Hipotermia terapêutica na encefalopatia hipóxico-isquêmica neonatal: revisão integrativa / Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: integrative review / Hipotermia terapéutica em la encefalopatía hipóxico-isquémica neonatal: revisión integrativa

Objetivo: identificar evidências acerca do uso seguro da hipotermia terapêutica em recém-nascidos. Método: revisão integrativa realizada entre junho e julho de 2018, em fontes eletrônicas da Biblioteca Virtual de Saúde e PubMed, por meio da pergunta:"Que evidências podem subsidiar o cuidado de enfermagem voltado para a redução de sequelas em recém-nascidos submetidos à hipotermia terapêutica?".Foram eleitos nove artigos para análise, sendo oito internacionais e um nacional. Resultados:o resfriamento deve acontecer por 72 horas, com hipotermia leve. As indicações para inclusão no protocolo foram: primeiras seis horas de vida, idade gestacional maior que 35 semanas e acidose na primeira hora de vida.São cuidados essenciais: monitoração hemodinâmica, observação da pele, controle térmico retal, vigilância do Eletroencefalograma de Amplitude Integrada. Conclusão: a terapêutica apresenta benefícios, porém sua aplicação depende de protocolo institucional e treinamento das equipes com foco nas potenciais complicações.

Objective: to identify the evidence on safe use of therapeutic hypothermia in newborns. Method: integrative review of the literature, conducted between June and July of 2018, in electronic sources from the Virtual Health Library and PubMed, through the question: "What evidence can support nursing care aimed at reducing sequelae in newborns undergoing therapeutic hypothermia?". Analysis was conducted for nine selected article, being eight from international literature and one from Brazilian national literature. Results: cooling should occur for 72 hours with mild hypothermia. Indications for inclusion in the protocol were: first six hours of life, gestational age greater than 35 weeks and acidosis in the first hour of life. Essential care includes hemodynamic monitoring, skin observation, rectal thermal control, Integrated Amplitude Electroencephalogram surveillance. Conclusion: the therapy has benefits, but its application depends on institutional protocol and team training focusing on potential complications.

Objetivo: identificar la evidencia sobre el uso seguro de la hipotermia terapéutica en recién nacidos. Método: revisión integradora de la literatura, realizada entre junio y julio de 2018, en fuentes electrónicas de la Biblioteca Virtual de Salud y PubMed, a través de la pregunta: "¿Qué evidencia puede apoyar la atención de enfermería dirigida a reducir las secuelas en los recién nacidos que sufren hipotermia terapéutica?". Se realizaron análisis para nueve artículos seleccionados, ocho de literatura internacional y uno de literatura nacional brasileña. Resultados: el enfriamiento debe ocurrir durante 72 horas con hipotermia leve. Las indicaciones para la inclusión en el protocolo fueron: primeras seis horas de vida, edad gestacional mayor de 35 semanas y acidosis en la primera hora de vida. El cuidado esencial incluye monitoreo hemodinámico, observación de la piel, control térmico rectal, vigilancia integrada de electroencefalograma de amplitud. Conclusión: la terapia tiene beneficios, pero su aplicación depende del protocolo institucional y del entrenamiento del equipo, enfocándose en posibles complicaciones.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

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.

Necrosis grasa subcutánea con hipercalcemia persistente en un neonato tratado con hipotermia terapéutica: Reporte de un caso / Subcutaneous fat necrosis and persistent hypercalcaemia in a newborn treated with therapeutic neonatal hypothermia: A case report

La hipotermia terapéutica constituye el tratamiento de elección para los recién nacidos con encefalopatía hipóxico-isquémica moderada-grave, que cambia el pronóstico de estos niños y se acepta como una técnica segura y con escasas complicaciones secundarias considerando su beneficio. Un posible efecto adverso es la necrosis grasa subcutánea, una paniculitis transitoria aguda de presentación durante las primeras semanas de vida. Se presenta un caso de un recién nacido a término afecto de encefalopatía hipóxico-isquémica con lesiones cutáneas en forma de eritema multiforme generalizado y placas eritematosas firmes e induradas en la espalda, los glúteos y las extremidades a los 12 días de vida, tras el tratamiento con hipotermia. El estudio histopatológico, tras la biopsia cutánea, confirmó la sospecha de necrosis grasa subcutánea. Al mes de vida, presentó cifras elevadas de calcio sérico, que precisaron tratamiento con hidratación intravenosa y diuréticos. La calcemia descendió hasta normalizarse a los 3 meses, con desaparición progresiva de las lesiones cutáneas.

