Adición de melatonina a terapia con hipotermia para encefalopatía hipóxico-isquémica neonatal / Addition of melatonin to hypothermia therapy for neonatal hypoxic-ischemic encephalopathy

Introducción La encefalopatía hipóxico-isquémica neonatal es una patología caracterizada por una disfunción neurológica aguda, de severidad variable, causada por un episodio asfíctico perinatal. Se presenta en uno a seis de cada 1000 recién nacidos de término, asociándose a una alta morbimortalidad neonatal y a desenlaces neurológicos adversos. El uso de hipotermia es considerado como la terapia estándar para esta condición. Sin embargo, debido a su limitada eficacia clínica, se han propuesto diferentes opciones terapéuticas adyuvantes, incluyendo el uso de fármacos como la melatonina. Existe controversia sobre si la terapia combinada con melatonina es superior a la monoterapia con hipotermia. Métodos Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método Grading of Recommendations Assessment, Development and Evaluation, GRADE Resultados Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Se incluyeron los dos ensayos aleatorizados en el análisis del presente trabajo. Conclusiones No es posible establecer con claridad si la adición de melatonina disminuye la mortalidad o la probabilidad de presentar alteraciones reflejadas en la resonancia magnética cerebral, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja. Por otro lado, adicionar melatonina a la terapia con hipotermia, comparado con la monoterapia con hipotermia, podría aumentar la probabilidad de que el examen neurológico sea normal a los seis meses, y que la cognición sea normal a los 18 meses. Finalmente, la adición de melatonina a la terapia con hipotermia probablemente disminuya la probabilidad de presentar convulsiones.

Introduction Neonatal hypoxic-ischemic encephalopathy is caused by perinatal asphyxia, resulting in an acute neurological dysfunction of variable severity. It occurs in one to six of every 1000 full-term newborns and is associated with high neonatal morbimortality and adverse neurological outcomes. The use of hypothermia is considered the standard therapy for this condition. However, different adjuvant therapeutic options have been proposed due to limited clinical efficacy, including drugs like melatonin. There is controversy about whether combined therapy with melatonin is superior to monotherapy with hypothermia. Methods We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of the findings table using the GRADE approach. Results We identified two systematic reviews that included two primary studies, both randomized trials. The two randomized trials were included in the analysis of the present work. Conclusion It is not possible to establish whether the addition of melatonin decreases mortality or the probability of alterations in brain magnetic resonance imaging because the certainty of the existing evidence has been assessed as very low. On the other hand, the addition of melatonin to hypothermia therapy, compared to hypothermia monotherapy, may increase the probability of normal neurological examination at six months and the probability of normal cognition at 18 months. Finally, adding melatonin to hypothermia therapy likely reduces the probability of seizures.

Prolongación del intervalo QT durante hipotermia terapéutica en un recién nacido con encefalopatía hipóxico isquémica: a propósito de un caso / Prolongation of the QT interval during therapeutic hypothermia in a newborn with hypoxic-ischemic encephalopathy: A case report / Prolongamento do intervalo QT durante hipotermia terapêutica em recém-nascido com encefalopatia hipóxico-isquêmica: relato de caso

Resumen: El síndrome de QT largo adquirido puede ser secundario a la hipotermia, tanto accidental como terapéutica. Es poco el conocimiento sobre el efecto de ésta en la actividad eléctrica cardíaca, sobre todo en recién nacidos, y sus potenciales complicaciones. Se presenta el caso clínico de un recién nacido con diagnóstico de encefalopatía hipóxico isquémica que presenta una prolongación del intervalo QT durante el tratamiento con hipotermia. Se discute la evolución del paciente, que es consistente con lo referido en la literatura sobre el tema: buena evolución, ausencia de arritmias graves o alteraciones hemodinámicas, y normalización del electrocardiograma luego de finalizado el tratamiento.

Summary: Acquired long QT syndrome may be secondary to hypothermia, both accidental and therapeutic. There is not enough knowledge about the effect of hypothermia in cardiac activity and its potential complications, especially in newborns. We present the clinical case of a newborn with a diagnosis of hypoxic ischemic encephalopathy who has a prolonged QT interval during treatment with hypothermia. The evolution of the patient is discussed, which is consistent with what is referred to in the literature on the subject: Good evolution, absence of serious arrhythmias or hemodynamic alterations, and normalization of the ECG after the end of treatment.

Resumo: A síndrome do QT longo adquirida pode ser secundária à hipotermia, tanto acidental quanto terapêutica. Pouco se sabe sobre seu efeito na atividade elétrica cardíaca, principalmente em recém-nascidos, e suas possíveis complicações. Apresentamos o relato de caso clínico de um recém-nascido com diagnóstico de encefalopatia hipóxica isquêmica que apresenta prolongamento do intervalo QT durante o tratamento com hipotermia. Discutimos a evolução do paciente, a que é consistente com a literatura sobre o assunto: boa evolução, ausência de arritmias graves ou alterações hemodinâmicas e normalização do ECG após o término do tratamento.

