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Biomedical subjects

P Montravers

Publications and source records attributed to P Montravers.

At least 19 recordsLinked to original sources
PubMed1995

[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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

[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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome.

Neutrophils and cytokines are directly involved in the pathophysiology of adult respiratory distress syndrome (ARDS). Pentoxifylline (PTX) has been shown in vitro to protect against the inflammatory effects of neutrophils and cytokines. The same protective effects have been demonstrated on animal models of lung injury. These results suggested that PTX might be useful in patients with ARDS. The cardiopulmonary effects of large doses of PTX were evaluated in a pilot study performed in six patients with severe ARDS. PTX was administered with an initial 1-mg/kg bolus, followed by infusion of 1.5 mg/kg/h over 6 h. No significant change was observed in the gas exchange and hemodynamic parameters, except for a 10 percent increase in the heart rate during the infusion period. Our results demonstrate that large doses of PTX induced only minor hemodynamic changes without worsening in pulmonary gas exchange. Further studies are warranted to evaluate human safety and ultimately the effectiveness of PTX in the treatment of ARDS.

Aged↗
PubMed1993

Cardiopulmonary effects of bronchoalveolar lavage in critically ill patients.

Bronchoalveolar lavage (BAL) has been proposed as a useful procedure for bacteriologic diagnosis of lower respiratory tract infection in mechanically ventilated patients. To determine the cardiopulmonary effects of this procedure and to identify the patients at risk of poor tolerance, 30 critically ill ventilated patients suspected of having pneumonia were studied. Hemodynamic and gas exchange parameters were continuously recorded using an arterial catheter, a Swan-Ganz catheter with SvO2 display, and a pulse oximeter. In addition to the basal sedation required by these patients, midazolam, 0.1 mg/kg intravenously, was administered 5 min prior to bronchoscopy. A moderate increase (10 percent from basal values) in heart rate, mean arterial pressure, and cardiac index was recorded at each measurement during the procedure. A marked decrease in PaO2 was observed during bronchoscopy associated with an increase in oxygen consumption. Maximal changes in SaO2 and SvO2 were recorded at the end of BAL. Two hours after the end of BAL, PaO2 values were still 20 percent lower than pre-BAL values in 40 percent of the patients. We conclude that BAL can be performed safely in most critically ill ventilated patients who have stable hemodynamic and ventilatory parameters. However, none of the recorded parameters allows identification of the patients at risk of poor tolerance of the procedure.

Analysis of Variance↗
PubMed1993

[State of activation of polynuclear neutrophils and cytokines in acute respiratory distress syndrome in adults].

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), the authors studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, 9 with severe pneumonia uncomplicated by ARDS, and 7 mechanically ventilated patients with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, the authors identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor alpha (TNF-alpha) in plasma, and both spontaneous and lipopolysaccharide (LPS)-induced TNF-alpha production by cultured monocytes. These biological expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.

Adult↗
PubMed1992

[Impairment of deglutition reflex after prolonged intubation].

This study was designed to assess the swallowing reflex after an endotracheal intubation of more than 24 h, as well as the influence of age and duration of intubation on swallowing. Twenty patients (aged 58 +/- 17 years) who had been intubated for more than 24 h were compared with fifteen others (63.1 +/- 16.7 years), who had never been intubated. All had a nasogastric tube. Swallowing was assessed after administration of 0.25, 0.5, 0.75 and 1 ml volumes of normal saline, in a random sequence, into the epipharynx through a thin catheter passing through the nostril after extubation (E0), and then at 1 (E1), 8 (E8), 24 (E24) and 48 h (E48) in the extubated patients, and once in the control patients. Swallowing responses were identified by an electromyogram of the floor of the oral cavity. The efficiency of the swallowing reflex was assessed by the delay between instillation and the first swallowing response obtained, and the number of swallows recorded during the first 15 seconds following each injection. There was a significant increase in swallowing delay in intubated patients for volumes less than 1 ml during the first three measurements. Recovery occurred for 0.5 and 0.75 ml at E24 and E48, when compared with the control group. However, delay remained increased throughout the study for 0.25 ml. The number of swallows was the same in both groups for each volume tested. There was no correlation between increased delay and age or duration of intubation. These data confirmed that prolonged endotracheal intubation impairs the swallowing reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of i.v. midazolam on upper airway resistance.

We have measured changes in supraglottic airway resistance (Rsg) produced by midazolam. Ten subjects were studied on two occasions, receiving in a random order either midazolam 0.1 mg kg-1 or placebo. Supraglottic pressures were measured using a balloon-tipped catheter and air flow with a pneumotachograph. Rsg were calculated at a flow rate of 0.3 litre s-1 during inspiration. No changes in Rsg and no apnoeic events were noted following placebo injection. Mean Rsg increased from 0.23 (SEM 0.07) kPa litre-1 s to 1.29 (0.38) kPa litre-1 s 5 min after injection of midazolam (P less than 0.01), and remained increased significantly for 20 min. Twenty-two apnoeic events were recorded in six subjects, including 11 obstructive events. We conclude that midazolam in sedative doses increases Rsg markedly and induces central apnoea during the first few minutes after i.v. administration and this is followed by obstructive apnoea.

Adult↗
PubMed1992

Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production.

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF-alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.

Flow Cytometry↗