Marc Gainnier

Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome

Objective:To evaluate the effects of neuromuscular blocking agents (NMBAs) on pulmonary and systemic inflammation in patients with acute respiratory distress syndrome ventilated with a lung-protective strategy. Design:Multiple-center, prospective, controlled, and randomized trial. Setting:One medical and two medical–surgical intensive care units. Patients:A total of 36 patients with acute respiratory distress syndrome (Pao2/Fio2 ratio of ≤200 at a positive end-expiratory pressure of ≥5 cm H2O) were included within 48 hrs of acute respiratory distress syndrome onset. Interventions:Patients were randomized to receive conventional therapy plus placebo (n = 18) or conventional therapy plus NMBAs (n = 18) for 48 hrs. Both groups were ventilated with a lung-protective strategy (tidal volume between 4 and 8 mL/kg ideal body weight, plateau pressure of ≤30 cm H2O). Measurements and Main Results:Bronchoalveolar lavages and blood samples were performed, before randomization and at 48 hrs, to determine the concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8. Pao2/Fio2 ratio was evaluated before randomization and at 24, 48, 72, 96, and 120 hrs. A decrease over time in IL-8 concentrations (p = .034) was observed in the pulmonary compartment of the NMBA group. At 48 hrs after randomization, pulmonary concentrations of IL-1β (p = .005), IL-6 (p = .038), and IL-8 (p = .017) were lower in the NMBA group as compared with the control group. A decrease over time in IL-6 (p = .05) and IL-8 (p = .003) serum concentrations was observed in the NMBA group. At 48 hrs after randomization, serum concentrations of IL-1β (p = .037) and IL-6 (p = .041) were lower in the NMBA group as compared with the control group. A sustained improvement in Pao2/Fio2 ratio was observed and was reinforced in the NMBA group (p < .001). Conclusion:Early use of NMBAs decrease the proinflammatory response associated with acute respiratory distress syndrome and mechanical ventilation.

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.

Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome*

Objective:Both prone position and high-frequency oscillatory ventilation (HFOV) have the potential to facilitate lung recruitment, and their combined use could thus be synergetic on gas exchange. Keeping the lung open could also potentially be lung protective. The aim of this study was to compare physiologic and proinflammatory effects of HFOV, prone positioning, or their combination in severe acute respiratory distress syndrome (ARDS). Design:Prospective, comparative randomized study. Setting:A medical intensive care unit. Patients:Thirty-nine ARDS patients with a Pao2/Fio2 ratio <150 mm Hg at positive end-expiratory pressure ≥5 cm H2O. Interventions:After 12 hrs on conventional lung-protective mechanical ventilation (tidal volume 6 mL/kg of ideal body weight, plateau pressure not exceeding the upper inflection point, and a maximum of 35 cm H2O; supine-CV), 39 patients were randomized to receive one of the following 12-hr periods: conventional lung-protective mechanical ventilation in prone position (prone-CV), HFOV in supine position (supine-HFOV), or HFOV in prone position (prone-HFOV). Measurements and Main Results:Prone-CV (from 138 ± 58 mm Hg to 217 ± 110 mm Hg, p < .0001) and prone-HFOV (from 126 ± 40 mm Hg to 227 ± 64 mm Hg, p < 0.0001) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio (from 134 ± 57 mm Hg to 138 ± 48 mm Hg). The oxygenation index ({mean airway pressure × Fio2 × 100}/Pao2) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group. Interleukin-8 increased significantly in the bronchoalveolar lavage fluid (BALF) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV. Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group. Conclusions:Although HFOV in the supine position does not improve oxygenation or lung inflammation, the prone position increases oxygenation and reduces lung inflammation in ARDS patients. Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation. In contrast, supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation.

Long-term outcome in medical patients aged 80 or over following admission to an intensive care unit

IntroductionThe aim of this study was to evaluate factors influencing short- and long-term survival in medical patients aged 80 and over following admission to an intensive care unit.MethodsAll patients aged 80 years or over and admitted between 2001 and 2006 were included in this study. Survival was evaluated between the time of admission and June 2009; factors associated with mortality were determined. Health-related quality of life was evaluated using Short Form (SF)-36 in long-term survivors.ResultsFor the 299 patients included (mean age, 84 ± 4 y), hospital mortality was 55%. Factors independently associated with hospital mortality were a higher SAPS II score at ICU admission; the existence of a fatal disease as reflected by the McCabe score and a cardiac diagnosis at admission. In the 133 hospital survivors, median survival time was 710 days (95% CI, 499-921). Two-year mortality rates were 79% of the initial cohort and 53% of hospital survivors. The standardized ratio of mortality at 2 years after hospital discharge was 2.56 (95% CI, 2.08-3.12) when compared with age- and gender-adjusted mortality of the general population. Factors independently associated with mortality at 2 years after hospital discharge were SAPS II score at ICU admission and the McCabe score. Conversely, functional status prior to admission as assessed by Knaus or Karnofsky scores was not associated with long-term mortality. In long-term survivors, SF-36 physical function scores were poor but scores for pain, emotional well-being and social function were not much affected.ConclusionsThe severity of acute disease at admission influences mortality at the hospital and following discharge in patients aged 80 or over. Although up to 50% of patients discharged from the hospital were still alive at 2 years, mortality was increased when compared with the general population. Physical function of long-term hospital survivors was greatly altered.

Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients.

