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The article discusses the optimal timing for discontinuing continuous renal replacement therapy (CRRT) in children with severe acute kidney injury (AKI). The authors highlight the lack of guidance on this topic and the need for better criteria for stopping CRRT. They present data from a study that identified factors associated with successful liberation from CRRT in children, including higher vasoactive-inotropic scores, shorter CRRT duration, and higher urine output prior to CRRT initiation. The authors also discuss the challenges of managing CRRT in children and the potential implications of prolonged CRRT. Further research is needed to determine the best criteria for discontinuing CRRT in pediatric patients. [Extracted from the article]

Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to determine the correlation between medial tibial slope (MTS) and anterior tibial translation (ATT) in female patients with an ACL-deficient knee. It was hypothesized that female patients with a greater medial tibial slope had an increased anterior tibial translation compared to males.Methods: MTS and ATT were analysed in 276 patients (138 females and 138 males) with a complete ACL rupture from 2012 to 2016. The mean age was 32 ± 12 years. Previous surgery or additional ligament injury was excluded. CT scan was used for measuring MTS. Meniscal findings were reported. Anterior tibial translation and side to side difference (SSD) were measured by bilateral Telos™ stress radiography with knee flexion of 20°.Results: There was no significant difference in ATT between females (5.4 ± 3.9) and males (5.8 ± 4.2), nor was there a difference in MTS between females (9.8 ± 2.8) and males (9.8 ± 2.7). A positive correlation was found between MTS and ATT absolute (r = 0.35, p < 0.001) and side to side difference (r = 0.12, p = 0.03). MTS greater or equal to 11° significantly increased the ATT (p < 0.05). For each degree of increase of the MTS, increases in ATT absolute of 0.6 mm and SSD of 0.18 mm were observed. Greater MTS was identified as a risk factor for an increase of ATT in females (r = 0.37, p < 0.001) but not in males (r = - 0.1, n.s). Increases of 1° of MTS increased ATT 0.57 mm in female patients (p < 0.001). MTS was influential in ATT despite the presence (r = 0.28 [0.11, 0.44], p = 0.001) or absence (r = 0.48 [0.35, 0.6], p < 0.001) of meniscal lesions.Conclusions: Greater medial tibial slope is associated with increased anterior tibial translation in females with ACL-deficient knees compared to males, despite the presence or absence of meniscal lesions. This could be due to a quadriceps/hamstring imbalance in females and the ability of the hamstring muscles to moderate ATT.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a very common complication of acute illnesses and is associated with poor short- and long-term outcomes [[1]]. Modifications of the AKI clinical course may be achievable by biomarker-guided timely adjustment of disease-modifying, patient-specific interventions according to Kidney Disease: Improving Global Outcomes (KDIGO) bundle [[13]]. In only one-fourth of patients, AKI reversal was complete or near-complete within 7 days, another fourth did not recover, about 10% had a late reversal, and the remaining patients relapsed after AKI reversal, with (22%) or without (15%) ultimate recovery. [Extracted from the article]

Purpose: Previous research has demonstrated that women have a higher risk of anterior cruciate ligament (ACL) injury than men. Tibiofemoral articular geometry may play a role in the occurrence of ACL tears. The purpose of this study was to analyze the gender-specific geometric characteristics differences in tibiofemoral morphology in ACL-deficient patients.Methods: Medial tibial slope (MTS), lateral tibial slope (LTS), medial tibial plateau concavity, medial and lateral femoral condyle convexity, and lateral plateau convexity were analyzed in 276 patients with complete ACL injuries (138 females and 138 males). Two blinded observers measured the anatomical parameters of tibiofemoral geometry with use of multiplanar CT scans. Intra- and inter-rater reliabilities were assessed and comparisons between anatomic measures were made between male and female patients.Results: The average ICC for all measurements was 0.90 (range 0.83-0.97) indicating good reliability. Male ACL injured patients demonstrated significantly greater LTS (10.5° ± 2.8) than female patients (9.6° ± 3.5°; p < 0.05). No gender difference in MTS was found (n.s.). Medial and lateral femoral condyle convexity and medial tibial plateau concavity were greater in males than females (all p < 0.05). Lateral tibial plateau convexity in females was higher than in males (p < 0.001). The medial and lateral compartments were found to be more incongruent in females than males (p < 0.01 and p < 0.001, respectively).Conclusions: Female patients were noted to have more incongruent medial and lateral compartments than male patients. These gender-specific differences in joint morphology may contribute to graft tear risk and outcomes of ACL reconstruction; however, comparative clinical studies are needed to confirm this possibility.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested.Methods: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients.Results: We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31).Conclusions: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. [ABSTRACT FROM AUTHOR]

