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

ABSTRACT: 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).

SUBMITTER: Davidson AJ

PROVIDER: S-EPMC5023520 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Davidson Andrew J AJ Disma Nicola N de Graaff Jurgen C JC Withington Davinia E DE Dorris Liam L Bell Graham G Stargatt Robyn R Bellinger David C DC Schuster Tibor T Arnup Sarah J SJ Hardy Pollyanna P Hunt Rodney W RW Takagi Michael J MJ Giribaldi Gaia G Hartmann Penelope L PL Salvo Ida I Morton Neil S NS von Ungern Sternberg Britta S BS Locatelli Bruno Guido BG Wilton Niall N Lynn Anne A Thomas Joss J JJ Polaner David D Bagshaw Oliver O Szmuk Peter P Absalom Anthony R AR Frawley Geoff G Berde Charles C Ormond Gillian D GD Marmor Jacki J McCann Mary Ellen ME

Lancet (London, England) 20151104 10015

<h4>Background</h4>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 ...[more]

PMID: 26507180

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Project description:BackgroundIn 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.MethodsIn 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-to-treat 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.FindingsBetween 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.InterpretationSlightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.FundingUS National Institutes of Health, US Food and Drug Administration, Thrasher Research Fund, Australian National Health and Medical Research Council, Health Technologies Assessment-National Institute for Health Research (UK), Australian and New Zealand College of Anaesthetists, Murdoch Children's Research Institute, Canadian Institutes of Health Research, Canadian Anesthesiologists Society, Pfizer Canada, Italian Ministry of Health, Fonds NutsOhra, UK Clinical Research Network, Perth Children's Hospital Foundation, the Stan Perron Charitable Trust, and the Callahan Estate.

Project description:BackgroundPatients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival.Methods/designA two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free (including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy.Trial registrationCurrent Controlled Trials ISRCTN00525237.

Project description:BackgroundFlexor tendon injuries most commonly occur following a penetrating injury to the hand or wrist. These are challenging injuries and the standard treatment is surgical repair under general or regional anaesthesia. 'Wide-awake' surgery is an emerging technique in hand surgery where a conscious patient is operated on under local anaesthetic. The vasoconstrictive effect of adrenaline (epinephrine) creates a 'bloodless' operating field and a tourniquet is not required. The potential advantages include intra-operative testing of the repair; removal of the risks of general anaesthesia; reduced costs; no aerosol generation from intubation therefore reduced risk of COVID-19 spread to healthcare professionals. The aim of this study will be to systematically evaluate the evidence to determine if wide-awake surgery is superior to general/regional anaesthetic in adults who undergo flexor tendon repair.MethodsWe designed and registered a study protocol for a systematic review and meta-analysis of comparative and non-comparative studies. The primary outcome will be functional active range of motion. Secondary outcomes will be complications, resource use (operative time) and patient-reported outcome measures. A comprehensive literature search will be conducted (from 1946 to present) in MEDLINE, EMBASE, CINAHL, and Cochrane Library. Grey literature will be identified through Open Grey, dissertation databases and clinical trials registers. All studies on wide-awake surgery for flexor tendon repair will be included. The comparator will be general or regional anaesthesia. No limitations will be imposed on peer review status or language of publication. Two investigators will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion or referral to a third author when necessary. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis.DiscussionThis systematic review will summarise the best available evidence and definitively establish if function, complications, cost, or patient-reported outcomes are improved when flexor tendons are repaired using wide-awake technique. It will determine if this novel approach is superior to general or regional anaesthesia. This knowledge will help guide hand surgeons by continuing to improve outcomes from flexor tendon injuries.Systematic review registrationPROSPERO CRD42020182196.

