Fluid Intake in Critically Ill Patients: The "Save Useless Fluids For Intensive Resuscitation" Multicenter Prospective Cohort Study.

OBJECTIVES: Patients at risk of adverse effects related to positive fluid balance could benefit from fluid intake optimization. Less attention is paid to nonresuscitation fluids. We aim to evaluate the heterogeneity of fluid intake at the initial phase of resuscitation. DESIGN: Prospective multicenter cohort study. SETTING: Thirty ICUs across France and one in Spain. PATIENTS: Patients requiring vasopressors and/or invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All fluids administered by vascular or enteral lines were recorded over 24 hours following admission and were classified in four main groups according to their predefined indication: fluids having a well-documented homeostasis goal (resuscitation fluids, rehydration, blood products, and nutrition), drug carriers, maintenance fluids, and fluids for technical needs. Models of regression were constructed to determine fluid intake predicted by patient characteristics. Centers were classified according to tertiles of fluid intake. The cohort included 296 patients. The median total volume of fluids was 3546 mL (interquartile range, 2441-4955 mL), with fluids indisputably required for body fluid homeostasis representing 36% of this total. Saline, glucose-containing high chloride crystalloids, and balanced crystalloids represented 43%, 27%, and 16% of total volume, respectively. Whatever the class of fluids, center of inclusion was the strongest factor associated with volumes. Compared with the first tertile, the difference between the volume predicted by patient characteristics and the volume given was +1.2 ± 2.0 L in tertile 2 and +3.0 ± 2.8 L in tertile 3. CONCLUSIONS: Fluids indisputably required for body fluid homeostasis represent the minority of fluid intake during the 24 hours after ICU admission. Center effect is the strongest factor associated with the volume of fluids. Heterogeneity in practices suggests that optimal strategies for volume and goals of common fluids administration need to be developed.

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.

Safety of inter-facility transport strategies for patients referred for severe acute respiratory distress syndrome.

BACKGROUND: Inter-facility transport of patients with acute respiratory distress syndrome (ARDS) in the prone position (PP) is a high-risk situation, compared to other strategies. We aimed to quantify the prevalence of complications during transport in PP, compared to transports with veno-venous extracorporeal membrane oxygenation (VV-ECMO) or in the supine position (SP). METHODS: We performed a retrospective, single center cohort study in Lyon university hospital, France. We included patients ≥ 16 years with ARDS (Berlin definition) transported to an ARDS referral center between 01/12/2016 and 31/12/2021. We compared patients transported in PP, to those transported in SP without VV-ECMO, and those transported with VV-ECMO (in SP), by a multidisciplinary and specialized medical transport team, including an emergency physician and an intensivist. The primary outcome was the rate of transport-related complications (hypoxemia, hypotension, cardiac arrest, cannula or tube dislodgement) in each study groups, compared using a Fisher test. RESULTS: One hundred thirty-four patients were enrolled (median PaO2/FiO2 70 [58-82] mmHg), of which 11 (8%) were transported in PP, 44 (33%) with VV-ECMO, and 79 (59%) in SP. The most frequent risk factor for ARDS in the PP group was bacterial pneumonitis, and viral pneumonitis in the other 2 groups. Transport-related complications occurred in 36% (n = 4) of transports in PP, compared to 39% (n = 30) in SP and 14% (n = 6) with VV-ECMO, respectively (p = 0.33). VV-ECMO implantation after transport was not different between SP and PP patients (n = 7, 64% vs. n = 31, 39%, p = 0.19). CONCLUSIONS: In the context of a specialized multi-disciplinary ARDS transport team, transport-related complication rates were similar between patients transported in PP and SP, while there was a trend of lower rates in patients transported with VV-ECMO.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Non-invasive quantification of acute macrophagic lung inflammation with [11C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome.

PURPOSE: Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of [11C](R)-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues. MATERIAL AND METHODS: We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BPND) were compared to lung macrophage presence, semi-quantified in pathology. RESULTS: The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BPND determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BPND (p = 0.03). Regional BPND was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03). CONCLUSION: To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [11C](R)-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review.

PURPOSE: Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM. METHODS: Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines. RESULTS: In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes. CONCLUSIONS: Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.

