Laurent Amigues

Superoxide anion overproduction in sepsis: Effects of vitamin E and simvastatin

Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2°−) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2°− production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2°− production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2°− production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2°− production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2°−. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation.

Outcome of renal transplant recipients admitted to an intensive care unit: a 10-year cohort study.

Background. Epidemiology and prognosis of severe complications related to renal transplantation requiring admission to intensive care unit (ICU) have not been assessed precisely. This study was undertaken to evaluate the outcome in this population and to identify the factors of prognosis. Methods. All records of adult renal transplant recipients admitted to our ICU from 1997 to 2007 were reviewed including transplant variables, clinical and biological parameters, use of mechanical ventilation, catecholamine support, or dialysis or both. Mortality was assessed and data were analyzed to identify predictive factors of outcome. Results. Twenty-seven women and 30 men, median age 54 years, were included in the study. Eighteen patients were oliguric, 35 were mechanically ventilated, 32 underwent hemodialysis, and 36 needed catecholamine. Twenty-three patients died (40.3%), a mortality significantly higher than in a matched by age and gravity scores control group of nontransplant ICU patients. By univariate analysis, survivors had a significantly lower ICU severity scores, a higher mean arterial pressure, a higher Glasgow Coma Score, a higher serum albumin, and a lower serum lactate on ICU admission. The need for catecholamine support, mechanical ventilation or dialysis or both during the ICU stay worsens the outcome significantly. Using the multivariate analysis, only the mean arterial pressure and the need for mechanical ventilation were predictive of mortality. Conclusion. The incidence of severe transplant-related complications requiring an admission to an ICU was at 16 of 1000 patients year with a mortality rate higher than the general ICU population (40% vs. 20%). These data suggest that immunosuppressive treatment of transplant patients with severe complications worsens significantly their outcome.

Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality.

The aim of this study was to evaluate and compare brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels as mortality prognosticator and predictor for myocardial dysfunction in severe sepsis and septic shock. Baseline clinical and biological variables were collected from 47 patients with severe sepsis or septic shock. Ventricular systolic function assessed by echocardiography was measured over a 5-day period. Both cTnI and BNP plasmatic levels were determined at intensive care unit (ICU) admission and during the following 15 days. At admission, cTnI and BNP levels were compared to those of 12 control critically ill nonseptic patients. The plasma levels of BNP and cTnI in patients with sepsis were elevated at admission and significantly higher than in the controls. Among patients with sepsis, BNP levels were significantly more elevated in nonsurvivors compared to survivors at admission and 1 day later. The cTnI levels were also significantly more elevated in nonsurvivors compared to survivors, but only at admission. From admission to day 5, patients with sepsis with left ventricular systolic dysfunction had higher BNP plasmatic concentrations than those without; differences were significant at days 3 and 4. In contrast, plasma cTnI levels were similar between the 2 groups. In critically ill patients, sepsis induces significant increase in BNP and cTnI levels. High BNP and cTnI plasma levels during ICU admission appear to be associated with poor outcome of sepsis. Time course of BNP levels seems helpful to discriminate between surviving and nonsurviving patients with sepsis and to detect myocardial dysfunction where troponin levels fail to do so.

Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients.

BackgroundThe soluble CD14 subtype, Presepsin, appears to be an accurate sepsis diagnostic marker, but data from intensive care units (ICUs) are scarce. This study was conducted to evaluate the diagnostic and prognostic value of Presepsin in ICU patients with severe sepsis (SS), septic shock (SSh) and severe community-acquired pneumonia (sCAP).MethodsPresepsin and procalcitonin (PCT) levels were determined for patients at admission to ICU. Four groups have been differentiated: (1) absence or (2) presence of systemic inflammatory response syndrome, (3) SS or (4) SSh; and 2 groups, among the patients admitted for acute respiratory failure: absence or presence of sCAP. Biomarkers were tested for diagnosis of SS, SSh and sCAP and for prediction of ICU mortality.ResultsOne hundred and forty-four patients were included: 44 SS and 56 SSh. Plasma levels of Presepsin and PCT were significantly higher in septic than in non-septic patients and in SSh as compared to others. The sepsis diagnostic accuracy of Presepsin was not superior to that of PCT (AUC: 0.75 vs 0.80). In the 72/144 patients admitted for acute respiratory failure, the capability of Presepsin to diagnose sCAP was significantly better than PCT. Presepsin levels were also predictive of ICU mortality in sepsis and in sCAP patients.ConclusionPlasma levels of Presepsin were useful for the diagnosis of SS, SSh and sCAP and may predict ICU mortality in these patients.

