Predictors of mortality and neurological function in ICU patients recovering from cardiac arrest: A Spanish nationwide prospective cohort study / Predictores de mortalidad y función neurológica en pacientes de UCI que se recuperan de una parada cardíaca: estudio prospectivo de cohortes a nivel nacional

OBJECTIVE: To identify predictors of mortality and neurological function in adult ICU patients recovering from cardiac arrest. DESIGN: A prospective cohort multicenter study was carried out. SETTINGS: Forty-six polyvalent ICUs. PATIENTS: A total of 595 patients recovering from out-of-hospital cardiac arrest (OHCA, n=285) or in-hospital cardiac arrest (IHCA, n=310). MAIN OUTCOME VARIABLES: Survival and recovery of neurological function. RESULTS: The mean cardiopulmonary resuscitation time was 18min (range 10-30). Moderate hypothermia was used in 197 patients, and 150 underwent percutaneous coronary intervention (PCI). Return of spontaneous circulation (ROSC) was achieved within 20min in 370 patients. Variables associated to mortality (ICU and in-hospital) were age (odds ratio [OR]=1.0, 95%CI 1.0-1.0 per year), non-cardiac origin of cardiac arrest (OR=2.16, 95%CI 1.38-3.38; P=0.001) and ROSC >20min (OR=3.07, 95%CI 1.97-4.78; P<0.001), whereas PCI and the presence of shockable rhythm exhibited a protective effect. Favorable neurological outcome was associated to shockable rhythm, ROSC <20min, and cardiac origin of arrest. Hypothermia did not affect survival or neurological outcome in the multivariate analysis. CONCLUSIONS: Age, non-cardiac origin of cardiac arrest and ROSC >20min were predictors of mortality. In contrast, cardiac arrest of cardiac origin, ROSC <20min, and defibrillable rhythms were associated to unfavorable neurological outcomes

OBJETIVO: Identificar predictores de mortalidad y de función neurológica en pacientes adultos ingresados en las UCI, recuperados de una parada cardíaca. DISEÑO: Estudio prospectivo de cohortes multicéntrico. ÁMBITO: Cuarenta y seis UCI polivalentes. PACIENTES: Se incluyeron 595 pacientes recuperados de una parada cardíaca extrahospitalaria (OHCA, n=285) o intrahospitalaria (IHCA, n=310). VARIABLES DE INTERÉS PRINCIPALES: Supervivencia y recuperación de la función neurológica. RESULTADOS: El tiempo medio de reanimación cardiopulmonar fue de 18min (rango: 10-30). Se usó hipotermia moderada en 197 pacientes, y 150 se sometieron a intervención coronaria percutánea (PCI). El retorno de la circulación espontánea (ROSC) se logró en 20min en 370 pacientes. Las variables asociadas con la mortalidad (UCI y en el hospital) fueron la edad (odds ratio [OR]: 1,0; IC 95%: 1,0-1,0 por año), origen no cardíaco de la parada cardíaca (OR: 2,16; IC 95%: 1,38-3,38; p = 0,001) y el ROSC>20min (OR: 3,07; IC 95%: 1,97-4,78; p < 0,001), mientras que la PCI y la presencia de ritmo desfibrilable mostraron un efecto protector. El resultado neurológico favorable se asoció con ritmo desfibrilable, ROSC<20min y origen cardíaco de la parada. En el análisis multivariable, la hipotermia no afectó a la supervivencia ni al resultado neurológico. CONCLUSIONES: La edad, el origen no cardíaco de la parada cardíaca y el ROSC>20min fueron predictores de mortalidad. Por el contrario, la parada cardíaca de origen cardíaco, el ROSC<20min, y los ritmos desfibrilables se asociaron con un resultado neurológico favorable

Predictors of mortality and neurological function in ICU patients recovering from cardiac arrest: A Spanish nationwide prospective cohort study.

