Showing papers in "BJA: British Journal of Anaesthesia in 2021"

Minimal clinically important differences in randomised clinical trials on pain management after total hip and knee arthroplasty: a systematic review.

Abstract: Background Sample size determination is essential for reliable hypothesis testing in clinical trials and should rely on adequate sample size calculations with alpha, beta, variance, and an effect size being the minimal clinically important difference (MCID). This facilitates interpretation of the clinical relevance of statistically significant results. No gold standard for MCIDs exists in postoperative pain research. Methods We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for English language articles on randomised trials investigating analgesic interventions after total hip or knee arthroplasty. Primary outcomes were the reported MCIDs for pain score and cumulated rescue opioid consumption. Secondary outcomes included reported sample size calculations and propensity to report statistical significance without reaching MCID. Trend analyses were conducted using statistical process control. Results We included 570 trials. Median MCID for 0-24 h opioid consumption was 10 mg i.v. morphine equivalents for absolute reductions (interquartile range [IQR]: 6.8-14.5) and relative 40% (IQR: 30–50%). Median MCIDs for pain scores were absolute 15 mm at rest (IQR: 10–20) and 18 mm during movement (IQR: 10–20) on a 0–100 mm VAS and relative 30% (IQR: 20–30%). No trends were demonstrated for MCIDs. Adequate sample size calculations were reported in 34% of trials. In 46% of trials with statistically significant primary outcomes, the differences did not reach the predetermined MCID. Conclusions We provide clinician-perceived MCID estimates for rescue opioid consumption and pain scores that can be used for sample size calculations until reliable evidence-based patient-rated MCIDs emerge. Nearly half of the trials with significant findings did not reach the predetermined MCID.

Anaesthetic depth and delirium after major surgery: a randomised clinical trial

Abstract: Background Postoperative delirium is a serious complication of surgery associated with prolonged hospitalisation, long-term cognitive decline, and mortality. This study aimed to determine whether targeting bispectral index (BIS) readings of 50 (light anaesthesia) was associated with a lower incidence of POD than targeting BIS readings of 35 (deep anaesthesia). Methods This multicentre randomised clinical trial of 655 at-risk patients undergoing major surgery from eight centres in three countries assessed delirium for 5 days postoperatively using the 3 min confusion assessment method (3D-CAM) or CAM-ICU, and cognitive screening using the Mini-Mental State Examination at baseline and discharge and the Abbreviated Mental Test score (AMTS) at 30 days and 1 yr. Patients were assigned to light or deep anaesthesia. The primary outcome was the presence of postoperative delirium on any of the first 5 postoperative days. Secondary outcomes included mortality at 1 yr, cognitive decline at discharge, cognitive impairment at 30 days and 1 yr, unplanned ICU admission, length of stay, and time in electroencephalographic burst suppression. Results The incidence of postoperative delirium in the BIS 50 group was 19% and in the BIS 35 group was 28% (odds ratio 0.58 [95% confidence interval: 0.38–0.88]; P=0.010). At 1 yr, those in the BIS 50 group demonstrated significantly better cognitive function than those in the BIS 35 group (9% with AMTS ≤6 vs 20%; P Conclusions Among patients undergoing major surgery, targeting light anaesthesia reduced the risk of postoperative delirium and cognitive impairment at 1 yr. Clinical trial registration ACTRN12612000632897.

Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study

Abstract: Background The role of repeated prone positioning in intubated subjects with acute respiratory distress syndrome caused by COVID-19 remains unclear. Methods We conducted a retrospective observational cohort study of critically ill intubated patients with COVID-19 who were placed in the prone position between March 18, 2020 and March 31, 2020. Exclusion criteria were pregnancy, reintubation, and previous prone positioning at a referring hospital. Patients were followed up until hospital discharge. The primary outcome was oxygenation assessed by partial pressure of oxygen/fraction of inspired oxygen ratio (Pao2/Fio2) ratio. A positive response to proning was defined as an increase in Pao2/Fio2 ratio ≥20%. Treatment failure of prone positioning was defined as death or requirement for extracorporeal membrane oxygenation (ECMO). Results Forty-two subjects (29 males; age: 59 [52–69] yr) were eligible for analysis. Nine subjects were placed in the prone position only once, with 25 requiring prone positioning on three or more occasions. A total of 31/42 (74%) subjects survived to discharge, with five requiring ECMO; 11/42 (26%) subjects died. After the first prone positioning session, Pao2/Fio2 (mean (standard deviation)) ratio increased from 17.9 kPa (7.2) to 28.2 kPa (12.2) (P Conclusion Patients with COVID-19 acute respiratory distress syndrome frequently responded to initial prone positioning with improved oxygenation. Subsequent prone positioning in subjects discharged from hospital was associated with greater improvements in oxygenation.

Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis.

Abstract: Background Whether exposure to a single general anaesthetic (GA) in early childhood causes long-term neurodevelopmental problems remains unclear. Methods PubMed/MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched from inception to October 2019. Studies evaluating neurodevelopmental outcomes and prospectively enrolling children exposed to a single GA procedure compared with unexposed children were identified. Outcomes common to at least three studies were evaluated using random-effects meta-analyses. Results Full-scale intelligence quotient (FSIQ); the parentally reported Child Behavior Checklist (CBCL) total, externalising, and internalising problems scores; and Behavior Rating Inventory of Executive Function (BRIEF) scores were assessed. Of 1644 children identified, 841 who had a single exposure to GA were evaluated. The CBCL problem scores were significantly higher (i.e. worse) in exposed children: mean score difference (CBCL total: 2.3 [95% confidence interval {CI}: 1.0–3.7], P=0.001; CBCL externalising: 1.9 [95% CI: 0.7–3.1], P=0.003; and CBCL internalising problems: 2.2 [95% CI: 0.9–3.5], P=0.001). Differences in BRIEF were not significant after multiple comparison adjustment. Full-scale intelligence quotient was not affected by GA exposure. Secondary analyses evaluating the risk of these scores exceeding predetermined clinical thresholds found that GA exposure was associated with increased risk of CBCL internalising behavioural deficit (risk ratio [RR]: 1.47; 95% CI: 1.08–2.02; P=0.016) and impaired BRIEF executive function (RR: 1.68; 95% CI: 1.23–2.30; P=0.001). Conclusions Combining results of studies utilising prospectively collected outcomes showed that a single GA exposure was associated with statistically significant increases in parent reports of behavioural problems with no difference in general intelligence.

Impaired fibrinolysis in critically ill COVID-19 patients.

Abstract: Background Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor. Methods We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT. Results Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test. Conclusion Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.

Cardiac output estimation using pulse wave analysis-physiology, algorithms, and technologies: a narrative review.

Abstract: Pulse wave analysis (PWA) allows estimation of cardiac output (CO) based on continuous analysis of the arterial blood pressure (AP) waveform. We describe the physiology of the AP waveform, basic principles of PWA algorithms for CO estimation, and PWA technologies available for clinical practice. The AP waveform is a complex physiological signal that is determined by interplay of left ventricular stroke volume, systemic vascular resistance, and vascular compliance. Numerous PWA algorithms are available to estimate CO, including Windkessel models, long time interval or multi-beat analysis, pulse power analysis, or the pressure recording analytical method. Invasive, minimally-invasive, and noninvasive PWA monitoring systems can be classified according to the method they use to calibrate estimated CO values in externally calibrated systems, internally calibrated systems, and uncalibrated systems.

Improving perioperative brain health: an expert consensus review of key actions for the perioperative care team

Abstract: Summary Delirium and postoperative neurocognitive disorder are the commonest perioperative complications in patients more than 65 yr of age. However, data suggest that we often fail to screen patients for preoperative cognitive impairment, to warn patients and families of risk, and to take preventive measures to reduce the incidence of perioperative neurocognitive disorders. As part of the American Society of Anesthesiologists (ASA) Perioperative Brain Health Initiative, an international group of experts was invited to review published best practice statements and guidelines. The expert group aimed to achieve consensus on a small number of practical recommendations that could be implemented by anaesthetists and their partners to reduce the incidence of perioperative neurocognitive disorders. Six statements were selected based not only on the strength of the evidence, but also on the potential for impact and the feasibility of widespread implementation. The actions focus on education, cognitive and delirium screening, non-pharmacologic interventions, pain control, and avoidance of antipsychotics. Strategies for effective implementation are discussed. Anaesthetists should be key members of multidisciplinary perioperative care teams to implement these recommendations.

Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study.

Abstract: Background Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium. Methods A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity. Results GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P Conclusions The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation. Clinical trial registration NCT02926417 and NCT03124303.

