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).

A signal detection analysis of executive control performance among adolescent inhalant and cannabis users.

BACKGROUND: Inhalant users have multiple comorbid issues (e.g., polydrug use) that complicate identifying inhalant-specific cognitive deficits. OBJECTIVES: The aim of the present study was to use signal detection theory to identify inhalant-specific differences in executive control. METHODS: We examined three well-matched groups: 19 inhalant users, 19 cannabis users, and 19 controls using Stroop and Go/No-Go tasks. RESULTS: Inhalant users demonstrated significantly lower d-prime scores relative to controls, but not cannabis users, on both tasks, suggesting possible executive deficits relative to controls. CONCLUSIONS/IMPORTANCE: The results of this study raise questions regarding inhalant toxicity and the vulnerability of the adolescent brain to drugs of abuse.

White-matter abnormalities in adolescents with long-term inhalant and cannabis use: a diffusion magnetic resonance imaging study.

BACKGROUND: There is growing evidence that inhalants are neurotoxic to white matter, yet limited work has been conducted to investigate the neurobiologic effects of long-term exposure among adolescent users, despite inhalant use being most prominent during this developmental period. METHODS: We used diffusion tensor imaging to examine white-matter integrity in 11 adolescents who used inhalants, 11 matched cannabis users and 8 drug-naive controls. RESULTS: Although both groups of drug users had white-matter abnormalities (i.e., lower fractional anisotropy), abnormalities were more pronounced in the inhalant group, particularly among early-onset users. LIMITATIONS: The findings of this study should be considered in light of its small sample size, cross-sectional design and the complex psychosocial background of long-term inhalant users. CONCLUSION: White-matter abnormalities may underpin long-term behavioural and mental health problems seen in individuals with long-term inhalant use.

Decreased thalamic volumes in adolescent inhalant users from Korea and Australia.

OBJECTIVES: Research investigating the impact of inhalant misuse on brain structure suggests abnormalities in subcortical regions. We investigated the association between inhalant misuse and subcortical brain volumes in adolescents. METHODS: Based on a collaborative dataset from South Korea (inhalant users: N = 15, mean age = 16.7, SD = 1.1; controls: N = 15, mean age = 15.4, SD = 1.2) and Australia (inhalant users: N = 7, mean age = 18.2, SD = 1.4; controls: N = 7, mean age = 18.9, SD = 2.6), the volumes of caudate nucleus, putamen, pallidum, amygdala, hippocampus, and thalamus were estimated in adolescent inhalant users and healthy adolescents using FreeSurfer. RESULTS: The results revealed a significantly decreased right thalamic volume in adolescent inhalant users (P = 0.042), along with a trend-level decrease in left thalamic volume (P = 0.061). A negative correlation (r = -0.544; P = 0.036) between thalamic volume and severity of inhalant use (i.e., reduced volumes associated with greater use) was identified among Korean participants. CONCLUSIONS: These findings suggest that compared with other subcortical structures, the thalamus is particularly sensitive to damage following chronic inhalant exposure during adolescence.

The impact of cannabis use on cognitive functioning in patients with schizophrenia: a meta-analysis of existing findings and new data in a first-episode sample.

Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP - CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients, who only developed psychosis after a relatively early initiation into cannabis use.

The dark side of sniffing: paint colour affects intoxication experiences among adolescent inhalant users.

INTRODUCTION AND AIMS: Inhalant abuse among adolescents is a significant health concern in many countries; however, limited research has explored whether the intoxication experience differs between commonly used inhalants. The aim of the present study was to examine how exposure to different types of paints (chrome vs. non-chrome) were experienced by adolescent users. DESIGN AND METHODS: Sixteen adolescent (aged 15-19 years) regular inhalant users completed a semistructured questionnaire enquiring about their inhalant use. Participants were divided into two groups based on paint colour preference [chrome paints (n = 10) and non-chrome paints (n = 6)] and were compared using appropriate statistical tests. RESULTS: Relative to non-chrome users, the chrome-using group were more likely to report deliberately inhaling to experience altered perceptions (such as visual and auditory hallucinations). In addition, a significantly greater proportion of chrome users reported that the perceptual alterations they experienced after sniffing paint differed between paint colours, with chrome colours being associated with more vivid hallucinations. DISCUSSION AND CONCLUSION: While both chrome and non-chrome users reported a comparable level of pleasure from paint sniffing, chrome paint users were more likely to be motivated by the potential to hallucinate. Our findings suggest that the type of inhalant used is an important consideration that may have relevance to clinical treatment.

Interpreting neuropsychological impairment among adolescent inhalant users: two case reports.

OBJECTIVE: To illustrate the need to carefully consider mental health, psychosocial and motivational factors when investigating cognitive and intellectual impairment among chronic inhalant users. METHODS: Two adolescent chronic inhalant users with similar psychosocial disadvantages (eg unstable and dysfunctional families, state-based care, school absenteeism and forensic issues) and histories of comorbid drug use and mental health problems were assessed using a battery of paper and pencil and computerised neuropsychological tests. RESULTS: Contrary to the expectations of her case manager, one participant performed within the normal range for her age in all domains of intellectual ability, while the other participant, in line with the expectations of her case manger, showed marked cognitive deficits and intellectual disability. CONCLUSIONS: The typically complex presentation of chronic inhalant users (ie disadvantaged psychosocial backgrounds, comorbid psychopathology and poor motivation/engagement) is rarely considered when investigating associated cognitive and intellectual functioning. Future research should more carefully consider the role of such factors, given the evidence suggesting that they can considerably alter (accentuate or diminish) the association between inhalant abuse and neuropsychological impairment.