RESUMO
Introducción. La hipotermia terapéutica (HT) reduce el riesgo de muerte o discapacidad en niños con encefalopatía hipóxico-isquémica (EHI) moderada-grave. Objetivo. Describir una población de pacientes con EHI que requirió HT y su evolución hasta el alta hospitalaria. Población y métodos. Estudio descriptivo de cohorte retrospectivo. Se analizaron todos los pacientes que ingresaron a HT entre 2013 y 2022. Se evaluaron datos epidemiológicos, clínicos, de monitoreo, tratamiento, estudios complementarios y condición al alta. Se compararon los factores de riesgo entre pacientes fallecidos y sobrevivientes, y de estos, los que requirieron necesidades especiales al alta (NEAS). Resultados. Se incluyeron 247 pacientes. Mortalidad: 11 %. Evento centinela más frecuente: período expulsivo prolongado (39 %). Inicio del tratamiento: mediana 5 horas de vida. Convulsiones: 57 %. Eritropoyetina intravenosa: 66,7 %. Patrón anormal de monitoreo de función cerebral: 52 %. Normalización del monitoreo: mediana 24 horas. Resonancia magnética patológica: 42 %. Variables predictoras de mortalidad: Sarnat y Sarnat grave, y ecografía patológica al ingreso. Conclusión. La mortalidad global fue del 11 %. Las derivaciones aumentaron en forma más evidente a partir del año 2018. El horario de inicio de HT fue más tardío que en reportes anteriores. Los signos neurológicos de gravedad según la escala de Sarnat y Sarnat y la ecografía cerebral basal patológica fueron predictores independientes de mortalidad al alta. Los pacientes con NEAS presentaron normalización del trazado del electroencefalograma de amplitud integrada más tardío. El hallazgo más frecuente en la resonancia fue la afectación de los ganglios basales. No se encontraron diferencias clínicas ni de complicaciones estadísticamente significativas entre los pacientes que recibieron eritropoyetina.
Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/terapia , Hipotermia Induzida/métodos , Fatores de Tempo , Estudos Retrospectivos , Fatores de Risco , Estudos de Coortes , Centros de Atenção Terciária , Hospitais PúblicosRESUMO
BACKGROUND: Cerebral blood flow dynamics can be explored through analysis of endothelial frequencies. Our hypothesis posits a disparity in endothelial activity among neonates with perinatal asphyxia, stratified by the presence or absence of neuronal lesions. METHODS: We conducted a retrospective longitudinal study involving newborns treated with hypothermia for moderate to severe asphyxia. Participants were grouped based on the presence or absence of neuronal damage to investigate temporal endothelial involvement in cerebral blood flow regulation. Regional cerebral oxygen saturation (rScO2) was measured using near-infrared spectroscopy (NIRS), and temporal series were analyzed in the frequency domain, utilizing the original frequency of the INVOS™ device. RESULTS: The study included 88 patients, with 53% (47/88) being male and 33% (29/88) demonstrating brain lesions on magnetic resonance imaging. Among them, 86% (76/88) had a gestational age exceeding 37 weeks according to the Ballard scale, and 81% (71/88) had a birth weight exceeding 2500 g. Cohen's d effect size was calculated to assess differences in endothelial frequency between groups, indicating a small effect size based on cerebral MRI findings (Cohen's d values for Day 2 = 0.2351 and Day 3 = 0.2325). CONCLUSION: NIRS represents a valuable tool for monitoring cerebral autoregulation in neonates affected by perinatal asphyxia, underscoring the utility of assessing endothelial frequency or energy on rScO2 measured by NIRS using the original INVOS™ device frequency.
