Heart failure diagnostic accuracy, intraoperative fluid management, and postoperative acute kidney injury: a single-centre prospective observational study.

BACKGROUND: The accurate diagnosis of heart failure (HF) before major noncardiac surgery is frequently challenging. The impact of diagnostic accuracy for HF on intraoperative practice patterns and clinical outcomes remains unknown. METHODS: We performed an observational study of adult patients undergoing major noncardiac surgery at an academic hospital from 2015 to 2019. A preoperative clinical diagnosis of HF was defined by keywords in the preoperative assessment or a diagnosis code. Medical records of patients with and without HF clinical diagnoses were reviewed by a multispecialty panel of physician experts to develop an adjudicated HF reference standard. The exposure of interest was an adjudicated diagnosis of heart failure. The primary outcome was volume of intraoperative fluid administered. The secondary outcome was postoperative acute kidney injury (AKI). RESULTS: From 40 659 surgeries, a stratified subsample of 1018 patients were reviewed by a physician panel. Among patients with adjudicated diagnoses of HF, those without a clinical diagnosis (false negatives) more commonly had preserved left ventricular ejection fractions and fewer comorbidities. Compared with false negatives, an accurate diagnosis of HF (true positives) was associated with 470 ml (95% confidence interval: 120-830; P=0.009) lower intraoperative fluid administration and lower risk of AKI (adjusted odds ratio:0.39, 95% confidence interval 0.18-0.89). For patients without adjudicated diagnoses of HF, non-HF was not associated with differences in either fluids administered or AKI. CONCLUSIONS: An accurate preoperative diagnosis of heart failure before noncardiac surgery is associated with reduced intraoperative fluid administration and less acute kidney injury. Targeted efforts to improve preoperative diagnostic accuracy for heart failure may improve perioperative outcomes.

Association between inspired oxygen fraction and development of postoperative pulmonary complications in thoracic surgery: a multicentre retrospective cohort study.

BACKGROUND: Limited data exist to guide oxygen administration during one-lung ventilation for thoracic surgery. We hypothesised that high intraoperative inspired oxygen fraction during lung resection surgery requiring one-lung ventilation is independently associated with postoperative pulmonary complications (PPCs). METHODS: We performed this retrospective multicentre study using two integrated perioperative databases (Multicenter Perioperative Outcomes Group and Society of Thoracic Surgeons General Thoracic Surgery Database) to study adult thoracic surgical procedures using one-lung ventilation. The primary outcome was a composite of PPCs (atelectasis, acute respiratory distress syndrome, pneumonia, respiratory failure, reintubation, and prolonged ventilation >48 h). The exposure of interest was high inspired oxygen fraction (FiO2), defined by area under the curve of a FiO2 threshold > 80%. Univariate analysis and logistic regression modelling assessed the association between intraoperative FiO2 and PPCs. RESULTS: Across four US medical centres, 141/2733 (5.2%) procedures conducted in 2716 patients (55% female; mean age 66 yr) resulted in PPCs. FiO2 was univariately associated with PPCs (adjusted OR [aOR]: 1.17, 95% confidence interval [CI]: 1.04-1.33, P=0.012). Logistic regression modelling showed that duration of one-lung ventilation (aOR: 1.20, 95% CI: 1.03-1.41, P=0.022), but not the time-weighted average FiO2 (aOR: 1.01, 95% CI: 1.00-1.02, P=0.165), was associated with PPCs. CONCLUSIONS: Our results do not support limiting the inspired oxygen fraction for the purpose of reducing postoperative pulmonary complications in thoracic surgery involving one-lung ventilation.

