Didier Demory

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.

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.

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.

Right ventricular function during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

Objective: To evaluate the effect of mean airway pressure under high-frequency oscillatory ventilation on right ventricular function. Design: Prospective randomized study. Setting: Intensive care unit of a tertiary care hospital. Patients: Sixteen consecutive patients within the first 48 hrs of mainly pulmonary acute respiratory distress syndrome. Interventions: After a 6-hr-period of protective conventional mechanical ventilation, patients were submitted to three 1-hr periods of high-frequency oscillatory ventilation (+ 5, + 10, + 15) in a randomized order, with a mean airway pressure level determined by adding 5, 10, or 15 cm H2O to the mean airway pressure recorded during conventional mechanical ventilation. Measurements and Main Results: Mean airway pressure was 18 ± 3 cm H2O during conventional mechanical ventilation and was increased until 33 ± 3 cm H2O at high-frequency oscillatory ventilation + 15. Right ventricular function was assessed using transesophageal echocardiography. During conventional mechanical ventilation, nine patients presented a right ventricular dysfunction (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.6) of whom four patients had a right ventricular failure (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.9). High-frequency oscillatory ventilation + 10 and + 15 further worsened right ventricular function, resulting in about a 40% increase in right ventricular end-diastolic area/left ventricular end-diastolic area ratio and a 30% increase in end-diastolic eccentricity index when compared with conventional mechanical ventilation or high-frequency oscillatory ventilation + 5 periods. At high-frequency oscillatory ventilation + 15, 15 patients had right ventricular dysfunction and nine had right ventricular failure. High-frequency oscillatory ventilation did not improve oxygenation whatever the mean airway pressure level. A significant redistribution of tidal variation to the posterior parts of the lung was observed on electrical impedance tomography measurements when increasing mean airway pressure. However, this redistribution was not observed in patients who presented a worsening of right ventricular function (right ventricular end-diastolic area/left ventricular end-diastolic area increase >40%) at high-frequency oscillatory ventilation + 15. Conclusions: In patients with mainly pulmonary acute respiratory distress syndrome, using high mean airway pressure under high-frequency oscillatory ventilation can worsen right ventricular function when compared with protective conventional mechanical ventilation, notably in patients in whom high-frequency oscillatory ventilation produced less alveolar recruitment of the posterior parts of the lungs. This study highlights the interest of monitoring right ventricular function during high-frequency oscillatory ventilation. (Crit Care Med 2012; 40:–6)

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

Does Admission During Morning Rounds Increase the Mortality of Patients in the Medical ICU

BACKGROUND Early optimization of treatment is crucial when admitting patients to the ICU and could depend on the organization of the medical team. The aim of this retrospective observational study was to determine whether admissions during morning rounds are independently associated with hospital mortality in a medical ICU. METHODS The 3,540 patients admitted from May 2000 to April 2010 to the medical ICU of Sainte Marguerite Hospital in Marseille, France, were divided into two groups based on the time of admission.The non-morning rounds group was admitted between 1:00 PM and 7:59 AM , and the morningrounds group was admitted between 8:00 AM and 12:59 PM . Hospital mortality (crude and adjusted)was compared between the two groups. RESULTS The 583 patients (16.5%) admitted during morning rounds were older and sicker upon admission compared with those patients admitted during non-morning rounds. The crude hospital mortality was 35.2% (95% CI , 31.4-39.1) in the group of patients admitted during morning rounds and 28.0% (95% CI, 26.4-29.7) in the other group ( P < .001). An admission during morning rounds was not independently associated with hospital death (adjusted hazard ratio, 1.10; 95% CI,0.94-1.28; P 5=.24). CONCLUSIONS Being admitted to the medical ICU during morning rounds is not associated with a poorer outcome than afternoon and night admissions. The conditions of the patients admitted during morning rounds were more severe, which underlines the importance of the ICU team’s availability during this time. Further studies are needed to evaluate if the presence of a specific medical team overnight in the wards would be able to improve patients’ outcome by preventing delayed ICU admission.

