Jean-Michel Arnal

Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

BACKGROUND In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

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.

Early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the MACOCHA score in a multicenter cohort study.

RATIONALE Difficult intubation in the intensive care unit (ICU) is a challenging issue. OBJECTIVES To develop and validate a simplified score for identifying patients with difficult intubation in the ICU and to report related complications. METHODS Data collected in a prospective multicenter study from 1,000 consecutive intubations from 42 ICUs were used to develop a simplified score of difficult intubation, which was then validated externally in 400 consecutive intubation procedures from 18 other ICUs and internally by bootstrap on 1,000 iterations. MEASUREMENTS AND MAIN RESULTS In multivariate analysis, the main predictors of difficult intubation (incidence = 11.3%) were related to patient (Mallampati score III or IV, obstructive sleep apnea syndrome, reduced mobility of cervical spine, limited mouth opening); pathology (severe hypoxia, coma); and operator (nonanesthesiologist). From the β parameter, a seven-item simplified score (MACOCHA score) was built, with an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.85-0.94). In the validation cohort (prevalence of difficult intubation = 8%), the AUC was 0.86 (95% CI, 0.76-0.96), with a sensitivity of 73%, a specificity of 89%, a negative predictive value of 98%, and a positive predictive value of 36%. After internal validation by bootstrap, the AUC was 0.89 (95% CI, 0.86-0.93). Severe life-threatening events (severe hypoxia, collapse, cardiac arrest, or death) occurred in 38% of the 1,000 cases. Patients with difficult intubation (n = 113) had significantly higher severe life-threatening complications than those who had a nondifficult intubation (51% vs. 36%; P < 0.0001). CONCLUSIONS Difficult intubation in the ICU is strongly associated with severe life-threatening complications. A simple score including seven clinical items discriminates difficult and nondifficult intubation in the ICU. Clinical trial registered with www.clinicaltrials.gov (NCT 01532063).

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.

Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy

IntroductionVentilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy.MethodsThis prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis.ResultsNinety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective.ConclusionsIn patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment.

Use of heliox in patients with severe exacerbation of chronic obstructive pulmonary disease.

Objective To assess whether patients with chronic obstructive pulmonary disease treated with heliox have a better prognosis than those treated with standard therapy. Design Retrospective analysis over 18 months. Setting Academic emergency department. Patients Eighty-one patients admitted with exacerbation of chronic obstructive pulmonary disease and respiratory acidosis. Interventions Use of helium-oxygen mixture as an adjunctive therapy. Measurements and Main Results The following data were collected: age, gender, medical history, vital signs, arterial blood gas at admission, emergency room treatment, requirement for intubation, admission in intensive care unit, length of stay, and evolution. Patients were classified into two groups according to whether heliox was used as a therapeutic agent (heliox group) or not (standard group). Chi-square test and Student’s t-test were used for statistical analysis (significant at p < .05). In both groups, the following data were similar: age, gender, medical history, vital signs, initial arterial blood gas, and emergency room treatment. Significant decreases in intubation, and mortality rate were identified in the heliox group. Significant decreases in intensive care unit stay and in-hospital stay were observed for survivors in the heliox group. Conclusion Use of heliox seems to improve prognosis in patients with severe acute exacerbation of chronic obstructive pulmonary disease. Prospective randomized studies are needed to confirm these results.

Feasibility study on full closed-loop control ventilation (IntelliVent-ASV ™ ) in ICU patients with acute respiratory failure: a prospective observational comparative study

IntroductionIntelliVent-ASV™ is a full closed-loop ventilation mode that automatically adjusts ventilation and oxygenation parameters in both passive and active patients. This feasibility study compared oxygenation and ventilation settings automatically selected by IntelliVent-ASV™ among three predefined lung conditions (normal lung, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD)) in active and passive patients. The feasibility of IntelliVent-ASV™ use was assessed based on the number of safety events, the need to switch to conventional mode for any medical reason, and sensor failure.MethodThis prospective observational comparative study included 100 consecutive patients who were invasively ventilated for less than 24 hours at the time of inclusion with an expected duration of ventilation of more than 12 hours. Patients were ventilated using IntelliVent-ASV™ from inclusion to extubation. Settings, automatically selected by the ventilator, delivered ventilation, respiratory mechanics, and gas exchanges were recorded once a day.ResultsRegarding feasibility, all patients were ventilated using IntelliVent-ASV™ (392 days in total). No safety issues occurred and there was never a need to switch to an alternative ventilation mode. The fully automated ventilation was used for 95% of the total ventilation time. IntelliVent-ASV™ selected different settings according to lung condition in passive and active patients. In passive patients, tidal volume (VT), predicted body weight (PBW) was significantly different between normal lung (n = 45), ARDS (n = 16) and COPD patients (n = 19) (8.1 (7.3 to 8.9) mL/kg; 7.5 (6.9 to 7.9) mL/kg; 9.9 (8.3 to 11.1) mL/kg, respectively; P 0.05). In passive ARDS patients, FiO2 and positive end-expiratory pressure (PEEP) were statistically higher than passive normal lung (35 (33 to 47)% versus 30 (30 to 31)% and 11 (8 to 13) cmH2O versus 5 (5 to 6) cmH2O, respectively; P< 0.05).ConclusionsIntelliVent-ASV™ was safely used in unselected ventilated ICU patients with different lung conditions. Automatically selected oxygenation and ventilation settings were different according to the lung condition, especially in passive patients.Trial RegistrationClinicalTrials.gov: NCT01489085

Prospective randomized crossover study of a new closed-loop control system versus pressure support during weaning from mechanical ventilation.

Background:Intellivent is a new full closed-loop controlled ventilation that automatically adjusts both ventilation and oxygenation parameters. The authors compared gas exchange and breathing pattern variability of Intellivent and pressure support ventilation (PSV). Methods:In a prospective, randomized, single-blind design crossover study, 14 patients were ventilated during the weaning phase, with Intellivent or PSV, for two periods of 24 h in a randomized order. Arterial blood gases were obtained after 1, 8, 16, and 24 h with each mode. Ventilatory parameters were recorded continuously in a breath-by-breath basis during the two study periods. The primary endpoint was oxygenation, estimated by the calculation of the difference between the PaO2/FIO2 ratio obtained after 24 h of ventilation and the PaO2/FIO2 ratio obtained at baseline in each mode. The variability in the ventilatory parameters was also evaluated by the coefficient of variation (SD to mean ratio). Results:There were no adverse events or safety issues requiring premature interruption of both modes. The PaO2/FIO2 (mean ± SD) ratio improved significantly from 245 ± 75 at baseline to 294 ± 123 (P = 0.03) after 24 h of Intellivent. The coefficient of variation of inspiratory pressure and positive end-expiratory pressure (median [interquartile range]) were significantly higher with Intellivent, 16 [11–21] and 15 [7–23]%, compared with 6 [5–7] and 7 [5–10]% in PSV. Inspiratory pressure, positive end-expiratory pressure, and FIO2 changes were adjusted significantly more often with Intellivent compared with PSV. Conclusions:Compared with PSV, Intellivent during a 24-h period improved the PaO2/FIO2 ratio in parallel with more variability in the ventilatory support and more changes in ventilation settings.