POLYPHARMACY: A FLAG FOR HIGH-RISK EMERGENCY SURGERY PATIENTS Melissa S Shears, MD1; Daniel I McIsaac, MD, MPH, FRCPC2;James S Green MBBS, FRCA1;Xiaming Wang, PhD4; Rachel G Khadaroo, MD, PhD, FRCSC5,6 1Department of Anesthesiology and Pain Medicine, University of Alberta, 2Department of Anesthesiology and Pain Medicine, University of Ottawa, 3School of Epidemiology and Public Health, University of Ottawa, 4Aberhart Centre, Research Facilitation, Alberta Health Services, 5Department of Surgery, University of Alberta, 6Department of Critical Care Medicine, University of Alberta

INTRODUCTION RESULTS RESULTS

• Older (≥65 years) population increasing require emergency general Table 3: Multivariable Outcome Analysis surgery (EGS) Outcomes Relative Association (95% CI) p value 30-day survival HR 2.70 (1.07 to 6.80) p=0.03 • Complexity of perioperative screening tools/risk calculators often limits use 6-month survival HR 2.07 (1.14 to 3.75) p=0.02 OR 2.05 (1.35 to 3.10) p<0.001 Readmission OR 1.41 (0.99 to 2.00) p=0.05 Postoperative LOS RR 1.20 (1.05 to 1.36) p=0.01 Table 1: Population Demographics Covariates include age, sex, BMI, race, surgery type. LOS = length of stay. HR = Hazard ratio. OR = Odds ratio. RR = Relative risk. No Total Polypharmacy Figure 1: Receiver Operating Curve (ROC) • Polypharmacy is associated with an increase risk of adverse outcomes Baseline Parameter Polypharmacy p value (N=684) (N = 321) Modeling for Survival (N = 363) A B • The Polypharmacy Score (CPS) was developed to quantify Age (mean, SD) 75.7 (7.6) 76.8 (7.7) 74.7 (7.5) <0.001 • Comparing c-indices for Female (N, %) 327 (47.8%) 132 (41.1%) 195 (53.7%) 0.001 the magnitude of both chronic disease and burden BMI (mean, SD) 27.1 (5.9) 27.5 (6.1) 26.7 (5.8) 0.03 survival between CCI (median, IQR) 1.0 (0.0-1.0) 1.0 (1.0-2.0) 0.0 (0.0-1.0) <0.001 Comorbidities (N, %) Polypharmacy and CPS 122 (17.8%) 100 (31.2%) 22 (6.1%) <0.001 models  no evidence of Congestive Heart Failure 32 (4.7%) 27 (8.4%) 5 (1.4%) <0.001 Peripheral Vascular Disease 21 (3.1%) 16 (5.0%) 5 (1.4%) 0.01 superiority (Figure 1) Cerebral Vascular Accident 53 (7.7%) 34 (10.6%) 19 (5.2%) 0.01 C D or Transient Ischemic Attack Dementia 22 (3.2%) 14 (4.4%) 8 (2.2%) 0.11 COPD 96 (14.0%) 72 (22.4%) 24 (6.6%) <0.001 OBJECTIVES Connective tissue disease 2 (0.3%) 2 (0.6%) 0 (0.0%) 0.13 Peptic ulcer disease 38 (5.6%) 25 (7.8%) 13 (3.6%) 0.02 Liver disease 16 (2.3%) 10 (3.1%) 6 (1.7%) 0.21 • To determine the impact of pre-hospital polypharmacy on postoperative mellitus 151 (22.1%) 113 (35.2%) 38 (10.5%) <0.001 Survival at 30-days (top) and 6-months (bottom) categorized by outcomes in older patients (≥65 years) undergoing EGS Hemiplegia 2 (0.3%) 0 (0.0%) 2 (0.6%) 0.18 Polypharmacy (left) and CPS (right). C-index values are as follows: A) Chronic Kidney Disease 59 (8.6%) 42 (13.1%) 17 (4.7%) <0.001 0.852, B) 0.807, C) 0.807, D) 0.811 Solid tumor 148 (21.6%) 78 (24.3%) 70 (19.3%) 0.11 All models were adjusted with age, sex, BMI, race, and surgery type • To compare the predictive value of polypharmacy alone to the CPS Leukemia 10 (1.5%) 4 (1.2%) 6 (1.7%) 0.66 Lymphoma 6 (0.9%) 3 (0.9%) 3 (0.8%) 0.88 AIDS-HIV 1 (0.1%) 0 (0.0%) 1 (0.3%) 0.35 (mean, SD) 4.7 (3.4) 7.6 (2.5) 2.1 (1.4) <0.001 DISCUSSION PATIENTS AND METHODS ASA score (median, IQR) 3.0 (2.0-3.0) 3.0 (3.0-3.0) 2.0 (2.0-3.0) <0.001 ASA score category (N, %) <0.001 1 21 (3.1%) 2 (0.6%) 19 (5.2%) • Polypharmacy is common and associated with adverse outcomes 2 274 (40.1%) 74 (23.1%) 200 (55.1%) 3 297 (43.4%) 179 (55.8%) 118 (32.5%) • Observational analysis, causality cannot be determined 4 83 (12.1%) 61 (19.0%) 22 (6.1%) 5 6 (0.9%) 4 (1.2%) 2 (0.6%) 6 3 (0.4%) 1 (0.3%) 2 (0.6%) • Generalizability limited in patients with severe frailty and terminal illness CFS Score (median, IQR) 3.0 (3.0-4.0) 4.0 (3.0-5.0) 3.0 (2.0-4.0) <0.001

