Esteban Lopez-de-Sa

Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest Pilot Trial Comparing 2 Levels of Target Temperature

Background— It is recommended that comatose survivors of out-of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome. Methods and Results— Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24 hours followed by 12 to 24 hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P =0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P =0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P =0.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2; P =0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups. Conclusions— The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms. Clinical Trial Registration— URL: [http://www.clinicaltrials.gov][1]. Unique identifier: [NCT01155622][2]. # Clinical Perspective {#article-title-25} [1]: http://www.clinicaltrials.gov. [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01155622&atom=%2Fcirculationaha%2F126%2F24%2F2826.atomBackground—It is recommended that comatose survivors of out-of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome. Methods and Results—Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24 hours followed by 12 to 24 hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P=0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P=0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P=0.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2; P=0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups. Conclusions—The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01155622.

Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study

Aims We explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial. Methods and results SHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized β-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65–0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55–0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54–0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations. Conclusion Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.

Is therapeutic hypothermia a risk factor for stent thrombosis

To the Editor: Pre-clinical and clinical hypothermia trials cooling subjects between 18°C and 33°C have suggested potential deleterious prothrombotic effects [(1)][1]. These data have raised major clinical concerns when considering that a large proportion of cardiac arrest survivors will undergo

Obstructive Sleep Apnea and Coronary Artery Disease: From Pathophysiology to Clinical Implications

Coronary artery disease (CAD) and obstructive sleep apnea (OSA) are both complex and significant clinical problems. The pathophysiological mechanisms that link OSA with CAD are complex and can influence the broad spectrum of conditions caused by CAD, from subclinical atherosclerosis to myocardial infarction. OSA remains a significant clinical problem among patients with CAD, and evidence suggesting its role as a risk factor for CAD is growing. Furthermore, increasing data support that CAD prognosis may be influenced by OSA and its treatment by continuous positive airway pressure (CPAP) therapy. However, stronger evidence is needed to definitely answer these questions. This paper focuses on the relationship between OSA and CAD from the pathophysiological effects of OSA in CAD, to the clinical implications of OSA and its treatment in CAD patients.

Computerized physician order entry in the cardiac intensive care unit: effects on prescription errors and workflow conditions.

PURPOSES To evaluate the effects of a computerized physician order entry (CPOE) system in the cardiac intensive care unit by detecting prescription errors (PEs) and also to assess the impact on working conditions. METHODS A longitudinal, prospective, before-after study was conducted during the periods before and after the implementation of the CPOE system. Clinical pharmacists were responsible for the registration, description and classification of PEs, and their causes and severity, according to an international taxonomy. Professionals were also surveyed for their opinion, concerns, and level of satisfaction. RESULTS A total of 470 treatment orders containing 5729 prescriptions were evaluated. The CPOE resulted in a marked reduction in the number of PEs: error rate was 44.8% (819 errors among 1829 prescriptions) with handwritten orders and 0.8% (16 among 2094 prescriptions) at the final electronic phase (P < .001). Lapses were the main cause of error in both prescription methods. Most errors did not reach the patients. Errors related with the computerized system were scarce. Most users were satisfied with many aspects of this technology, although a higher workload was reported. CONCLUSIONS Computerized physician order entry in the cardiac intensive care unit proved to be a safe and effective strategy in reducing PEs and was globally well received by professionals.

Influence of the temperature on the moment of awakening in patients treated with therapeutic hypothermia after cardiac arrest

INTRODUCTION Target temperature management (TTM) has shown to reduce brain damage after an out-of-hospital cardiac arrest (CA), but the time to neurological recovery is not defined yet. We sought to determine the time these patients need to regain consciousness, as well as factors associated with a late post-arrest awakening. METHODS We performed a retrospective analysis of patients cooled to 32-34°C during 24h after CA, who regained neurological responsiveness after rewarming. We measured the time until awakening, defined as obedience to verbal commands. RESULTS We included 163 CA survivors (84.7% male, 60.2 years) who regained consciousness after TTM: target temperature was either 32°C (36.2%), 33°C (56.4%) or 34°C (6.7%). Mean time of awakening was 3.8 days. Thirty-four patients (20.9%) regained neurological responsiveness after 5 days after CA. All of them had been cooled to either 32°C (18 patients) or 33°C (16), and no patient cooled to 34°C awakened after day 5. A lower target temperature was associated with a later awakening (p<0.001). The time to advanced cardiopulmonary resuscitation (CPR) was shorter among the early awakers (p=0.04), but we found no other predictors of an earlier awakening. CONCLUSIONS A high proportion of CA survivors induced to TTM regained consciousness after 5 days, and cooling to a lower target temperature may influence on a late neurological recovery. Therefore, withdrawal of life supporting treatment should be delayed to more than 5 days in patients cooled to 33°C or less. Time to advanced CPR was found to be a predictor of early awakening.

Uso de antagonistas de los receptores de aldosterona tras el infarto de miocardio. Datos del registro REICIAM

