Pierre Michelet

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.

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.

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.

Indications and outcome of salvage surgery for oesophageal cancer

OBJECTIVE Some patients with localised oesophageal cancer are treated with definitive chemoradiotherapy (CRT) rather than surgery. A subset of these patients experiences local failure, relapse or treatment-related complication without distant metastases, with no other curative treatment option but salvage oesophagectomy. The aim of this study was to assess the benefit/risk ratio of surgery in such context. METHODS Review of a single institution experience with 24 patients: 18 men and 6 women, with a mean age of 59 years (+/-9). Histology was squamous cell carcinoma in 18 cases and adenocarcinoma in 6. Initial stages were cIIA (n=5), cIIB (n=1) and cIII (n=18). CRT consisted of 2-6 sessions of the association 5-fluorouracil/cisplatin concomitantly with a 50-75 Gy radiation therapy. Salvage oesophagectomy was considered for the following reasons: relapse of the disease with conclusive (n=11) or inconclusive biopsies (n=7), intractable stenosis (n=3), and perforation or severe oesophagitis (n=3), at a mean delay of 74 days (14-240 days) following completion of CRT. RESULTS All patients underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy. Thirty-day and 90-day mortality rates were 21% and 25%, respectively. Anastomotic leakage (p=0.05), cardiac failure (p=0.05), length of stay (p=0.03) and the number of packed red blood cells (p=0.02) were more frequent in patients who received more than 55 Gy, leading to a doubled in-hospital mortality when compared to that of patients having received lower doses. A R0 resection was achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was observed in 3 patients (12.5%). Overall and disease-free 5-year survival rates were 35% and 21%, respectively. There was no long-term survivor following R1-R2 resections. Functional results were good in more than 80% of the long-term survivors. CONCLUSION Salvage surgery is a highly invasive and morbid operation after a volume dose of radiation exceeding 55 Gy. The indication must be carefully considered, with care taken to avoid incomplete resections. Given that long-term survival with a fair quality of life can be achieved, such high-risk surgery should be considered in selected patients at an experienced centre.

Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study.

Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.

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.

Early onset pneumonia in severe chest trauma: a risk factor analysis.

BACKGROUND The development of an early-onset pneumonia (EOP), occurring within the first 72 hours after admission, represents a critical event in severe thoracic trauma population. The aim of this study was to determine risk factors associated with the occurrence of this complication in this specific population. METHODS A retrospective review of a prospective implemented trauma registry was conducted during a 4-year period in a Level I trauma center. Over the study period, 223 severely injured patients were admitted with severe thoracic trauma (Injury Severity Score >16 and Thorax Abbreviated Injury Score >2). Multiple logistic regression analysis was used to determine the independent predictors of EOP based on the clinical characteristics and the initial management both in the field and after admission in the trauma center. RESULTS Independent predictors of EOP were the necessity of intubation and mechanical ventilation in the field (adjusted odds ratio [OR]: 11.8; 95% confidence interval [CI]: 4.3-32.7), a history of aspiration (OR: 28.6; 95% CI: 4.0-203.5), the presence of pulmonary contusion (OR: 7.0; 95% CI: 2.0-23.9), and the occurrence of a hemothorax (OR: 3.2; 95% CI: 1.4-7.6). CONCLUSION These results emphasize the influence of prehospital and early factors in the further occurrence of EOP, which allows the development of early and specific clinical management to prevent it.

Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide.

Background:In senescent heart, β-adrenergic response is altered in parallel with β1- and β2-adrenoceptor down-regulation. A negative inotropic effect of β3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that β3-adrenoceptor plays a role in β-adrenergic dysfunction in senescent heart. Methods:β-Adrenergic responses were investigated in vivo (echocardiography–dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and β-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline ± SD. Results:An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 ± 23 vs. 162 ± 16%; P < 0.05) and in vitro (127 ± 10 vs. 179 ± 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor NG-nitro-l-arginine methylester (l-NAME; 183 ± 19%), the selective NOS1 inhibitor vinyl-l-N-5(1-imino-3-butenyl)-l-ornithine (l-VNIO; 172 ± 13%), or the selective NOS2 inhibitor 1400W (183 ± 19%). In the senescent group, in parallel with β3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by l-NAME (151 ± 8%; P < 0.05) and l-VNIO (149 ± 7%; P < 0.05) but not by 1400W (132 ± 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific β3-adrenoceptor agonist BRL 37344 (167 ± 10 vs. 142 ± 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. Conclusions:In senescent cardiomyopathy, β3-adrenoceptor overexpression plays an important role in the altered β-adrenergic response via induction of NOS1-nitric oxide.