Arrhythmogenesis in the developing heart during anoxia-reoxygenation and hypothermia-rewarming: an in vitro model.

INTRODUCTION: The spatio-temporal pattern of arrhythmias in the embryonic/fetal heart subjected to a transient hypoxic or hypothermic stress remains to be established. METHODS AND RESULTS: Spontaneously beating hearts or isolated atria, ventricles, and conotruncus from 4-day-old chick embryos were subjected in vitro to 30-minute anoxia and 60-minute reoxygenation. Hearts were also submitted to 30-minute hypothermia (0-4 degrees C) and 60-minute rewarming. ECG disturbances and alterations of atrial and ventricular electromechanical delay (EMD) were systematically investigated. Baseline functional parameters were stable during at least 2 hours. Anoxia induced tachycardia, followed by bradycardia, atrial ectopy, first-, second-, and third-degree atrio-ventricular blocks and, finally, transient electromechanical arrest after 6.8 minutes, interquartile ranges (IQR) 3.1-16.2 (n = 8). Reoxygenation triggered also Wenckebach phenomenon and ventricular escape beats. At the onset of reoxygenation QT, PR, and ventricular EMD increased by 68%, 70%, and 250%, respectively, whereas atrial EMD was not altered. No fibrillations, no ventricular ectopic beats, and no electromechanical dissociation were observed. Arrhythmic activity of the isolated atria persisted throughout anoxia and upon reoxygenation, whereas activity of the isolated ventricles abruptly ceased after 5 minutes of anoxia and resumed after 5 minutes of reoxygenation. During hypothermia-rewarming, cardiac activity stopped at 17.9 degrees C, IQR 16.2-20.6 (n = 4) and resumed at the same temperature with no arrhythmias. All preparations fully recovered after 40 minutes of reoxygenation or rewarming. CONCLUSION: In the embryonic heart, arrhythmias mainly originated in the sinoatrial tissue and resembled those observed in the adult heart. Furthermore, oxygen readmission was by far more arrhythmogenic than rewarming and the chronotropic, dromotropic, and inotropic effects were fully reversible.

Hyperkalemia. A prognostic factor during acute severe hypothermia.

When hypothermic patients appear to be dead, the decision to resuscitate may be difficult due to lack of reliable criteria of death. To discover useful prognostic indicators, we reviewed the hospital charts of nine hypothermic victims of snow avalanches (group A: median value of rectal temperature, 29.6 degrees C; range, less than 12 degrees C to 34 degrees C) and of 15 patients with hypothermia following acute drug intoxication and/or cold exposure (group B: 28.8 degrees C; range, 25.5 degrees C to 32 degrees C. In group A, plasma potassium level on admission was extremely high (14.5 mmol/L; range, 6.8 to 24.5 mmol/L) compared with that obtained in group B (3.5 mmol/L; range, 2.7 to 5.3 mmol/L). All patients in group A were in cardiorespiratory arrest. None could be successfully resuscitated despite effective rewarming by cardiopulmonary bypass or peritoneal lavage. In contrast, all of the patients in group B recovered from hypothermia, including two in cardiorespiratory arrest. Thus, extreme hyperkalemia during acute hypothermia appears to be a reliable marker of death. It might be used to select those patients in whom heroic resuscitation efforts can be useful.

Controle de temperatura em intervenção cirúrgica abdominal convencional: comparação entre os métodos de aquecimento por condução e condução associada à convecção

JUSTIFICATIVA E OBJETIVOS: Hipotermia intra-operatória é complicação frequente, favorecida por operação abdominal. A eficácia da associação dos métodos de aquecimento por condução e convecção na prevenção de hipotermia e seus efeitos no período de recuperação pós-operatória foram os objetivos deste estudo. MÉTODO: Quarenta e três pacientes de ambos os sexos de 18 a 88 anos de idade, submetidos à laparotomia xifopúbica sob anestesia geral e monitorização da temperatura esofágica, foram distribuídos de modo aleatório em dois grupos de aquecimento: COND (n = 24), com colchão de circulação de água a 37°C no dorso e COND + CONV (n = 19), com a mesma condição associada à manta de ar aquecido a 42°C sobre o tórax e membros superiores. Analisados peso, sexo, idade, duração da operação e anestesia, temperaturas na indução anestésica (Mi), horas consecutiva (M1, M2), final da operação (Mfo) e anestesia (Mfa), entrada (Me-REC) e saída (Ms-REC) da recuperação pós-anestésica (SRPA), além das incidências de tremores e queixas de frio no pós-operatório. RESULTADOS: Os grupos foram semelhantes em todas as variáveis analisadas, exceto nas temperaturas em M2, M3, M4, Mfo e Mfa. O grupo COND reduziu a temperatura a partir da segunda hora da indução anestésica, mas o grupo COND + CONV só na quarta hora. Em COND, observou-se hipotermia na entrada e saída da SRPA. CONCLUSÕES: Associar métodos de aquecimento retardou a instalação e diminui a intensidade da hipotermia intra-operatória, mas não reduziu a incidência das queixas de frio e tremores.

