Vincent Das

Cirrhotic patients in the medical intensive care unit: Early prognosis and long-term survival*

Objectives:To reassess the prognosis of patients with cirrhosis admitted to the intensive care unit. Design:A retrospective study in a medical intensive care unit in a teaching hospital in France. Patients:All patients with cirrhosis without previous liver transplantation admitted in the period from 2005 to 2008. Interventions:None. Main Results:One hundred thirty-eight patients were studied. Survival rates in the intensive care unit, in hospital, and at 6 months were 59% (95% confidence interval, 50%–67%), 46% (95% confidence interval, 38%–54%), and 38% (95% confidence interval, 30%–47%), respectively. In-hospital survival rates for patients requiring vasopressors, mechanical ventilation, or renal replacement therapy were 20%, 33%, and 31%, respectively. On day 1, independent risk factors for inhospital mortality were age, albuminemia, international normalized ratio, and the Sequential Organ Failure Assessment score computed after discarding points for hematologic failure (modified Sequential Organ Failure Assessment score). Liver disease severity, assessed using a clinical classification, did not correlate with in-hospital mortality. In patients still alive after 3 days, the only prognostic factor was the modified Sequential Organ Failure Assessment score computed after 3 days. To predict inhospital mortality, the modified Sequential Organ Failure Assessment score on day 1 had a greater area under the receiver operating characteristic curve (0.84) than the Simplified Acute Physiology Score II (0.78), the Child-Pugh score (0.76), the model for end-stage liver disease score (0.77), or the model for end-stage liver disease–natremia score (0.75). The inhospital mortality rate with three or four nonhematologic organ failures on day 1 was not >70%, whereas it was 89% with three nonhematologic organ failures after 3 days spent in the intensive care unit. Conclusion:In-hospital survival rate of intensive care unit-admitted cirrhotic patients seemed acceptable, even in patients requiring life-sustaining treatments and/or with multiple organ failure on admission. The most important risk factor for in-hospital mortality was the severity of nonhematologic organ failure, as best assessed after 3 days. A trial of unrestricted intensive care for a few days could be proposed for select critically ill cirrhotic patients.

Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study

IntroductionSeveral factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea.MethodsWe conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges).ResultsA total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar.ConclusionsFeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.

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.

Clinical Features and Outcomes in Patients With Disseminated Toxoplasmosis Admitted to Intensive Care: A Multicenter Study

BACKGROUND Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described. METHODS We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected. RESULTS Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality. CONCLUSIONS Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Severe post‐renal acute kidney injury, post‐obstructive diuresis and renal recovery

Study Type – Therapy (case series)

Prognostic scores for cirrhotic patients admitted to an intensive care unit: Which consequences for liver transplantation?

Mortality is increased in cirrhotic patients admitted in ICU whatever the admission reason. Prognosis scores assessed in critically ill cirrhotic patients in ICU can be classified in three main categories: liver-specific (CTP and MELD) scores, general (SAPS II and APACHE) scores, and organ failure (OSF and SOFA) scores. The components of the liver-specific scores can be influenced by the acute disease indicating the admission to ICU but those of the non liver-specific scores can be influenced by the underlying liver cirrhosis. Many studies reported that organ failure scores are the best predictors of outcome in cirrhotic patients in ICU. We may wonder if cirrhotic patients with acute organ failures should receive prioritization for organ allocation to save their life or should be denied for a potential futile LT. According to recent studies, the SOFA score is associated with a higher risk of death for patients waiting for LT but could not be associated with a worse outcome after LT. It becomes of paramount importance to correctly identify the cirrhotic patients who will maximally benefit from LT after admission to ICU. The EASL-CLIF Consortium defines the CLIF-SOFA score, redefining the SOFA score with cut-off levels based on mortality prediction. The CLIF-SOFA could represent the ideal score in ICU since it is based on organ failures with cut-off values specifically identified in cirrhotic patients. The validation of the CLIF-SOFA score in critically ill cirrhotic patients admitted to ICU and its usefulness to identify patients who could benefit from LT should be the next steps.

Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation

Objectives To identify the factors associated with the interindividual pharmacokinetic (PK) variability of micafungin and to evaluate the probability of reaching the previously determined PK/pharmacodynamic efficacy thresholds (AUC/MIC >5000 for non-parapsilosis Candida sp. and ≥285 for Candida parapsilosis) with the recommended 100 mg daily dose in ICU patients with sepsis and mechanical ventilation. Methods One hundred patients were included and 436 concentrations were available for PK analysis performed with NONMEM software. PTA was determined by Monte Carlo simulations. Results Micafungin obeyed a two-compartment model with first-order elimination from the central compartment. Mean parameter estimates (percentage interindividual variability) were 1.34 L/h (34%) for clearance (CL), 11.80 L (38%) and 7.68 L (39%) for central (Vc) and peripheral (Vp) distribution volumes, respectively, and 4.67 L/h (37%) for distribution clearance. CL, Vc and Vp increased by 14% when the albumin level was ⩽25 g/L and CL decreased by 25% when SOFA score was ≥10. Body weight was related to CL, Vc and Vp by allometric models. PTA was ≥90% in Candida albicans and Candida glabrata infections, except when the MIC was ≥0.015 mg/L, and ranged between 0% and 40% for C. parapsilosis infections with MIC ≥0.5 mg/L. Conclusions A possible increase in the dose should be evaluated for infections due to C. parapsilosis and for infections due to C. albicans and C. glabrata with MICs ≥0.015 mg/L.

Insuffisances rénales aiguës secondaires à une rhabdomyolyse ou à une hémolyse

La rhabdomyolyse est une lesion du muscle strie, reversible ou non, alterant suffisamment l’integrite de la membrane des cellules pour permettre la liberation de leur contenu dans le milieu extracellulaire (1). Depuis la description princeps, par Bywaters, de l’insuffisance renale aigue (IRA) secondaire au « syndrome d’ecrasement » (« crush syndrome »), au cours des bombardements de Londres durant la seconde Guerre mondiale, de nombreuses autres causes medicales de rhabdomyolyse ont ete identifiees, qui peuvent aussi etre responsables d’IRA (2). Selon les definitions utilisees et le contexte (traumatique ou non), 4 a 80 % des patients ayant une rhabdomyolyse developpent une IRA (1, 3, 4), et une rhabdomyolyse serait a l’origine de 4 a 9 % des episodes d’IRA, en general (5, 6) comme en reanimation (7). La litterature medicale s’est enrichie ces dernieres annees d’etudes menees dans un contexte de medecine « de catastrophe », situation a part ou l’IRA est souvent severe, accompagnee d’une mortalite elevee, et ou les contraintes logistiques ont autant d’importance que l’application de l’« evidence-based medicine ».