Xavier Thirion

Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome

ObjectiveTo evaluate the effects of a 48-hr neuromuscular blocking agents (NMBA) infusion on gas exchange over a 120-hr time period in patients with acute respiratory distress syndrome. DesignMultiple center, prospective, controlled, and randomized trial. SettingFour adult medical or mixed medical-surgical intensive care units. PatientsA total of 56 patients with acute respiratory distress syndrome with a Pao2/Fio2 ratio of <150 at a positive end-expiratory pressure of ≥5 cm H2O. InterventionsAfter randomization, patients received either conventional therapy without NMBA (control group) or conventional therapy plus NMBA for the next 48 hrs. The initial ventilator mode was volume-assist/control. The ventilator remained on assist-control mode throughout the initial 48-hr period in both groups. Tidal volume was 6–8 mL/kg ideal body weight. Measurements and Main ResultsWhen analyzed for the entire 120 hrs, there was a significant effect of the NMBA on the course of Pao2/Fio2 ratio (p = .021). Separate comparisons at each time point indicated that patients randomized to the NMBA group had a higher Pao2/Fio2 at 48, 96, and 120 hrs after randomization. Moreover, a decrease of positive end-expiratory pressure (p = .036) was only found in the NMBA group. Two-way repeated-measures analysis of variance exhibited a decrease in positive end-expiratory pressure over time (p = .036). Concerning short-term effects, there was no modification of Pao2/Fio2 ratio 1 hr after randomization in either group. Only one patient (from the control group) developed pneumothorax. ConclusionsUse of NMBA during a 48-hr period in patients with acute respiratory distress syndrome is associated with a sustained improvement in oxygenation.

Upregulation of chemokines in bronchoalveolar lavage fluid as a predictive marker of post-transplant airway obliteration

BACKGROUND The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB. METHODS Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 +/- 164 days and 307 +/- 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 +/- 323 and 152 +/- 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups. CONCLUSIONS These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.

Is ventilator-associated pneumonia an independent risk factor for death?

BackgroundVentilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation. MethodsDuring the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP. ResultsAnalysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia. ConclusionVentilator-associated pneumonia does not appear to be an independent risk factor for death.

Prone position and positive end-expiratory pressure in acute respiratory distress syndrome*

ObjectiveTo determine whether positive end-expiratory pressure (PEEP) and prone position present a synergistic effect on oxygenation and if the effect of PEEP is related to computed tomography scan lung characteristic. DesignProspective randomized study. SettingFrench medical intensive care unit. PatientsTwenty-five patients with acute respiratory distress syndrome. InterventionsAfter a computed tomography scan was obtained, measurements were performed in all patients at four different PEEP levels (0, 5, 10, and 15 cm H2O) applied in random order in both supine and prone positions. Measurements and Main ResultsAnalysis of variance showed that PEEP (p < .001) and prone position (p < .001) improved oxygenation, whereas the type of infiltrates did not influence oxygenation. PEEP and prone position presented an additive effect on oxygenation. Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2 related to PEEP whatever the position, whereas patients presenting localized infiltrates did not have improved oxygenation status when PEEP was increased in both positions. Prone position (p < .001) and PEEP (p < .001) reduced the true pulmonary shunt. Analysis of variance showed that prone position (p < .001) and PEEP (p < .001) reduced the true pulmonary shunt. The decrease of the shunt related to PEEP was more pronounced in patients presenting diffuse infiltrates. A lower inflection point was identified in 22 patients (88%) in both supine and prone positions. There was no difference in mean lower inflection point value between the supine and the prone positions (8.8 ± 2.7 cm H2O vs. 8.4 ± 3.4 cm H2O, respectively). ConclusionsPEEP and prone positioning present additive effects. The prone position, not PEEP, improves oxygenation in patients with acute respiratory distress syndrome with localized infiltrates.

Long-term outcome in intensive care unit survivors after mechanical ventilation for intracerebral hemorrhage.

ObjectiveTo evaluate long-term survival and functional outcome in intensive care unit survivors after mechanical ventilation for intracerebral hemorrhage. DesignRetrospective chart review and prospective follow-up study. SettingOutpatient follow-up. PatientsBetween 1997 and 2000, 120 patients were mechanically ventilated for an intracerebral hemorrhage at our intensive care unit. Sixty-two patients were discharged from hospital (in-hospital mortality = 48%). Sixty patients were evaluated for survival and functional outcome (two were lost to follow-up). Time between discharge and follow-up was ≥1 yr and was a mean of 27 ± 14 months (range, 12–56). InterventionsNone. Measurements and Main ResultsPatients’ physicians were first asked about survival, and patients or proxies were interviewed by phone. Barthel Index and modified Rankin Scale scores were collected, and demographic information and general data were reviewed. The estimated life-table survival curve after discharge was 64.6% at 1 yr and 57% at 3 yrs. In the 24 patients who died, the mean time between discharge and death was 5 ± 6 months. Probability of death after discharge significantly increased if age at admission was >65 yrs (p < .01; odds ratio, 3.5; 95% confidence interval, 1.4–9.1) and if Glasgow Coma Scale score at discharge was <15 (p < .01; odds ratio, 3.9; 95% confidence interval, 1.6–9.5). In the 36 long-term survivors, Barthel Index was 67.5 ± 15 (median ± median absolute dispersion) and modified Rankin Scale score was 2.6 ± 0.5. Fifteen patients (42%) had a slight or no disability (Barthel Index ≥90 and modified Rankin Scale score ≤2), whereas 21 patients (58%) had moderate or severe disability (Barthel Index ≤85 and modified Rankin Scale score >2). ConclusionsProbability of survival at 3 yrs after mechanical ventilation for an intracerebral hemorrhage was >50%. Age was an important determinant of long-term survival. Forty-two percent of long-term survivors were independent for activities of daily living. Only a few long-term survivors had a very high degree of disability.

