Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study.

BACKGROUND AND AIM: The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real-life use are lacking. METHODS: This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. RESULTS: A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 µmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury-hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44-54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1-year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant-free survival. CONCLUSION: Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

Is Inappropriate Response to Cosyntropin Stimulation Test an Indication of Corticosteroid Resistance in Septic Shock?

We recently published a comparison of two hydrocortisone dosage regimens in patients with septic shock. We compare the results conferred by the two regimens as a function of the response to cosyntropin stimulation test (CST). Patients with septic shock were treated by one of two hydrocortisone regimens: either a 50-mg intravenous bolus every 6 h during 7 days (200 mg group; n = 49), or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300 mg group; n = 50). Nonresponders was defined as a CST response of 9 µg/dL or less. Nonresponders had more severe septic shock, greater fluid resuscitation needs, and greater vasopressor dependence than responders. When analyzed only as a function of CST results, there was no difference in survival between responders and nonresponders. However, analyses crossing CST results and the treatment regimens showed that patients who were responders and in the 300 mg group had significantly less intensive care unit mortality compared with responders in the 200 mg group (respective mortality of 24% vs. 55% [relative risk 0.43, 95% confidence interval, 0.20 to 0.94, P = 0.018]). Multivariate analysis identified baseline blood cortisol as an independent prognostic factor for 28-day mortality in all groups (hazard ratio 1.002, 95% confidence interval, 1.001 to 1.002, P ≤ 0.0001). The results suggest that in patients who respond to CST, hydrocortisone can provide a dose-dependent benefit. In contrast, nonresponse may indicate corticosteroid resistance. This heterogeneity of response to hydrocortisone may explain the difficulties encountered when trying to demonstrate its benefit in septic shock.

[Intestinal transplantation]. / La greffe intestinale.

Even though surgical techniques for isolated intestine, liver-intestine, and multivisceral transplantations were developed in the 1960's, very few patients were transplanted before 1990 because initial immunosuppression regimens were insufficient, making intestine transplantation impossible. Intestine transplantation resulted in death in most patients within days or months. The discouraging results of the first clinical trials were due to technical complications, sepsis, and the failure of conventional immunosuppression to control rejection. By 1990 the development of tacrolimus-based immunosuppression and improved surgical techniques, the increased array of potent immunosuppressive medications, infection prophylaxis, and suitable patient selection helped improve actuarial graft and patient survival rates for all types of intestine transplantation. The aims of this review are to describe the current status of intestine transplantation including the underlying diseases and conditions that may be indications for intestine transplantation, to identify patient populations for this indication, to provide key steps for patient evaluation, to summarize current recommendations for immunosuppression, to list the most common postoperative complications, and to discuss the international experience of small bowel transplantation compiled and analyzed by the International Intestine Transplant Registry since 1985.

Effects of Increasing Hydrocortisone to 300 mg Per Day in the Treatment of Septic Shock: a Pilot Study.

PURPOSE: The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock. METHODS: We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment. RESULTS: There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group. CONCLUSION: We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate.

Performance of target-controlled sufentanil infusion in obese patients.

BACKGROUND: Because obesity might affect pharmacokinetic parameters, the authors evaluated the accuracy of target-controlled sufentanil infusion in morbidly obese patients using a pharmacokinetic model usually applied to a normal-weight population. METHODS: Target-controlled propofol and sufentanil coinfusions were administered to 11 morbidly obese patients (body mass index: 45.0 +/- 6.5 kg/m2 ) undergoing laparoscopic gastroplasty. The target plasma propofol concentration was 3 micro g/ml. The effect-site sufentanil target concentration was initially 0.4 ng/ml but was modified during surgery as a function of blood pressure and heart rate. Plasma sufentanil concentrations were measured from the onset of infusion until 24 h after its termination. The predicted sufentanil target concentrations were calculated by STANPUMP software. Intrasubject data analyzed included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble. Pharmacokinetic analysis was performed using a nonlinear mixed effect model. RESULTS: Applied sufentanil target concentrations ranged from 0.3 to 0.65 ng/ml. The mean +/- SD plasma sufentanil concentration measured during spontaneous ventilation was 0.13 +/- 0.03 ng/ml. Median performance error (range) was -13% (-42 to 36%). Median absolute performance error was 26% (8-44%) during infusion and 17% (12-59%) for the 24 h after its completion. The pharmacokinetic sets used slightly overpredicted the concentrations, with a median divergence of -3.4% (-10.2 to 3.1%) during infusion. For body mass index greater than 40, the overestimation of plasma sufentanil concentrations was greater. A two-compartment model with proportional error for interindividual variability best fitted the data. The residual variability was modeled as an additive (0.016 ng/ml) or proportional error (23%). Clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution (coefficient of variation) were 1.27 l/min (23%), 37.1 l (20%), 0.87 l/min (44%), and 92.7 l (22%), respectively. CONCLUSION: The pharmacokinetic parameter set derived from a normal-weight population accurately predicted plasma sufentanil concentrations in morbidly obese patients.