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© 2003 European Association of Cardio-Thoracic Surgery
Cardiovascular function during the first 24 hours after off pump coronary artery bypass grafting–a prospective, randomized study
a Department of Thoracic Surgery, Karolinska Hospital, Stockholm 171 76, Sweden
* Corresponding author. Tel: +46-8-51770000; fax: +46-8-322701 Received December 23, 2002; received in revised form May 21, 2003; accepted May 31, 2003
We hypothetized that cardiovascular performance during the first 24 postoperative hours would be better in patients after off pump coronary artery bypass grafting compared to conventional on pump surgery. Fifty-nine patients were randomized to on or off pump coronary artery bypass grafting. Hemodynamic parameters, including cardiac index and systemic vascular resistance index were measured before and at 1, 4, and 20 h after surgery. Troponin T and creatine kinase-MB (CK-MB) were measured before and at 1, 6, and 20 h after surgery. There was no difference in age, sex, ejection fraction or number of grafts between groups. Cardiac index was higher (  ) and systemic vascular resistance index was lower ( ) in the off pump group 1 h after arrival in the intensive care unit. CK-MB and troponin T were significantly lower in the off pump group after 1 h (CK-MB  , troponin T ) and after 6 h (CK-MB  , troponin T ). After 24 h there was no difference between the two groups. In conclusion, immediately after surgery there was better cardiovascular performance and less release of markers of myocardial damage after off pump coronary surgery. After 24 h all differences were eliminated.
Key Words: Coronary artery bypass grafting; Cardiopulmonary bypass; Hemodynamics; Myocardial damage
Coronary artery bypass grafting with cardiopulmonary bypass (ONCAB) is a routine operation with well-documented long-term results. However, cardiopulmonary bypass (CPB) per se leads to a systemic inflammatory reaction which may cause postoperative dysfunction of the heart, lungs, kidney, and brain [1]. Furthermore, aortic cross clamping and cardioplegic arrest induces an ischemic insult to the heart and is a risk factor for neurologic injury [2,3]. During the last 10 years off pump coronary artery bypass grafting (OFFCAB) has become an established and safe alternative to ONCAB. OFFCAB can be performed in a large percentage of the patients on all coronary artery systems with good graft patency [4] and good early [5] and midterm [6] results. Previous studies show less release of cardiac enzymes [5,7,8], fewer myocardial infarctions [9], reduced incidence of arrhythmias [7] and reduced frequency of low cardiac output [10] following OFFCAB. However, others fail to show such differences [11,12]. Studies also show shorter stay in the intensive care unit (ICU) and overall shorter length of stay in hospital [6]. Unfortunately, however, the majority of studies comparing ONCAB and OFFCAB are non-randomized and retrospective with differences in patient characteristics between groups. In this randomized study we hypothetized that OFFCAB would improve cardiovascular function in a population of standard, low risk patients undergoing elective coronary artery bypass surgery.
The study was approved by the Karolinska Hospital Research Ethics Committee. Informed consent was obtained from all patients. Fifty-nine patients admitted for elective coronary artery bypass grafting (CABG) surgery between October 1999 and October 2001 were randomized to either ONCAB or OFFCAB. During this time approximately 1400 patients had CABG surgery at our department. Exclusion criteria were: age under 50 or over 80 years, ejection fraction <30%, serum creatinine >150 µmol/l, left main stem stenosis (>70%), redo operation, diffuse distal coronary artery disease, small and short branches of the circumflex artery, unstable angina, and history of cerebrovascular disease. One patient in the OFFCAB group was converted to on pump surgery because of serious bleeding from a septal branch at the anastomotic site during suturing of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery. This patient was excluded from the study. 2.1. Surgery The patients were operated through a median sternotomy by six different surgeons. All proximal anastomoses were performed by the use of a side-biting clamp. Protamine was administered at the end of the operation to fully reverse the heparin effect.