Bronchial Blocker Versus Endobronchial Intubation in Young Children Undergoing One-Lung Ventilation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Thoracic surgery and one-lung ventilation in young children carry significant risks. Approaches to one-lung ventilation in young children include endobronchial intubation (mainstem intubation) and use of a bronchial blocker. We hypothesized that endobronchial intubation is associated with a greater prevalence of airway complications compared to use of a bronchial blocker. METHODS: The Multicenter Perioperative Outcomes Group database was queried from 2004 to 2022 for one-lung ventilation cases in children, 2 months to 3 years of age, inclusive. Airway notes and free-text comments were manually reviewed for airway complications. Documented airway complications were considered the primary outcome and were divided into "Moderate" and "Critical." Moderate airway complications were bronchial blocker or endotracheal tube movement leading to loss of isolation, hypoxemia requiring ventilatory intervention, bronchial blocker migration into the trachea, significant impairment of ventilation, and other. Critical complications included reintubation or airway replacement intraoperatively, complete endotracheal tube occlusion, cardiac arrest or airway-related bradycardia, and procedure aborted due to an airway issue. An adjusted propensity score-matched analysis was then used to assess the impact of a bronchial blocker on the outcomes of moderate and critical complications. RESULTS: After exclusions, 704 patients were included in the primary analysis. In unadjusted analyses, no statistically significant difference was observed in moderate airway complications between endobronchial intubation and bronchial blocker cohorts: 37 of 444 (8.3%; 95% confidence interval [CI], 5.9%-11.3%) vs 28 of 260 (10.8%; 95% CI, 7.3%-15.2%) with P = .281. In the unadjusted analysis, the prevalence of critical airway complications was significantly higher in the endobronchial intubation cohort compared to the bronchial blocker cohort: 28 of 444 (6.3%; 95% CI, 4.2%-9.0%) vs 5 of 260 (1.9%; 95% CI, 0.6%-4.4%) with P = .008. In the propensity-matched cohort analysis, endobronchial intubation was associated with a slightly increased risk of critical complications compared to use of a bronchial blocker: 14 of 243 (5.8%; 95% CI, 2.8%-8.7%) vs 5 of 243 (2.1%; 95% CI, 0.3%-3.8%) with P = .035. CONCLUSIONS: Endobronchial intubation might be associated with a slightly increased risk of critical airway complications compared to use of a bronchial blocker in young children undergoing thoracic surgery and one-lung ventilation. Further, prospective studies are needed before a definitive change in practice is recommended.

Opioid Dose Variation in Cardiac Surgery: A Multicenter Study of Practice.

BACKGROUND: Although high-opioid anesthesia was long the standard for cardiac surgery, some anesthesiologists now favor multimodal analgesia and low-opioid anesthetic techniques. The typical cardiac surgery opioid dose is unclear, and the degree to which patients, anesthesiologists, and institutions influence this opioid dose is unknown. METHODS: We reviewed data from nonemergency adult cardiac surgeries requiring cardiopulmonary bypass performed at 30 academic and community hospitals within the Multicenter Perioperative Outcomes Group registry from 2014 through 2021. Intraoperative opioid administration was measured in fentanyl equivalents. We used hierarchical linear modeling to attribute opioid dose variation to the institution where each surgery took place, the primary attending anesthesiologist, and the specifics of the surgical patient and case. RESULTS: Across 30 hospitals, 794 anesthesiologists, and 59,463 cardiac cases, patients received a mean of 1139 (95% confidence interval [CI], 1132-1146) fentanyl mcg equivalents of opioid, and doses varied widely (standard deviation [SD], 872 µg). The most frequently used opioids were fentanyl (86% of cases), sufentanil (16% of cases), hydromorphone (12% of cases), and morphine (3% of cases). 0.6% of cases were opioid-free. 60% of dose variation was explainable by institution and anesthesiologist. The median difference in opioid dose between 2 randomly selected anesthesiologists across all institutions was 600 µg of fentanyl (interquartile range [IQR], 283-1023 µg). An anesthesiologist's intraoperative opioid dose was strongly correlated with their frequency of using a sufentanil infusion (r = 0.81), but largely uncorrelated with their use of nonopioid analgesic techniques (|r| < 0.3). CONCLUSIONS: High-dose opioids predominate in cardiac surgery, with substantial dose variation from case to case. Much of this variation is attributable to practice variability rather than patient or surgical differences. This suggests an opportunity to optimize opioid use in cardiac surgery.