Résumé L’instabilité du genou est un motif très fréquent de consultation en orthopédie, séquellaire le plus souvent d’un traumatisme rapporté par le patient. L’interrogatoire ainsi qu’un examen clinique minutieux ont une place prépondérante dans la démarche diagnostique. Les antécédents du patient, le type de traumatisme, la notion de craquement sont tout aussi importants que l’hémarthrose initiale, les testings ligamentaires, la course rotulienne. Les examens complémentaires sont indispensables pour une définition précise des lésions et la planification opératoire, que ce soit les examens réalisés en consultation pour objectiver les symptômes, ou le bilan radiographique standard, puis en stress, l’imagerie par résonance magnétique et le scanner tridimensionnel. Ce même symptôme fait en réalité appel à de nombreuses étiologies. L’instabilité peut siéger dans le plan frontal ou sagittal et être surtout d’origine ligamentaire, allant de la simple entorse du ligament latéral interne à la rupture du ligament croisé antérieur voire jusqu’à la luxation du genou. Le terme instabilité inclut aussi les luxations de rotule, stade le plus grave de l’instabilité fémoro-patellaire, autant que les lésions tendineuses et méniscales. Une fois le type d’instabilité défini et les lésions anatomiques identifiées, le traitement sera alors adapté à chaque patient ; il sera alors fonctionnel, orthopédique ou chirurgical, selon les lésions, l’âge, l’activité physique, la motivation et la gêne ressentie. Il est important d’avoir connaissance de l’évolution naturelle de ces instabilités afin de prévenir les lésions qui en découlent, principalement arthrosiques. Chronic knee instability is a very common reason for consultation in orthopaedics, most often after injury reported by the patient. Physical examination has an important place for the diagnostic approach. Previous patient history, type of trauma are also important as well as initial hemarthrosis, ligament testing and patellar tracking. Further investigations (X-rays and MRI) enable to confirm clinical diagnosis and to analyse associated lesions (meniscus, cartilage). Instability as the main symptom may cover numerous etiologies. Knee instability may be observed in the frontal or sagittal plan or both. There are several grades of severity from the common medial collateral ligament sprain to the complete tear of the anterior cruciate ligament or even knee dislocation. The term instability also includes the patellar dislocations, the most serious stage of the femoropatellar instability. Once the type of instability defined and the anatomical lesions identified, the treatment will be selected for each patient; it may be functional, medical or surgical, according to the types of lesion, age and physical activity, motivation and patient discomfort. It is important to be aware of the natural outcome of these instabilities in order to prevent lesions leading to osteoarthritis (OA). [ABSTRACT FROM AUTHOR]

The article discusses literature describing strategies aiming to decrease the rate of dialysis catheter (DC)-related infections. Topics include association between antimicrobial-coated central venous catheters (CVCs) and lower rate of colonisation and catheter-related blood stream infection (CRBSI), the first choice for DC insertion, and importance of dressing application on DCs.

The article focus on acute kidney injury (AKI). Topics discussed include "My Paper 20 Years Later" article by Druml et al. on the metamorphosis of acute renal failure to AKI, review of 18 studies by Villeneuve et al using validated instruments to measure health related quality-of-life (HRQOL) among survivors of AKI in the intensive care units (ICU) and modality of renal replacement therapy (RRT) for ICU patients.

Background: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. Methods/Design: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. Discussion: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified. [ABSTRACT FROM AUTHOR]

Background: Terlipressin improves renal function in some patients with type-1 hepato-renal syndrome (HRS). Renal contrast-enhanced ultrasound (CEUS), a novel imaging modality, may help to predict terlipressin responsiveness. Objectives: We used CEUS to estimate the effect of terlipressin on the renal cortical microcirculation in type-1 HRS. Methods: We performed renal CEUS scans with destruction-replenishment sequences using Sonovue® (Bracco, Milano Italy) as a contrast agent at baseline and after the intravenous administration of 1 mg of terlipressin, in four patients with type-1 HRS. We analyzed video sequences offline using dedicated software. We derived a perfusion index (PI) at each time point for each patient. Results: Patients 1 and 2 had severe presentation and were admitted to the intensive care unit. Both showed a marked increase in PI (+216% and + 567% of baseline) in response to terlipressin. Patients 3 and 4 had less severe presentations and had a decrease in PI (−53% and −20% of baseline) in response to terlipressin. Patients 1, 2, and 4, but not patient 3, responded to terlipressin therapy with a decrease in serum creatinine to <150 µmol/L. Conclusions: CEUS detected changes in renal cortical microcirculation in response to terlipressin and demonstrated heterogeneous microvascular responses to terlipressin. These initial proof-of-concept findings justify future investigations. [ABSTRACT FROM AUTHOR]

