British journal of anaesthesia最新文献

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles). Unsupervised hierarchical cluster analysis identified distinct groups of patients with similar RAAS activation from samples obtained before induction of anaesthesia, quantified by enzyme-linked immunoassays for plasma renin, aldosterone, angiotensin-converting enzyme 2, and dipeptidyl peptidase-3. The primary outcome, masked to investigators and participants, was myocardial injury (plasma high-sensitivity troponin-T).

Results: We identified three clusters, with similar proportions of RAAS inhibitors randomised to stop or continue. Cluster 1 (n=52; mean age [standard deviation], 75 yr [8 yr]; 54% female) and cluster 3 (n=25; 75 yr [6 yr]; 44% female) had higher rates of myocardial injury (23/52 [44%] and 13/25 [52%], respectively), compared with cluster 2 with 51/164 (31.1%; n=153; 70 yr [6] yr; 46% female; odds ratio: 1.95, 95% confidence interval (CI) 1.12-3.39, P=0.018). Cluster 2 was characterised by lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration (mean difference 698 pg ml^-1, 95% CI 576-820 pg ml^-1) and higher renin concentration (mean difference 350 pg ml^-1, 95% CI 123-577 pg ml^-1), compared with clusters 1 and 3 which had higher rates of myocardial injury.

Conclusions: This mechanistic exploratory analysis suggests that effective preoperative RAAS inhibition is associated with lower risk of myocardial injury after noncardiac surgery, independent of stopping or continuing RAAS inhibitors before surgery.

Clinical trial registration: ISRCTN17251494.

Background: Sex-differences in pain perception have been documented; however, the role of sex hormones in chronic musculoskeletal pain (CMP) remains unclear. Therefore, this study investigated whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CMP.

Methods: We utilised data from the UK Biobank (n=357 424; females: 51.6%; white: 95.2%). Serum concentrations of oestradiol (E2), testosterone (T), and SHBG were measured at baseline. Chronic pain (≥3 months) in the neck/shoulder, back, hip, knee, or 'all over the body' was assessed at baseline and three follow-ups. Mixed-effects multinomial/logistic regression models were used.

Results: In multivariable analyses, greater concentrations of T and T/SHBG were associated with a lower number of CMP sites in both males (T: relative risk ratio=0.81 per standard deviation, 95% confidence interval [0.77-0.86] and T/SHBG: 0.85 [0.80-0.92]) and females (T: 0.85 [0.81-0.89] and T/SHBG: 0.93 [0.89-0.97] [all P-values for trend ≤0.001]). Greater T concentrations and T/SHBG were also associated with lower odds of CMP across all sites, while higher concentrations of SHBG were associated with lower odds of neck/shoulder CMP in both sexes. There was no association between concentrations of E2, SHBG, or E2/SHBG and number of CMP or site-specific CMP in either sex.

Conclusion: In both sexes, greater T concentrations and T/SHBG were associated with lower number of CMP sites and site-specific CMP, while greater concentrations of SHBG were linked to lower odds of neck/shoulder CMP. These findings suggest a potential involvement of sex steroids in the pathogenesis of CMP and underscore the need for further investigation into their potential in chronic pain management strategies.

Background: Systemic inflammation after heart valve replacement surgery commonly results in complications including cognitive impairment. This study was designed to investigate whether valvular heart disease itself and inflammation after valve replacement surgery affects cognition and the related functional connectivity (FC) of the hippocampal memory network.

Methods: Forty-three patients with valvular heart disease were screened for recruitment and assessed with cognition function tests, blood inflammatory cytokine measurements, and functional magnetic resonance imaging scans before surgery and on postoperative day 7 and 30. Age- and sex-matched healthy controls (n=30) were recruited for comparison. The brain FC networks using the hippocampus as a seed were analysed. Bivariate correlation and structural equation model analyses were carried out to investigate the association between altered FC, memory, and inflammation.

Results: Thirty-five patients and 29 healthy controls completed the study, and their data were finally analysed and reported. Compared with healthy controls, the surgery group had increased FC in the bilateral precuneus and middle cingulate and paracingulate gyri before surgery. They exhibited impaired memory, increased plasma concentrations of proinflammatory cytokines, and decreased hippocampal FC at postoperative day 7. At 30 days after surgery, the FC abnormalities seen before surgery and at postoperative day 7 were restored to the level comparable with the healthy controls. High systemic inflammation was significantly associated with worse memory and lower FC in the hippocampal memory network.

Conclusions: Valve replacement surgery temporarily disrupts the hippocampal memory network with transient associated memory decline.

Clinical trial registration: ChiCTR2300069614.

Large, randomised trials are the bedrock of evidence-based medicine, but the resources required to complete such trials greatly limit the number of important clinical questions that can be addressed within a reasonable period of time. Adaptive platform trials can identify effective, ineffective, or harmful treatments faster. These trials have been shown to deliver rapid evidence through the COVID-19 pandemic and are now being adopted across surgery and anaesthesia, with many opportunities for surgeons, anaesthetists, and other perioperative physicians to conduct and collaborate in platform trials.

Acute hypoxic ventilatory response is an important reflex that helps maintain breathing during low oxygen levels, but it is attenuated by most general anaesthetics. Analgesic doses of ketamine and esketamine are known to have respiratory stimulant effects. In their recent study in the British Journal of Anaesthesia, Jansen and colleagues show that low-dose esketamine preserved the acute hypoxic ventilatory response, while increasing breathing rate, systolic blood pressure, and heart rate. Participants also exhibited higher levels of alertness and unpleasant psychotropic effects compared with the control condition. We review the pharmaco-physiological effects of acute hypoxia and its interactions with esketamine. We provide a summary of the effects of hypoxia and esketamine on the neurocircuitry that leads to arousal, activation of the sympathetic nerve system, and increased drive to upper airway dilator and respiratory pump muscles.