Keeping cool in acute liver failure: rationale for the use of mild hypothermia.

Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.

Effects of hypothermia on brain glucose metabolism in acute liver failure: a H/C-nuclear magnetic resonance study.

Mild hypothermia has a protective effect on brain edema and encephalopathy in both experimental and human acute liver failure. The goals of the present study were to examine the effects of mild hypothermia (35°C) on brain metabolic pathways using combined 1H and 13C-Nuclear Magnetic Resonance (NMR) spectroscopy, a technique which allows the study not only of metabolite concentrations but also their de novo synthesis via cell-specific pathways in the brain. :1H and 13C NMR spectroscopy using [1-13C] glucose was performed on extracts of frontal cortex obtained from groups of rats with acute liver failure induced by hepatic devascularization whose body temperature was maintained either at 37°C (normothermic) or 35°C (hypothermic), and appropriate sham-operated controls. At coma stages of encephalopathy in the normothermic acute liver failure animals, glutamine concentrations in frontal cortex increased 3.5-fold compared to sham-operated controls (P < 0.001). Comparable increases of brain glutamine were observed in hypothermic animals despite the absence of severe encephalopathy (coma). Brain glutamate and aspartate concentrations were respectively decreased to 60.9% ± 7.7% and 42.2% ± 5.9% (P < 0.01) in normothermic animals with acute liver failure compared to control and were restored to normal values by mild hypothermia. Concentrations of lactate and alanine in frontal cortex were increased to 169.2% ± 15.6% and 267.3% ± 34.0% (P < 0.01) respectively in normothermic rats compared to controls. Furthermore, de novo synthesis of lactate and alanine increased to 446.5% ± 48.7% and 707.9% ± 65.7% (P < 0.001), of control respectively, resulting in increased fractional 13C-enrichments in these cytosolic metabolites. Again, these changes of lactate and alanine concentrations were prevented by mild hypothermia. Mild hypothermia (35°C) prevents the encephalopathy and brain edema resulting from hepatic devascularization, selectively normalizes lactate and alanine synthesis from glucose, and prevents the impairment of oxidative metabolism associated with this model of ALF, but has no significant effect on brain glutamine. These findings suggest that a deficit in brain glucose metabolism rather than glutamine accumulation is the major cause of the cerebral complications of acute liver failure.

Mild hypothermia prevents brain edema and attenuates up-regulation of the astrocytic benzodiazepine receptor in experimental acute liver failure.

BACKGROUND/AIMS: Mild hypothermia has proven useful in the clinical management of patients with acute liver failure. Acute liver failure in experimental animals results in alterations in the expression of genes coding for astrocytic proteins including the "peripheral-type" (astrocytic) benzodiazepine receptor (PTBR), a mitochondrial complex associated with neurosteroid synthesis. To gain further insight into the mechanisms whereby hypothermia attenuates the neurological complications of acute liver failure, we investigated PTBR expression in the brains of hepatic devascularized rats under normothermic (37 degrees C) and hypothermic (35 degrees C) conditions. METHODS: PTBR mRNA was measured using semi-quantitative RT-PCR in cerebral cortical extracts and densities of PTBR sites were measured by quantitative receptor autoradiagraphy. Brain pregnenolone content was measured by radioimmunoassay. RESULTS: At coma stages of encephalopathy, animals with acute liver failure manifested a significant increase of PTBR mRNA levels. Brain pregnenolone content and [(3)H]PK 11195 binding site densities were concomitantly increased. Mild hypothermia prevented brain edema and significantly attenuated the increased receptor expression and pregnenolone content. CONCLUSIONS: These findings suggest that an attenuation of PTBR up-regulation resulting in the prevention of increased brain neurosteroid content represents one of the mechanisms by which mild hypothermia exerts its protective effects in ALF.