Intensive care-related loss of quality of life and autonomy at 6 months post-discharge: Does COVID-19 really make things worse?

OBJECTIVE: To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. DESIGN: Comparison of two prospective multi-centric studies. SETTING: This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). PATIENTS: We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. CONCLUSIONS: COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.

Response to PEEP in COVID-19 ARDS patients with and without extracorporeal membrane oxygenation. A multicenter case-control computed tomography study.

BACKGROUND: PEEP selection in severe COVID-19 patients under extracorporeal membrane oxygenation (ECMO) is challenging as no study has assessed the alveolar recruitability in this setting. The aim of the study was to compare lung recruitability and the impact of PEEP on lung aeration in moderate and severe ARDS patients with or without ECMO, using computed tomography (CT). METHODS: We conducted a two-center prospective observational case-control study in adult COVID-19-related patients who had an indication for CT within 72 h of ARDS onset in non-ECMO patients or within 72  h after ECMO onset. Ninety-nine patients were included, of whom 24 had severe ARDS under ECMO, 59 severe ARDS without ECMO and 16 moderate ARDS. RESULTS: Non-inflated lung at PEEP 5 cmH2O was significantly greater in ECMO than in non-ECMO patients. Recruitment induced by increasing PEEP from 5 to 15 cmH2O was not significantly different between ECMO and non-ECMO patients, while PEEP-induced hyperinflation was significantly lower in the ECMO group and virtually nonexistent. The median [IQR] fraction of recruitable lung mass between PEEP 5 and 15 cmH2O was 6 [4-10]%. Total superimposed pressure at PEEP 5 cmH2O was significantly higher in ECMO patients and amounted to 12 [11-13] cmH2O. The hyperinflation-to-recruitment ratio (i.e., a trade-off index of the adverse effects and benefits of PEEP) was significantly lower in ECMO patients and was lower than one in 23 (96%) ECMO patients, 41 (69%) severe non-ECMO patients and 8 (50%) moderate ARDS patients. Compliance of the aerated lung at PEEP 5 cmH2O corrected for PEEP-induced recruitment (CBABY LUNG) was significantly lower in ECMO patients than in non-ECMO patients and was linearly related to the logarithm of the hyperinflation-to-recruitment ratio. CONCLUSIONS: Lung recruitability of COVID-19 pneumonia is not significantly different between ECMO and non-ECMO patients, with substantial interindividual variations. The balance between hyperinflation and recruitment induced by PEEP increase from 5 to 15 cmH2O appears favorable in virtually all ECMO patients, while this PEEP level is required to counteract compressive forces leading to lung collapse. CBABY LUNG is significantly lower in ECMO patients, independently of lung recruitability.

The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. RESULTS: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Hemodynamic Response to Fluid Boluses for Hypotension in Children in a Cardiac ICU.

OBJECTIVES: To describe the hemodynamic response to fluid boluses for hypotension in children in a cardiac ICU. DESIGN: A prospective, observational study. SETTING: Single-centered cardiac ICU. PATIENTS: Children in a cardiac ICU with hypotension. INTERVENTIONS: Clinician prescribed fluid bolus. MEASUREMENTS AND MAIN RESULTS: Sixty-four fluid boluses were administered to 52 children. Fluid composition was 4% albumin in 36/64 (56%), 0.9% saline in 18/64 (28%), and cardiopulmonary bypass pump blood in 10/64 (16%). The median volume and duration were 5.0 mL/kg (interquartile range, 4.8-5.4) and 8 minutes (interquartile range, 4-19), respectively. Hypovolemia/low filling pressures was the most common additional indication (25/102 [25%]). Mean arterial pressure response, defined as a 10% increase from baseline, occurred in 42/64 (66%) of all fluid boluses at a median time of 6 minutes (interquartile range, 4-11). Mean arterial pressure responders had a median peak increase in the mean arterial pressure of 15 mm Hg (43 mm Hg [interquartile range, 29-50 mm Hg] to 58 mm Hg [interquartile range, 49-65 mm Hg]) at 17 minutes (interquartile range, 14-24 min) compared with 4 mm Hg (48 mm Hg [interquartile range, 40-51 mm Hg] to 52 mm Hg [interquartile range, 45-56 mm Hg]) at 10 minutes (interquartile range, 3-18 min) in nonresponders. Dissipation of mean arterial pressure response, when defined as a subsequent decrement in mean arterial pressure below 10%, 5%, and 2% increases from baseline, occurred in 28/42 (67%), 18/42 (43%), and 13/42 (31%) of mean arterial pressure responders, respectively. Cardiopulmonary bypass pump blood was strongly associated with peak change in mean arterial pressure from baseline (coefficient 11.0 [95% CI, 4.3-17.7]; p = 0.02). Fifty out of 64 (78%) were receiving a vasoactive agent. However, change in vasoactive inotrope score was not associated with change in mean arterial pressure (coefficient 2.3 [95% CI, -2.5 to -7.2]; p = 0.35). Timing from admission, nor fluid bolus duration, influenced mean arterial pressure response. CONCLUSIONS: In children with hypotension in a cardiac ICU, the median dose and duration of fluid boluses were 5 mL/kg and 8 minutes. Peak response occurred shortly following administration and commonly returned to baseline.