The effect of mild hypothermia plus rutin on the treatment of spinal cord injury and inflammatory factors by repressing TGF-β/smad pathway

ABSTRACT Purpose To probe the mechanism of mild hypothermia combined with rutin in the treatment of spinal cord injury (SCI). Methods Thirty rats were randomized into the following groups: control, sham, model, mild hypothermia (MH), and mild hypothermia plus rutin (MH+Rutin). We used modified Allen's method to injure the spinal cord (T10) in rats, and then treated it with MH or/and rutin immediately. BBB scores were performed on all rats. We used HE staining for observing the injured spinal cord tissue; ELISA for assaying TNF-α, IL-1β, IL-8, Myeloperoxidase (MPO), and Malondialdehyde (MDA) contents; Dihydroethidium (DHE) for measuring the reactive oxygen species (ROS) content; flow cytometry for detecting apoptosis; and both RT-qPCR and Western blot for determining the expression levels of TGF-β/Smad pathway related proteins (TGF-β, Smad2, and Smad3). Results In comparison with model group, the BBB score of MH increased to a certain extent and MH+Rutin group increased more than MH group (p < 0.05). After treatment with MH and MH+Rutin, the inflammatory infiltration diminished. MH and MH+Rutin tellingly dwindled TNF-β, MDA and ROS contents (p < 0.01), and minified spinal cord cell apoptosis. MH and MH+Rutin could patently diminished TGF-β1, Smad2, and Smad3 expression (p < 0.01). Conclusions MH+Rutin can suppress the activation of TGF-β/Smad pathway, hence repressing the cellular inflammatory response after SCI.

Falso aneurisma del sitio de canulación aórtico después de cirugía cardíaca: Informe de un caso y revisión de la literatura / False aneurysm of ascending aortic cannulation site after cardiac surgery. Case report and literature review

RESUMEN El pseudoaneurisma de aorta ascendente, como complicación en cirugía cardíaca, tiene una incidencia menor del 0,5%, pero una mortalidad que varía del 6,7 al 60%. La manipulación aórtica y la infección son los principales factores predisponentes. Su clínica puede ser variada y constituir un hallazgo casual en controles posteriores. Se presenta el caso de una paciente operada de cirugía valvular mitral que a los 11 meses del postoperatorio se le diagnostica un pseudoaneurisma de aorta ascendente, que requirió tratamiento quirúrgico de emergencia. La cirugía fue llevada a cabo con la utilización de canulación periférica extramediastínica, sin requerir parada circulatoria, ni hipotermia para su correcta disección. El caso muestra una variante técnica para enfrentar una enfermedad poco frecuente, pero altamente desafiante, por la necesidad de reintervención y una correcta estrategia quirúrgica.

ABSTRACT False ascending aortic aneurysm, as a complication in cardiac surgery, has an incidence of less than 0.5%, but a mortality that ranges from 6.7% to 60%. Aortic manipulation and infection are the main predisposing factors. Its clinical presentation is non-specific and may be found incidentally on subsequent check-ups. The case of a patient undergoing mitral valve surgery who was diagnosed with ascending aortic false aneurysm, eleven months after postoperative period, requiring emergency surgical treatment is presented. The surgery was performed using extra-mediastinal peripheral cannulation, without induced circulatory arrest or hypothermia for proper dissection. The case shows a technical version to face an uncommon but highly challenging disease as it needs re-interventions and successful surgical strategies.

Targeted temperature management is related to improved clinical outcome of out-of-hospital cardiac arrest with non-shockable initial rhythm

OBJECTIVE: The benefits of targeted temperature management (TTM) for resuscitated out of hospital cardiac arrest (OHCA) with an initial non-shockable rhythm are still unclear. This study examined whether TTM reduces the mortality and improves the neurological outcomes of OHCA with a non-shockable initial rhythm. METHODS: This study analyzed the clinical outcome of 401 resuscitated patients with an initial non-shockable rhythm among a total of 1,616 OHCA patients who were registered in Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance. The impact of TTM was investigated after accounting for the patients' propensity for TTM. The primary outcome was a 30-day in-hospital course with a neurologically favorable outcome defined by a cerebral performance categories scale ≤2. RESULTS: TTM was performed in 89 patients (22%) with an initial non-shockable rhythm. Patients who has received TTM had a tendency to be younger, more likely to be female, and more likely to undergo percutaneous coronary intervention. The clinical outcome of the patients in the initial non-shockable rhythm treated by TTM was superior to those without TTM (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.27–0.46). Further analysis after propensity score matching or inverse probability of treatment weighting (IPTW) showed consistent findings (propensity score matching: HR, 0.32; 95% CI, 0.22–0.45; IPTW: HR, 0.40; 95% CI, 0.31–0.52; P<0.001, all). CONCLUSION: In this nationwide OHCA registry, TTM was related to an approximately three-fold better 30-day neurologically favorable survival of resuscitated patients with TTM treatment than patients without TTM in the initial non-shockable rhythm.

