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Biomedical subjects

Marc Leone

Publications and source records attributed to Marc Leone.

At least 19 recordsLinked to original sources
PubMed2007

Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse.

OBJECTIVE: To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia. DESIGN: Prospective observational study during a 36-month period. SETTING: Medical-surgical intensive care unit of a university hospital. PATIENTS: One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p=.04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria. CONCLUSIONS: A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.

Adult↗
PubMed2006

Comparison of methylprednisolone and ketoprofen after multiple third molar extraction: a randomized controlled study.

In a prospective, double blind, and randomized study, we compared methylprednisolone and ketoprofen after anesthesia for multiple third molar extraction. In addition to paracetamol, 90 patients were allocated to receive intravenously either ketoprofen 100 mg or methylprednisolone 1 mg/kg. Severity of pain was measured with visual analogue scale (VAS) in recovery room. Sixty-three percent of patients receiving methylprednisolone had a VAS score <30 mm compared with 42% of those receiving ketoprofen (P = 0.04), with no difference in the consumption of morphine. We observed only marginal difference between methylprednisolone and ketoprofen to relieve pain after this surgery.

Adult↗
PubMed2006

[Surviving sepsis: where we are today].

The mortality induced by severe sepsis and septic shock remains very elevated despite progress in diagnosis and treatment. All the experts in the field consider that further progress is possible with better and more prompt use of the treatments now available. The "Surviving Sepsis" campaign reviews the diverse treatments that can be used and the best ways to prescribe them. It also proposes two bundles of objectives to be completed systematically for all patients: the first within the first 6 hours, the second between the sixth and 24th hour. Encouraging results show that applying these therapeutic principles can reduce mortality by 30% (relative percentage) compared with a treatment without specific objectives.

Anti-Bacterial Agents↗
PubMed2006

Decreased vasopressin responsiveness in vasodilatory septic shock-like conditions.

OBJECTIVE: To determine the effect of vasodilatory septic shock-like conditions on vasoconstricting responses to vasopressin and norepinephrine in isolated resistance arteries. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male adult Sprague-Dawley rats. INTERVENTIONS: Small mesenteric arteries (outside diameter, 50-150 microm) were cannulated and studied in vitro under physiologic conditions. A vasodilatory septic shock-like state was produced by treatment with the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Vasoconstricting concentration-response relationships were determined for norepinephrine and vasopressin before and after application of SNAP or SNAP+ IBMX. Synergism between low-dose vasopressin and norepinephrine and between low-dose norepinephrine and vasopressin was determined before and after SNAP or SNAP+IBMX. MAIN RESULTS: Norepinephrine and vasopressin produced concentration-dependent contractions (half-maximal effective concentration [EC(50)] = 2.5 microM and 3.9 nM, respectively) that were significantly inhibited by 1 microM SNAP (EC(50) = 3.6 microM and 8.1 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 10 microM and 8.2 nM, respectively). Low-dose vasopressin significantly increased the responsiveness to norepinephrine (EC50 = 0.5 microM) just as a low-dose norepinephrine significantly enhanced the vasopressin response (EC(50) = 2.3 nM). The synergistic effects of low-dose vasopressin and norepinephrine, or low-dose norepinephrine and vasopressin, were also significantly inhibited by 1 microM SNAP (EC(50) = 2.5 microM and 4.2 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 9 microM and 8.4 nM, respectively). CONCLUSIONS: Vasoconstriction produced by vasopressin or norepinephrine, and the synergistic vasoconstriction produced by the combinations, was inhibited in vasodilatory septic shock-like conditions. Thus, in addition to the well-described vasopressin deficiency in vasodilatory septic shock, these studies indicate that decreased vasopressin responsiveness further contributes to a state of relative vasopressin insufficiency in this condition.

Animals↗
PubMed2006

A reappraisal of isoproterenol in goal-directed therapy of septic shock.

