SummaryBackgroundThere is pre-clinical evidence that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia may have an increased risk of poorer neurodevelopmental outcome. This trial aims to determine if GA in infancy has any impact on neurodevelopmental outcome. The primary outcome for the trial is neurodevelopmental outcome at 5 years of age. The secondary outcome is neurodevelopmental outcome at two years of age and is reported here.MethodsWe performed an international assessor-masked randomised controlled equivalence trial in infants less than 60 weeks post-menstrual age, born at greater than 26 weeks gestational age having inguinal herniorrhaphy. Infants were excluded if they had existing risk factors for neurologic injury. Infants were randomly assigned to awake-regional (RA) or sevoflurane-based general anaesthesia (GA). Web-based randomisation was performed in blocks of two or four and stratified by site and gestational age at birth. The outcome for analysis was the composite cognitive score of the Bayley Scales of Infant and Toddler Development, Third Edition. 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. The trial was registered at ANZCTR, ACTRN12606000441516 and ClinicalTrials.gov, NCT00756600.FindingsBetween February 2007, and January 2013, 363 infants were randomised to RA and 359 to GA. Outcome data were available for 238 in the RA and 294 in the GA arms. The median duration of anaesthesia in the GA arm was 54 minutes. For the cognitive composite score there was equivalence in means between arms (RA-GA: +0·169, 95% CI −2·30 to +2·64).InterpretationFor this secondary outcome we found no evidence that just under an hour of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at two years of age compared to RA.

Background In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-totreat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600. Findings Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41-70). The mean FSIQ score was 99•08 (SD 18•35) in the awake-regional anaesthesia group and 98•97 (19•66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0•23 (95% CI-2•59 to 3•06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis. Interpretation Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia ...

We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were ,48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were ,60 mm Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were ,1 SD of the mean definition of hypotension (,45 mm Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (,35 mm Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants. Pediatrics 2014;133:e751-e757 AUTHORS:

Background: Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss. Evidence supporting its efficacy in surgery for adolescent idiopathic scoliosis is not robust. This trial was designed to validate the clinical efficacy of TXA in surgery for adolescent idiopathic scoliosis. Methods: This institutional review board-approved prospective double-blinded trial involved 111 patients with adolescent idiopathic scoliosis who were randomized to receive either a placebo or TXA (50-mg/kg loading dose and 10-mg/kg/h infusion). Power analysis indicated that 50 patients per group would provide power to detect a >20% difference in blood loss. Two-way analysis of variance (ANOVA) was applied to compare blood loss rates (slopes) using the group-by-time interaction F test. Results: The risk of clinically relevant blood loss (>20 mL/kg) was more than twice as high in the placebo group than in the TXA group (44% versus 21%, relative risk = 2.1, 95% confidence interval = 1.2 to 3.7). Compared with the placebo group, the TXA group had a 27% reduction in intraoperative blood loss, a significantly lower rate of intraoperative bleeding per hour (mean and standard deviation, 190 ± 73 versus 230 ± 80 mL, p = 0.01; F = 9.77, p < 0.001) and per fused spinal level (82 ± 32 versus 110 ± 40 mL, p < 0.001), less intraoperative blood loss (836 ± 373 versus 1,031 ± 484 mL, p = 0.02), and less postoperative bleeding (in the drain) (498 ± 228 versus 645 ± 318 mL, p = 0.009). Six patients who received a placebo and no patient who received TXA required an allogenic blood transfusion. No perioperative adverse events, including thromboembolic events or seizures, were observed. Three independent factors were predictive of blood loss: TXA administration, duration of surgery, and number of levels fused. Greater intraoperative blood loss was the only independent variable predictive of a longer hospital stay. Conclusions: Use of TXA in patients undergoing surgery for adolescent idiopathic scoliosis significantly reduced blood loss, by 27%, compared with that in the placebo group. The rate of intraoperative blood loss per hour and per level fused and the amount of postoperative blood loss were significantly lower in the TXA group. More placebo-treated patients received allogenic blood. Patients with greater intraoperative blood loss spent a longer time in the hospital. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.