Identifying Variation in Intraoperative Management of Brain-Dead Organ Donors and Opportunities for Improvement: A Multicenter Perioperative Outcomes Group Analysis.

BACKGROUND: Intraoperative events and clinical management of deceased organ donors after brain death are poorly characterized and may consequently vary between hospitals and organ procurement organization (OPO) regions. In a multicenter cohort, we sought to estimate the incidence of hypotension and anesthetic and nonanesthetic medication use during organ recovery procedures. METHODS: We used data from electronic anesthetic records generated during organ recovery procedures from brain-dead adults across a Multicenter Perioperative Outcomes Group (MPOG) cohort of 14 US hospitals and 4 OPO regions (2014-2020). Hypotension, defined as mean arterial pressure or MAP <60 mm Hg for at least 10 cumulative minutes was the primary outcome of interest. The associations between hypotension and age, sex, race, anesthesia time, OPOs, and OPO case volume were examined using multivariable mixed-effects Poisson regression analyses with robust standard error estimates. We calculated intraclass correlation coefficients (ICCs) to describe the variation between-MPOG centers and the OPO regions in the use of medications, time of the operation, and duration of the operation. RESULTS: We examined 1338 brain-dead adult donors, with a mean age of 42± (standard deviation [SD] 15) years; 60% (n = 801) were males and 67% (n = 891) non-Hispanic White. During the entire intraoperative monitoring period, 321 donors (24%, 95% confidence interval [CI], 22%-26%) had hypotension for a median of 13.8% [quartile1-quartile 3: 9.4%-21%] of the monitoring period and a minimum of 10 minutes to a maximum of 96 minutes [(median: 17, quartile1-quartile 3: 12-24]). The probability having hypotension in donors 35 to 64 years and 65 years and older were approximately 30% less than in donors 18 to 34 years of age (adjusted relative risk ratios, aRR, 0.68, 95% CI, 0.55-0.82, aRR, 0.63, 95% CI, 0.42-0.94, respectively). Donors received intravenous heparin (96.4%, n = 1291), neuromuscular blockers (89.5%, n = 1198), vasoactive medications (82.7%, n = 1108), crystalloids (76.2%, n = 1020), halogenated anesthetic gases (63.5%, n = 850), diuretics (43.8%, n = 587), steroids (16.7%, n = 224), and opioids (23.2%, n = 310). The largest practice heterogeneity observed between the MPOG center and OPO regions was steroids (between-center ICCs = 0.65, 95% CI, 0.62-0.75, between-region ICCs = 0.39, 95% CI, 0.27-0.63) and diuretics (between-center ICCs = 0.44, 95% CI, 0.36-0.6, between-region ICCs = 0.30, 95% CI, 0.22-0.49). CONCLUSIONS: Despite guidelines recommending maintenance of MAP >60 mm Hg in adult brain-dead organ donors, hypotension during recovery procedures was common. Future research is needed to clarify the relationship between intraoperative events with donation and transplantation outcomes and to identify best practices for the anesthetic management of brain-dead donors in the operating room.

Intraoperative Use of Albumin in Major Noncardiac Surgery: Incidence, Variability, and Association With Outcomes.