SD = standard deviation. IQR = interquartile range. BMI = body mass index. CCI = Charlson Comorbidity Index. COPD = • Future directions aimed to compare polypharmacy with frailty scores chronic obstructive pulmonary disease. AIDS = acquired immunodeficiency syndrome. HIV = human immunodeficiency virus. ASA = American Society of Anesthesiologists. CFS = Clinical Frailty Scale. *For patients receiving multicomponent surgery, more than one procedure type was assigned. CONCLUSIONS

• Screening for polypharmacy is a simple, objective, and pragmatic approach to identify high-risk older EGS patients

• The CPS may not add any additional prognostic benefit over screening for polypharmacy alone Table 2: Unadjusted Outcome Analysis Total Polypharmacy No Polypharmacy • Polypharmacy may be useful in guiding preoperative discussion, as well Outcomes p value (N=684) (N = 321) (N = 363) as planning postoperative disposition 30-day Mortality 28 (4.1%) 22 (6.9%) 6 (1.7%) <0.001 6-month Mortality 53 (7.7%) 37 (11.5%) 16 (4.4%) <0.001 Postoperative delirium 135 (19.7%) 87 (27.1%) 48 (13.2%) <0.001 Postoperative LOS 6.0 (2.0-10.0) 7.0 (3.0-13.0) 5.0 (2.0-9.0) <0.001 • Elder Friendly Approaches to the Surgical Environment (EASE) was (median (IQR)) ACKNOWLEDGEMENTS conducted at two tertiary care hospitals in Alberta, 2014-2017 Discharge status <0.001 Discharged home 573 (83.8%) 242 (75.4%) 331 (91.2%) Discharged to 81 (11.8%) 55 (17.1%) 26 (7.2%) • Outcomes were estimated using multivariable analysis, adjusting for facility • Department of Surgery, University of Alberta Hospital (Edmonton, AB) covariates. A concordance index (c-index) analysis was conducted to Others 30 (4.4%) 24 (7.5%) 6 (1.7%) Readmission 174 (25.4%) 95 (29.6%) 79 (21.8%) 0.02 compare discrimination of polypharmacy vs CPS models on survival Data presented as N (%). LOS = length of stay