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Background Little is known about the outcomes of elderly patients admitted to the intensive care unit (ICU) with severe acute cholangitis (SAC). The objectives were to describe the 6-month mortality in patients with SAC ≥75 years and to identify factors associated with this mortality. Methods Bi-center retrospective study of critically ill elderly patients with SAC conducted between 2013 and 2017. Demographic and clinical variables of ICU and hospital stays with a 6-month follow-up were analyzed. Results 85 patients, with a median [Q1–Q3] age of 83 [80–89] years were enrolled of whom 51 (60%) were men. SAC was due to choledocholithiasis in 72 (85%) patients. Median [Q1–Q3] ICU length of stay was 3 [2–6] days. Median [Q1–Q3] admission SAPS II was 50 [42–70]. The ICU and 6-month mortality rates were 18% and 48% respectively. Multivariate analysis showed that malnutrition (OR = 34.5, 95% CI [1.4–817.9]) and a decrease in SOFA score at 48 h (OR by unit 0.7, 95% CI [0.5–0.9]) were associated with higher 6-month mortality. Conclusion In their decision-making process, ICU physicians and hepato-pancreato-biliary surgeons could use these data to estimate the probability of survival of an elderly patient presenting with SAC and to offer time-limited trials of intensive care. Trial registration NCT03831529.

Background Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage. Objectives To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes. Methods This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum β-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606). Results Forty-eight patients were included with a median (IQR) age of 64 (53–74) years and a SAPS II of 40 (32–65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered β-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64–0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target. Conclusions In severe IAIs, high doses of β-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal β-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.

SUMMARYLittle is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR. For 5 patients, SARS-CoV-2-specific T-cell polyfunctionality was assessed against Spike and Nucleoprotein SARS-CoV-2 peptides. Non-specific inflammation markers were increased in all patients. Median monocyte HLA-DR expression was below the 8,000 AB/C threshold defining acquired immunodepression. A “V” trend curve for lymphopenia, monocyte numbers, and HLA-DR expression was observed with a nadir between days 11-14 after symptoms’ onset. Intermediate CD14++CD16+monocytes increased early with a reduction in classic CD14++CD16-monocytes. Polyfunctional SARS-Cov-2-specific CD4 T-cells were present and functional, whereas virus-specific CD8 T-cells were less frequent and not efficient. We report a temporal variation of both innate and adaptive immunity in severe COVID-19 patients, helpful in guiding therapeutic decisions (e.g. anti-inflammatoryvs. immunostimulatory ones). We describe a defect in virus-specific CD8 T-cells, a potential biomarker of clinical severity. These combined data also provide helpful knowledge for vaccine design.Trial registration numberNCT04386395

Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been used as a biomarker in acute kidney injury (AKI). AKI is a common postoperative complication of aortic surgery. We sought to evaluate the performance of the immediately postoperative pNGAL level in comparison with the serum creatinine (SCr) level in predicting AKI and the need for renal replacement therapy (RRT).Prospective non-interventional study in a university hospital. Fifty patients undergoing elective or emergent major intra-abdominal aortic surgery were included. Comparisons between groups of patients with or without postoperative AKI, according to KDIGO staging, were made. Performance of NGAL was determined by examining the area under receiver operating characteristic (AUROC) curve.The incidence of AKI was 36%. At H+2, pNGAL values in AKI and non-AKI patients, respectively, were 221 [133-278] versus 50 [50-90] ng/mL (P0.0001), and SCr values were 115 [96-178] versus 90 [72-99] μmol/L (P0.0008). The AUROC of pNGAL for prediction of AKI was 0.90 (95% CI: 0.81-0.98) with an optimal cutoff of 112ng/mL, a sensitivity of 83%, specificity of 84%, and positive and negative predictive values of 75% and 90%, respectively. SCr produced an AUROC curve of 0.79 (0.65-0.92) at a cutoff of 110μmol/L. The diagnostic performance of pNGAL was significantly better than that of SCr (P=0.039). PNGAL at H+2 better predicted the RRT requirement [0.96 (0.90-1.0)] compared to SCr [0.86 (0.73-0.98)], but this difference was not statistically significant.A 2-hour postoperative determination of pNGAL outperformed SCr level in predicting postoperative AKI after major aortic surgery.

