Differential effect on mortality of the timing of initiation of renal replacement therapy according to the criteria used to diagnose acute kidney injury: an IDEAL-ICU substudy.

BACKGROUND: This substudy of the randomized IDEAL-ICU trial assessed whether the timing of renal replacement therapy (RRT) initiation has a differential effect on 90-day mortality, according to the criteria used to diagnose acute kidney injury (AKI), in patients with early-stage septic shock. METHODS: Three groups were considered according to the criterion defining AKI: creatinine elevation only (group 1), reduced urinary output only (group 2), creatinine elevation plus reduced urinary output (group 3). Primary outcome was 90-day all-cause death. Secondary endpoints were RRT-free days, RRT dependence and renal function at discharge. We assessed the interaction between RRT strategy (early vs. delayed) and group, and the association between RRT strategy and mortality in each group by logistic regression. RESULTS: Of 488 patients enrolled, 205 (42%) patients were in group 1, 174 (35%) in group 2, and 100 (20%) in group 3. The effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity (adjusted interaction p = 0.021). Mortality was 58% vs. 42% for early vs. late RRT initiation, respectively, in group 1 (p = 0.028); 57% vs. 67%, respectively, in group 2 (p = 0.18); and 58% vs. 55%, respectively, in group 3 (p = 0.79). There was no significant difference in secondary outcomes. CONCLUSION: The timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria. In patients with elevated creatinine only, early RRT initiation was associated with significantly increased mortality. In patients with reduced urine output only, late RRT initiation was associated with a nonsignificant, 10% absolute increase in mortality.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. DESIGN: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. SETTING: Four ICUs of French university hospitals. PATIENTS: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). CONCLUSIONS: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.

Role of gut microbiota and bacterial translocation in acute intestinal injury and mortality in patients admitted in ICU for septic shock.

Introduction: Sepsis is a life-threatening organ dysfunction with high mortality rate. The gut origin hypothesis of multiple organ dysfunction syndrome relates to loss of gut barrier function and the ensuing bacterial translocation. The aim of this study was to describe the evolution of gut microbiota in a cohort of septic shock patients over seven days and the potential link between gut microbiota and bacterial translocation. Methods: Sixty consecutive adult patients hospitalized for septic shock in intensive care units (ICU) were prospectively enrolled. Non-inclusion criteria included patients with recent or scheduled digestive surgery, having taken laxatives, pre- or probiotic in the previous seven days, a progressive digestive neoplasia, digestive lymphoma, chronic inflammatory bowel disease, moribund patient, and pregnant and lactating patients. The primary objective was to evaluate the evolution of bacterial diversity and richness of gut microbiota during seven days in septic shock. Epidemiological, clinical and biological data were gathered over seven days. Gut microbiota was analyzed through a metagenomic approach. 100 healthy controls were selected among healthy blood donors for reference basal 16S rDNA values. Results: Significantly lower bacterial diversity and richness was observed in gut microbiota of patients at Day 7 compared with Day 0 (p<0.01). SOFA score at Day 0, Acute Gastrointestinal Injury (AGI) local grade, septic shock origin and bacterial translocation had an impact on alpha diversity. A large increase in Enterococcus genus was observed at Day 7 with a decrease in Enterobacterales, Clostridiales, Bifidobacterium and other butyrate-producing bacteria. Discussion: This study shows the importance of bacterial translocation during AGI in septic shock patients. This bacterial translocation decreases during hospitalization in ICUs in parallel to the decrease of microbiota diversity. This work highlights the role of gut microbiota and bacterial translocation during septic shock.

Short- and Long-Term Outcome of Chronic Dialyzed Patients Admitted to the ICU and Assessment of Prognosis Factors: Results of a 6-Year Cohort Study.

OBJECTIVES: Data about end-stage kidney disease patients admitted to the ICU are scarce, dated, and mostly limited to short-term survival. The aim of this study was to assess the short- and long-term outcome and to determine the prognostic factors for end-stage kidney disease patients admitted to the ICU. DESIGN: Prospective observational study. SETTING: Medical ICUs in two university hospitals. PATIENTS: Consecutive end-stage kidney disease patients admitted in two ICUs between 2012 and 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Renal replacement therapy variables, demographic, clinical, and biological data were collected. The requirement of mechanical ventilation and vasopressive drugs were also collected. In-ICU and one-year mortality were estimated and all data were analyzed in order to identify predictive factors of short and long-term mortality. A total of 140 patients were included, representing 1.7% of total admissions over the study period. Septic shock was the main reason for admission mostly of pulmonary origin. Median Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score were at 63 and 6.7, respectively. In-ICU, hospital, and 1-year mortality were 41.4%, 46.4%, and 63%, respectively. ICU mortality was significantly higher as compared with ICU control group non-end-stage kidney disease (25% vs 41.4%; p = 0.005). By multivariate analysis, the short-term outcome was significantly associated with nonrenal Sequential Organ Failure Assessment score, and with the requirement of mechanical ventilation or/and vasoconstrictive agents during ICU stay. One-year mortality was associated with increased dialysis duration (> 3 yr) and phosphatemia (> 2.5 mmol/L), with lower albuminemia (< 30 g/L) and nonrenal Sequential Organ Failure Assessment greater than 8. CONCLUSIONS: End-stage kidney disease patients presented frequently severe complications requiring critical care that induced significant short- and long-term mortality. ICU and hospital mortality depended mainly on the severity of the critical event reflected by Sequential Organ Failure Assessment score and the need of mechanical ventilation and/or catecholamines. One-year mortality was associated with both albuminemia and phosphatemia and with prior duration of chronic dialysis treatment, and with organ failure at ICU admission.

