American Society of Critical Care Anesthesiologists Section Editor: Michael J. Murray Dopexamine Has No Additional Benefit in High-Risk Patients Receiving Goal-Directed Fluid Therapy Undergoing Major Abdominal Surgery Simon J. Davies, MB ChB, FRCA, David Yates, MB ChB, FRCA, and R. Jonathan T. Wilson, MB ChB, FRCA BACKGROUND: Dopexamine has been shown to reduce both mortality and morbidity in major surgery when it is used as part of a protocol to increase oxygen delivery in the perioperative period. A European multicenter study has examined the use of dopexamine in patients undergoing major abdominal surgery, showing a trend toward improved survival and reduced 06/03/2019 on BhDMf5ePHKbH4TTImqenVDiEotxSR1UH6qgZ0KTpZGnXi4j8RvKUYsPCtYLlyHBK+E0J1A+diWw= by http://journals.lww.com/anesthesia-analgesia from Downloaded complications in high-risk patients when receiving low-dose dopexamine (0.5 ␮g ⅐ kgϪ1 ⅐ minϪ1). A reduced oxygen uptake at the anaerobic threshold (AT) has been shown to confer a significant Downloaded risk of mortality in patients undergoing major abdominal surgery and allows objective identifica- tion of a high-risk operative group. In this study, we assessed the effects of low-dose dopexamine from on morbidity after major abdominal surgery in patients who were at increased risk by virtue of a http://journals.lww.com/anesthesia-analgesia reduced AT. METHODS: Patients undergoing elective major colorectal or urological surgery who had an AT of Ͻ11 mL ⅐ kgϪ1 ⅐ minϪ1 or an AT of 11 to 14 mL ⅐ kgϪ1 ⅐ minϪ1 with a history of ischemic heart disease were recruited. Before surgery, a radial arterial cannula was placed and attached to an Edwards Lifesciences FloTrac/Vigileo™ system for measuring cardiac output. Patients were given a 250-mL bolus of Voluvenா (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride) until the stroke volume no longer increased by 10%, then received either dopexamine (0.5 ␮g ⅐ kgϪ1 ⅐ minϪ1) or saline 0.9% for 24 hours. During surgery, fluid boluses of Voluven were given if the stroke volume variation was by Ͼ10%. No crystalloid was given during surgery. A standardized postoperative fluid regime with BhDMf5ePHKbH4TTImqenVDiEotxSR1UH6qgZ0KTpZGnXi4j8RvKUYsPCtYLlyHBK+E0J1A+diWw= Hartmann solution was prescribed at 1.5 mL ⅐ kgϪ1 ⅐ hϪ1 for 24 hours. The primary outcome measure was postoperative morbidity measured by the Postoperative Morbidity Survey. RESULTS: One hundred twenty-four patients were recruited over a 23-month period. The incidence of morbidity as measured by the Postoperative Morbidity Survey on day 5 was 55% in the control group versus 47% in the dopexamine group (P ϭ 0.14). There was no significant reduction in morbidity on any measured postoperative day. Complication rates, mortality, and hospital length of stay were similar between the 2 groups; however, administration of dopexamine was associated with earlier return of tolerating an enteral diet. CONCLUSION: With the effective use of goal-directed fluid therapy in elective surgical patients, the routine use of dopexamine does not confer an additional clinical benefit. (Anesth Analg 2011;112:130–8) opexamine has been shown to reduce both mortal- A European multicenter study has examined the use of ity and morbidity in major surgery when it is used dopexamine in patients undergoing major abdominal sur- Das part of a protocol to increase oxygen delivery gery.3 The majority of patients were deemed high risk 1,2 (DO2) in the perioperative period. Further interest has based on the nature of their surgery alone, and no survival on 06/03/2019 been generated from these trials, because the use of dopex- advantage was seen; however, those who underwent emer- amine was associated with reductions in postoperative gency surgery, or had Ͼ1 high-risk criterion showed a complications, mortality, and an associated decrease in tendency toward improved outcomes when receiving low- Ϫ Ϫ hospital length of stay (LOS) that was specific to its use, yet dose dopexamine (0.5 ␮g ⅐ kg 1 ⅐ min 1). not explained by the increase of DO2. Many criteria have been used to attempt to define a high-risk population and one of the most widely used is the Shoemaker criteria,4 later simplified by Boyd et al.1 These From the Department of Anaesthesia, York Teaching Hospitals NHS Foun- dation Trust, North Yorkshire, United Kingdom. criteria contain a considerable subjective element, and Accepted for publication August 29, 2010. many are either not applicable to an elective population, or Supported by the Association of Anaesthetists of Great Britain and Ireland; occur intraoperatively and are therefore not useful as preop- Elsie May Sykes Fund; and York Hospitals NHS Foundation Trust. erative identifiers of a high-risk population, in which subse- The authors report no conflicts of interest. quent intervention may improve outcome. Additional scoring Reprints will not be available from the author. systems have been developed to specifically predict cardiac Address correspondence to Simon J. Davies, MB ChB, FRCA, Department of risk, but these predict only the incidence of cardiac events and Anaesthesia, York