Project description:BackgroundPrevious studies have suggested that monitoring the levels of both hypnosis and antinociception could reduce periods of inadequate anaesthesia. However, the evidence regarding associated benefits of this monitoring is still limited.ObjectiveThe primary objective of this study was to confirm that guidance of anaesthesia by depth of hypnosis and antinociception monitoring decreases the number of inadequate anaesthesia events in comparison with standard clinical practice.DesignA multicentre, single-blinded, randomised controlled trial.SettingThe study was conducted in four European University hospitals in four different countries between December 2013 and November 2016.PatientsThe study population consisted of a total of 494 adult patients undergoing elective surgery requiring tracheal intubation.InterventionsThe patients were allocated to one of two groups. The first group was treated using Entropy for depth of hypnosis and surgical pleth index to determine depth of antinociception (adequacy of anaesthesia group; AoA group). The second group was monitored using standard monitoring alone (control group). Anaesthesia was conducted with target-controlled infusions of propofol and remifentanil.Main outcome measuresThe primary outcome of the study was the number of total unwanted events for example signs of inadequately light or unintentionally deep anaesthesia.ResultsEvidence of inadequate anaesthesia had an incidence of around 0.7 events per patient in both groups with no difference between groups (P?=?0.519). In the AoA group, the overall consumption of propofol was significantly reduced (6.9 vs. 7.5?mg?kg?h, P?=?0.008) in comparison with the control group. The consumption of remifentanil was equal in both groups. The times to emergence [8.0 vs. 9.6?min (P?=?0.005)] and full recovery in the postanaesthesia care unit (P?=?0.043) were significantly shorter in the AoA group. No differences were seen in postoperative pain scores or in the use of analgesics.ConclusionIn the current study, the guidance of total intravenous anaesthesia by Entropy and surgical pleth index in comparison with standard monitoring alone was not able to validate reduction of unwanted anaesthesia events. However, there was a reduction in the use of propofol, and shorter times for emergence and time spent in the postanaesthesia care unit.Trial registrationat ClinicalTrials.gov NCT01928875.

Project description:BACKGROUND:The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 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:A total of 722 infants ?60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 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. RESULTS:The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol 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 versus 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 the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Project description:BackgroundArthroscopic excision has currently become popular for the treatment of wrist ganglions. The objective of this study was to evaluate the clinical outcomes and cost effectiveness of arthroscopic wrist ganglion excisions under Wide-Awake Local Anaesthesia No Tourniquet versus general anaesthesia.MethodsWe retrospectively reviewed patients who underwent arthroscopic ganglionectomy from April 2009 to October 2016 at our institute. They were separated into two groups according to anaesthesia techniques: general anaesthesia and Wide-Awake Local Anaesthesia No Tourniquet. We compared the clinical outcomes and cost-effectiveness of the two groups.ResultsSeventy-four patients were included. Both groups were matched with regard to the demographics and preoperative clinical assessments. We found no significant differences between groups in postoperative visual analog scale, modified Mayo wrist score, Disabilities of Arm, Shoulder and Hand score, recurrence, residual pain, or complications. Recurrence was found in five of 74 patients, one (4.3%) in the Wide-Awake Local Anaesthesia No Tourniquet group and four (7.8%) in the general anaesthesia group. One extensor tendon injury and four extensor tenosynovitis cases occurred in the general anaesthesia group. Regarding cost effectiveness, the mean operating time in the Wide-Awake Local Anaesthesia No Tourniquet and general anaesthesia groups were 88.7 ± 24.51 and 121.5 ± 25.75 min, respectively (p < 0.001). The average total costs of the Wide-Awake Local Anaesthesia No Tourniquet and general anaesthesia groups were €487.4 ± 89.15 and €878.7 ± 182.13, respectively (p < 0.001).ConclusionsFor arthroscopic wrist ganglion resections, both anaesthesia techniques were effective and safe regarding recurrence rates, complications, and residual pain. The most important finding of this study was that arthroscopic ganglionectomy under Wide-Awake Local Anaesthesia No Tourniquet was superior to that under general anaesthesia for cost-effectiveness.Level of evidenceLevel III, Retrospective comparative study.

Dataset Information

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

Publications

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

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