Hipotermia terapéutica controlada. Experiencia en un Hospital de Tercer Nivel / Therapeutic hypothermia. Experience in a Third Level Hospital / Hipotermia terapêutica controlada experiência em um hospital de alta complexidade

Resumen: Objetivo: Presentar la experiencia relacionada a hipotermia terapéutica controlada en pacientes graves que presentaron lesión neurológica aguda. Material y métodos: Estudio clínico, retrospectivo, observacional y descriptivo, en el Departamento de Medicina Crítica de Adultos de un Hospital de Tercer Nivel en un periodo comprendido del 01 de enero de 2016 al 31 de julio de 2017. Pacientes llevados a hipotermia terapéutica. Resultados: Cinco pacientes incluidos en el estudio, con una media de edad de 52.4 años, 80% con padecimientos neurocríticos. El promedio de estancia en la UCI fue de 15.2 días, y de hospitalización 63 días. La media de días de ventilación mecánica fue de 13.8 días. Sesenta porciento de los pacientes desarrolló neumonía asociada a la ventilación mecánica. Cuarenta porciento de los pacientes presentó una discapacidad grave. Conclusiones: La hipotermia terapéutica en el grupo estudiado no impactó de manera positiva en los desenlaces neurológicos. La complicación más frecuente fue la neumonía asociada a la ventilación mecánica.

Abstract: Objective: To present the experience related to controlled therapeutic hypothermia in severe patients who presented acute neurological injury. Material and methods: Clinical, retrospective, observational and descriptive study in the Department of Critical Care of Adults of a Hospital of Third Level in a period between January 1, 2016 and July 31, 2017. Patients taken to therapeutic hypothermia. Results: Five patients included in the study, with a mean age of 52.4 years, 80% with neurocritical conditions. The average stay in the ICU was 15.2 days, and hospitalization was 63 days. The mean number of days of mechanical ventilation was 13.8 days. Sixty percent of patients developed ventilator-associated pneumonia. Forty percent of the patients had a severe disability. Conclusions: Therapeutic hypothermia in the study group did not positively impact neurological outcomes. The most frequent complication was ventilator-associated pneumonia.

Resumo: Objetivo: Apresentar a experiência relacionada à hipotermia terapêutica controlada em pacientes graves que apresentaram lesão neurológica aguda. Material e métodos: Estudo clínico, retrospectivo, observacional e descritivo, no Departamento de Medicina Crítica de adultos, no período de 1 de janeiro de 2016 a 31 de julho de 2017. Pacientes submetidos à Hipotermia Terapêutica. Resultados: Foram incluídos no estudo 5 pacientes com idade média de 52.4 anos, 80% com alterações neurológicas. A permanência média na UTI foi de 15.2 dias e de hospitalização 63 dias. A média de dias de ventilação mecânica foi de 13.8. 60% dos pacientes desenvolveram pneumonia associada à ventilação mecânica. 40% dos pacientes tinham um incapacidade grave. Conclusões: A hipotermia terapêutica no grupo estudado não teve impacto positivo nos desfechos neurológicos. A complicação mais frequente foi pneumonia associada à ventilação mecânica.

Encefalopatía hipóxica-isquémica neonatal / Neonatal hypoxic-ischemic encephalopathy

La encefalopatía hipóxica-isquémica es un síndrome bien definido que afecta a los recién nacidos a término debido a asfixia fetal al nacer. La incidencia es 1-8 de cada 1000 nacidos en países desarrollados y asciende hasta 25 cada 1000 nacidos en países en desarrollo. Las causas más frecuentes son desprendimiento de la placenta, prolapso del cordón umbilical y rotura uterina. El criterio diagnóstico incluye incapacidad parcial o total del recién nacido para llorar y respirar al ser estimulado que requiere ventilación asistida en la sala de partos, Apgar < 5 en 5 y 10 minutos, acidemia (pH ≤ 7 y/o déficit de bases ≥ 12 mmol/l), alteraciones del estado de vigilia/sueño, de los reflejos primitivos y estiramiento muscular y tono muscular. En la forma leve la recuperación es total en tres días y sin (o con mínimas) secuelas de neurodesarrollo. En las formas moderadas y graves existen déficits neurológicos permanentes y alteraciones del neurodesarrollo (48%), 27% mueren y 25% son normales. El EEG regular o amplitud integrada y la resonancia magnética y espectroscópica realizados entre las 24 y las 96 horas y los 7 y 21 días de nacido respectivamente tienen un gran valor diagnóstico y pronóstico. Se recomienda hipotermia corporal (33.5 °C por 72 horas) antes de las 6 horas de nacido en las formas moderadas y graves. El resultado es una disminución de la mortalidad (de 35% a 27%) y de la morbilidad (de 48% a 27%).

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).

Resultados preliminares de hipotermia tópica do fígado em modelo de isquemia/reperfusão hepática em ratos / Preliminary results of topical hepatic hypothermia in a model of liver ischemia/reperfusion injury in rats

