Johan Decruyenaere

Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial

BACKGROUND Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis. METHODS We did a double-blind, randomised, multinational non-inferiority study to compare micafungin (100 mg/day) with liposomal amphotericin B (3 mg/kg per day) as first-line treatment of candidaemia and invasive candidosis. The primary endpoint was treatment success, defined as both a clinical and a mycological response at the end of treatment. Primary analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00106288. FINDINGS 264 individuals were randomly assigned to treatment with micafungin; 267 were randomly assigned to receive liposomal amphotericin B. 202 individuals in the micafungin group and 190 in the liposomal amphotericin B group were included in the per-protocol analyses. Treatment success was observed for 181 (89.6%) patients treated with micafungin and 170 (89.5%) patients treated with liposomal amphotericin B. The difference in proportions, after stratification by neutropenic status at baseline, was 0.7% (95% CI -5.3 to 6.7). Efficacy was independent of the Candida spp and primary site of infection, as well as neutropenic status, APACHE II score, and whether a catheter was removed or replaced during the study. There were fewer treatment-related adverse events--including those that were serious or led to treatment discontinuation--with micafungin than there were with liposomal amphotericin B. INTERPRETATION Micafungin was as effective as--and caused fewer adverse events than--liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.

Acute Renal Failure in Patients with Sepsis in a Surgical ICU: Predictive Factors, Incidence, Comorbidity, and Outcome

Acute renal failure (ARF) is a common complication in intensive care unit (ICU) patients. Although there are several reports on outcome of septic patients with ARF, there are no data regarding predisposing factors for ARF. Therefore, the incidence of ARF was investigated in 185 sepsis patients admitted in a surgical ICU during a 16-mo period. Variables predisposing to ARF on day 1 of sepsis were evaluated with univariate and multivariable analyses. APACHE II and SOFA scores were compared during a 14-d period. Additionally, the impact of organ failure on mortality was evaluated. ARF developed in 16.2% of the patients, and 70.0% of these needed renal replacement therapy (RRT). Patients with ARF were more severely ill and had a higher mortality. Remarkably, serum creatinine was already increased on day 1. Creatinine > 1 mg/dl and pH < 7.30, both on day 1 of sepsis, were independently associated with ARF. Age, need for vasoactive therapy, mechanical ventilation, and RRT, but not ARF itself, were associated with mortality. In conclusion, ARF was a frequent complication in sepsis. Sepsis patients with ARF were more severely ill and had a higher mortality. Need for RRT was independently associated with mortality. A simple risk model for ARF, on basis of two readily available parameters on day 1 of sepsis, was developed. This model allows initiating specific therapeutic measures earlier in the course of sepsis, hopefully resulting in a lower incidence of ARF and needi for RRT, thereby lowering mortality.

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

RATIONALE Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. OBJECTIVES We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. METHODS Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. MEASUREMENTS AND MAIN RESULTS Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. CONCLUSIONS Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients

Abstract Monitoring the depth of sedation in patients under intensive care is difficult. Clinical assessment by the different scoring systems produces insufficient information, especially once deeply sedated patients become unresponsive to any external stimulation. Recently, the bispectral index (BIS), the result of computerized bispectral electroencephalographic monitoring, was found to be the best predictor of depth of anaesthesia during surgical intervention. This report concerns BIS monitoring in 18 randomly selected, deeply sedated, surgical patients in the intensive care unit, who were unresponsive to standard clinical stimulation (Ramsay sedation score). A wide range of BIS was observed, with 15 of the patients having a BIS below 60, indicating a state of deep sedation (or possibly oversedation). Therefore, further studies using BIS monitoring in patients under intensive care are needed to determine if this method can guide sedation and prevent oversedation in this context and, most importantly, to analyse its final cost – benefit ratio.

Modulation of Portal Graft Inflow: A Necessity in Adult Living-donor Liver Transplantation?

ObjectiveTo evaluate the clinical significance of modulating the recipient portal inflow (rPVF) through perioperative ligation of the splenic artery in adult living-donor liver transplantation (ALDLTx) by focusing on vascular complications, intractable ascites production, and the prevention of small-for-size syndrome (SFSS). Summary Background DataIn ALDLTx, portal graft flow is enhanced to at least twice the donor value, raising the total liver inflow. Recipient hepatic arterial flow (rHAF) is lower than expected. Portal hyperperfusion of small grafts in larger recipients is thought to be one of the main causes of posttransplant graft dysfunction/SFSS. MethodsSeventeen ALDLTx were reviewed for a minimum of 2 months. Patients were divided retrospectively into two groups: G1 (n = 7), without modulation of rPVF, and G2 (n = 10), with splenic artery ligation to decrease rPVF perioperatively. Donor and recipient hepatic hemodynamics were evaluated against graft function and outcome, including correlations between rPVF, graft weight, graft:recipient body weight ratio, and recipient weight. ResultsFollowing portal and arterial reperfusion, mean rPVF and rPVF/graft weight were much higher than in the donors, whereas mean rHAF and rHAF/graft weight were much lower. No differences were found between groups, except for rPVF and rHAF, which were much more higher and lower, respectively, before splenic artery ligation. In G1 patients, SFSS was seen in two patients and vascular complications occurred in two others. In G2 patients, splenic artery ligation permitted a significant decrease in rPVF, an improvement in rHAF, and the resolution of refractory ascites. Neither SFSS nor vascular complications were seen in G2 patients. ConclusionsWhen a suboptimal graft:recipient body weight ratio is accompanied by high rPVF in ALDLTx, the portal flow should be modulated perioperatively; splenic artery ligation is a simple and safe method that is sufficient to allow this modulation in most patients.