Assuntos
Asfixia Neonatal , Circulação Cerebrovascular , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Recém-Nascido , Estudos Retrospectivos , Asfixia Neonatal/fisiopatologia , Masculino , Feminino , Circulação Cerebrovascular/fisiologia , Estudos Longitudinais , Saturação de Oxigênio/fisiologia , Imageamento por Ressonância Magnética , Hipotermia Induzida , Endotélio Vascular/fisiopatologiaRESUMO
OBJECTIVE: To evaluate variations in management of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) among international clinical sites and to identify areas for harmonization. STUDY DESIGN: An electronic survey was sent to Children's Hospitals Neonatal Consortium site sponsors, Canadian Neonatal Network site investigators, members of the Newborn Brain Society, and American Academy of Pediatrics Neonatology chiefs. RESULTS: One hundred five sites responded, with most from high-income regions (n = 95). Groupings were adapted from the United Nations regional groups: US (n = 52 sites); Canada (n = 20); Western Europe and other states excluding Canada and US Group (WEOG, n = 18); and non-WEOG (central and eastern Europe, Asia, Africa, Latin America, and Caribbean, n = 15). Regional variations were seen in the eligibility criteria for TH, such as the minimum gestational age, grading of HIE severity, use of electroencephalography, and the frequency of providing TH for mild HIE. Active TH during transport varied among regions and was less likely in smaller volume sites. Amplitude-integrated electroencephalogram and/or continuous electroencephalogram to determine eligibility for TH was used by most sites in WEOG and non-WEOG but infrequently by the US and Canada Groups. For sedation during TH, morphine was most frequently used as first choice but there was relatively high (33%) use of dexmedetomidine in the US Group. Timing of brain magnetic resonance imaging and neurodevelopmental follow-up were variable. Neurodevelopmental follow occurred earlier and more frequently, although for a shorter duration, in the non-WEOG. CONCLUSIONS: We found significant variations in practices for TH for HIE across regions internationally. Future guidelines should incorporate resource availability in a global perspective.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Padrões de Prática Médica/estatística & dados numéricos , Eletroencefalografia , Pesquisas sobre Atenção à Saúde , Canadá , InternacionalidadeRESUMO
Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.
Introducción. La hipotermia terapéutica (HT) reduce el riesgo de muerte o discapacidad en niños con encefalopatía hipóxico-isquémica (EHI) moderada-grave. Objetivo. Describir una población de pacientes con EHI que requirió HT y su evolución hasta el alta hospitalaria. Población y métodos. Estudio descriptivo de cohorte retrospectivo. Se analizaron todos los pacientes que ingresaron a HT entre 2013 y 2022. Se evaluaron datos epidemiológicos, clínicos, de monitoreo, tratamiento, estudios complementarios y condición al alta. Se compararon los factores de riesgo entre pacientes fallecidos y sobrevivientes, y de estos, los que requirieron necesidades especiales al alta (NEAS). Resultados. Se incluyeron 247 pacientes. Mortalidad: 11 %. Evento centinela más frecuente: período expulsivo prolongado (39 %). Inicio del tratamiento: mediana 5 horas de vida. Convulsiones: 57 %. Eritropoyetina intravenosa: 66,7 %. Patrón anormal de monitoreo de función cerebral: 52 %. Normalización del monitoreo: mediana 24 horas. Resonancia magnética patológica: 42 %. Variables predictoras de mortalidad: Sarnat y Sarnat grave, y ecografía patológica al ingreso. Conclusión. La mortalidad global fue del 11 %. Las derivaciones aumentaron en forma más evidente a partir del año 2018. El horario de inicio de HT fue más tardío que en reportes anteriores. Los signos neurológicos de gravedad según la escala de Sarnat y Sarnat y la ecografía cerebral basal patológica fueron predictores independientes de mortalidad al alta. Los pacientes con NEAS presentaron normalización del trazado del electroencefalograma de amplitud integrada más tardío. El hallazgo más frecuente en la resonancia fue la afectación de los ganglios basales. No se encontraron diferencias clínicas ni de complicaciones estadísticamente significativas entre los pacientes que recibieron eritropoyetina.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Estudos Retrospectivos , Feminino , Masculino , Estudos de Coortes , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Hipotermia Induzida/métodos , Hospitais Públicos , Lactente , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Pré-EscolarRESUMO
OBJECTIVE: To determine whether an enteral, clonidine-based sedation strategy (CLON) during therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy would decrease opiate use while maintaining similar short-term safety and efficacy profiles to a morphine-based strategy (MOR). STUDY DESIGN: This was a single-center, observational study conducted at a level IV neonatal intensive care unit from January 1, 2017, to October 1, 2021. From April 13, 2020, to August 13, 2020, we transitioned from MOR to CLON. Thus, patients receiving TH for hypoxic-ischemic encephalopathy were grouped to MOR (before April 13, 2020) and CLON (after August 13, 2020). We calculated the total and rescue morphine milligram equivalent/kg (primary outcome) and frequency of hemodynamic changes (secondary outcome) for both groups. RESULTS: The MOR and CLON groups (74 and 25 neonates, respectively) had similar baseline characteristics and need for rescue sedative intravenous infusion (21.6% MOR and 20% CLON). Both morphine milligram equivalent/kg and need for rescue opiates (combined bolus and infusions) were greater in MOR than CLON (P < .001). As days in TH advanced, a lower percentage of patients receiving CLON needed rescue opiates (92% on day 1 to 68% on day 3). Patients receiving MOR received a greater cumulative dose of dopamine and more frequently required a second inotrope and hydrocortisone for hypotension. MOR had a lower respiratory rate during TH (P = .01 vs CLON). CONCLUSIONS: Our CLON protocol is noninferior to MOR, maintaining perceived effectiveness and hemodynamic safety, with an apparently reduced need for opiates and inotropes.