Generation of a single pulmonary pressure-volume curve does not durably affect oxygenation in patients with acute respiratory distress syndrome

IntroductionIt is possible that taking a static pressure-volume (PV) measurement could durably affect oxygenation and thus interfere with early evaluation of a therapeutic intervention delivered just after that measurement. The aim of the present study was to investigate the effects over time of a single static PV measurement on gas exchange and haemodynamics; the PV measurements were taken using a super syringe and by using the constant flow method in patients with acute respiratory distress syndrome.MethodWe conducted a prospective, randomized and controlled interventional study in an intensive care unit. The study was conducted in 17 patients with early acute respiratory distress syndrome ventilated with a tidal volume of 6.9 ± 1.0 ml/kg, a plateau pressure of 27 ± 7 cmH2O and a positive end-expiratory pressure [PEEP] of 10 cmH2O. They were all evaluated for 1 hour after each of the following two measurements was taken and during a control period (in a randomized order): generation of a PV curve using a 2 l super syringe (PVSS; insufflated volume = 1824 ± 381 ml, plateau pressure = 46 ± 9 cmH2O); and generation of a PV curve using the constant flow method on the ventilator (PVCF; insufflated volume = 1120 ± 115 ml in zero end-expiratory pressure after 20 s expiratory pause, plateau pressure = 46 ± 11 cmH2O). The maximal airway pressure allowed during PV measurement was 60 cmH2O. PEEP was set to 10 cmH2O immediately after PV measurement. Partial arterial oxygen tension (Pao2), partial carbon dioxide tension (Paco2) and mean arterial pressure were recorded each minute.ResultsPV measurement did not significantly affect Pao2, Paco2, mean arterial pressure and lung mechanics. Two patients exhibited a sustained increase in Pao2 by more than 20% after PVCF (>60 minutes). Two patients exhibited a decrease in Pao2 by more than 20% after PVSS, which was sustained in one. These latter patients had an upper inflection point identified on the PV curve. After PVSS, Paco2 increased by more than 10 mmHg in two patients and returned to baseline values after 15 minutes. One patient exhibited a decrease in mean arterial pressure by more than 10 mmHg for less than 5 minutes after PVSS and one patient after PVCF.ConclusionEvaluation of the effects of a strategy aimed at improving oxygenation can be reliably recorded early after a single PV measurement that is not followed by a change in PEEP level. PV measurement using the constant flow method improves oxygenation in a limited number of patients.

Sclérose latérale amyotrophique

La sclerose laterale amyotrophique (SLA) est une degenerescence progressive des neurones moteurs de la corne anterieure. Les causes d’admission en reanimation sont d’ordre respiratoire le plus souvent (pneumopathie d’inhalation, bronchite...) chez un patient connu. Parfois la SLA est revelee en reanimation devant un echec de sevrage. Le diagnostic positif se fait par l’anamnese, l’examen clinique et l’electromyogramme. Le seul traitement etiologique valide a ce jour est le Riluzole. La prise en charge symptomatique est primordiale et repose sur une approche pluridisciplinaire. Le traitement symptomatique comprend le support ventilatoire a domicile par VNI ou tracheotomie en cas de forme bulbaire, les techniques d’aide a la toux et l’assistance nutritionnelle. La reflexion ethique doit etre menee tout au long de l’evolution de la maladie.

Maladie de Crohn ou tuberculose digestive: complications liées à une erreur diagnostique

Resume Introduction Nous rapportons l’observation d’un patient atteint de tuberculose avec manifestations digestives mais traite initialement pour maladie de Crohn. Le traitement immunosuppresseur a conduit a une majoration et a une dissemination de l’atteinte tuberculeuse. Observation Un patient de 50 ans a ete hospitalise en reanimation pour detresse respiratoire dans le cadre d’une tuberculose disseminee. Apres une evolution respiratoire satisfaisante sous traitement anti-tuberculeux, un syndrome abdominal occlusif a revele une stenose ileale post-tuberculeuse. Commentaires Il est essentiel de differencier les 2 pathologies en raison des implications therapeutiques de la maladie de Crohn, pouvant amener a une explosion de la symptomatologie tuberculeuse. La prise en charge de cette derniere est medicale, avec une chirurgie reservee aux complications de type obstruction, fistulisation, perforations ou hemorragies.