ABSTRACT BACKGROUND Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

RESUMO CONTEXTO: A isquemia/reperfusão leva a grave lesão de órgãos, mas ocorre obrigatoriamente no transplante hepático, no trauma e em outras cirurgias hepáticas complexas, quando a manobra de Pringle é aplicada com o intuito de minimizar o sangramento durante os procedimentos. É bem conhecido que a isquemia/reperfusão do fígado leva a distúrbios microcirculatórios e lesões celulares. Neste cenário, a hipotermia é conhecida por reduzir a demanda de oxigênio, diminuindo o metabolismo intracelular. OBJETIVO: Avaliar os efeitos da hipotermia na lesão de isquemia/reperfusão hepática utilizando-se um novo modelo de hipotermia isolada do fígado. MÉTODOS: Utilizaram-se ratos Wistar do sexo masculino com peso aproximado de 250 gramas, mantidos em regime de alimentação ad libitum e divididos aleatoriamente em dois grupos de nove animais: 1) Grupo Normotérmico - os ratos foram submetidos a isquemia normotérmica dos lobos hepáticos mediano e esquerdo, com posterior ressecção dos lobos direito e caudado durante a reperfusão hepática; e 2) Grupo Hipotérmico - os ratos foram submetidos a isquemia hepática sob hipotermia a 10°C. A isquemia hepática foi realizada durante 45 minutos. Os animais foram sacrificados 48 horas após a reperfusão hepática para coleta de sangue e tecido hepático para análise. RESULTADOS: As transaminases AST e ALT apresentaram diminuição significativa no grupo Hipotérmico (P<0,01) em relação ao grupo Normotérmico (1403±1234 x 454±213 e 730±680 x 271±211 U/L, respectivamente). A histologia mostrou necrose grave em 50% e necrose leve em 50% dos casos no grupo Normotérmico, porém, necrose grave em 10% e necrose leve ou ausente em 90% dos casos no grupo Hipotérmico. CONCLUSÃO: Foi demonstrado modelo simplificado de isquemia/reperfusão do fígado que simula o autotrasplante de fígado. A hipotermia tópica dos lóbulos hepáticos isolados mostrou proteção do fígado a ischemia/reperfusão, sendo um método viável e prático para qualquer tipo de estudo de preservação hepática in vivo.

Association between lactate clearance during post-resuscitation care and neurologic outcome in cardiac arrest survivors treated with targeted temperature management

OBJECTIVE: We investigated the association between lactate clearance or serum lactate levels and neurologic outcomes or in-hospital mortality in cardiac arrest survivors who were treated with targeted temperature management (TTM). METHODS: A retrospective analysis of data from cardiac arrest survivors treated with TTM between 2012 and 2015 was conducted. Serum lactate levels were measured on admission and at 12, 24, and 48 hours following admission. Lactate clearance at 12, 24, and 48 hours was also calculated. The primary outcome was neurologic outcome at discharge. The secondary outcome was in-hospital mortality. RESULTS: The study included 282 patients; 184 (65.2%) were discharged with a poor neurologic outcome, and 62 (22.0%) died. Higher serum lactate levels at 12 hours (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.006 to 1.331), 24 hours (OR, 1.320; 95% CI, 1.084 to 1.607), and 48 hours (OR, 2.474; 95% CI, 1.459 to 4.195) after admission were associated with a poor neurologic outcome. Furthermore, a higher serum lactate level at 48 hours (OR, 1.459; 95% CI, 1.181 to 1.803) following admission was associated with in-hospital mortality. Lactate clearance was not associated with neurologic outcome or in-hospital mortality at any time point after adjusting for confounders. CONCLUSION: Increased serum lactate levels after admission are associated with a poor neurologic outcome at discharge and in-hospital mortality in cardiac arrest survivors treated with TTM. Conversely, lactate clearance is not a robust surrogate marker of neurologic outcome or in-hospital mortality.

Neuroprotección en pacientes con asfixia perinatal / Neuroprotection in patients with perinatal asphyxia

Introducción: la asfixia perinatal (APN) y su consecuencia, la encefalopatía hipóxico isquémica (EHI), son responsables de la elevada morbimortalidad neonatal e infantil. El desarrollo de una estrategia integral de neuroprotección que incluya hipotermia terapéutica busca mitigar sus efectos. Objetivo: evaluar la implementación de un protocolo global de neuroprotección en un servicio de recién nacidos. Metodología: estudio monocéntrico, retrospectivo y observacional de una cohorte de pacientes que recibieron hipotermia controlada entre 2011 y 2014 internados en el Centro Hospitalario Pereira Rossell (CHPR). El protocolo incluyó la formación del personal de enfermería y el equipo médico así como la adecuación tecnológica a tales efectos. Resultados: 20 pacientes cumplieron con criterios de inclusión, 2/20 no completaron las 72 horas necesarias de enfriamiento por alteración de la coagulación y sangrado activo refractario y 4/20 fallecieron. El enfriamiento activo se inició con una mediana de 60 minutos, y el objetivo de 33,5°C se alcanzó con una mediana de 2 horas. Se observó hiperoxia e hipocapnia en la asistencia inicial y acidosis metabólica, hiponatremia e hiperglicemia durante el período de mantenimiento así como sobre-diagnóstico de crisis convulsivas. Los trastornos de la coagulación fueron los efectos adversos más graves. Conclusión: la implementación de un protocolo de asistencia del paciente asfíctico con EHI moderada-severa permite la introducción de hipotermia controlada como estrategia para reducir la mortalidad, colocándola en los niveles observados para los países de altos ingresos. Muestra la necesidad de mejorar la asistencia inicial, de controlar alteraciones del metabolismo ácido-base, metabolismo glucídico, del sodio y sobre todo de las alteraciones de la coagulación como los fenómenos asociados de mayor gravedad.

