Abstract 12327: Intravenous Waveform Analysis Correlates With Volume Status in Resuscitation in In-Vivo Rat Model

Introduction: Current volume status markers under-perform. Dynamic markers demonstrate improved outcomes in goal directed fluid therapy but maintain validity in a narrow range of clinical parameters. In addition, they assess volume responsiveness over total volume status. Repeated echo assessments may be infeasible. Hypothesis: Intravenous waveform analysis-derived F1 more closely models volume status than current markers in a rat resuscitation model. Methods: Seven Sprague Dawley rats were anesthetized and mechanically ventilated. Pressure transductions occurred via cannulation of the right femoral vein, left femoral artery and right internal jugular vein. Hemorrhage and resuscitation occurred via the left femoral vein. Heparinized rats were bled to 80% of the estimated blood volume (EBV) then resuscitated with their own whole blood in increments of 2% of the EBV until euvolemia was reached. Cardiac output (CO) and left ventricular end diastolic area (LVEDA) were calculated with echocardiography. Fast Fourier transform was performed on venous waveforms to obtain the heart rate linked F1 amplitude. Pearson’s correlation coefficients were compared using Fisher’s Z transformation. Mixed effects modeling goodness-of-fit was assessed with Akaike information criterion (AIC). Significance was set at p=.05. Results: F1 had the strongest correlation with volume status, r= .70, followed by CO, r=.55, LVEDA, r=.55, mean arterial pressure (MAP), r=.50, central venous pressure r= -.02, and pulse pressure variation (PPV), r=.01. When compared, F1 rho was significantly greater than that of all variables except CO and LVEDA, p=.09 and p=.07, respectively. In mixed effects regression, F1 displayed the most significant AIC, -274, followed by CO at -239. Conclusions: The novel marker F1 is strongly correlated with volume status during whole blood resuscitation. F1 may be superior to current markers for directing volume resuscitation therapy.

Changes in Cardiac Index Induced by Unilateral Passive Leg Raising: a Novel Way for Assessing Fluid Responsiveness

Background: To evaluate the fluid responsiveness of patients, we examined the change in cardiac index (CI) during a unilateral passive leg raising (PLR) test using the ProAQT/Pulsioflex. In addition, we compared the change of CI triggered by bilateral PLR test and unilateral PLR test, and the ability to estimate volume responsiveness in patients.Methods: This was a prospective, observational study, and we enrolled 40 individuals thought of volume expansion. The data of cardiac index, stroke variation in volume, stroke volume index, along with variation in pulse pressure were obtained with ProAQT/Pulsioflex at a semi-recumbent position, during unilateral PLR, bilateral PLR, as well as after expansion of volume (500 ml saline over 15 min). If CI improved more than 15% to the expansion of volume, patients were defined as responders.Results: We excluded three patients. We found that a unilateral PLR-triggered CI increment ≥7.455% forecasted a fluid-triggered CI increment ≥15% with 77.27% sensitivity and 83.33% specificity. Meanwhile, bilateral PLR-triggered increases in CI ≥9.8% forecasted a fluid-triggered CI increment ≥15% with 95.45% sensitivity and 77.78% specificity. The area under the ROC curves constructed for unilateral and bilateral PLR-triggered changes in CI was not significantly different (p=0.1544).Conclusions: The change of CI induced by unilateral PLR may estimate volume responsiveness in patients.Trial registration: Unilateral passive leg raising test to assess patient volume responsiveness: Single-Center Observational Clinical Study, ChiCTR2100046762. Registered 28 May 2021, https://www.chictr.org.cn/edit.aspx?pid=127104&htm=4

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

Background Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. Methods This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. Discussion This study aims to generate evidence regarding which regimen—a gelatine-crystalloid regimen or a pure crystalloid regimen—is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. Trial registration The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466. Registered on 17 March 2016.

Comparison of global end-diastolic volume index derived from jugular and femoral indicator injection: a prospective observational study in patients equipped with both a PiCCO-2 and an EV-1000-device

Transpulmonary thermodilution (TPTD)-derived global end-diastolic volume index (GEDVI) is a static marker of preload which better predicted volume responsiveness compared to filling pressures in several studies. GEDVI can be generated with at least two devices: PiCCO and EV-1000. Several studies showed that uncorrected indicator injection into a femoral central venous catheter (CVC) results in a significant overestimation of GEDVI by the PiCCO-device. Therefore, the most recent PiCCO-algorithm corrects for femoral indicator injection. However, there are no systematic data on the impact of femoral indicator injection for the EV-1000 device. Furthermore, the correction algorithm of the PiCCO is poorly validated. Therefore, we prospectively analyzed 14 datasets from 10 patients with TPTD-monitoring undergoing central venous catheter (CVC)- and arterial line exchange. PiCCO was replaced by EV-1000, femoral CVCs were replaced by jugular/subclavian CVCs and vice-versa. For PiCCO, jugular and femoral indicator injection derived GEDVI was comparable when the correct information about femoral catheter site was given (p = 0.251). By contrast, GEDVI derived from femoral indicator injection using the EV-1000 was obviously not corrected and was substantially higher than jugular GEDVI measured by the EV-1000 (846 ± 250 vs. 712 ± 227 ml/m2; p = 0.001). Furthermore, measurements of GEDVI were not comparable between PiCCO and EV-1000 even in case of jugular indicator injection (p = 0.003). This is most probably due to different indexations of the raw value GEDV. EV-1000 could not be recommended to measure GEDVI in case of a femoral CVC. Furthermore, different indexations used by EV-1000 and PiCCO should be considered even in case of a jugular CVC when comparing GEDVI derived from PiCCO and EV-1000.