Background. The obective of this study was to perform a costeffectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). Methods. Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from $200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). Results. Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental costeffectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. Conclusions. Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivors. [ABSTRACT FROM AUTHOR]

Recovery of kidney function following an episode of acute kidney injury (AKI) is now acknowledged as a vital patient-centered outcome with clear health economic implications. In approximately 5-8% of critically ill patients with more severe forms of AKI, support with renal replacement therapy (RRT) is provided. Recent data have suggested that rates of RRT utilization in AKI are increasing. Despite advances in our understanding of how best to prescribe acute RRT in critically ill patients with AKI, additional aspects remain uncertain, predisposing to suboptimal delivery and variation in practice. Importantly, if, when, how, and by what principles we apply acute RRT for AKI are all treatment decision-related factors that are modifiable and may interact with recovery of kidney function. Limited data, mostly from observational studies and secondary analyses, have explored the specific association between acute RRT and recovery. Available data are not able to clarify whether providing any RRT in otherwise eligible patients with AKI impacts recovery. They are also unable to inform whether the timing or circumstance under which RRT is started impacts recovery. No studies have evaluated whether there is an optimal time to start RRT to maximize the probability of recovery. Accumulated evidence, mostly derived from observational studies, suggests initial therapy in critically ill patients with AKI with continuous RRT, compared with intermittent modalities, improves the probability of recovery to dialysis independence. Evidence from high-quality randomized trials failed to show any association between delivered dose intensity of RRT and recovery. The use of biocompatible membranes for acute RRT may improve recovery in AKI; however, data are inconsistent. Limited data have evaluated the impact of membrane flux properties on recovery. Preliminary data have suggested that circuit anticoagulation with citrate, which results in a reduction in membrane-induced oxidative stress and leukocyte activation, may be associated with improved recovery; however, further corroborative data are needed. Additional evidence, ideally from randomized trials, is clearly needed to inform best practice in the delivery of acute RRT to optimize probability of recovery of kidney function for survivors of AKI. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients. Methods: We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL and uNGAL] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L. Measurements and main results: Bland-Altman analysis demonstrated that, despite correlating well ( r = 0.988), uNGAL and uNGAL were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03-450.44 ng/mg creatinine; limits of agreement: −1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction. Conclusions: uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker. [ABSTRACT FROM AUTHOR]

Abstract: Background: Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. Methods and results: Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 <35mmHg), 6705 (40.5%) into the normo- (35–45mmHg) and 6827 (41.3%) into the hypercapnia (>45mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p =0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p <0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p <0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p =0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p =0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p =0.52]). Cox-proportional hazards modelling supported these findings. Conclusions: Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors. [Copyright &y& Elsevier]

Purpose: Choice of renal replacement therapy (RRT) modality may affect renal recovery after acute kidney injury (AKI). We sought to compare the rate of dialysis dependence among severe AKI survivors according to the choice of initial renal replacement therapy (RRT) modality applied [continuous (CRRT) or intermittent (IRRT)]. Methods: Systematic searches of peer-reviewed publications in MEDLINE and EMBASE were performed (last update July 2012). All studies published after 2000 reporting dialysis dependence among survivors from severe AKI requiring RRT were included. Data on follow-up duration, sex, age, chronic kidney disease, illness severity score, vasopressors, and mechanical ventilation were extracted when available. Results were pooled using a random-effects model. Results: We identified 23 studies: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % confidence interval (CI) 0.78-1.68], I = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IRRT as compared with CRRT (RR 1.99 [95 % CI 1.53-2.59], I = 42 %). These findings were consistent with adjusted analyses (performed in 7/16 studies), which found a higher rate of dialysis dependence in IRRT-treated patients [odds ratio (OR) 2.2-25 (5 studies)] or no difference (2 studies). Conclusions: Among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT. However, this finding largely relies on data from observational trials, potentially subject to allocation bias, hence further high-quality studies are necessary. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To measure the triage performance of the efferent arm of a rapid response system (RRS) by assessing the 24h outcome of patients triaged to remain on the ward after rapid response team (RRT) review. Methods: We performed a retrospective observational study of all consecutive RRS activations between August 2005 and December 2011 in a university-affiliated hospital. Calls involving patients with documented limitations of medical therapy (LOMT) orders were excluded. We determined patients who were triaged to stay on the ward at the end of their first (index) call and analyzed their vital status and location 24h later. Finally, we reviewed medical charts of patients triaged to remain on the ward and had a cardiac arrest and/or died within 24h of RRT review. Results: We studied 8304 RRT calls. We excluded 1794 calls involving patients with LOMT, 2165 that were repeat calls, 20 where data was missing, 650 where patients were immediately transferred to a high dependency (HDU) or an intensive care unit (ICU) and 92 where calls were rapidly upgraded to cardiac arrest calls. Thus, we identified 3583 index calls at the end of which patients were triaged to remain on the ward. Within 24h, 454 (12.7%) of those had a repeat RRT activation and 378 were transferred to HDU/ICU. 12 (0.3%) suffered a cardiac arrest on the ward. Altogether, 14 (0.4%) patients died within 24h of the index RRT activation. Of those 6 had LOMT applied after the call, 4 had been admitted to ICU in a further call and 6 (0.2%) patients had unexpected cardiac arrest on the ward. Conclusions: The rate of unexpected cardiac arrest in the 24h following RRT activation is very low for patients triaged to stay on the ward. Major triage errors by the RRT appear uncommon. [Copyright &y& Elsevier]

