Dexamethasone and Surgical-Site Infection.

BACKGROUND: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. METHODS: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. RESULTS: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. CONCLUSIONS: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).

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.

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.

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.

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).

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.

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.

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.

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.

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.

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).

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.

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.

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.

Maternal mortality, safe abortion, and the anaesthetist.

Reproductive health is an active area of practice and research for anaesthetists, intensivists, and pain medicine specialists. The purpose of the British Journal of Anaesthesia is to promote the health, welfare, and safety of all persons by disseminating knowledge to further our understanding of anaesthetic principles and improve practice and skills. This includes supporting safe abortion care as an integral part of safe reproductive health.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

BACKGROUND: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials. METHODS: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the 'total effect' of sex on the outcome. RESULTS: Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio [RR] 0.92; 95% confidence interval [CI]: 0.81-1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81-1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79-1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79-1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex. CONCLUSIONS: Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy. CLINICAL TRIAL REGISTRATION: International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).

Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.

BACKGROUND: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown. METHODS: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery. RESULTS: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001). CONCLUSIONS: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated. CLINICAL TRIAL REGISTRATION: NCT04978285 (ClinicalTrials.gov).

Postoperative analgesia for complex spinal surgery.

PURPOSE OF REVIEW: Complex spinal surgery is associated with significant postoperative pain. The purpose of this paper is to review recent literature on postoperative pain management in adult and adolescent patients having complex spinal surgery. RECENT FINDINGS: We conducted a literature search using the Medline database for relevant publications from 2020 to 2022 on postoperative pain after complex spinal surgery. Although opioids remain the mainstay to manage pain after complex spinal surgery, they are associated with adverse effects. Multimodal analgesia may be used to reduce these adverse effects by combining different drugs targeting different parts of the pain pathway. Recent publications suggest continuous low dose fentanyl or morphine infusion, methadone, intravenous paracetamol and ibuprofen, ketorolac, ketamine, magnesium infusion, lidocaine infusion and dexmedetomidine appear to be effective and safe to manage pain after complex spinal surgery. Regional techniques including bilateral erector spinae block, interfascial plane block and intrathecal morphine also appear to be effective and safe. SUMMARY: Pain management after complex spinal surgery remains challenging. Therefore, further studies are still required to determine the optimal multimodal analgesic regimen for these patients.

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

BACKGROUND: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).