Michael R. Bronsert

Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery.

Background:Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. Methods:This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. Results:Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. Conclusion:Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.

Statin Prescribing Patterns in a Cohort of Cancer Patients with Poor Prognosis

BACKGROUND There are no evidence-based recommendations for statin continuation or discontinuation near the end of life. However, some expert opinion recommends continuing statins prescribed for secondary versus primary prevention of cardiovascular disease. OBJECTIVES Our aim was to explore statin prescribing patterns in a longitudinal cohort of individuals with life-limiting illness, and to evaluate differences in these patterns based on secondary versus primary prevention of cardiovascular disease. DESIGN AND SETTING This study was a retrospective cohort analysis of 539 persons in an integrated, not-for-profit health maintenance organization (HMO) setting who were receiving statins at diagnosis of a cancer with 0% to 25% predicted 5-year survival. Of the cohort patients, 343 were taking statins for secondary prevention and 196 for primary prevention of cardiovascular disease. Measurements included number and timing of statin refills between diagnosis and date of death, disenrollment, or the end of the observation period. RESULTS Four hundred and ninety-six cohort members died within the observation period. Fifty-eight percent of the secondary prevention and 62% of the primary prevention group had at least one statin refill after diagnosis. There were no significant differences between groups for number of days between diagnosis and last refill, or between last refill and death. Two deaths were attributable to cardiovascular causes in each group. CONCLUSIONS Our retrospective cohort analysis of persons with incident poor-prognosis cancer describes diminished, but persistent statin refills after diagnosis. Neither timing of statin discontinuation nor cardiovascular mortality differed by prescribing indication. There may be an opportunity to reevaluate medication burden in persons taking statins for primary prevention, and it is unclear whether continuing statins prescribed for secondary prevention affects cardiovascular outcomes.

Feasibility and acceptability of a decision aid designed for people facing advanced or terminal illness: a pilot randomized trial

Background  Patients nearing the end of their lives face an array of difficult decisions.

Comparative Effectiveness of Antihypertensive Therapeutic Classes and Treatment Strategies in the Initiation of Therapy in Primary Care Patients: A Distributed Ambulatory Research in Therapeutics Network (DARTNet) Study

Background: Few comparative effectiveness studies of treatment strategies using antihypertensive therapeutic classes in hypertension control have been assessed in a primary care environment. The objectives are to compare the effectiveness of common antihypertensive therapeutic classes initiated as monotherapy and of fixed-dose combinations (FDCs), free-equivalent combinations (FECs), and monotherapy on hypertension control. Methods: This article reports observational comparative effectiveness analyses of data electronically extracted from electronic health records. The study population consisted of 8,676 patients with an incident prescription for an antihypertensive agent of a total of 79,176 patients receiving antihypertensive therapy in 33 geographically diverse primary care clinics. The main measures were reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and rates of attaining goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). Results: There were small, clinically insignificant differences in blood pressure reductions between the monotherapy classes. Higher rates of blood pressure control were obtained when patients were initiated on an angiotensin-converting enzyme inhibitor than a thiazide or thiazide-like diuretic (47.8% vs 39.9%) or a β-blocker versus a thiazide (45.9% vs 39.9%). Patients initiated on FDCs had significantly larger reductions in blood pressure than patients initiated on FECs (−17.3 vs −12.0 mm Hg SBP; −10.1 vs −6.0 mm Hg DBP) or monotherapy (−17.3 vs −13.6 mm Hg SBP; −10.1 vs −7.9 mm Hg DBP). Rates of attaining JNC7 goals also were better for FDCs than FECs (57.2% vs 42.5%) and for FDCs versus monotherapy (57.2% vs 44.9%). Conclusions: Patients initiated on angiotensin-converting enzyme inhibitors and β-blockers had slightly higher rates of blood pressure control. The use of FDCs as initial therapy is more effective in the control of hypertension than monotherapy or FECs.

Surgical Risk Preoperative Assessment System (SURPAS): I. Parsimonious, Clinically Meaningful Groups of Postoperative Complications by Factor Analysis.

