Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2 ; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate- (P < .05) and thrombin receptor activating peptide-induced (P < .05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P = .013). Additionally, levels of the inflammatory chemokine interleukin-8 were elevated (P < .05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P = .002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro-inflammatory and oxidative stress response, however, exposure to supra-physiologic oxygen does not amplify that response. Extended-duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes.

Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

INTRODUCTION: Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated. DESIGN: Randomized clinical trial. SETTINGS: Nine-month monocentric study. PATIENTS: Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation. INTERVENTIONS: After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory pressure-very low driving pressure); 2) high pressure 24 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-high driving pressure); and 3) high pressure 17 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step. MEASUREMENTS AND MAIN RESULTS: Sixteen patients on ECMO after 7 days (1-11 d) of mechanical ventilation were included. "Ultra-protective" mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure. CONCLUSIONS: ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. (Crit Care Med 2019; 47:1505-1512).

The risk of atrial fibrillation after pneumonectomy is not impaired by preoperative administration of dexamethasone. A cohort study.

INTRODUCTION: Atrial fibrillation (AF) is one of the most frequent complications occurring after thoracic surgery especially after lung resection. It is associated with an increase in postoperative morbidity and mortality. Recent data having documented the preventive role of corticosteroids on the occurrence of AF in cardiac surgery, we sought to evaluate the effect of preoperative administration of dexamethasone on the incidence of AF after pneumonectomy. METHODS: We reviewed the files of all consecutive patients who underwent a pneumonectomy in one single centre between July 2004 and July 2012. For each patient, demographics, medical status, the surgical procedure and treatments administered including dexamethasone, were recorded. The data were analysed using a univariate analysis and a multivariate logistic regression. RESULTS: Among them, 153 patients were included and analysed; 35 (23%) presented with at least one episode of AF occurring within 48hours after surgery. Mortality was higher in these patients (26.5% versus 12.1%, P=0.06). The univariate analysis indicated that patients who had a postoperative course complicated by the occurrence of AF were older (P=0.003), had a higher SAPS2 score (P=0.002) and a higher CHADS score (P=0.05). Older age (OR=1.08; P=0.048) and preoperative treatment by anti-arrhythmics (OR=3.9; P=0.029) were documented as independent risk factors in the multivariate analysis. Preoperative administration of dexamethasone 8-12mg did not impair the incidence of AF. DISCUSSION: AF is a frequent complication after pneumonectomy associated with increased mortality. Whereas corticosteroids have been documented as preventing AF following cardiac surgery, no such effect was found after pneumonectomy.

Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA).

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap. METHODS: A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015). RESULTS: Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14-18 h) with standard oxygen therapy and 15 h (interquartile range 12-18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI -8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53-1.43; p = 0.58). Over the 7-day postoperative follow-up period, there was no statistically significant difference between the groups in the proportion of patients who remained free of any pulmonary complication (ARR 7, 95 % CI -6 to 20 %; p = 0.40). Other secondary outcomes also did not differ significantly between the two groups. CONCLUSIONS: Among patients undergoing major abdominal surgery, early preventive application of high-flow nasal cannula oxygen therapy after extubation did not result in improved pulmonary outcomes compared with standard oxygen therapy.