Health Outcomes with and without Use of Inotropic Therapy in Cardiac Surgery Results of a Propensity Score–matched Analysis Dorthe Viemose Nielsen, M.D., Malene Kærslund Hansen, M.B.B.S., Søren Paaske Johnsen, M.D., Ph.D., Mads Hansen, M.D., Karsten Hindsholm, M.D., H.D., Carl-Johan Jakobsen, M.D. This article has been selected for the ANESTHESIOLOGY CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue. Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/120/5/1098/265993/20140500_0-00017.pdf by guest on 29 September 2021 ABSTRACT Background: Inotropes used to obtain short-term hemodynamic benefits in cardiac surgery may carry a risk of increased myocardial ischemia and adverse outcomes. This study investigated the association between intra- and postoperative use of inotropes and mortality and postoperative complications. Methods: A historic cohort study using prospective data from the Western Denmark Heart Registry on 6,005 consecutive car- diac surgery cases from three university hospitals. Propensity matching on pre- and intraoperative variables was used to identify a subgroup of patients receiving inotropic therapy (n = 1,170) versus comparable nonreceivers (n = 1,170) for outcome analysis. Results: Two thousand ninety-seven patients (35%) received inotropic therapy; 3,908 (65%) did not receive any inotropic or vasopressor support perioperatively. Among propensity-matched cohort including 2,340 patients 30-day mortality was 3.2% and 1-yr mortality was 7.6%. In the matched cohort, patients exposed to inotropes had a higher 30-day mortality (adjusted hazards ratio, 3.7; 95% CI, 2.1 to 6.5) as well as a higher 1-yr mortality rate (adjusted hazards ratio, 2.5; 95% CI, 1.8 to 3.5) compared with nonreceivers. Among propensity-matched, the following absolute events rates were observed: myocardial infarction 2.4%, stroke 2.8%, arrhythmia 35%, and renal replacement therapy 23.9%. Inotropic therapy was independently associated with postoperative myocardial infarction (adjusted odds ratio, 2.1; 95% CI, 1.4 to 3.0), stroke (adjusted odds ratio, 2.4; 95% CI, 1.4 to 4.3), and renal replacement therapy (adjusted odds ratio, 7.9; 95% CI, 3.8 to 16.4). Conclusion: Use of intra- and postoperative inotropes was associated with increased mortality and major postoperative mor- bidity. (ANESTHESIOLOGY 2014; 120:1098-108) OW cardiac output syndrome is a common complica- What We Already Know about This Topic Ltion in cardiac surgery patients1 and inotropic support is frequently initiated to improve postbypass ventricular func- • Previous studies have suggested that inotropic therapy after cardiac surgery may be associated with increased morbidity tion. Inotropes may improve hemodynamics, but there is a but the impact of these drugs on overall survival is unknown. potential risk for increased myocardial oxygen consumption resulting in cardiac ischemia and potential damage of hiber- What This Article Tells Us That Is New nating but viable myocardium, particularly in patients with • In an observational study of 6,005 patients using propensity score matching, perioperative use of inotropes was indepen- ischemic heart disease. The clinical efficacy of perioperative dently associated with increased 1-yr mortality (adjusted haz- inotropes has been assessed in randomized clinical trials pri- ard ratio of 2.5). The results indicate that the beneficial effects of current inotropic drugs may be limited to only short-term marily in relation to hemodynamic endpoints. Most previous hemodynamic improvement in patients after cardiac surgery. randomized trials have not been powered to study the effi- cacy in relation to “hard” clinical outcomes, including cardiac morbidity and mortality.2 Use of inotropes has been associ- However, the study sample was too small to investigate mor- ated with adverse clinical outcomes in a few observational tality, and the association between inotrope exposure and studies3–5: In a sentinel study by Fellahi et al.,3 use of dobuta- short- and long-term mortality thus remained unclear. At mine was associated with increased postoperative morbidity. present, there is only limited data to guide practice patterns This article is featured in “This Month in Anesthesiology,” page 1A. Corresponding article on page 1067. Submitted for publication January 10, 2013. Accepted for publication January 22, 2014. From the Department of Anesthesiology and Intensive Care (D.V.N., C.-J.J.) and Department of Clinical Epidemiology (M.K.H., S.P.J.), Aarhus University Hospital, Aarhus, Denmark; Department of Anesthesia and Intensive Care, Odense University Hospital, Odense, Denmark (M.H.); and Department of Anesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark (K.H.). Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2014; 120:1098-108 Anesthesiology, V 120 • No 5 1098 May 2014 PERIOPERATIVE MEDICINE and evidence-based use of inotropes in cardiac surgery. This on patient history, type of procedure, intra- and postopera- has resulted in an ongoing debate on the value or harm asso- tive management including inotropic therapy and in-hospital ciated with use of inotropes in cardiac surgery.6 Thus, clinical complications. The registry provides the Danish Heart Regis- practice in inotrope management is highly dependent on the try (DHR) with data on all consecutive patients undergoing individual center and physician preferences.7–10 cardiac surgery in the western part of Denmark. Data quality The aim of the current study was to investigate whether is ensured using automatic validation rules at data entry com- use of inotropes was associated with short- and long-term bined with systematic validation procedures and random spot- mortality and an increased incidence of postoperative checks of data after entry. Coverage of the DHR is routinely complications such as myocardial infarction (MI), stroke, evaluated by comparing with data from the Danish National arrhythmia, and renal failure in patients undergoing cardiac Patient Register including data on all procedures performed in surgery. To obtain a sufficient sample size to investigate the both private and public hospitals in Denmark. These analyses Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/120/5/1098/265993/20140500_0-00017.pdf by guest on 29 September 2021 association between perioperative inotropic therapy and have shown a high coverage of the DHR, with greater than 95% these rare adverse clinical outcomes, a historical cohort study reporting of all CABG procedures.11 Random samples of the was conducted using data from a population-based clinical data reported to the DHR from WDHR have been validated cardiac registry. A propensity score–matched analysis was against the local patient files (both electronic and paper files). used to minimize the risk of selection bias and confounding. The main finding was that the data in the WDHR were correct with κ values between 0.91 to 1 (DHR—Annual Report 2007, Materials and Methods University of Southern Denmark: The Board of Danish Heart Patient Population Registry and National Institute of Public Health, 2008), but This study was a multicenter, historical cohort study involv- there was a high proportion of missing data especially concern- 11 ing 6,005 consecutive adult patients undergoing cardiac sur- ing patient history and late complications. Missing data have gery with or without cardiopulmonary bypass (CPB) at three been retrieved later from local patient files (both electronic and Danish university cardiac centers (Odense University Hospi- paper) and overall missing data constituted less than 0.3 and tal, Aarhus University Hospital, and Aalborg University Hos- 0% for outcome data. The WDHR has proven a valuable data pital) from April 1, 2006 to December 31, 2009. Patients source in research, providing ongoing longitudinal registration 12 met the following inclusion criteria: Coronary artery bypass of detailed data on patients and procedures. grafting (CABG) or CABG with valve surgery or combined with other procedures or surgery involving the thoracic aorta. Perioperative Management Patients were excluded if they had undergone procedures All preoperative cardiac medication was continued until only offered at one of the participating cardiac centers such as the morning of surgery except for angiotensin-converting heart transplantation, pulmonary thrombendarterectomy, or enzyme inhibitors, aspirin, and thrombocyte function percutaneous valve replacement. Patients dying during sur- inhibitors. β-Blocking agents were continued on the day of gery and patients regarded inoperable after sternotomy were surgery in chronically treated patients. All patients received excluded. Patients who underwent more than one cardiac standard premedication in the form of a benzodiazepine 60 surgical procedure during the study period were included to 90 min before surgery. Cardiac centers B: Standard total with only the first surgical procedure to ensure independency. intravenous anesthesia using propofol 40 to 80 μg/kg/min, In case of missing data on procedure type, CPB, or exposure sufentanil 3 to 5 μg/kg, and pancuronium. Cardiac centers A to inotropes patients were excluded (fig. 1). and C: anesthesia induction with midazolam or pentobarbi- Study start was determined as the time when data on ino- tal together with fentanyl 0.01 to 0.025 mg/kg or sufentanil trope treatment were included