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P Montravers

Publications and source records attributed to P Montravers.

At least 37 records · Page 2Linked to original sources

Microbiological and inflammatory effects of murine recombinant interleukin-10 in two models of polymicrobial peritonitis in rats.

A protective effect of interleukin-10 (IL-10) against the development of lethal shock has been demonstrated in various animal models. In contrast, the immunosuppressant properties of this mediator have been minimally evaluated in low-mortality models of infections. The clinical, microbiological, and inflammatory effects of murine recombinant IL-10 (mrIL-10) therapy were evaluated in two models of peritonitis in rats, which differed in the degree of severity of peritoneal inflammation 3 days after inoculation of Escherichia coli and Bacteroides fragilis with or without Enterococcus faecalis. The severity of the disease remained unchanged compared to that in control animals. A dose-related decrease in the peritoneal phagocyte count was observed in the treated groups compared to the counts in control animals. The subsequent experiments were performed exclusively in the mixed gram-positive-gram negative model, which exhibits an intense and prolonged inflammatory response with similar criteria. The early effects of mrIL-10 (evaluated 6 h after inoculation), repeated injections of mrIL-10 (four doses injected from 0 to 9 h after bacterial challenge), and pretreatment (two doses injected 6 and 3 h before inoculation) were evaluated. The clinical and microbiological parameters remained unchanged in the treated animals. Decreases in the peritoneal phagocyte count and the peritoneal concentration of tumor necrosis factor were observed following repeated injections of mrIL-10. In summary, our data suggest that mrIL-10 does not worsen the manifestations of sepsis. However, these results need to be confirmed in clinical practice.

Animals↗

Halogenated anesthetics inhibit Pseudomonas aeruginosa growth in culture conditions reproducing the alveolar environment.

UNLABELLED: We assessed the effects of halogenated anesthetics on Pseudomonas aeruginosa growth in a liquid nutrient broth. Sterile Petri dishes (3.5-cm diameter) were filled with a 1-mL suspension of a Pseudomonas aeruginosa strain and incubated at 37 degrees C. Exposure of bacterial plates to halothane, isoflurane, and enflurane administered at 1 and 2 minimum alveolar anesthetic concentration (MAC) were studied for different exposure times (1, 2, 3, and 4 h) using an airtight chamber. For each time, a control point was obtained. Serial dilutions and agar plates were made, and developed colonies were counted. A significant decrease in bacterial growth was observed from the second hour of exposure to every halogenated anesthetic. For long periods of exposure (3 and 4 h), bacterial growth was significantly reduced in the plates exposed to 2 MAC compared with 1 MAC. The maximal inhibition was observed after a 4-h exposure at 2 MAC and reached 60%, 49%, and 42% for halothane, isoflurane, and enflurane, respectively. We conclude that a decrease in Pseudomonas aeruginosa growth is observed after exposure to halogenated anesthetics, but whether this inhibition is clinically important remains to be demonstrated. IMPLICATIONS: Bacterial pneumonia is a major source of morbidity after general anesthesia. We measured the effects of volatile anesthetics on the growth of Pseudomonas aeruginosa, one of the pathogens most often isolated in hospital-acquired pneumonia. The experiments were performed in vitro in culture conditions reproducing those observed in the alveolar space. Volatile anesthetics inhibited the growth of these bacteria, but the clinical significance of this fact remains to be determined.

Anesthetics, Inhalation↗

Disparate findings on the role of virulence factors of Enterococcus faecalis in mouse and rat models of peritonitis.

The role of Enterococcus faecalis in polymicrobial peritonitis is still debated. Virulence factors expressed in some enterococcal strains might be involved in the pathogenicity of these organisms. To clarify their role, three of these virulence factors (cytolysin, gelatinase, and aggregation substance) were studied in six isogenic strains of E. faecalis expressing various combinations of these factors. Since the pathogenic effects of enterococci are only moderate, the expression of their virulence might vary from one animal species to another and from one type of infection to another. Therefore, we evaluated these effects in two animal models, i.e., a systemic infection in mice in which we assessed the virulence of the strains in 50% lethal dose studies and a model of compartmentalized infection in rats in which the microbiologic and inflammatory effects of the strains were evaluated in monomicrobial or polymicrobial infection. In mice, significant differences were observed in the cumulative survival curves depending on the virulence factors (P < 0.0001 [log rank test]). In rats, monomicrobial infection induced only mild changes. In polymicrobial peritonitis, the virulence factors mainly increased the inflammatory response while the changes observed in the microbiologic response were minimal. The combination of two virulence factors did not significantly increase the severity of infection either in the mice model or the polymicrobial rat model. These data argue for species and model dependence of the role of the virulence factors studied here and suggest that other important factors may be involved in the pathogenicity of enterococci.

