Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI) : a pilot randomized controlled feasibility trial

Purpose We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation. Methods This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization. Results Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm. Conclusions In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.Peer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Classic and Nonclassic Renin-Angiotensin Systems in the Critically Ill

Classic and nonclassic renin-angiotensin systems (RAS) are 2 sides of an ubiquitous endocrine/paracrine cascade regulating blood pressure and homeostasis. Angiotensin II and angiotensin-converting enzyme (ACE) levels are associated with severity of disease in the critically ill, and are central to the physiology and the pathogenesis of circulatory shock. Angiotensin (1-7) and ACE2 act as an endogenous counterregulatory arm to the angiotensin II/ACE axis. The tissue-based RAS has paracrine effects dissociated from those of the circulating RAS. Exogenous angiotensin II or ACE2 may improve the outcome of septic shock and acute respiratory distress syndrome, respectively

Non-invasive quantification of macrophagic lung recruitment during experimental ventilation-induced lung injury

International audienc

Supplementary Material for: Presence of Kidney Disease as an Outcome Predictor in Patients with Pulmonary Arterial Hypertension

<b><i>Background:</i></b> Pulmonary arterial hypertension (PAH) may lead to right heart failure and subsequently alter glomerular filtration rates (GFR). Chronic kidney disease (CKD, GFR <60 mL/min/1.73 m²) may also adversely affect PAH prognosis. This study aimed to assess how right heart hemodynamics was associated with reduced estimated GFR (eGFR) and the association of CKD with survival in PAH patients. <b><i>Methods:</i></b> In a prospective PAH cohort (2003–2012), invasive hemodynamics and eGFR were collected at diagnosis (179 patients) and during follow-up (159 patients). The prevalence of CKD was assessed at PAH diagnosis. Variables, including hemodynamics, associated with reduced eGFR at diagnosis and during follow-up were tested in multivariate analysis. The association of CKD with survival was evaluated using a multivariate Cox regression model. <b><i>Results:</i></b> At diagnosis, mean age was 60.4 ± 16.5 years, mean pulmonary arterial pressure was 43 ± 12 mm Hg, and eGFR was 74.4 ± 26.4 mL/min/1.73 m². CKD was observed in 52 incident patients (29%). Independent determinants of reduced eGFR at diagnosis were age, systemic hypertension, and decreased cardiac index. Independent determinants of reduced eGFR during follow-up were age, female gender, PAH etiology, systemic hypertension, decreased cardiac index, and increased right atrial pressure. Age ≥60 years, female gender, NYHA 4, and CKD at diagnosis were independently associated with decreased survival. The adjusted hazards ratio for death associated with CKD was 1.81 (95% confidence interval [1.01–3.25]). <b><i>Conclusion:</i></b> CKD is frequent at PAH diagnosis and is independently associated with increased mortality. Right heart failure may induce renal hypoperfusion and congestion, and is associated with eGFR decrease