INTRODUCTION AND OBJECTIVES Although of proven effectiveness, there are no data available on the patterns of aldosterone antagonists use in the setting of acute myocardial infarction. METHODS The REICIAM registry is a prospective study designed to provide data regarding the incidence and management of heart failure after acute myocardial infarction. The aim of the present analysis was to determine the patterns of aldosterone antagonists use in this situation. RESULTS From a total of 2703 patients with acute myocardial infarction, 416 (15.4%) were considered optimal candidates to receive aldosterone antagonists, but only 228 (54.8%) received the treatment. The independent factors associated with their administration were male sex (odds ratio=2.06; 95% confidence interval, 1.23-3.49; P=.006), absence of prior kidney failure (odds ratio=3.31; 95% confidence interval, 1.26-9.06; P=.02), presentation with ST elevation (odds ratio=2.01; 95% confidence interval, 1.21-3.35; P=.007) and the development of malignant arrhythmias (odds ratio=2.75; 95% confidence interval, 1.3-6.05; P=.009). The lower the ejection fraction, the higher the likelihood of receiving aldosterone antagonists. The major independent predictor for receiving aldosterone antagonists was the prescription of diuretics during hospitalization (odds ratio=7.11; 95% confidence interval, 3.72-14.23; P <.00001), but also treatment with clopidogrel, beta-blockers, and statins. Although patients treated with aldosterone antagonists had a higher risk profile, they had a better 30-day survival rate than untreated patients (88.3% and 77.7% respectively; P <.0001). CONCLUSIONS The use of aldosterone antagonists in post-acute myocardial infarction is only 54.8% of the optimal candidates. Their use is associated with male sex, a higher risk profile, and the use of diuretics and other drugs of proven efficacy in secondary prevention.

A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries—The SPAME trial results

INTRODUCTION International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. METHODS This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. RESULTS The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34°C for 24h, and 33% had changed the target temperature to 36°C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p<0.01), as well as the use of a computer feedback device (p=0.03) for TTM. CONCLUSION This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.

What Should Be Done With Survivors of a Cardiac Arrest? Induce Hypothermia or Just Avoid Hyperthermia?

Hace mas de 100 anos, se senalo que la hipotermia terapeutica podria ser util tras una parada cardiaca, sobre la base de estudios animales y observaciones en pacientes aislados. Sin embargo, las guias de reanimacion cardiopulmonar solo han recomendado su empleo desde 2003, para pacientes con ritmo cardiovertible que no recuperan la conciencia despues de recuperar la circulacion espontanea, basandose en dos pequenos estudios aleatorizados publicados en 2002. Desde entonces la incorporacion de este tratamiento a las unidades de criticos ha sido lenta. Su utilidad parecia evidente, y han aparecido multiples series nacionales y extranjeras que han resaltado la mejora del pronostico en sus centros desde la incorporacion de la hipotermia en sus protocolos asistenciales. Las preguntas que empezaron a surgir entonces se centraban en el metodo, el momento de inicio, la temperatura objetivo y la duracion de esta. Todo el conocimiento adquirido en el ultimo siglo se ha tambaleado con la publicacion, hace un ano, de los 2 mayores estudios aleatorizados en pacientes recuperados de parada cardiaca extrahospitalaria (PCEH), en los que la hipotermia no mostro beneficio. Ambas publicaciones han tenido un importante impacto en el manejo de estos pacientes. Aunque sin validez cientifica, en 18 blogs y 7 podcasts analizados por el Global Emergency Medicine Journal Club, mas del 65% de los participantes de una encuesta online han respondido que, a la vista de los resultados de estos estudios, el protocolo de manejo de estos pacientes en sus centros ha cambiado a un objetivo de 36 8C o deberia fijarse en ese umbral para evitar la hipertermia, en lugar de inducir hipotermia. No obstante, solo unos meses despues de conocerse los resultados la mayoria reconocia que aun no lo habia hecho. Fuera de la hipotermia, ninguna medida ha mostrado en ensayos clinicos aleatorizados beneficio alguno para los pacientes en coma recuperados de una PCEH. Los profesionales que atendemos a estos pacientes nos preguntamos: ? que debemos hacer ahora en la practica clinica diaria? Resulta evidente que el pronostico de los pacientes ha mejorado y que estos resultados coinciden en el tiempo con la instauracion de la hipotermia, pero se

Electrocardiographic changes during induced therapeutic hypothermia in comatose survivors after cardiac arrest.

AIM To assess the safety of therapeutic hypothermia (TH) concerning arrhythmias we analyzed serial electrocardiograms (ECG) during TH. METHODS All patients recovered from a cardiac arrest with Glasgow < 9 at admission were treated with induced mild TH to 32-34 °C. TH was obtained with cool fluid infusion or a specific intravascular device. Twelve-lead ECG before, during, and after TH, as well as ECG telemetry data was recorded in all patients. From a total of 54 patients admitted with cardiac arrest during the study period, 47 patients had the 3 ECG and telemetry data available. ECG analysis was blinded and performed with manual caliper by two independent cardiologists from blinded copies of original ECG, recorded at 25 mm/s and 10 mm/mV. Coronary care unit staff analyzed ECG telemetry for rhythm disturbances. Variables measured in ECG were rhythm, RR, PR, QT and corrected QT (QTc by Bazett formula, measured in lead v2) intervals, QRS duration, presence of Osborns J wave and U wave, as well as ST segment displacement and T wave amplitude in leads II, v2 and v5. RESULTS Heart rate went down an average of 19 bpm during hypothermia and increased again 16 bpm with rewarming (P < 0.0005, both). There was a non-significant prolongation of the PR interval during TH and a significant decrease with rewarming (P = 0.041). QRS duration significantly prolonged (P = 0.041) with TH and shortened back (P < 0.005) with rewarming. QTc interval presented a mean prolongation of 58 ms (P < 0.005) during TH and a significant shortening with rewarming of 22.2 ms (P = 0.017). Osborn or J wave was found in 21.3% of the patients. New arrhythmias occurred in 38.3% of the patients. Most frequent arrhythmia was non-sustained ventricular tachycardia (19.1%), followed by severe bradycardia or paced rhythm (10.6%), accelerated nodal rhythm (8.5%) and atrial fibrillation (6.4%). No life threatening arrhythmias (sustained ventricular tachycardia, polymorphic ventricular tachycardia or ventricular fibrillation) occurred during TH. CONCLUSION A 38.3% of patients had cardiac arrhythmias during TH but without life-threatening arrhythmias. A concern may rise when inducing TH to patients with long QT syndrome.