Impact of computerized physician order entry on medication prescription errors in the intensive care unit: a controlled cross-sectional trial

IntroductionMedication errors in the intensive care unit (ICU) are frequent and lead to attributable patient morbidity and mortality, increased length of ICU stay and substantial extra costs. We investigated if the introduction of a computerized ICU system (Centricity Critical Care Clinisoft, GE Healthcare) reduced the incidence and severity of medication prescription errors (MPEs).MethodsA prospective trial was conducted in a paper-based unit (PB-U) versus a computerized unit (C-U) in a 22-bed ICU of a tertiary university hospital. Every medication order and medication prescription error was validated by a clinical pharmacist. The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines. An independent panel evaluated the severity of MPEs. We identified three groups: minor MPEs (no potential to cause harm); intercepted MPEs (potential to cause harm but intercepted on time); and serious MPEs (non-intercepted potential adverse drug events (ADE) or ADEs, being MPEs with potential to cause, or actually causing, patient harm).ResultsThe C-U and the PB-U each contained 80 patient-days, and a total of 2,510 medication prescriptions were evaluated. The clinical pharmacist identified 375 MPEs. The incidence of MPEs was significantly lower in the C-U compared with the PB-U (44/1286 (3.4%) versus 331/1224 (27.0%); P < 0.001). There were significantly less minor MPEs in the C-U than in the PB-U (9 versus 225; P < 0.001). Intercepted MPEs were also lower in the C-U (12 versus 46; P < 0.001), as well as the non-intercepted potential ADEs (21 versus 48; P < 0.001). There was also a reduction of ADEs (2 in the C-U versus 12 in the PB-U; P < 0.01). No fatal errors occurred. The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups. Patients with renal failure experienced less dosing errors in the C-U versus the PB-U (12 versus 35 serious MPEs; P < 0.001).ConclusionThe ICU computerization, including the medication order entry, resulted in a significant decrease in the occurrence and severity of medication errors in the ICU.

Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class

Objective:To evaluate whether a real-time electronic alert system or “AKI sniffer,” which is based on the RIFLE classification criteria (Risk, Injury and Failure), would have an impact on therapeutic interventions and acute kidney injury progression. Design:Prospective intervention study. Setting:Surgical and medical intensive care unit in a tertiary care hospital. Patients:A total of 951 patients having in total 1,079 admission episodes were admitted during the study period (prealert control group: 227, alert group: 616, and postalert control group: 236). Interventions:Three study phases were compared: A 1.5-month prealert control phase in which physicians were blinded for the acute kidney injury sniffer and a 3-month intervention phase with real-time alerting of worsening RIFLE class through the Digital Enhanced Cordless Technology telephone system followed by a second 1.5-month postalert control phase. Measurements and Main Results:A total of 2593 acute kidney injury alerts were recorded with a balanced distribution over all study phases. Most acute kidney injury alerts were RIFLE class risk (59.8%) followed by RIFLE class injury (34.1%) and failure (6.1%). A higher percentage of patients in the alert group received therapeutic intervention within 60 mins after the acute kidney injury alert (28.7% in alert group vs. 7.9% and 10.4% in the pre- and postalert control groups, respectively, p &mgr; .001). In the alert group, more patients received fluid therapy (23.0% vs. 4.9% and 9.2%, p &mgr; .01), diuretics (4.2% vs. 2.6% and 0.8%, p &mgr; .001), or vasopressors (3.9% vs. 1.1% and 0.8%, p &mgr; .001). Furthermore, these patients had a shorter time to intervention (p &mgr; .001). A higher proportion of patients in the alert group showed return to a baseline kidney function within 8 hrs after an acute kidney injury alert “from normal to risk” compared with patients in the control group (p = .048). Conclusions:The real-time alerting of every worsening RIFLE class by the acute kidney injury sniffer increased the number and timeliness of early therapeutic interventions. The borderline significant improvement of short-term renal outcome in the RIFLE class risk patients needs to be confirmed in a large multicenter trial. (Crit Care Med 2012; 40:–1170)

Development and validation of a model for prediction of mortality in patients with acute burn injury

The objective was to develop a user‐friendly model to predict the probability of death from acute burns soon after injury, based on burned surface area, age and presence of inhalation injury.

Thrombocytopenia and outcome in critically ill patients with bloodstream infection.

OBJECTIVE Thrombocytopenia is common in intensive care units (ICUs), and is associated with a poor prognosis. An acute decrease in total platelet count is frequently observed in severe sepsis, followed by a relative increase indicating organ-failure recovery. However, few data are available describing this effect and its relationship with outcomes in specific subgroups of ICU patients. METHODS A retrospective, observational cohort study was conducted to investigate the incidence and prognosis of thrombocytopenia in a cohort of critically ill patients (n=155) with a microbiologically documented nosocomial bloodstream infection. RESULTS Thrombocytopenia occurred more frequently in nonsurvivors. The ICU mortality rates increased according to severity of thrombocytopenia. Thrombocytopenia was independently associated with worse outcomes in ICU patients with nosocomial bloodstream infection. CONCLUSION Determining trends in platelet counts is of additional prognostic value, compared with single measurements.

Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?

BackgroundCorrect antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.MethodsThis was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.ResultsWe obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% f T>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% f T>MIC.ConclusionsIn this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.