Prevalence of Reverse Triggering in Early ARDS: Results From a Multicenter Observational Study.

BACKGROUND: The prevalence of reverse triggering (RT) in the early phase of ARDS is unknown. RESEARCH QUESTION: During early ARDS, what is the proportion of patients affected by RT, what are its potential predictors, and what is its association with clinical outcomes? STUDY DESIGN AND METHODS: This was prospective, multicenter, and observational study. Patients who met the Berlin definition of ARDS with less than 72 h of mechanical ventilation and had not been paralyzed with neuromuscular blockers were screened. A 30-min recording of respiratory signals was obtained from the patients as soon as they were enrolled, and the number of breaths with RT were counted. RESULTS: One hundred patients were included. ARDS was mild to moderate in 92% of them. The recordings were obtained after a median of 1 day (interquartile range, 1-2 days) of ventilation. Fifty patients had RT, and most of these events (97%) were not associated with breath stacking. Detecting RT was associated with lower tidal volume (Vt) and less opiate infusion. The presence of RT was not associated with time to discontinuation of mechanical ventilation (subdistribution hazard ratio, 1.03; 95% CI, 0.6-1.77), but it possibly was associated with a reduced hospital mortality (hazard ratio, 0.65; 95% CI, 0.57-0.73). INTERPRETATION: Fifty percent of patients receiving assist-control ventilation for mild or moderate ARDS, sedated and nonparalyzed, demonstrate RT without breath stacking on the first day of mechanical ventilation. RT may be associated with low VTS and opiate doses. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02732041; URL: www.clinicaltrials.gov.

Automatic detection of reverse-triggering related asynchronies during mechanical ventilation in ARDS patients using flow and pressure signals.

Asynchrony due to reverse-triggering (RT) may appear in ARDS patients. The objective of this study is to validate an algorithm developed to detect these alterations in patient-ventilator interaction. We developed an algorithm that uses flow and airway pressure signals to classify breaths as normal, RT with or without breath stacking (BS) and patient initiated double-triggering (DT). The diagnostic performance of the algorithm was validated using two datasets of breaths, that are classified as stated above. The first dataset classification was based on visual inspection of esophageal pressure (Pes) signal from 699 breaths recorded from 11 ARDS patients. The other classification was obtained by vote of a group of 7 experts (2 physicians and 5 respiratory therapists, who were trained in ICU), who evaluated 1881 breaths gathered from recordings from 99 subjects. Experts used airway pressure and flow signals for breaths classification. The RT with or without BS represented 19% and 37% of breaths in Pes dataset while their frequency in the expert's dataset were 3% and 12%, respectively. The DT was very infrequent in both datasets. Algorithm classification accuracy was 0.92 (95% CI 0.89-0.94, P < 0.001) and 0.96 (95% CI 0.95-0.97, P < 0.001), in comparison with Pes and experts' opinion. Kappa statistics were 0.86 and 0.84, respectively. The algorithm precision, sensitivity and specificity for individual asynchronies were excellent. The algorithm yields an excellent accuracy for detecting clinically relevant asynchronies related to RT.

Identification and characterization of human interferon alpha inhibitors through a WISH cell line-based reporter gene assay.

Interferons (IFNs) are important glycoproteins which can stimulate or inhibit up to three hundred different genes encoding proteins involved in antiviral defense mechanisms, inflammation, adaptive immunity, angiogenesis and among other processes. Nevertheless, different genetic alterations may lead to interferon alpha (IFN-α) overproduction in human autoimmune diseases like systemic lupus erythematosus. As a consequence, IFN-α is a central molecule whose activity must be regulated to block their harmful effect on those disorders where the endogenous cytokine production constitutes the etiology of the illnesses. In this work, we evaluate the biological activity of eighty-eight compounds, from our own chemo-library, to find potential IFN-α inhibitors by using a reporter gene assay (RGA) WISH-Mx2/EGFP. We identified some compounds able to modulate negatively the IFN-α activity. The most active IFN-α inhibitors were further studied achieving promising results. In addition, some combinations of the most active compounds were analyzed accomplishing a stronger effect to decrease the IFN-α activity than each compound alone. Furthermore, the complete inhibition of the cytokine activity was reached with some combinations of compounds.