Background Smartphone to-do list app was hypothesized to be more efficient than a paper-based list in the management of workflow and to provide additional benefits. Purpose To analyze the impact of a mobile task-management application on the workflow of an ICU medical staff. Methods Superiority by a margin test, quasi-experimental study comparing the use of a smartphone application versus standard practice regarding tasks management in an academic ICU. Superiority margin was set at 8 % based on a pilot study. During two periods of 20 working days each (October 2018 and January 2019), medical staff managed tasks with both methods on a weekly rotation basis. Primary outcome was the proportion of daily tasks completed. Secondary outcomes assessed users’ satisfaction and the impact of the app in terms of changes in clinical practice. Results 25 ICU physicians were enrolled. A total of 1983 tasks were recorded. The proportion of completed tasks per day was higher when using the smartphone app (99 % [96–100] versus 95 % [93–98] for the standard group, p = 0.006), but did not reach the superiority margin. Smartphone application was perceived as positive experience, as participants felt that they forgot fewer tasks (p = 0.02), were more aware of their progress on ongoing or remaining tasks (p = 0.03) and observed an improvement in communication among the medical staff (p = 0.03). Conclusion This study failed to demonstrate the superiority of a smartphone app over paper-based lists regarding the proportion of daily tasks completed. However, positive feedback regarding the application was received from the medical staff.

BACKGROUND Decision to start an anti-fungal therapy in intra-abdominal candidiasis (IAC) is complex. Yeast culture, considered the gold standard, suffers from a delayed response time and exposes the patient to delayed introduction of anti-fungal therapy. We sought to evaluate the performance and feasibility of measuring 1,3-β-D-glucan (1,3-BDG) in the peritoneal fluid (PF) for the diagnosis of IAC. METHODS We analyzed retrospectively all PF obtained during abdominal surgery for critically ill adult patients presenting intra-abdominal infections. For each PF sample, direct examination, bacterial and fungal culture, fungal PCR and 1,3-BDG measurements were performed. The diagnostic performance of each technique and the Peritonitis score were calculated considering the positive yeast culture as the reference. The levels of 1,3-BDG were compared between IAC and non-IAC patients. RESULTS During an 8-month period in 2016, 33 PF samples were recovered. Median (interquartile range) SAPS 2 and SOFA scores were 44 (9-94) and 9 (4-15), respectively. There were seven cases of IAC, 14 of bacterial peritonitis and 12 of undocumented peritonitis. All IAC cases were secondary peritonitis, with a 1,3-BDG level of 1461 (325-5000) versus 224 (68-1357) pg/mL in the non-IAC group (P=0.03). When the 1,3-BDG level was ≤310 pg/mL, its negative predictive value was 100%. CONCLUSIONS In secondary peritonitis, a peritoneal measurement of 1,3-BDG ≤310 pg/mL could rule out IAC.

Summary Background & aims Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. Methods A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). Results Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5–2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. Conclusion The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.

International audience; Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.