Introduction: perinatal asphyxia and its consequence, the hypoxic-ischemic encephalopathy are responsible for the high level of morbidity (and mortality) in neonates and children. The development of a comprehensive neuroprotective strategy that includes therapeutic hypothermia, aims to mitigate its effects. Objective: our goal is to achieve the implementation of a global neuroprotection protocol in a newborn service. Methodology: monocentric, retrospective and observational study of a cohort of patients that received controlled hypothermia between 2011 and 2014 and were hospitalized in the Pereira Rossell Hospital Center (CHPR). The protocol included the training of the nursing staff and the medical team as well as the necessary technological adaptation. Results: 20 patients matched the inclusion criteria, 2/20 did not fulfill the 72 hours needed for the cooling by alteration of the coagulation and active refractory bleeding and 4/20 died. The active cooling started with a mean of 60 minutes, and the goal of 33,5°C was reached with a mean of 2 hours. Both hyperoxia and hypocapnia were observed in the initial assistance and metabolic acidosis, hyponatremia and hyperglicemia were also observed during the maintenance period, as well as over-diagnosis of convulsive crisis. Coagulation disorders were the most severe side effects. Conclusion: the implementation of a protocol of assistance of the asphyctic newborn with mild-severe HIE allows the introduction of controlled hypothermia as a strategy to reduce mortality, placing it on the levels observed in higher-income countries. It shows the need of improving the initial assistance, of controlling alterations in the acid-base metabolism, glucidic metabolism, sodium metabolism and above all, of the alterations of the coagulation as the associated phenomena of greatest severity.

Advances in targeted temperature management in sepsis and the clinical value of application in ;patients / 中华急诊医学杂志

Sepsis is one of the serious illnesses leading to high mortality in ICU.Some animal experiments and clinical trails show that target temperature management has a protective effect on target organ function in sepsis,but the optimal timing,length of targeted temperature managment continued,intervention measures,and optimal target temperature obtained in sepsis remains in the great controversy.Whether the patients with sepsis would be truly benefited from the body temperature management is still worthy issue for further study.The aim of this article reviews is to trace the recent research progress on the body temperature management in sepsis.

ANÁLISE DO DESEMPENHO FÍSICO E DO EQUILÍBRIO SOB INFLUÊNCIA DA CRIOTERAPIA EM ATLETAS DE FUTSAL / PHYSICAL PERFORMANCE AND BALANCE ANALYSIS UNDER INFLUENCE OF CRYOTHERAPY IN INDOOR SOCCER ATHLETES / ANÁLISIS DEL DESEMPEÑO FÍSICO Y EQUILÍBRIO SOB INFLUENCIA DE CRIOTERAPIA EN JUGADORES DE FÚTBOL SALA

Introdução Crioterapia é a aplicação de modalidades de frio com temperatura de 0ºC a 18,3ºC, podendo interferir no desempenho físico e equilíbrio, dependendo da capacidade do indivíduo em manter a estabilização, direcionar padrões de movimentos, controlar a postura e posição articular. Objetivo Avaliar o desempenho físico, a frequência cardíaca e o equilíbrio estático com olhos abertos, em atletas de futsal (futebol de salão), antes e depois da crioimersão nos membros inferiores. Métodos Trinta e dois indivíduos do gênero masculino participaram do estudo, distribuídos aleatoriamente em dois grupos: (A) grupo controle, imersão em água a 24°C por 10 min; (B) grupo intervenção, crioimersão em água com gelo a 10°C por 10 min. Os voluntários realizavam a avaliação do equilíbrio no baropodômetro, em seguida corriam em linha reta e em ziguezague por 100 m, entravam na crioimersão, terminando com uma nova avaliação. Foram analisados o desempenho físico, através dos tempos das corridas, a frequência cardíaca, por meio de um frequencímetro e o equilíbrio, através da baropodometria e estabilometria em apoio bipodal de olhos abertos. Resultados O desempenho físico foi alterado após a crioimersão quando das análises intra e intergrupos. A frequência cardíaca apresentou diferença ao comparar-se antes e após a crio, porém sem diferenças em comparação ao controle. O equilíbrio não foi alterado após a crioimersão e nem em comparação com o grupo controle. Conclusão A crioimersão prejudicou o desempenho físico, quando a atividade foi imediatamente após a mesma, sendo desta forma o gelo não aconselhável quando se deseja desempenho na atividade desportiva. Porém não apresentou interferência na frequência cardíaca e no equilíbrio de atletas de futsal, que podem não ter sido alterados devido ao tempo da crioimersão.

Introduction Cryotherapy is the application of methods of cold temperature of 0°C to 18.3°C, which may interfere in physical performance and balance, depending on the individual's capacity of maintaining stabilization, targeting movement patterns, controlling posture and joint position. Objective To evaluate physical performance, heart rate and static balance with eyes open, in indoor soccer players before and after cold-water immersion of lower limbs. Methods Thirty-two male subjects participated in the study, being randomly divided into two groups: (A) control group, immersion in water at 24°C for 10 minutes, (B) intervention group, immersion in cold-water at 10°C for 10 minutes. The volunteers performed evaluation of balance through a baropodometer, then they ran straight and in zigzag for 100 meters, entered in cold-water immersion, ending with a new assessment. We analyzed physical performance throughout the time of race, the heart rate by means of a frequency counter, and balance through a baropodometer and stabilometry in bipedal support with their eyes open. Results The physical performance was modified after immersion in cold-water in intragroup and intergroup analysis. The heart rate showed difference when comparing before and after cryotherapy, but no differences compared to control. The balance showed no alteration after cryotherapy nor in comparison with the control group. Conclusion Cryotherapy impaired physical performance when the activity was performed immediately thereafter, therefore ice is not recommended when you want performance in sporting activities. Nevertheless, ice had no interference on heart rate and balance of indoor soccer players, which may not have been altered due to the time of immersion.