BACKGROUND: The impact of albumin use during major surgery is unknown, and a dearth of evidence governing its use in major noncardiac surgery has long precluded its standardization in clinical guidelines. OBJECTIVE: In this study, we investigate institutional variation in albumin use among medical centers in the United States during major noncardiac surgery and explore the association of intraoperative albumin administration with important postoperative outcomes. METHODS: The study is an observational retrospective cohort analysis performed among 54 U.S. hospitals in the Multicenter Perioperative Outcomes Group and includes adult patients who underwent major noncardiac surgery under general anesthesia between January 2014 and June 2020. The primary endpoint was the incidence of albumin administration. Secondary endpoints are acute kidney injury (AKI), net-positive fluid balance, pulmonary complications, and 30-day mortality. Albumin-exposed and albumin-unexposed cases were compared within a propensity score-matched cohort to evaluate associations of albumin use with outcomes. RESULTS: Among 614,215 major surgeries, predominantly iso-oncotic albumin was administered in 15.3% of cases and featured significant inter-institutional variability in use patterns. Cases receiving intraoperative albumin involved patients of higher American Society of Anesthesiologists physical status and featured larger infused crystalloid volumes, greater blood loss, and vasopressor use. Overall, albumin was most often administered at high-volume surgery centers with academic affiliation, and within a propensity score-matched cohort (n=153,218), the use of albumin was associated with AKI (aOR 1.24, 95% CI 1.20-1.28, P <0.001), severe AKI (aOR 1.45, 95% CI 1.34-1.56, P <0.001), net-positive fluid balance (aOR 1.18, 95% CI 1.16-1.20, P <0.001), pulmonary complications (aOR 1.56, 95% CI 1.30-1.86, P <0.001), and 30-day all-cause mortality (aOR 1.37, 95% CI 1.26-1.49, P <0.001). CONCLUSIONS: Intravenous albumin is commonly administered among noncardiac surgeries with significant inter-institutional variability in use in the United States. Albumin administration was associated with an increased risk of postoperative complications.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

Patient-, Clinician-, and Institution-level Variation in Inotrope Use for Cardiac Surgery: A Multicenter Observational Analysis.

BACKGROUND: Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use. METHODS: In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied. RESULTS: Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non-mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86). CONCLUSIONS: Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.

Cardiometabolic disease and obesity patterns differentially predict acute kidney injury after total joint replacement: a retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) is a frequent yet understudied postoperative total joint arthroplasty complication. This study aimed to describe cardiometabolic disease co-occurrence using latent class analysis, and associated postoperative AKI risk. METHODS: This retrospective analysis examined patients ≥18 years old undergoing primary total knee or hip arthroplasties within the US Multicenter Perioperative Outcomes Group of hospitals from 2008 to 2019. AKI was defined using modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Latent classes were constructed from eight cardiometabolic diseases including hypertension, diabetes, and coronary artery disease, excluding obesity. A mixed-effects logistic regression model was constructed for the outcome of any AKI and the exposure of interaction between latent class and obesity status adjusting for preoperative and intraoperative covariates. RESULTS: Of 81 639 cases, 4007 (4.9%) developed AKI. Patients with AKI were more commonly older and non-Hispanic Black, with more significant comorbidity. A latent class model selected three groups of cardiometabolic patterning, labelled 'hypertension only' (n=37 223), 'metabolic syndrome (MetS)' (n=36 503), and 'MetS+cardiovascular disease (CVD)' (n=7913). After adjustment, latent class/obesity interaction groups had differential risk of AKI compared with those in 'hypertension only'/non-obese. Those 'hypertension only'/obese had 1.7-fold increased odds of AKI (95% confidence interval [CI]: 1.5-2.0). Compared with 'hypertension only'/non-obese, those 'MetS+CVD'/obese had the highest odds of AKI (odds ratio 3.1, 95% CI: 2.6-3.7), whereas 'MetS+CVD'/non-obese had 2.2 times the odds of AKI (95% CI: 1.8-2.7; model area under the curve 0.76). CONCLUSIONS: The risk of postoperative AKI varies widely between patients. The current study suggests that the co-occurrence of metabolic conditions (diabetes mellitus, hypertension), with or without obesity, is a more important risk factor for acute kidney injury than individual comorbid diseases.

Optimizing the Design and Analysis of Future AKI Trials.

AKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment. This article, derived from the "AKI" session of the "Kidney Disease Clinical Trialists" virtual workshop held in October 2021, reviews barriers to and strategies for improving the design and implementation of clinical trials in patients with, or at risk of, developing AKI. The novel approaches to trial design included in this review span adaptive trial designs that increase the knowledge gained from each trial participant; pragmatic trial designs that allow for the efficient enrollment of sufficiently large numbers of patients to detect small, but clinically significant, treatment effects; and platform trial designs that use one trial infrastructure to answer multiple clinical questions simultaneously. This review also covers novel approaches to clinical trial analysis, such as Bayesian analysis and assessing heterogeneity in the response to therapies among trial participants. We also propose a road map and actionable recommendations to facilitate the adoption of the reviewed approaches. We hope that the resulting road map will help guide future clinical trial planning, maximize learning from AKI trials, and reduce the risk of missing important signals of benefit (or harm) from trial interventions.

Prediction of Postoperative Deterioration in Cardiac Surgery Patients Using Electronic Health Record and Physiologic Waveform Data.

BACKGROUND: Postoperative hemodynamic deterioration among cardiac surgical patients can indicate or lead to adverse outcomes. Whereas prediction models for such events using electronic health records or physiologic waveform data are previously described, their combined value remains incompletely defined. The authors hypothesized that models incorporating electronic health record and processed waveform signal data (electrocardiogram lead II, pulse plethysmography, arterial catheter tracing) would yield improved performance versus either modality alone. METHODS: Intensive care unit data were reviewed after elective adult cardiac surgical procedures at an academic center between 2013 and 2020. Model features included electronic health record features and physiologic waveforms. Tensor decomposition was used for waveform feature reduction. Machine learning-based prediction models included a 2013 to 2017 training set and a 2017 to 2020 temporal holdout test set. The primary outcome was a postoperative deterioration event, defined as a composite of low cardiac index of less than 2.0 ml min-1 m-2, mean arterial pressure of less than 55 mmHg sustained for 120 min or longer, new or escalated inotrope/vasopressor infusion, epinephrine bolus of 1 mg or more, or intensive care unit mortality. Prediction models analyzed data 8 h before events. RESULTS: Among 1,555 cases, 185 (12%) experienced 276 deterioration events, most commonly including low cardiac index (7.0% of patients), new inotrope (1.9%), and sustained hypotension (1.4%). The best performing model on the 2013 to 2017 training set yielded a C-statistic of 0.803 (95% CI, 0.799 to 0.807), although performance was substantially lower in the 2017 to 2020 test set (0.709, 0.705 to 0.712). Test set performance of the combined model was greater than corresponding models limited to solely electronic health record features (0.641; 95% CI, 0.637 to 0.646) or waveform features (0.697; 95% CI, 0.693 to 0.701). CONCLUSIONS: Clinical deterioration prediction models combining electronic health record data and waveform data were superior to either modality alone, and performance of combined models was primarily driven by waveform data. Decreased performance of prediction models during temporal validation may be explained by data set shift, a core challenge of healthcare prediction modeling.

Multicentre analysis of practice patterns regarding benzodiazepine use in cardiac surgery.

BACKGROUND: There is controversy regarding optimal use of benzodiazepines during cardiac surgery, and it is unknown whether and to what extent there is variation in practice. We sought to describe benzodiazepine use and sources of variation during cardiac surgeries across patients, clinicians, and institutions. METHODS: We conducted an analysis of adult cardiac surgeries across a multicentre consortium of USA academic and private hospitals from 2014 to 2019. The primary outcome was administration of a benzodiazepine from 2 h before anaesthesia start until anaesthesia end. Institutional-, clinician-, and patient-level variables were analysed via multilevel mixed-effects models. RESULTS: Of 65 508 patients cared for by 825 anaesthesiology attending clinicians (consultants) at 33 institutions, 58 004 patients (88.5%) received benzodiazepines with a median midazolam-equivalent dose of 4.0 mg (inter-quartile range [IQR], 2.0-6.0 mg). Variation in benzodiazepine dosage administration was 54.7% attributable to institution, 14.7% to primary attending anaesthesiology clinician, and 30.5% to patient factors. The adjusted median odds ratio for two similar patients receiving a benzodiazepine was 2.68 between two randomly selected clinicians and 4.19 between two randomly selected institutions. Factors strongly associated (adjusted odds ratio, <0.75, or >1.25) with significantly decreased likelihoods of benzodiazepine administration included older age (>80 vs ≤50 yr; adjusted odds ratio=0.04; 95% CI, 0.04-0.05), university affiliation (0.08, 0.02-0.35), recent year of surgery (0.42, 0.37-0.49), and low clinician case volume (0.44, 0.25-0.75). Factors strongly associated with significantly increased likelihoods of benzodiazepine administration included cardiopulmonary bypass (2.26, 1.99-2.55), and drug use history (1.29, 1.02-1.65). CONCLUSIONS: Two-thirds of the variation in benzodiazepine administration during cardiac surgery are associated with institutions and attending anaesthesiology clinicians (consultants). These data, showing wide variations in administration, suggest that rigorous research is needed to guide evidence-based and patient-centred benzodiazepine administration.

