Application of the Estimand Framework to Anesthesia Trials.

SUMMARY: Events occurring after randomization, such as use of rescue medication, treatment discontinuation, or death, are common in randomized trials. These events can change either the existence or interpretation of the outcome of interest. However, appropriate handling of these intercurrent events is often unclear. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9(R1) addendum introduced the estimand framework, which aligns trial objectives with the design, conduct, statistical analysis, and interpretation of results. This article describes how the estimand framework can be used in anesthesia trials to precisely define the treatment effect to be estimated, key attributes of an estimand, common intercurrent events in anesthesia trials with strategies for handling them, and use of the estimand framework in a hypothetical anesthesia trial on postoperative delirium. When planning anesthesia trials, clearly defining the estimand is vital to ensure that what is being estimated is clearly understood, is clinically relevant, and helps answer the clinical questions of interest.

The safety of nitrous oxide: glass half-full or half-empty?

A systematic review of clinical trials confirms that including nitrous oxide in the gas mixture for general anaesthesia has minor short-term benefits and does not impact most patient safety outcomes. However, no risk-benefit analysis of nitrous oxide should ignore its known environmental effects. If continued nitrous oxide use is supported, strategies to minimise and monitor the contribution of medical nitrous oxide to global warming are vital.

Associations between the intraoperative fraction of inspired intraoperative oxygen administration and days alive and out of hospital after surgery.

Background: There is limited knowledge about the effect of liberal intraoperative oxygen on non-infectious complications and overall recovery from surgery. Methods: In this retrospective cohort study, we investigated associations between mean intraoperative fraction of inspired oxygen (FiO2), and outcome in adults undergoing elective surgery lasting more than 2 h at a large metropolitan New Zealand hospital from 2012 to 2020. Patients were divided into low, medium, and high oxygen groups (FiO2 ≤ 0.4, 0.41-0.59, ≥0.6). The primary outcome was days alive and out of hospital at 90 days (DAOH90). The secondary outcomes were post-operative complications and admission to the ICU. Results: We identified 15,449 patients who met the inclusion criteria. There was no association between FiO2 and DAOH90 when high FiO2 was analysed according to three groups. Using high FiO2 as the reference group there was an adjusted mean (95% confidence interval [CI]) difference of 0.09 (-0.06 to 0.25) days (P = 0.25) and 0.28 (-0.05 to 0.62) days (P = 0.2) in the intermediate and low oxygen groups, respectively. Low FiO2 was associated with increased surgical site infection: the adjusted odds ratio (OR) for low compared with high FiO2 was 1.53 (95% CI 1.12-2.10). Increasing FiO2 was associated with respiratory complications: the adjusted OR associated with each 10% point increase in FiO2 was 1.17 (95% CI 1.08-1.26) and the incidence of being admitted to an ICU had an adjusted OR of 1.1 (95% CI 1.03-1.18). Conclusions: We found potential benefits, and risks, associated with liberal intraoperative oxygen administration indicating that randomised controlled trials are warranted.

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort.

BACKGROUND: Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence. METHODS: A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables. RESULTS: Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI. CONCLUSIONS: Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk-benefit ratio of these drugs in the perioperative period.

Intraoperative dexamethasone and chronic postsurgical pain: a propensity score-matched analysis of a large trial.