Therapeutic hypothermia is the current standard treatment in newborns with moderate to severe hypoxic-ischemic encephalopathy, changing the outcome of these children. It is considered a safe technique with almost no side effects. A possible adverse side event is subcutaneous fat necrosis, which is an acute self-limiting panniculitis that develops during the first weeks of life. We report a case of a newborn at term suffering hypoxic-ischemic encephalopathy with a generalized multiform erythematous rash and firm and indurated plaques over the back, buttocks and extremities on his 12th day of life after being treated with therapeutic hypothermia. Histopathological study after skin punchbiopsy confirmed the suspicion of subcutaneous fat necrosis. The infant developed asymptomatic moderate hypercalcaemia within the first month of life, which was treated with intravenous fluids and diuretics. Serum calcium levels decreased and normalized in 3 months, with progressive disappearance of skin lesions.

Hipotermia terapêutica para recém-nascidos com encefalopatia hipóxico isquêmica / Hypothermia therapy for newborns with hypoxic ischemic encephalopathy

Resumo Objetivo: A hipotermia terapêutica reduz a lesão cerebral e melhora o desfecho neurológico de recém-nascidos após insulto hipóxico isquêmico. Indicada para recém-nascidos a termo ou próximo do termo com evidência de asfixia perinatal e encefalopatia hipóxico isquêmica (EHI). Fontes dos dados: Foi feita uma procura no PubMed por publicações sobre hipotermia terapêutica em recém-nascidos com asfixia perinatal e selecionadas aquelas julgadas mais relevantes pelos autores. Síntese dos dados: Há duas técnicas de resfriamento corpóreo: hipotermia seletiva da cabeça e hipotermia corpórea total. A temperatura de resfriamento deve ser 34,5 ºC para seletiva de cabeça e 33,5 ºC para corpórea total; temperaturas inferiores a 32 ºC são menos neuroprotetoras e abaixo de 30 ºC há efeitos adversos sistêmicos graves. Indica-se o início da hipotermia terapêutica até seis horas após o nascimento, pois estudos evidenciaram que essa é a janela terapêutica da agressão hipóxico e isquêmica. A hipotermia deve ser mantida por 72 horas com rigorosa monitoração da temperatura corporal do recém-nascido. A hipotermia tem sido efetiva em reduzir sequelas neurológicas, principalmente em recém-nascidos de termo ou próximo do termo com encefalopatia hipóxico isquêmica moderada e em melhorar o prognóstico em longo prazo dos recém-nascidos com EHI. Conclusão: A hipotermia terapêutica é uma técnica neuroprotetora indicada para recém-nascidos com asfixia perinatal.

Abstract Objective: Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). Sources: A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. Summary of the findings: There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 ºC for selective head cooling and 33.5 ºC for total body cooling. Temperatures lower than 32 ºC are less neuroprotective, and temperatures below 30 ºC are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6 hours after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 hours, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate HIE. Conclusion: Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and HIE.

Neuroprotective body hypothermia among newborns with hypoxic ischemic encephalopathy: three-year experience in a tertiary university hospital. A retrospective observational study / Hipotermia corpórea neuroprotetora em recém-nascidos com encefalopatia hipóxico-isquêmica: três anos de experiência em hospital universitário terciário. Um estudo observacional retrospectivo

CONTEXT AND OBJECTIVE:Neonatal hypoxic-ischemic encephalopathy is associated with high morbidity and mortality. Studies have shown that therapeutic hypothermia decreases neurological sequelae and death. Our aim was therefore to report on a three-year experience of therapeutic hypothermia among asphyxiated newborns.DESIGN AND SETTING:Retrospective study, conducted in a university hospital.METHODS:Thirty-five patients with perinatal asphyxia undergoing body cooling between May 2009 and November 2012 were evaluated.RESULTS:Thirty-nine infants fulfilled the hypothermia protocol criteria. Four newborns were removed from study due to refractory septic shock, non-maintenance of temperature and severe coagulopathy. The median Apgar scores at 1 and 5 minutes were 2 and 5. The main complication was infection, diagnosed in seven mothers (20%) and 14 newborns (40%). Convulsions occurred in 15 infants (43%). Thirty-one patients (88.6%) required mechanical ventilation and 14 of them (45%) were extubated within 24 hours. The duration of mechanical ventilation among the others was 7.7 days. The cooling protocol was started 1.8 hours after birth. All patients showed elevated levels of creatine phosphokinase, creatine phosphokinase- MB and lactate dehydrogenase. There was no severe arrhythmia; one newborn (2.9%) presented controlled coagulopathy. Four patients (11.4%) presented controlled hypotension. Twenty-nine patients (82.9%) underwent cerebral ultrasonography and 10 of them (34.5%) presented white matter hyper-echogenicity. Brain magnetic resonance imaging was performed on 33 infants (94.3%) and 11 of them (33.3%) presented hypoxic-ischemic changes. The hospital stay was 23 days. All newborns were discharged. Two patients (5.8%) needed gastrostomy.CONCLUSION:Hypothermia as therapy for asphyxiated newborns was shown to be safe.