Comparison of the Hemodynamic and Temperature Effects of a 500-mL Bolus of 4% Albumin at Room Versus Body Temperature in Cardiac Surgery Patients.

OBJECTIVE: To compare the hemodynamic effect of room temperature (cold) 4% albumin fluid bolus therapy (FBT) with body temperature (warm) albumin FBT. DESIGN: Prospective, before-after trial. SETTING: A tertiary intensive care unit (ICU). PARTICIPANTS: Sixty ventilated, post-cardiac surgery patients prescribed with 4% albumin FBT. INTERVENTION: Cold or warm 4% albumin 500 ml FBT. MEASUREMENTS AND MAIN RESULTS: We recorded hemodynamic parameters before and for 30 minutes after FBT. Cardiac index (CI) and mean arterial pressure (MAP) responses were defined by a CI increase >15% and a MAP increase >10%, respectively. Immediately after FBT, median [interquartile range] core temperature changed by -0.3 [-0.4; -0.3] °C with cold albumin vs. 0.0 [0.0; 0.1]°C with warm albumin (P<0.001). The median CI increase was 0.3 [0.0; 0.5] L/min/m2 with 14 CI-responders (47%) in both groups (P>0.99). The median immediate MAP increase was 9 [3; 15] mmHg with cold albumin vs. 11 [5; 13] mmHg with warm albumin (P=0.79), with a MAP-response in 16 vs. 17 patients (P=0.99). There was an interaction between group and time for MAP (P=0.002), mean pulmonary artery pressure (PAP) (P=0.002) and core temperature (P<0.001). In the cold albumin group, after the initial response, MAP and mean PAP decreased more slowly than with warm albumin and, after the initial fall, core temperature increased toward baseline. CONCLUSION: In postoperative cardiac surgery patients, warm albumin FBT prevents the decrease in core temperature and, after an initial similar increase, is associated with a faster return of MAP and mean PAP toward baseline.

Prolonged postoperative cerebral oxygen desaturation after cardiac surgery: A prospective observational study.

BACKGROUND: Near-infrared spectroscopy (NIRS) is used routinely to monitor cerebral tissue oxygen saturation (SctO2) during cardiopulmonary bypass (CPB) but is rarely employed outside the operating room. Previous studies indicate that patients are at risk of postoperative cerebral oxygen desaturation after cardiac surgery. OBJECTIVES: We aimed to assess perioperative and postoperative changes in NIRS-derived SctO2 in cardiac surgery patients. DESIGN: Prospective observational study. SETTING: The study was conducted in a tertiary referral university hospital in Australia from December 2017 to December 2018. PATIENTS: We studied 34 adult patients (70.6% men) undergoing cardiac surgery requiring CPB and a reference group of 36 patients undergoing non-cardiac surgical procedures under general anaesthesia. MAIN OUTCOME MEASURES: We measured SctO2 at baseline, during and after surgery, and then once daily until hospital discharge, for a maximum of 7 days. We used multivariate linear mixed-effects modelling to adjust for all relevant imbalances between the two groups. RESULTS: In the cardiac surgery group, SctO2 was 63.7% [95% confidence interval (CI), 62.0 to 65.5] at baseline and 61.0% (95% CI, 59.1 to 62.9, P = 0.01) on arrival in the ICU. From day 2 to day 7 after cardiac surgery, SctO2 progressively declined. At hospital discharge, SctO2 was significantly lower than baseline, at 53.5% (95% CI, 51.8 to 55.2, P < 0.001). In the reference group, postoperative SctO2 was not significantly different from baseline. On multivariable analysis, cardiac surgery, peripheral vascular disease and time since the operation were associated with greater cerebral desaturation, whereas higher haemoglobin concentrations were associated with slightly better cerebral oxygenation. CONCLUSION: After cardiac surgery on CPB, but not after non-cardiac surgery, most patients experience prolonged cerebral desaturation. Such postoperative desaturation remained unresolved 7 days after surgery. The underlying mechanisms and time to resolution of such cerebral desaturations require further investigation.

