| BackgroundFluid administration is the cornerstone of managing patients with septic shock.However,excessive fluid has been associated with increased complications in patients who are considered ’fluid non-responders’.Assessment of patient response to volume expansion presents a key part to fluid therapy.Despite the fact that a fluid challenge is a common way to define fluid responsiveness,there is little agreement regarding how to perform it,with varying fluid types,volumes,infusion rates,durations of response and time of assessment.Physiological changes over time after fluid challenge will be different if different types of fluid are administered.Previous studies were observed that the effect of a fluid challenge with crystalloids on hemodynamics was dissipated within 10 minutes after the end of the fluid infusion while colloids maintained a longer time.As a result,the timing of assessment of fluid responsiveness should be performed respectively when different types of fluid were infused.Moreover,our research team has found that,compared to central venous oxygen saturation(ScvO2)before volume expansion,ScvO2 variations(AScvO2)immediately after fluid challenge can be suggested as an alternative marker to define fluid responsiveness.However,△ScvO2 at 10-120 minutes after completion of the fluid challenge cannot be an alternative marker to classify responders and non-responders.Different fluid responsiveness at 10-120 minutes after the end of the fluid challenge may be the reason for the poor predictive value of △ScvO2 immediately after fluid challenge.Objective:1.To observe the physiological changes of a fluid challenge with colloids over a 120-minute period and define fluid responsiveness at the optimal time.2.To evaluate the value of △ScvO2 and other physiological changes as markers to define fluid responsiveness in septic shock patients.Methods1.This is a prospective observational study performed in medical intensive care unit.Septic shock patients monitored with a pulmonary artery catheter who required a fluid challenge with 4%gelatin(500ml infused over 10-15 minutes)were included.Hemodynamic variables,arterial blood gas,central and mixed venous blood gas,hemoglobin,hematocrit and serum creatinine were measured at baseline,immediately and at 10,30,45,60,90,120 minutes after completion of the fluid challenge.Oxygen metabolism variables were recorded and calculated at the same time.2.Fluid responsiveness was defined as increase in cardiac output index(CI)of at least 10%at any time point after fluid challenge.Physiological change(AX)referred to the variation between physiological variable measured at 0-120 minutes after the end of fluid challenge and one measured before fluid challenge in a same patient.The datas were analyzed to compare the differences between before and at different time after fluid challenge in each group respectively.3.Receiver operator characteristic(ROC)curves were constructed to detect the ability of△ScvO2 and other physiological changes at different time after fluid bolus to identify the fluid responders assessed at the corresponding time points.The effects of oxygen consumption index(VO2I)and Hemoglobin(Hb)on the predictive value of △ScvO2 were also assessed.Results1.Different Fluid responsiveness and groups.Forty-three septic shock patients were included in this trial.Their age was 61(48-71)years old.Patients were divided into three groups according to their fluid responsiveness.Patients with an increase in CI greater than 10%immediately after the fluid challenge were considered immediate responders.Twenty-three patients were immediate responders.All of them remained effective response to volume expansion with an increase in CI greater than 10%for 45 minutes and 16 patients for 120 minutes.Twenty patients were non-responders to volume expansion immediate after fluid challenge.Interestingly enough,six of them became responders at 10 minutes after fluid challenge with an increase in CI greater than 10%,three of them became responders at 30 minutes after fluid challenge.Patients with an increase in CI greater than 10%at 10 and 30 minutes after the fluid challenge were considered later responders.The rest patients,with an increase in CI less than or equal to 10%at any time after the fluid challenge were called persistent non-responders.According to the definition described above,there were 23 patients in the immediate responders group,9 patients in the later responders group,and 11 patients in the persistent non-responders group.2.Physiological changes before and after fluid challengeBefore fluid challenge,CI in the immediate responders group and later responders group was significantly lower than that in persistent non-responders group respectively and the later responders group showed the lowest value.In the immediate responders group,CI increased significantly at any time after fluid challenge.Volume expansion increased the CI significantly to maximum at 30 minutes after fluid challenge.In the later responders group,compared with CI measured before fluid challenge,CI at 10-60minutes after fluid challenge was notably higher.The maximal effect was observed at 45 minutes after the end of the fluid infusion.At 120 minutes after fluid challenge,an increase in CI greater than 10%was also observed.△CI at different time after fluid challenge was various among three group.CI in the immediate responders group increased faster than that in the later responders group after fluid challenge.CI did not increase over time in persistent non-responders group compared before.Compared with persistent non-responders group,central venous pressure(CVP)was notably lower at any time after fluid challenge in the immediate responders group.There were no remarkable differences of other physiological variables among the three groups.Oxygen delivery index increased parallelly to CI in the immediate responders group.VO2I increased to the maximum at 45 minutes after fluid challenge and showed no significant difference among the three groups before and after fluid challenge.In the immediate responders group,ScvO2 increased to the maximum immediately after fluid challenge,being notably higher than that measured before fluid challenge.ScvO2 in the immediate responders group was significantly higher than that in the later responders group at any time after fluid challenge.3.The predictive values of AScvO2 and other Physiological changesAScvO2 immediately and at 10,30,45,60,120 minutes after completion of the fluid challenge could identify responders to fluid challenge assessed at the corresponding time points after fluid challenge.AScvO2 demonstrated a better discriminative power if Hb decreased within 14 g/L after fluid challenge.The area under ROC of AScvO2 to predict fluid responsiveness was up to 0.81-0.91 when AVO2I after fluid challenge increased less than 20 ml/min/m2 and decreased less than 11 ml/min/m2.△Pcv-aCO2,△HR,△MAP,△ SBP and △DBP at different time after fluid challenge could not discriminated between responders and non-responders assessed at the corresponding time points.△CVP immediately after completion of the fluid challenge could differentiate fluid responders and non-responders assessed immediately after fluid bolus,with the area under ROC of 0.68(95%CI,0.52-0.84).But ACVP at 10-120 minutes after fluid challenge could not predict fluid responsiveness assessed accordingly at 10-120 minutes after fluid challenge.Conclusion1.CI increases to maximum at 30 minutes after fluid challenge with 4%gelatin in septic shock patients and remains an increase greater than 10%for 120 minutes.2.Patients who are defined as fluid non-responders immediately after fluid bolus present response to fluid infusion at a later time and an increase in CI of greater than 10%is sustaining for 120 minutes.Optimal timing of assessment of fluid responsiveness should be choosed in these patients.3.△ScvO2 at different time after completion of the fluid challenge can identify responders to fluid challenge defined at the corresponding time points.As long as VO2I and Hb change within a certain range,△ScvO2 can be a promising surrogate for ACI to define fluid responsiveness in septic shock patients without invasive CI measurement. |
