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BackgroundParkinson’s disease has been identified as a risk factor for severe Coronavirus disease 2019 (COVID-19) outcomes. However, whether the significant high risk of death from COVID-19 in people with Parkinson’s disease is specific to the disease itself or driven by other concomitant and known risk factors such as comorbidities, age, and frailty remains unclear.ObjectiveTo investigate clinical profiles and outcomes of people with Parkinson’s disease and atypical parkinsonian syndromes who tested positive for COVID-19 in the hospital setting in a multicentre UK-based study.MethodsA retrospective cohort study of Parkinson’s disease patients with a positive COVID-19 test admitted to hospital between February 2020 and July 2021. An online survey was used to collect data from clinical care records, recording patient, Parkinson’s disease and COVID-19 characteristics. Associations with time-to-mortality and severe outcomes were analysed using either the Cox proportional hazards model or logistic regression models, as appropriate.ResultsData from 552 admissions were collected: 365 (66%) male; median (inter-quartile range) age 80 (74-85) years. The 34-day mortality rate was 38.4%; male sex, increased age and frailty, Parkinson’s dementia syndrome, requirement for respiratory support and no vaccination were associated with increased mortality risk. Community-acquired COVID-19 and co-morbid chronic neurological disorder were associated with increased odds of requiring respiratory support. Hospital-acquired COVID-19 and delirium were associated with requiring an increase in care level post-discharge.ConclusionsThis first, multicentre, UK-based study on people with Parkinson’s disease or atypical parkinsonian syndromes, hospitalised with COVID-19, adds and expands previous findings on clinical profiles and outcomes in this population.

Intraoperative and postoperative hypotension occur commonly and are associated with organ injury and poor outcomes. Changes in arterial blood pressure (BP) during procedural sedation are not well described.Individual patient data from five trials of propofol sedation for colonoscopy and a clinical database were pooled and explored with logistic and linear regression. A literature search and focused meta-analysis compared the incidence of hypotension with propofol and alternative forms of procedural sedation. Hypotensive episodes were characterised by the original authors' definitions (typically systolic BP90 mm Hg).In pooled individual patient data (n=939), 36% of procedures were associated with episodes of hypotension. Longer periods of propofol sedation and larger propofol doses were associated with longer-lasting and more-profound hypotension. Amongst 380 patients for whom individual BP measurements were available, 107 (28%) experienced systolic BP90 mm Hg for5 min, and in 89 (23%) the episodes exceeded 10 min. Meta-analysis of 18 RCTs identified an increased risk ratio for the development of hypotension in procedures where propofol was used compared with the use of etomidate (two studies; n=260; risk ratio [RR] 2.0 [95% confidence interval: 1.37-2.92]; P=0.0003), remimazolam (one study; n=384; RR 2.15 [1.61-2.87]; P=0.0001), midazolam (14 studies; n=2218; RR 1.46 [1.18-1.79]; P=0.0004), or all benzodiazepines (15 studies; n=2602; 1.67 [1.41-1.98]; P0.00001). Hypotension was less likely with propofol than with dexmedetomidine (one study; n=60; RR 0.24 [0.09-0.62]; P=0.003).Hypotension is common during propofol sedation for colonoscopy and of a magnitude and duration associated with harm in surgical patients.

Rapid elimination of remifentanil facilitates application of intense opioid effect during general anaesthesia whilst maintaining prompt emergence. Interruptions in remifentanil supply mean clinicians must relearn titration of pharmacokinetically longer-acting opioids to achieve appropriate levels of opioid effect whilst maintaining acceptable recovery times. Opioid-free anaesthesia is achievable for many minor and intermediate surgical procedures for which remifentanil might have been used previously.

Summary Anaesthesiologists and non-anaesthesiologist sedationists have a limited set of available i.v. hypnotics, further reduced by the withdrawal of thiopental in the USA and its near disappearance in Europe. Meanwhile, demand for sedation increases and new clinical groups are using what traditionally are anaesthesiologists' drugs. Improved understanding of the determinants of perioperative morbidity and mortality has spotlighted hypotension as a potent cause of patient harm, and practice must be adjusted to respect this. High-dose propofol sedation may be harmful, and a critical reappraisal of drug choices and doses is needed. The development of remimazolam, initially for procedural sedation, allows reconsideration of benzodiazepines as the hypnotic component of a general anaesthetic even if their characterisation as i.v. anaesthetics is questionable. Early data suggest that a combination of remimazolam and remifentanil can induce and maintain anaesthesia. Further work is needed to define use cases for this technique and to determine the impact on patient outcomes.

Purpose of review Anaesthesia and sedation are ubiquitous in contemporary medical practice. Developments in anaesthetic pharmacology are targeted on reducing physiological disturbance whilst maintaining or improving titrateability, recovery profile and patient experience. Remimazolam is a new short-acting benzodiazepine in the final stages of clinical development. Recent findings Clinical experience with remimazolam comprises volunteer studies and a limited number of clinical investigations. In addition, laboratory investigations explore the implications of its 'soft drug' pharmacology. Summary Remimazolam provides effective procedural sedation with superior success rates and recovery profile when compared to midazolam. Comparisons with propofol are required. Preliminary studies suggest potential for using remimazolam as the hypnotic component of general anaesthesia. Definitive studies are awaited. As a benzodiazepine, remimazolam could be evaluated as an anticonvulsant and for intensive care sedation.

Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein-coupled receptor kinase 2, a key negative regulator of cardiac function.Laboratory/clinical investigations.University laboratory/medical centers.Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2-deficient mice; elective surgical patients.Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein-coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of6 ms mm Hg). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed.Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein-coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein-coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein-coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with baroreflex dysfunction (relative risk, 1.66 [95% CI, 1.16-2.39]; p = 0.006).Reduced baroreflex sensitivity is associated with nicotinamide adenine dinucleotide phosphate oxidase subunit-2-mediated upregulation of G-protein-coupled receptor kinase 2 expression in cardiomyocytes and impaired cardiac contractility. Autonomic dysfunction predisposes patients to the development of critical illness and increases mortality.

BackgroundThe Evaluation of Nitrous oxide in the Gas Mixture for Anesthesia II trial randomly assigned 7,112 noncardiac surgery patients to a nitrous oxide or nitrous oxide–free anesthetic; severe postoperative nausea and vomiting (PONV) was a prespecified secondary end point. Thus, the authors evaluated the association between nitrous oxide, severe PONV, and effectiveness of PONV prophylaxis in this setting.MethodsUnivariate and multivariate analyses of patient, surgical, and other perioperative characteristics were used to identify the risk factors for severe PONV and to measure the impact of severe PONV on patient outcomes.ResultsAvoiding nitrous oxide reduced the risk of severe PONV (11 vs. 15%; risk ratio [RR], 0.74 [95% CI, 0.63 to 0.84]; P < 0.001), with a stronger effect in Asian patients (RR, 0.55 [95% CI, 0.43 to 0.69]; interaction P = 0.004) but lower effect in those who received PONV prophylaxis (RR, 0.89 [95% CI, 0.76 to 1.05]; P = 0.18). Gastrointestinal surgery was associated with an increased risk of severe PONV when compared with most other types of surgery (P < 0.001). Patients with severe PONV had lower quality of recovery scores (10.4 [95% CI, 10.2 to 10.7] vs. 13.1 [95% CI, 13.0 to 13.2], P < 0.0005); severe PONV was associated with postoperative fever (15 vs. 20%, P = 0.001). Patients with severe PONV had a longer hospital stay (adjusted hazard ratio, 1.14 [95% CI, 1.05 to 1.23], P = 0.002).ConclusionsThe increased risk of PONV with nitrous oxide is near eliminated by antiemetic prophylaxis. Severe PONV, which is seen in more than 10% of patients, is associated with postoperative fever, poor quality of recovery, and prolonged hospitalization.

Anaesthesia education is uniquely placed to allow safe and supervised workplace teaching and training delivered in a personalized, contextual one-to-one basis. Trainers and trainees need to manage their expectations in training, enabling flexible and opportunistic capturing of these learning episodes, as well as structured learning. Structured planning of individualized training is imperative to facilitate learning in trainees with different learning styles. Role modelling of trainers in the workplace is an essential component of both clinical and professional teaching. Critical reflection and high-quality trainee feedback enhances this experiential learning. A robust framework of education governance is fundamental in maintaining a high standard of training; this includes trainer accreditation, recognizing the importance of trainer development, and an appropriate infrastructure to support training and education in the clinical workplace.

Clinicians need critical appraisal skills to weigh up the quality of the literature and to decide whether it has implications for their practice. Every belief in medicine is a construct created from the limited information available and carries a degree of uncertainty. A centralized approach to research identifies the highest priority areas of uncertainty so as to bring about the most improvement for the largest number of patients. This patient-centred model classifies studies into basic science, translational, and clinical research. Adequately powered mega-trials are required to bridge the translational gap between efficacy (does a treatment work?) and effectiveness (does a treatment work when applied in ordinary clinical practice?). There is a paucity of these in perioperative medicine.

After finding out about a distant forebear’s execution, J Robert Sneyd acted as an expert witness in a US court to try to prevent the use of a new drug for lethal injection, appalled that untrained government workers were using lifesaving drugs to kill

Safe sedation is fundamental to many modern cardiological procedures, and following the publication of the report on safe sedation by the Academy of Medical Royal Colleges, this report discusses sedation specifically in cardiological practice. The major areas within cardiology that use sedation are cardioversion, catheter ablation particularly of atrial fibrillation, transoesophageal echocardiography, implantable device (cardiovascular implantable electronic device) procedures and other procedures such as transcatheter aortic valve replacement. There is increasing demand for cardiological sedation but there is wide geographical variation in its use and there are also growing data to support non-anaesthetists giving sedation. The use of benzodiazepines, particularly for short procedures, is common, but even here good record-keeping and audit together with an understanding of the continuum of sedation and having appropriately trained staff and the necessary facilities are vital. Nurse administration of propofol may be appropriate for some procedures in cardiology that require at least moderate sedation. Appropriate training is essential and the use of capnography and target controlled infusion pumps for propofol administration is recommended.

Retired GP leader Pereira Gray snipes at medical schools in general and his local universities in particular.1 2 He might better direct his attention to those who have driven primary care into chaos and made it a less popular choice for trainees. Had he asked before firing his broadsides we could have told him that …