Una causa poco frecuente de hemoptisis / A rare cause of hemoptysis

Se trata de una paciente de 61 años de edad, con antecedentes de tabaquismo leve (5 paquetes/año), diabetes tipo 2 (insulino requiriente), hipertensión arterial y obesidad, que consultó por hemoptisis de 1 año de evolución. Este síntoma se presentaba en forma intermitente, sin asociación con fiebre ni pérdida de peso. Previamente se había realizado una TAC de tórax que no revelaba lesiones y una fibrobroncoscopía donde se observaba sangre roja en lóbulo inferior derecho, aunque sin lesiones endobronquiales; el cultivo del BAL resultó negativo para gérmenes comunes y BAAR

The role of surveillance cultures in guiding ventilator-associated pneumonia therapy.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is the most frequent cause of death among the nosocomial infections acquired in the ICU. Routine surveillance endotracheal aspirate (ETA) cultures in patients on mechanical ventilation have been proposed to predict the cause of VAP. Our aim is to review the available experience regarding the role of surveillance ETA cultures in guiding VAP antimicrobial therapy. RECENT FINDINGS: Microorganisms arrive in the lower respiratory tract by aspiration from the oropharynx or gastric reflux, extension from a contiguous infection, air contamination or by hematogenous seeding. Bacterial colonization of the airway leads to the development of VAP and may result from the aspiration of oropharyngeal or gastric secretions. Recent studies have suggested that surveillance cultures could provide a rationale for prescribing appropriate antibiotics, while waiting for culture results, in up to 95% of patients in whom VAP is ultimately diagnosed by bronchoalveolar lavage fluid culture. However, some authors observed that guiding therapy with those routine surveillance cultures leads to unacceptably low coverage of the pathogens producing VAP. SUMMARY: This article describes the evidence supporting the use of routine ETA cultures to prescribe appropriate initial empirical therapy compared with the current practice dictated by guidelines.

Hipertensión arterial pulmonar en un paciente con telangiectasia hemorrágica hereditaria / Pulmonary Arterial Hypertension in a Patient With Hereditary Hemorrhagic Telangiectasia

La telangiectasia hemorrágica hereditaria (THH) es una enfermedad autosómica dominante caracterizada por la tríada de epistaxis, telangiectasias y malformaciones vasculares. Las complicaciones vasculares pulmonares asociadas a esta enfermedad incluyen malformaciones arteriovenosas (MAV) pulmonares y, de forma menos frecuente, hipertensión pulmonar (HP). El presente caso clínico hace referencia a un paciente con múltiples MAV pulmonares e HP en el contexto de posible THH. Se procedió a embolización de una MAV y se inició tratamiento específico de hipertensión arterial pulmonar con un antagonista de receptores de endotelina. A continuación se describe su mejoría funcional y hemodinámica tras 3 años de seguimiento(AU)

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the triad of epistaxis, telangiectasia and vascular malformations. Pulmonary vascular complications associated with this disease include pulmonary arteriovenous malformations (AVM) and, less frequently, pulmonary hypertension (PH). We report the case of a patient who presented multiple pulmonary AVM and PH probably due to HHT. Embolization was carried out on one of the AVM and the patient received specific pulmonary arterial hypertension treatment with an endothelin receptor antagonist. We also described the patient's functional and hemodynamic improvement after almost 3 years of follow-up(AU)

Pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the triad of epistaxis, telangiectasia and vascular malformations. Pulmonary vascular complications associated with this disease include pulmonary arteriovenous malformations (AVM) and, less frequently, pulmonary hypertension (PH). We report the case of a patient who presented multiple pulmonary AVM and PH probably due to HHT. Embolization was carried out on one of the AVM and the patient received specific pulmonary arterial hypertension treatment with an endothelin receptor antagonist. We also described the patient's functional and hemodynamic improvement after almost 3 years of follow-up.