Objective:To assess the incidence, risk factors, and outcome of active cytomegalovirus (CMV) infection in nonimmunosuppressed intensive care unit (ICU) patients. Design:Prospective epidemiologic study. Setting:A medical ICU in a university hospital. Patients:Two hundred forty-two nonimmunosuppressed ICU patients mechanically ventilated for ≥2 days. Interventions:Routine pp65 antigenemia and serology for CMV were performed at admission, and then weekly. Bronchoalveolar lavage viral cultures were done when pneumonia was suspected. Measurements and Main Results:Thirty-nine of the 242 ICU patients (16.1%, confidence interval 11.5% to 20.7%) developed an active CMV infection, as diagnosed by positive antigenemia (85%) and/or positive rapid viral culture in bronchoalveolar lavage (26%). Antiviral treatment was initiated in 21 (54%) patients. ICU mortality (54% vs. 37%, p = 0.082) and in-hospital mortality (59% vs. 41%, p = 0.058) were increased in patients with active CMV infection, as compared with those without active CMV infection. Active CMV infection and Simplified Acute Physiology Score II at admission were associated with ICU death on multivariate analysis. The patients with active CMV infection had longer mechanical ventilation and longer ICU stay and were significantly more prone to developing bacterial nosocomial infections (p < 0.001). Logistic regression analysis showed that prior admission to other wards (p = 0.043; odds ratio [OR], 2.49), blood transfusions (p = 0.04; OR, 3.31), enteral feeding (p = 0.005; OR, 3.00), recent corticosteroid use before ICU admission (p = 0.08; OR, 2.26), and age (p = 0.07; OR, 1.026) were associated with the occurrence of active CMV infection. Conclusions:Active CMV infection is common among previously healthy patients under mechanical ventilation in a medical ICU. Further studies are needed to evaluate the role of antiviral treatments to reduce both the incidence and the outcome impact of active CMV infection.

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.

High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation.

Objective: The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High‐frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position. Design: Prospective, comparative randomized study. Setting: A medical intensive care unit. Patients: Forty‐three ARDS patients with a Pao2/Fio2 ratio <150 at positive end‐expiratory pressure ≥5 cm H2O. Interventions: After an optimization period, the patients were assigned to one of three groups: a) conventional lung‐protective mechanical ventilation in the prone position (12 hrs) followed by a 12‐hr period of conventional lung‐protective mechanical ventilation in the supine position (CVprone‐CVsupine); b) conventional lung‐protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CVsupine‐HFOVsupine); or c) conventional lung‐protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CVprone‐HFOVsupine group). Measurements and Main Results: Pao2/Fio2 ratio was higher at the end of the study period in the CVprone‐HFOVsupine group than in the CVprone‐CVsupine group (p < .02). Venous admixture at the end of the study period was lower in the CVprone‐HFOVsupine group than in the two other groups. Conclusions: HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.

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.

Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine green and extravascular lung water during prone positioning in patients with ARDS: a randomized crossover study

IntroductionProne positioning (PP) on an air-cushioned mattress is associated with a limited increase in intra-abdominal pressure (IAP) and an absence of organ dysfunction. The respective influence of posture by itself and the type of mattress on these limited modifications during the PP procedure remains unclear. The aim of this study was to evaluate whether the type of support modifies IAP, extravascular lung water (EVLW) and the plasma disappearance rate of indocyanine green (PDRICG) during PP.MethodsA prospective, randomized, crossover study of 20 patients with acute respiratory distress syndrome (ARDS) was conducted in a medical intensive care unit in a teaching hospital. Measurements were made at baseline and repeated after 1 and 6 hours of two randomized periods of 6 hours of PP with one of two support types: conventional foam mattress or air-cushioned mattress.ResultsAfter logarithmic transformation of the data, an analysis of variance (ANOVA) showed that IAP and PDRICG were significantly influenced by the type of support during PP with an increase in IAP (P < 0.05 by ANOVA) and a decrease in PDRICG on the foam mattress (P < 0.05 by ANOVA). Conversely, the measurements of EVLW did not show significant modification between the two supports whatever the posture. The ratio of the arterial oxygen tension to the fraction of inspired oxygen significantly increased in PP (P < 0.0001 by ANOVA) without any influence of the support.ConclusionIn comparison with a conventional foam mattress, the use of an air-cushioned mattress limited the increase in IAP and prevented the decrease in PDRICG related to PP in patients with ARDS. Conversely, the type of support did not influence EVLW or oxygenation.

Expiratory trigger setting in pressure support ventilation: from mathematical model to bedside.

Objective:To evaluate the feasibility of relying on a mathematical model to adjust the optimal level of expiratory trigger, materialized by the ratio of inspiratory flow at the end of inspiratory effort (V′ti) and peak inspiratory flow (V′peak), or V′ti/V′peak, during pressure support, by comparing its predicted values with those measured in intubated patients. Design:Prospective observational study. Setting:Medical intensive care unit, university hospital. Patients:There were 28 intubated patients undergoing pressure support. Interventions:Pressure support as set by the clinician in charge. Measurements and Main Results:A significant correlation was found between predicted and measured V′ti/V′peak ratios (r = .70; p < .001; mean ± sd difference, −0.025 ± 0.07; 95% confidence interval, −0.161 to 0.111). Overall, delayed cycling occurred in obstructive conditions, the delay increasing as obstructive disease was more severe. Conclusions:A significant correlation was observed between predicted values of V′ti/V′peak and those values measured in patients undergoing pressure support. These findings should stimulate further research into the possible applications of this mathematical model to optimize expiratory trigger setting. Furthermore, our findings suggest that expiratory trigger should be adjustable and provide a wider range of cutoff levels than that which is currently available.