Risk Factors of AKI in Acute Respiratory Distress Syndrome: A Time-Dependent Competing Risk Analysis on Severe COVID-19 Patients.

Introduction: Acute kidney injury (AKI) is frequently observed in patients with COVID-19 admitted to intensive care units (ICUs). Observational studies suggest that cardiovascular comorbidities and mechanical ventilation (MV) are the most important risk factors for AKI. However, no studies have investigated the renal impact of longitudinal covariates such as drug treatments, biological variations, and/or MV parameters. Methods: We performed a monocentric, prospective, longitudinal analysis to identify the dynamic risk factors for AKI in ICU patients with severe COVID-19. Results: Seventy-seven patients were included in our study (median age: 63 [interquartile range, IQR: 53-73] years; 58 (75%) men). Acute kidney injury was detected in 28 (36.3%) patients and occurred at a median time of 3 [IQR: 2-6] days after ICU admission. Multivariate Cox cause-specific time-dependent analysis identified a history of hypertension (cause-specific hazard (CSH) = 2.46 [95% confidence interval, CI: 1.04-5.84]; P = .04), a high hemodynamic Sequential Organ Failure Assessment score (CSH = 1.63 [95% CI: 1.23-2.16]; P < .001), and elevated Paco2 (CSH = 1.2 [95%CI: 1.04-1.39] per 5 mm Hg increase in Pco2; P = .02) as independent risk factors for AKI. Concerning the MV parameters, positive end-expiratory pressure (CSH = 1.11 [95% CI: 1.01-1.23] per 1 cm H2O increase; P = .04) and the use of neuromuscular blockade (CSH = 2.96 [95% CI: 1.22-7.18]; P = .02) were associated with renal outcome only in univariate analysis but not after adjustment. Conclusion: Acute kidney injury is frequent in patients with severe COVID-19 and is associated with a history of hypertension, the presence of hemodynamic failure, and increased Pco2. Further studies are necessary to evaluate the impact of hypercapnia on increasing the effects of ischemia, particularly in the most at-risk vascular situations.

Introduction: L'insuffisance rénale aiguë (IRA) est fréquemment observée chez les patients atteints de COVID-19 admis dans les unités de soins intensifs (USI). Des études observationnelles suggèrent que les comorbidités cardiovasculaires et la ventilation mécanique (VM) seraient les plus importants facteurs de risque de l'IRA. Aucune étude n'a cependant examiné l'impact sur la fonction rénale de covariables longitudinales telles que les traitements médicamenteux, les variations biologiques et/ou les paramètres de la VM. Méthodologie: Nous avons procédé à une analyse prospective et longitudinale dans un seul centre hospitalier afin d'identifier les facteurs de risque dynamiques de l'IRA chez les patients hospitalisés aux USI en raison d'une forme grave de la COVID-19. Résultats: Soixante-dix-sept patients ont été inclus dans notre étude (75 % d'hommes [n=58]; âge médian: 63 ans [ÉIQ: 53-73]). L'IRA a été détectée chez 28 patients (36,3 %) et est survenue dans un délai médian de 3 jours (ÉIQ: 2-6 jours) après l'admission à l'USI. Une analyse de Cox multivariée, spécifique à la cause et tenant compte du temps, a permis de dégager les éléments suivants comme étant des facteurs de risque indépendants pour l'IRA: des antécédents d'hypertension (probabilité par cause [PPC]=2,46 [IC 95 %: 1,04-5,84]; p=0,04), un score SOFA hémodynamique élevé (PPC=1,63 [IC 95 %: 1,23-2,16]; p<0,001) et une concentration élevée de PaCO2 (PPC=1,2 [IC 95 %: 1,04-1,39] pour chaque augmentation de 5 mmHg de pCO2; p = 0,02). En ce qui concerne les paramètres de la VM, une pression expiratoire positive (PPC=1,11 [IC 95 %: 1,01-1,23] pour chaque augmentation de 1 cm H2O; p = 0,04) et l'utilisation d'un bloc neuromusculaire (PPC=2,96 [IC 95 %: 1,22-7,18]; p=0,02) ont été associés à l'IRA dans l'analyse univariée seulement, et non après ajustement. Conclusion: L'IRA est fréquente chez les patients atteints d'une forme grave de COVID-19 et elle est associé à des antécédents d'hypertension, à la présence d'une instabilité hémodynamique et à une augmentation de la pCO2. D'autres études sont nécessaires pour évaluer l'impact de l'hypercapnie sur l'augmentation des effets de l'ischémie, en particulier dans les situations vasculaires les plus à risque.