Introducción Crioterapia es la aplicación de diferentes modalidades de frio con temperatura de 0ºC a 18,3ºC, pudiendo interferir en el rendimiento físico y en el equilibrio, dependiendo de la capacidad del individuo de mantener la estabilización, direccionar padrones de movimientos, controlar la postura y posición articular. Objetivo Evaluar el rendimiento físico, la frecuencia cardíaca y el equilibrio estático con ojos abiertos, en jugadores de fútbol sala, antes y después de crioinmersión en los miembros inferiores. Métodos Treinta y dos individuos del género masculino participaron del estudio, distribuidos aleatoriamente en dos grupos: (A) grupo control, inmersión en agua a 24°C por 10 minutos; (B) grupo intervención, crioinmersión en agua con hielo a 10°C durante 10 minutos. Los voluntarios realizaban la evaluación del equilibrio en un baropodómetro, luego corrían en línea recta y en zigzag durante 100 metros, entraban en la crioinmersión, finalizando con una nueva evaluación. El rendimiento físico fue analizado a través de los tempos de carreras, la frecuencia cardíaca, por medio de un frecuencímetro cardiaco, y el equilibrio a través de baropodometría y estabilometría en apoyo bipodal con ojos abiertos. Resultados El rendimiento físico fue modificado después de la crioinmersión, tanto cuando analizados intra como intergrupal. La frecuencia cardíaca presentó diferencia significativa al comparar-se antes e después de la crioterapia, pero sin diferencias en comparación al control. El equilibrio no fue alterado después de la crioterapia ni en comparación con el grupo control. Conclusión La crioinmersión afectó negativamente el rendimiento físico, cuando la actividad fue realizada inmediatamente después de la misma, siendo de esta manera la crioinmersión no aconsejable cuando se desea incrementar el rendimiento en la actividad deportiva. Pero no presentó interferencia en la frecuencia cardíaca ni en el equilibrio en jugadores de fútbol sala, que pueden no haber sido alterados debido al tempo da crioinmersión.

The Analysis of Factors Related to Reaching to Therapeutic Range in Patients with Receiving Therapeutic Hypothermia after Return of Spontaneous Circulation after Out-of hospital Cardiac Arrest

PURPOSE: The relationship between prognostic factors and outcomes of post-cardiac arrest patients treated with therapeutic hypothermia was analyzed. METHODS: We conducted a tertiary center retrospective study of post-cardiac arrest patients treated with therapeutic hypothermia between January 2008 and December 2012. We investigated the association of the following factors with outcomes: BMI, time to ROSC, number of vasoactive drugs, smoking, alcohol, and short time to therapeutic range in hypothermia. RESULTS: A total of 251 patients were enrolled in this study. Large number of vasoactive drugs was a prognostic factor of 3-month mortality (adjusted OR 1.96, 95% CI:1.41-2.71, p or =25 kg/m2) was not associated with delayed time to therapeutic range in hypothermia. Both univariate and multivariate analysis showed that high initial BT (beta(SE)=63.64 (11.53), p<0.001) and a small number of vasoactive drugs (beta(SE)=18.66(8.74), p=0.034) were independent predictors of delayed time to therapeutic range in hypothermia. CONCLUSION: In this study, a small number of vasoactive drugs showed a significant influence on delayed time to therapeutic range in patients receiving therapeutic hypothermia after return of spontaneous circulation after out-of-hospital cardiac arrest.

Complicações da hipotermia terapêutica: diagnósticos e intervenções de enfermagem / Complicaciones de la hipotermia: los diagnósticos y las intervenciones de enfermería / Complications in therapeutic hypothermia: diagnosis and interventions

Objective: To identify nursing diagnoses according to the NANDA, upon the potential complications of patients undergoing Therapeutic Hypothermia after Cardiorespiratory arrest and propose nursing interventions, according to the Nursing Interventions Classification (NIC). Method: this is a bibliometric review of the literature from January 2003 to May 2013, in LILACS, MEDLINE, and SCIELO. Results: Five articles selected, which enabled us to identify eight Nursing diagnoses, as well as the corresponding nursing interventions. Conclusion: Despite the high efficacy of Therapeutic Hypothermia to reduce the extent of neurological damage Post-Cardiopulmonary arrest, their use is not as widespread in clinical practice. Thus, this research has aimed to provide an initial basis for considering the practice of the professional nurse assisting this patient.

Objetivo: Identificar os diagnósticos de enfermagem, segundo a NANDA, mediante as complicações potenciais dos pacientes submetidos à Hipotermia Terapêutica Pós-parada Cardiorrespiratória e propor as intervenções de enfermagem, conforme a Classificação de Intervenções de Enfermagem (NIC). Método: trata-se de uma revisão bibliométrica de literatura a partir de janeiro de 2003 até maio 2013, nas bases de dados LILACS, MEDLINE e SCIELO. Resultados: foram selecionados 5 artigos, os quais possibilitou identificar 8 diagnósticos de Enfermagem, bem como, as intervenções de Enfermagem correspondentes. Conclusão: apesar da alta eficácia da Hipotermia Terapêutica em reduzir a extensão do dano neurológico Pós-parada Cardiorrespiratória, sua utilização não é tão ampla na prática clínica. Dessa forma, esta pesquisa tem intuito de fornecer uma base inicial de reflexão para a prática do profissional enfermeiro que assiste este paciente.