Opportunities Beyond the Anesthesiology Department: Broader Impact Through Broader Thinking.

Ensuring a productive clinical and research workforce requires bringing together physicians and communities to improve health, by strategic targeting of initiatives with clear and significant public health relevance. Within anesthesiology, the traditional perspective of the field's health impact has focused on providing safe and effective intraoperative care, managing critical illness, and treating acute and chronic pain. However, there are limitations to such a framework for anesthesiology's public health impact, including the transient nature of acute care episodes such as the intraoperative period and critical illness, and a historical focus on analgesia alone-rather than the complex psychosocial milieu-for pain management. Due to the often episodic nature of anesthesiologists' interactions with patients, it remains challenging for anesthesiologists to achieve their full potential for broad impact and leadership within increasingly integrated health systems. To unlock this potential, anesthesiologists should cultivate new clinical, research, and administrative roles within the health system-transcending traditional missions, seeking interdepartmental collaborations, and taking measures to elevate anesthesiologists as dynamic and trusted leaders. This special article examines 3 core themes for how anesthesiologists can enhance their impact within the health care system and pursue new collaborative health missions with nonanesthesiologist clinicians, researchers, and administrative leaders. These themes include (1) reframing of traditional anesthesiologist missions toward a broader health system-wide context; (2) leveraging departmental and institutional support for professional career development; and (3) strategically prioritizing leadership attributes to enhance system-wide anesthesiologist contributions to improving overall patient health.

Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients.

BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.

Identification of intraoperative management strategies that have a differential effect on patients with reduced left ventricular ejection fraction: a retrospective cohort study.

BACKGROUND: There are few data to guide the intraoperative management of patients with reduced left ventricular ejection fraction (LVEF). This study aimed to describe how patients with reduced LVEF are managed differently and to identify and treatments had a different risk profile in this population. METHODS: We performed a retrospective cohort study of adult patients who underwent general anesthesia for non-cardiac surgery. The effect of anesthesia medications and fluid balance was compared between those with and without a reduced preoperative LVEF. The primary outcome was a composite of acute kidney injury, myocardial injury, pulmonary complications, and 30-day mortality. Multivariable logistic regression was used to adjust for confounders. Treatments that affected patients with reduced LVEF differently were defined as those associated with the primary outcome that also had a significant interaction with LVEF. RESULTS: A total of 9420 patients were included. Patients with reduced LVEF tended to have a less positive fluid balance. Etomidate, calcium, and phenylephrine were use more frequently, while propofol and remifentanil were used less frequently. Remifentanil affected patients with reduced LVEF differently than those without (interaction term OR 2.71, 95% CI 1.30-5.68, p = 0.008). While the use of remifentanil was associated with fewer complications in patients with normal systolic function (OR 0.54, 95% CI 0.42-0.68, p < 0.001), it was associated with an increase in complications in patients with reduced LVEF (OR = 3.13, 95% CI 3.06-5.98, p = 0.026). CONCLUSIONS: Patients with a reduced preoperative LVEF are treated differently than those with a normal LVEF when undergoing non-cardiac surgery. An association was found between the use of remifentanil and an increase in postoperative adverse events that was unique to this population. Future research is needed to determine if this relationship is secondary to the medication itself or reflects a difference in how remifentanil is used in patients with reduced LVEF.