2.1.1. ONCAB
2.1.2. OFFCAB 2.2. Hemodynamics A radial artery line, a central venous catheter and a Swan–Ganz catheter were used. Cardiac output was measured by thermodilution. The following measurements and calculations were performed: heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output, cardiac index (CI), stroke volume (SV), systemic vascular resistance index (SVRI) and left ventricular stroke work index (LVSWI). Measurements were made during anesthesia before surgery, postoperatively after 1 and 4 h in the ICU, and in the morning after surgery, approximately after 20 h.2.3. Blood sampling Blood was sampled during anesthesia before surgery and 1 and 6 h after admission to the ICU, and in the morning after surgery. Troponin T and creatine kinase-MB (CK-MB) were analyzed with electrochemiluminescence immunoassay technique (Elecsys 1010/2010 Systems, Roche, Basel, Switzerland). Perioperative myocardial infarction was defined as CK-MB>50 µg/l and a new q-wave on the ECG [13].2.4. Anesthesia and postoperative care All patients were anesthetized according to the standard clinical routines of the department. After premedication with morphine, anesthesia was induced with fentanyl, midazolam and propofol and maintained with intermittent fentanyl and isoflurane. Continuous propofol was used as a supplement when needed. Pancuronium or atracurium was used for muscular relaxation. Volume-controlled ventilation with 40–50% O2 in air was performed. Mean arterial pressure was maintained over 60 mmHg and norepinephrine was given if required.To standardize the hemodynamic measurements all patients were kept sedated with propofol and on mechanical ventilation until the measurements at 4 h. Patients who received a radial artery graft were given nitroglycerine infusion (0.5 µg/kg min) for 18–24 h postoperatively. These patients were given Felodipin orally before the operation and from the first postoperative day for 3 months to prevent spasm. Postoperative bleeding was measured from the time the drains were activated in the operating room until they were removed on the first postoperative day. 2.5. Statistics For between group analysis of operative and postoperative data, t-test and Fisher's exact p-test were used. Descriptive data are presented as mean (95% confidence intervals) or frequency counts. For data measured during 24 h, repeat measures analysis of variance was used. CK-MB and troponin T, which did not have equal variances, were analyzed with Mixed Model in SAS (SAS Institute Inc., Cary, NC, USA).
In the text, hemodynamic data are presented as the differences between baseline and measuring time points. In the graphs, data are presented as mean with 95% confidence interval for hemodynamic data and as median with lower and upper quartiles and non-outlier range for markers of myocardial injury. The exact p value is given except when
There were no major inter-group differences in baseline characteristics (Table 1). There was no stroke, acute renal failure or sternal wound infection during the hospital stay. There was one death, see below. Two patients in the OFFCAB group had prolonged ICU stay. One patient became circulatory unstable the day after surgery and received an intraaortic balloon pump. Coronary angiography showed thrombosis (but open anastomosis) of the vein graft to the RCA, which was subsequently stented. The remaining postoperative course was uneventful. Another patient in the OFFCAB group initially had a normal postoperative course. This patient died of sepsis and multiorgan failure after 60 days in the ICU due to intestinal perforation by placement of the mediastinal drainage. He received approximately 100 units of red blood cells. Since this complication was unrelated to ONCAB or OFFCAB, this patient was excluded from calculations of length of stay and hemoglobin value at discharge in Table 2.
Postoperatively, there were no important differences between groups in HR (  ), MAP ( ), CVP () and PCWP (). SV ( ) and CI () were higher, SVRI ( ) was lower and LVSWI tended ( ) to be higher in the OFFCAB patients (Fig. 1).
SV decreased less in the OFFCAB group than in the ONCAB group between the measurement at baseline and 1 h (  ), and there was a tendency also at 4 h ( ). The measurements at 20 h did not differ () between groups. CI increased more from baseline to the 1 h measurement in the OFFCAB group (). This difference was eliminated at 4 and 20 h (). SVRI decreased from baseline to 1 h in the OFFCAB group, but increased in the ONCAB group ( between groups). The groups did not differ at the two final measurements (). More patients in the OFFCAB group (11 versus 6) received radial artery grafts and thus intravenous nitroglycerine infusion during the first 18–24 postoperative hours. A subgroup analysis showed that this had no effect on the SVRI.