[Severe respiratory disease in an intensive care unit during influenza A(H1N1) 2009 pandemia]. / Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1) 2009.

We describe characteristics of patients admitted to our intensive care unit with severe acute respiratory illness and influenza-like syndrome during the first months of the pandemic influenza A(H1N1) 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66). A 54% (17) had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections) was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively). Six patients died (19%); they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset) was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043). There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities.

Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1) 2009 / Severe respiratory disease in an intensive care unit during influenza A(H1N1)2009 pandemia

Se describen pacientes hospitalizados en una unidad de terapia intensiva por enfermedad respiratoria aguda grave con características de influenza durante los primeros meses de la pandemia por influenza A(H1N1) 2009 en la Argentina. Evaluamos datos clínicos, scores de gravedad, pruebas de laboratorio, microbiología y radiología torácica al ingreso, evolución y mortalidad hospitalaria, comparando pacientes con y sin confirmación de H1N1 por test de reacción de polimerasa en cadena, transcriptasa reversa (RT-PCR). Entre junio y julio de 2009 se internaron 31 pacientes adultos con una mediana de edad de 54 años (percentilo 25-75: 33-66). Presentaron test positivo para H1N1, 17 pacientes. Tenían al menos una condición concurrente 16 pacientes. La expresión radiográfica más frecuente fue infiltrados intersticio-alveolares bilaterales en 20 casos; 5 tenían consolidación lobar unilateral. La coinfección bacteriana (aislamiento de bacterias o IgM positiva para infecciones bacterianas), se demostró en 21 pacientes. Requirieron ventilación mecánica 23 pacientes y 18 desarrollaron síndrome de distrés respiratorio agudo (SDRA). La linfopenia y elevación de creatinina-fosfoquinasa fue frecuente (83% y 65%, respectivamente). Los 6 pacientes que murieron (19%) eran mayores de 75 años o tenían cáncer o inmunodepresión. El tratamiento antiviral temprano (≤ 48 horas) se asoció a menor necesidad de ventilación mecánica (54% vs. 89%; p: 0.043). No hubo diferencia significativa en las variables analizadas entre el grupo H1N1 positivo y el negativo, lo que sugiere tener igual enfoque terapéutico frente a una epidemia. La infección por H1N1 determinó falla respiratoria aguda y SDRA. La mortalidad ocurrió en pacientes añosos o con co-morbilidades graves.

We describe characteristics of patients admitted to our intensive care unit with severe acute respiratory illness and influenza-like syndrome during the first months of the pandemic influenza A(H1N1) 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66). A 54% (17) had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections) was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively). Six patients died (19%); they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset) was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043). There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities.

Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis.

Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycoprotein VI agonist convulxin resulted in a rapid loss of mitochondrial transmembrane potential (Deltapsi(m)) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H(2)O(2), a known activator of MPTP formation, also increased high-level surface fibrinogen retention, phosphatidylserine externalization, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis.

Monitoreo respiratorio y su rol en Terapia intensiva / Respiratory monitoring and its role in intensive therapy

El monitoreo respiratorio (MR) complementa al juicio clínico y puede estar asociado a la asistencia respiratoria mecánica (ARM) o no. Se reconocen tres períodos asociados al desarrollo del MR: entre 1964 y 1974 el MR lo constituía la medición de pH y gases en sangre arterial, y la medición de volumen minuto respiratorio era excepcional. Entre 1975 y 1985 seintrodujeron componentes electrónicos en los respiradores y se disponía de respiradores volumétricos con espirómetro incorporado, permitiendo desarrollar técnicas de mediciónde compliance y otros valores derivados. También se desarrolló la oxicapnometría, que se transformó en un auxiliar para el control de la respiración. El último período comenzó en 1985 y se caracteriza por la aparición de respiradores microprocesados, que suministrandiferentes modos ventilatorios y de monitores simples y fáciles de operar, capaces de determinar variables mecánicas antes reservadas a laboratorios de fisiopatología. Estosrespiradores de alta tecnología contienen monitores que informan en tiempo real sobre diversas variables durante la ARM, pero que al retirar el respirador dejan de informar. Sedebería aprovechar la disponibilidad de monitores aislados para continuar con el monitoreo, aún después del retiro del respirador, lo cual ha demostrado ser beneficioso.