Patients with serious thermal burn injuries require immediate and specialized care in order to minimize morbidity and mortality. Optimal fluid resuscitation, nutritional support, pulmonary care, burn wound care, and infection control practices represent key aspects of patient care in burn centers. When severely burned, the patient usually presents a systemic inflammatory response syndrome, soon balanced by a counter anti-inflammatory response syndrome. These may lead to immune dysregulation/exhaustion favoring infectious complications that dramatically impair the prognosis of burn patients. This narrative review provides an overview of the main concepts, current understanding, and potential applications of extracorporeal blood purification techniques for burn patient management. Current understanding of burn patients' immune responses is reported. Hypotheses and data on the potential value of immunoregulation are reviewed. Finally, how extracorporeal blood purification may be of interest in this specific population is discussed. [ABSTRACT FROM AUTHOR]

As highlighted by the last international consensus definition for sepsis and septic shock (sepsis-3), sepsis comes from a complex relationship between a pathogen and a dysregulated host response. To date, the treatment of sepsis is based on antimicrobial treatment, source control, and organ support. Extracorporeal blood purification therapies have been proposed as adjuvant therapies to modulate the dysregulated inflammatory response. These therapies aim mostly at removing inflammatory mediators (cytokines) and endotoxins from the blood. However, so far, they failed to clearly demonstrate an improvement in patient survival when evaluated in randomized trials. Recently, new devices directly targeting the primary determinants of sepsis, e.g., the pathogen itself and the host immune cells, have been developed. This short review aimed at presenting new blood purification devices that have recently been developed to target pathogens and immune cells. For each, we will present the mechanism of action of the therapy and discuss the related literature. [ABSTRACT FROM AUTHOR]

Background. Only a proportion of critically ill patients with severe [RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria, class-F] acute kidney injury (AKI) appear to receive renal replacement therapy (RRT). The aim of this study was to study the characteristics and outcome of patients with severe (RIFLE-F) AKI who did not receive RRT. Methods. We identified all consecutive patients admitted to our institution that developed RIFLE-F AKI by creatinine criteria over a 3-year period and did not receive RRT, and compared their characteristics and outcomes with those of RIFLE-F RRT-treated patients. Results. Within the study period, 20 126 patients were admitted to our institution for >24 h. Among them, 2949 were admitted to the intensive care unit (ICU) and 195 developed RIFLE-F AKI. Of these, 90 received RRT (RRT patients) and 105 did not (no-RRT patients). Compared with RRT patients, no-RRT patients were similar in terms of age, gender and ward of origin. However, they had a shorter median ICU stay (2.7 versus 7.9 days; P < 0.001), required less mechanical ventilation (56.2 versus 70%; P < 0.05) and had a lower mean Acute Physiology and Chronic Health Evaluation III score (82.7 versus 86.7; P < 0.05). The two main reasons these patients did not receive RRT were limitations of medical therapy (LOMT) orders in 41 (39%) cases and expected renal functional improvement in 59 (56.2%). Mortality in no-RRT patients was 58.1% compared with 55.5% in the RRT group (P = 0.72). After exclusion of LOMT patients, the mortality of the no-RRT group, although lower than that of the RRT group, remained high (30.5 versus 55%; P < 0.001). Most of these deaths occurred after ICU discharge and appeared secondary to underlying chronic diseases or recurrence of the initial insult. Conclusions. After exclusion of LOMT patients, about a third of critically ill patients with severe (RIFLE-F) AKI did not receive RRT. A third of these patients died in hospital. The timing of the deaths and their underlying causes do not suggest that a broader application of RRT would have changed patient outcomes. [ABSTRACT FROM PUBLISHER]