Use of double filtration plasmapheresis for the treatment of acquired thrombocytopenic thrombotic purpura.

Double filtration plasmapheresis (DFPP) could be an alternative method to simple plasma exchange plasmapheresis in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). In a retrospective single center case series, we studied clinical presentation, management care, and prognosis of aTTP patients from our academic center treated with DFPP and IV infusion of fresh frozen plasma (FFP) between 2009 and 2018. Nine patients were included for 11 episodes. Median age was 38 years old (IQR 26-53) with 78% women. Six episodes (55%) required admission to the ICU, four of which required mechanical ventilation. Median FFP volume transfused was 35.2 mL/kg/d of session. Response was complete for nine episodes (82%). Four patients presented an early relapse, two a late relapse. Four patients died: one had an active untreated HCV infection, and two were over 80-year-old polymorbid patients. DFPP seems to be an efficient method of therapeutic plasmapheresis in TTP when combined with FFP transfusion and immunosuppressive treatments.

Heterogeneity of Cause, Care, and Prognosis in Severe Acute Kidney Injury in Hospitalized Patients: A Prospective Observational Study.

BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations. OBJECTIVE: To describe severe AKI heterogeneity by department of hospitalization. DESIGN: This is a prospective observational single-center study. SETTING: Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017. PATIENTS: All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 µmol/L. MEASUREMENTS: Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI. METHODS: A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others. RESULTS: The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards. LIMITATIONS: We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery. CONCLUSION: Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.

CONTEXTE: Le KDIGO définit l'insuffisance rénale aigüe (IRA) uniquement par une variation de la créatinine sérique (SCr) et de la diurèse. L'IRA grave est un syndrome couvrant diverses situations cliniques. OBJECTIF: Décrire l'hétérogénéité de l'IRA grave selon l'unité d'hospitalisation. TYPE D'ÉTUDE: Étude observationnelle prospective menée dans un seul centre. SUJETS: Des adultes hospitalisés entre août 2016 et décembre 2017 dans un centre de soins tertiaires en France. PARTICIPANTS: Tous les adultes atteints d'IRA grave, définie par un traitement de dialyse ou un taux de SCr au-delà de 354 µmol/l. MESURES: Les caractéristiques du patient, le tableau clinique et de laboratoire, l'étiologie de l'IRA, l'indication médicale pour une thérapie de remplacement rénal (TRR), le plan de soins palliatifs et le statut vital 30 jours après l'épisode d'IRA grave. MÉTHODOLOGIE: Une description globale des caractéristiques des patients, des soins et du pronostic, ainsi qu'une comparaison selon l'unité d'hospitalisation: unité de soins intensifs (USI), néphrologie et autres. RÉSULTATS: L'étude portait sur 480 patients (73 % d'hommes) âgés de 64 à 83 ans (âge médian: 72 ans) avec des antécédents incluant maladies cardiovasculaires, diabète, cancer ou insuffisance rénale chronique. Les principales causes de l'IRA grave étaient une septicémie (104, 22 %), une hypovolémie (98, 20 %), une IRA obstructive (84, 18 %), une nécrose tubulaire aigüe (74, 15 %) ou un syndrome cardio-rénal (51, 11 %). Le diagnostic avait été posé à l'USI pour 188 patients (39 %), en néphrologie pour 130 patients (27 %) et dans d'autres unités pour 162 patients (34 %). Les caractéristiques des patients différaient entre les unités de soins en ce qui concerne l'âge, les comorbidités, l'étiologie et les indications de TRR. Un plan de soins palliatifs existait pour 72 patients (15 %), le plus souvent dans les autres unités. LIMITES: Nous avons étudié un sous-groupe de patients atteints d'IRA de stade 3 (classification KDIGO) dans un seul centre sans chirurgie cardiaque. CONCLUSION: Les patients hospitalisés pour une IRA grave présentent des comorbidités, des tableaux cliniques, des soins et des pronostics variés et sont admis dans différentes unités d'hospitalisation. Cette hétérogénéité de l'IRA grave met en relief le besoin de soins personnalisés qui nécessitent des outils pronostics basés sur des informations autres que la SCr et la diurèse.

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

BACKGROUND: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial. METHODS: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days. RESULTS: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients). CONCLUSIONS: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).