Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers.

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (n = 15) or as surgical prophylaxis (n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

Population Pharmacokinetics of Amikacin in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support leads to complex pharmacokinetic alterations, whereas adequate drug dosing is paramount for efficacy and absence of toxicity in critically ill patients. Amikacin is a major antibiotic used in nosocomial sepsis, especially for these patients. We aimed to describe amikacin pharmacokinetics on V-A ECMO support and to determine relevant variables to improve its dosing. All critically ill patients requiring empirical antimicrobial therapy, including amikacin for nosocomial sepsis supported or not by V-A ECMO, were included in a prospective population pharmacokinetic study. This population pharmacokinetic analysis was built with a dedicated software, and Monte Carlo simulations were performed to identify doses achieving therapeutic plasma concentrations. Thirty-nine patients were included (control n = 15, V-A ECMO n = 24); 215 plasma assays were performed and used for the modeling process. Patients received 29 (24-33) and 32 (30-35) mg/kg of amikacin in control and ECMO groups, respectively. Data were best described by a two-compartment model with first-order elimination. Inter-individual variabilities were observed on clearance, central compartment volume (V1), and peripherical compartment volume (V2). Three significant covariates explained these variabilities: Kidney Disease Improving Global Outcomes (KDIGO) stage on amikacin clearance, total body weight on V1, and ECMO support on V2. Our simulations showed that the adequate dosage of amikacin was 40 mg/kg in KDIGO stage 0 patients, while 25 mg/kg in KDIGO stage 3 patients was relevant. V-A ECMO support had only a secondary impact on amikacin pharmacokinetics, as compared to acute kidney injury.

Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality.

OBJECTIVES: We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections. DESIGN: We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy. SETTING: Twelve intensive care units. PATIENTS: We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups. CONCLUSION: The infectious process may not exert as strong a prognostic effect when severity, organ dysfunction and, above all, appropriateness of early antimicrobials are taken into account. Our findings emphasize the importance of developing valid recommendations for early antimicrobial therapy.

Out-of-hospital use of an automated chest compression device: facilitating access to extracorporeal life support or non-heart-beating organ procurement.

OBJECTIVE: The aim of the study was to assess the ease-of-use, safety, and usefulness of an automated external chest compression device for cardiopulmonary resuscitation. METHODS: Adults with out-of-hospital cardiac arrest (OHCA) were included prospectively. The emergency medical services (EMS) in a large suburb northeast of Paris (France) recorded data for standard criteria for EMS care for CA and specific criteria on device use-application time, ease of application and use (visual analog scale score: 0, impossible; 5, very easy), technical incidents, and clinical complications. RESULTS: We attended 4868 OHCA patients (January 2005 to April 2010) and used the device in 285 patients (6%) (212 males [74%], 73 females [26%]; median age, 56 [43-70] years). Results (medians with 25-75 percentiles) were as follows: time to apply device, 30 seconds (20-60); ease of application and activation, 5 (4-5) and 5 (5-5), respectively; duration of use, 30 (20-41) minutes; return to spontaneous circulation (ROSC), 76 patients (27%); and time to ROSC, 19 (12-32) minutes after placement. Twenty-seven patients (9%) with refractory CA benefited from extracorporeal life support. Overall, 32 patients were alive after 24 hours, 11 at 7 days, and 3 at 1 month. An additional 23 patients (8%) with refractory CA were selected for non-heart-beating kidney procurement. Ten patients were used to harvest kidneys and 15 were transplanted. There were 21 technical incidents (7%) and 19 clinical complications (7%). CONCLUSION: The device was easy to use in routine emergency practice and of particular value in facilitating access to extracorporeal life support or non-heart-beating organ procurement. These uses should be itemized in all OHCA studies.

Infectious risk associated with arterial catheters compared with central venous catheters.

