Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

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.).

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.

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).

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

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<0.001). 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.

Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.

BACKGROUND: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia. METHODS: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual. FINDINGS: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms. INTERPRETATION: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor. FUNDING: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.

Is cerebrovascular autoregulation associated with outcomes after major noncardiac surgery? A prospective observational pilot study.

BACKGROUND: Studies have identified multiple risk factors for development of cognitive decline after surgery. Impaired cerebrovascular autoregulation may be a contributor to postoperative cognitive decline. METHODS: One hundred and forty patients admitted for major elective noncardiac surgery were recruited. Near-infrared spectroscopy was used to calculate the tissue oxygenation index of dynamic autoregulation (TOx). The primary endpoint was Day 3 cognitive recovery as assessed using the Postoperative Quality of Recovery Scale. The secondary endpoint was a combined major adverse event of death, acute myocardial infarction, cardiac arrest, stroke, pulmonary embolism, sepsis, and acute kidney injury at Day 30. RESULTS: Higher optimal TOx values, signifying impaired autoregulation, were associated with worse outcomes. Patients who cognitively recovered at Day 3 (n = 47) had lower optimal TOx values (TOxopt ) than patients who did not recover (n = 22): 0.06 (0.24) vs 0.18 (0.16) (mean [SD]), P = 0.02. Patients who did not suffer a major adverse event (n = 102) had lower TOxopt than patients who did (n = 17): 0.09 (0.21) vs 0.20 (0.27), P = 0.04. When dichotomized as having impaired or intact autoregulation based on TOxopt levels, a value of TOxopt ≥0.1 correctly identified 72.7% of patients who did not cognitively recover, OR 3.3 (1.1-9.9) (Odds ratio, [95% CI]), P = 0.03. TOxopt ≥0.1 correctly identified 82.4% of patients who suffered a major adverse event, OR 4.7 (1.3-17.2), P = 0.02. CONCLUSIONS: In older and higher risk patients having major noncardiac surgery, impaired cerebrovascular autoregulation was associated with failure of cognitive recovery in the early postoperative period and with 1-month mortality and morbidity.

Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery.

Importance: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. Objectives: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. Design, Setting, and Participants: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. Exposures: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. Main Outcomes and Measures: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. Results: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy. Conclusions and Relevance: Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

Microbiological Contamination of Drugs during Their Administration for Anesthesia in the Operating Room.

BACKGROUND: The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections. METHODS: A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-µm filter was performed. The authors cultured microorganisms, if present, from the 0.2-µm filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case. RESULTS: Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants' average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult). CONCLUSIONS: Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation.

Refining Target-Controlled Infusion: An Assessment of Pharmacodynamic Target-Controlled Infusion of Propofol and Remifentanil Using a Response Surface Model of Their Combined Effects on Bispectral Index.

BACKGROUND: Propofol and remifentanil are commonly combined for total IV anesthesia. The pharmacokinetics (PK), pharmacodynamics (PD), and drug interactions of the combination are well understood, but the use of a combined PK and PD model to control target-controlled infusion pumps has not been investigated. In this study, we prospectively tested the accuracy of a PD target-controlled infusion algorithm for propofol and remifentanil using a response surface model of their combined effects on Bispectral Index (BIS). METHODS: Effect-site, target-controlled infusions of propofol and remifentanil were given using an algorithm based on standard PK models linked to a PD response surface model of their combined effects on BIS. The combination of a targeted BIS value and adjustable ratio of propofol to remifentanil was used to adjust infusion rates. The standard model performance measures of median performance error (bias) and median absolute performance error (inaccuracy), expressed as percentages, were used to assess accuracy of the infusions in a convenience sample of 50 adult patients undergoing surgery with general anesthesia. The influence of age and weight on the performance of the model was also assessed. RESULTS: Patients had a mean (range) age of 48 (19-73) years, weight of 80 (45-169) kg, and body mass index of 28 (19-45) kg/m. The overall model had a bias of 8% (SD 24%) and inaccuracy of 25% (SD 13%). Performance was least accurate during the early induction phase of anesthesia. There was no significant bias in BIS predictions with increasing age (P = 0.44) or weight (P = 0.56). CONCLUSIONS: The algorithm performed adequately in a clinical setting. The algorithm could be further refined, and assessment of its accuracy and utility in comparison to current clinical practice for giving IV anesthesia is warranted.

Anesthetic depth and long-term survival: an update.

PURPOSE: The purpose of this paper is to review the current evidence relating anesthetic depth to long-term survival after surgery. SOURCE: Using PubMed as the principal source, this review included published studies in all languages comparing mortality in patients with low- and high-processed electro-encephalo-graphic index values. PRINCIPAL FINDINGS: All published studies used the bispectral index (BIS) monitor to measure anesthetic depth. The majority of the published observational studies were post hoc analyses of studies undertaken for other purposes. Most of these studies report a statistically significant association between deep general anesthesia (i.e., BIS values < 45) and death. Some studies also suggest an association between deep general anesthesia and myocardial infarction or postoperative cognitive decline. The combination of low BIS values and low delivered anesthetic concentrations (thus defining increased anesthetic sensitivity) may identify patients at particularly high risk. One of the three available randomized controlled trials reports worse outcomes in the BIS = 50 group compared with the BIS > 80 group, and two report no difference in mortality between the BIS = 35 and BIS = 50-55 groups. CONCLUSIONS: The available evidence on anesthetic depth and long-term survival is inconclusive. Randomized controlled trials with carefully controlled arterial blood pressure are required.

Rationale and Design of the Balanced Anesthesia Study: A Prospective Randomized Clinical Trial of Two Levels of Anesthetic Depth on Patient Outcome After Major Surgery.