OBJECTIVE: To identify predictors of mortality and neurological function in adult ICU patients recovering from cardiac arrest. DESIGN: A prospective cohort multicenter study was carried out. SETTING: Forty-six polyvalent ICUs. PATIENTS: A total of 595 patients recovering from out-of-hospital cardiac arrest (OHCA, n=285) or in-hospital cardiac arrest (IHCA, n=310). MAIN OUTCOME VARIABLES: Survival and recovery of neurological function. RESULTS: The mean cardiopulmonary resuscitation time was 18min (range 10-30). Moderate hypothermia was used in 197 patients, and 150 underwent percutaneous coronary intervention (PCI). Return of spontaneous circulation (ROSC) was achieved within 20min in 370 patients. Variables associated to mortality (ICU and in-hospital) were age (odds ratio [OR]=1.0, 95%CI 1.0-1.0 per year), non-cardiac origin of cardiac arrest (OR=2.16, 95%CI 1.38-3.38; P=0.001) and ROSC >20min (OR=3.07, 95%CI 1.97-4.78; P<0.001), whereas PCI and the presence of shockable rhythm exhibited a protective effect. Favorable neurological outcome was associated to shockable rhythm, ROSC <20min, and cardiac origin of arrest. Hypothermia did not affect survival or neurological outcome in the multivariate analysis. CONCLUSIONS: Age, non-cardiac origin of cardiac arrest and ROSC >20min were predictors of mortality. In contrast, cardiac arrest of cardiac origin, ROSC <20min, and defibrillable rhythms were associated to unfavorable neurological outcomes.

Análisis comparativo de 2 registros de infarto agudo de miocardio tras una década de cambios. Estudio IBERICA (1996-1998) y Código Infarto-Illes Balears (2008-2010) / Comparative analysis between 2 periods of acute myocardial infarction after a decade in Mallorca. IBERIA Study (996-1998) and Infarction-Code (2008-2010)

OBJETIVO: Investigar las diferencias en la mortalidad a 28 días y otras variables pronósticas en 2 periodos: IBERICA-Mallorca (1996-1998) y Código Infarto-Illes Balears (CI-IB) (2008-2010). DISEÑO: Dos cohortes prospectivas observacionales. Ámbito: Hospital Universitario Son Dureta, 1996-1998 y 2008-2010. PACIENTES: Síndrome coronario agudo con elevación de ST de≤24h, de localización anterior e inferior. Variables principales de interés: Edad, sexo, factores de riesgo cardiovascular, localización, tiempos de actuación, tratamiento de reperfusión con fibrinólisis y angioplastia primaria, administración de ácido acetilsalicílico, betabloqueantes e inhibidores de la enzima conversora de la angiotensina. Se incluyeron el grado de Killip, las arritmias malignas, las complicaciones mecánicas y el fallecimiento a los 28 días. RESULTADOS: Se analizaron 442 pacientes de los 889 incluidos en el IBERICA-Mallorca y 498 de los 847 registrados en el CI-IB. La localización y el Killip fueron similares en ambas cohortes. Las principales diferencias significativas entre el grupo IBERICA y el CI-IB fueron: edad (64 vs. 58 años), infarto previo (17,9 vs. 8,1%), tiempo síntomas-primer ECG (120 vs. 90min), tiempo primer ECG-fibrinólisis (60 vs. 35min), tratamiento fibrinolítico (54,8 vs. 18,7%), pacientes sin reperfusión (45,9 vs. 9,2%), angioplastia primaria (1,0 vs. 92,0%). La mortalidad a los 28 días fue inferior en el CI-IB (12,2 vs. 7,2%; hazard ratio 0,560; IC 95% 0,360-0,872; p = 0,010). CONCLUSIÓN: La mortalidad a los 28 días en el síndrome coronario agudo con elevación de ST en Mallorca ha disminuido en la última década, probablemente debido a un mayor tratamiento de reperfusión con angioplastia primaria y a una reducción de los tiempos de reperfusión

