CaCl2-Citrate Regional Anticoagulation with Continuous Veno-Venous Haemodialysis Leads to Unwanted Chloride Loading Compared to Continuous Veno-Venous Hemofiltration with Systemic Anticoagulation.

INTRODUCTION: Chloride transfers during continuous renal replacement therapy (CRRT) have not been adequately described and may differ based on CRRT technique. We aimed to measure chloride mass transfer (JS,Cl) during CRRT and identify associated determinants. METHODS: We performed a two-centre, prospective, observational study in France and Australia in ICU patients with CRRT initiated for <24 h. Patients received continuous veno-venous hemofiltration (CVVH) or continuous veno-venous haemodialysis (CVVHD, with citrate-CaCl2 regional anticoagulation). Over a 24 h period, plasma and effluent chloride concentrations were measured every 4 h to compute chloride mass transfer (JS,Cl, in mmol.min-1) using a modality-specific model, with negative value indicating chloride transfer towards the patient. Secondary outcomes were the identification of CRRT settings associated with JS,Cl (using multivariate mixed effects regression). Results are presented with median (interquartile range). RESULTS: Between February 2021 and August 2022, we enrolled 37 patients (64 [56-71] years, 67% male), for a total of 20 CVVHD and 20 CVVH sessions. Over 24 h, plasma chloride concentrations were significantly higher, and JS,Cl significantly lower during CVVHD, compared to CVVH (-0.10 [-0.33 to 0.15] vs. 0.01 [-0.10 to 0.13] mmol.min-1, p < 0.05). With both modalities, net ultrafiltration (QUFNET) and plasma chloride concentrations were the principal determinants of JS,Cl, with higher QUFNET being associated with an increase in JS,Cl during CVVHD. Also, CVVHD sessions demonstrated a concentration gradient between the plasma and the effluent chamber of -6 [-9 to -4] mmol.L-1. Finally, CaCl2 reinjection during CVVHD accounted for 35% [32-60%] of total JS,Cl in sessions with a negative JS,Cl. CONCLUSION: Compared to CVVH, CVVHD with regional citrate anticoagulation was associated with greater chloride mass transfer to the patient and higher plasma chloride concentrations. This was due to high dialysate chloride concentrations and CaCl2 reinjection. This effect could only be controlled by high net ultrafiltration flow rates.

Determinants of Urine Output Using Advanced Hemodynamic Monitoring in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

INTRODUCTION: Low cardiac output and hypovolemia are candidate macrocirculatory mechanisms explanatory of de novo anuria in intensive care unit (ICU) patients undergoing continuous renal replacement therapy (CRRT). We aimed to determine the hemodynamic parameters and CRRT settings associated with the longitudinal course of UO during CRRT. METHODS: This is an ancillary analysis of the PRELOAD CRRT observational, single-center study (NCT03139123). Enrolled adult patients had severe acute kidney injury treated with CRRT for less than 24 h and were monitored with a calibrated continuous cardiac output monitoring device. Hemodynamics (including stroke volume index [SVI] and preload-dependence, identified by continuous cardiac index variation during postural maneuvers), net ultrafiltration (UFNET), and UO were reported 4-hourly, over 7 days. Two study groups were defined at inclusion: non-anuric participants if the cumulative 24 h UO at inclusion was ≥0.05 mL kg-1 h-1, and anuric otherwise. Quantitative data were reported by its median [interquartile range]. RESULTS: Forty-two patients (age 68 [58-76] years) were enrolled. At inclusion, 32 patients (76%) were not anuric. During follow-up, UO decreased significantly in non-anuric patients, with 25/32 (78%) progressing to anuria within 19 [10-50] hours. Mean arterial pressure (MAP) and UFNET did not significantly differ between study groups during follow-up, while SVI and preload-dependence were significantly associated with the interaction of study group and time since inclusion. Higher UFNET flow rates were significantly associated with higher systemic vascular resistances and lower cardiac output during follow-up. Multivariate analyses showed that (1) lower UO was significantly associated with lower SVI, lower MAP, and preload-independence; and (2) higher UFNET was significantly associated with lower UO. CONCLUSIONS: In ICU patients treated with CRRT, those without anuria showed a rapid loss of diuresis after CRRT initiation. Hemodynamic indicators of renal perfusion and effective volemia were the principal determinants of UO during follow-up, in relation with the hemodynamic impact of UFNET setting.

Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study.

Background: Experimentally, ultra-protective ventilation (UPV, tidal volumes [VT] < 4 mL.kg-1) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS. Methods: ARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (VT 1 mL.kg-1, positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH2O and respiratory rate [RR] at 5 min-1 under VV-ECMO) or PV (VT 6 mL.kg-1, PEEP set to obtain plateau pressure between 28 and 30 cmH2O and RR at 25 min-1) during 4 h. After 4 h, a positron emission tomography with [11C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [11C](R)-PK11195 lung uptake. [11C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis. Results: Five pigs were randomized to each study group. Arterial O2 partial pressure to inspired O2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68-80] mmHg in a PV group vs. 87 [69-133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [11C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20-0.59] in UPV animals and 1.01 [IQR, 0.75-1.59] in PV animals, p = 0.01). Regional [11C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance. Conclusion: In an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of VT-derived determinants of VILI.

Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial.

PURPOSE: Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care. METHODS: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UFNET ≥ 100 ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25 ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population. RESULTS: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms. CONCLUSION: In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Bias, trending ability and diagnostic performance of a non-calibrated multi-beat analysis continuous cardiac output monitor to identify fluid responsiveness in critically ill patients.

Objective: To evaluate the accuracy of non-calibrated multi-beat analysis continuous cardiac output (CCOMBA), against calibrated pulse-contour analysis continuous cardiac output (CCOPCA) during a passive leg raise (PLR) and/or a fluid challenge (FC). Design: Observational, single-centre, prospective study. Setting: Tertiary academic medical intensive care unit, Lyon, France. Participants: Adult patients receiving norepinephrine, monitored by CCOPCA, and in which a PLR and/or a FC was indicated. Main outcome measures: CCOMBA and CCOPCA were recorded prior to and during the PLR/FC to evaluate bias and evaluate changes in CCOMBA and CCOPCA (∆%CCOMBA and ∆%CCOPCA). Fluid responsiveness was identified by an increase >15% in calibrated cardiac output after FC, to identify the optimal ∆%CCOMBA threshold during PLR to predict fluid responsiveness. Results: 29 patients (median age 68 [IQR: 57-74]) performed 28 PLR and 16 FC. The bias between methods increased with higher CCOPCA values, with a percentage error of 64% (95%confidence interval: 52%-77%). ∆%CCOMBA adequately tracked changes in ∆%CCOPCA with an angular bias of 2 ± 29°. ∆%CCOMBA during PLR had an AUROC of 0.92 (P < 0.05), with an optimal threshold >14% to predict fluid responsiveness (sensitivity: 0.99, specificity: 0.87). Conclusions: CCOMBA showed a non-constant bias and a percentage error >30% against calibrated CCOPCA, but an adequate ability to track changes in CCOPCA and to predict fluid responsiveness.

Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial.

BACKGROUND: The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation. METHODS: The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH2O) and PEEP (5 cmH2O). In case of SBT success, an additional SBT with TP was performed. Failure of this SBT-TP was an additional criterion for post-extubation NIV in this group in addition to other recommended criteria. In the standard weaning group, SBT was performed with TP, and NIV was performed according to international guidelines. The primary outcome criterion was the time between inclusion and successful extubation evaluated with a Cox model with adjustment on randomization strata. RESULTS: From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58-73] vs. 62 [55-71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50-436] vs. 95 [47-232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55-1.42] using the standard weaning group as a reference; p = 0.60). All secondary outcomes were not significantly different between groups. CONCLUSION: An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy. Trial registration The trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient. https://clinicaltrials.gov/study/NCT03861117 .