Animals↗

Evidence of the proinflammatory role of Enterococcus faecalis in polymicrobial peritonitis in rats.

Although the role of members of the Enterobacteriaceae and anaerobes in the pathogenesis of intra-abdominal infections has been extensively demonstrated, the role played by enterococci in these infections remains controversial. The pathophysiological mechanisms induced by enterococci in intra-abdominal infection were studied in a nonfatal model of peritonitis in rats by implanting a gelatin capsule containing Escherichia coli and Bacteroides fragilis with or without increasing concentrations of Enterococcus faecalis or heat-inactivated enterococci. The ability of the rat peritoneal cavity to sterilize itself after bacterial challenge was evaluated by quantifying the inflammatory response in the peritoneal cavity, reflected by both phagocyte and cytokine responses. Effects were evaluated 6, 12, and 24 h and 3 and 6 days after inoculation. On day 6 after inoculation, the highest enterococcal concentration (10(8) CFU/ml) was accompanied by significantly increased concentrations of E. coli in peritoneal fluid and peritoneal phagocytes when compared to other groups. In the first 12 h after inoculation, tumor necrosis factor and interleukin-6 concentrations were significantly increased in the peritoneal fluid of the animals that had received the highest inoculum of enterococci or heat-inactivated enterococci. In the late period of the study (3 and 6 days), significantly increased leukocyte counts were observed in the peritoneal fluid of these animals. These results suggest that E. faecalis somehow inhibited phagocytosis and intracellular killing of the other pathogens and also played an inflammatory role, which might account for the bacterial synergy observed in this model.

Animals↗

Emergence of antibiotic-resistant bacteria in cases of peritonitis after intraabdominal surgery affects the efficacy of empirical antimicrobial therapy.

In cases of community-acquired peritonitis, the adequacy of emprical antibiotic treatment has been shown to attenuate mortality and morbidity. The impact of empirical antibiotics on the outcome of postoperative peritonitis has never been evaluated. This study included 100 consecutively studied patients with postoperative peritonitis. The adequacy of emprical treatment was determined by means of culture and susceptibility data obtained at the time of reoperation, and the effect of such treatment on outcome was evaluated. One hundred resistant pathogens were isolated from 70 patients, of whom 45% died; by comparison, mortality among those from whom susceptible organisms were isolated was 16% (P < .05). Inadequate empirical treatment was administered to 54 patients and was associated with poorer outcome (P < or = .05). The outcome of postoperative peritonitis is affected by the choice and adequacy of the initial empirical antibiotic therapy. Late changes in antibiotic therapy based on culture results did not affect outcome when the initial regimen was inadequate.

APACHE↗

[Severity scores underestimate the seriousness of acute renal failure after emergency surgery].

OBJECTIVES: The predictive value of APACHE II and SAPS severity scores were evaluated in a group of patients with acute renal failure admitted in ICU after emergency surgery. The criteria of poor prognosis identified in the 24 hours following admission were also evaluated. STUDY DESIGN: Open prospective study. PATIENTS AND METHODS: During 22 months, we included every patient admitted in ICU after emergency surgery with a serum creatinine concentration > or = 130 mumol.L-1. Clinical and biological parameters were collected in the first 24 hours following admission and the severity scores were calculated. Prediction of hospital outcome, based on APACHE II score, was calculated. The standard mortality ratio (observed mortality/predicted mortality) was calculated. Accuracy of SAPS and APACHE II score was compared using ROC curves and comparison of the areas under the curves. RESULTS: Death in ICU occurred in 44% of the patients while hospital mortality was 51%. The standard mortality ratio for APACHE II score was 1.35. The areas under the curves for SAPS and APACHE II scores were not statistically different. The criteria of poor prognosis, identified in the first 24 hours following admission, were cardiovascular failure, oliguria and sepsis. CONCLUSION: Conventional severity scores are inaccurate for prediction of mortality in patients with acute renal failure following emergency surgery.

Acute Kidney Injury↗

[Effects of midazolam on respiratory drive in healthy volunteers].