Preoperative combined with intraoperative skin-surface warming avoids hypothermia caused by general anesthesia and surgery

Study Objectives: To evaluate the effects of intraoperative skin-surface warming with and without 1 hour of preoperative warming, in preventing intraoperative hypothermia, and postoperative hypothermia, and shivering, and in offering good conditions to early tracheal extubation. Design: Prospective, randomized, blind study. Setting: Teaching hospital. Patients: 30 ASA physical status I and II female patients scheduled for elective abdominal surgery. Interventions: Patients received standard general anesthesia. In 10 patients, no special precautions were taken to avoid hypothermia. Ten patients were submitted to preoperative and intraoperative active warming. Ten patients were only warmed intraoperatively. Measurements and Main Results: Temperatures were recorded at 15-minute intervals. The patients who were warmed preoperatively and intraoperatively had core temperatures significantly more elevated than the other patients during the first two hours of anesthesia. All patients warmed intraoperatively were normothermic only at the end of the surgery. The majority of the patients warmed preoperatively and intraoperatively or intraoperatively only were extubated early, and none had shivering. In contrast, five unwarmed patients shivered. Conclusions: One hour of preoperative warning combined with intraoperative skin-surface warming, not simply intraoperative warming alone, avoided hypothermia caused by general anesthesia during the first two hours of surgery. Both methods prevented postoperative hypothermia and shivering and offered good conditions for early tracheal extubation. © 2003 by Elsevier B.V.

Thermoregulatory management for mild therapeutic hypothermia

In recent years the use of mild therapeutic hypothermia as a means of neuroprotection has become an important concept for treatment after cerebral ischemic hypoxic injury. Mild therapeutic hypothermia has been shown to improve outcome after out-of-hospital cardiac arrest, and many studies suggest a beneficial effect of mild therapeutic hypothermia on patient outcome after traumatic brain injury, cerebrovascular damage and neonatal asphyxia. This review article explores the numerous possibilities and methods for the induction of mild therapeutic hypothermia, reviews thermoregulatory management during maintenance and discusses associated risks and complications.

Bleeding Complications In Dengue Are Not Associated With Significant Changes In The Modulators Of The Endothelial Barrier.

Bleeding complications in dengue may occur irrespective of the presence of plasma leakage. We compared plasma levels of modulators of the endothelial barrier among three dengue groups: bleedings without plasma leakage, dengue hemorrhagic fever, and non-complicated dengue. The aim was to evaluate whether the presence of subtle alterations in microvascular permeability could be detected in bleeding patients. Plasma levels of VEGF-A and its soluble receptors were not associated with the occurrence of bleeding in patients without plasma leakage. These results provide additional rationale for considering bleeding as a complication independent of endothelial barrier breakdown, as proposed by the 2009 WHO classification.

Use Of Electrocautery For Coagulation And Wound Complications In Caesarean Sections.

To evaluate the safety of electrocautery for coagulation during Caesarean sections. A randomized, controlled, clinical pilot study was performed at a university maternity hospital. After admission for delivery and decision to perform a C-section, volunteers were randomized to either the intervention group (use of electrocautery for coagulation) or nonintervention group. The women were examined at the time of postpartum discharge (day 3), at days 7 to 10, and again at days 30 to 40 for signs of infection, hematoma, seroma, or dehiscence. Data were analyzed using an intention-to-treat analysis, and risk ratios were calculated. No significant differences were found between the two groups. Only 2.8% of patients in the intervention group developed surgical wound complications during hospitalization. However, 7 to 10 days following discharge, these rates reached 23.0% and 15.4% in the intervention and nonintervention groups, respectively (RR = 1.50, 95% CI = 0.84-2.60). Further studies should confirm whether the use of electrocautery for coagulation does not increase the risk of surgical wound complications in patients undergoing Caesarean sections.

Hypothermia And Early Neonatal Mortality In Preterm Infants.

To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis.

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Meningites bacterianas agudas complicações vasculares: vascular complications

The authors present the study of four children with arteritis as vascular complication of acute bacterial meningitis. They report pathophysiological mechanisms involved in vascular lesions, and progress in the understanding of these complications.