Assuntos
Analgésicos Opioides , Clonidina , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Clonidina/administração & dosagem , Clonidina/uso terapêutico , Recém-Nascido , Hipotermia Induzida/métodos , Masculino , Feminino , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Hipóxia-Isquemia Encefálica/terapia , Morfina/administração & dosagem , Morfina/uso terapêutico , Administração Oral , Hipnóticos e Sedativos/administração & dosagem , Unidades de Terapia Intensiva NeonatalRESUMO
SUMMARY OBJECTIVE: The aim of this study was to evaluate the impact of therapeutic hypothermia on maternal and perinatal outcomes in newborns with Apgar score<7 at the 5th min. METHODS: A retrospective cohort study was carried out with 55 newborns who had an Apgar score<7 at the 5th min (35 without and 20 with therapeutic hypothermia) from low-risk pregnancies between 33 and 41 weeks gestation. The Apgar score was calculated through an objective assessment by a neonatologist in the delivery room. Therapeutic hypothermia was indicated by a neonatologist in the delivery room, according to the protocol established by the Brazilian Society of Pediatrics. The maternal and perinatal outcomes of both groups (without and with therapeutic hypothermia) were compared. RESULTS: A rate of Apgar score<7 at the 5th min was 1.02%. No statistical differences were observed between the two groups (without and with therapeutic hypothermia) regarding maternal/perinatal complications. The presence of maternal/perinatal complications did not increase the odds ratio of neonatal therapeutic hypothermia in newborns with Apgar score<7 at the 5th min. CONCLUSION: The rate of Apgar score<7 at the 5th min was low, and it was not associated with any maternal/perinatal complications. There was no significant difference in maternal/perinatal complications between newborns who received therapeutic hypothermia and those who did not.
RESUMO
We evaluated the association between left cardiac 3-dimensional echocardiographic parameters and brain injury in a single-center prospective study of neonates with neonatal encephalopathy. On day 2 of life, neonates with brain injury had greater left ventricle end-diastolic and stroke volume but also greater peak global circumferential strain detected by 3-dimensional echocardiogram.
Assuntos
Lesões Encefálicas , Ecocardiografia Tridimensional , Disfunção Ventricular Esquerda , Recém-Nascido , Humanos , Lactente , Função Ventricular Esquerda , Estudos Prospectivos , Ecocardiografia/métodos , Ecocardiografia Tridimensional/métodos , Volume Sistólico , Ventrículos do Coração/diagnóstico por imagem , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Introduction: Ocular and periocular traumatisms may result in loss of vision. Our previous work showed that therapeutic hypothermia prevents retinal damage caused by traumatic neuropathy. We also generated and characterized small molecules that elicit the beneficial effects of hypothermia at normal body temperature. Here we investigate whether one of these mimetic molecules, zr17-2, is able to preserve the function of eyes exposed to trauma. Methods: Intraorbital optic nerve crush (IONC) or sham manipulation was applied to Sprague-Dawley rats. One hour after surgery, 5.0 µl of 330 nmol/L zr17-2 or PBS, as vehicle, were injected in the vitreum of treated animals. Electroretinograms were performed 21 days after surgery and a- and b-wave amplitude, as well as oscillatory potentials (OP), were calculated. Some animals were sacrificed 6 days after surgery for TUNEL analysis. All animal experiments were approved by the local ethics board. Results: Our previous studies showed that zr17-2 does not cross the blood-ocular barrier, thus preventing systemic treatment. Here we show that intravitreal injection of zr17-2 results in a very significant prevention of retinal damage, providing preclinical support for its pharmacological use in ocular conditions. As previously reported, IONC resulted in a drastic reduction in the amplitude of the b-wave (p < 0.0001) and OPs (p < 0.05), a large decrease in the number of RGCs (p < 0.0001), and a large increase in the number of apoptotic cells in the GCL and the INL (p < 0.0001). Interestingly, injection of zr17-2 largely prevented all these parameters, in a very similar pattern to that elicited by therapeutic hypothermia. The small molecule was also able to reduce oxidative stress-induced retinal cell death in vitro. Discussion: In summary, we have shown that intravitreal injection of the hypothermia mimetic, zr17-2, significantly reduces the morphological and electrophysiological consequences of ocular traumatism and may represent a new treatment option for this cause of visual loss.
