Anestesia y el cerebro neonatal/Anesthesia and neonatal brain

Septiembre 6, 2015. No. 2077

En animales inmaduros que son expuestos a los anestésicos generales se ha visto muerte celular, daño neuronal, y deterioro neurocognitivo. Esto ha preocupado a los investigados y a los clínicos sobre los efectos similares que puedan ocurren en los niños pequeños. Aunque los estudios epidemiológicos no son concluyentes por diversos factores, los descubrimientos actuales  sugieren que la anestesia general para un procedimiento quirúrgico en la primera infancia puede estar asociada con la disminución a largo plazo de las habilidades del lenguaje y la cognición, así como alteraciones volumétricas regionales en la estructura del cerebro.   In immature animals exposed to general anesthetics has been demosntrated  cell death, neuronal damage, and neurocognitive impairment. This has worried investigators and clinicians about that similar effects can occur in young children. Although epidemiological studies are inconclusive by several factors, the current findings suggest that general anesthesia for a surgical procedure in early childhood may be associated with long-term decline of language skills and cognition, as well as regional volumetric changes in brain structure   Em animais imaturos são expostos a anestésicos gerais tem sido a morte celular, as lesões neuronais e comprometimento neurocognitivo. Isso tem preocupado investigados e clínicos sobre os efeitos semelhantes podem ocorrer em crianças pequenas. Embora os estudos epidemiológicos são inconclusivos por diversos fatores, os resultados atuais sugerem que a anestesia geral para um procedimento cirúrgico na primeira infância pode estar associada com declínio a longo prazo das competências linguísticas e cognição, bem como mudanças volumétricas regionais na estrutura do cérebro Efectos de la anestesia en el cerebro de niños en desarrollo Effects of Anesthesia on Children's Brain Development Hernández-Cortez E J Anesth Crit Care Open Access 2015; 2(6): 00079. DOI: 10.15406/ jaccoa.2015.02.00079 J Anesth Crit Care Open Access 2015, 2(6): 00079 Abstract Nowadays, the administration of most of the anesthetics is being questioned. The quality of reversibility of these medications is being questioned, especially when administered to children under 3 years old. The administration of isoflurane elevates intracellular calcium levels which are critical for cell damage resulting in apoptosis. The NMDA and GABA receptors are indirectly involved in the effect of immature brains. The immaturity of the central nervous system associated to the administration of anesthetic agents such as inhaled anesthetics, ketamine, midazolam, nitrous oxide, and others, produces important changes in the brain that  have  an  impact  in  the  child's  later  life.  There  are  two  important  elements in the neurotoxicity of anesthetics, dosage and time administration. Repeating anesthetics produces more brain changes. There are two important elements in the neurotoxicity of anesthetics, dosage and time administration. Repeating anesthetics produces more brain changes. These modifications have resulted in serious behavioral and memory changes in experiments. Keywords. Apotosis, anesthesia, children  PDF Asociación entre daño cerebral, exposición perioperatoria a los anestésicos, y el neurodesarrollo a los 12 meses después de cirugía cardiaca neonatal. Estudio retrospectivo de cohortes The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study. Andropoulos DB, Ahmad HB, Haq T, Brady K, Stayer SA, Meador MR, Hunter JV, Rivera C, Voigt RG,Turcich M, He CQ, Shekerdemian LS, Dickerson HA, Fraser CD, Dean McKenzie E, Heinle JS, Blaine Easley R. Paediatr Anaesth. 2014 Mar;24(3):266-74. doi: 10.1111/pan.12350. Abstract BACKGROUND: Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI). METHODS: Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7-day postoperative brain MRI and 12-month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life. RESULTS: From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley-III (P < 0.02). CONCLUSIONS: After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes. PDF Daño perioperatorio del sistema nervioso central en neonatos Perioperative central nervous system injury in neonates. McCann ME, Soriano SG. Br J Anaesth. 2012 Dec;109 Suppl 1:i60-i67. doi: 10.1093/bja/aes424.Author information Abstract Anaesthetic-induced developmental neurotoxicity (AIDN) has been clearly established in laboratory animal models. The possibility of neurotoxicity during uneventful anaesthetic procedures in human neonates or infants has led to serious questions about the safety of paediatric anaesthesia. However, the applicability of animal data to clinical anaesthesia practice remains uncertain. The spectre of cerebral injury due to cerebral hypoperfusion, metabolic derangements, coexisting disease, and surgery itself further muddles the picture. Given the potential magnitude of the public health importance of this issue, the clinician should be cognisant of the literature and ongoing investigations on AIDN, and raise awareness of the risks of both surgery and anaesthesia. PDF Anestesia general en pediatría. Influencias sobre el cerebro en desarrollo General anesthetics in pediatric anesthesia: influences on the developing brain. McCann ME, Soriano SG. Curr Drug Targets. 2012 Jun;13(7):944-51. Abstract Millions of newborn and infants receive anesthetic, sedative and analgesic drugs for surgery and painful procedures on a daily basis. However, recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models. This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia. Most clinically utilized anesthetic drugs have been found to induce neuronal cell death in the developing brain and to potentially cause long-term neurological impairment. Conversely, painful stimuli without analgesia and anesthesia have been implicated in triggering neuro-apoptosis in juvenile mammalian models. Published retrospective reviews demonstrate temporary neurological sequelae after prolonged anesthetic exposure in young children and larger studies identify long-term neurodevelopmental impairment after neonatal surgery and anesthesia. This paper examines the evidence for the effects of commonly used anesthetics on neuronal structure and neurocognitive function in laboratory models and reviews the relevant clinical human epidemiologic data. PDF  Control de dolor neonatal y efectos neurológicos de los anestésicos y sedantes en infantes de pretérmino Neonatal pain control and neurologic effects of anesthetics and sedatives in preterm infants. McPherson C, Grunau RE. Clin Perinatol. 2014 Mar;41(1):209-27. doi: 10.1016/j.clp.2013.10.002. Epub 2013 Dec 17. Abstract Preclinical and clinical studies have demonstrated the adverse consequences of untreated pain and stress on brain development in the preterm infant. Sucrose has widely been implemented as standard therapy for minor procedural pain. Anesthetics are commonly utilized in preterm infants during major surgery. Pharmacologic agents (benzodiazepines and opioids) have been examined in clinical trials of preterm infants requiring invasive mechanical ventilation. Controversy exists regarding the safety and long-term impact of these interventions. Ongoing multidisciplinary research will help define the impact of these agents and identify potential alternative therapies. PDF

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