Objetivo: Identificar los diagnósticos de enfermería según la NANDA, sobre las posibles complicaciones de los pacientes sometidos a Hipotermia Terapéutica después parada cardiorrespiratoria y proponer intervenciones de enfermería, de acuerdo con la Clasificación de Intervenciones de Enfermería (NIC). Método: se trata de una revisión bibliométrica de la literatura entre enero de 2003 mayo de 2013, en LILACS, MEDLINE y SCIELO. Resultados: 5 artículos fueron seleccionados, lo que nos ha permitido identificar 8 Diagnósticos de enfermería, así como las intervenciones de enfermería correspondientes. Conclusión: A pesar de la alta eficacia de la hipotermia terapéutica para reducir la magnitud del daño neurológico post-paro cardiopulmonar, su uso no está tan extendido en la práctica clínica. Por lo tanto, esta investigación ha tenido como objetivo proporcionar una base inicial para la consideración de la práctica de la enfermera profesional asistiendo a este paciente.

Temperature of cutaneous and subcutaneous tissue during the application of aerosols in rats / Comportamento térmico dos tecidos cutâneo e subcutâneo durante a aplicação de diferentes tipos de aerossóis em ratos

This study compared the thermal changes of cutaneous and subcutaneous tissues exposed to different aerosols. Thirty-six adults Wistar rats were arranged in two treatment groups, one exposed to methyl salicylate (GSM; n = 9 skin and n = 9 subcutaneous) and the other exposed to diclofenac diethylammonium (GDD; n = 9 skin and n = 9 subcutaneous) aerosols. Five jets were applied for one-second through an apparatus to reduce spray dispersion (3 cm diameter) in the lateral left thigh of the animals. Temperatures were measured every minute (min.) during 30 min., with a digital thermometer. In the skin tissue the sensor was positioned manually, in the subcutaneous tissue it was surgically inserted through the rear face and positioned in the lateral thigh. The skin temperature has homogeneously reduced in both groups. In the subcutaneous tissue the GDD has induced hypothermia from the 2nd to 20th min., the lowest temperature was recorded on the 7th min. (-3.6 0.2ºC in relation to basal). Lowering the temperature by GSM took place from the 1st to 21st min, and the lowest temperature occurred on the 1st min (-9.7 0.5ºC in relation to basal). In the three initial minutes the GSM had temperatures 25, 10 and 5% lower than the GDD. Aerosols have induced hypothermia in the tissues, while the GSM has decreased faster and reached lower values of temperature shown in the subcutaneous tissue.

A proposta do estudo foi comparar as alterações térmicas dos tecidos cutâneo e subcutâneo submetidos à aplicação de diferentes aerossóis. Trinta e seis ratos adultos da raça Wistar foram divididos em dois grupos submetidos à aplicação de aerossóis contendo salicilato de metila (GSM; n = 9 cutâneo e n = 9 subcutâneo) e diclofenaco dietilamônio (GDD; n = 9 cutâneo e n = 9 subcutâneo). Cinco jatos de duração de um segundo foram aplicados com um redutor de dispersão (diâmetro: 3 cm) na face lateral da coxa esquerda dos animais. As temperaturas foram avaliadas a cada minuto durante 30 min., por meio de termômetro digital. No tecido cutâneo, o sensor foi posicionado manualmente, para o tecido subcutâneo este foi inserido cirurgicamente por meio da face posterior e posicionado na face lateral da coxa. A temperatura cutânea foi homogeneamente reduzida em ambos os grupos. No tecido subcutâneo, o GDD induziu a hipotermia do 2 ao 20º min., a menor temperatura (- 3,6 0,2ºC em relação ao basal) foi registrada no 7º min. A redução da temperatura pelo GSM ocorreu do primeiro ao 21º min., sendo que a menor temperatura ocorreu no primeiro min (-9.7 0,5ºC em relação ao basal). Nos 3 min. iniciais, o GSM apresentou temperaturas 25, 10 e 5% menores que o GDD. Os aerossóis induziram a hipotermia nos tecidos estudados, sendo que o GSM reduziu mais rapidamente e atingiu menores valores de temperatura evidenciados no tecido subcutâneo.

