Kada Klouche

Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial

BACKGROUND Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial. In this study, we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome. METHODS Our prospective, randomised, multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France. Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer. 360 patients were randomised, and the primary endpoint was 60-day survival based on an intention-to-treat analysis. FINDINGS Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any other time. INTERPRETATION These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.

Predicting the success of defibrillation by electrocardiographic analysis

BACKGROUND We investigated an electrocardiographic signal analysis technique for predicting whether an electrical shock would reverse ventricular fibrillation (VF) in an effort to minimize the damaging effects of repetitive shocks during CPR. METHODS AND RESULTS An established model of CPR was utilized. VF was electrically induced in anesthetized 40 kg domestic pigs. Defibrillation was attempted after either 4 or 7 min of untreated VF. Failing to reverse VF, a 1 min interval of precordial compression and mechanical ventilation preceded each subsequent defibrillation attempt. The amplitude frequency spectrum of digitally filtered VF wavelets was computed with Fourier analysis during uninterrupted precordial compression from conventional right infraclavicular and left apical electrodes. Of a total of 34 electrical defibrillation attempts, 24 animals were restored to spontaneous circulation (ROSC). An amplitude spectrum analysis (AMSA) value of 21 mV Hz had a negative predictive value of 0.96 and a positive predictive value of 0.78. CONCLUSIONS AMSA predicted when an electrical shock failed to restore spontaneous circulation during CPR with a high negative predictive value. This method potentially fulfills the need for minimizing ineffective defibrillation attempts and their attendant adverse effects on the myocardium.

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial

IMPORTANCE Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear. OBJECTIVE To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAIN OUTCOMES AND MEASURES The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01915719.

Superoxide anion overproduction in sepsis: Effects of vitamin E and simvastatin

Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2°−) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2°− production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2°− production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2°− production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2°− production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2°−. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation.

Alpha-methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation☆

OBJECTIVES The purpose of this study was to investigate the effects of a selective alpha2-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR). BACKGROUND For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha1-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction. METHODS Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha2-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt40, negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation. RESULTS Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt40 and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with vohimbine abolished the beneficial effects of alphaMNE. CONCLUSIONS The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.

A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients

BACKGROUND Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Osteoprotegerin (OPG) could play a key role in bone-vascular calcification imbalance and could be a marker of vascular calcification extent and progression. The purpose of this study was to evaluate relationships between vascular risk biomarkers (including classic risk factors and OPG) and coronary artery calcification (CAC) extent in chronic kidney disease (CKD) patients and to establish within the markers the appropriate cut-off value to predict CAC. METHODS A total of 133 non-dialyzed CKD patients at various stages of kidney disease [75 males/58 females, median age: 69.9 (27.4-94.6)] were enrolled, excluding extrarenal replacement therapy patients. All underwent chest multidetector computed tomography for CAC scoring. Blood samples were collected for measurement of vascular risk markers (kidney disease, inflammation, nutrition, calcium phosphate and OPG). A potential relationship between CAC and these biological markers was investigated, and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of involved markers that best predicted the presence of CAC. RESULTS After adjustment for age, diabetes, smoking and gender, among biological markers, only low-estimated glomerular filtration rate using Modification of Diet in Renal Disease [OR = 3.63 (1.10-12.02)], high FEPO(4) [OR = 3.99 (1.17-13.6)] and high OPG levels [OR = 8.54 (2.14-34.11)] were associated with the presence of CAC. A protective effect of 1.25(OH)(2) vitamin D [OR = 0.20 (0.05-0.79)] and LDL cholesterol [OR = 0.27 (0.08-0.94)] on CAC was also observed. ROC curve analysis showed that the OPG best cut-off value predicting CAC was 757.7 pg/mL. CONCLUSION These results suggest that a CAC increase is strongly associated with a plasma OPG increase in CKD patients. The values of OPG >757.7 pg/mL allow us to predict the presence of CAC in these patients.

Prohormone brain natriuretic peptide (proBNP), BNP and N-terminal-proBNP circulating levels in chronic hemodialysis patients. Correlation with ventricular function, fluid removal and effect of hemodiafiltration

Abstract Background: Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and to a lesser extent prohormone proBNP are recognized as biochemical markers of left ventricular dysfunction. In renal failure, interpretation of natriuretic peptide remains unclear, as natriuretic peptide levels may be not only be dependent on cardiac function and dimensions but also on renal function, fluid volume and removal by dialysis procedure including hemodiafiltration (HDF). The purpose of this study was (i) to assess BNP, NT-proBNP and proBNP levels and their correlation with clinical and echocardiographic data in chronic hemodialysis patients, and (ii) to investigate basal level alteration following HDF. Methods: Baseline clinical and echocardiographic parameters were collected in 31 dialysis patients without evidence of cardiac failure. Pre- and post-HDF BNP, NT-proBNP and proBNP concentrations were measured. Correlations between echocardiographic measurements and basal circulating peptides, between changes in peptide values and changes in fluid volume after HDF were investigated. Results: Baseline plasmatic levels were elevated (BNP=517±840 pg/mL, NT-proBNP=5340±6132 pg/mL and proBNP=3569±4683 pg/mL) and correlated with left auricular diameter and left ventricular mass index. HDF session induced a significant decrease of 39%, 59% and 36% for BNP, NT-proBNP and proBNP levels, respectively. This decrease was not correlated to post-HDF fluid removal or weight decrease. Correlation between BNP and proBNP was stronger (r2=0.88) than between NT-proBNP and proBNP (r2=0.54). Conclusions: Despite their elimination, BNP, NT-proBNP and proBNP could be potential markers of left ventricular remodeling in chronic renal failure patients on hemodialysis. According to these results, their cut-off values, however, need to be re-evaluated. Clin Chem Lab Med 2008;46:1019–24.

Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial

Importance Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. Objective To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. Design, Setting, and Participants Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. Interventions Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). Main Outcomes and Measures The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. Results Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P = .008). Conclusions and Relevance Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28. Trial Registration clinicaltrials.gov Idenitfier: NCT01773876.

Acute respiratory failure in kidney transplant recipients: a multicenter study

IntroductionData on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients.MethodsWe conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008.ResultsOf 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99).ConclusionsIn kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.

Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications

BACKGROUND Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population. METHODS A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers. RESULTS Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed. CONCLUSIONS Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.