The goal of the study was to evaluate the effect of isoproterenol prescribed in goal-directed therapy for septic shock. Out of a cohort of 89 patients with septic shock, 14 patients treated with fluid and norepinephrine had inappropriate mixed venous oxygen saturation (SvO2<70%) not responding to correction of hypoxemia and anemia (>8 g.dL-1). Isoproterenol administration was started at a dose of 0.04 microg.kg-1.minute-1 with 0.025 microg.kg-1.minute-1 increments every 30 minutes until SvO2 was greater than 70%. Mean arterial pressure was maintained>or=65 mm.Hg by adjusting the norepinephrine infusion. Hemodynamic, oxygen, and renal variables were collected during a 12-h period. Patients with a known prior history of coronary disease were not eligible. Isoproterenol administration increased significantly SvO2 (62%+/-10% to 71%+/-9%), cardiac index (3.1+/-0.6 to 4.4+/-1.4 L.min-1.m-2), stroke index (27+/-3.4 to 38+/-6.1 mL.m-2), and left ventricular stroke work index (24+/-3.4 to 40+/-5.0 g.m-1.m-2). Heart rate rise did not reach a significant level. Arterial lactate concentration decreased significantly during the study period (5.7+/-2.8 to 3.4+/-1.6 mmol.L-1). No cardiac adverse events occurred with any electrocardiographic aspects of myocardial ischemia. This study suggests that isoproterenol is efficient to improve hemodynamics and oxygen variables in septic shock patients. There is a need for future investigations in larger groups of patients to determine whether isoproterenol can be an alternative to dobutamine.

Adrenergic beta-Agonists↗
PubMed2006

Rescue therapy in septic shock--is terlipressin the last frontier?

Use of terlipressin, an analogue of vasopressin, can be considered in septic shock patients with intractable hypotension and high cardiac output in whom fluid resuscitation and high-dose conventional catecholamines have failed. The effects of this agent on organ function are poorly evaluated in humans. The limited number of patients evaluated precludes any analysis of adverse outcomes and prognosis.

Animals↗
PubMed2005

Decreased circulating elastin peptide levels in humans with sepsis.

OBJECTIVE: Sepsis is a potentially life-threatening medical condition induced by viral, bacterial or fungal infection, which is characterized by systemic inflammation, hypotension and vasodilation that can lead to cardiovascular collapse. Increased activity of elastases, enzymes which degrade the extracellular matrix components including elastin, has been demonstrated in plasma of septic patients. Since elastin peptides (EP), by binding to an elastin-laminin receptor on vascular endothelial and smooth muscle cells, induce dose-dependent vasodilation, we hypothesized that elevated circulating EP could contribute to the vasodilation that occurs in septic patients. MATERIALS AND METHODS: Blood for measurement of EP was collected from not-septic and septic patients admitted to the intensive care unit (ICU), as well as from healthy subjects. Plasma EP concentrations were measured using a competitive ELISA technique. RESULTS: The plasma EP level in the septic patients was approximately half that of the not-septic patients and the healthy controls, with similar EP levels in the latter two groups. There was no apparent association between EP levels and age or gender in any of the groups. CONCLUSIONS: Plasma EP levels were actually decreased in septic patients, possibly indicating that the balance between EP production vs. elimination favors elimination. This result further suggests that circulating EP may not be important in the development of the vasodilation and hypotension that occurs in septic shock. Alternatively, however, increased degradation of EP by elastase or other enzymes could lead to the appearance of biologically active EP, which may not be recognized by the ELISA assay.

Adult↗
PubMed2005

Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function.

OBJECTIVE: To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. DESIGN: Prospective, open-label, randomized, controlled study. SETTING: Medical-surgical intensive care unit of a tertiary care teaching hospital. PATIENTS: Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure > or =60 mm Hg. INTERVENTIONS: Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8-6.0) to 5.8 (4.3-6.9) L.min.m. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14-127) and 70 (15-121) mL; serum creatinine, 170 (117-333) and 153 (112-310) mumol.L; and creatinine clearance, 50 (12-77) and 67 (13-89) mL.min.1.73 m. CONCLUSIONS: Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function.

