Antoine Roch

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.)

Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study.

Background:Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy. Methods:The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time). Results:Plasmatic levels of interleukin (IL)-1&bgr;, IL-6, IL-8, and tumor necrosis factor &agr; were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1&bgr;, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15–0.40] vs. 0.56 [0.38–0.89] pg/ml, P < 0.001; 91 [61–117] vs. 189 [127–294] pg/ml, P < 0.001; and 30 [22–45] vs. 49 [29–69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13–0.30] vs. 0.43 [0.34–0.54] pg/ml, P < 0.001; 54 [36–89] vs. 116 [78–208] pg/ml, P < 0.001; 16 [11–24] vs. 35 [28–53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 ± 38 vs. 171 ± 57 min, P < 0.001). Conclusion:A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

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.

A contributive result of open-lung biopsy improves survival in acute respiratory distress syndrome patients.

Objective:The impact of a contributive result of open-lung biopsy on the outcome of patients with acute respiratory distress syndrome (ARDS) has not been extensively investigated. The aim of this study was therefore to determine the rate of contributive open-lung biopsy and whether it improved the prognosis of ARDS patients. Design:Prospective study conducted during an 8-yr period. Setting:A 14-bed medico-surgical intensive care unit and a 12-bed medical intensive care unit from the same hospital. Patients:One hundred open-lung biopsies were performed in 100 patients presenting ARDS. Interventions:Open-lung biopsy was performed after ≥5 days of evolution of ARDS when there was no improvement in the respiratory status despite negative microbiological samples cultures and potential indication for corticosteroid treatment. Measurements and Main Results:Ten patients presented a mechanical complication following open-lung biopsy (two pneumothoraces and eight moderate air leaks). The unique independent factor associated with this complication was the minute ventilation when open-lung biopsy was performed (odds ratio, 1.20; 95% confidence interval, 1.03–1.41; p = .02). Fibrosis was noted in 53 patients but was associated with an infection in 29 of these 53 patients (55%). A contributive result of open-lung biopsy (defined as the addition of a new drug) was noted in 78 patients. Simplified Acute Physiology Score II was the only independent predictive factor of a contributive open-lung biopsy (odds ratio, 0.96; 95% confidence interval, 0.92–0.99; p = .04). Survival was higher in patients with a contributive open-lung biopsy (67%) than in patients in whom open-lung biopsy results did not modify the treatment (14%) (p < .001). The factors predicting survival were a contributive result of open-lung biopsy, female gender, and the Organ System Failures score the day of open-lung biopsy. Conclusions:The present study shows that open-lung biopsy provided a contributive result in 78% of ARDS patients with a negative bronchoalveolar lavage. Survival of ARDS patients improved when open-lung biopsy was contributive.

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.

Forty-minute endovascular aortic occlusion increases survival in an experimental model of uncontrolled hemorrhagic shock caused by abdominal trauma.

BACKGROUND To evaluate the feasibility of aortic balloon catheter occlusion in intra-abdominal hemorrhage. METHODS Effects of transfemoral diaphragmatic aortic balloon occlusion (ABO) have been evaluated in 25 pigs. The animals were submitted to incontrollable hemorrhage by a splenic trauma. Group 1 (n = 9) received fluid resuscitation with normal saline (NS) without aortic occlusion; group 2 (n = 8) underwent 60 minutes ABO and NS. Groups 3 (n = 4) and 4 (n = 4) underwent ABO during 40 minutes and 60 minutes, respectively, NS, and splenectomy. RESULTS Aortic balloon location was adequate in all animals. ABO increased the portion of 2-hour survivors significantly (7/16 vs. 0/9; p = 0.03). ABO increased mean arterial blood pressures (p < 0.05). There was a significant decrease of bleeding and volume of fluid resuscitation (p < 0.05) in ABO groups. Blood potassium and lactate levels at death were significantly higher in groups 2 and 4 compared with those of the control group: 29 ± 0.54 and 6.08 mmol/L ± 0.44 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L (p < 0.02), and 11.39 mmol/L ± 0.37 mmol/L and 9.59 mmol/L ± 1.19 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L (p < 0.001), respectively. There were no significant differences between group 3 and the control group: 4.83 mmol/L ± 0.32 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L and 5.2 mmol/L ± 0.13 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L, respectively. At necropsy, there were no significant differences in terms of visceral (bowel and kidney) ischemia between the different experimental groups. CONCLUSION A 40-minute ABO followed by surgical damage control improved survival in this animal model of uncontrolled hemorrhagic shock caused by abdominal trauma. ABO could be considered for the management of severe abdominal trauma.