Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial.

BACKGROUND: Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. METHODS: In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. FINDINGS: Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean [SD]) was 98.6 (14.2) in the awake-regional group and 98.2 (14.7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0.169, 95% CI -2.30 to 2.64). The median duration of anaesthesia in the general anaesthesia group was 54 min. INTERPRETATION: For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. FUNDING: Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study--Comparing Apnea and Neurodevelopmental Outcomes, a Randomized Controlled Trial.

BACKGROUND: Postoperative apnea is a complication in young infants. Awake regional anesthesia (RA) may reduce the risk; however, the evidence is weak. The General Anesthesia compared to Spinal anesthesia study is a randomized, controlled trial designed to assess the influence of general anesthesia (GA) on neurodevelopment. A secondary aim is to compare rates of apnea after anesthesia. METHODS: Infants aged 60 weeks or younger, postmenstrual age scheduled for inguinal herniorrhaphy, were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born less than 26 weeks gestation. The primary outcome of this analysis was any observed apnea up to 12 h postoperatively. Apnea assessment was unblinded. RESULTS: Three hundred sixty-three patients were assigned to RA and 359 to GA. Overall, the incidence of apnea (0 to 12 h) was similar between arms (3% in RA and 4% in GA arms; odds ratio [OR], 0.63; 95% CI, 0.31 to 1.30, P = 0.2133); however, the incidence of early apnea (0 to 30 min) was lower in the RA arm (1 vs. 3%; OR, 0.20; 95% CI, 0.05 to 0.91; P = 0.0367). The incidence of late apnea (30 min to 12 h) was 2% in both RA and GA arms (OR, 1.17; 95% CI, 0.41 to 3.33; P = 0.7688). The strongest predictor of apnea was prematurity (OR, 21.87; 95% CI, 4.38 to 109.24), and 96% of infants with apnea were premature. CONCLUSIONS: RA in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.

A novel balanced isotonic sodium solution vs normal saline during major surgery in children up to 36 months: a multicenter RCT.

BACKGROUND: The use of isotonic electrolytic solutions for the intraoperative fluid management in children is largely recognized, but the exact composition still needs to be defined. OBJECTIVES: The primary objective of this randomized controlled open trial was to compare the changes in chloride plasma concentration using two intraoperative isotonic fluid regimens (Sterofundin vs. normal saline, both added with 1% of glucose) in children undergoing major surgery. Secondary objectives were to compare changes in other electrolytes, renal function, and the occurrence of hypoglycemia. METHODS: Children aged between 1 and 36 months, scheduled for major surgery, were randomized to receive Sterofundin or saline during the intraoperative time. Children with preoperative electrolyte abnormalities, hemodynamic instability, and severe renal or hepatic dysfunction were excluded. The primary outcome was the Δ of Cl(-) (Δ = change in plasma concentration between post- and pre-infusion), and secondary outcomes included Δ of other electrolytes and intraoperative hypoglycemia. RESULTS: A total of 240 patients were included in the two study sites and randomized to receive Sterofundin plus 1% glucose or normal saline plus 1% glucose, in a open fashion (229 were finally analyzed). Δ of Cl- and Mg++ was statistically less relevant in patients who received intraoperative Sterofundin, and Δ of the other electrolytes was comparable between the two study groups. Relative risk of hyperchloremia was significantly higher when large volumes were infused (over than 46.7 ml·kg(-1) ), regardless of type of crystalloid infused. Hypoglycemia occurred in two of 229 patients. CONCLUSIONS: Sterofundin is safer than normal saline in protecting young children undergoing major surgery against the risk of increasing plasma chlorides and the subsequent metabolic acidosis.

The optimum initial pediatric epidural bolus: a comparison of four local anesthetic solutions.