OBJECTIVE: To compare the effects of a sedative dose of midazolam on mean inspiratory flow (VT/TI = index of central respiratory activity), known as being decreased by midazolam and the intercostal muscle activity, known as being increased by this agent. STUDY DESIGN: Laboratory study. PATIENTS: Seven healthy volunteers. METHODS: After assessment of baseline values of ventilatory variables and intercostal electromyographic activity (in arbitrary units), midazolam 0.1 mg.kg-1 was administered by iv route. The measurements were repeated after 5 and 10 min, and finally 2 min after the i.v. injection of flumazenil 1 mg. RESULTS: Midazolam decreased VE and VT. Similarly VT/TI ratio decreased from 0.44 +/- 0.04 (baseline value) to 0.26 +/- 0.03 (5 min) and 0.3 +/- 0.03 L.s-1 (10 min later) respectively (P < 0.05). Conversely, midazolam increased the intercostal electromyographic activity from 4.0 +/- 0.7 (baseline value) to 26.5 +/- 16.6 (5 min) and 28.4 +/- 16.6 U (10 min later) respectively (P < 0.05). Within 2 min after flumazenil administration all variables returned to baseline values. CONCLUSIONS: The decrease of VT/TI ratio is probably linked to increased resistances in the upper airways. This ratio cannot act as an indicator of respiratory drive during sedation or anaesthesia. The assessment of the ventilatory effects of benzodiazepines must be based simultaneously of the various other indicators of the ventilatory drive, as these agents act on the different stages of the ventilatory cycle and therefore cannot be characterized by a unique variable.

Adjuvants, Anesthesia↗

Alteration in swallowing reflex after extubation in intensive care unit patients.

OBJECTIVES: To assess the swallowing reflex after prolonged endotracheal intubation and to assess the influence of age and duration of intubation on this reflex. DESIGN: Prospective, observational, clinical study. SETTING: The intensive care unit of a university teaching hospital. PATIENTS: The swallowing reflex was studied after extubation in 34 patients and compared with the deglutition in 30 nonintubated patients with a nasogastric tube and 15 nonintubated patients without a nasogastric tube. INTERVENTIONS: Four volumes of normal saline (0.25, 0.50, 0.75, and 1 mL) were injected at the epipharynx level. Swallowing efficiency was assessed by the latency between instillation and the first swallow, as identified on a submental electromyogram. The tests were performed immediately (day 0), and at 1 (day 1), 2 (day 2), and 7 (day 7) days after extubation in the intubated group. Nonintubated patients were tested once. MEASUREMENTS AND MAIN RESULTS: On day 0, the latency was increased for each bolus in the extubated group when compared with the control groups. Significant shortening of latency after 0.50, 0.75, and 1 mL injections of normal saline occurred on days 1 and 2 when compared with day 0, whereas no change was observed after 0.25 mL of normal saline was injected. On day 7, a significant improvement was observed, regardless of the volume injected. There was no correlation between swallowing latency and either the age of the patients or the duration of endotracheal intubation. CONCLUSIONS: These data indicate that prolonged endotracheal intubation impairs the swallowing reflex, with improvement within 1 wk. This phenomenon could contribute to microinhalations and aspiration pneumonia after extubation.

Aged↗

Lymphatic release of cytokines during acute lung injury complicating severe pancreatitis.

In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory distress syndrome (ARDS) are usually attributed to the release of active enzymes and vasoactive substances from the pancreas. Thoracic duct drainage has been proposed as a means of removing the portion of these substances that drain through retroperitoneal lymphatics before they reach the systemic circulation. This technique was used in six patients with ARDS complicating SAP. The levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at the end of the drainage (Day 8). High plasma concentrations of these products were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase, and trypsin, while similar levels in plasma and lymph were recorded for the other substances. Plasma levels of pancreatic enzymes were weakly correlated with the lung injury score and lymph level of cytokines. These results suggest that in patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could contribute to the development of the lung injury, and that lymphatics are potential vectors of these mediators.

Acute Disease↗

Investigation of the potential role of Enterococcus faecalis in the pathophysiology of experimental peritonitis.

Two nonfatal models of peritonitis differing by the duration and the severity of the disease were studied in rats by implantation of Escherichia coli and Bacteroides fragilis with or without increasing concentrations of Enterococcus faecalis. Results were evaluated at 3 or 6 days after inoculation. The highest enterococcal concentrations (10(9) cfu/mL) enhanced the severity of the infection, evident by increased emaciation, increased peritoneal counts of E. coli and B. fragilis, and increased frequency of E. coli and B. fragilis bacteremia compared with enterococcus-free animals. Six therapeutic regimens (low-dose amoxicillin + low-dose gentamicin, high-dose amoxicillin + high-dose gentamicin, pefloxacin, ornidazole, pefloxacin + ornidazole, imipenem + gentamicin) were tested. All treatments failed to eradicate E. faecalis except the combination pefloxacin + ornidazole, which achieved a significant reduction of local bacterial counts and suppressed bacteremia. Enterococcus played an important role in the mechanisms of bacterial synergy in experimental peritonitis. However, eradication of enterococcus did not seem possible by conventional antienterococcal therapy.

