Original Article

Predictors of gastrointestinal complications after conventional and beating heart coronary surgery

S.G. Raja* Z. Haider M. Ahmad
Department of Cardiovascular Surgery, Mayo Hospital, Lahore, Pakistan

Correspondence to: S.G. Raja, Department of Cardiothoracic Surgery, Harefield Hospital, Parkwood Hospital, Hill End Road, Harefield, Middlesex, UB9 6JH, U.K.

Introduction Materials and Methods  Operative technique Statistical analysis

Results Discussion Conclusions References

Keywords: Predictors, gastrointestinal complications, cardiopulmonary bypass, off-pump surgery, myocardial revascularisation 
Surg J R Coll Surg Edinb Irel., 1 August 2003, 221-228

Background: Gastrointestinal complications after cardiac surgery remain a significant problem despite improvements in pre-operative, operative and post-operative care. The pathophysiology is uncertain, and their prevention remains suboptimal. This prospective, randomised study was designed to define the role of cardiopulmonary bypass (CPB) and cardioplegic arrest in the pathogenesis of gastrointestinal complications following coronary artery surgery. Methods and Results: Three hundred patients were prospectively randomised to (1) on-pump conventional coronary artery surgery [150 patients, 114 men, mean age 64 (45-75 years)] with mild hypothermic (32 c) CPB and cardioplegic arrest of the heart or (2) off-pump surgery [150 patients, 113 men, mean age 64 (38-66) years] on the beating heart. The association of peri-operative factors with gastrointestinal complications was investigated by univariate analysis. Significant variables were then included into a stepwise logistic regression model to ascertain their independent influence on the occurrence of gastrointestinal complications. There were no significant baseline differences between the groups. Eleven patients in the on-pump group and one patient in the off-pump group had post-operative gastrointestinal complications. Univariate analysis showed that CPB inclusive of cardioplegic arrest, left ventricular ejection fraction<50%, emergency surgery, prolonged aortic cross clamp and CPB time, post-operative low cardiac output syndrome, post-operative inotropic requirement, new onset atrial fibrillation (AF), excessive post-operative blood loss and redo thoracotomy<24 hours were predictors of gastrointestinal complications after coronary artery surgery (all p<0.05). However, stepwise multivariate regression analysis identified CPB inclusive of cardioplegic arrest as the only predictor of post-operative gastrointestinal complications (OR7.4; CI 3.4-17.9). Conclusions: Cardiopulmonary bypass, inclusive of cardioplegic arrest, is the main independent predictor of postoperative gastrointestinal complications in patients undergoing coronary revascularisation

INTRODUCTION
Gastrointestinal complications may occur in the post-operative period after cardiac surgery, increasing morbidity, length of hospital stay and mortality. Gastrointestinal complications after cardiac surgery with CPB have an incidence of 0.3 to 3%.^1-3 Peptic ulcer disease with perforation and bleeding, pancreatitis, acute cholecystitis, hepatic failure, bowel ischaemia, pseudomembranous colitis, paralytic ileus and diverticulitis are reportedly the most common complications.^4-8 Identification of these gastrointestinal complications may be difficult because manifestations may be masked by postoperative analgesia or not reported by patients because they are sedated or require prolonged mechanical ventilation.⁹ Despite major technological and medical advances, CPB still imposes considerable physiologic stress on the patient.^10,11Intraabdominal ischaemic injury is a likely contributing factor in most gastrointestinal complications after cardiac surgery.^3-12

Myocardial revascularisation on the beating heart does not require atrial cannulation, CPB and cardioplegic arrest and it has been suggested to be associated with a reduction in postoperative complications after coronary artery surgery.^13-16

The present prospective randomised study investigated the incidence of gastrointestinal complications in similar cohorts of patients undergoing coronary artery bypass grafting (CABG) with or without CPB and cardioplegic arrest. Further analysis included variables considered by other authors to have a possible association with gastrointestinal complications after coronary artery surgery.

MATERIALS AND METHODS

Patient Selection
Over an 18-month period (January 2000 to June 2001), 300 patients who met the eligibility criteria, from a total population of 500 patients, were randomised. They underwent CABG for the first time under the supervision of a single consultant. On the basis of their eligibility for off-pump coronary artery surgery, half of these 300 patients underwent on-pump conventional surgery [150 patients, 114 men, mean age 64(45-75) years] with mild hypothermic (32.C) CPB and cardioplegic arrest of the heart. The other half [150 patients, 113 men, mean age 64 (38-66) years] underwent off-pump surgery on the beating heart. The randomisation sequence was obtained by card allocation and strictly followed. This was a simple procedure and the patient picked up one of the two envelopes. Each envelope contained one card that had written either an on-pump or offpump operation on it. Patients with previous abdominal surgery were excluded and the patients with the following angiographic findings were also excluded from the study due to expected technical difficulty in grafting these vessels:-

• Patients with coronary artery disease involving very distal obtuse marginal/distal circumflex vessels

• Atherosclerosed coronary arteries considered to be less than 2mm in diameter, especially on the back of the heart and involving the posterior descending artery

• Calcified coronary arteries

The study was approved by the Mayo Hospital Medical Ethics Committee, and all patients gave informed consent.

