Esmolol Corrects Severe Hypoxemia in Patients with Femoro-Femoral Venoarterial Extracorporeal Life Support for Lung Transplantation.

Competitive flows syndrome result in severe regional hypoxemia when the deoxygenated flow from the native left ventricle (LV) competes with oxygenated flow from extracorporeal life support (ECLS) pump with potentially severe consequences for the cerebral and coronary circulations. Fast correction of hypoxemia could be obtained by decreasing native LV flow by infusion of a short-acting beta-blocker (esmolol). Our purpose was to retrospectively review the efficacy of esmolol in this situation and hypothesize on the potential mechanisms of action and the associated risks. This is a retrospective analysis of five clinical cases, who underwent lung transplantation and a femoro-femoral venoarterial (VA) ECLS. The patients presented severe hypoxemia (SpO2 < 85%) measured through photoplethysmography on a right hand finger. From the patients' medical records and anesthesia flowcharts, hemodynamic, right heart catheterization, echocardiography variables, and arterial blood gas results were noted before and after injection of esmolol. Mechanical ventilation and VA ECLS function variables were optimized and unchanged before and after esmolol injection. All patients had terminal respiratory failure with pulmonary hypertension and conserved LV systolic function. Immediately following esmolol injection (1.3 ± .7 mg/kg; mean ± 1 SD), SpO2 increased from 73% ± 12 to 95% ± 6; blood to arterial partial pressure in CO2 (PaCO2) decreased from 52 ± 18 to 35 ± 7 mmHg systolic pulmonary artery pressure decreased from 61 ± 8 to 50 ± 12 mmHg; the pulmonary artery oxygen saturation (SvO2); increased from 51% ± 24 to 77% ± 12; systemic arterial pressure or catecholamine requirements were unchanged. In conclusion, these results suggest that injection of esmolol allowed rapid correction of regional hypoxemia occurring during lung transplantation despite femoro-femoral VA ECLS. The mechanism is probably a decreased cardiac output of the native LV due to esmolol-induced negative inotropic and chronotropic effects without significant adverse effects on systemic tissue perfusion.

High Level of Endotoxemia Following Out-of-Hospital Cardiac Arrest Is Associated With Severity and Duration of Postcardiac Arrest Shock.

OBJECTIVE: To investigate the contribution of endotoxemia to the severity of postcardiac arrest shock. DESIGN: A prospective monocentric study. SETTING: A tertiary hospital in Paris, France. PATIENTS: Patients admitted in our ICU after a successfully resuscitated out-of-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endotoxin measurement was performed in the 12 hours following return of spontaneous circulation using the endotoxin activity assay. Endotoxin level was classified as low (< 0.4 endotoxin activity), intermediate (0.4 to < 0.6 endotoxin activity), or high (≥ 0.6 endotoxin activity) according to manufacture guidelines. Severity of shock was assessed by the vasopressor-free days and by the mean daily dose of vasopressor to insure a mean arterial pressure of 65-75 mm Hg. Among 92 patients included in the study, 60 presented a postcardiac arrest shock. Endotoxemia level was higher in patients with postcardiac arrest shock. Among these patients, by multivariate linear regression, high endotoxin class (adjusted estimate -2.0; 95% CI, -3.90 to -0.11), public place of cardiac arrest (adjusted estimate, 1.47; 95% CI, 0.007 to 2.93), and time to return of spontaneous circulation (adjusted estimate -0.08; 95% CI, -0.13 to -0.03) were independently associated with the number of vasopressor-free days. Furthermore, high endotoxin class (adjusted estimate, 97.95; 95% CI, 20.5 to 175.4) and a nonshockable rhythm (adjusted estimate, 59.9; 95% CI, 6.2 to 113.7) were the sole factors independently associated with the mean daily dose of vasopressors. CONCLUSIONS: In patients successfully resuscitated from cardiac arrest with a postcardiac arrest shock, high level of endotoxemia is independently associated with duration of postcardiac arrest shock and the amount of vasopressive drugs. Whether treatment targeting endotoxemia could be beneficial in the management of postcardiac arrest shock needs to be studied in further randomized controlled studies.