Comparison of two strategies for initiating renal replacement therapy in the intensive care unit: study protocol for a randomized controlled trial (AKIKI).

BACKGROUND: There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT. METHODS/DESIGN: This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 < 35 mmHg) or in a context of mixed acidosis with a PaCO2 ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all. DISCUSSION: The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01932190.

Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients.

STUDY OBJECTIVES: The association between genotype and phenotype in cystic fibrosis (CF) has been clearly established for pancreatic status, but not for lung disease. DESIGN: Retrospective study. SETTING: A respiratory unit of a teaching hospital. PATIENTS: We studied 51 adult CF patients for whom current data and genotype were available. Thirty-seven patients carried two severe mutations associated with pancreatic insufficiency phenotype (group S). Fourteen patients carried at least one mild (and dominant) mutation associated with pancreatic sufficiency phenotype (group M). MEASUREMENTS: We compared the course of the disease between the two groups, looking for a genotype/phenotype association for lung disease. RESULTS: The mean age of the population was 30 years. Patients with two severe mutations presented more severe disease with earlier onset (1.7 years vs 7.9 years, p = 0.0001). They presented with a more severe respiratory impairment, with a lower mean FEV(1) (29% of predictive value vs 58% of predictive value, p < 0.001); a higher Pseudomonas colonization rate (97% vs 57%, p < 0.01); a more frequent end-stage respiratory insufficiency, defined by a FEV(1) < 30% (73% vs 29%, p < 0.05); and a more marked yearly decline of FEV(1) (3% vs 1.4%, p < 0.001). By multivariate logistic regression analysis, carrying two severe mutations was the only independent predictor of a terminal respiratory insufficiency (relative risk, 6.75; 95% confidence interval, 1.79 to 26.50; p = 0.003). CONCLUSION: This study suggests that pulmonary disease appears to be associated with the severity of CF transmembrane regulator mutations.

Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients.

OBJECTIVE: To evaluate the extent to which respiratory changes in inferior vena cava (IVC) diameter can be used to predict fluid responsiveness. DESIGN: Prospective clinical study. SETTING: Hospital intensive care unit. PATIENTS: Twenty-three patients with acute circulatory failure related to sepsis and mechanically ventilated because of an acute lung injury. MEASUREMENTS: Inferior vena cava diameter (D) at end-expiration (Dmin) and at end-inspiration (Dmax) was measured by echocardiography using a subcostal approach. The distensibility index of the IVC (dIVC) was calculated as the ratio of Dmax - Dmin / Dmin, and expressed as a percentage. The Doppler technique was applied in the pulmonary artery trunk to determine cardiac index (CI). Measurements were performed at baseline and after a 7 ml/kg volume expansion using a plasma expander. Patients were separated into responders (increase in CI > or =15%) and non-responders (increase in CI <15%). RESULTS: Using a threshold dIVC of 18%, responders and non-responders were discriminated with 90% sensitivity and 90% specificity. A strong relation (r = 0.9) was observed between dIVC at baseline and the CI increase following blood volume expansion. Baseline central venous pressure did not accurately predict fluid responsiveness. CONCLUSION: Our study suggests that respiratory change in IVC diameter is an accurate predictor of fluid responsiveness in septic patients.