BACKGROUND: Scheduled replacement of central venous catheters and, by extension, arterial catheters, is not recommended because the daily risk of catheter-related infection is considered constant over time after the first catheter days. Arterial catheters are considered at lower risk for catheter-related infection than central venous catheters in the absence of conclusive evidence. OBJECTIVES: To compare the daily risk and risk factors for colonization and catheter-related infection between arterial catheters and central venous catheters. METHODS: We used data from a trial of seven intensive care units evaluating different dressing change intervals and a chlorhexidine-impregnated sponge. We determined the daily hazard rate and identified risk factors for colonization using a marginal Cox model for clustered data. RESULTS: We included 3532 catheters and 27,541 catheter-days. Colonization rates did not differ between arterial catheters and central venous catheters (7.9% [11.4/1000 catheter-days] and 9.6% [11.1/1000 catheter-days], respectively). Arterial catheter and central venous catheter catheter-related infection rates were 0.68% (1.0/1000 catheter-days) and 0.94% (1.09/1000 catheter-days), respectively. The daily hazard rate for colonization increased steadily over time for arterial catheters (p = .008) but remained stable for central venous catheters. Independent risk factors for arterial catheter colonization were respiratory failure and femoral insertion. Independent risk factors for central venous catheter colonization were trauma or absence of septic shock at intensive care unit admission, femoral or jugular insertion, and absence of antibiotic treatment at central venous catheter insertion. CONCLUSIONS: The risks of colonization and catheter-related infection did not differ between arterial catheters and central venous catheters, indicating that arterial catheter use should receive the same precautions as central venous catheter use. The daily risk was constant over time for central venous catheter after the fifth catheter day but increased significantly over time after the seventh day for arterial catheters. Randomized studies are needed to investigate the impact of scheduled arterial catheter replacement.

Chlorhexidine-impregnated sponges and less frequent dressing changes for prevention of catheter-related infections in critically ill adults: a randomized controlled trial.

CONTEXT: Use of a chlorhexidine gluconate-impregnated sponge (CHGIS) in intravascular catheter dressings may reduce catheter-related infections (CRIs). Changing catheter dressings every 3 days may be more frequent than necessary. OBJECTIVE: To assess superiority of CHGIS dressings regarding the rate of major CRIs (clinical sepsis with or without bloodstream infection) and noninferiority (less than 3% colonization-rate increase) of 7-day vs 3-day dressing changes. DESIGN, SETTING, AND PATIENTS: Assessor-blind, 2 x 2 factorial, randomized controlled trial conducted from December 2006 through June 2008 and recruiting patients from 7 intensive care units in 3 university and 2 general hospitals in France. Patients were adults (>18 years) expected to require an arterial catheter, central-vein catheter, or both inserted for 48 hours or longer. INTERVENTIONS: Use of CHGIS vs standard dressings (controls). Scheduled change of unsoiled adherent dressings every 3 vs every 7 days, with immediate change of any soiled or leaking dressings. MAIN OUTCOME MEASURES: Major CRIs for comparison of CHGIS vs control dressings; colonization rate for comparison of 3- vs 7-day dressing changes. RESULTS: Of 2095 eligible patients, 1636 (3778 catheters, 28,931 catheter-days) could be evaluated. The median duration of catheter insertion was 6 (interquartile range [IQR], 4-10) days. There was no interaction between the interventions. Use of CHGIS dressings decreased the rates of major CRIs (10/1953 [0.5%], 0.6 per 1000 catheter-days vs 19/1825 [1.1%], 1.4 per 1000 catheter-days; hazard ratio [HR], 0.39 [95% confidence interval {CI}, 0.17-0.93]; P = .03) and catheter-related bloodstream infections (6/1953 catheters, 0.40 per 1000 catheter-days vs 17/1825 catheters, 1.3 per 1000 catheter-days; HR, 0.24 [95% CI, 0.09-0.65]). Use of CHGIS dressings was not associated with greater resistance of bacteria in skin samples at catheter removal. Severe CHGIS-associated contact dermatitis occurred in 8 patients (5.3 per 1000 catheters). Use of CHGIS dressings prevented 1 major CRI per 117 catheters. Catheter colonization rates were 142 of 1657 catheters (7.8%) in the 3-day group (10.4 per 1000 catheter-days) and 168 of 1828 catheters (8.6%) in the 7-day group (11.0 per 1000 catheter-days), a mean absolute difference of 0.8% (95% CI, -1.78% to 2.15%) (HR, 0.99; 95% CI, 0.77-1.28), indicating noninferiority of 7-day changes. The median number of dressing changes per catheter was 4 (IQR, 3-6) in the 3-day group and 3 (IQR, 2-5) in the 7-day group (P < .001). CONCLUSIONS: Use of CHGIS dressings with intravascular catheters in the intensive care unit reduced risk of infection even when background infection rates were low. Reducing the frequency of changing unsoiled adherent dressings from every 3 days to every 7 days modestly reduces the total number of dressing changes and appears safe. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00417235.