BACKGROUND: Dexamethasone has been shown to reduce acute pain after surgery, but there is uncertainty as to its effects on chronic postsurgical pain (CPSP). We hypothesised that in patients undergoing major noncardiac surgery, a single intraoperative dose of dexamethasone increases the incidence of CPSP. METHODS: We devised a propensity score-matched analysis of the ENIGMA-II trial CPSP dataset, aiming to compare the incidence of CPSP in patients who had received dexamethasone or not 12 months after major noncardiac surgery. The primary outcome was the incidence of CPSP. We used propensity score matching and inverse probability weighting to balance baseline variables to estimate the average marginal effect of dexamethasone on patient outcomes, accounting for confounding to estimate the average treatment effect on those treated with dexamethasone. RESULTS: We analysed 2999 patients, of whom 116 of 973 (11.9%) receiving dexamethasone reported CPSP, and 380 of 2026 (18.8%) not receiving dexamethasone reported CPSP, unadjusted odds ratio 0.76 (95% confidence interval 0.78-1.00), P=0.052. After propensity score matching, CPSP occurred in 116 of 973 patients (12.2%) receiving dexamethasone and 380 of 2026 patients (13.8%) not receiving dexamethasone, adjusted risk ratio 0.88 (95% confidence interval 0.61-1.27), P=0.493. There was no difference between groups in quality of life or pain interference with daily activities, but 'least pain' (P=0.033) and 'pain right now' (P=0.034) were higher in the dexamethasone group. CONCLUSIONS: Dexamethasone does not increase the risk of chronic postsurgical pain after major noncardiac surgery. CLINICAL TRIAL REGISTRATION: Open Science Framework Registration DOI https://doi.org/10.17605/OSF.IO/ZDVB5.

The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations.

Background: Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir. Methods: We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.5-30 days) of oral nirmatrelvir/ritonavir outside (n=11) of and within (n=2) the context of an acute SARS-CoV-2 infection. Participants reported on symptoms and health experiences before, during, and after their use of nirmatrelvir/ritonavir. Results: Among those who took a long course of nirmatrelvir/ritonavir outside of the context of an acute infection, some experienced a meaningful reduction in symptoms, although not all benefits persisted; others experienced no effect on symptoms. One participant reported intense stomach pain that precluded her from continuing her course. Among the two participants who took a long course of nirmatrelvir/ritonavir within the context of an acute reinfection, both eventually returned to their pre-re-infection baseline. Discussion: Long courses of nirmatrelvir/ritonavir may have meaningful benefits for some people with Long COVID but not others. We encourage researchers to study who, how, and why nirmatrelvir/ritonavir benefits some and what course length is most effective, with the goal of informing clinical recommendations for using nirmatrelvir/ritonavir and/or other antivirals as a potential treatment for Long COVID.

Anaesthetist prediction of postoperative opioid use: a multicentre prospective cohort study.

Background: The Apfel simplified risk score includes four risk factors: female sex, non-smoking status, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use. The score is calculated preoperatively, so postoperative opioid use must be predicted. We aimed to determine whether anaesthetists can predict patients' postoperative opioid use and dose. Methods: Specialist anaesthetists from eight hospitals preoperatively predicted opioid use and dose in the post-anaesthesia care unit (PACU) and for the first 24 h postoperatively, which was compared with actual opioid use and dose. Opioid doses were converted to oral morphine equivalents (MEQ). Correlations between predicted and actual opioid use and dose were analysed with Spearman's rho and linear regression. Results: A total of 487 anaesthetist-patient pairs were included. Anaesthetists overpredicted opioid use (398 [82%] predicted vs 251 [52%] actual patients requiring opioids in the PACU; 396 [81%] predicted vs 291 [60%] actual in the first 24 h) (Spearman's rho [95% confidence interval] 0.24 [0.16-0.33], P<0.001 in the PACU; 0.36 [0.28-0.44], P<0.001 in the first 24 h). Anaesthetists also overpredicted opioid dose (median [inter-quartile range] 12 [8-20] mg predicted MEQ vs 4 [0-18] mg actual MEQ in the PACU; 32 [18-60] mg vs 24 [0-65] mg MEQ in the first 24 h) (Spearman's rho 0.21 [0.13-0.29], P<0.001 in the PACU; 0.53 [0.40-0.60], P<0.001 in the first 24 h). Conclusions: Specialist anaesthetists cannot accurately predict opioid use or dose in the PACU or the first 24 postoperative hours. The Apfel risk criterion for postoperative opioid use may be inaccurate in clinical practice.

Vasopressors to treat postoperative hypotension after adult noncardiac, non-obstetric surgery: a systematic review.