Protocol and statistical analysis plan for the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-REVERSE-AKI randomized controlled pilot trial.

BACKGROUND: Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setting of established AKI. Here, we present the protocol and statistical analysis plan of the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-the REVERSE-AKI trial that compares a restrictive fluid therapy regimen to standard therapy in critically ill patients with AKI. METHODS: REVERSE-AKI is an investigator-initiated, multinational, open-label, randomized, controlled, feasibility pilot trial conducted in seven ICUs in five countries. We aim to randomize 100 critically ill patients with AKI to a restrictive fluid treatment regimen vs standard management. In the restrictive fluid therapy regimen, the daily fluid balance target is neutral or negative. The primary outcome is the cumulative fluid balance assessed after 72 hours from randomization. Secondary outcomes include safety, feasibility, duration, and severity of AKI, and outcome at 90 days (mortality and dialysis dependence). CONCLUSIONS: This is the first multinational trial investigating the feasibility and safety of a restrictive fluid therapy regimen in critically ill patients with AKI. TRIAL REGISTRATION: clinical.trials.gov NCT03251131.

Circuit Survival during Continuous Venovenous Hemodialysis versus Continuous Venovenous Hemofiltration.

BACKGROUND: Continuous renal replacement therapy (CRRT) technique may affect circuit lifespan. A shorter circuit life may reduce CRRT efficacy and increase costs. METHODS: In a before-and-after study, we compared circuit median survival time during continuous venovenous hemofiltration (CVVH) versus continuous venovenous hemodialysis (-CVVHD). We performed log-rank mixed effects univariate analysis and Cox mixed effect regression modeling to define predictors of circuit lifespan. RESULTS: We compared 197 -CVVHD and 97 CVVH circuits in 39 patients. There was no overall difference in circuit lifespan. When no anticoagulation was used, median circuit survival time was shorter for CVVH circuits (5 h, 95% CI 3-7 vs. 10 h, 95% CI 8-13, p < 0.01). Moreover, CVVHD, lower platelets levels, and longer activated partial thromboplastin time independently predicted longer circuit median survival time. CONCLUSIONS: CVVHD is associated with longer circuit median survival time than CVVH when no anticoagulation is used and is an independent predictor of circuit survival.

A Pilot, Double-Blind, Randomized, Controlled Trial of High-Dose Intravenous Vitamin C for Vasoplegia After Cardiac Surgery.

OBJECTIVE: To conduct a pilot feasibility and physiologic efficacy study of high-dose vitamin C in patients with vasoplegia after cardiac surgery. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Two tertiary intensive care units (ICUs). PARTICIPANTS: Post-cardiac surgery patients with vasoplegia. INTERVENTIONS: The authors randomly assigned the patients to receive either high-dose intravenous vitamin C (1,500 mg every 6 hours) or placebo. The primary outcome was time from randomization to resolution of vasoplegia. Secondary outcomes included total norepinephrine equivalent dose in the first 2 days, ICU length of stay, ICU mortality, and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The authors studied 50 patients (25 patients in each arms). The mean (standard deviation) time to resolution of vasoplegia was 27.0 (16.5) hours in the vitamin C group versus 34.7 (41.1) hours in the placebo group (mean decrease with vitamin C of 7.7 hours, 95% confidence interval -10.5 to 25.9, p = 0.40). The median (interquartile range) norepinephrine equivalent dose in the first 2 days was 64.9 (23.5-236.5) µg/kg versus 47.4 (21.4-265.9) µg/kg in the vitamin C and placebo group (p = 0.75). The median duration of ICU admission was similar (1.4 [0.5-2.5] days and 1.5 [0.5-3.3] days in the vitamin C and placebo group; p = 0.36). Only 1 patient, in the vitamin C arm, died. CONCLUSION: In patients with post-cardiac surgery vasoplegia, high-dose vitamin C infusion was feasible, appeared safe, and, within the limitations of a pilot study, did not achieve statistically faster resolution of vasoplegia.