An underrecognized source of organ donors: patients with brain death after successfully resuscitated cardiac arrest.

OBJECTIVE: To identify predictors of brain death after successful resuscitation of out-of-hospital cardiac arrest (OHCA), with the goal of improving the detection of brain death, and to evaluate outcomes of solid organs harvested from these patients. DESIGN AND SETTING: Prospective observational cohort study in a medical and surgical unit of a nonuniversity hospital. PATIENTS: Patients with successfully resuscitated OHCA were prospectively included in a database over a 7-year period. We looked for early predictors of brain death and compared outcomes of organ transplants from these patients to those from patients with brain death due to head injury or stroke. RESULTS: Over the 7-year period 246 patients were included. No early predictors of brain death were found. Of the 40 patients (16%) who met criteria for brain death, after a median ICU stay of 2.5 days (IQR 2.0-4.2), 19 donated 52 solid organs (29 kidneys, 14 livers, 7 hearts, and 2 lungs). Outcomes of kidneys and livers did not differ between donors with and without resuscitated cardiac arrest. CONCLUSIONS: Brain death may occur in about one-sixth of patients after successfully resuscitated OHCA, creating opportunities for organ donation.

Aspergillus mediastinitis after cardiac surgery.

BACKGROUND: Mediastinitis is a serious complication after cardiac surgery. While bacteria are the more common pathogens, fungal infections are rare. In particular, several cases of postoperative Aspergillus mediastinitis have been reported, the majority of which had an extremely poor outcome. METHODS: A case of mediastinitis in a 42-year-old patient due to Aspergillus fumigatus after cardiac surgery is described. Two main risk factors were found: cardiogenic shock requiring veno-arterial extracorporeal life support and failure of primary closure of the sternum. A full recovery was attained after surgical drainage and antifungal therapy with liposomal amphotericin B, followed by a combination of voriconazole and caspofungin. The patient was followed for 18 months without relapse. RESULTS: This is an extremely rare case of postoperative Aspergillus mediastinitis exhibiting a favourable outcome. Based on a systematic review of the literature, previous cases were examined with a focus on risk factors, antifungal therapies, and outcomes. CONCLUSION: The clinical features of postoperative Aspergillus mediastinitis may be paucisymptomatic, emphasizing the need for a low index of suspicion in cases of culture-negative mediastinitis or in indolent wound infections. In addition to surgical debridement, the central component of antifungal therapy should include amphotericin B or voriconazole.

Impact of early nutrition and feeding route on outcomes of mechanically ventilated patients with shock: a post hoc marginal structural model study.

PURPOSE: Few data are available about optimal nutrition modalities in mechanically ventilated patients with shock. Our objective was to assess associations linking early nutrition (<48 h after intubation), feeding route and calorie intake to mortality and risk of ventilator-associated pneumonia (VAP) in patients with invasive mechanical ventilation (IMV) and shock. METHODS: In the prospective OutcomeRea database, we identified adults with IMV >72 h and shock (arterial systolic pressure <90 mmHg) within 48 h after intubation. A marginal structural Cox model was used to create a pseudo-population in which treatment was unconfounded by subject-specific characteristics. RESULTS: We included 3,032 patients. Early nutrition was associated with lower day-28 mortality [HR 0.89, 95 % confidence interval (CI) 0.81-0.98, P = 0.01] and day-7 mortality (HR 0.76, CI 0.66-0.87, P < 0.001) but not with lower day-7 to day-28 mortality (HR 1.00, CI 0.89-1.12, P = 0.98). Early nutrition increased VAP risk over the 28 days (HR 1.08, CI 1.00-1.17, P = 0.046) and until day 7 (HR 7.17, CI 6.27-8.19, P < 0.001) but decreased VAP risk from days 7 to 28 (HR 0.85, CI 0.78-0.92, P < 0.001). Compared to parenteral feeding, enteral feeding was associated with a slightly increased VAP risk (HR 1.11, CI 1.00-1.22, P = 0.04) but not with mortality. Neither mortality nor VAP risk differed between early calorie intakes of ≥20 and <20 kcal/kg/day. CONCLUSION: In mechanically ventilated patients with shock, early nutrition was associated with reduced mortality. Neither feeding route nor early calorie intake was associated with mortality. Early nutrition and enteral feeding were associated with increased VAP risk.

Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in intensive care unit patients with alcoholic cirrhosis.

INTRODUCTION: Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. PATIENTS: Ninety-three patients with compensated or decompensated cirrhosis (CLF group) but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group), were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at -80°C until (1)H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. RESULTS: The predictability of the model was 0.73 (Q(2) Y) and the explained variance was 0.63 (R(2) Y). The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. CONCLUSION: A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with (1)H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function.

Acute respiratory distress syndrome and risk of AKI among critically ill patients.

BACKGROUND AND OBJECTIVES: Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded. RESULTS: This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001). CONCLUSIONS: ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.

Influence of early dysnatremia correction on survival of critically ill patients.

Increasing evidence suggests that dysnatremia at intensive care unit (ICU) admission may predict mortality. Little information is available, however, on the potential effect of dysnatremia correction. This is an observational multicenter cohort study in patients admitted between 2005 and 2012 to 18 French ICUs. Hyponatremia and hypernatremia were defined as serum sodium concentration less than 135 and more than 145 mmol/L, respectively. We assessed the influence on day 28 mortality of dysnatremia correction by day 3 and of the dysnatremia correction rate. Of 7,067 included patients, 1,830 (25.9%) had hyponatremia and 634 (9.0%) had hypernatremia at ICU admission (day 1). By day 3, hyponatremia had been corrected in 1,019 (1,019/1,830; 55.7%) and hypernatremia in 393 (393/634; 62.0%) patients. After adjustment for confounders, persistent hyponatremia or hypernatremia on day 3 was independently associated with higher day 28 mortality (odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.06 - 1.61; and OR, 1.86; 95% CI, 1.37 - 2.54; respectively). Hyponatremia corrected by day 3, hypernatremia corrected by day 3, and ICU-acquired hyponatremia were not associated with day 28 mortality. Median correction rate from days 1 to 3 was 2.58 mmol/L per day (interquartile range, 0.67 - 4.55). Higher natremia correction rate was associated with lower crude and adjusted day 28 mortality rates (OR per mmol/L per day, 0.97; 95% CI, 0.94 - 1.00; P = 0.04; and OR per mmol/L per day, 0.93; 95% CI, 0.90 - 0.97; P = 0.0003, respectively). Our results indicate that dysnatremia correction is independently associated with survival, with the effect being greater with faster correction rates of up to 12 mmol/L per day.

Usefulness of routine laboratory parameters in the decision to treat refractory cardiac arrest with extracorporeal life support.

