Downloaded from http://journals.lww.com/anesthesia-analgesia by BhDMf5ePHKbH4TTImqenVLIlg0cBmue4kY0n3YfC70uQ/8LyDH1kTNDIIg41PVF1EcdOWEPPR5g= on 08/20/2020 Copyright © 2020 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited. 822 www.anesthesia-analgesia.org September 2020 • Volume 131 • Number 3 DOI: 10.1213/ANE.0000000000005033 E ORIGINAL CLINICAL RESEARCH REPORT GLOSSARY AIC = Akaike Information Criteria; ASA = American Society of Anesthesiologists; AUC = area under the curve; BALANCED = A Prospective, Randomized Clinical Trial of 2 Levels of Anesthetic Depth on Patient Outcome After Major Surgery; CCS = Clinical Classifcations Software; CI = confdence interval; ENIGMA-II = Nitrous oxide and perioperative cardiac morbidity-II; HCUP = Healthcare Cost and Utilization Project; ICD-9 = International Classification of Diseases, Ninth Revision; MAP = mean arterial pressure; MINS = myocardial injury after noncardiac surgery; PACE = Preoperative Assessment Clearance Education; POD = postoperative day; POISE-2 = Perioperative Ischemia Evaluation-2; SD = standard deviation; TWA = time-weighted average; VISION = Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study KEY POINTS • Question: Is postoperative pain associated with myocardial injury after noncardiac surgery? • Findings: In this retrospective cohort analysis of 2892 adults who had noncardiac surgery, higher time-weighted average pain score was associated with increased odds (estimated odds ratio for 1-unit increase in pain scores were 1.22; 95% confidence interval [CI], 1.09–1.38; P < .001) of myocardial injury. • Meaning: Effective postoperative analgesia may reduce postoperative cardiovascular risk. BACKGROUND: Uncontrolled pain after noncardiac surgery activates the sympathetic ner- vous system, which causes tachycardia, hypertension, and increased cardiac contractility—all of which may increase myocardial oxygen demand. We therefore determined whether time- weighted average pain scores over the initial 72 postoperative hours are associated with myo- cardial injury after noncardiac surgery (MINS). METHODS: We conducted a retrospective cohort analysis of adults with routine postoperative troponin monitoring after noncardiac surgery under general, regional, or combined anesthesia at tertiary level centers in Cleveland from January 2012 to December 2015. Time-weighted aver- age pain scores were calculated from all the available pain scores, typically at 4-hour intervals, until a troponin elevation was detected. MINS was defned as peak troponin T concentrations exceeding 0.03 ng/mL within 72 hours after surgery. We used a generalized linear mixed model to assess the association between pain and MINS with 3 hospitals as clusters, adjusting for potential confounders. RESULTS: Among 2892 eligible patients, 4.5% had myocardial injury within 72 hours after surgery. Higher time-weighted average pain scores were associated with increased hazard of myocardial injury. The estimated hazard ratio for a 1-unit increase in pain score was 1.12 (95% confdence interval [CI], 1.02–1.22; P = .013), adjusting for confounding variables. CONCLUSIONS: Among patients undergoing noncardiac surgery, time-weighted average pain scores within 72 hours after surgery were signifcantly associated with myocardial injury. (Anesth Analg 2020;131:822–9) Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery Alparslan Turan, MD,*† Steve Leung, MD,*‡ Gausan Ratna Bajracharya, MD,*§ Rovnat Babazade, MD,*‖ Theresa Barnes, MD,§ Yehoshua Nadav Schacham, MD,*¶ Guangmei Mao, PhD,*# Nicole Zimmerman, MS,*# Kurt Ruetzler, MD,*† Kamal Maheshwari, MD,*† Wael Ali Sakr Esa, MD,*† and Daniel I. Sessler, MD* From the *Department of Outcomes Research and †Department of General Anesthesia, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio; ‡Department of Radiology, Metro Health, Cleveland, Ohio; §Department of General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio; ‖Department of Anesthesiology, University of Texas Medical Branch at Galveston, Galveston, Texas; ¶Department of Internal Medicine, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel; and #Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio. Cardiovascular Pathophysiology and Outcomes Accepted for publication May 28, 2020. Funding: None. The authors declare no conficts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org). Reprints will not be available from the authors. Address correspondence to Alparslan Turan, MD, Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, P-77, Cleveland, OH 44195. Address e-mail to turana@ccf.org. Copyright © 2020 International Anesthesia Research Society