RESUMO
Nowadays, the only treatment for human babies suffering from hypoxia-ischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI. Seven-day-old Wistar rats underwent a surgery for unilateral occlusion of the right common carotid artery and were exposed to a hypoxic atmosphere (8% oxygen) for 75 min. Then, the animals in the TH group were submitted to TH (scalp temperature of 32°C) for 5 h. In the behavioral tests, no remarkable differences triggered by HI or TH were observed relative to SHAM animals. Only females of the HI group presented lower latency to complete the righting reflex test. TH reduced the volume of brain injury in males, but not in females. The animals of the HI group showed a reduction in the number of neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus and TH partially prevented neuronal death. In the CA1 region of the hippocampus, animals from the HI group showed more degenerating cells relative to the SHAM, which was reversed by TH. In the DG, animals from the HI group showed an increase in the number of degenerating neurons, which was partially reversed by TH only in males. Our data show that HI leads to a brain injury, which was attenuated by TH in a sex-dependent way and clarify the importance of the assessment of males and females in order to outline specific strategies for the treatment of each sex in newborns suffering from HI.
Assuntos
Lesões Encefálicas , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Ratos , Animais , Masculino , Feminino , Ratos Wistar , Animais Recém-Nascidos , Hipóxia-Isquemia Encefálica/terapia , Isquemia/terapia , Hipóxia , EncéfaloRESUMO
Therapeutic hypothermia (TH) is the standard treatment for neonatal hypoxia-ischemia (HI) with a time window limited up to 6 h post injury. However, influence of sexual dimorphism in the therapeutic window for TH has not yet been elucidated in animal models of HI. Therefore, the aim of this study was to investigate the most effective time window to start TH in male and female rats submitted to neonatal HI. Wistar rats (P7) were divided into the following groups: NAÏVE and SHAM (control groups), HI (submitted to HI) and TH (submitted to HI and TH; 32ºC for 5 h). TH was started at 2 h (TH-2 h group), 4 h (TH-4 h group), or 6 h (TH-6 h group) after HI. At P14, animals were subjected to behavioural tests, volume of lesion and reactive astrogliosis assessments. Male and female rats from the TH-2 h group showed reduction in the latency of behavioral tests, and decrease in volume of lesion and intensity of GFAP immunofluorescence. TH-2 h females also showed reduction of degenerative cells and morphological changes in astrocytes. Interestingly, females from the TH-6 h group showed an increase in volume of lesion and in number of degenerative hippocampal cells, associated with worse behavioral performance. Together, these results indicate that TH neuroprotection is time- and sex-dependent. Moreover, TH started later (6 h) can worsen volume of brain lesion in females. These data indicate the need to develop specific therapeutic protocols for each sex and reinforce the importance of early onset of the hypothermic treatment.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Animais , Masculino , Feminino , Ratos , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/patologia , Gliose/terapia , Gliose/patologia , Ratos Wistar , Animais Recém-Nascidos , Encéfalo , Isquemia/patologia , Isquemia/terapia , Modelos Animais de DoençasRESUMO