CONTEXTO E OBJETIVO:A encefalopatia hipóxico-isquêmica neonatal apresenta alta morbi-mortalidade. Estudos com hipotermia comprovam diminuição de sequelas neurológicas e morte. Nosso objetivo foi então relatar experiência de três anos da hipotermia terapêutica em recém-nascidos (RN) asfixiados.TIPO DE ESTUDO E LOCAL:Estudo restrospectivo, conduzido em hospital universitário.MÉTODOS:Trinta e cinco pacientes com asfixia perinatal submetidos a resfriamento corporal entre maio de 2009 e novembro de 2012 foram avaliados.RESULTADOS:Trinta e nove RN preencheram os critérios do protocolo de hipotermia. Quatro RN foram excluídos devido a choque séptico refratário, não manutenção da temperatura e coagulopatia grave. A mediana do Apgar de 1 e 5 minutos foi de 2 e 5. A maior complicação foi infecção, diagnosticada em sete mães (20%) e 14 RN (40%). Convulsão ocorreu em 15 RN (43%). 31 pacientes (88,6%) necessitaram da ventilação mecânica e 14 (45%) foram extubados em 24 horas. O tempo de ventilação mecânica dos demais foi de 7,7 dias. O início do resfriamento ocorreu com 1,8 horas de vida. Todos os pacientes apresentaram níveis elevados de creatinofosfoquinase, creatinofosfoquinase-MB e desidrogenase lática. Não se observou arritmia grave; um RN (2,9%) apresentou coagulopatia controlada. Quatro pacientes (11,4%) tiveram hipotensão controlada. Realizou-se ultrassonografia cerebral em 29 pacientes (82,9%), 10 (34,5%) com hiperecogenicidade da substância branca. 33 RN (94,3%) fizeram ressonância magnética cerebral, 11 (33,3%) com alterações hipóxico-isquêmicas. O tempo de internação foi de 23 dias e todos receberam alta. Dois pacientes (5,8%) necessitaram de gastrostomia.CONCLUSÃO:A hipotermia como terapêutica para RN asfixiados demonstrou ser segura.

Hipotermia terapéutica en la lesión traumática cerebral / Therapeutic hypothermia in traumatic brain injury

El trauma craneoencefálico severo es una causa importante de mortalidad en pacientes jóvenes a nivel internacional. La hipertensión intracraneal es la causa de más del 80 por ciento de los pacientes con lesión traumática cerebral. Al presentar una traumática secundaria, se inician una seria de mecanismos metabólicos que incrementan la lesión al tejido cerebral, la inducción de hipotermia ha demostrado que puede alterar el curso natural del proceso patológico. Los fundamentos biológicos apuntan a que la hipotermia puede tener un potencial beneficio, aunque algunas publicaciones no han demostrado mejoría, es claro que en un grupo de pacientes principalmente jóvenes, la hipotermia temprana puede ser beneficiosa. Presentamos una práctica revisión de la literatura sobre esta temática.

The severe head trauma is a major cause of mortality in young patients worldwide. Intracranial hypertension is the cause of more than 80 percent of patients with traumatic brain injury. When a traumatic secondary presenter, begin a series of mechanisms that increase metabolic injury to brain tissue, induction of hypothermia has been shown to alter the natural course of the disease process. The biological foundations suggest that hypothermia may have a potential benefit, although some publications have not shown improvement, it is clear that in a group of mostly young patients, early hypothermia may be beneficial. We present a practical review of the literature on this subject.