Hospitals NHS Foundation Trust, Wigginton Rd., York, 5 North Yorkshire, UK, YO31 8HE. Address e-mail to [email protected]. not perioperative mortality or complications as a whole. Copyright © 2010 International Anesthesia Research Society Functional capacity has been shown to be a good DOI: 10.1213/ANE.0b013e3181fcea71 predictor of outcome after both abdominal and thoracic 130 www.anesthesia-analgesia.org January 2011 • Volume 112 • Number 1 surgery.6–10 Cardiopulmonary exercise testing (CPET) pro- stenosis Ͼ50% of the vessel diameter. Electrocardiogram vides an objective measurement of cardiorespiratory fit- changes deemed significant during CPET were defined as ST ness, and hence functional capacity. A reduced oxygen depression of Ͼ2 mm from baseline in 2 adjacent leads, uptake at the anaerobic threshold (AT) has been shown to ventricular tachycardia, or new onset atrial fibrillation. confer a significant risk of mortality in patients undergoing We excluded patients younger than 55 years without Ϫ Ϫ major abdominal surgery. If AT is Ͻ11 mL ⅐ kg 1 ⅐ min 1 or comorbidities; those with hypertrophic cardiomyopathy, Ϫ Ϫ between 11 and 14 mL ⅐ kg 1 ⅐ min 1 with ischemic heart significant aortic stenosis, a low preoperative platelet count disease (IHD), patients are at an increased risk of compli- (Ͻ150 ϫ 109/L), pheochromocytoma, or monoamine oxi- cations after surgery.11 A recent large cohort study has dase inhibitor use within the last 14 days; or those deemed shown that in patients undergoing nonvascular major unable to give informed consent. abdominal surgery, a reduced AT is associated with a Significant comorbidities were recorded and included a 6-fold relative risk of hospital mortality.12 CPET can there- history of IHD as defined above: prior coronary artery fore identify a higher-risk surgical population in whom any bypass graft surgery, atrial fibrillation, hypertension re- potential benefits of dopexamine may be seen. quiring treatment with Ն1 antihypertensive medication, A meta-regression analysis of data from all the available peripheral vascular disease (intermittent claudication dopexamine trials in major abdominal surgery has shown a known to be caused by atherosclerotic disease, a history of statistically significant improvement both in mortality and lower extremity arterial bypass surgery, or angiographic hospital LOS for low-dose dopexamine use (Յ1 evidence demonstrating Ͼ70% stenosis), diabetes requiring Ϫ Ϫ ␮g ⅐ kg 1 ⅐ min 1)13; however, a meta-analysis of the same current treatment either by insulin or oral hypoglycemics, data showed no overall benefit,14 leaving an uncertainty as renal insufficiency with a preoperative creatinine of Ͼ150 Ϫ to whether dopexamine confers a survival advantage or ␮mol ⅐ L 1, cerebrovascular disease (history and/or radio- reduction in perioperative complications. The reason for logical evidence of cerebral infarction or hemorrhage, or a this difference in outcomes in what is essentially the same clinical history of transient ischemic attack), and chronic data lies within the chosen methods of analysis. Gopal et obstructive pulmonary disease (clinical history and docu- al.14 chose to express the data as more conservative relative mented forced expiratory volume in 1 second/forced vital risk, whereas Pearse et al.,13 using a meta-regression anal- capacity Ͻ70%). ysis, were confined to using odds ratio.15 Odds ratio can potentially exaggerate treatment effects when the event rate Protocol is high. Caution is required when interpreting results when On arrival in the theater suite, IV cannulae were inserted Ͻ Ͼ the odds ratio is 0.5, and the event rate is 10% as in the into forearm veins for administration of fluid and study 16 dopexamine trials. This may be why such dichotomous drug. An arterial cannula was placed into a radial artery for conclusions were reached. Therefore, the aim of this study continuous arterial blood pressure measurement, and con- was to clarify the role of dopexamine by assessing whether nected to an Edwards Lifesciences FloTrac/Vigileo™ sys- a low fixed dose reduces morbidity after major abdominal tem (Edwards Lifesciences, Irvine, CA; software version surgery in patients who are at increased risk by virtue of a 1.10) for measuring stroke volume and preload responsive- reduced AT. ness via stroke volume variation (SVV). Baseline measures of hemodynamic variables were re- METHODS corded before induction of anesthesia (heart rate, stroke The protocol was approved by an NHS research ethics volume, arterial blood pressure), and an arterial blood committee and sponsored by York Teaching Hospitals sample was taken for analysis. Patients were then given a NHS Foundation Trust. Clinical trial authorization was 250-mL bolus of colloid (Voluven௡; Fresenius Kabi, Bad obtained from the Medicines and Health Regulation Au- Homburg, Germany). If the stroke volume increased 10% thority. The trial was placed on the ISRCTN register before or more above baseline, then the bolus was repeated until patient recruitment (ISRCTN33549216, accepted August 8, no further increases in stroke volume were seen.