Can the tomographic aspect characteristics of patients presenting with acute respiratory distress syndrome predict improvement in oxygenation-related response to the prone position?

BACKGROUND In some patients with acute respiratory distress syndrome, the prone position is able to improve oxygenation, whereas in others it is not. It could be hypothesized that the more opacities that are present in dependent regions of the lung when the patient is in the supine position, the better the improvement in oxygenation is observed when the patients are turned prone. Therefore, we conducted a prospective study to identify computed tomographic scan aspects that could accurately predict who will respond to the prone position. METHODS We included 46 patients with acute respiratory distress syndrome (31 responders and 15 nonresponders). Computed tomographic scan was performed in the 6-h period preceding prone position. Blood gas analyses were performed before and at the end of the first 6-h period of prone position. RESULTS Arterial oxygen partial pressure/fraction of inspired oxygen increased from 117 +/- 42 (mean +/- SD) in the supine position to 200 +/- 76 mmHg in the prone position (P < 0.001). There were 31 responders and 15 nonresponders. There was a vertebral predominance of the opacities (P < 0.0001). However, there was no difference between responders and nonresponders. When only the amount of consolidated lung located under the heart was evaluated, there was more consolidated tissue under the heart relative to total lung area in nonresponders than in responders (P = 0.01). CONCLUSIONS There are no distinctive morphologic features in the pattern of lung disease measured by computed tomographic scanning performed with the patient in the supine position that can predict response to the prone position.

A randomized, single-blind crossover comparison of the effects of chronic DDD and dual sensor VVIR pacing mode on quality-of-life and cardiopulmonary performance in complete heart block

The aim of this study was to compare DDD and dual sensor VVIR (activity and QT) pacing modes in complete AV block (CAVB). Eighteen patients (14 men and 4 women, aged 70 ± 6.5 years) implanted with a dual chamber, dual sensor pacemaker for CAVB with normal sinus node chronotropic function were studied. A quality‐of‐life and cardiovascular symptom questionnaire, and a treadmill exercise test were completed after a period of VVIR and a period of DDD pacing, each lasting 1 month. Overall quality‐of‐life and cardiovascular symptoms did not significantly differ, though three patients felt discomfort during VVIR mode. There was no significant statistical difference in Cardiopulmonary parameters. DDD and VVIR modes yielded the following respective data: maximum heart rate = 105.7 ± 21.8 beats/minute versus 107.6 ± 21.6 beats/minute (NS); maximum workload = 60 ± 33.4 W versus 59.3 ± 37.8 W (NS); treadmill duration = 10.1 ± 3.8 minute versus 10.1 ± 3.6 minute (NS); oxygen consumption at anaerobic threshold = 14.6 ± 4.1 ml/kg per minute versus 14.9 ± 4.6 mL/kg per minute (NS); maximum minute ventilation = 49.6 ± 9 L/min versus 46 ± 12 L/min (NS); and respiratory quotient = 1.08 ± 0.15 versus 1.08 ± 0.13 (NS). We conclude that, during a 1‐month follow‐up period, no difference was found between DDD and dual sensor VVIR (QT and activity) pacing modes in CAVB patients with regard to quality‐of‐life and Cardiopulmonary performance, though a trend toward an increased sense of well being was noted with the DDD mode.

Does Norepinephrine Modify the Effects of Inhaled Nitric Oxide in Septic Patients with Acute Respiratory Distress Syndrome

Background Hypoxia‐related pulmonary vasoconstriction enhanced by norepinephrine could be deleterious in patients with the acute respiratory distress syndrome (ARDS) and sepsis. A prospective study compared the effects of nitric oxide on cardiorespiratory parameters, including the evaluation of right ventricular function in patients with ARDS and sepsis who were receiving or not receiving norepinephrine. Methods During a 15‐month period, 27 patients with ARDS and sepsis were prospectively investigated (group 1: 15 patients not receiving norepinephrine; group 2: 12 patients receiving norepinephrine). Right ventricular ejection fraction was measured by thermodilution. After baseline measurements, nitric oxide was administered at increasing inspiratory concentrations. Results The ratio of oxygen tension in arterial blood to the fractional concentration of oxygen in inspired gas increased in the two groups. After logarithmic transformation of the data, an analysis of variance was performed that did not show any difference between the two groups. A dose‐dependent decrease in mean pulmonary arterial pressure was observed in the two groups. This decrease and the increase in right ventricular ejection fraction induced by inhaled nitric oxide were more marked when patients received norepinephrine (P < 0.0001). Conclusion Norepinephrine did not influence the beneficial effects of inhaled nitric oxide administered to patients with ARDS and sepsis on oxygenation.

Long-term pacemaker dependency after radiofrequency ablation of the atrioventricular junction

This prospective study was conducted to determine the percentage of patients with long-term pacemaker dependency after successful radiofrequency ablation of the atrioventricular junction. Abrupt inhibition of the pacemaker was performed 13.5 +/- 8.1 months after ablation in 59 patients. A > or =5-second asystole was considered to indicate pacemaker dependency. Pacemaker dependency was present in 18 patients. Absence of escape rhythm immediately after ablation was strongly associated with a higher incidence of long-term pacemaker dependency. The following variables were not associated with pacemaker dependency: age, presence of cardiac disease, presence of preablation bundle branch block, number of radiofrequency applications, a bilateral approach for ablation, and continuation of antiarrhythmic therapy after ablation. We concluded that (1) long-term pacemaker dependency is present in 30.5% of the patients after successful atrioventricular junction radiofrequency ablation and (2) absence of escape rhythm immediately after ablation predicts long-term pacemaker dependency.