Hypoxemia in Young Children Undergoing One-lung Ventilation: A Retrospective Cohort Study.

BACKGROUND: One-lung ventilation in children remains a specialized practice with low case numbers even at tertiary centers, preventing an assessment of best practices. The authors hypothesized that certain case factors may be associated with a higher risk of intraprocedural hypoxemia in children undergoing thoracic surgery and one-lung ventilation. METHODS: The Multicenter Perioperative Outcomes database and a local quality improvement database were queried for documentation of one-lung ventilation in children 2 months to 3 yr of age inclusive between 2010 and 2020. Patients undergoing vascular or other cardiac procedures were excluded. All records were reviewed electronically for the presence of hypoxemia, oxygen saturation measured by pulse oximetry (Spo2) less than 90% for 3 min or more continuously, and severe hypoxemia, Spo2 less than 90% for 5 min or more continuously during one-lung ventilation. Records were also assessed for hypercarbia, end-tidal CO2 greater than 60 mmHg for 5 min or more or a Paco2 greater than 60 on arterial blood gas. Covariates assessed for association with these outcomes included age, weight, American Society of Anesthesiologists (Schaumburg, Illinois) Physical Status 3 or greater, duration of one-lung ventilation, preoperative Spo2 less than 98%, bronchial blocker versus endobronchial intubation, left operative side, video-assisted thoracoscopic surgery, lower tidal volume ventilation (tidal volume less than or equal to 6 ml/kg plus positive end expiratory pressure greater than or equal to 4 cm H2O for more than 80% of the duration of one-lung ventilation), and type of procedure. RESULTS: Three hundred six cases from 15 institutions were included for analysis. Hypoxemia and severe hypoxemia occurred in 81 of 306 (26%) patients and 56 of 306 (18%), respectively. Hypercarbia occurred in 153 of 306 (50%). Factors associated with lower risk of hypoxemia in multivariable analysis included left operative side (odds ratio, 0.45 [95% CI, 0.251 to 0.78]) and bronchial blocker use (odds ratio, 0.351 [95% CI, 0.177 to 0.67]). Additionally, use of a bronchial blocker was associated with a reduced risk of severe hypoxemia (odds ratio, 0.290 [95% CI, 0.125 to 0.62]). CONCLUSIONS: Use of a bronchial blocker was associated with a lower risk of hypoxemia in young children undergoing one-lung ventilation.

A Lower Tidal Volume Regimen during One-lung Ventilation for Lung Resection Surgery Is Not Associated with Reduced Postoperative Pulmonary Complications.