Both CK-MB (
This prospective, randomized trial showed that patients undergoing OFFCAB had improved cardiovascular performance immediately after surgery as compared to ONCAB patients. This may be important during this very early, critical period, because hemodynamic stability during the first few hours after cardiac surgery is important for the further postoperative course. The present study was primarily intended only to study continuous hemodynamic data as primary endpoints, and was not planned to and thus not powered to investigate outcome data. 4.1. Hemodynamics SVRI was lower and CI and SV higher 1 h after admission to the ICU in the OFFCAB compared to the ONCAB group. The improved cardiovascular performance may be due to a better cardic function and/or peripheral vasodilation in the OFFCAB patients. This is in agreement with a lower incidence of low cardiac output syndrome in OFFCAB patients [10]. However, Louagie et al. [14] found no difference between ONCAB and OFFCAB regarding CI, LVSWI and SVRI, but the OFFCAB patients needed less inotropic support. OFFCAB can also be performed safely in patients with left ventricular dysfunction [15]. In retrospect, patients with markedly reduced cardiac function ought to have been included.4.2. Markers of myocardial damage Release of CK-MB and troponin T was less after 1 and 6 h in the OFFCAB group. This is in agreement with other investigators. Ascione et al. [7] found lower troponin I release at 1, 4, 12 and 24 h postoperatively, Kilger et al. [8] found lower CK-MB and troponin I up to 24 (CK-MB) and 36 (troponin I) h after OFFCAB surgery and van Dijk et al. [5] found lower CK-MB levels up to 20 h after OPCAB.4.3. Blood loss There was no inter-group difference in peroperative or postoperative bleeding or in the number of patients receiving red blood transfusions. The OFFCAB patients had higher hemoglobin concentration at discharge from hospital. Other studies [4,9,11] show less bleeding and less red blood cell transfusions [4,11] in OFFCAB patients. These are all non-randomized trials where the number of anastomoses differs between groups. In randomized trials, Angelini et al. [6] showed less bleeding and less red blood cell transfusions and van Dijk et al. [5] showed less intraoperative but no difference in postoperative transfusions in OFFCAB patients and no difference in hemoglobin at discharge.Most studies are not randomized and have less anastomoses performed in the OFFCAB patients. In this randomized study the number of anastomoses was equal in both groups and higher than in other studies. The operation time of the OFFCAB group increased with the number of anastomoses and bleeding increased with longer operating time.
In summary this prospective, randomized study suggests a better cardiovascular performance observed as higher cardiac index and improved vasodilation during the first hours after OFFCAB versus ONCAB surgery. After 24 h all differences were eliminated. The difference between groups were modest, but may still be clinically important in the initial critical hours.
ICVTS on-line discussion Author: Dr. Hitoshi Hirose, Cardiovascular Surgery, Shin-Tokyo Hospital, Juntendo University, Hongo, Bunkyo-ku, Tokyo Date: 01-Sep-2003 Message: I agree with the authors that one of the advantages of off-pump coronary artery bypass (off-pump CABG) is less myocardial injury than on-pump CABG. Our experiences of off-pump CABG regarding the postoperative creatine kinase isoenzyme (CKMB) were similar to theirs. Between 1998 and 2002, a total of 851 patients underwent isolated but complete revascularization by either on-pump (n=372) or off-pump CABG (n=479) at the Shin-Tokyo Hospital Group. The number of distal anastomoses were not significantly different between the two groups (3.6±1.2 in the off-pump group versus 3.7±1.1 in the on-pump group, p=NS by student t-test). However, the postoperative peak CKMB was lower in the off-pump group (21.1±40.1 in the off-pump group vs. 39.8±96.2 in the on-pump group, p<0.001). Interestingly there were no associations between the postoperative CKMB and local coronary clamp time in off-pump CABG. We believe that off-pump CABG provides less myocardial damage than the on-pump CABG.
We are grateful to Peter Holm MD, Karun Korkmaz MD, and Mikael Runsiö MD, for operating some of the patients. For statistical analysis we gratefully acknowledge the assistance of Elisabeth Berg MSc and Lisa Jerlvall BSc, Department of Medical Informatics and Educational development, The Karolinska Institute, Stockholm, Sweden.
The present work was supported by grants from The Swedish Heart and Lung Foundation, The Swedish Research Council (grant no. 11235), The V
Presented at The Annual Meeting of the Scandinavian Association for Thoracic Surgery, Oslo, Norway, June 15, 2001. doi:10.1016/S1569-9293(03)00119-1
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Abstract
1. Introduction
; OFFCAB, 
, see text for details.
for CK-MB, 
rdal Foundation, The Karolinska Institute and The Karolinska Hospital. 