Perioperative hypothermia and incidence of surgical wound infection: a bibliographic study / Hipotermia perioperatória e aumento de infecção da ferida cirúrgica: estudo bibliográfico

The purpose of this review article was to understand and analyze the scientific production related to the occurrence of perioperative hypothermia and the incidence of infection on the surgical site. For this purpose, a search was conducted in the databases LILACS, MEDLINE, PubMed, CINAHL and Cochrane, using the health science descriptors DECS, from 2004 to 2009. A total of 91 articles were found. After eliminating duplicate items and using selection criteria for inclusion, six manuscripts remained for analysis. The studies were classified as retrospective, prospective, case studies, and clinical trials. After analysis, the majority of studies showed that hypothermia must be prevented during the perioperative period to reduce complications in the healing process of the surgical incision. Therefore, unadverted hypothermia directly influences in surgical site healing, increasing the incidence of infection in the surgical wound.

A proposta deste artigo foi conhecer e analisar a produção científica relacionada à ocorrência de hipotermia perioperatória e à incidência de infecção no sítio cirúrgico. Foi realizado um levantamento nas bases de dados LILACS, MEDLINE, PubMed, CINAHL e Cochrane, com descritores do DECS, em um período de 2004 a 2009. Foram encontrados 91 artigos. Após a eliminação dos artigos duplicados e da seleção por critérios de inclusão, restaram seis manuscritos para análise. Os estudos foram divididos em análise retrospectiva, estudos de caso, ensaio clínico e estudo prospectivo. Após a análise dos estudos, a maioria apontou que a hipotermia deve ser prevenida durante o perioperatório, a fim de diminuir as complicações na cicatrização da incisão cirúrgica. Assim, a hipotermia inadvertida influi diretamente no processo de cicatrização do sítio cirúrgico, aumentando a incidência de infecção da ferida operatória.

Effects of perioperative hypothermia and reactive oxygen species in the healing of colonic anastomosis in rats

PURPOSE: We evaluated the hypothesis that induced perioperative hypothermia (32 ± 1ºC) affects the redox balance in the tissue of colonic anastomosis in rats by modifying biochemical enzymatic and non-enzymatic markers related to oxidative stress. METHODS: Forty-eight male Wistar rats were randomly divided into eight experimental groups of six animals each and underwent laparotomy, sigmoid section and immediate anastomosis. Four groups were operated under normothermia (36 ± 1ºC), and the other four under hypothermia (32 ± 1ºC). The animals were reoperated on days 3, 7 and 14 postoperatively, and two groups underwent SHAM at 3 days. From the scar tissue samples, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated, and the levels of non-enzymatic markers of oxidative stress, such as reduced glutathione (GSH) and lipid peroxidation, were measured by the thiobarbituric acid reactive substances (TBARS) assay. The means were compared between groups corresponding to each day of sampling and euthanasia. RESULTS: The hypothermic groups showed a significant reduction on the activity of SOD on day 7 postoperatively, on the activity of CAT on days 7 and 14 postoperatively and on the levels of GSH on day 7 postoperatively. The level of lipid peroxidation was increased in the hypothermia group on day 7 postoperatively and decreased on day 14 compared with the normothermic groups. CONCLUSION: Perioperative hypothermia reduced the activity of the antioxidant enzymes catalase and superoxide dismutase, glutathione levels and increased lipid peroxidation in the scar tissue of colonic anastomoses in rats. .

Unexpected Fatal Hypernatremia after Successful Cardiopulmonary Resuscitation with Therapeutic Hypothermia: A Case Report

Central diabetes insipidus (DI), characterized by unexpected fatal hypernatremia, is a rare complication after successful cardiopulmonary resuscitation with therapeutic hypothermia, but may be potentially fatal if recognition is delayed. We describe here a patient who experienced cardiac arrest due to a pulmonary embolism, followed by successful resuscitation after induction of therapeutic hypothermia. The patient, however, suddenly developed unexpected hypernatremia with increased urine output and was diagnosed with central DI as a complication of cerebral edema, and eventually died. Our findings suggest that central DI should be considered as a possible complication following unexpected hypernatremia with increased urine output during therapeutic hypothermia and that desmopressin acetate should be used to treat central DI.

Electric countershock and cold stress effects on liver and adrenal gland

OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300-mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to -8ºC temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats.

