| BackgroundOptimizing fluid therapy aims to prevent patients from both inadequate tissue perfusion and fluid overload.Fluid challenge is the gold standard way to evaluate patient's response to fluid therapy.In recent decade,using a minimal volume to practice fluid challenge has attracted more physicians.However,there is a wide divergence in how to perform it and the minimal volume varies with different monitoring techniques.Therefore,patients may be possibly misclassified if an inappropriate practice being applied.Moreover,although cardiac output(CO)evaluation is the gold standard of fluid responsiveness,hypotension is commonly the trigger of fluid challenge and blood pressure is the main indicator to evaluate fluid responsiveness.Arterial load is the main factor determining interaction between CO and blood pressure.The effective arterial elastance(Ea)is a simple index to characterize arterial load and its reliability in evaluating arterial load has been proved.Therefore,it is worth exploring the profound value of Ea in predicting fluid responsiveness and early initiation of norepinephrine weaning.ObjectivesFirst,to explore the minimal volume of fluid challenge in effectively predicting septic shock patients' fluid responsiveness using pulmonary artery catheter continuous CO monitoring[PAC(STAT-CCO)].Second to observe the effects of fluid administration on arterial load and assess Ea's ability in detecting patient who is possibly benefit from fluid therapy and capable of norepinephrine weaning at early phase of septic shock.MethodsThis study contains two parts.The first part is a prospective study.Septic shock patients were recruited from July 2019 to September 2020 in Medical Intensive Care Unit(MICU),Peking Union Medical College Hospital.All patients received continuous monitoring of PAC(STAT-CCO).The fluid challenge was performed with 100 mL 4%gelatin for 5 times.The hemodynamic parameters including CO,stroke volume(SV),heart rate(HR),systolic arterial pressure(SAP)and mean arterial pressure(MAP)were measured before fluid challenge and immediately after each time of 100 mL gelatin infusion.Ea,net arterial compliance(C),arterial time constant(Tau)and systemic vascular resistance(SVR)were calculated and blood gas were collected as well.An increase in CO greater than 10%after a total infusion of 500 ml 4%gelatin was defined as positive fluid responsiveness,and ?MAP500?10%was regarded as positive blood pressure responsiveness with the assuming of an optimal arterial pressure-flow coupling.Pearson correlation analysis was used to analyze the correlation between ?CO100%,?CO200%,?CO300%,?CO400%and ?CO500%.The receiver operating characteristic(ROC)curves were drawn to analyze the predictive abilities of different fluid volume in detecting fluid responders and explore the minimal volume in effectively predicting fluid responsiveness as traditional volume of 500 mL does.Patients were divided into two groups according to CO changes:preload-responders(preload-R group)and preload-nonresponders(preload-NR group).The effects of fluid administration on arterial load were analyzed.In addition,the pressure responsiveness was compared in these two groups as well.The clinical significance of Ea in regulating blood pressure and CO was analyzed.In the second part of this study,we selected septic shock patients who still needed norepinephrine supporting after receiving 30 mL/kg fluid administration in MICU of Peking Union Medical College Hospital from October 2016 to October 2020.The hemodynamic parameters before and after fluid challenge,the norepinephrine dose,fluid intake,diuresis,total output and fluid balance at 6 hours,12 hours,24hours,48 hours,72 hours after fluid challenge,and duration of norepinephrine use,28-day outcome were collected.According to the norepinephrine dose change at six hours after fluid challenge,patients were divided into norepinephrine weaning group(NE-weaning)and norepinephrine worsening group(NE-worsening),in where NE-weaning was defined as norepinephrine reduction at 6 hours after fluid challenge,and NE-worsening was defined on the contrary.The univariate analyses and multivariate analyses were applied to explore the indicators associated with norepinephrine weaning.The Ea's predictive ablity in detecting the possibility of initiating norepinephrine weaning was evaluated.In addition,according to the patients'response to fluid challenge,the Ea's capability in predicting fluid responsiveness and pressure responsiveness were assessed.ResultsIn the first part of the study,forty-seven septic shock patients were included.Thirty-five(74.5%)of them were preload responders and twelve(25.5%)patients were preload nonresponders.The main findings were as follows:?The minimal volume was 200 mL which can effectively evaluate the fluid responsiveness.The area under ROC curve(AUC)was 0.93,and the 95%confidence interval(CI)was 0.84-1.00,P<0.001.There was no significant difference between the AUCs of 200 mL and 500 mL,P=0.102.The least significant change(LSC)of PAC(STAT-CCO)was 3.4%,thus,when applying the fluid challenge of 200 mL,an increase in CO more than 5.2%could be regarded as preload responder.The sensitivity and specificity were 80.0%and 91.7%.?Fluid administration affected the arterial load of the two groups.The baseline Ea of the preload responders was significantly higher than that of the preload nonresponders,2.23(1.46-2.78)mmHg/mL versus 1.60(1.41-1.65)mmHg/mL(P=0.003).?Among 35 preload responders,19 patients(54.3%)were pressure nonresponders.In these patients,Ea decreased significantly from 2.37(1.65-2.91)mmHg/mL to 1.91(1.34-2.22)mmHg/mL after fluid administration(P<0.001),whereas Ea remained stable in patients with both positive preload and pressure responsiveness.In the second part of the study,a total of 108 patients with septic shock were included.75 patients(69.4%)began to norepinephrine weaning(NE-weening)at 6 hours after fluid challenge,while norepinephrine increased in 33 patients(30.6%,NE-worsening).?The univariate analyses showed that the change of Ea(?Ea%)was associated with norepinephrine weaning,with odds ratio(OR)of 1.025(95%CI:1.000-1.050;P=0.042).To predict norepinephrine weaning,the cut-off of ?Ea%was 5.2%,with a sensitivity of 61.3%and a specificity of 66.7%.Multivariate analyses showed that a combination of ?Ea%,the change of systemic vascular resistance(?SVR%)and the change of CO(?CO%)could provide a better prediction.The AUC was 0.73(P<0.001).?In the NE-weaning group,54 patients weaned off norepinephrine while 21 patients did in the NE-worsening group.The median duration of norepinephrine use in the two groups was 48.0(34.0-89.0)hours versus 72.0(54.0-90.0)hours(P=0.037).?Baseline Ea predicted the fluid responsiveness with an AUC at 0.74(95%CI:0.60-0.88,P<0.001),and the best cut-off was 1.97 mmHg/mL with a sensitivity of 71.4%and specificity of 60.4%.Conclusions1.In septic shock patients,a minimal volume of 200 mL 4%gelatin could reliably detect fluid responders.TheLSC of PAC was 3.4%.Therefore,when 200 mL of fluid challenge was applied,an increase in CO greater than 5.2%could be considered as positive fluid responsiveness.2.Change in Ea after fluid challenge helps clinicians identify patients who can initiate norepinephrine weaning at early phase of septic shock.A combination of ?Ea%,?S VR%and ?CO%strengthen the prediction ability.3.A high level of Ea before fluid challenge might be able to predict preload responsiveness,the higher the baseline Ea,the patients are more likely to be positive response to fluid challenge.A significant decrease in Ea after fluid challenge explains why patients increase their cardiac output after volume expansion without improving blood pressure. |
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