The impact of COVID-19 on anaesthesia and critical care services in the UK: a serial service evaluation

Between October 2020 and January 2021, we conducted three national surveys to track anaesthetic, surgical and critical care activity during the second COVID-19 pandemic wave in the UK. We surveyed all NHS hospitals where surgery is undertaken. Response rates, by round, were 64%, 56% and 51%. Despite important regional variations, the surveys showed increasing systemic pressure on anaesthetic and peri-operative services due to the need to support critical care pandemic demands. During Rounds 1 and 2, approximately one in eight anaesthetic staff were not available for anaesthetic work. Approximately one in five operating theatres were closed and activity fell in those that were open. Some mitigation was achieved by relocation of surgical activity to other locations. Approximately one-quarter of all surgical activity was lost, with paediatric and non-cancer surgery most impacted. During January 2021, the system was largely overwhelmed. Almost one-third of anaesthesia staff were unavailable, 42% of operating theatres were closed, national surgical activity reduced to less than half, including reduced cancer and emergency surgery. Redeployed anaesthesia staff increased the critical care workforce by 125%. Three-quarters of critical care units were so expanded that planned surgery could not be safely resumed. At all times, the greatest resource limitation was staff. Due to lower response rates from the most pressed regions and hospitals, these results may underestimate the true impact. These findings have important implications for understanding what has happened during the COVID-19 pandemic, planning recovery and building a system that will better respond to future waves or new epidemics

Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset

Acute postoperative pain is common, distressing and associated with increased morbidity. Targeted interventions can prevent its development. We aimed to develop and internally validate a predictive tool to pre-emptively identify patients at risk of severe pain following major surgery. We analysed data from the UK Peri-operative Quality Improvement Programme to develop and validate a logistic regression model to predict severe pain on the first postoperative day using pre-operative variables. Secondary analyses included the use of peri-operative variables. Data from 17,079 patients undergoing major surgery were included. Severe pain was reported by 3140 (18.4%) patients; this was more prevalent in females, patients with cancer or insulin-dependent diabetes, current smokers and in those taking baseline opioids. Our final model included 25 pre-operative predictors with an optimism-corrected c-statistic of 0.66 and good calibration (mean absolute error 0.005, p = 0.35). Decision-curve analysis suggested an optimal cut-off value of 20–30% predicted risk to identify high-risk individuals. Potentially modifiable risk factors included smoking status and patient-reported measures of psychological well-being. Non-modifiable factors included demographic and surgical factors. Discrimination was improved by the addition of intra-operative variables (likelihood ratio χ2 496.5, p < 0.001) but not by the addition of baseline opioid data. On internal validation, our pre-operative prediction model was well calibrated but discrimination was moderate. Performance was improved with the inclusion of peri-operative covariates suggesting pre-operative variables alone are not sufficient to adequately predict postoperative pain

V-ATPase-Mediated Granular Acidification Is Regulated by the V-ATPase Accessory Subunit Ac45 in POMC-Producing Cells

The regulation of the V-ATPase, the proton pump mediating intraorganellar acidification, is still elusive. We find that excess of the neuroendocrine V-ATPase accessory subunit Ac45 reduces the intragranular pH and consequently disturbs prohormone convertase activation and prohormone processing. Thus, Ac45 represents the first V-ATPase regulator

Mycobacteria Attenuate Nociceptive Responses by Formyl Peptide Receptor Triggered Opioid Peptide Release from Neutrophils

In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR) and/or toll like receptor (TLR) agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively). Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, β-endorphin) antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim at selective FPR agonists to boost endogenous analgesia

The impact of COVID-19 on anaesthesia and critical care services in the UK: a serial service evaluation.

Between October 2020 and January 2021, we conducted three national surveys to track anaesthetic, surgical and critical care activity during the second COVID-19 pandemic wave in the UK. We surveyed all NHS hospitals where surgery is undertaken. Response rates, by round, were 64%, 56% and 51%. Despite important regional variations, the surveys showed increasing systemic pressure on anaesthetic and peri-operative services due to the need to support critical care pandemic demands. During Rounds 1 and 2, approximately one in eight anaesthetic staff were not available for anaesthetic work. Approximately one in five operating theatres were closed and activity fell in those that were open. Some mitigation was achieved by relocation of surgical activity to other locations. Approximately one-quarter of all surgical activity was lost, with paediatric and non-cancer surgery most impacted. During January 2021, the system was largely overwhelmed. Almost one-third of anaesthesia staff were unavailable, 42% of operating theatres were closed, national surgical activity reduced to less than half, including reduced cancer and emergency surgery. Redeployed anaesthesia staff increased the critical care workforce by 125%. Three-quarters of critical care units were so expanded that planned surgery could not be safely resumed. At all times, the greatest resource limitation was staff. Due to lower response rates from the most pressed regions and hospitals, these results may underestimate the true impact. These findings have important implications for understanding what has happened during the COVID-19 pandemic, planning recovery and building a system that will better respond to future waves or new epidemics