BACKGROUND This prospective observational study aimed to assess the relevance of serial postoperative plasma neutrophil gelatinase-associated lipocalin (NGAL) measurements on prediction of early renal transplant function. METHODS Plasma NGAL (pNGAL) was measured (Triage NGAL Test; Biosite Inc., Inverness Medical) in 41 patients scheduled for kidney transplantation from deceased or living donors, immediately before and after surgery, and at 12 hr, day 1, day 3, and day 7. A delayed graft function (DGF) was defined as the need for dialysis during the first week. The results were expressed as median (Q1, Q3). RESULTS Of the 41 consecutive patients enrolled, all had a high preoperative pNGAL level: 453 ng/mL (382, 595). Fifteen (36.6%) presented a DGF. In patients with DGF, pNGAL was significantly higher at 12 hr (571 [467, 634] vs. 242 [158, 299] ng/mL, P

Continuous positive airway pressure (CPAP) is a useful treatment for patients with acute cardiogenic pulmonary oedema (CPE). However, its usefulness in the out-of-hospital setting has been poorly investigated and only by small and single-centre studies. We designed a multicentre randomised study to assess the benefit of CPAP initiated out of hospital. A total of 207 patients with CPE were randomly allocated by emergency mobile medical units to receive either standard treatment alone or standard treatment plus CPAP. CPAP was maintained after admission to the intensive care unit (ICU). Inclusion criteria were orthopnoea, respiratory rate greater than 25 breaths/min, pulse oximetry less than 90% in room air and diffuse crackles. The primary end point was assessed during the first 48 h and combined: death, presence of intubation criteria, persistence of either all inclusion criteria or circulatory failure at the second hour or their reappearance before 48 h. Absence of all criteria defined successful treatment. CPAP was used for 60 min [40, 65] (median [Q1, Q3]) in the pre-hospital setting and 120 min [60, 242] in ICU and was well tolerated in all patients. Treatment was successful in 79% of patients in the CPAP group and 63% in the control group (p = 0.01), especially for persistence of inclusion criteria after 2 h (12 vs. 26%) and for intubation criteria (4 vs. 14%). CPAP was beneficial irrespective of the initial PaCO2 or left ventricular ejection fraction. Immediate use of CPAP in out-of-hospital treatment of CPE and until CPE resolves after admission significantly improves early outcome compared with medical treatment alone.

Background and Purpose— Attempts to reverse cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) rely on a limited number of treatments. Calcium channel blockers have proven a benefit but their vasodilating effect on spastic cerebral arteries is relatively modest. Milrinone, a phosphodiesterase inhibitor, combines vasodilating and inotropic properties, but limited data exist to support its use for the treatment of CVS. We assessed the efficacy and tolerance of milrinone in patients with CVS secondary to aSAH. Methods— Twenty-two consecutive patients with angiographically-proven CVS (arterial diameter reduction >40%) have been studied. Intraarterial milrinone was infused in the cerebral territory(ies) involved and followed by continuous intravenous infusion until Day 14 after initial bleeding. We evaluated angiographic reversal of CVS, hemodynamic tolerance, and neurological outcome 1 year after aSAH. Results— Thirty-four selective intraarterial infusions of milrinone were required to treat 72 vasospastic territories. Intraarterial milrinone resulted in 53±37% increase in arterial diameter ( P Conclusion— This study suggests that milrinone is effective and safe for reversal of CVS after aSAH and should be tested in a large randomized trial.

Nocardia farcinica is an emerging pathogen in immunosuppressed patients causing both localized and disseminated infections. Many strains of this species are multidrug-resistant and require long-term antibiotic therapy, and consequently the choice of an oral treatment can be problematic. We report here the first case of successful treatment of N. farcinica brain abscess in a renal transplant recipient with an extended-spectrum fluoroquinolone, moxifloxacin.