Background. Contrast-enhanced ultrasonography (CEUS) is a novel imaging technique that is safe and applicable on the bedside. Recent developments seem to enable CEUS to quantify organ perfusion. We performed an exploratory study to determine the ability of CEUS to detect changes in renal perfusion and to correlate them with effective renal plasma flow. Methods. CEUS with destruction-refilling sequences was studied in 10 healthy subjects, at baseline and during infusion of angiotensin II (AngII) at low (1 ng/kg/min) and high dose (3 ng/kg/min) and 1 h after oral captopril (50 mg). Perfusion index (PI) was obtained and compared with the effective renal plasma flow (ERPF) obtained by parallel para-aminohippurate (PAH) clearance. Results. Median PI decreased from 188.6 (baseline) to 100.4 with low-dose AngII (−47%; P < 0.02) and to 66.1 with high-dose AngII (−65%; P < 0.01) but increased to 254.7 with captopril (+35%; P > 0.2). These changes parallelled those observed with ERPF, which changed from a median of 672.1 mL/min (baseline) to 572.3 (low-dose AngII, −15%, P < 0.05) and to 427.2 (high-dose AngII, −36%, P < 0.001) and finally 697.1 (captopril, +4%, P < 0.02). Conclusions. This study demonstrates that CEUS is able to detect changes in human renal cortical microcirculation as induced by AngII infusion and/or captopril administration. The changes in perfusion indices parallel those in ERPF as obtained by PAH clearance. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Use of non-invasive ventilation (NIV) is normally limited to the Emergency Department, Intensive Care Unit (ICU), Coronary Care Unit (CCU) or High Dependency Unit (HDU). However, NIV is sometimes used by the Medical Emergency Team (MET) as respiratory support for ward patients. Objectives: We reviewed the characteristics and outcome of ward patients treated with NIV in the setting of a MET Call and determined the clinical and prognostic significance of such treatment. Methods: We used our MET database to assess the characteristics and outcome of patients treated with NIV and compared them to a control group of patients with similar MET diagnoses but not treated with NIV. Results: We studied 5389 calls in 3880 patients. NIV was delivered during 483 (9.0%) calls to 426 patients (11% of the total). The four most common MET diagnoses associated with NIV were acute pulmonary edema (156 calls, 32.3%), pneumonia (84 calls, 17.4%), acute respiratory failure of unclear origin (59 calls, 12.2%) and exacerbation of chronic obstructive pulmonary disease (32 calls, 6.6%). Limitations of medical therapy (LOMT) were documented in 151 (35.4%) patients. Among NIV patients without LOMT, 115 (41.8%) were transferred to ICU and 50 (18.2%) to the coronary care or high dependency unit (CCU/HDU) compared with only 50 (18.0%) and 16 (5.8%) respectively in the control group (p <0.001). Overall, 76 NIV patients (27.6%) received endotracheal intubation (ETT) compared with 61 (21.9%) in controls. Mortality was 23.6% in the NIV group versus 18.8% in the control group. Conclusion: One in ten MET call patients received NIV. In those without LOMT, two thirds were transferred to ICU/HDU/CCU, one in four received ETT, and one in four died. NIV use at the time of a MET call identified high risk patients for whom admission to ICU/HDU/CCU should be strongly considered. [Copyright &y& Elsevier]

Abstract: Introduction: Atrial fibrillation (AF) in hospitalized patients may lead to activation of the medical emergency team (MET). We sought to assess the baseline characteristics and outcomes of the patients presenting AF as a cause of MET call activation. Methods: Using a prospectively constructed MET database, we retrospectively reviewed all patients with AF as a trigger for MET activation between August 2005 and April 2010. Demographics, principal diagnostic and outcome of these patients were compared with those of a control group of patients matched for age, sex and ward of origin, randomly selected from the database. Results: We studied 5431 MET calls of which 557 (10.3%), in 458 patients were triggered by AF. Mean age for AF patients was 74.8 years, 230 (50.2%) were female and 271 (59.1%) were in a surgical ward. 92 (20.1%) AF patients died in hospital compared with 131 (28.6%) in the control group. Among the 336 patients without limitations of medical therapy (LOMT), 46 (13.7%) died in hospital. In total, 46 (13.7%) patients were transferred to a higher level care ward while 290 (86.3%) remained on the ward. Only 2 (4.3%) of these patients died compared with 44 (15.2%) among those who remained in the general ward (p =0.03). Conclusions: In our hospital, AF triggers one tenth of MET activations and mortality associated with it is high even when issues of LOMT are excluded. The decreased mortality among patients admitted to a higher level ward suggests that some of these deaths may be avoidable. [Copyright &y& Elsevier]

Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1–1.5 g/kg/day of proteins during CRRT. We aim to evaluate the net effect of CRRT on amino acids (AA), vitamins A and C (Vit A, Vit C) levels. This is a prospective observational study embedded within a randomised controlled trial comparing two CRRT doses in patients with septic shock. CRRT was provided in continuous veno-venous haemofiltration mode at a dose of either 35 ml/kg/h or 70 ml/kg/h. All patients received parenteral nutrition with standard trace elements and vitamins (protein intake 1 g/kg/d). We measured serum levels of glutamine, valine and alanine as well as Vit A and Vit C upon randomisation, study day four and eight. In addition, we measured a larger panel of AA in a subset of 11 patients. We included 30 patients (17 allocated to 70 ml/kg/h and 13 to 35 ml/kg/h CRRT). Before CRRT initiation, mean plasma levels of glutamine and valine, Vit A and Vit C were low. CRRT was not associated with any significant change in AA levels except for a decrease in cystein. It was associated with an increase in Vit A and a decrease in Vit C levels. CRRT dose had no impact on those nutrients blood levels. Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT. [ABSTRACT FROM AUTHOR]

Few patients with coronavirus disease 2019–associated severe acute respiratory distress syndrome (ARDS) require veno-venous extracorporeal membrane oxygenation (VV-ECMO). Prolonged VV-ECMO support necessitates repeated oxygenator replacement, increasing the risk for complications. Transient hypoxemia, induced by VV-ECMO stop needed for this procedure, may induce transient myocardial ischemia and acutely declining cardiac output in critically ill patients without residual pulmonary function. This is amplified by additional activation of the sympathetic nervous system (tachycardia, pulmonary vasoconstriction, and increased systemic vascular resistance). Immediate reinjection of the priming solution of the new circuit and induced acute iatrogenic anemia are other potentially reinforcing factors. The case of a critically ill patient presented here provides an instructive illustration of the hemodynamic relationships occurring during VV-ECMO support membrane oxygenator exchange. [ABSTRACT FROM AUTHOR]

The article focuses on acute kidney injury (AKI) which is associated with morbidity and mortality. It states that biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1) and interleukin (IL)-18 are used for identifying renal injury. It further states that as per a retrospective study off-pump coronary artery bypass graft (CABG) surgery was associated with decreased need for renal replacement therapy benefiting patients with poor renal functions.

On the other hand, the increasing utilization of electronic patient records and associated massive datasets, creates the opportunity to detect patterns associated with increased risk of AKI or AKI progression. Several machine-learning predictions for AKI, severe AKI and need for KRT in intensive care unit (ICU) and hospitalized patients have been developed. The syndrome of acute kidney injury (AKI) is defined by a reduced glomerular filtration rate (GFR) and manifests through an increased serum creatinine (sCr) relative to baseline and/or decreased urine output (UO) as proposed by the Kidney Disease Improving Global Outcome (KDIGO) 2012 consensus criteria. [Extracted from the article]

Acute kidney injury (AKI) remains associated with short- and long-term mortality and morbidity. Doppler-based renal resistive index (RI) is a rapid and non-invasive tool that was proposed to assess renal perfusion, identify early risk of AKI, or predict renal recovery course. Central venous pressure and mean perfusion pressure have been associated with risk of AKI in observational studies but may reflect macrovascular perfusion and congestion rather than intra-renal hemodynamic dysregulation [[1]]. Although magnetic resonance imaging (MRI) may assess renal perfusion and oxygenation changes, relevancy of this technique at bedside for critically ill patients is debatable [[3]]. [Extracted from the article]