Respiratory monitoring (RM) complements the clinical judgement and may be associated or not with mechanical ventilation (MV). Three periods in relation to the development of RM could be recognized: from 1964 to 1974 RM was done by pH and blood gases measurements, the measurement of minute ventilation was not routinely performed. Between 1975 and 1985 electronic components were introduced in the ventilators and volumetric ventilators with incorporated spirometer became available permitting the measuring of compliance and other derived measurements. After becoming available, oxicapnometry was considereda useful tool for monitoring respiration. The last period began in 1985 and was characterized by the arising of microprocessed ventilators able to provide different ventilatory modalities,equipped with simple and easy to operate monitors that could calculate mechanical variables that in the past were limited to respiratory physiology laboratories. These high tech ventilators are equipped with monitors informing at real time about physiological variables,however, after the weaning this information stops to be available. The availability of those stand alone monitors should be taken into account to continue the monitoring, even after the weaning; as this has been demonstrated to be beneficial.

[Argentine consensus of non-invasive ventilation]. / Consenso argentino de ventilación no invasiva.

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.

Consenso argentino de ventilación no invasiva. / [Argentine consensus of non-invasive ventilation]

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.

Complicaciones respiratorias en el postoperatorio inmediato de la cirugia coronaria / Respiratory complications immediately after coronary surgery

La influencia de la incisión quirúrgica, anestesia y condiciones específicas de la cirugía cardíaca sobre las alteraciones de la función pulmonar es analizada. La hipoxemia (presente aún en los post-operatorios no complicados) puede adjudicar-se a hipoventilación alveolar, alteraciones de la relación ventilación-perfusión o shunt. Los mecanismos de producción de atelectasias (presentes en 50-92 por ciento de los pacientes) y derrame pleural (42-87 por ciento) son discutidos. El daño del frénico se debe habitualmente a injuria térmica. Otras complicaciones menos frecuentes son descriptas. Se analiza la influencia de la edad, el tabaquismo y la enfermedad pulmonar previa sobre las complicaciones respiratorias. Se discuten los distintos aspectos del manejo respiratorio post-operatorio como el momento e indicaciones de extubación y los resultados de las distintas modalidades respiratorias (uso de PEEP, CPAP, y dispositivos de incentivación inspiratoria). (AU)

Complicaciones respiratorias en el postoperatorio inmediato de la cirugia coronaria / Respiratory complications immediately after coronary surgery

La influencia de la incisión quirúrgica, anestesia y condiciones específicas de la cirugía cardíaca sobre las alteraciones de la función pulmonar es analizada. La hipoxemia (presente aún en los post-operatorios no complicados) puede adjudicar-se a hipoventilación alveolar, alteraciones de la relación ventilación-perfusión o shunt. Los mecanismos de producción de atelectasias (presentes en 50-92 por ciento de los pacientes) y derrame pleural (42-87 por ciento) son discutidos. El daño del frénico se debe habitualmente a injuria térmica. Otras complicaciones menos frecuentes son descriptas. Se analiza la influencia de la edad, el tabaquismo y la enfermedad pulmonar previa sobre las complicaciones respiratorias. Se discuten los distintos aspectos del manejo respiratorio post-operatorio como el momento e indicaciones de extubación y los resultados de las distintas modalidades respiratorias (uso de PEEP, CPAP, y dispositivos de incentivación inspiratoria).