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.).

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults.

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

The relative merits of using a high-sensitivity cardiac Troponin T assay compared to a nonhigh-sensitivity troponin T assay after noncardiac surgery.

INTRODUCTION: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement. METHODS: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure). RESULTS: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001). CONCLUSIONS: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification.

The Gathering Storm: The 2023 Rovenstine Lecture.

Anesthesiologists are currently in demand and highly compensated. What appears to be a great success from our perspective is considered problematic from every other healthcare perspective. Consequently, there are powerful healthcare forces seeking to improve anesthesia access and reduce service cost. They will try to impose solutions that may radically change operative anesthesia. The Rovenstine lecture, delivered on World Anesthesia Day 2023, identified substantial challenges our specialty faces and discusses solutions that might be forced on us. It also presented opportunities in perioperative care.

Lost in Translation: Failure of Preclinical Studies to Accurately Predict the Effect of Regional Analgesia on Cancer Recurrence.

The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not-and what can be learned from the disconnect.

Comparison of differences in cohort (forwards) and case control (backwards) methodological approaches for validation of the Hypotension Prediction Index.

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique. METHODS: We conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance. RESULTS: Two thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77. CONCLUSION: Using an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

Incidence and risk factors of chronic postoperative pain in same-day surgery: A prospective cohort study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: We assessed pain 90 days after ambulatory surgery in an international, multicentre prospective cohort study of patients ≥45 years old with comorbidities or ≥65 years old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change ≥1 in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain as a score ≥4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain prior to surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were: active smoking (OR 1.82; 95% CI 1.20 to 2.76), orthopaedic surgery (OR 4.7; 95% CI 2.24 to 9.7), plastic surgery (OR 4.3; 95% CI 1.97 to 9.2), breast surgery (OR 2.74; 95% CI 1.29 to 5.8), vascular surgery (OR 2.71; 95% CI 1.09 to 6.7), and ethnicity (i.e., Hispanic/Latino ethnicity OR 3.41; 95% CI 1.68 to 6.9 and First Nations/Native persons OR 4.0; 95% CI 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, usually moderate to severe in nature, and occurs mostly in patients without chronic pain prior to surgery.

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

PeriOperative Quality Initiative (POQI) international consensus statement on perioperative arterial pressure management.

Arterial pressure monitoring and management are mainstays of haemodynamic therapy in patients having surgery. This article presents updated consensus statements and recommendations on perioperative arterial pressure management developed during the 11th POQI PeriOperative Quality Initiative (POQI) consensus conference held in London, UK, on June 4-6, 2023, which included a diverse group of international experts. Based on a modified Delphi approach, we recommend keeping intraoperative mean arterial pressure ≥60 mm Hg in at-risk patients. We further recommend increasing mean arterial pressure targets when venous or compartment pressures are elevated and treating hypotension based on presumed underlying causes. When intraoperative hypertension is treated, we recommend doing so carefully to avoid hypotension. Clinicians should consider continuous intraoperative arterial pressure monitoring as it can help reduce the severity and duration of hypotension compared to intermittent arterial pressure monitoring. Postoperative hypotension is often unrecognised and might be more important than intraoperative hypotension because it is often prolonged and untreated. Future research should focus on identifying patient-specific and organ-specific hypotension harm thresholds and optimal treatment strategies for intraoperative hypotension including choice of vasopressors. Research is also needed to guide monitoring and management strategies for recognising, preventing, and treating postoperative hypotension.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Metformin Use in Type 2 Diabetics and Delirium After Noncardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive. METHODS: We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables. RESULTS: No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13). CONCLUSIONS: Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.

Virtual Reality Distraction for Reducing Acute Postoperative Pain After Hip Arthroplasty: A Randomized Trial.

BACKGROUND: Relaxation and distraction provided by virtual reality presentations might be analgesic and reduce the need for opioid analgesia. We tested the hypothesis that a virtual reality program (AppliedVR) decreases acute postoperative pain and opioid requirements in patients recovering from hip arthroplasty. We also evaluated whether virtual reality distraction improves patient mobility and reduces the need for antiemetics. METHODS: We evaluated 106 adults who were recovering from elective primary total hip arthroplasty. Participating patients were randomized to 2- to 8-minute-long 3-dimensional immersive virtual reality relaxation and distraction video presentations (eg, guided breathing exercises, games, mindfulness) or to 2-dimensional presentations of nature short films (eg, forest wildlife) with neutral music that was chosen to be neither overly relaxing nor distracting, presented through identical headsets. Our primary outcome was pain after virtual reality or sham video presentations, adjusted for pretreatment scores. Secondary outcomes included total opioid consumption, pain scores obtained per routine by nurse staff, perception of video system usability, and pain 1 week after hospital discharge. RESULTS: Fifty-two patients were randomized to virtual reality distraction and relaxation, and 54 were assigned to 2-dimensional sham presentations. Virtual reality presentations were not found to affect pain scores before and after presentations, with an estimated difference in means (virtual reality minus sham video) of -0.1 points (95% confidence interval [CI], -0.5 to 0.2; P = .391) on a 0 to 10 scale, with 10 being the worst. The mean (standard error [SE]) after-intervention pain score was estimated to be 3.4 (0.3) in the virtual reality group and 3.5 (0.2) in the reference group. Virtual reality treatment was not found to affect postoperative opioid consumption in morphine milligram equivalents, with an estimated ratio of geometric means (virtual reality/sham video) of 1.2 (95% CI, 0.6-2.1; P = .608). Virtual reality presentations were not found to reduce pain scores collected every 4 hours by nursing staff, with an estimated difference in means of 0.1 points (95% CI, -0.9 to 0.7; P = .768). CONCLUSIONS: We did not observe statistically significant or clinically meaningful reductions in average pain scores or opioid consumption. As used in our trial, virtual reality did not reduce acute postoperative pain.