OBJECTIVE: To investigate the prognostic accuracy of longitudinal analysis of amplitude-integrated electroencephalography (aEEG) background activity to predict long-term neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: This single-center observational study included 149 neonates for derivation and 55 neonates for validation with moderate-severe HIE and of gestational age ≥35 weeks at a tertiary neonatal intensive care unit. Single-channel aEEG background pattern, sleep-wake cycling, and seizure activity were monitored over 84 hours during therapeutic hypothermia and rewarming, then scored for each 6-hour interval. Neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition. Favorable outcome was defined as having both a Mental Development Index (MDI) score and Psychomotor Development Index (PDI) score ≥70, and adverse outcome was defined as either an MDI or a PDI <70 or death. Regression modeling for longitudinal analysis of repeatedly measured data was applied, and area under the receiver operating characteristic curve (AUC) was calculated. RESULTS: Longitudinal aEEG background analysis combined with sleep-wake cycling score had excellent predictive value (AUC, 0.90; 95% CI, 0.85-0.95), better than single aEEG scores at any individual time point. The model performed well in the independent validation cohort (AUC, 0.87; 95% CI, 0.62-1.00). The reclassification rate of this model compared with the conventional analysis of aEEG background at 48 hours was 18% (24 patients); 14% (18 patients) were reclassified correctly. Our results were used to develop a user-friendly online outcome prediction tool. CONCLUSIONS: Longitudinal analysis of aEEG background activity and sleep-wake cycling is a valuable and accurate prognostic tool.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Criança , Eletroencefalografia/métodos , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Lactente , Recém-Nascido , Prognóstico , Curva ROCRESUMO
BACKGROUND: Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI. METHODS AND RESULTS: We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System (Zoll Circulation Inc™, San Jose, CA, USA). The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Afterwards, the EHT protocol was successfully validated in a trial randomizing 50 patients for 18 minutes cooling before coronary recanalization at the target temperature of 32 ± 1.0 ∘C or PCI-only. A total of 35 patients underwent ETH (85.7% [30/35] in 90 ± 15 minutes), without delays in the mean door-to-balloon time for primary PCI when compared to 15 control group patients (92.1 minutes versus 87 minutes, respectively; p = 0.509). CONCLUSIONS: Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI. CLINICALTRIALS: gov: NCT02664194.
Assuntos
Hipotermia Induzida , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Hipotermia Induzida/efeitos adversos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the incidence of hypoglycemia among infants with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia, and to assess whether infants with hypoglycemia had more brain injury on magnetic resonance imaging (MRI) or differences in neurodevelopmental outcome. STUDY DESIGN: Single-center, retrospective cohort study including infants cooled for HIE. Hypoglycemia (blood glucose <36.0 mg/dL <2 hours and <46.8 mg/dL ≥2 hours after birth) was analyzed in the period before brain MRI. Brain injury was graded using a validated score. Motor and neurocognitive outcomes were assessed at 2 years for all survivors, and 5.5 years for a subset who had reached this age. RESULTS: Of 223 infants analyzed, 79 (35.4%) had hypoglycemia. MRI was performed in 187 infants. Infants with hypoglycemia (n = 65) had higher brain injury scores (P = .018). After adjustment for HIE severity, hypoglycemia remained associated with higher injury scores (3.6 points higher; 95% CI, 0.8-6.4). Hyperglycemia did not affect MRI scores. In survivors at 2 years (n = 154) and 5.5 years (n = 102), a univariable analysis showed lower 2-year motor scores and lower motor and cognitive scores at preschool age in infants with hypoglycemia. After adjustment for HIE severity, infants with hypoglycemia had 9 points lower IQs (P = .023) and higher odds of adverse outcomes at preschool age (3.6; 95% CI, 1.4-9.0). CONCLUSIONS: More than one-third of infants cooled for HIE had hypoglycemia. These infants had a higher degree of brain injury on MRI and lower cognitive function at preschool age. Strategies to avoid hypoglycemia should be optimized in this setting.
