yun, Liu Dawei, Zhou Xiang, Ince Can
Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
Department of Intensive Care, Erasmus MC University Hospital, Rotterdam, The Netherlands.
Ann Transl Med. 2021 Apr;9(7):561. doi: 10.21037/atm-20-6686.
The present study investigated the cardiovascular determinants of cardiac output (CO), mean systemic filling pressure analogue (Pmsa) derived by Geoffrey Parkin, efficiency of heart (Eh) and related parameters to a norepinephrine (NE) challenge [an increase of 10 mmHg mean arterial pressure (MAP) by NE] in septic shock patients using of a mathematical model.
Twenty-seven septic shock patients with pulse index continuous cardiac output (PiCCO) monitoring were enrolled. These patients required NE to maintain an individualized MAP for organ perfusion after early fluid resuscitation based on their clinical condition. NE was decreased to obtain a decrease of 10 mmHg from base MAP (MAP), and the NE doses were adjusted to return MAP to baseline (MAP) and produce an increase of 10 mmHg from MAP (MAP). Two NE challenge episodes were analyzed for each patient: from MAP to MAP and from MAP to MAP. The Pmsa, pressure gradient for venous return (PG), and Eh (PGvr relative to Pmsa) were estimated using a mathematical model for the three MAP levels (MAP, MAP and MAP).
A total of 54 episodes of NE challenges were obtained in 27 patients. Significant and consistent increases were observed in the central venous pressure (CVP), Pmsa, and PGvr in response during the NE titration. ΔCO negatively and significantly correlated with ΔCVP (r=-0.722, P<0.0001), ΔPmsa (r=-0.549, P<0.0001), ΔResistance of venous return (Rvr) (r=-0.597, P<0.0001), and ΔResistance of systemic vascular beds (Rsys) (r=-0.597, P<0.0001). Episodes of decreasing CO/Eh were associated with a higher ΔCVP than the CO/Eh-increasing episodes. The area under the curve (AUC) of ΔCVP to predict decreased CO by the incremental NE was 0.86, and the AUC of ΔCVP to predict decreased Eh was 0.94. A cutoff of ΔCVP >1.5 mmHg for detecting decreased CO resulted in a sensitivity of 75% and a specificity of 94.1%. A cutoff of ΔCVP >1.5 mmHg for detecting decreased Eh resulted in a sensitivity of 64.3% and a specificity of 100%.
There were a highly divergent response in Eh and CO to afterload challenge episodes of an NE-induced 10mmHg increase in MAP. An increase in CVP may be an early alarm to identify the reduction in CO/Eh during an NE-induced increase of MAP.
本研究使用数学模型调查了脓毒症休克患者的心输出量（CO）、杰弗里·帕金推导的平均体循环充盈压类似值（Pmsa）、心脏效率（Eh）的心血管决定因素以及与去甲肾上腺素（NE）激发试验[NE使平均动脉压（MAP）升高10 mmHg]相关的参数。
纳入27例接受脉搏指示连续心输出量（PiCCO）监测的脓毒症休克患者。这些患者在基于临床状况进行早期液体复苏后需要NE来维持个体化的MAP以进行器官灌注。降低NE剂量以使MAP从基础MAP（MAP）降低10 mmHg，并调整NE剂量以使MAP恢复至基线（MAP）并使MAP升高10 mmHg。对每位患者分析两次NE激发试验：从MAP到MAP以及从MAP到MAP。使用数学模型针对三个MAP水平（MAP、MAP和MAP）估算Pmsa、静脉回流压力梯度（PG）和Eh（相对于Pmsa的PGvr）。
27例患者共获得54次NE激发试验结果。在NE滴定过程中，观察到中心静脉压（CVP）、Pmsa和PGvr出现显著且一致的升高。ΔCO与ΔCVP（r = -0.722，P < 0.0001）、ΔPmsa（r = -0.549，P < 0.0001）、Δ静脉回流阻力（Rvr）（r = -0.597，P < 0.0001）以及Δ体循环血管床阻力（Rsys）（r = -0.597，P < 0.0001）呈负相关且具有显著性。CO/Eh降低的试验比CO/Eh升高的试验具有更高的ΔCVP。ΔCVP预测因NE增量导致CO降低的曲线下面积（AUC）为0.86，ΔCVP预测Eh降低的AUC为0.94。检测CO降低时ΔCVP > 1.5 mmHg的临界值，敏感性为75%，特异性为94.1%。检测Eh降低时ΔCVP > 1.5 mmHg的临界值，敏感性为64.3%，特异性为100%。
在NE诱导MAP升高10 mmHg的后负荷激发试验中，Eh和CO存在高度不同的反应。CVP升高可能是在NE诱导MAP升高期间识别CO/Eh降低的早期警报。