Background: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). Methods: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. Results: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75–1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66–0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39–0.94). Conclusions: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation (RCA) enables prolonged continuous kidney replacement therapy (CKRT) filter lifespan. However, membrane diffusive performance might progressively decrease and remain unnoticed. We prospectively evaluated the kinetics of solute clearance and factors associated with decreased membrane performance in 135 consecutive CKRT-RCA circuits (35 patients). We recorded baseline patients' characteristics and clinical signs of decreased membrane performance. We calculated effluent/serum ratios (ESR) as well as respective clearances for urea, creatinine and β2-microglobuline at 12, 24, 48 and 72 h after circuit initiation. Using mixed-effects logistic regression model analyses, we assessed the effect of time on those values and determined independent predictors of decreased membrane performance as defined by an ESR for urea < 0.81. We observed a minor but statistically significant decrease in both ESR and solute clearance across the duration of therapy for all three solutes. We observed decreased membrane performance in 31 (23%) circuits while clinical signs were present in 19 (14.1%). The risk of decreased membrane performance significantly increased over time: 1.8% at T1 (p = 0.16); 7.3% at T2 (p = 0.01); 15.7% at T3 (p = 0.001) and 16.4% at T4 (p < 0.003). Four factors present within 24 h of circuit initiation were independently associated with decreased membrane performance: arterial blood bicarbonate level (OR 1.50; p < 0.001), activated partial thromboplastin time (aPTT; OR = 0.93; p = 0.02), fibrinogen level (OR 6.40; p = 0.03) and Charlson score (OR 0.10; p < 0.01). COVID-19 infection was not associated with increased risk of decreased membrane performance. Regular monitoring of ESR might be appropriate in selected patients undergoing CKRT. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss the article "The Association Between Renal Replacement Therapy Modality and Long-Term Outcomes Among Critically Ill Adults With Acute Kidney Injury: A Retrospective Cohort Study" by Ron Wald and colleagues published within the issue.

The authors discuss studies related to fluid therapy in kidney patients that were released in 2012. They describe a study which investigated patients with severe sepsis who were assigned to fluid resuscitation with six percent hydroxyethyl starch (HES). They also mention a study which examined the link between a chloride-liberal or a chloride-restrictive fluid administration strategy and acute kidney injury. They conclude that the studies pave way for more evidence-based fluid administration.

References 1 Schmitt J, Aries P, Desert M, Le Roux A, Giacardi C. Before AKI, renal microcirculation stress may be detected by urine biochemistry. Before AKI, renal microcirculation stress may be detected by urine biochemistry. Altogether, we agree that the evaluation of urine biochemistry is attractive on a physiological point of view and that it is easy to perform especially when integrated in a continuous urine output measurement tool. [Extracted from the article]

The article focuses on the hemoadsorption with CytoSorb. Topics include contain biocompatible polystyrene divinylbenzene copolymer beads capable of adsorbing molecules of medium molecular weight using a combination of size exclusion and hydrophobic interactions; mentions septic animal models have demonstrated the ability of CytoSorb to clear key cytokines from the blood and improve survival; and also mentions the effect of CytoSorb hemoadsorption on drugs requires particular attention.

Aim Of the Work: Injury to the anterior cruciate ligament (ACL) is frequently accompanied by tears of the menisci. Some of these tears occur at the time of injury, but others develop over time in the ACL-deficient knee. The aim of this study was to evaluate the effects of the patient characteristics, time from injury (TFI), and posterior tibial slope (PTS) on meniscal tear patterns. Our hypothesis was that meniscal tears would occur more frequently in ACL-deficient knees with increasing age, weight, TFI, PTS, and in male patients.Methods: Of the ACL-injured patients, 362 were analyzed, and details of meniscal lesions were collected. The medial and lateral tibial slopes (MTS, LTS) were measured via computed tomography. Patient demographics, TFI, MTS, and LTS were correlated with the diagnosed meniscal tears.Results: Of the patients, 113 had a medial meniscus (MM) tear, 54 patients had a lateral meniscus (LM) tear, 34 patients had tears of both menisci, and 161 patients had no meniscal tear. The most common tear location was the posterior horn (PH) of the MM, followed by tear involving the whole MM. Patient age, BMI, and TFI were significantly associated with the incidence of MM tear. Female patients had a higher incidence of injury than males in all tear sites except in the body and PH. Male patients had more vertical and peripheral tears. The median MTS and LTS for patients with MM tears were 7.0°and 8.7°, respectively, while those of patients with LM tears were 6.9° and 8.1°. Steeper LTS was significantly associated with tears of LM and of both menisci.Conclusion: Older age, male sex, increased BMI, and prolonged TFI were significant factors for the development of MM tears. An increase in the tibial slope, especially of the lateral plateau, seems to increase the risk of tear of the LM and of both menisci.Level Of Evidence: Level III. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented reporting the use of recombinant factor VIIa (rFVIIa) is increasingly reported for refractory bleeding in patients with circulatory assist devices.