Assuntos
Lesões Encefálicas , Hipoglicemia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Pré-Escolar , Humanos , Hipoglicemia/complicações , Hipoglicemia/epidemiologia , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/terapia , Lactente , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
OBJECTIVES: Data on cardiac arrest survivors from developing countries are scarce. This study investigated clinical characteristics associated with in-hospital mortality in resuscitated patients following cardiac arrest in Brazil. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Ninety-two general ICUs from 55 hospitals in Brazil between 2014 and 2015. PATIENTS: Adult patients with cardiac arrest admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 2,296 patients (53% men; median 67 yr (interquartile range, 54-79 yr]). Eight-hundred patients (35%) had a primary admission diagnosis of cardiac arrest suggesting an out-of-hospital cardiac arrest; the remainder occurred after admission, comprising an in-hospital cardiac arrest cohort. Overall, in-hospital mortality was 83%, with only 6% undergoing withholding/withdrawal-of-life support. Random-effects multivariable Cox regression was used to assess associations with survival. After adjusting for age, sex, and severity scores, mortality was associated with shock (adjusted odds ratio, 1.25 [95% CI, 1.11-1.39]; p < 0.001), temperature dysregulation (adjusted odds ratio for normothermia, 0.85 [95% CI, 0.76-0.95]; p = 0.007), increased lactate levels above 4 mmol/L (adjusted odds ratio, 1.33 [95% CI, 1.1-1.6; p = 0.009), and surgical or cardiac cases (adjusted odds ratio, 0.72 [95% CI, 0.6-0.86]; p = 0.002). In addition, survival was better in patients with probable out-of-hospital cardiac arrest, unless ICU admission was delayed (adjusted odds ratio for interaction, 1.63 [95% CI, 1.21-2.21]; p = 004). CONCLUSIONS: In a large multicenter cardiac arrest cohort from Brazil, we found a high mortality rate and infrequent withholding/withdrawal of life support. We also identified patient profiles associated with worse survival, such as those with shock/hypoperfusion and arrest secondary to nonsurgical admission diagnoses. Our findings unveil opportunities to improve postarrest care in developing countries, such as prompt ICU admission, expansion of the use of targeted temperature management, and implementation of shock reversal strategies (i.e., early coronary angiography), according to modern guidelines recommendations.
RESUMO
Therapeutic hypothermia (TH) using servo-controlled cooling devices has proved to be a safe and effective method to reduce mortality and sequelae in neonates with hypoxic-ischemic encephalopathy (HIE). However, such cooling devices can be expensive and have limited availability in low- and middle-income countries. To evaluate the feasibility and effectiveness of low-cost cooling devices (ice packs) to reach and maintain the target temperature in newborns with moderate or severe HIE. Descriptive retrospective cross-sectional study, including newborns with gestational age ≥35 weeks, weight ≥1800 g, with diagnosis of moderate or severe HIE, submitted to whole body hypothermia using ice packs for 72 hr. Data was obtained from medical records and databases. The thermal curves of each patient, time spent at the target temperature and rewarming time were evaluated. Complications directly related to therapeutic hypothermia, evolution, and early outcomes before hospital discharge were analyzed. Seventy-one newborns met the criteria for TH, and 61 completed the entire cooling period and were included in the final analysis. The average time to reach the target temperature was 1.50 ± 1.3 hr. The mean temperature during the cooling period was 33.5°C (±0.62). 82.32% of the measurements were within the target temperature range (from 33 to 34°C). The following adverse events were observed during TH: pulmonary hypertension 11.3%, arrhythmia 4.2%, and coagulopathy 26.7%. Whole body hypothermia using low-cost devices proved to be an effective method in the absence of availability of servo-controlled devices, representing a plausible option in restricted resource settings.
Assuntos
Temperatura Corporal , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxia-induced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration.