Usefulness of CT-scan in the management of chest stab trauma: a prospective observational study.

PURPOSE: The management of chest stab wounds necessitates to perform an efficient imaging strategy. Compared to chest X-ray, computed tomography (CT) scan has a higher sensitivity. Nevertheless, the utility of diagnosing occult injuries remains controversial. Previous studies reported very different rates of management modifications induced by CT-scan. Indeed, no study specifically addressed the issue of ruling out traumatic diaphragmatic injury (TDI) in the specific population of chest stab trauma. The aim of the study was to evaluate the rate of thoracic procedures induced or guided by the results of thoracic CT-scan in the specific population of chest stab wounds. Secondary objective was to evaluate the utility of CT-scan for the diagnosis of TDI. METHODS: We conducted a prospective observational study. All consecutive patients referred to the acute care unit were included. We recorded the general characteristics of patients, the localization of wounds, all imaging tests, the final injury diagnosis, and the patients' management. We compared patients with modifications of management induced by CT-scan results to other patients. We evaluated the performance of CT-scan for the diagnosis of TDI by calculating its sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: 153 patients were included. There were 92 patients with normal chest X-ray. 67 of them received a CT-scan. 34 (51%) patients had an abnormal CT-scan, including 19 (21%) patients with thoracic new findings, with 3 (4.5%) modification of management. There were 50 patients who had an abnormal chest X-ray. 31 of them received a CT-scan, and 31 (100%) had an abnormal CT-scan, including 19 thoracic new findings, with 11 (36%) modifications of management. The diagnostic performance of CT-scan for TDI was: sensitivity 50%; specificity 95%; NPV 72%; PPV 88%. CONCLUSIONS: In chest stab trauma, CT-scans may be unnecessary outside the thoracoabdominal zone when chest X-ray is normal. In other cases, CT-scan seems to have an impact on the decision-making. In case of thoracoabdominal wounds, CT-scan helps to detect intra-abdominal injuries. The performance of CT-scan to diagnose TDI is not high enough to reliably rule out all TDI.

Performance of pre-hospital evaluations in ruling out invasive chest stab wounds.

BACKGROUND: Some guidelines advocate for managing patients with penetrating thoracic wounds in trauma centres with cardiothoracic surgery. This systematic approach is questionable. Only 15% of these patients require surgery. It is known that clinical examination fails to detect hemopneumothorax in penetrating trauma. However, no studies have evaluated the combined diagnostic performance of vital signs and the clinical evaluation of wounds. The clinical characteristics of wounds have not been investigated. We aimed to evaluate the ability of combinations of pre-hospital signs to rule out invasive chest stab trauma. METHODS: This was a prospective observational study. All consecutive adult patients hospitalized in the perioperative acute care unit of a tertiary university hospital were included. Injury diagnoses were provided by exploratory surgery and imaging tests. Patients with a final diagnosis of invasive wounds (IWs) and patients with only superficial wounds were compared. Data regarding management and outcome were analysed. RESULTS: A total of 153 patients were included. After imaging or surgery, 58 (38%) patients were diagnosed with only superficial wounds, and 95 (62%) were diagnosed with thoracic or abdominal IWs. The false-negative rate of pre-hospital evaluations in the diagnosis of IWs was 42% [31-51]IQR25-75. In stable patients, pre-hospital data could not rule out IWs, with a negative predictive value of 58% and a positive predictive value of 70%. Twenty-nine (19%) patients required early emergent cardiothoracic surgery. Among these patients, 8 (28%) had no evidence of IWs in the pre-hospital period. Among the 59 patients without pre-hospital signs of IWs, 19 (33%) underwent at least one emergent procedure. CONCLUSIONS: The combination of pre-hospital vital signs, visual evaluation of wounds, and physical examination failed to rule out IWs in patients with chest stab wounds. This implies that caution is needed in triage decision-making.