Objective:To use factor analysis to cluster the 18 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) perioperative complications into a reproducible, smaller number of clinically meaningful groups of postoperative complications, facilitating and streamlining future study and application in live clinical settings. Background:The ACS NSQIP collects and reports on eighteen 30-day postoperative complications (excluding mortality), which are variably grouped in published analyses using ACS NSQIP data. This hinders comparison between studies of this widely used quality improvement dataset. Methods:Factor analysis was used to develop a series of complication clusters, which were then analyzed to identify a parsimonious, clinically meaningful grouping, using 2,275,240 surgical cases in the ACS NSQIP Participant Use File (PUF), 2005 to 2012. The main outcome measures are reproducible, data-driven, clinically meaningful clusters of complications derived from factor solutions. Results:Factor analysis solutions for 5 to 9 latent factors were examined for their percent of total variance, parsimony, and clinical interpretability. Applying the first 2 of these criteria, we identified the 7-factor solution, which included clusters of pulmonary, infectious, wound disruption, cardiac/transfusion, venous thromboembolic, renal, and neurological complications, as the best solution for parsimony and clinical meaningfulness. Applying the last (clinical interpretability), we combined the wound disruption with the infectious clusters resulting in 6 clusters for future clinical applications. Conclusions:Factor analysis of ACS NSQIP postoperative complication data provides 6 clinically meaningful complication clusters in lieu of 18 postoperative morbidities, which will facilitate comparisons and clinical implementation of studies of postoperative morbidities.

Intermediate-acting Nondepolarizing Neuromuscular Blocking Agents and Risk of Postoperative 30-day Morbidity and Mortality, and Long-term Survival

BACKGROUND: Nondepolarizing neuromuscular blocking drugs (NNMBDs) are commonly used as an adjunct to general anesthesia. Residual blockade is common, but its potential adverse effects are incompletely known. This study was designed to assess the association between NNMBD use with or without neostigmine reversal and postoperative morbidity and mortality. METHODS: This is a retrospective observational study of 11,355 adult patients undergoing general anesthesia for noncardiac surgery at 5 Veterans Health Administration (VA) hospitals. Of those, 8984 received NNMBDs, and 7047 received reversal with neostigmine. The primary outcome was a composite of respiratory complications (failure to wean from the ventilator, reintubation, or pneumonia), which was “yes” if a patient had any of the 3 component events and “no” if they had none. Secondary outcomes were nonrespiratory complications, 30-day and long-term all-cause mortality. We adjusted for differences in patient risk using propensity matched (PM) followed by assessment of the association of interest by logistic regression between the matched pairs as our primary analysis and multivariable logistic regression (MLR) as a sensitivity analysis. RESULTS: Our primary aim was to assess the adverse outcomes in the patients who had received NNMBDs with and without neostigmine. Administration of an NNMBD without neostigmine reversal compared with NNMBD with neostigmine reversal was associated with increased odds of respiratory complications (PM odds ratio [OR], 1.75 [95% confidence interval [CI], 1.23–2.50]; MLR OR, 1.71 [CI, 1.24–2.37]) and a marginal increase in 30-day mortality (PM OR, 1.83 [CI, 0.99–3.37]; MLR OR, 1.78 [CI, 1.02–3.13]). However, there were no statistically significant associations with nonrespiratory complications or long-term mortality. Patients who were administered an NNMBD followed by neostigmine had no differences in outcomes compared with patients who had general anesthesia without an NNMBD. CONCLUSIONS: The use of NNMBDs without neostigmine reversal was associated with increased odds of our composite respiratory outcome compared with patients reversed with neostigmine. Based on these data, we conclude that reversal of NNMBDs should become a standard practice if extubation is planned.

Surgical Risk Preoperative Assessment System (SURPAS): II. Parsimonious Risk Models for Postoperative Adverse Outcomes Addressing Need for Laboratory Variables and Surgeon Specialty-specific Models.

Objective: To develop parsimonious prediction models for postoperative mortality, overall morbidity, and 6 complication clusters applicable to a broad range of surgical operations in adult patients. Summary Background Data: Quantitative risk assessment tools are not routinely used for preoperative patient assessment, shared decision making, informed consent, and preoperative patient optimization, likely due in part to the burden of data collection and the complexity of incorporation into routine surgical practice. Methods: Multivariable forward selection stepwise logistic regression analyses were used to develop predictive models for 30-day mortality, overall morbidity, and 6 postoperative complication clusters, using 40 preoperative variables from 2,275,240 surgical cases in the American College of Surgeons National Surgical Quality Improvement Program data set, 2005 to 2012. For the mortality and overall morbidity outcomes, prediction models were compared with and without preoperative laboratory variables, and generic models (based on all of the data from 9 surgical specialties) were compared with specialty-specific models. In each model, the cumulative c-index was used to examine the contribution of each added predictor variable. C-indexes, Hosmer-Lemeshow analyses, and Brier scores were used to compare discrimination and calibration between models. Results: For the mortality and overall morbidity outcomes, the prediction models without the preoperative laboratory variables performed as well as the models with the laboratory variables, and the generic models performed as well as the specialty-specific models. The c-indexes were 0.938 for mortality, 0.810 for overall morbidity, and for the 6 complication clusters ranged from 0.757 for infectious to 0.897 for pulmonary complications. Across the 8 prediction models, the first 7 to 11 variables entered accounted for at least 99% of the c-index of the full model (using up to 28 nonlaboratory predictor variables). Conclusions: Our results suggest that it will be possible to develop parsimonious models to predict 8 important postoperative outcomes for a broad surgical population, without the need for surgeon specialty-specific models or inclusion of laboratory variables.