BACKGROUND: Postoperative hypotension is common after major surgery and is associated with patient harm. Vasopressors are commonly used to treat hypotension without clear evidence of benefit. We conducted a systematic review to better understand the use, impact, and rationale for vasopressor administration after noncardiac, non-obstetric surgery in adults. METHODS: We conducted a prospectively registered systematic review. Cochrane CENTRAL, EMBASE, MEDBASE, and MEDLINE were searched for RCTs and cohort studies of adult patients receiving vasopressors after noncardiac, non-obstetric surgery. Study quality was critically appraised by two investigators. Findings from the review were synthesised, but formal meta-analysis was not performed because of significant variability in study populations and outcomes. RESULTS: A total of 3201 articles were screened, of which seven RCTs, two prospective cohort studies, and 15 retrospective cohort studies were included in the analysis (24 in total). One study was graded as high quality, two as moderate quality, and the remaining 21 as low quality. Sixteen studies relied on clinical assessment alone to decide on therapeutic interventions. Vasodilation was the most common suggested physiological disturbance. The median proportion of patients receiving vasopressors was 42% (interquartile range: 11.5-74.7%). Norepinephrine was the most common vasopressor used. CONCLUSIONS: The evidence supporting the use of vasopressors to treat postoperative hypotension is limited. Future research should focus on whether vasodilatation or other physiological disturbance is driving postoperative hypotension to allow rational decision-making.

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.

Diversity, inclusion, and equity at the British Journal of Anaesthesia: 100 years of progress.

The past century, especially the past decade, has seen re-examination and evolution in our views about sex, gender, race, and ethnicity. The British Journal of Anaesthesia is part of an ongoing effort in research and medical publishing, and in health and education more generally, to improve diversity, inclusion, and equity. This editorial highlights the contributions and evolution of the Journal in these areas from its origin until today.

Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis.

BACKGROUND: Suggested anaesthetic dose ranges do not differ by sex, likely because of limited studies comparing sexes. Our objective was to systematically synthesise studies with outcomes of unintended anaesthesia awareness under anaesthesia, intraoperative connected consciousness, time to emergence from anaesthesia, and dosing to achieve adequate depth of anaesthesia, and to compare between females and males. METHODS: Studies were identified from MEDLINE, Embase, and the Cochrane library databases until August 2, 2022. Controlled clinical trials (randomised/non-randomised) and prospective cohort studies that reported outcomes by sex were included. Results were synthesised by random effects meta-analysis where possible, or narrative form. RESULTS: Of the 19 749 studies identified, 64 (98 243 participants; 53 143 females and 45 100 males) were eligible for inclusion, and 44 citations contributed to meta-analysis. Females had a higher incidence of awareness with postoperative recall (33 studies, odds ratio 1.38, 95% confidence interval [CI] 1.09-1.75) and connected consciousness during anaesthesia (three studies, OR 2.09, 95% CI 1.04-4.23) than males. Time to emergence was faster in females, including time to eye-opening (10 studies, mean difference -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (six studies, mean difference -2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous, limiting synthesis to a qualitative review which did not identify sex differences. CONCLUSIONS: Female sex was associated with a greater incidence of awareness under general anaesthesia, and faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336087.

Triggers for medical emergency team activation after non-cardiac surgery.

Deterioration after major surgery is common, with many patients experiencing a medical emergency team (MET) activation. Understanding the triggers for MET calls may help design interventions to prevent deterioration. We aimed to identify triggers for MET activation in non-cardiac surgical patients. A retrospective cohort study of adult patients who experienced a postoperative MET call at a single tertiary hospital was undertaken. The trigger and timing of each MET call and patient characteristics were collected.Four hundred and one MET calls occurred after 23,258 surgical procedures, a rate of 1.7% of all non-cardiac surgical procedures, accounting for 11.7% of all MET calls over the study period. Hypotension (41.4%) was the most common trigger, followed by tachycardia (18.5%), altered conscious state (11.0%), hypoxia (10.0%), tachypnoea (5.7%), 'other' (5.7%), clinical concern (4.0%), increased work of breathing (1.5%) and bradypnoea (0.7%). Cardiac and/or respiratory arrest triggered 1.2% of MET activations. Eighty-six percent of patients had a single MET call, 10.2% had two, 1.8% had three and one patient (0.3%) had four. The median interval between post-anaesthetic care unit (PACU) discharge and MET call was 14.7 h (95% confidence interval 4.2 to 28.9 h). MET calls resulted in intensive care unit (ICU) admission in 40 patients (10%), while 82% remained on the ward, 4% had a MET call shortly after ICU discharge and returned there, 2% returned to theatre, and 2% went to a high dependency unit.Hypotension was the most common trigger for MET calls after non-cardiac surgery. Deterioration frequently occurred within 24 h of PACU discharge. Future research should focus on prevention of hypotension and tachycardia after surgery.