Inflammatory Cellular Response to Mechanical Ventilation in Elastase-Induced Experimental Emphysema: Role of Preexisting Alveolar Macrophages Infiltration.

An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed. C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) or maintained on spontaneous ventilation (SV) during two hours. As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while bronchoalveolar lavage cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice. In an elastase-induced model of pulmonary emphysema, normal tidal volume mechanical ventilation may produce an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response seems to be observed only when the emphysema model shows an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.

Pulmonary Effects of Adjusting Tidal Volume to Actual or Ideal Body Weight in Ventilated Obese Mice.

Obese patients could be more susceptible to mechanical ventilation (MV)-induced lung injury than non-obese patients due to weight-dependent changes in lung properties. The aim of this study was therefore to evaluate the pulmonary effects of 2 hours low VT MV in a diet-induced obese mice model, with VT calculated on either the actual body weight (VTaw) or the ideal body weight (VTiw) . First, we hypothesized that a MV with VTaw would be associated with altered lung mechanics and an increased lung inflammation. Second, we hypothesised that a MV with a VTiw would preserve lung mechanics and limit lung inflammation. We analyzed lung mechanics and inflammation using bronchoalveolar lavage (BAL) cell counts, flow cytometry tissue analysis and histology. Lung mechanics and inflammation were comparable in control and obese mice receiving VTiw. By contrast, obese mice receiving VTaw had significantly more alterations in lung mechanics, BAL cellularity and lung influx of monocytes as compared to control mice. Their monocyte expression of Gr1 and CD62L was also increased. Alveolar neutrophil infiltration was significantly increased in all obese mice as compared to controls. In conclusion, our findings suggest that protective MV with a VTaw is deleterious, with a marked alteration in lung mechanics and associated lung inflammation as compared to lean mice. With VTiw, lung mechanics and inflammation were close to that of control mice, except for an increased alveolar infiltrate of polymorphonuclear neutrophils. This inflammation might be attenuated by a blunted recruitment of inflammatory cells associated with obesity.

Current and Future Considerations for the Treatment of Hospital-Acquired Pneumonia.

UNLABELLED: Hospital-acquired pneumonia (HAP) and health-care-associated pneumonia (HCAP) are leading causes of death, morbidity, and resource utilization in hospitalized patients, and are associated with a broad range of Gram-positive and Gram-negative pathogens. Here, we discuss the different definitions of HAP and HCAP, review current guidelines regarding the treatment of these conditions, highlight the shortcomings of current therapeutic options, and discuss new antibiotic treatments. To optimize therapeutic outcomes in patients with HAP/HCAP, initial antimicrobial treatment must be appropriate and should be given as soon as possible; inappropriate or delayed therapy greatly increases morbidity and mortality. Selection of the most appropriate antimicrobial agent depends on the causative pathogen(s); initial broad-spectrum therapy is commonly recommended and should cover all pathogens that may be present. Treatment selection should also take into consideration the following factors: knowledge of underlying local risk factors for antimicrobial resistance, disease staging, and risk factors related to specific pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus (MRSA). Guidelines consistently emphasize the importance of treating HAP and HCAP with early and appropriate broad-spectrum antibiotics, and recent developments in this field have resulted in the availability of several additional treatment options. Telavancin shows potent activity against Gram-positive bacteria including MRSA and can be administered once daily; it was approved in the USA and European Union for the treatment of HAP after demonstrating non-inferiority to vancomycin. Ceftobiprole medocaril exhibits rapid antimicrobial activity against a broad range of both Gram-positive and Gram-negative pathogens, including MRSA. It was approved for the treatment of HAP (excluding ventilator-associated pneumonia) and community-acquired pneumonia in Europe in 2013. These new treatments may offer effective alternative therapeutic options for the management of HAP. FUNDING: Basilea Pharmaceutica Ltd., Basel, Switzerland.