To determine the regional cerebral oxygen saturation of hemoglobin (rcSO2) in severe preeclamptic parturients exhibiting neurologic symptoms compared with healthy pregnant women (control) and to describe the effects of MgSO4 infusion on rcSO2 and cerebral and systemic hemodynamic variables.Prospective, observational study.Obstetric critical care unit in a university-affiliated hospital.Twenty severe preeclamptic parturients presenting with neurologic signs before any administration of MgSO4, and 20 control parturients.Infusion of MgSO4 in severe preeclamptic patients.We measured rcSO2 using near-infrared spectroscopy, blood flow velocities of the middle cerebral artery, and cardiac output at baseline, 5 minutes, 1 hour, and 6 hours after the MgSO4 bolus (4 g), followed by continuous MgSO4 infusion (1 g/h). These measurements were also obtained in 20 control parturients at baseline and 6 hours. Baseline rcSO2 was significantly lower in the severe preeclamptic group: 61% (56-69) vs 66% (63-71) (p = 0.037). At inclusion, blood pressures were significantly higher in the severe preeclamptic group compared with the control group, whereas cardiac output and transcranial Doppler readings were similar. Five minutes after the MgSO4 bolus infusion, a median increase of 8.6% (3.2-18.1) in rcSO2 was observed (p = 0.007), reaching values of the control group that were maintained up to 6 hours. Blood pressures and systolic velocities of the middle cerebral artery significantly decreased (p0.01) after the MgSO4 bolus, whereas cardiac output did not change. The percentage increase in rcSO2 was negatively correlated to the mean blood pressure (r = 0.60, p0.0001).Cerebral oxygenation impairment can be detected by near-infrared spectroscopy monitoring in severe preeclamptic parturients. These results suggested the presence of disorders in cerebral microcirculation and/or changes in cerebral oxygenation. MgSO4 infusion in patients with severe preeclampsia restored rcSO2 to control levels with no systemic side effects. Further studies are needed to confirm the usefulness of near-infrared spectroscopy monitoring in patients with preeclampsia and to assess the action of other antihypertensive therapies on rcSO2.

Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

Animal studies have shown that halothane decreases total hepatic blood flow (THBF) by reducing both arterial (HABF) and portal (PVBF) inflow, whereas isoflurane appears to preserve them. In this study we assessed the effect of halothane and isoflurane on HABF and PVBF in surgical patients by using the pulsed Doppler technique. A validation study was conducted in six cynomolgus monkeys to compare the values of THBF obtained by the pulsed Doppler and indocyanine green clearance methods. Subsequently, six patients (ASA status I and II) undergoing elective open cholecystectomy were studied after surgery by using implanted pulsed Doppler probes. THBF and liver flow partition were compared during 1% halothane and 1.5% isoflurane (end-tidal concentrations). In the animal study, there was good agreement between the techniques (Bland and Altmann representation). In flunitrazepam-anesthetized patients, THBF was 1120 +/- 284 mL/min. Compared with this baseline and for a similar mean arterial blood pressure decrease (10%), THBF was maintained with isoflurane, whereas it decreased by 36% (P0.05) under halothane. With isoflurane, PVBF increased (25%; P = 0.067) with a maintained HABF. With halothane, both PVBF (-44%; P0.05) and HABF (-20%; P0.05) were reduced. Halothane acted mainly as a vasoconstrictor of the hepatic circulation, whereas isoflurane was a vasodilator, confirming the beneficial effect of isoflurane on hepatic oxygen supply.Volatile anesthetics may alter liver circulation with serious adverse effects. Using implanted pulsed Doppler probes in six anesthetized patients, we showed that halothane acted mainly as a vasoconstrictor of the liver vascular bed, whereas isoflurane was a vasodilator, confirming the beneficial effect of isoflurane on liver oxygen supply.

ContextTumor necrosis factor alpha (TNF-α) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-α gene promoter, has been associated with enhanced TNF-α production and negative outcome in some severe infections.ObjectivesTo investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock.DesignMulticenter case-control study conducted from March 1996 to June 1997.SettingSeven medical intensive care units in university hospitals.SubjectsEighty-nine patients with septic shock and 87 healthy unrelated blood donors.Main Outcome MeasuresFrequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-α concentrations.ResultsMortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P=.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P=.008). Concentrations of TNF-α were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24).ConclusionThe TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.

