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 ...

Hematopoietic stem cell transplantation prior to 2 years of age reduces the incidence of difficult mask ventilation and difficult intubation in children with MPS I. ERT was initiated late in the clinical course of MPS II and VI and induced improvements in upper airway patency but did not reduce the incidence of difficult airway management.

Background Post-operative 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 (GAS) 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 ≤ 60 weeks postmenstrual age scheduled for inguinal herniorraphy were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born < 26 weeks’ gestation. The primary outcome of this analysis was any observed apnea up to 12 hours post-operatively. Apnea assessment was unblinded. Results 363 patients were assigned to RA and 359 to GA. Overall the incidence of apnea (0 to 12 hours) was similar between arms (3% in RA and 4% in GA arms, Odds Ratio (OR) 0.63, 95% Confidence Intervals (CI): 0.31 to 1.30, P=0.2133), however the incidence of early apnea (0 to 30 minutes) was lower in the RA arm (1% versus 3%, OR 0.20, 95%CI: 0.05 to 0.91, P=0.0367). The incidence of late apnea (30 minutes to 12 hours) 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 herniorraphy reduces apnea in the early post-operative period. Cardio-respiratory monitoring should be used for all ex-premature infants.

No abstract

In a single-centre, retrospective, case-controlled study of patients attending the Alfred Hospital in Prahran, Victoria, we assessed the effect of hyperbaric oxygen therapy (HBOT) in reducing mortality or morbidity in patients with necrotising fasciitis (NF) over a 13-year period from 2002 to 2014. A total of three hundred and forty-one patients with NF were included in the study, of whom 275 received HBOT and 66 did not. The most commonly involved sites were the perineum (33.7%), lower limb (29.9%) and trunk (18.2%). The commonest predisposing factor was diabetes mellitus (34.8%). Polymicrobial NF (type 1 NF) occurred in 50.7% and Group A streptococcal fasciitis (type 2 NF) occurred in 25.8% of patients. Mortality was 14.4% overall, 12% in those treated with, and 24.3% in those not treated with, HBOT. ICU support was required in 248 (72.7%) patients. Independent factors impacting on mortality included HBOT (odds ratio [OR] 0.42 [0.22 to 0.83], P=0.01), increased age (OR 1.06 [1.03 to 1.08], P=0.001) and immunosuppression (OR 2.6 [1.23 to 5.51], P=0.01). Mortality was linked to illness severity at presentation, however when adjusted for severity score and need for intensive care management, HBOT was associated with significant reduction in mortality.

Sevoflurane and desflurane anesthesia were associated with similar incidences of ED in children undergoing sub-umbilical surgery and receiving effective regional anesthesia. High scores on the first three items of the PAED scale were highly correlated with ED. The items restlessness and inconsolability had lower sensitivity for the diagnosis of ED.

Background The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multi-site, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at five years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. Methods 722 infants ≤ 60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine RA or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born < 26 weeks’ gestation. Moderate hypotension was defined as mean arterial pressure (MAP) measurement of < 35 mm Hg. Any hypotension was defined as mean arterial pressure (MAP) of <45 mm Hg. Epochs were defined as a 5 minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol (APP). Results The relative risk of general anesthesia compared with regional anesthesia predicting any measured hypotension<35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (CI 2.0, 4.1, p value <0.001) by ITT analysis and 4.5 (CI 2.7,7.4, p value <0.001) by APP analysis In the GA group 87% and 49% and in the RA group 41% and 16% exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA vs. RA), weight at the time of surgery and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (Relative Risk 2.8, 95% CI:1.7,4.4 by ITT). Conclusions RA reduces the incidence of hypotension and chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.