Factors associated with rebound pain after peripheral nerve block for ambulatory surgery.

Abstract: Background Rebound pain is a common, yet under-recognised acute increase in pain severity after a peripheral nerve block (PNB) has receded, typically manifesting within 24 h after the block was performed. This retrospective cohort study investigated the incidence and factors associated with rebound pain in patients who received a PNB for ambulatory surgery. Methods Ambulatory surgery patients who received a preoperative PNB between March 2017 and February 2019 were included. Rebound pain was defined as the transition from well-controlled pain (numerical rating scale [NRS] ≤3) while the block is working to severe pain (NRS ≥7) within 24 h of block performance. Patient, surgical, and anaesthetic factors were analysed for association with rebound pain by univariate, multivariable, and machine learning methods. Results Four hundred and eighty-two (49.6%) of 972 included patients experienced rebound pain as per the definition. Multivariable analysis showed that the factors independently associated with rebound pain were younger age (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.97–0.99), female gender (OR 1.52 [1.15–2.02]), surgery involving bone (OR 1.82 [1.38–2.40]), and absence of perioperative i.v. dexamethasone (OR 1.78 [1.12–2.83]). Despite a high incidence of rebound pain, there were high rates of patient satisfaction (83.2%) and return to daily activities (96.5%). Conclusions Rebound pain occurred in half of the patients and showed independent associations with age, female gender, bone surgery, and absence of intraoperative use of i.v. dexamethasone. Until further research is available, clinicians should continue to use preventative strategies, especially for patients at higher risk of experiencing rebound pain.

Noninvasive respiratory support and patient self-inflicted lung injury in COVID-19: a narrative review.

Abstract: COVID-19 pneumonia is associated with hypoxaemic respiratory failure, ranging from mild to severe. Because of the worldwide shortage of ICU beds, a relatively high number of patients with respiratory failure are receiving prolonged noninvasive respiratory support, even when their clinical status would have required invasive mechanical ventilation. There are few experimental and clinical data reporting that vigorous breathing effort during spontaneous ventilation can worsen lung injury and cause a phenomenon that has been termed patient self-inflicted lung injury (P-SILI). The aim of this narrative review is to provide an overview of P-SILI pathophysiology and the role of noninvasive respiratory support in COVID-19 pneumonia. Respiratory mechanics, vascular compromise, viscoelastic properties, lung inhomogeneity, work of breathing, and oesophageal pressure swings are discussed. The concept of P-SILI has been widely investigated in recent years, but controversies persist regarding its mechanisms. To minimise the risk of P-SILI, intensivists should better understand its underlying pathophysiology to optimise the type of noninvasive respiratory support provided to patients with COVID-19 pneumonia, and decide on the optimal timing of intubation for these patients.

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Abstract: Background Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 Conclusions Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants. Clinical trial registration NCT02350348.

Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment.

Abstract: Background Remimazolam is a new benzodiazepine for procedural sedation and general anaesthesia. The aim of this study was to characterise its pharmacokinetic properties and safety in renally and hepatically impaired subjects. Methods Two separate trials were conducted in patients with hepatic (n=11) or renal impairment (n=11) compared with matched healthy subjects (n=9 and n=12, respectively). The hepatic impairment trial was an open-label adaptive ‘Reduced Design' trial, using a single bolus of remimazolam 0.1 mg kg−1 i.v., whereas the renal impairment trial was an open-label trial of a single bolus dose of remimazolam 1.5 mg i.v. Remimazolam plasma concentrations over time were analysed by population pharmacokinetic modelling. Results Remimazolam pharmacokinetic properties were adequately described by a three-compartment, recirculatory model. Exposure in subjects with severe hepatic impairment was 38.1% higher (i.e. clearance was 38.1% lower) compared with healthy volunteers. This increase caused a slightly delayed recovery (8.0 min for healthy, 12.1 min for moderate, and 16.7 min for severe hepatic impairment). With renal impairment, plasma clearance was comparable with that measured in healthy subjects. Simulations of Cmax after a bolus dose of 10 mg showed no relevant impact of hepatic or renal impairment. The overall incidence of adverse events was low, and all adverse events were mild. Conclusions As Cmax after a remimazolam bolus i.v. was not affected by hepatic or renal impairment, no dose adjustments are required. No unexpected adverse events related to remimazolam were seen in subjects with renal or hepatic impairment. Clinical trial registration Hepatic impairment trial: ClinicalTrials.gov, NCT01790607 (https://clinicaltrials.gov/ct2/show/NCT01790607). Renal impairment trial: EudraCT Number: 2014-004575-23.

Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.

Abstract: Background A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic. Methods We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021. Results The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740–5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066–2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587–3 100 808) up to December 31, 2021. Conclusions The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.

High-flow nasal oxygenation or standard oxygenation for gastrointestinal endoscopy with sedation in patients at risk of hypoxaemia: a multicentre randomised controlled trial (ODEPHI trial).

Abstract: Background We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. Methods This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min−1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min−1) or nasopharyngeal tube (5 L min−1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. Results In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, –23.4% [95% confidence interval (CI), –28.9 to –16.7]; P 1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P Conclusions In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. Clinical trial registration NCT03829293.

Association of weaning failure from mechanical ventilation with transthoracic echocardiography parameters: a systematic review and meta-analysis

Abstract: Background Weaning from mechanical ventilation is a challenging step during recovery from critical illness. Weaning failure or early reintubation are associated with increased morbidity and mortality, exposing patients to life-threatening complications. Cardiac dysfunction represents the most common cause of weaning failure. We conducted a systematic review and meta-analysis to evaluate the association between transthoracic echocardiographic parameters and weaning failure. Methods We performed a systematic search of MEDLINE and EMBASE screening for prospective studies providing echocardiographic data collected just before the beginning of spontaneous breathing trial and outcome of the weaning attempt. We primarily focused on parameters currently recommended for evaluation of left ventricular (LV) systolic or diastolic dysfunction. Results We included 11 studies in our primary analysis, which included data on LV ejection fraction (LVEF, n=10 studies) and parameters recommended for the assessment of LV diastolic function (E/e′ ratio n=10; E/A ratio n=9; E wave n=8; and e′ wave n=7). Weaning failure was significantly associated to a higher E/e′ ratio (standardised mean difference [SMD]=1.70, 95% confidence interval [CI; 0.78–2.62]; P Conclusions Weaning failure is associated with parameters indicating worse LV diastolic function (E/e′, e′ wave, E wave) and increased LV filling pressure (E/e′ ratio). The association between weaning failure and LV systolic dysfunction as evaluated by LVEF is more unclear. More studies are needed to clarify this aspect and regarding the role of right ventricular function.

Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis

Abstract: Background Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of these interventions during and after major surgery. Methods Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I2. Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730). Results Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I2=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I2=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective. Conclusions In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.

A comparison of videolaryngoscopy using standard blades or non-standard blades in children in the Paediatric Difficult Intubation Registry.

Abstract: Background The design of a videolaryngoscope blade may affect its efficacy. We classified videolaryngoscope blades as standard and non-standard shapes to compare their efficacy performing tracheal intubation in children enrolled in the Paediatric Difficult Intubation Registry. Methods Cases entered in the Registry from March 2017 to January 2020 were analysed. We compared the success rates of initial and eventual tracheal intubation, complications, and technical difficulties between the two groups and by weight stratification. Results Videolaryngoscopy was used in 1313 patients. Standard and non-standard blades were used in 529 and 740 patients, respectively. Both types were used in 44 patients. In children weighing Conclusions In infants weighing

Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group

Abstract: Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics or succinylcholine. Because of the rarity of malignant hyperthermia and ethical limitations, there is no evidence from interventional trials to inform the optimal perioperative management of patients known or suspected with malignant hyperthermia who present for surgery. Furthermore, as the concentrations of residual volatile anaesthetics that might trigger a malignant hyperthermia crisis are unknown and manufacturers' instructions differ considerably, there are uncertainties about how individual anaesthetic machines or workstations need to be prepared to avoid inadvertent exposure of susceptible patients to trigger anaesthetic drugs. The present guidelines are intended to bundle the available knowledge about perioperative management of malignant hyperthermia-susceptible patients and the preparation of anaesthesia workstations. The latter aspect includes guidance on the use of activated charcoal filters. The guidelines were developed by members of the European Malignant Hyperthermia Group, and they are based on evaluation of the available literature and a formal consensus process. The most crucial recommendation is that malignant hyperthermia-susceptible patients should receive anaesthesia that is free of triggering agents. Providing that this can be achieved, other key recommendations include avoidance of prophylactic administration of dantrolene; that preoperative management, intraoperative monitoring, and care in the PACU are unaltered by malignant hyperthermia susceptibility; and that malignant hyperthermia patients may be anaesthetised in an outpatient setting.

Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

Abstract: Background Prone positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure. Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool. Results Fourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference –23.10; 95% confidence interval [CI]: –34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32–0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43–1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2–16). Conclusions Prone positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain.

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study.

Abstract: Background Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2 Conclusions The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration NCT02350348.

Controversies in airway management of COVID-19 patients: updated information and international expert consensus recommendations.

Abstract: Controversies in airway management of COVID-19 patients: updated information and international expert consensus recommendations Huafeng Wei1,*,y, Bailin Jiang1,2,y, Elizabeth C. Behringer, Ross Hofmeyr, Sheila N. Myatra, David T. Wong, Ellen P. O’ Sullivan, Carin A. Hagberg, Barry McGuire, Paul A. Baker, Jane Li, Maksym Pylypenko, Wuhua Ma, Mingzhang Zuo, Nuzhet M. Senturk and Uwe Klein Department of Anaesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, USA, Department of Anaesthesiology, Peking University People’s Hospital, Beijing, China, Division of Cardiovascular Surgery & Critical Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA, Department of Anaesthesia & Perioperative Medicine, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa, Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada, Department of Anaesthesia and Intensive Care Medicine, St James’s Hospital, Dublin, Ireland, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Department of Anaesthesia, Ninewells Hospital, Dundee, UK, Department of Anaesthesia, Starship Children’s Health, Auckland, New Zealand, Department of Anaesthesia and Pain Management, Central Coast Local Health District, NSW, Australia, Department of Anesthesiology and Intensive Care, Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine, Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China, Department of Anaesthesiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China, Istanbul Universitesi, Istanbul Tıp Fakültesi, Anesteziyoloji AD, Istanbul, Turkey and Südharz-Klinikum Nordhausen, Nordhausen, Germany

Infant isoflurane exposure affects social behaviours, but does not impair specific cognitive domains in juvenile non-human primates.

Abstract: Background Clinical studies show that children exposed to anaesthetics for short times at young age perform normally on intelligence tests, but display altered social behaviours. In non-human primates (NHPs), infant anaesthesia exposure for several hours causes neurobehavioural impairments, including delayed motor reflex development and increased anxiety-related behaviours assessed by provoked response testing. However, the effects of anaesthesia on spontaneous social behaviours in juvenile NHPs have not been investigated. We hypothesised that multiple, but not single, 5 h isoflurane exposures in infant NHPs are associated with impairments in specific cognitive domains and altered social behaviours at juvenile age. Methods Eight Rhesus macaques per group were anaesthetised for 5 h using isoflurane one (1×) or three (3×) times between postnatal days 6 and 12 or were exposed to room air (control). Cognitive testing, behavioural assessments in the home environment, and provoked response testing were performed during the first 2 yr of life. Results The cognitive functions tested did not differ amongst groups. However, compared to controls, NHPs in the 3× group showed less close social behaviour (P=0.016), and NHPs in the 1× group displayed increased anxiety-related behaviours (P=0.038) and were more inhibited towards novel objects (P Conclusions 5 h exposures of NHPs to isoflurane during infancy are associated with decreased close social behaviour after multiple exposures and more anxiety-related behaviours and increased behavioural inhibition after single exposure, but they do not affect the cognitive domains tested. Our findings are consistent with behavioural alterations in social settings reported in clinical studies, which may guide future research.

Association between postoperative haemoglobin and myocardial injury after noncardiac surgery: a retrospective cohort analysis

Abstract: Background Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply–demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. Methods We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml−1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. Results Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl−1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was Conclusion Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of anaemia remains to be determined.

Preoperative inflammatory mediators and postoperative delirium: systematic review and meta-analysis.