OBJECTIVE: To investigate the differences in mortality at 28 days and other prognostic variables in 2 periods: IBERICA-Mallorca (1996-1998) and Infarction Code of the Balearic Islands (IC-IB) (2008-2010). DESIGN: Two observational prospective cohorts. SETTING: Hospital Universitario Son Dureta, 1996-1998 and 2008-2010. PATIENTS: Acute coronary syndrome with ST elevation of≤24h of anterior and inferior site. Main variables of interest: Age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with fibrinolysis and primary angioplasty, administration of acetylsalicylic acid, beta blockers and angiotensin converting enzyme inhibitors. Killip class, malignant arrhythmias, mechanical complications and death at 28 days were included. RESULTS: Four hundred and forty-two of the 889 patients included in the IBERICA-Mallorca and 498 of 847 in the IC-IB were analyzed. The site and Killip class on admission were similar in both cohorts. The main significant difference between IBERICA and IC-IB group were age (64 vs. 58 years), prior myocardial infarction (17.9 vs. 8.1%), the median symtoms to first ECG time (120 vs. 90min), median first ECG to fibrinolysis time (60 vs. 35min), fibrinolytic therapy (54.8 vs. 18.7%), patients without revascularization treatment (45.9 vs. 9.2%), primary angioplasty (1.0% vs. 92.0%). The mortality at 28 days was lower in the IC-IB (12.2 vs. 7.2%; hazard ratio 0.560; 95% CI 0.360-0.872; P=.010). CONCLUSION: The 28-day mortality in acute coronary syndrome with ST elevation in Mallorca has declined in the last decade, basically due to increased reperfusion therapy with primary angioplasty and reducing delays time to reperfusion

Comparative analysis between 2 periods of acute myocardial infarction after a decade in Mallorca. IBERIA Study (996-1998) and Infarction-Code (2008-2010). / Análisis comparativo de 2 registros de infarto agudo de miocardio tras una década de cambios. Estudio IBERICA (1996-1998) y Código Infarto-Illes Balears (2008-2010).

OBJECTIVE: To investigate the differences in mortality at 28 days and other prognostic variables in 2 periods: IBERICA-Mallorca (1996-1998) and Infarction Code of the Balearic Islands (IC-IB) (2008-2010). DESIGN: Two observational prospective cohorts. SETTING: Hospital Universitario Son Dureta, 1996-1998 and 2008-2010. PATIENTS: Acute coronary syndrome with ST elevation of≤24h of anterior and inferior site. MAIN VARIABLES OF INTEREST: Age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with fibrinolysis and primary angioplasty, administration of acetylsalicylic acid, beta blockers and angiotensin converting enzyme inhibitors. Killip class, malignant arrhythmias, mechanical complications and death at 28 days were included. RESULTS: Four hundred and forty-two of the 889 patients included in the IBERICA-Mallorca and 498 of 847 in the IC-IB were analyzed. The site and Killip class on admission were similar in both cohorts. The main significant difference between IBERICA and IC-IB group were age (64 vs. 58 years), prior myocardial infarction (17.9 vs. 8.1%), the median symtoms to first ECG time (120 vs. 90min), median first ECG to fibrinolysis time (60 vs. 35min), fibrinolytic therapy (54.8 vs. 18.7%), patients without revascularization treatment (45.9 vs. 9.2%), primary angioplasty (1.0% vs. 92.0%). The mortality at 28 days was lower in the IC-IB (12.2 vs. 7.2%; hazard ratio 0.560; 95% CI 0.360-0.872; P=.010). CONCLUSION: The 28-day mortality in acute coronary syndrome with ST elevation in Mallorca has declined in the last decade, basically due to increased reperfusion therapy with primary angioplasty and reducing delays time to reperfusion.

Early non-invasive ventilation treatment for severe influenza pneumonia.

The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009-10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.