Association Between Age- and Sex-Specific Body Mass Index Percentile and Multiple Intubation Attempts: A Retrospective Cohort Analysis.

BACKGROUND: Obesity distorts airways and slightly complicates intubations in adults, but whether obesity complicates pediatric intubations remains unclear. We, therefore, tested the primary hypothesis that increasing age- and sex-specific body mass index (BMI) percentile is associated with difficult intubation, defined as >1 intubation attempt. METHODS: We conducted a retrospective analysis of pediatric patients between 2 and 18 years of age who had noncardiac surgery with oral endotracheal intubation. We assessed the association between BMI percentile and difficult intubation, defined as >1 intubation attempt, using a confounder-adjusted multivariable logistic regression model. Secondarily, we assessed whether the main association depended on preoperative substantial airway abnormality status or age group. RESULTS: A total of 9339 patients were included in the analysis. Median [quartiles] age- and sex-specific BMI percentile was 70 [33, 93], and 492 (5.3%) patients had difficult intubation. There was no apparent association between age- and sex-specific BMI percentile and difficult intubation. The estimated odds ratio (OR) for having difficult intubation for a 10-unit increase in BMI percentile was 0.98 (95% confidence interval [CI], 0.95-1.005) and was consistent across the 3 age groups of early childhood, middle childhood, and early adolescence (interaction P = .53). Patients with preoperative substantial airway abnormalities had lower odds of difficult intubation per 10-unit increase in BMI percentile, with OR (95% CI) of 0.83 (0.70-0.98), P = .01. CONCLUSIONS: Age- and sex-specific BMI percentile was not associated with difficult intubation in children between 2 and 18 years of age. As in adults, obesity in children does not much complicate intubation.

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. RESULTS: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. CONCLUSIONS: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

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.

Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room: A Cluster Randomized Clinical Trial.

Importance: Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. Objective: To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Design, Setting, and Participants: Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Interventions: Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. Main Outcomes and Measures: The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Results: Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). Conclusion and Relevance: In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04701762.

Innovative designs for trials informing the care of cardiac surgical patients: Part II.

PURPOSE OF REVIEW: This review examines advances in clinical trial methodologies relevant to cardiac anesthesia. It focuses on innovative approaches, including factorial randomization, composite outcomes, and cluster randomized trials, which enhance the efficiency, practical relevance, and generalizability of trial outcomes. RECENT FINDINGS: Factorial randomization is becoming popular because the approach allows investigators to simultaneously evaluate two or more interventions. Furthermore, factorial designs can evaluate interactions among treatments which is highly relevant information that cannot be obtained from separate trials. Composite outcomes are also increasingly utilized, combining multiple individual outcomes into a single measure, which increases statistical power and can better represent relevant physiology. Designing valid composites requires careful consideration of component outcome severity and incidence. Cluster randomized trials, including stepped wedge and multiple crossover designs, address the challenges of group-level effects and shared environments. SUMMARY: The evolution of clinical trial designs is marked by a shift towards methodologies that enhance efficiency and provide more nuanced insights into treatment effects. These include factorial designs for simultaneous intervention assessment, composite outcomes for comprehensive physiological representation, and cluster trials for group-level effect analysis. Such advancements are shaping the future of clinical research, making it more relevant, efficient, and broadly applicable.

Innovative designs for trials informing the care of cardiac surgical patients: part I.

PURPOSE OF REVIEW: Randomized clinical trials, now commonplace and regarded as top-tier evidence, are actually a recent development. The first randomized trial took place in 1948, just six decades ago. As anticipated from a relatively young field, rapid progress continues in response to an ever-increasing number of medical questions that demand answers. We examine evolving methodologies in cardiac anesthesia clinical trials, focusing on the transition towards larger sample sizes, increasing use of pragmatic trial designs, and the innovative adoption of real-time automated enrollment and randomization. We highlight how these changes enhance the reliability and feasibility of clinical trials. RECENT FINDINGS: Recent understanding in clinical trial methodology acknowledges the importance of large sample sizes, which increase the reliability of findings. As illustrated by P value fragility, small trials can mislead despite statistical significance. Pragmatic trials have gained prominence, offering real-world insights into the effectiveness of various treatments. Additionally, the use of real-time automated enrollment and randomization, particularly in situations where obtaining prior consent is impractical, is an important methodological advance. SUMMARY: The landscape of cardiac anesthesia clinical trials is rapidly evolving, with a clear trend towards large sample sizes and innovative approaches to enrollment. Recent developments enhance the quality and applicability of research findings, thus providing robust guidance to clinicians.