Assuntos
Hipocampo/crescimento & desenvolvimento , Hipotermia Induzida/métodos , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/terapia , Memória Espacial/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Hipóxia Encefálica/psicologia , Lactação/fisiologia , Masculino , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
Endovascular Therapeutic hypothermia (ETH) reduces the damage caused by postischemia reperfusion injury syndrome in cardiopulmonary arrest and has already established its role in patients with sudden death; however, its role in ST-segment elevation myocardial infarction (STEMI) remains controversial. The objectives of this study were to investigate the safety, feasibility, and 30-day efficacy of rapid induction of therapeutic hypothermia as adjunctive therapy to percutaneous coronary intervention (PCI) in patients with anterior and inferior STEMIs. This was a prospective, controlled, randomized, two-arm, prospective, interventional study of patients admitted to the emergency department within 6 hours of angina onset, with anterior or inferior STEMI eligible for PCI. Subjects were randomized to the hypothermia group (primary PCI+ETH) or to the control group (primary PCI) at a 4:1 ratio. The ETH was induced by 1 L cold saline (1-4°C) associated with the Proteus™ System, by cooling for at least 18 minutes before coronary reperfusion with a target temperature of 32°C ± 1°C. Maintenance of ETH was conducted for 1-3 hours, and active reheating was done at a rate of 1°C/h for 4 hours. Primary safety outcomes were the feasibility of ETH in the absence of (1) door-to-balloon (DTB) delay; (2) major adverse cardiac events (MACE) within 30 days after randomization. The primary outcomes of effectiveness were infarct size (IS) and left ventricular ejection fraction (LVEF) at 30 days. An as-treated statistical analysis was performed. Fifty patients were included: 35 (70%) randomized to the hypothermia group and 15 (30%) to the control group. The mean age was 58 ± 12 years; 78% were men; and associated diseases were 60% hypertension, 42% diabetes, and 72% dyslipidemia. The compromised myocardial wall was anterior in 38% and inferior in 62%, and the culprit vessels were left anterior descending artery (LAD) (40%), right coronary artery (38%), and left circumflex (18%). All 35 patients who attempted ETH (100%) had successful cooling, with a mean endovascular coronary reperfusion temperature of 33.1°C ± 0.9°C. The mean ischemic time was 375 ± 89.4 minutes in the hypothermia group and 359.5 ± 99.4 minutes in the control group. The mean DTB was 92.1 ± 20.5 minutes in the hypothermia group and 87 ± 24.4 minutes in the control group. The absolute difference of 5.1 minutes was not statistically significant (p = 0.509). The MACE rates were similar between both groups (21.7% vs. 20% respectively, p = 0.237). In the comparison between the hypothermia and control groups, no statistically significant differences were observed at 30 days between mean IS (13.9% ± 8% vs. 13.8% ± 10.8%, respectively, p = 0.801) and mean final LVEF (43.3% ± 11.2% vs. 48.3 ± 10.9%, respectively; p = 0.194). Hypothermia as an adjunctive therapy to primary PCI in STEMI is feasible and can be implemented without delay in coronary reperfusion. Hypothermia was safe regarding the incidence of MACE at 30 days. However, there was a higher incidence of arrhythmia and in-hospital infection in the hypothermia group, with no increase in mortality. Regarding efficacy, there was no difference in IS or LVEF at 30 days that would suggest additional myocardial protection with ETH. ClinicalTrials.gov: NCT02664194.
Assuntos
Hipotermia Induzida , Infarto do Miocárdio , Intervenção Coronária Percutânea , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
OBJECTIVE: To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country. STUDY DESIGN: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings. RESULTS: Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p < .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p < .001; p = .001; p = .001, and p = .011, respectively). CONCLUSIONS: Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.
Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética/métodos , Adulto , Asfixia Neonatal/complicações , Brasil/epidemiologia , Estudos de Casos e Controles , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipotermia Induzida/mortalidade , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Ischemia-reperfusion (I/R)-induced oxidative stress is one of the main mechanisms of tissue injury after cardiac arrest (CA). A decrease in antioxidant defenses may contribute to I/R injury. The present study aims to investigate the influence of mild therapeutic hypothermia (MTH) on levels of nonenzymatic antioxidants after CA. We investigated antioxidant levels at 6, 12, 36, and 72 hours after CA in central venous blood samples of patients admitted to intensive care. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 hours of MTH (33°C). Erythrocyte glutathione (GSH) levels were elevated by MTH, increasing at 6, 12, 36, and 72 hours after CA in hypothermic patients (mean GSH levels in normothermic patients: 6 hours = 73.89, 12 hours = 56.45, 36 hours = 56.46, 72 hours = 61.80 vs. hypothermic patients: 6 hours = 176.89, 12 hours = 198.78, 36 hours = 186.96, and 72 hours = 173.68 µmol/g of protein). Vitamin C levels decreased significantly at 6 and 12 hours after CA in hypothermic patients (median vitamin C levels in normothermic patients: 6 hours = 7.53, 12 hours = 9.40, 36 hours = 8.56, and 72 hours = 8.51 vs. hypothermic patients: 6 hours = 5.46, 12 hours = 5.44, 36 hours = 6.10, and 72 hours = 5.89 mmol/L), coinciding with the period of therapeutic hypothermia. Vitamin E and nitric oxide levels were not altered by hypothermic treatment. These findings suggest that MTH alters nonenzymatic antioxidants differently, decreasing circulating vitamin C levels during treatment; however, MTH elevates GSH levels, possibly protecting tissues from I/R injury after CA.