The Prognostic Value of 20-minute Spot Electroencephalography within 72 hr after Resuscitation for Comatose Cardiac Arrest Survivors Treated with Therapeutic Hypothermia

PURPOSE: This study evaluated the utility of 20-minute spot electroencephalography (sEEG) for prognostication in patients treated with therapeutic hypothermia after cardiac arrest. METHODS: This was a retrospective, observational study using a prospectively collected hypothermia registry conducted at a single tertiary hospital over three years. We included patients who were monitored by sEEG within three days after resuscitation. We evaluated the prognostic value of continuous activity pattern (diffuse slowing or normal wave) for good outcome predictor and malignant pattern (epileptiform, burst suppression, and isoelectric pattern) for poor outcome predictors during hypothermia and normothermia period. RESULTS: Of 98 patients, continuous activity was displayed in 45 patients. Of these, 27 were included in the good outcome group, resulting in a positive predictive value (PPV) of 60.0% (sensitivity and specificity of 100.0 and 74.6%, respectively). Malignant patterns resulted in a PPV of 100.0% for poor outcomes (sensitivity and specificity of 35.2% and 100.0%, respectively). Continuous activity during hypothermia showed better prognostic performance for good outcome than those during normothermia (area under the curve (AUC)=0.900 (95% confidence interval (CI) 0.825-0.975) and AUC=0.827 (95% CI 0.692-0.962), respectively). For the poor outcome prediction, the AUC was 0.712 (95% CI 0.536-0.887) for malignant patterns during normothermia, and 0.656 (95% CI 0.522-0.789) for those during hypothermia. CONCLUSION: For patients treated with TH, continuous activity on sEEG, particularly during hypothermia, could contribute to the prediction of good outcomes with high specificity. Epileptiform discharge, burst suppression, and isoelectric patterns accurately predicted poor outcomes in this cohort.

Outcome and Current Status of Therapeutic Hypothermia Following Out-of-hospital Cardiac Arrest in Korea from the Korea Hypothermia Network Registry

PURPOSE: Therapeutic hypothermia (TH) has become a standard strategy for reducing brain damage in the postresuscitation period. The aim of this study is to investigate the outcomes and current performance of TH with out-of-hospital cardiac arrest (OHCA) survivors through the Korean hypothermia network (KORHN) registry. METHODS: We used the KORHN registry, a web-based, multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH from 2007 to 2012 were included. The primary outcomes were neurologic outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. RESULTS: A total of 930 patients were included; of these, 556 (59.8%) patients survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 (interquartile range (IQR): 46-200) minutes. The induction, maintenance, and rewarming durations were 150 (IQR: 80-267) minutes, 1440 (IQR: 1290-1440) minutes, and 708 (IQR: 420-900) minutes, respectively. The time from the ROSC to coronary angiography was 1,045 (IQR: 121-12,051) hours. Hyperglycemia (46.3%) was the most frequent adverse event. CONCLUSION: Over one quarter of OHCA survivors (26.8%) were discharged with good neurologic outcome. TH performance was managed appropriately in terms of the factors related to the timing of TH, which were the start time for cooling and the rewarming duration.

A Case of Successful Resuscitation of 10,150 J Shocks and Therapeutic Hypothermia on Aconitine-induced Cardiovascular Collapse

Aconitine, found in the Aconitum species, is highly extremely toxic, and has been known to cause fatal cardiac arrhythmias and cardiovascular collapse. Although several reports have described treatment of aconitine intoxication, management strategy for the patient in a hemodynamically compromised state who experienced cardiopulmonary collapse is unknown. We report here on a case of a successful cardiopulmonary resuscitation and therapeutic hypothermia in an aconitine-induced cardiovascular collapsed patient. A 73-year-old male who presented with nausea, vomiting, chest discomfort, and drowsy mental state after eating an herbal decoction made from aconite roots was admitted to the emergency department. He showed hemodynamic compromise with monomorphic ventricular tachycardia resistant to amiodarone and lidocaine. After 3 minutes on admission, he collapsed, and cardiopulmonary resuscitation was initiated. We treated him with repeated cardioversion/defibrillation of 51 times, 10,150 joules and cardiopulmonary resuscitation of 12 times, 69 minutes for 14 hours and therapeutic hypothermia for 36 hours. He recovered fully in 7 days.

The Relationship between EEG Findings and Prognosis in Out-of-Hospital Cardiac Arrest Patients during Therapeutic Hypothermia

PURPOSE: Prediction of neurologic outcome in survivors after cardiac arrest is difficult. In particular, since therapeutic hypothermia has emerged as the standard treatment for post cardiac arrest syndrome, the prediction has been more difficult. Methods for prediction of neurologic prognosis include the general neurologic examination, SSEPs, EEG, serum biomarkers, and so on. Among these, EEG was recommended for detection of non-convulsive seizure since early phase of post cardiac arrest syndrome. However, the relationship between EEG finding and neurologic outcome is not yet clear. METHODS: We conducted a retrospective observational study using a prospectively collected hypothermia database. We collected EEG findings during hypothermia and other data from January 2010 to December 2012. The EEG findings were classified according to five patterns as extremely low voltage, continuous slow wave, burst suppression, status epilepticus, and other. We analyzed the relationship between EEG pattern and one-month CPC score after cardiac arrest. RESULTS: During the study period, 121 patients were enrolled in the hypothermia database. Among these patients, 84 patients underwent EEG during hypothermia and were enrolled. The EEG patterns of enrolled patients were 20 extremely low voltage, 39 generalized slow wave, 15 burst suppression, 8 status epilepticus, and 2 alpha coma. None of the periodic, status eplilepticus, and alpha coma pattern patients showed a good neurologic outcome (CPC 1 or 2). Two of 20 extremely low voltage and 28 of 39 continuous slow wave pattern patients recovered to good neurologic outcome. CONCLUSION: Burst suppression and status epilepticus EEG pattern during hypothermia treatment showed an association with poor neurologic outcome.