BACKGROUND: There is no consensus on the concentration or type of local anesthetic used for initiation of epidural anesthesia. The aim of this randomized, double-blind, controlled trial was to compare the clinical effectiveness of epidural administration of both levobupivacaine and bupivacaine in 0.2% and 0.25% concentrations in pediatric patients undergoing abdominal and urological surgery. METHODS: One hundred and forty-one children scheduled for lower abdominal and urological surgery were randomized to receive 0.4-0.6 ml.kg(-1) epidural, 0.25% bupivacaine, 0.2% bupivacaine, 0.25% levobupivacaine or 0.2% levobupivacaine. Initial epidural volumes, onset times; hemodynamic consequences, postoperative pain scores and degree of residual postoperative motor block were all recorded. RESULTS: There were no significant differences in the proportion of children with effective analgesia after incision [0.20% bupivacaine 97%, 0.25% bupivacaine 94%, 0.20% levobupivacaine 91%, 0.25% levobupivacaine 92% (P=0.73)] when a median volume of 0.55 ml.kg(-1) was used. There was no association between the volume used for thoracic, lumbar, or sacral epidural anesthesia and the effectiveness of the agents used. There was a significantly greater incidence of pain on awakening with the 0.2% solutions compared with the 0.25% solutions, but no differences in the incidence of residual motor block between groups. CONCLUSIONS: While there is no difference in the proportion of effective surgical anesthesia, the lower incidence of pain and distress with the 0.25% solutions suggests that this concentration has clinical advantages over the 0.2% solutions for pediatric epidural anesthesia.

Evaluación prospectiva de bloqueos regionales centrales en pediatría: ventajas, desventajas y complicaciones / Prospective evaluation of pediatric central blocks: advantage, disadvantage and complications

Antecedentes: Las técnicas de anestesia regional y combinada en pediatría son utilizadas desde hace años en cirugías de alto impacto aferente o en pacientes con problemas especiales. Objetivo: Evaluación de las ventajas, desventajas y complicaciones de técnicas de anestesia regional y combinada con bloqueos centrales en pediatría. Lugar de aplicación: Servicio de Anestesiología del Hospital Nacional de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina. Unità Operativa di Anestesia e Rianimazione III. Terapia Intensiva Pediatrica, Azienda Ospiedaliera "Ospedali Riuniti", Bergamo, Italia. Diseño: case control study. Población: 250 pacientes ASA I a III, menores de 16 años. Método: Selección de pacientes con beneficios teóricos de recibir anestesia regional o combinada, según el tipo de intervención, por el tipo de estimulación quirúrgica o por riesgo potencial frente al uso de anestesia general convencional. Resultados: 100 bloqueos epidurales lumbares o torácicos, 100 caudales, 50 raquídeos. Efectividad: 97 por ciento. Se registraron complicaciones menores en 10 pacientes. Conclusiones: Las técnicas de anestesia regional o combinada en pediatría permiten un excelente nivel de bloqueo aferente, brindando excelentes condiciones quirúrgicas. Presentan múltiples ventajas en cirugía pediátrica con adecuados niveles de seguridad.

Evaluación prospectiva de bloqueos regionales centrales en pediatría: ventajas, desventajas y complicaciones / Prospective evaluation of pediatric central blocks: advantage, disadvantage and complications

Antecedentes: Las técnicas de anestesia regional y combinada en pediatría son utilizadas desde hace años en cirugías de alto impacto aferente o en pacientes con problemas especiales. Objetivo: Evaluación de las ventajas, desventajas y complicaciones de técnicas de anestesia regional y combinada con bloqueos centrales en pediatría. Lugar de aplicación: Servicio de Anestesiología del Hospital Nacional de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina. UnitO Operativa di Anestesia e Rianimazione III. Terapia Intensiva Pediatrica, Azienda Ospiedaliera "Ospedali Riuniti", Bergamo, Italia. Diseño: case control study. Población: 250 pacientes ASA I a III, menores de 16 años. Método: Selección de pacientes con beneficios teóricos de recibir anestesia regional o combinada, según el tipo de intervención, por el tipo de estimulación quirúrgica o por riesgo potencial frente al uso de anestesia general convencional. Resultados: 100 bloqueos epidurales lumbares o torácicos, 100 caudales, 50 raquídeos. Efectividad: 97 por ciento. Se registraron complicaciones menores en 10 pacientes. Conclusiones: Las técnicas de anestesia regional o combinada en pediatría permiten un excelente nivel de bloqueo aferente, brindando excelentes condiciones quirúrgicas. Presentan múltiples ventajas en cirugía pediátrica con adecuados niveles de seguridad. (AU)