Electrolytes-Enriched Hemodiafiltration Solutions for Continuous Renal Replacement Therapy in Acute Kidney Injury: A Crossover Study.

Aims: To evaluate the capability of an electrolytes-enriched solution to prevent metabolic disorders during continuous veno-venous hemodiafiltration (CVVHDF). Methods: Serum biochemistry and clinical tolerance were compared during CVVHDF treatments with an electrolyte-enriched (Phoxilium) or standard solutions in 10 acute renal failure patients. Results: As compared to standard fluids, serum potassium and phosphate levels were maintained in the normal range with Phoxilium without any supplementation but total serum calcium levels were significantly lower. Bicarbonatemia was slightly higher (24-26 vs. 21.5-24.5 mmol/l, p < 0.05) with conventional solutions and was associated with a significant increased level of pH (>7.44). Despite the absence of glucose in the Phoxilium solution, blood glucose levels and glucose supplementation were similar between treatments. Clinical tolerance and efficiency of CVVHDF sessions were comparable. Conclusion: Phoxilium effectively prevented hypophosphatemia and hypokalemia during CVVHDF. It was, however, associated with a slight metabolic acidosis and hypocalcemia compared with conventional solutions.

Implementing on-line hemodiafiltration as a renal replacement therapy for ICU acute renal failure: a single-center report of feasibility, safety and hemodynamic tolerance over a seven-year period.

Background/Aims: On-line hemodiafiltration (HDF) is not yet routinely used in ICUs given the potential risk of microbial contamination of dialysis fluids. We evaluated the safety and the tolerance of its use in our ICU. Methods: A weekly measurement of bacterial growth (CFU/ml) and endotoxin level (endotoxin units/ml) was performed in dialysis fluids over a 7-year period. Intradialytic hypotensive events and pyrogenic reactions were collected during 466 on-line HDF sessions. Results: A bacterial count <0.1 CFU/ml was achieved in 977/978, 288/290, and 278/280, and an endotoxin level <0.03 endotoxin units/ml in 564/576, 330/337 and 318/323 ultrapure water, dialysate, and infusate samples, respectively. Seventy-six intradialytic hypotensive events but no pyrogenic reaction occurred. Conclusion: The great majority of dialysis fluid samples were considered suitable with a 99% compliance rate. Use of on-line HDF, at a large scale of dialysate and infusate flows, is well tolerated and may be safely performed in critically ill.

Continuous Veno-Venous High Cut-Off Hemodialysis Compared to Continuous Veno-Venous Hemodiafiltration in Intensive Care Unit Acute Kidney Injury Patients

Aims: High cut-off (HCO) continuous veno-venous hemodialysis (CVVHD) was compared to high-flux membrane (HFM) continuous veno-venous hemodiafiltration (CVVHDF) in intensive care unit (ICU) acute kidney injury (AKI) in terms of efficiency, hemodynamic tolerance, medium-sized molecules removal, albumin loss, and inflammatory system activation. Methods: In a prospective cross-over randomized study, 10 AKI patients underwent successively HCO (Ultraflux EmiC2: β2-microglobulin [β2M] sieving coefficient [SC]: 0.9) CVVHD and HFM (Ultraflux AV1000S: β2M SC: 0.65) CVVHDF. Results: Over the 20 sessions, hypotensive and febrile episodes, reduction rates of urea, creatinine, and β2M were similar in both modalities. Though dialysis dose was higher with CVVHDF (36 ± 4 vs. 21 ± 6 mL/Kg/h), urea, creatinine, and β2M instantaneous and plasmatic clearances did not differ except for urea at 12 h. Protein loss, superoxide anion production, cytokines, and growth factors variations were also comparable. Conclusion: HCO CVVHD is well tolerated and is as effective as HFM CVVHDF in clearance of solutes and removal of β2M. It induces neither protein loss nor overproduction of superoxide anion. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=489082.

Front & Back Matter

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