Dexamethasone and persistent wound pain: a prespecified analysis of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial.

BACKGROUND: Dexamethasone is commonly administered intraoperatively to prevent postoperative nausea and vomiting and is believed to have analgesic properties. It is unknown whether it has an impact on chronic wound pain. METHODS: In this prespecified embedded superiority substudy of the randomised PADDI trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and were followed up for 6 months postoperatively. The primary outcome was the incidence of pain in the surgical wound at 6 months. Secondary outcomes included acute postoperative pain and correlates of chronic postsurgical pain. RESULTS: We included 8478 participants in the modified intention-to-treat population (4258 in the dexamethasone group and 4220 in the matched placebo group). The primary outcome occurred in 491 subjects (11.5%) in the dexamethasone arm and 404 (9.6%) subjects in the placebo arm (relative risk 1.2, 95% confidence interval 1.06-1.41, P=0.003). Maximum pain scores at rest and on movement in the first 3 postoperative days were lower in the dexamethasone group compared with the control group {median 5 (inter-quartile range [IQR] 3.0-8.0) vs 6 (IQR 3.0-8.0) and median 7 (IQR 5.0-9.0) vs 8 (IQR 6.0-9.0), P<0.001 for both}. Severity of postoperative pain was not predictive of chronic postsurgical pain. The severity of chronic postsurgical pain and the frequency of neuropathic features did not differ between treatment groups. CONCLUSION: Administration of dexamethasone 8 mg i.v. was associated with an increase in the risk of pain in the surgical wound 6 months after surgery. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Consensus guidelines for the perioperative management of patients undergoing endoscopic retrograde cholangiopancreatography.

Deep sedation without tracheal intubation (monitored anaesthesia care) and general anaesthesia with tracheal intubation are commonly used anaesthesia techniques for endoscopic retrograde cholangiopancreatography (ERCP). There are distinct pathophysiological differences between monitored anaesthesia care and general anaesthesia that need to be considered depending on the nature and severity of the patient's underlying disease, comorbidities, and procedural risks. An international group of expert anaesthesiologists and gastroenterologists created clinically relevant questions regarding the merits and risks of monitored anaesthesia care vs general anaesthesia in specific clinical scenarios for planning optimal anaesthetic approaches for ERCP. Using a modified Delphi approach, the group created practical recommendations for anaesthesiologists, with the aim of reducing the incidence of perioperative adverse outcomes while maximising healthcare resource utilisation. In the majority of clinical scenarios analysed, our expert recommendations favour monitored anaesthesia care over general anaesthesia. Patients with increased risk of pulmonary aspiration and those undergoing prolonged procedures of high complexity were thought to benefit from general anaesthesia with tracheal intubation. Patient age and ASA physical status were not considered to be factors for choosing between monitored anaesthesia care and general anaesthesia. Monitored anaesthesia care is the favoured anaesthesia plan for ERCP. An individual risk-benefit analysis that takes into account provider and institutional experience, patient comorbidities, and procedural risks is also needed.

Perioperative oxygen administration in patients undergoing major non-cardiac surgery under general anaesthesia in Australia and New Zealand.