Abscess↗

Effects of intravenous midazolam on the work of breathing.

Midazolam at sedative doses induces an increase in upper airway resistance, but its effects on the work of breathing have not been established. The flow-resistive work of breathing and pulmonary resistance (RL) of eight healthy volunteers were measured, with either midazolam 0.1 mg/kg or placebo in a random order. Esophageal pressures were measured using a balloon-tipped catheter, airflow using a pneumotachograph. Total resistive work expressed per minute (WTOT) and per liter of ventilation (WTOT/VE), and their inspiratory (WI) and expiratory (WE) components were determined. No change was observed after placebo injection. Five minutes after midazolam injection, an increase was observed in WTOT (from 3 +/- 0.4 J/min [mean +/- SEM] at control to 6.3 +/- 1.1 J/min; P < 0.01) and in WTOT/VE (from 360 +/- 30 mJ/L at control to 1250 +/- 120 mJ/L; P < 0.01), involving both WI and WE components. An increased inspiratory RL was observed from 13.7 +/- 2.6 cm H2O.L-1.s-1 at control to 32.8 +/- 3.9 cm H2O.L-1.s-1 after midazolam. Changes in inspiratory RL were correlated to changes in WI and WI/VE (r = 0.574, P < 0.001; and r = 0.762, P < 0.001, respectively). Our results suggest that airway obstruction plays a major role in the increased work of breathing observed during sedation with midazolam.

Adult↗

Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.

PURPOSE: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.

Acinetobacter Infections↗

[Effects of acute alcoholic intoxication on the upper respiratory tract function].

Acute alcohol intake may be of potential hazard in anaesthesia emergency procedures because of consciousness alterations. Alcohol ingestion alters indeed the functions of upper airway muscles and increases the risk of obstructive sleep apnea. However, no data are available on the effects of alcohol on the swallowing reflex (SR), which is a major protective mechanism against pulmonary inhalation and on upper airway resistances (UAR) following external inspiratory load application. This study was designed to investigate the effects of acute alcohol intake on SR and UAR in healthy volunteers. After informed consent, 8 male volunteers (29 +/- 3 years) were studied in the supine position. The tip of a catheter was placed through the naris at the epipharynx level for injection of 3 series of 2 volumes of distilled water (0.25 and 1 ml respectively). Swallows were identified by a submental electromyogram. SR efficiency was assessed by recording 1) the latency (L) between injection and the first swallow, and 2) the number of swallows (N) elicited by each bolus. The subjects were breathing through a facial mask connected to a pneumotachograph. Supraglottic airway pressures (UAP) were recorded using a small balloon catheter placed at the tip of the epiglottis. UAR were calculated as the ration of UAP (cmH2O) on air-flow (l.s-1) at the airflow's peak. After a control set of measurements (TC), including SR assessment and UAR at rest (UARo) and during application of an external inspiratory resistive load (12 cmH2O.l-1 x s-1) (UARr) to sensitize the experiment, the subjects ingested 1 ml.kg-1 of alcohol as 40 degrees vodka.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome.

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.

Adult↗

Follow-up protected specimen brushes to assess treatment in nosocomial pneumonia.

To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.

Adolescent↗

Effects of midazolam on respiratory muscles in humans.

Midazolam at sedative doses alters the breathing pattern; however, its effects on respiratory load and respiratory muscle activity have not been established completely. Therefore, the effects of midazolam (0.1 mg/kg) on total pulmonary resistances and on diaphragmatic, intercostal, and abdominal muscle patterns were studied in nine volunteers. Measurements were performed during control, 5 and 10 min after midazolam, and then 2 min after 1.0 mg of intravenous flumazenil. After midazolam, total pulmonary resistance increased from 6.3 +/- 0.65 to 36.6 +/- 8.1 cm H2O-L-1 x s-1 (P < 0.01), a pattern associated with an increased intercostal electromyographic activity (peak and slope; P < 0.05). By contrast, the ratio of gastric pressure on esophageal pressure changes decreased from 65.5% +/- 6.2% to 16.3% +/- 3.9% (P < 0.01), indicating reduced diaphragmatic activity. In 7/9 subjects, there was expiratory abdominal muscle activity. Flumazenil reversed all these effects. We conclude that midazolam 0.1 mg/kg increases total pulmonary resistance and elicits a compensatory load response characterized by an increase in inspiratory intercostal and expiratory abdominal muscle activities whereas diaphragmatic contribution is reduced.

Abdominal Muscles↗