A model of hemodialysis after acute kidney injury in rats.

BACKGROUND: Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance. METHODS: Eighteen Sprague-Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent. RESULTS: After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7-46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2-33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1-191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2-140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7-250.3 µg). CONCLUSIONS: This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Two-year follow-up of 196 interstitial lung disease patients after ICU stay.

OBJECTIVE: Interstitial lung diseases (ILDs) are associated with poor prognosis in the intensive care unit (ICU). We aimed to assess factors associated with hospital mortality in ILD patients admitted to the ICU and to investigate long-term outcome.MATERIAL AND METHODS: This was a retrospective study in a teaching hospital specialised in ILD management. Patients with ILD who were hospitalised in the ICU between 2000 and 2014 were included. Independent predictors of hospital mortality were identified using logistic regression.RESULTS: A total of 196 ILD patients were admitted to the ICU during the study period. Overall hospital mortality was 55%. Two years after ICU admission, 70 (36%) patients were still alive. Of the 196 patients, 108 (55%) required invasive mechanical ventilation, of whom 21 (20%) were discharged alive from hospital. Acute exacerbation of ILD and multi-organ failure were highly associated with hospital mortality (OR 5.4, 95% CI 1.9-15.5 and OR 12.6, 95% CI 4.9-32.5, respectively).CONCLUSION: Hospital mortality among ILD patients hospitalised in the ICU was high, but even where invasive mechanical ventilation was required, a substantial number of patients were discharged alive from hospital. Multi-organ failure could lead to major ethical concerns.

Use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study.

BACKGROUND: No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock. PATIENTS AND METHODS: This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset). RESULTS: Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5-47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14-65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis. CONCLUSION: Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics. Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

Tuberculosis in the intensive care unit: a descriptive analysis in a low-burden country.

BACKGROUND: Although tuberculosis (TB) is not a major public health issue in low-burden countries, severe cases are still a matter of concern. OBJECTIVE: To assess the risk factors for mortality due to TB in a low-burden setting. DESIGN: A retrospective study of 97 patients hospitalised with active TB in the intensive care unit (ICU) of the Bichat-Claude Bernard Hospital, Paris, France, from 2000 to 2009. RESULTS: The mean age was 47.4 ± 14.7 years; 40 patients were human immunodeficiency virus (HIV) infected, with a median CD4 cell count of 74 cells/mm(3). The survival analysis showed that 21 patients died during their time in the ICU. The observed risk factors for ICU mortality were organ failure, high Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment scores, and concomitant non-tuberculous infection. In multivariate analysis, only SAPS II score was significantly associated with mortality. CONCLUSION: Risk factors identified in this study are different from those in high-burden countries, and were not associated with the site of TB disease. There was no difference in TB presentation between HIV-infected and non-HIV-infected patients, and HIV was not a mortality risk factor. Low-burden countries still experience high death rates due to severe TB.

[New therapeutic strategies in ARDS]. / Nouveautés thérapeutiques sur le SDRA.

Treatment of acute respiratory distress syndrome (ARDS) has been subject to many researches, sometimes leading to intense controversy. New findings in this field are varied. Effects on prognosis of commonly used treatments for ARDS have recently been investigated. Consistently, prone position, previously known to improve oxygenation without effect on mortality, has been shown to improve survival of the most severely hypoxemic patients. Administration of neuromuscular blocking agents in the acute phase of ARDS has been also shown to be beneficial on survival. In contrast, the exact place of extracorporeal membrane oxygenation (ECMO) in ARDS management remains to be defined despite data suggesting its possible efficiency. In addition, a new era of research has emerged with the advent of cell therapy. Mesenchymal stem cells are able to both promote alveolar epithelium repair and prevent infections. Their efficacy in animal models of ARDS still needs to be confirmed by clinical trials. Finally, other promising therapies including beta-2 adrenergic agonists and omega-3 fatty acids have shown significant limitations in large clinical studies on ARDS.

Gender and age as factors in the inhibition of renal clearance of amantadine by quinine and quinidine.

We studied the short-term effect of oral doses of quinine and quinidine on the renal clearance of amantadine in healthy young (age range, 27 to 39 years) and older (age range, 60 to 72 years) adults of both genders in a three-limbed randomized crossover study. Renal clearance of amantadine (13.2 +/- 5.8 L/hr) was significantly inhibited by quinine (9.7 +/- 4.8 L/hr) and quinidine (8.9 +/- 4.0 L/hr) only in male subjects and was not associated with age. The chiral selectivity for the renal clearance of quinidine over quinine was confirmed and extended with the suggestion of both age- and gender-associated changes on the renal clearance ratio for these two diastereomeric drugs. These data support the continued use of amantadine for studies on the renal elimination of organic cationic drugs.