Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

PURPOSE: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. METHODS: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization. RESULTS: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. CONCLUSION: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Transthoracic Echocardiography with Doppler Tissue Imaging predicts weaning failure from mechanical ventilation: evolution of the left ventricle relaxation rate during a spontaneous breathing trial is the key factor in weaning outcome.

INTRODUCTION: There is growing evidence to suggest that transthoracic echocardiography (TTE) should be used to identify the cardiac origin of respiratory weaning failure. THE AIMS OF OUR STUDY WERE: first, to evaluate the ability of transthoracic echocardiography, with mitral Doppler inflow E velocity to annular tissue Doppler Ea wave velocity (E/Ea) ratio measurement, to predict weaning failure from mechanical ventilation in patients, including those with atrial fibrillation; and second, to determine whether the depressed left ejection fraction and/or diastolic dysfunction participate in weaning outcome. METHODS: The sample included patients on mechanical ventilation for over 48 hours. A complete echocardiography was performed just before the spontaneous breathing trial (SBT) and 10 minutes after starting the SBT. Systolic dysfunction was defined by a left ventricle ejection fraction under 50% and relaxation impairment by a protodiastolic annulus mitral velocity Ea under or equal to 8 cm/second. RESULTS: A total of 68 patients were included. Twenty failed the weaning process and the other 48 patients succeeded. Before the SBT, the E/Ea ratio was higher in the failed group than in the successful group. The E/Ea measured during the SBT was also higher in the failed group. The cut-off value, obtained from receiver operating characteristics (ROC) curve analysis, to predict weaning failure gave an E/Ea ratio during the SBT of 14.5 with a sensitivity of 75% and a specificity of 95.8%. The left ventricular ejection fraction did not differ between the two groups whereas Ea was lower in the failed group. Ea increased during SBT in the successful group while no change occurred in the failed group. CONCLUSIONS: Measurement of the E/Ea ratio with TTE could predict weaning failure. Diastolic dysfunction with relaxation impairment is strongly associated with weaning failure. Moreover, the impossibility of enhancing the left ventricle relaxation rate during the SBT seems to be the key factor of weaning failure. In contrast, the systolic dysfunction was not associated with weaning outcome.

Echocardiography is a good way to diagnose and monitor type 1 cardiorenal syndrome in ICU.

BACKGROUND: Type-one cardiorenal syndrome (CRS) is defined by acute decompensated heart failure leading to secondary acute kidney injury. No study evaluates the reliability of transthoracic echocardiography as a help tool for diagnosis and optimization of CRS. Therefore, the aim of this study was to assess echocardiographic parameters in patients with CRS in the Intensive Care Unit. METHODS: We conducted an observational, prospective, single-center study in the ICU department of a general hospital. Patients admitted in the ICU and presenting with type 1 CRS were included. Transthoracic echocardiography was performed at baseline and at day end after treatment by the same trained operator for the same patients. We report various echocardiographic indices at these two timepoints. RESULTS: Twenty-seven patients were included. At baseline 96.3% of patients had signs of congestion (IVC dilation >2 cm), 76% had an altered S-wave (<11.5 cm/s), 72.73% had an altered TAPSE (<17 mm), 85.19% had an elevated RV/LV diameter ratio (>0.6). Between baseline and D end, IVC size and, the number of patients with an elevated RV/LV diameter ratio significantly decreased. Weight decreased, whereas natriuresis significantly increased, and the amount of vasopressors support decreased. Diuresis, and S-wave velocity showed non-significant changes. CONCLUSIONS: Main echocardiographic findings at baseline in patients with type 1 CRS consist of a right ventricular dysfunction associated an IVC dilation. We report that weight, RV/LV diameter ratio, and IVC diameter might constitute good follow-up parameters to monitor treatment response.

Incidence, clinical features and outcome of Takotsubo syndrome in the intensive care unit.

BACKGROUND: Most diseases encountered in the intensive care unit are associated with major stress that can potentially trigger Takotsubo syndrome. Many severe cardiovascular complications are associated with Takotsubo syndrome, yet little is known about Takotsubo syndrome in the intensive care unit. AIMS: We sought to determine the incidence of Takotsubo syndrome, and to describe its clinical features and outcome in an intensive care unit. METHODS: This prospective single-centre study included all patients admitted consecutively over a 12-month period who had transthoracic echocardiography, electrocardiography and a troponin I assay performed on admission, at 24 and 48hours after admission, and at discharge and in the case of clinical worsening. RESULTS: The incidence of Takotsubo syndrome was 4.6% (13/280 patients) and female sex predominated (69.2%). The median age of the subgroup with Takotsubo syndrome was 64 (56-72) years. Pulmonary disease and sepsis were the most frequent triggers (46.2% and 38.5%, respectively). Median left ventricular ejection fraction was 29.0% (20.0-37.0). Patients with Takotsubo syndrome presented with shock and arrhythmias and needed ventilation more frequently than patients without Takotsubo syndrome (69.2% vs. 36.3%, P=0.035; 46.2% vs. 13.5%, P=0.006; and 92.3% vs. 60.7%, P=0.021), but mortality rates were similar. The median delay to cardiac index recovery, when impaired, was 2.0 (1.0-2.75) days, and that of left ventricular ejection fraction was 12.5 (7-14.75) days. CONCLUSION: Takotsubo syndrome in the intensive care unit is not uncommon and is associated with substantial haemodynamic and respiratory instability. New-onset arrhythmias and respiratory and haemodynamic worsening could arouse suspicion of and prompt screening for Takotsubo syndrome in the intensive care unit.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial.

BACKGROUND: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy"). METHODS/DESIGN: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. DISCUSSION: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.

Tako-Tsubo cardiomyopathy presenting with cardiogenic shock successfully treated with milrinone: a case report.

We report the case of a middle age patient presenting with Tako-Tsubo cardiomyopathy (TTC) complicated by cardiogenic shock that was successfully handled with milrinone. A 64-year old man presented with cardiogenic shock after benzodiazepine and alcohol intoxication. A slight elevation of troponin and typical left ventricular ballooning without coronary lesions suggested TTC. Within a few hours milrinone infusion normalized the cardiac index. TTC is responsible for severe transient left ventricular dysfunction occurring after physical or psychological stress. The major pathophysiological mechanism involved is disproportionate catecholamine secretion, which may stun the myocardium. We considered if treatment of this unique physiopathology with catecholamines could be dangerous in these patients and if alternative inotropes such as milrinone should be preferred.