Effect of sedation with inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review protocol

Introduction The COVID-19 pandemic has renewed interest in the use of inhaled anaesthetics for sedation of ventilated critically ill patients. Preliminary data show that inhaled anaesthetics reduce lung inflammation, time to extubation and intensive care unit length of stay compared with intravenous sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes is not well described in this setting. Randomised controlled trials are underway to establish if inhaled anaesthetics affect these and other patient and health system outcomes. Our aim is to summarise the known effects of inhaled sedatives on cognitive and psychiatric outcomes. Methods and analysis In this systematic review, we will use MEDLINE, EMBASE, and PsycINFO to identify studies from 1970 to 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anaesthetics. We will include case series, observational and cohort studies and randomised controlled trials. We will exclude case studies due to the heterogeneity of reporting in these studies. For randomised controlled trials comparing inhaled to intravenous sedation, we will report cognitive and psychiatric outcomes for both study arms. Studies will be selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data will be extracted using a standardised data extraction tool by two independent reviewers. Studies will be assessed for bias using the Cochrane risk of bias tool for randomised controlled trials, or the Newcastle-Ottawa Scale for cohort and case-control studies. Findings will be reported according to outcome and descriptive statistics will be used to illustrate findings in a narrative fashion. Ethics and dissemination The systematic review uses published data and therefore does not require ethics approval. Results will be disseminated via publication in peer-reviewed journals and presentation at conferences related to the field. PROSPERO registration number CRD42021236455

Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS)trial

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

Minimal exhaled nitric oxide production in the lower respiratory tract of healthy children aged 2 to 7 years

<b>BACKGROUND</b> : Exhaled nitric oxide (eNO) is elevated in inflammatory airway conditions, e.g. asthma. We measured eNO levels in normal preschool children for whom there is little data available and in whom the prevalence of asthma is high. <b>SUBJECTS AND METHODS</b> : Fifty children, 2-7 years old, undergoing elective surgery, excluding airway procedures, were recruited. Children with known respiratory disease or acute viral infections were excluded. Gas for eNO measurement was collected in a non-diffusion bag via 1) the mask after inhalation induction of anesthesia, 2) endotreacheal tube (ETT) or laryngeal mask airway (LMA), and 3) during emergence. Measurement was off-line by chemiluminescent analyzer. <b>RESULTS</b> : Mean eNO level by mask was 10.23 ppb (mean value&#177;SD of 8.8-11.1 ppb) after induction and 8.35 ppb (mean value&#177;SD of 5.9-10.8 ppb) on emergence. Mean eNO for the intubated group (n=25) was 0.75 ppb (mean value(SD of 0.4-1 ppb) (<i> P</i> &#60; 0.0001 vs mask); mean eNO for the LMA group (n=25) was 2.6 ppb (mean value&#177;SD of 2-3.2 ppb), which differed from the mask (<i> P</i> &#60; 0.0001), and from ETT values (<i> P</i> &lt; 0.0001). <b>CONCLUSIONS</b> : Most eNO is produced by the upper airway in healthy pre-school children. The lower airway constitutive eNO production is very low. The LMA does not completely isolate the upper airway and current mask collection techniques allow significant contamination of samples by sino-nasal eNO production in young children