Gripe A pandémica en una unidad de cuidados intensivos: experiencia en España y Latinoamérica (Grupo Español de Trabajo de Gripe A Grave/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias) / Pandemic Influenza A in the ICU: Experience in Spain and Latin America GETGAG/SEMICYUC/(Spanish Work Group on Severe Pandemic Influenza A/SEMICYUC)

Introducción: La pandemia de gripe A (H1N1)v es la primera pandemia en la que las unidades de cuidados intensivos (UCI) desempeñan un papel fundamental. Su evolución ha sido muy rápida desde los primeros casos diagnosticados en México y la afectación posterior de países del cono sur hasta su llegada a Europa durante la época estival. Objetivo: Comparar las características clínicas y de evolución de los pacientes críticos ingresados hasta el 31 de julio de 2009 en España con algunas series de Latinoamérica. Material y método: Se consideraron 6 series de pacientes ingresados en la UCI. Se realizaron comparaciones de las características clínicas, complicaciones y evolución entre las series. Resultados: Los datos evidencian una población joven (35-45 años) con predominio de ingresos por neumonía viral con grave insuficiencia respiratoria y una elevada necesidad de ventilación mecánica (60-100%). Si bien algunas determinadas poblaciones, como los obesos, las embarazadas y los pacientes con enfermedad pulmonar crónica, parecen estar expuestas a un riesgo más elevado, la ausencia de comorbilidades alcanza un porcentaje considerable en casi todas las series (40-50%). La mortalidad superior en Latinoamérica osciló entre el 25 y el 50%, y demostró el particular potencial patogénico del nuevo virus. El uso del tratamiento antiviral es tardío (entre 3 y 6 días) y poco generalizado, con mayor retraso en Latinoamérica respecto de España. Conclusiones: Estos datos indican que una estrategia de tratamiento más intensivo con un acceso más precoz y fácil al antiviral podría reducir el número de pacientes que requieren UCI y su mortalidad (AU)

Introduction: Pandemic Influenza A (H1N1)v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. Objective: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. Material and method: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome were compared between series. Results: Young patients (35-45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60-100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40-50%). Mortality rate was between 25-50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. Conclusions: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality (AU)

[Pandemic influenza A in the ICU: experience in Spain and Latin America. GETGAG/SEMICYUC/(Spanish Working Group on Severe Pandemic Influenza A/SEMICYUC)]. / Gripe A pandémica en una unidad de cuidados intensivos: experiencia en España y Latinoamérica (Grupo Español de Trabajo de Gripe A Grave/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias).

INTRODUCTION: Pandemic Influenza A (H1N1)v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. OBJECTIVE: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. MATERIAL AND METHOD: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome were compared between series. RESULTS: Young patients (35-45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60-100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40-50%). Mortality rate was between 25-50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. CONCLUSIONS: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality.

The Salmonella enterica sv. Typhimurium smvA, yddG and ompD (porin) genes are required for the efficient efflux of methyl viologen.

In Gram-negative bacteria, a subset of inner membrane proteins in the major facilitator superfamily (MFS) acts as efflux pumps to decrease the intracellular concentrations of multiple toxic substrates and confers multidrug resistance. The Salmonella enterica sv. Typhimurium smvA gene encodes a product predicted to be an MFS protein most similar to QacA of Staphylococcus aureus. Like mutations in qacA, mutations in smvA confer increased sensitivity to methyl viologen (MV). Mutations in the adjacent ompD (porin) and yddG (drug/metabolite transporter) genes also confer increased sensitivity to MV, and mutations in smvA are epistatic to mutations in ompD or yddG for this phenotype. YddG and OmpD probably comprise a second efflux pump in which the OmpD porin acts as an outer membrane channel (OMC) protein for the efflux of MV and functions independently of the SmvA pump. In support of this idea, the pump dependent on YddG and OmpD has a different substrate specificity from the pump dependent on SmvA. Mutations in tolC, which encodes an OMC protein, confer increased resistance to MV. TolC apparently facilitates the import of MV, and a subset of OMC proteins including the OmpD porin and TolC may facilitate both import and export of distinct subsets of toxic substrates.