Surgical Risk Preoperative Assessment System (SURPAS): III. Accurate Preoperative Prediction of 8 Adverse Outcomes Using 8 Predictor Variables.

Objective: To develop accurate preoperative risk prediction models for multiple adverse postoperative outcomes applicable to a broad surgical population using a parsimonious common set of risk variables and outcomes. Summary Background Data: Currently, preoperative assessment of surgical risk is largely based on subjective clinician experience. We propose a paradigm shift from the current postoperative risk adjustment for cross-hospital comparison to patient-centered quantitative risk assessment during the preoperative evaluation. Methods: We identify the most common and important predictor variables of postoperative mortality, overall morbidity, and 6 complication clusters from previously published prediction analyses that used forward selection stepwise logistic regression. We then refit the prediction models using only the 8 most common and important predictor variables, and compare the discrimination and calibration of these models to the original full-variable models using the c-index, Hosmer-Lemeshow analysis, and Brier scores. Results: Accurate risk models for 30-day outcomes of mortality, overall morbidity, and 6 clusters of complications were developed using a set of 8 preoperative risk variables. C-indexes of the 8 variable models are between 97.9% and 99.2% of those of the full models containing up to 28 variables, indicating excellent discrimination using fewer predictor variables. Hosmer-Lemeshow analyses showed observed to expected event rates to be nearly identical between parsimonious models and full models, both showing good calibration. Conclusions: Accurate preoperative risk assessment of postoperative mortality, overall morbidity, and 6 complication clusters in a broad surgical population can be achieved with as few as 8 preoperative predictor variables, improving feasibility of routine preoperative risk assessment for surgical patients.

Bringing Quantitative Risk Assessment Closer to the Patient and Surgeon: A Novel Approach to Improve Outcomes.

Two recently published studies raise serious questions about the effectiveness of the current use of risk-adjusted outcomes comparisons between hospitals in reducing perioperative mortality, morbidity, and costs. In this Perspectives article, we provide historical background, discuss the limitations, and offer a new paradigm for the application of quantitative risk assessment to the care of the surgical patient.

Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer

Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment mortality may influence the comparative effectiveness of surgery and stereotactic body radiotherapy (SBRT), with implications for shared decision making among high-risk surgical candidates. We analyzed early mortality after these interventions using the National Cancer Database. Patients and Methods We abstracted patients with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were calculated and compared using Cox regression and propensity score-matched analyses. Results We identified 76,623 patients who underwent surgery (78% lobectomy, 20% sublobar resection, 2% pneumonectomy) and 8,216 patients who received SBRT. In the unmatched cohort, mortality rates were moderately increased with surgery versus SBRT (30 days, 2.07% v 0.73% [absolute difference (Δ), 1.34%]; P < .001; 90 days, 3.59% v 2.93% [Δ, 0.66%]; P < .001). Among the 27,200 propensity score-matched patients, these differences increased (30 days, 2.41% v 0.79% [Δ, 1.62%]; P < .001; 90 days, 4.23% v 2.82% [Δ, 1.41%]; P < .001). Differences in mortality between surgery and SBRT increased with age, with interaction P < .001 at both 30 days and 90 days (71 to 75 years old: 30-day Δ, 1.87%; 90-day Δ, 2.02%; 76 to 80 years old: 30-day Δ, 2.80%; 90-day Δ, 2.59%; > 80 years old: 30-day Δ, 3.03%; 90-day Δ, 3.67%; all P ≤ .001). Compared with SBRT, surgical mortality rates were higher with increased extent of resection (30-day and 90-day multivariate hazard ratio for mortality: sublobar resection, 2.85 and 1.37; lobectomy, 3.65 and 1.60; pneumonectomy, 14.5 and 5.66; all P < 0.001). Conclusion Differences in 30- and 90-day post-treatment mortality between surgery and SBRT increased as a function of age, with the largest differences in favor of SBRT observed among patients older than 70 years. These representative mortality data may inform shared decision making among patients with early-stage NSCLC who are eligible for both interventions.