Uso de hipotermia en el paro cardiorrespiratorio extrahospitalario: reporte de un caso / Use of hypothermia in out of hospital pediatric arrest: a case report

Moderate hypothermia decreases mortality and improves neurological outcome in adults as well as newborns affected with Neonatal Asphyxia. The effect of hypothermia among children with cardiac arrest (CRA) is not known. Objective: Case description of the use of therapeutic hypothermia in a pediatric patient with cardiac arrest. Clinical Case: Four-year-old girl who presented extra-hospitalary CRA, where moderate hypothermia (34 degrees Celsius) was used for neurological protection in a PICU. The patient was discharged in satisfactory neurological condition, as rated through a Pediatric Cerebral Performance Category (PCPC) Test assessment, with a score of 2, similar to her baseline evaluation. Use of Hypothermia in PICU is discussed, as well as methods to induce this state and potential side effects of the treatment.

La hipotermia moderada mejora la mortalidad y el pronóstico neurológico en el paro cardíaco en adultos y en recién nacidos con asfixia neonatal. El efecto de la hipotermia en niños con paro cardiorrespiratorio (PCR) no se conoce. Objetivo: Describir el uso de la Hipotermia terapéutica en el PCR en una paciente pediátrica, y actualizar el conocimiento en dicha materia. Caso clínico: Preescolar sexo femenino, 4 años de edad que presentó un PCR extra hospitalario en la que se uso como neuroprotección hipotermia moderada (34 °C) durante 48 horas en la unidad de cuidados intensivos pediátricos, lo que permitió su alta en una condición neurológica satisfactoria, estimada por la escala Pediatric Cerebral Performance Category (PCPC) de 2, similar a su condición basal. También se revisa el uso de hipotermia en cuidado intensivo pediátrico, los métodos para inducir hipotermia y potenciales efectos secundarios de esta terapia.

Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³) compared to the IH group (108 ± 1.7 μm³; p<0.05). CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

Cold stress effects on cardiomyocytes nuclear size in rats: light microscopic evaluation / Efeitos do estresse pelo frio sobre o tamanho nuclear do cardiomiócito em ratos: avaliação por microscopia de luz

INTRODUÇÃO: Hipotermia corporal induzida e resfriamento do miocárdio são métodos efetivos em relação à proteção domiocárdio durante cirurgias cardíacas e isquemia. É descrito na literatura que a exposição a temperaturas extremamente baixas causa comprometimentos de miofilamentos e de cristas mitocondriais em cardiomiócitos, entretanto, nenhum estudo analisou os efeitos do estresse pelo frio no tamanho do núcleo dos cardiomiócios. OBJETIVOS: Analisar os efeitos do estresse agudo pelo frio sobre o tamanho do núcleo dos cardiomiócitos. MÉTODOS: O estudo foi realizado em ratos Wistar adultos, pesando 300-310g (n=20). Os ratos foram divididos em dois grupos: 1) Controle (CON) e; 2) Hipotermia induzido (IH). Os animais do grupo IH foram expostos a uma temperatura controlada de -8ºC, durante 4 horas uma única vez. Foi realizada análise histológica de fígados e glândulas adrenais para examinar a condição de estresse. O tamanho do núcleo dos cardiomiócitos foi examinado por três investigadores independentes com o mesmo critério padronizado e posteriormente analisado pelo coeficiente de correlação de Bartko (R>0,75=concordância positiva). Teste t de Student foi aplicado. O nível de significância foi considerado como P<0,05. RESULTADOS: O grupo exposto ao estresse pelo frio apresentou maior depleção de lipídio nas glândulas adrenais (P<0,05) e de glicogênio no fígado (P<0,05). O grupo induzido à hipotermia mostrou menor volume do núcleo de seus cardiomiócitos (108 + 1,7 µm³; P<0,05), reduziu em 76 por cento comparado ao grupo controle (142 + 2,3 µm³). Correlação de Bartko: CON=0,44; IH=0,96, a variação entre a média dos grupos foi significativamente diferente. CONCLUSÃO: Esses resultados sugerem que a exposição ao estresse agudo pelo frio induz redução do núcleo dos cardiomiócitos em ratos.