Adult↗
PubMed2005

Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study.

OBJECTIVE: To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function. DESIGN: Prospective, randomized, open-label study. SETTING: Intensive care unit of a university, tertiary, and referral center. PATIENTS: Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation. INTERVENTIONS: Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 +/- 17 to 104 +/- 11 beats.min(-1), p < .01) and cardiac index (from 5.1 +/- 1.7 to 4.2 +/- 1.6 L.min(-1).m(-2)) was observed, with no change in stroke volume. Oxygen delivery index (from 784 +/- 131 to 701 +/- 92 mL.min(-1).m(-2)) and consumption index (from 244 +/- 69 to 210 +/- 54 mL.min(-1).m(-2)) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs. CONCLUSIONS: In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.

Adult↗
PubMed2004

Risk factors for late-onset ventilator-associated pneumonia in trauma patients receiving selective digestive decontamination.

OBJECTIVE: To determine the independent risk factors for late-onset ventilator-associated pneumonia (VAP) in trauma patients receiving selective digestive decontamination (SDD). DESIGN: A 4-year, prospective cohort study of trauma patients meeting the following criteria: injury severity score >15, and duration of mechanical ventilation >5 days. Predictors of late-onset VAP occurrence were assessed by logistic regression analysis. POPULATION: All patients received SDD consisting of polymixin E, gentamicin, and amphotericin B applied in nostrils, mouth, and gut with a 3-day course of parenteral cefazolin. VAP was suspected on clinical and radiological signs, and confirmed by the presence of at least one microorganism at a concentration of at least 10(4) CFU/ml on the broncho-alveolar lavage. MEASUREMENT: Independent risk factors for late-onset VAP. RESULTS: A late-onset VAP was diagnosed in 90 (56%) out of 159 patients. Predicting factors for late-onset VAP were: use of non-depolarizing muscle relaxant agents for intubation [3.4 (CI 1.08-10.73)], duration of intubation [1.06 (CI 1.01-1.17)], length of intensive care unit (ICU) stay [1.05 (CI 1.02-1.09)], and prior tracheal colonization [1.03 (CI 1.02-1.21)]. Exposure to prior antimicrobial treatment, except SDD, conferred protection [0.3 (0.12-0.74)]. CONCLUSION: This study confirms the role of duration of intubation, length of ICU stay, and prior tracheal colonization in the development of late-onset VAP. The results also highlight the importance of the initial management on the development of late-onset VAP. The type of neuromuscular blocking agents to intubate trauma patients should be evaluated in future studies.

Adult↗
PubMed2004

Clinical review: Vasopressin and terlipressin in septic shock patients.

Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01-0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock.

Adult↗
PubMed2004

Survey of the use of catecholamines by French physicians.

OBJECTIVE: The objective of the study was to perform a descriptive approach of the current use of catecholamines by French physicians. DESIGN: A questionnaire of 12 questions with 4 items established by a group of French intensivists. POPULATION: French physicians from 433 departments working in the following practicing areas: intensive care unit (ICU), emergency department, and pre-hospital setting. MEASUREMENTS: Responding physicians were asked about the catecholamine that they would select in various clinical settings. RESULTS: The response rate was 82%. Of the responding physicians, 277 (78%) worked in an ICU, 28 (8%) in an emergency department, and 21 (6%) in a pre-hospital setting. Dobutamine was chosen for patients with cardiogenic shock by 90% of the respondents. Norepinephrine was the first choice agent as vasopressor in patients with septic shock in 52% of the cases. Dopamine was selected in a clinical setting requiring an optimization of regional blood flow, as in the concept of high-risk surgical patients. Dopexamine was used as a second or third choice agent to improve regional blood flow and cardiac output. The indications of epinephrine for anaphylactic shock and cardio-circulatory arrest were obvious for more than 90% of responding physicians. CONCLUSION: A lack of standardization appears in the use of catecholamines by French physicians, particularly for improvement of regional circulation and management of high-risk surgical patients. Guidelines that define the place of each catecholamine in these settings are required to improve the quality of prescription.