BACKGROUND: Protective ventilation may improve outcomes after major surgery. However, in the context of one-lung ventilation, such a strategy is incompletely defined. The authors hypothesized that a putative one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after thoracic surgery. METHODS: The authors merged Society of Thoracic Surgeons Database and Multicenter Perioperative Outcomes Group intraoperative data for lung resection procedures using one-lung ventilation across five institutions from 2012 to 2016. They defined one-lung protective ventilation as the combination of both median tidal volume 5 ml/kg or lower predicted body weight and positive end-expiratory pressure 5 cm H2O or greater. The primary outcome was a composite of 30-day major postoperative pulmonary complications. RESULTS: A total of 3,232 cases were available for analysis. Tidal volumes decreased modestly during the study period (6.7 to 6.0 ml/kg; P < 0.001), and positive end-expiratory pressure increased from 4 to 5 cm H2O (P < 0.001). Despite increasing adoption of a "protective ventilation" strategy (5.7% in 2012 vs. 17.9% in 2016), the prevalence of pulmonary complications did not change significantly (11.4 to 15.7%; P = 0.147). In a propensity score matched cohort (381 matched pairs), protective ventilation (mean tidal volume 6.4 vs. 4.4 ml/kg) was not associated with a reduction in pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32). In an unmatched cohort, the authors were unable to define a specific alternative combination of positive end-expiratory pressure and tidal volume that was associated with decreased risk of pulmonary complications. CONCLUSIONS: In this multicenter retrospective observational analysis of patients undergoing one-lung ventilation during thoracic surgery, the authors did not detect an independent association between a low tidal volume lung-protective ventilation regimen and a composite of postoperative pulmonary complications.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Clinically applicable approach for predicting mechanical ventilation in patients with COVID-19.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) requiring mechanical ventilation have high mortality and resource utilisation. The ability to predict which patients may require mechanical ventilation allows increased acuity of care and targeted interventions to potentially mitigate deterioration. METHODS: We included hospitalised patients with COVID-19 in this single-centre retrospective observational study. Our primary outcome was mechanical ventilation or death within 24 h. As clinical decompensation is more recognisable, but less modifiable, as the prediction window shrinks, we also assessed 4, 8, and 48 h prediction windows. Model features included demographic information, laboratory results, comorbidities, medication administration, and vital signs. We created a Random Forest model, and assessed performance using 10-fold cross-validation. The model was compared with models derived from generalised estimating equations using discrimination. RESULTS: Ninety-three (23%) of 398 patients required mechanical ventilation or died within 14 days of admission. The Random Forest model predicted pending mechanical ventilation with good discrimination (C-statistic=0.858; 95% confidence interval, 0.841-0.874), which is comparable with the discrimination of the generalised estimating equation regression. Vitals sign data including SpO2/FiO2 ratio (Random Forest Feature Importance Z-score=8.56), ventilatory frequency (5.97), and heart rate (5.87) had the highest predictive utility. In our highest-risk cohort, the number of patients needed to identify a single new case was 3.2, and for our second quintile it was 5.0. CONCLUSION: Machine learning techniques can be leveraged to improve the ability to predict which patients with COVID-19 are likely to require mechanical ventilation, identifying unrecognised bellwethers and providing insight into the constellation of accompanying signs of respiratory failure in COVID-19.

Reduced Echocardiographic Inotropy Index after Cardiopulmonary Bypass Is Associated With Complications After Cardiac Surgery: An Institutional Outcomes Study.

OBJECTIVE: Despite advances in echocardiography and hemodynamic monitoring, limited progress has been made to effectively quantify left ventricular function during cardiac surgery. Traditional measures, including left ventricular ejection fraction (LVEF) and cardiac index, remain dependent on loading conditions; more complex measures remain impractical in a dynamic surgical setting. However, the Smith-Madigan Inotropy Index (SMII) and potential-to-kinetic energy ratio (PKR) offer promise as measures calculable during cardiac surgery and potentially predictive of outcomes. Using echocardiographic and hemodynamic monitoring data, the authors aimed to calculate SMII and PKR values after cardiopulmonary bypass and understand associations with postoperative outcomes, adjusting for previously identified risk factors. DESIGN: Observational cohort study. SETTING: Tertiary care academic hospital. PATIENTS: The study comprised 189 elective adult cardiac surgical procedures from 2015-2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was postoperative mortality or organ system complication (stroke, prolonged ventilation, reintubation, cardiac arrest, acute kidney injury, new-onset atrial fibrillation). After adjustment, SMII <0.83 W/m2 independently predicted the primary outcome (adjusted odds ratio 2.19, 95% confidence interval 1.08-4.42); whereas PKR, LVEF, and cardiac index demonstrated no associations. When SMII and PKR were incorporated into a EuroSCORE II risk model, predictive performance improved (net reclassification index improvement 0.457; p = 0.001); whereas a model incorporating LVEF and cardiac index demonstrated no improvement (0.130; p = 0.318). CONCLUSION: The present study demonstrated that SMII, but not PKR, as a measure of cardiac function was associated with major complications. The study's data may guide investigations of more suitable perioperative goal-directed therapies to reduce complications after cardiac surgery.