Abstract: Background Postoperative delirium has eluded attempts to define its complex aetiology and describe specific risk factors. The role of neuroinflammation as a risk factor, determined by measuring blood levels of preoperative ‘innate' inflammatory mediator levels, has been investigated. However, results have been conflicting. We conducted a systematic review and meta-analysis of the evidence on associations between preoperative blood levels of inflammatory mediators and postoperative delirium in the older person. Influence of type of surgery was also assessed. Methods Original, low risk of bias studies, published in peer-reviewed journals, which fulfilled the eligibility criteria were included. Seventeen articles fulfilled study criteria. Data extraction, synthesis, and risk of bias analysis were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and quality in prognostic studies guidelines. Meta-analyses used a random-effects model. Inflammatory mediators included C-reactive protein, interleukin-6, -8, and -10, tumour necrosis factor-α, insulin-like growth factor-1, cortisol, and neopterin. Surgical groups were cardiac, noncardiac, and hip fracture. Results Higher preoperative interleukin-6 was associated with postoperative delirium with a standardised mean difference (95% confidence interval) of 0.33 (0.11–0.56) and P=0.003. Higher neopterin was also associated with postoperative delirium. Conclusions The association of preoperative blood levels of inflammatory mediators with postoperative delirium may be influenced by the type of surgery and the specific mediator. The potential modulating effect of type of surgery, intrinsic brain vulnerability, and the complex interactions between inflammatory mediators and binding proteins will need to be considered in future studies. Clinical trial registration CRD42019159471 (PROSPERO).

Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer

Abstract: Background Opioid-induced immunomodulation may be of particular importance in triple-negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and oncological outcomes and explored patterns of opioid receptor expression in TNBC. Methods Consecutive patients with stage I–III primary TNBC were identified from a prospectively maintained database. Opioid receptor expression patterns in the tumour microenvironment were analysed using publicly available bulk and single-cell RNA-seq data. Results A total of 1143 TNBC cases were retrospectively analysed. In multivariable analysis, higher intraoperative opioid dose was associated with favourable recurrence-free survival, hazard ratio 0.93 (95% confidence interval 0.88–0.99) per 10 oral morphine milligram equivalents increase (P=0.028), but was not significantly associated with overall survival, hazard ratio 0.96 (95% confidence interval 0.89–1.02) per 10 morphine milligram equivalents increase (P=0.2). Bulk RNA-seq analysis of opioid receptors showed that OPRM1 was nearly non-expressed. Compared with normal breast tissue OGFR, OPRK1, and OPRD1 were upregulated, while TLR4 was downregulated. At a single-cell level, OPRM1 and OPRD1 were not detectable; OPRK1 was expressed mainly on tumour cells, whereas OGFR and TLR4 were more highly expressed on immune cells. Conclusions We found a protective effect of intraoperative opioids on recurrence-free survival in TNBC. Opioid receptor expression was consistent with a net protective effect of opioid agonism, with protumour receptors either not expressed or downregulated, and antitumour receptors upregulated. In this era of personalised medicine, efforts to differentiate the effects of opioids across breast cancer subtypes (and ultimately individual patients) should continue.

National survey on sedation for gastrointestinal endoscopy in 2758 Chinese hospitals.

Abstract: Background Although sedation during gastrointestinal endoscopy is widely used in China, the characteristics of sedation use, including regional distribution, personnel composition, equipment used, and drug selection, remain unclear. The present study aimed to provide insights into the current practice and regional distribution of sedation for gastrointestinal endoscopy in China. Methods A questionnaire consisting of 19 items was distributed to directors of anaesthesiology departments and anaesthesiologists in charge of endoscopic sedation units in mainland China through WeChat. Results The results from 2758 participating hospitals (36.7% of the total) showed that 9 808 182 gastroscopies (69.3%) and 4 353 950 colonoscopies (30.7%), with a gastroscopy-to-colonoscopy ratio of 2.3, were conducted from January to December 2016. Sedation was used with 4 696 648 gastroscopies (47.9%) and 2 148 316 colonoscopies (49.3%), for a ratio of 2.2. The most commonly used sedative was propofol (61.0% for gastroscopies and 60.4% for colonoscopies). Haemoglobin oxygen saturation (SpO2) was monitored in most patients (96.1%). Supplemental oxygen was routinely administered, but the availability of other equipment was variable (anaesthesia machine in 64.9%, physiological monitor in 84.4%, suction device in 72.3%, airway equipment in 75.5%, defibrillator in 32.7%, emergency kit in 57.0%, and difficult airway kit in 20.8% of centres responding). Conclusions The sedation rate for gastrointestinal endoscopy is much lower in China than in the USA and in Europe. The most commonly used combination of sedatives was propofol plus an opioid (either fentanyl or sufentanil). Emergency support devices, such as difficult airway devices and defibrillators, were not usually available.