High daily caffeine intake is associated with lower propofol requirements for anesthetic induction.

Background and Aims: There is significant interindividual variation in the dose of propofol required for anesthetic induction. Factors dictating this are poorly described, but understanding them would be useful for anesthetic drug dosing. It has been shown in rats and recently in humans that caffeine administration accelerates recovery from anesthesia, but no study has assessed the effect on anesthetic induction. Material and Methods: Forty American Society of Anesthesiologists (ASA)-I, 18-65-year-old patients, undergoing day case general anesthesia with propofol and fentanyl took part in this observational study. Total daily caffeine intake (mg) was estimated using the caffeine assessment tool and caffeine content values from the US Department of Agriculture National Nutrient Database. Pharmacokinetic-pharmacodynamic modeling was used to estimate the effect site concentration of propofol at loss of consciousness (Ce(p) LOC). Results: Median (interquartile range [IQR]) daily caffeine intake was 106 (51-193) mg. Ce(p) LOC was lower in those with caffeine intake greater than or equal to the median of 106 mg (median (IQR) = 0.64 µg/ml (0.51-0.72) vs. 0.70 µg/ml (0.57-1.10), P = 0.04). The effect was robust when controlling for weight-adjusted fentanyl dose, age, smoking status, and alcohol intake (F (1,34) = 4.66, P = 0.04). Conclusion: High daily caffeine intake is associated with lower propofol requirements for day case anesthetic induction. We propose that high daily caffeine intake may cause lower arousal levels prior to surgery due to a relative caffeine deficit caused by being nil by mouth. As such, assessment of daily caffeine intake preoperatively may aid anesthetic drug dosing.

Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness.

Accurately measuring the neural correlates of consciousness is a grand challenge for neuroscience. Despite theoretical advances, developing reliable brain measures to track the loss of reportable consciousness during sedation is hampered by significant individual variability in susceptibility to anaesthetics. We addressed this challenge using high-density electroencephalography to characterise changes in brain networks during propofol sedation. Assessments of spectral connectivity networks before, during and after sedation were combined with measurements of behavioural responsiveness and drug concentrations in blood. Strikingly, we found that participants who had weaker alpha band networks at baseline were more likely to become unresponsive during sedation, despite registering similar levels of drug in blood. In contrast, phase-amplitude coupling between slow and alpha oscillations correlated with drug concentrations in blood. Our findings highlight novel markers that prognosticate individual differences in susceptibility to propofol and track drug exposure. These advances could inform accurate drug titration and brain state monitoring during anaesthesia.

A systematic review of structural and functional MRI differences between psychotic and nonpsychotic depression.

BACKGROUND: Psychotic depression is widely accepted as a specific subtype of unipolar major depression. Magnetic resonance imaging studies have begun to investigate the neurobiological changes that differentiate this subtype of major depression from non-psychotic depression. Any differences may eventually be useful in aiding diagnosis patients for whom there is diagnostic uncertainty. This review collates the currently available evidence. SUBJECTS AND METHODS: A systematic search of the Medline, PubMed, Embase & Web of Science databases was used to identify all articles comparing structural grey matter or functional magnetic resonance imaging (MRI) differences between adults (18+) with previously diagnosed psychotic and nonpsychotic depression in predefined regions of interest (hippocampus, amygdala, cingulate, insula & frontal cortices). The results were collated and organised according to brain region. RESULTS: There is a paucity of studies addressing structural and functional changes differentiating these two disorders and recommendations regarding use of these modalities in diagnosis cannot be made. From the available studies decreases in frontal cortex grey matter volumes may differentiate psychotic from non-psychotic depression whilst further studies are required to confirm decreases in insula cortex volumes. fMRI studies show associations between altered activity in these two regions and cognitive impairments in patients with psychotic depression. The volumes of putative emotional processing regions including the amygdala, hippocampus and anterior cingulate show no difference between psychotic and nonpsychotic depression. CONCLUSIONS: Structural and functional changes in the higher associative regions of the frontal and insular cortices appear to differentiate psychotic and nonpsychotic depression to a greater degree than changes in putative emotional processing regions. The quality of the evidence both in terms of numbers of studies available and sample sizes involved is very poor but in regard to directing future study, understanding the neurobiology of psychotic depression may benefit from a more detailed assessment of these two regions.

Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network.

BACKGROUND: Long-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from burns intensive care units (BICUs), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN). METHODS: Fifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans. Functional connectivity, fractional anisotropy and cortical thickness of the main DMN subdivisions (anterior DMN (aDMN), posterior DMN (pDMN) and right (rTPJ) and left (lTPJ) temporo-parietal junctions) were compared between patients and volunteers, with differences correlated against cognitive performance. RESULTS: Functional connectivity between rTPJ and pDMN (t = 2.91, p = 0.011) and between rTPJ and lTPJ (t = 3.18, p = 0.008) was lower in patients compared to volunteers. Functional connectivity between rTPJ and pDMN correlated with cognitive performance (r2 =0.33, p < 0.001). Mean fractional anisotropy of rTPJ (t = 2.70, p = 0.008) and lTPJ (T = 2.39, p = 0.015) was lower in patients but there was no difference in cortical thickness. CONCLUSIONS: Patients previously admitted to BICU show structural and functional disruption of the DMN. Since functional changes correlate with cognitive performance, this should direct further research into intensive-care-related cognitive impairment.

Peer-led live research demonstrations: challenging medical student misconceptions about research.

Modern health care provision is now fundamentally evidence based, meaning competency in academic medicine is integral to medical training. The Integrated Academic Training pathway provides focussed training in this area at a postgraduate level but no such provision exists at an undergraduate level. A number of peer-led academic societies have emerged across the UK to provide education and support for undergraduates but there is little evidence about the type of peer-led interventions that are effective. We report here the findings of one such peer-led organization, the Warwick Academic Medicine Society. We found that traditional educational interventions, including didactic lectures and small-group teaching, are effective at inspiring students regarding academic medicine but poor at translating this enthusiasm into sustained involvement in research. We find this disparity to be centred on misconceptions amongst students regarding the time and skills required to meaningfully contribute to a research project. Further, we introduce the concept of the Live Research Demonstration (LRD), a novel peer-led educational intervention which aims to address these misconceptions and improve involvement of students in research. Initial pilots of the LRD concept have shown significant promise and we recommend a larger trial across multiple localities to confirm its educational benefits.