The practice of anaesthetists relating to the administration of intraoperative oxygen has not been previously quantified in Australia and New Zealand. The optimal regimen of intraoperative oxygen administration to patients undergoing surgery under general anaesthesia is not known, and international recommendations for oxygen therapy are contradictory; the World Health Organization (WHO) recommend administering an intraoperative fraction of inspired oxygen of at least 0.8, while the World Federation of Societies of Anaesthesiologists, British Thoracic Society, and Thoracic Society of Australia and New Zealand recommend a more restrictive approach. We conducted a prospective observational study to describe the pattern of intraoperative oxygen administration among anaesthetists in Australia and New Zealand and, second, to determine the proportion of anaesthetists who administer intraoperative inspired oxygen in accordance with the WHO recommendations. We identified 150 anaesthetists from ten metropolitan hospitals in Australia and New Zealand and observed the patterns of intraoperative oxygen administration to American Society of Anesthesiologists physical status classification (ASA) 3 or 4 patients undergoing prolonged surgery under general anaesthesia. The median (interquartile range) intraoperative time-weighted mean fraction of inspired oxygen (FiO2) for all participants in the study was 0.47 (0.40-0.55). Three out of 150 anaesthetists (2%, 95% confidence interval 0.4 to 5.7) administered an average intraoperative FiO2 of at least 0.8. These findings indicate that most anaesthetists routinely administer an intermediate level of oxygen for ASA 3 or 4 adult patients undergoing prolonged surgery in Australia and New Zealand, rather than down-titrating inspired oxygen to a target pulse oximetry reading (SpO2) or administering liberal perioperative oxygen therapy in line with the current WHO recommendation.

Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis.

BACKGROUND: Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide. The larger ENIGMA II trial randomized patients to nitrous oxide or air at a fraction of inspired oxygen of 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study, post hoc data were collected to determine whether atelectasis and pneumonia incidences were higher with nitrous oxide in patients who were recruited to the Australian cohort of ENIGMA II. METHODS: Digital health records of patients who participated in the trial at 10 Australian hospitals were examined blinded to trial treatment allocation. The primary endpoint was the incidence of atelectasis, defined as lung atelectasis or collapse reported on chest radiology. Pneumonia, as a secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the nitrous oxide and nitrous oxide-free groups was done according to intention to treat using chi-square tests. RESULTS: Data from 2,328 randomized patients were included in the final data set. The two treatment groups were similar in surgical type and duration, risk factors, and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with nitrous oxide (171 of 1,169 [14.6%] vs. 210 of 1,159 [18.1%]; odds ratio, 0.77; 95% CI, 0.62 to 0.97; P = 0.023). There was no difference in pneumonia incidence (60 of 1,169 [5.1%] vs. 52 of 1159 [4.5%]; odds ratio, 1.15; 95% CI, 0.77 to 1.72; P = 0.467) or combined pulmonary complications (odds ratio, 0.84; 95% CI, 0.69 to 1.03; P = 0.093). CONCLUSIONS: In contrast to the earlier ENIGMA trial, nitrous oxide anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery.

Processed electroencephalography-guided general anaesthesia to reduce postoperative delirium: a systematic review and meta-analysis.

BACKGROUND: Postoperative delirium (POD) is the most common serious postoperative complication in older adults. It has uncertain aetiology, limited preventative strategies, and poor long-term outcomes. This updated systematic review and meta-analysis aimed to estimate the effect of processed electroencephalography (pEEG)-guided general anaesthesia during surgery on POD incidence. METHODS: We performed a systematic review and meta-analysis by searching OVID MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. Studies of adult patients having general anaesthesia for any surgery where pEEG was used and POD was an outcome measure were included. Full-text reports of RCTs published from database inception until August 28, 2021, were included. Trials were excluded if sedation rather than general anaesthesia was administered, or the setting was intensive care. The primary outcome was POD assessed by validated tools. The study was prospectively registered with PROSPERO. RESULTS: Nine studies, which included 4648 eligible subjects, were identified. The incidence of POD in the pEEG-guided general anaesthesia or lighter pEEG target group was 19.0% (440/2310) compared with 23.3% (545/2338) in the usual care or deeper pEEG target group (pooled odds ratio=0.78; 95% confidence interval, 0.60-1.00; P=0.054). Significant heterogeneity was detected (I2=53%). CONCLUSIONS: Our primary analysis demonstrated a highly sensitive result with a pooled analysis of trials in which the intervention group adhered to manufacturer's recommended guidelines, showing reduced incidence of POD with pEEG guidance. High clinical heterogeneity limits inferences from this and any future meta-analyses. CLINICAL TRIAL REGISTRATION: CRD42020199404 (PROSPERO).