Literature Updates from May 2016

Sleep Apnoea and the Brain: A Complex Relationship

Intermittent hypoxia, reoxygenation, and hypercapnia or hypocapnia occur in both adults and children during untreated apnoea and hypopnoea, along with changes in cerebral blood flow and sleep fragmentation. These effects can result in cognitive deficits with functional effects on work and school efficiency. The assessment of how obstructive sleep apnoea affects cognition depends on the specificity and sensitivity of the tests, which are rarely developed specifically for obstructive sleep apnoea. In this Review, we discuss both the neural adaptive and maladaptive processes in response to hypoxaemia. The net result on cognitive and emotional performance depends on the stage of this dynamic process, effects on other body systems, cognitive reserve, and idiosyncratic susceptibility. We also explore the contribution of fragmented sleep, and the disruption of sleep structure, with focus on the effect at different times in the development of disease. This Review will address the gap in the underlying pathophysiology of new clinical and translational findings, and argue their contribution to the inherent complexity of the association between obstructive sleep apnoea and the brain.

Circadian Gene Variants Influence Sleep and the Sleep Electroencephalogram in Humans

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

Changes in the Composition of Brain Interstitial Ions Control the Sleep-Wake Cycle

Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K(+) concentration ([K(+)]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K(+)]e concomitant with decreases in [Ca(2+)]e, [Mg(2+)]e, [H(+)]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K(+)]e while increasing [Ca(2+)]e, [Mg(2+)]e, and [H(+)]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.

Association Between Type of Sedation and the Adverse Events Associated with Gastrointestinal Endoscopy: An Analysis of Five Years’ Data from a Tertiary Center in the USA

This is a retrospective, single institution study, based in the analysis of more than 70000 procedures. A total of 163 adverse events were reported including 13 cases of cardiac arrest. The analysis shows that propofol anesthesia was associated with more incidence of adverse events than midazolam-fentanyl combined. It might look controversial although several factors still need to be considered.

Dexmedetomidine vs Propofol-Remifentanil Conscious Sedation for Awake Craniotomy: A Prospective Randomized Controlled Trial

Another successful application of dexmedetomidine as a sedative agent in the clinical setting, in this case for awake craniotomies. Dexmedetomidine exhibits similar efficacy as the combination of propofol and remifentanil but with a significantly less number of respiratory depression related events.

The Feasibility and Utility of Continuous Sleep Monitoring in Critically Ill Patients Using a Portable Electroencephalography Monitor

This study suggests the utility of a portable EEG monitor to measure different sleep stages, transitions, and arousal in the ICU setting.

Quality Measures for the Care of Pediatric Patients with Obstructive Sleep Apnea

This document describes measurement methods for five desirable process measures: assessment of symptoms and risk factors of OSA, initiation of an evidence-based action plan, objective evaluation of high-risk children with OSA by obtaining a polysomnogram (PSG), reassessment of signs and symptoms of OSA within 12 months, and documentation of objective assessment of positive airway pressure adherence. When these five process measures are met, clinicians should be able to achieve the two defined outcomes: improve detection of childhood OSA and reduce signs and symptoms of OSA after initiation of a management plan.

Sleep Disordered Breathing and Academic Performance: A Meta-Analysis

Clear links between SDB and poorer academic performance in school-age children are demonstrated. ES statistics were in the small to medium range, but nevertheless the findings serve to highlight to parents, teachers, and clinicians that SDB in children may contribute to academic difficulties some children face.

Anesthesiological Considerations for Children with Obstructive Sleep Apnea

Perioperative deaths in children with OSA occur at a low frequency. Hypoxia-induced opioid sensitivity combined with an approximate 1-2% incidence of rapid conversion of codeine to morphine suggest the need for new approaches for providing preoperative assessment of risk, extended postoperative observation and the need for alternative opioids to codeine. Additionally, new less painful surgical approaches may help to reduce postoperative opioid requirements and therefore perhaps less risk for opiate-induced apnea in this vulnerable population.