BACKGROUND: An association between relatively deep anesthesia, as guided by the bispectral index (BIS), and increased postoperative mortality has been demonstrated in 6 of 8 published observational studies, but association does not necessarily mean causality. Small clinical trials of anesthetic depth have demonstrated increased delirium and postoperative cognitive dysfunction in patients who were relatively deeply anesthetized, but have been inadequately powered to study mortality. A large-scale randomized study is required to determine whether causality exists. METHODS: The primary hypothesis of our study is that "light" anesthesia, defined as a BIS target of 50, will reduce all-cause mortality within 1 year of surgery in comparison with "deep" anesthesia, defined as a BIS target of 35, in patients aged ≥60 years presenting for major surgery under general anesthesia. The trial is an international multicenter, randomized, parallel-group, double-blind (patients and investigators) prospective, intention-to-treat, safety and efficacy study. The relative reduction in mortality in the light anesthesia group is expected to be 20%, giving an absolute risk reduction from 10% to 8%. Power analysis using a = 0.049 and b = 0.2 indicates that 3250 patients are required in each group. RESULTS: The study is underway, and 1325 patients have been recruited in 40 centers in 5 countries. It is anticipated that the study will be completed in 3 years. CONCLUSIONS: This randomized controlled trial should definitively answer the question of whether titrating anesthetic depth makes a difference to patient outcome in a vulnerable patient group.

A pilot study for a prospective, randomized, double-blind trial of the influence of anesthetic depth on long-term outcome.

BACKGROUND: Deep general anesthesia has been associated with increased mortality in 5 observational studies. The association may be causal or an epiphenomenon due to increased anesthetic sensitivity in high-risk patients. We conducted a pilot study to assess the feasibility of performing a definitive randomized controlled trial. The aims of the study were to determine whether anesthetic depth targeting in a high-risk group was feasible and to document anesthetic doses and arterial blood pressures associated with "deep" and "light" general anesthesia. METHODS: ASA physical status III and IV patients, aged ≥60 years, having surgery lasting ≥2 hours, with expected hospital stay ≥2 days, and receiving general anesthesia were randomly allocated to a Bispectral Index (BIS) or spectral entropy (SE) target of 35 ("low" group) or 50 ("high" group). The primary end point was mean BIS or SE. Secondary end points were postanesthesia care unit length of stay and pain scores, quality of recovery score, hospital length of stay, postoperative complications, and death. A composite end point of postoperative complications (pneumonia, myocardial infarction, stroke, pulmonary embolism, heart failure, and death) was determined at 1 year. RESULTS: One hundred twenty-five patients were recruited. The mean of the median BIS/SE values for each patient during the maintenance phase of anesthesia in the low and high groups was significantly different: 39 vs 48 (mean difference 8 [95% confidence interval {CI95}, 6 to 10], P < 0.001). There was also a significant difference in mean volatile anesthetic administration (minimum alveolar concentration): 0.98 vs 0.64 (mean difference -0.35 [CI95, -0.44 to -0.26], P < 0.001) and target propofol concentrations: 4.0 vs 3.1 µg/mL (mean difference -0.8 [CI95, -1.2 to -0.3], P = 0.004). Intraoperative mean arterial blood pressures were similar (85 vs 87 mm Hg; mean difference 2 [CI95, -2 to 6], P = 0.86), and there were no differences in short-term recovery characteristics or hospital length of stay. There was a significant difference in the incidence of wound infection at 30 days (13% vs 3%; risk difference -10% [CI95, -21 to -0.1], P = 0.04). At 1 year, the composite rates of complications in the low and high groups were 28% and 17% (risk difference -11 [CI95, -25 to 4], P = 0.15) and mortality rates were 12% and 9%, respectively (risk difference -2 [CI95, -14 to 9], P = 0.70). CONCLUSIONS: This pilot study demonstrated that depth of anesthesia targeting with BIS or SE was achievable in a high-risk population with adequate separation of processed electroencephalogram monitor targets. The expected incidence of postoperative complications and mortality occurred. We conclude that a large, multicenter, randomized controlled trial is feasible.

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.

Incidence of postoperative delirium in surgical patients: An observational retrospective cohort study.

SummaryPerioperative neurocognitive disorders including postoperative delirium (POD) are common complications of anaesthesia and surgery, associated with morbidity, mortality and a large economic cost. Currently, limited data are available on the incidence of POD in the New Zealand population. The objective of this study was to utilise New Zealand national level datasets to identify the incidence of POD. Our primary outcome was defined as a diagnosis of delirium via ICD 9/10 coding within seven days of surgery. We also analysed demographic, anaesthetic and surgical characteristics. All adult patients undergoing any surgical intervention under sedation, regional, general or neuraxial anaesthesia were included, and patients who received surgical intervention under local anaesthetic infiltration alone were excluded. We reviewed ten years of patient admissions from 2007 to 2016. Our sample size was 2,249,910 patients. The incidence of POD was 1.9%, much lower than previously observed, potentially indicating significant under-reporting of POD in this national level database. With acknowledgement of the limitations of potential undercoding and under-reporting, we found that the incidence of POD was higher with increasing age, male sex, general anaesthesia, Maori ethnicity, increasing comorbidity, surgical severity and emergency surgery. A diagnosis of POD was associated with increased mortality and hospital length of stay. Our results highlight potential risk factors of POD and disparities in health outcomes in New Zealand. Additionally, these findings suggest systemic under-reporting of POD in national level datasets.

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.

Protocol for the MAnagement of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischemic STROKE randomized clinical trial: The MASTERSTROKE trial.

REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p. RATIONALE: Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery. AIM: To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension. DESIGN: Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes. PROCEDURES: Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with 'wake up' stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist. STUDY OUTCOMES: The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days. ANALYSIS: The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.