AIM: To evaluate the usefulness of routine laboratory parameters in the decision to treat refractory cardiac arrest patients with extracorporeal life support (ECLS). METHODS: Sixty-six adults with witnessed cardiac arrest of cardiac origin unrelated to poisoning or hypothermia undergoing cardiopulmonary resuscitation without return of spontaneous circulation (duration: 155 min [120-180], median, [25-75%-percentiles]) were included in a prospective cohort-study. ECLS was implemented under cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane-oxygenator, aiming to maintain ECLS flow ≥ 2.5 l/min and mean arterial pressure ≥ 60 mm Hg. RESULTS: Forty-seven of 66 patients died within 24 h from multiorgan failure and massive capillary leak. Of 19/66 patients who survived ≥ 24 h with stable circulatory conditions permitting neurological evaluation, four became conscious and were transferred for further cardiac assistance, while three became organ donors. Ultimately, one patient survived without neurologic sequelae after cardiac transplantation. Using multivariate analysis, only pre-cannulation peripheral venous oxygen saturation (SpvO2, 28% [15-52]) independently predicted inability to maintain targeted ECLS conditions ≥ 24 h (odds ratio for each 10%-decrease [95%-confidence interval]: 1.65 [1.21; 2.25], p=0.002). The area under the receiver-operating-characteristics curve was 0.78 [0.63; 0.93]. SpvO2 cut-off value of 33% was associated with a sensitivity of 0.68 [0.50; 0.83] and specificity of 0.81 [0.54; 0.96]. SpvO2 ≤ 8%, lactate concentration ≥ 21 mmol/l, fibrinogen ≤ 0.8 g/l, and prothrombin index ≤ 11% predicted premature ECLS discontinuation with a specificity of 1. CONCLUSION: SpvO2 is useful to predict the inability of maintaining refractory cardiac arrest victims on ECLS without detrimental capillary leak and multiorgan failure until neurological evaluation.

[Screening for carbon monoxide (CO) poisoning by general practitioners in home visits]. / Dépistage des intoxications au monoxyde de carbone (CO) par des médecins généralistes effectuant des visites à domicile.

OBJECTIVE: To evaluate the interest of carbon monoxide (CO) detector used by general practionners visiting patients at home. METHODS: CO detector (cost: 200 euros) was attributed to 300 general practionners visiting at least 20 patients at home per week. Alarm was triggered when ambient CO concentration exceeded 80ppm. Measurement of CO in expired breath was also possible. Activity and alarms were prospectively collected. Circumstances of intoxication were recorded. Evaluation was finally performed. The end-poind was to quantify CO-poisoning detected by the use of the device and the cost of this stratégy. RESULTS: From November 2001 to November 2004, 65 scenes of intoxication with 79 victims were prospectively reported by 12 general practionners. Final evaluation revealed that 23 physicians omitted to declare alarms. Alarm incidence was of 1 for 17.527 visits; with a related cost of approximately 858 euros for 24 months. Ambient carbon monoxide concentration exceeded 200ppm in 25% of cases. Hospital admission was required for 91% of the victims. Hyperbaric oxygen therapy was performed in two cases. General practionners (n=272) considered that CO detector was useful for safety reasons (91%), they wanted to continue the experience, but did not plan to buy such device (59%). DISCUSSION: Use of CO detectors by general practionners visiting patients at home allowed to identify 65 scenes of CO intoxication. In most cases, the cause of the visit did not suggested CO poisoning. The cost of the device seems to limits its large use. CONCLUSION: CO detector is a safety tool for both general prationners and patients. Its large use has to be questioned.

Immune status and apoptosis activation during brain death.

The present study evaluates the role of the inflammatory status and apoptosis activation in the development of organ dysfunction after brain death using plasma assays and macroarray analysis on skeletal muscle biopsies to look for evidence of remote tissue damage in two intensive care units in France and one in Belgium. As controls, we used patients undergoing hip surgery and healthy volunteers. Causes of brain death in the 85 consecutive patients included in the study were cardiac arrest (n = 29; 34%), stroke (n = 42; 49%, with 38 patients having hemorrhagic stroke), and head injury (n = 14; 17%). Of the 85 patients, 45 donated 117 organs. Plasma endotoxin and cytokine levels indicated a marked systemic inflammatory response in brain-dead patients, which was strongest in the cardiac arrest group. Leukocyte dysfunction, as assessed by cytokines production in response to various stimuli, was noted in a subgroup of patients with brain death after stroke. Interestingly, skeletal muscle biopsies showed no increase in mRNAs for genes related to inflammation, whereas mRNAs for both antiapoptotic and proapoptotic genes were increased, the balance being in favor of apoptosis induction. The increased activation of the proapoptotic caspase 9 was further confirmed by Western blot. In conclusion, the presence of inflammation and apoptosis induction may explain the rapid organ dysfunction seen after brain death. Both abnormalities may play a role in organ dysfunction associated with brain death. However, the level of systemic inflammation or the presence of circulating endotoxin was not associated with lower graft survival.