Background Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has suggested a potentially harmful effect on lactate metabolism and hepatic function. Methods Arterial oxygenation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (defined as a ratio of arterial oxygen pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with intravenous almitrine. In 21 of 25 patients, acute lung injury was related to primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and lung contusions. Results Intravenous almitrine increased the ratio of arterial oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107 mmHg (mean +/- SD). In eight patients (three men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decreased during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administration, and the results of other hepatic function tests, such as aspartate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almitrine was discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17 patients (14 men), the plasma lactate concentration and the hepatic function tests remained unaltered during intravenous almitrine therapy for > 60 h. Univariate and multivariate analyses revealed that an abnormal plasma concentration of total bilirubin before almitrine administration and female gender were the two factors significantly linked with lactic acidosis during almitrine infusion. Conclusions This study confirms that intravenous almitrine greatly improves arterial oxygenation in patients with acute lung injury but may also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic acidosis and hepatic dysfunction in the same patients strongly suggests that the liver is the primary source of intravenous almitrine-induced lactic acidosis.

The liver is implicated in many processes, and its failure induces severe consequences for metabolism, immune response, detoxification and antimicrobial defenses. The mechanisms involved in liver injury are complex and interactive, and can be artificially separated as chemical and immune injuries. The biochemical mechanisms concern various chemicals that are detoxified in the liver via cytochrome P-450 and conjugation. Toxic metabolites may alter plasma membrane, mitochondria, intracellular ion homeostasis, or degratative enzyme activity. Immune mechanisms involve cell cooperation, and are mediated by cytokines, nitric oxide, and complement. Pathologic apoptosis is potentially an important mechanism of acute liver injury. Specific attention is paid here to the more frequent causes of acute liver failure: hypoxia/reoxygenation, liver congestion, acetaminophen poisoning, posttransplant acute liver rejection, severe sepsis, viral hepatitis, and alcoholic liver disease. Knowledge of the intimate mechanisms of liver injury at the cellular level may lead to adaptation of therapeutic strategies that will prevent end-stage liver failure.

The physiological response to blood glucose elevation is the pancreatic release of insulin, which blocks hepatic glucose production and release, and stimulates glucose uptake and storage in insulin-dependent tissues. When this first regulatory level is overwhelmed (that is, by exogenous glucose supplementation), persistent hyperglycaemia occurs with intricate consequences related to the glucose acting as a metabolic substrate and as an intracellular mediator. It is thus very important to unravel the glucose metabolic pathways that come into play during stress as well as the consequences of these on cellular functions. During acute injuries, activation of serial hormonal and humoral responses inducing hyperglycaemia is called the 'stress response'. Central activation of the nervous system and of the neuroendocrine axes is involved, releasing hormones that in most cases act to worsen the hyperglycaemia. These hormones in turn induce profound modifications of the inflammatory response, such as cytokine and mediator profiles. The hallmarks of stress-induced hyperglycaemia include 'insulin resistance' associated with an increase in hepatic glucose output and insufficient release of insulin with regard to glycaemia. Although both acute and chronic hyperglycaemia may induce deleterious effects on cells and organs, the initial acute endogenous hyperglycaemia appears to be adaptive. This acute hyperglycaemia participates in the maintenance of an adequate inflammatory response and consequently should not be treated aggressively. Hyperglycaemia induced by an exogenous glucose supply may, in turn, amplify the inflammatory response such that it becomes a disproportionate response. Since chronic exposure to glucose metabolites, as encountered in diabetes, induces adverse effects, the proper roles of these metabolites during acute conditions need further elucidation.