INTRODUCTION: Total body induced hypothermia and myocardial cooling are effective methods regarding myocardial protection during heart surgery and ischemia. It is described in previous studies that extreme low temperature exposure causes mitochondrial cristae and myofilament disarrangement in cardiomyocytes, however, no investigation has analyzed the effects of cold stress on nuclear size of cardiomyocytes. OBJECTIVES: To evaluate the effects of acute cold stress exposure on the nuclear size of cardiomyocytes in rats. METHODS: The experimental study procedures were performed on 300-310g adult male Wistar rats. Rats (n=20) were divided into two groups: 1) Control (CON) and; 2) Induced hypothermic (IH) group. Animals of IH group were exposed during 4 hours once at a controlled temperature of - 8ºC. It was performed histological analysis of liver and adrenal gland to examine the stress condition of animals. Cardiomyocytes nucleus size were examined by three independent investigators with the same and standardized criteria and analyzed by Bartko's intra-class correlation coefficient (R>0.75 = positive concordance). Student's t test was applied. The significance level was set at P<0.05. RESULTS: The induced hypothermic group presented higher lipid depletion in adrenal gland cells (P<0.05) and higher glycogen depletion in liver glycogen (P<0.05). The experimental group showed lower cardiomyocytes nuclear volume (108 + 1.7 µm³; P<0.05), it decreased in 76 percent compared to the control group (142 + 2.3 µm³). Bartko's correlation: CON=0.44; IH=0.96, variation analysis between group's means differences was significant. CONCLUSION: These data suggest that acute cold stress exposure induces cardiomyocytes nucleus size reduction in rats.

Estudo funcional e morfológico da hipotermia sistêmica ou tópica no fígado de cães / Functional and morphological study of the local and systemic hypothermia on dog's liver

OBJETIVO: Estudar as alterações morfo-funcionais hepáticas produzidas por dois tipos de hipotermia; a sistêmica ou tópica (localizada). MÉTODOS: 20 cães foram distribuídos em dois grupos: G I (n=10) submetido a hipotermia tópica e G II (n=10) submetido à hipotermia sistêmica. Dosagens bioquímicas de alanina aminotransferase (ALT), aspartato aminotransferase (AST), bilirrubina direta (BD) e estudo morfológico à microscopia óptica (MO) e microscopia eletrônica de transmissão (MET) foram realizados antes da hipotermia (T0), após a estabilização da temperatura corporal em 10°C menor que a temperatura inicial (Test) e após sessenta minutos de hipotermia (T60). RESULTADOS: A dosagem bioquímica das enzimas, aspartato aminotransferase e bilirrubina direta, evidenciaram maiores níveis de lesões no grupo submetido à hipotermia tópica, quando comparado ao grupo de animais submetidos à hipotermia sistêmica. Por sua vez, a dosagem da Alanina aminotransferase não apresentou alterações em ambos os grupos. Tanto a MO quanto a MET, revelou que nos animais do grupo com hipotermia tópica, as lesões hepáticas foram mais intensas quando comparadas ao do grupo com hipotermia sistêmica. CONCLUSÃO: A hipotermia tópica é mais lesiva ao fígado do que a sistêmica.

Neuroprotección por hipotermia / Hypothermic neuroprotection

La hipotermia es una técnica terapéutica de enfriamiento que busca minimizar los efectos de la isquemia o de otros insultos directos sobre uno o más órganos. Ahora contamos con un mejor conocimiento de sus fundamentos fisiopatológicos, a partir principalmente de modelos animales, han surgido nuevas evidencias clínicas y nuevos temas de controversias. Recientemente se han ido estableciendo con más evidencias sus potenciales beneficios en neuroprotección. Se presenta un artículo de revisión de esta técnica.

Alteraciones cardíacas inducidas por el frío en la esclerosis sistémica / Cold-induced cardiac abnormalities in systemic sclerosis

Cardiac abnormalities are frequent in patients with systemic sclerosis (SS). These abnormalities have been demonstrated in over 80 percent of patients with SS and there are some clues that suggest that an intermittent vascular spasm (i.e. coronary Raynaud's phenomenon) is one of the causes of myocardial dysfunction in this group of patients. The aim of this prospective study was to evaluate the ventricular performance and regional wall motion during exposure to cold in patients with SS and Raynaud's phenomenon without overt cardiac disease. Twenty-four patients and 10 normal volunteers underwent radionuclide ventriculograms (RV). In each subject the RV was done thrice: basal, 20 minutes after chilling with thermic blanket and post reheating. The left ventricular ejection fraction (LVEF) decreased during the cold test (p = 0.03) with reversible abnormalities in wall motion. Basal Right Ventricular Ejection Fraction (RVEF) was lower than that of normal subjects (p = 0.02) and decreased during the cold test (p = 0.04). Therefore, we were able to demonstrate an early cardiac dysfunction associated with impaired wall motion after corporal chilling. These findings suggest that coronary spasm in SS would be an early and frequent phenomenon that would precede the development of symptomatic cardiac disease in some patients with this illness.