Objectives: Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge.Design: Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database.Setting: Two hundred ninety-one ICUs in France.Patients: A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis.Interventions: None.Measurements Main Results: PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958.Conclusions: In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited. [ABSTRACT FROM AUTHOR]

Introduction: The measurement of renal functional reserve (RFR) can unmask glomerular hyperfiltration in residual nephrons, but its determination is time-consuming. In this study, we assessed whether contrast-enhanced ultrasound (CEUS) is a valuable alternative to the gold standard inulin clearance and whether L-arginine or protein shakes lead to similar changes in glomerular filtration rate (GFR) as animal proteins in men and women. Methods: Changes in GFR and renal microperfusion were studied in 25 healthy subjects (8 men, 17 women) by simultaneously performing inulin clearance and CEUS (perfusion index, PI) before and 1 and 2 h after different protein loads (L-arginine, protein shake or meat). The Doppler parameters – renal resistive index (RRI) and pulsatility index (PuI) – were also measured. Results: None of the oral protein loads induced significant changes in CEUS-assessed PI. Only meat increased inulin clearance (from 111.2 ± 16.0 to 149.8 ± 27.2 mL/min, p < 0.05) and mobilized RFR, while L-arginine decreased GFR (106.7 ± 45.3 to 86.3 ± 42.6 mL/min, p < 0.05). Protein shakes had a neutral effect. There were no correlations between changes in inulin clearance and PI. At Doppler, RRI and PuI increased after meat intake (from 0.647 ± 0.029 to 0.694 ± 0.050 a.u., p < 0.05 and from 1.130 ± 0.087 to 1.318 ± 0.163 a.u., p < 0.05, respectively), but their changes also did not correlate with changes in inulin clearance. Results were similar in both sexes. Conclusions: CEUS is not a valuable alternative for inulin clearance to measure RFR. Meat ingestion leads to modest changes in renal Doppler parameters and to glomerular hyperfiltration in both women and men, while protein shakes and L-arginine do not. [ABSTRACT FROM AUTHOR]

Introduction: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). Methods: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and β2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. Results: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and β2-microglobulin across the entire duration of circuit lifetime. Conclusion: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible. [ABSTRACT FROM AUTHOR]

Background: COVID-19 related acute respiratory distress syndrome (ARDS) has specific characteristics compared to ARDS in other populations. Proning is recommended by analogy with other forms of ARDS, but few data are available regarding its physiological effects in this population. This study aimed to assess the effects of proning on oxygenation parameters (PaO2/FiO2 and alveolo-arterial gradient (Aa-gradient)), blood gas analysis, ventilatory ratio (VR), respiratory system compliance (CRS) and estimated dead space fraction (VD/VT HB). We also looked for variables associated with treatment failure.Methods: Retrospective monocentric study of intubated COVID-19 ARDS patients managed with an early intubation, low to moderate positive end-expiratory pressure and early proning strategy hospitalized from March 6 to April 30 2020. Blood gas analysis, PaO2/FiO2, Aa-gradient, VR, CRS and VD/VT HB were compared before and at the end of each proning session with paired t-tests or Wilcoxon tests (p < 0.05 considered as significant). Proportions were assessed using Fischer exact test or Chi square test.Results: Forty-two patients were included for a total of 191 proning sessions, median duration of 16 (5-36) hours. Considering all sessions, PaO2/FiO2 increased (180 [148-210] vs 107 [90-129] mmHg, p < 0.001) and Aa-gradient decreased (127 [92-176] vs 275 [211-334] mmHg, p < 0.001) with proning. CRS (36.2 [30.0-41.8] vs 32.2 [27.5-40.9] ml/cmH2O, p = 0.003), VR (2.4 [2.0-2.9] vs 2.3 [1.9-2.8], p = 0.028) and VD/VT HB (0.72 [0.67-0.76] vs 0.71 [0.65-0.76], p = 0.022) slightly increased. Considering the first proning session, PaO2/FiO2 increased (186 [165-215] vs 104 [94-126] mmHg, p < 0.001) and Aa-gradient decreased (121 [89-160] vs 276 [238-321] mmHg, p < 0.001), while CRS, VR and VD/VT HB were unchanged. Similar variations were observed during the subsequent proning sessions. Among the patients who experienced treatment failure (defined as ICU death or need for extracorporeal membrane oxygenation), fewer expressed a positive response in terms of oxygenation (defined as increase of more than 20% in PaO2/FiO2) to the first proning (67 vs 97%, p = 0.020).Conclusion: Proning in COVID-19 ARDS intubated patients led to an increase in PaO2/FiO2 and a decrease in Aa-gradient if we consider all the sessions together, the first one or the 4 subsequent sessions independently. When considering all sessions, CRS increased and VR and VD/VT HB only slightly increased. [ABSTRACT FROM AUTHOR]