Catecholamines↗
PubMed2004

Effect of sex on Coxiella burnetii infection: protective role of 17beta-estradiol.

Q fever is a zoonosis caused by Coxiella burnetii and recently has been recognized as a potential agent of bioterrorism. In Q fever, men are symptomatic more often than women, despite equal seroprevalence. We hypothesized that sex hormones play a role in the pathogenesis of C. burnetii infection. When C57/BL6 mice were injected with C. burnetii, bacteria load and granuloma numbers were lower in females than in males. Ovarectomized mice showed increased bacteria load in the spleen and the liver, similar to that found in males. The granuloma number was also increased in ovarectomized mice and reached the levels found in males. Tissue infection and granulomatous response are largely under the control of estrogens: treatment of ovarectomized mice with 17beta-estradiol reduced both bacteria loads and granuloma numbers. These results show that sex hormones control host response to C. burnetii infection and may account for host-dependent clinical presentation of Q fever.

Animals↗
PubMed2004

Catheter-associated urinary tract infections in intensive care units.

The purpose of this review is to analyze literature concerning the diagnosis, prevention, and management of catheter-associated urinary tract infection (CAUTI) occurring in patients hospitalized in the intensive care unit (ICU). Analysis was performed from personal and "Pubmed" data, crossing the following keywords: "urinary tract infection", "catheter', and "intensive care unit". Few clinical trials including ICU patients were found despite the abundance of expert opinions. There is no consensus on the use of urinary reagent tests for diagnosis. The prevention of CAUTI in ICU patients does not require expensive devices. Neither complex closed drainage systems nor silver-coated urinary catheters have demonstrated efficacy in comparative randomized clinical trials. Bladder irrigation should not be used, except when an obstruction of the catheter is highly likely. The administration of prophylactic antimicrobial therapy, although effective in reducing the incidence of urinary bacteria, cannot be recommended in ICU patients. The management of CAUTI in ICU patients has not been evaluated in clinical trials. The level of evidence provided in this field is weak, and underlines the need for randomized studies to improve management of patients.

Cross Infection↗
PubMed2004

Cell adhesion molecules as a marker reflecting the reduction of endothelial activation induced by glucocorticoids.

In vitro, steroids down-regulate the expression of cell adhesion molecules (CAMs) in endothelial cells stimulated by lipopolysaccharide. Low-dose hydrocortisone is a new treatment of patients with septic shock, a state that is characterized by an endothelial injury. The aim of the present study was to investigate whether the plasma levels of soluble CAMs, reflecting in vivo endothelial activation, could be modulated in patients with septic shock treated by hydrocortisone. This was a prospective and observational study conducted in the intensive care unit at a university hospital. The subjects included 40 patients with septic shock (American College of Chest Physicians Consensus Conference/Society of Critical Care Medicine definition); 45 healthy blood donors served as controls. The patients receiving the standard care ("reference group") during the first 6 months were compared with the patients receiving the hydrocortisone therapy ("hydrocortisone group") for the next 6 months. Measurements of sCAMs were performed on days 1 and 3 of the disease. On day 1, sE-selectin, sP-selectin, sVCAM-1, and sICAM-1 were significantly elevated in patients with septic shock compared with healthy donors. sE-selectin levels significantly decreased between days 1 and 3 in the "hydrocortisone group," whereas there was no significant change in the "reference group". Surprisingly, sICAM-1 levels significantly increased between days 1 and 3 only in patients treated by hydrocortisone. No significant changes were observed for sP-selectin and sVCAM-1 levels in the two groups. In patients with septic shock, glucocorticoids differently affected the pattern of evolution of sCAMs, with sE-selectin being decreased and sICAM-1 being increased. Expression of sP-selectin and sVCAM-1 was not affected.

Adult↗