To investigate the effects of local ophthalmic arterial fibrinolysis on central retinal venous occlusion (CRVO).Thirteen patients had recent severe nonischemic CRVO for which no alternative therapy was available. A flow-guide microcatheter was introduced coaxially via the femoral artery into the ophthalmic arterial ostium, and urokinase was perfused for 40 minutes. Vision, funduscopic findings, and retinal perfusion were assessed during 1 year of follow-up.Five of the 13 patients treated experienced visual improvement (P =.05) and retinal perfusion within 24-48 hours. Vision returned to normal within 24-48 hours in three patients, within 1 week in one patient, and within 1 month in one patient. These five patients exhibited progressive lesion regression within 2-4 weeks at funduscopy. Their clinical course prior to treatment resembled that of combined central retinal arterial occlusion (CRAO) and CRVO, which typically has a poor visual outcome. One patient relapsed 1 month after fibrinolysis. Of the remaining eight patients, one had normal vision at 12 months, and seven had no improvement. No technical complications were observed.Although there was no control group, the short period between fibrinolysis and substantial visual improvement, combined with marked retinal perfusion improvement, suggests that fibrinolysis is beneficial for CRVO, especially for recent CRAO and CRVO.

Introduction: The study objectives were to evaluate septic shockinduced alterations in skeletal muscle hemoglobin oxygenation saturation (StO 2 ) using near-infrared spectroscopy (NIRS) and forearm skin blood flow velocity using laser Doppler (LD) to determine the relationship of macroperfusion and microperfusion parameters, and to test the relationship of the worst NIRS parameters during the first 24 hours of shock with 28-day prognosis. Methods: A prospective, observational study was performed in a 21-bed university hospital surgical intensive care unit. Forty-three septic shock patients with at least another organ failure underwent a 3-minute, upper arm (brachial artery) vascular occlusion test (VOT). Microperfusion parameters (thenar eminence StO2 and forearm LD skin blood flow) were collected on days 1, 2 and 3, before (baseline StO2 and LD values) and during the 3-minute VOT with calculation of occlusion and reperfusion slopes for StO2 and LD. Daily Sequential Organ Failure Assessment (SOFA) score, macrohemodynamic parameters (systolic arterial blood pressure, cardiac output (pulmonary artery catheter or transesophageal Doppler), mixed venous oxygen saturation (pulmonary artery or superior vena cava catheter)) and metabolic parameters (pH, base excess, lactate) were determined. Results: Baseline StO 2 (82% (75 to 88) vs. 89% (85 to 92), P = 0.04) and reperfusion slope (2.79%/second (1.75 to 4.32) vs. 9.35%/second (8.32 to 11.57), P

Introduction To counter the shortage of kidney grafts in France, a non heart beating donor (NHBD) program has recently been implemented. The aim of this study was to describe this pilot program for kidney retrieval from "uncontrolled" NHBD meaning those for whom attempts of resuscitation after a witnessed out-of-hospital cardiac arrest (CA) have failed (Maastricht 1 and 2), in a centre previously trained for retrieval from brain dead donors. Methods A prospective, monocentric, descriptive study concerning NHBD referred to our institution from February 2007 to June 2008. The protocol includes medical transport of refractory CA under mechanical ventilation and external cardiac massage, kidney protection by insertion of an intraaortic double-balloon catheter (DBC) with perfusion of a hypothermic solution, kidney retrieval and kidney preservation in a hypothermic pulsatile perfusion machine. Results 122 potential NHBD were referred to our institution after a mean resuscitation attempt of 35 minutes (20–95). Regarding the contraindications, 63 were finally accepted and 56 had the DBC inserted. Organ retrieval was performed in 27 patients (43%) and 31 kidneys out of the 54 procured (57%) have been transplanted. Kidney transplantation exclusion was related to family refusal (n = 15), past medical history, time constraints, viral serology, high vascular ex vivo resistance of the graft and macroscopic abnormalities. The 31 kidneys exhibited an expected high delayed graft function rate (92%). Despite these initial results transplanted kidney had good creatinine clearance at six months (66 ± 24 ml/min) with a 89% graft survival rate at six months. Conclusions This study shows the feasibility and efficacy of an organ procurement program targeting NHBD allowing a 10% increase in the kidney transplantation rate over 17 months. With a six months follow-up period, the results of transplanted kidney function were excellent.