Continuous Magnesium Infusion to Prevent Atrial Fibrillation After Cardiac Surgery: A Sequential Matched Case-Controlled Pilot Study.

OBJECTIVE: The authors aimed to test whether a bolus of magnesium followed by continuous intravenous infusion might prevent the development of atrial fibrillation (AF) after cardiac surgery. DESIGN: Sequential, matched, case-controlled pilot study. SETTING: Tertiary university hospital. PARTICIPANTS: Matched cohort of 99 patients before and intervention cohort of 99 consecutive patients after the introduction of a continuous magnesium infusion protocol. INTERVENTIONS: The magnesium infusion protocol consisted of a 10 mmol loading dose of magnesium sulphate followed by a continuous infusion of 3 mmol/h over a maximum duration of 96 hours or until intensive care unit discharge. MEASUREMENTS AND MAIN RESULTS: The study groups were balanced except for a lower cardiac index in the intervention cohort. The mean duration of magnesium infusion was 27.93 hours (95% confidence interval [CI]: 24.10-31.76 hours). The intervention group had greater serum peak magnesium levels: 1.72 mmol/L ± 0.34 on day 1, 1.32 ± 0.36 on day 2 versus 1.01 ± 1.14 and 0.97 ± 0.13, respectively, in the control group (p < 0.01). Atrial fibrillation occurred in 25 patients (25.3%) in the intervention group and 40 patients (40.4%) in the control group (odds ratio 0.49, 95% CI, 0.27-0.92; p = 0.023). On a multivariate Cox proportional hazards model, the hazard ratio for the development of AF was significantly less in the intervention group (hazard ratio 0.45, 95% CI, 0.26-0.77; p = 0.004). CONCLUSION: The magnesium delivery strategy was associated with a decreased incidence of postoperative AF in cardiac surgery patients. These findings provide a rationale and preliminary data for the design of future randomized controlled trials.

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial.

Importance: It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. Objective: To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. Interventions: Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. Main Outcomes and Measures: The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. Results: Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. Conclusions and Relevance: In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone. Trial Registration: ClinicalTrials.gov Identifier: NCT03333278.

Effect of Furosemide on Urinary Oxygenation in Patients with Septic Shock.

BACKGROUND: Renal medullary hypoxia precedes the development of acute kidney injury in experimental sepsis and can now be assessed by continuous measurement of urinary oxygen tension (PuO2). OBJECTIVES: We aimed to test if PuO2 measurements in patients with septic shock would be similar to those shown in experimental sepsis and would detect changes induced by the administration of furosemide. METHOD: Pilot prospective observational cohort study in a tertiary intensive care unit (ICU). Seven adult patients with septic shock admitted to ICU had PuO2 measurements recorded minutely. There were 29 episodes of intravenous furosemide (20 mg n = 19; 40 mg n = 10). RESULTS: The median pre-furosemide PuO2 was low at 21.2 mm Hg (interquartile range [IQR] 17.73-24.86) and increased to 26 mm Hg (IQR 20.27-29.95) at 20 min (p < 0.01), to 27.5 mm Hg (IQR 24.06-33.18) at 40 min (p < 0.01) and to 28.5 mm Hg (IQR 22.65-31.03) at 60 min (p < 0.01). The increase in PuO2 was greater in episodes with a diuretic response >2 mL/kg/h than during episodes without such a response (p < 0.01). CONCLUSIONS: PuO2 measurements in patients are reflective of the low values reported in experimental models of sepsis. PuO2 values increased following furosemide administration with a response independently associated with greater diuresis.