ANAESTHETIC TECHNIQUE
In both groups, anaesthetic technique consisted of propofol infusion (3 mg/kg/hr) combined with fentanyl infusion (0.5 to 1µg/kg/min). Neuromuscular blockade was achieved by 0.1 to 0.5 mg/kg pancuronium bromide or vecuronium and the lungs ventilated to normocapnia with air and oxygen (45% to 50%). Heparin was given at a dose of 300 IU/kg to achieve a target activated clotting time (ACT) of 480 seconds before commencement of CPB in the on-pump group. An additional 3000IU of heparin were administered, if required. In the offpump group, heparin (100 IU/kg) was administered before the start of the first anastomosis to achieve an ACT of 250 to 350 seconds. On completion of all anastomoses, protamine was given to reverse the effect of heparin and return the ACT to preoperative levels. Our routine prophylaxis against upper gastrointestinal bleeding was to use ranitidine (3x50 mg/day) on the intensive care unit (ICU). A proton pump inhibitor (omeprazole 20 mg/day) was only used in patients with a history of peptic ulcer disease. Cefuroxime (750mgx3) was given perioperatively to all patients.

OPERATIVE TECHNIQUE
On-Pump: Cardiopulmonary bypass was instituted with the use of ascending aortic cannulation and 2-stage venous cannulation of the right atrium. A standard circuit was used: a Bard tubing set, which included a 40µm filter (Sorin Biomedica), and a hollow-fibre membrane oxygenator. A non-pulsatile blood flow rate of not less than 2.4L/min/m2 was used, whenever possible. Systemic temperature was kept at 32°C. Myocardial protection was achieved by using intermittent cold crystalloid cardioplegia.

Off-Pump: The anaesthetist plays an active role during the performance of OPCAPB, as the maintenance of systolic pressure is important because the heart does not tolerate haemodynamically unfavourable positioning. Alpha agents and inotropic drugs are important to maintain cardiac output during manipulations. Median sternotomy was performed in all cases. All conduits were harvested as for traditional CABG. The left internal mammary was made as long as possible. This helped to avoid excessive tension when the heart was elevated after the graft to the left anterior descending was performed. The coronary arteries were grafted in the following sequence; anterior wall vessels, followed by inferior wall vessels and finally lateral wall vessels. The left internal mammary to the left anterior descending graft was usually the first, the inferior wall grafts (posterior descending, right coronary) were usually next and the lateral wall grafts (obtuse marginal) were usually the last. The distal anastomoses were constructed first followed by proximal anastomoses. Stabilisation of target site was accomplished with Medtronic Octopus-II Stabilizer (Medtronic Inc, Minneapolis, MN, USA). Proximal occlusion of target vessel was accomplished with an encircling suture to the vessel proximal to the site chosen for anastomosis. No distal occlusion was necessary. Distal anastomoses were performed with a single suture continuous technique. Visualisation of the anastomotic site was enhanced by the use of a surgical blowerhumidifier (Research Medical Inc, Midvale, UT).

POST-OPERATIVE MANAGEMENT
At the end of surgery, patients were transferred to the ICU. The lungs were ventilated with 60% oxygen with volumecontrolled ventilation and a tidal volume of 10ml/kg with 5 cmH₂O of positive end-expiratory pressure. Adjustments in FIO2 and respiratory rate were made according to the blood gas analysis to maintain PaO2 between 90 and 100 mm Hg and PaCO2 between 35 and 40 mm Hg. Forced air warming was used until a stable nasopharyngeal temperature of 37°C was reached. Patients were extubated as soon as they met the following criteria: haemodynamic stability, no excessive bleeding (<30 ml/hr), normothermia and consciousness with pain control. Fluid management after surgery consisted of 5% dextrose infused at 1ml/kg/hr, with additional colloid or blood to maintain normovolaemia and haematocrit>28%. Potassium deficiency was promptly treated as necessary to maintain electrolyte balance within the normal range.

RISK FACTORS 
Our definition of pre-existing gastrointestinal disease included all patients with a history of gastric or duodenal ulcer(s), colitis, as well as hepatobiliary disease such as pancreatitis, cholelithiasis and cholecystitis. Renal insufficiency was considered significant with a serum creatinine level of more than 2mg/dl. All other preoperative risk factors are given along with demographic data in Table 1. Intra-operatively, CPB and aortic cross-clamping time were considered potential risk factors. During the post-operative period we looked for low cardiac output syndrome with a cardiac index of less than 2.0L/min/m2, inotropic requirement, new onset of AF, blood loss and need for redo thoracotomy within the first 24 hours post-operatively.

GASTROINTESTINAL COMPLICATIONS
We defined post-operative gastrointestinal complications as follows: gastrointestinal bleeding confirmed by endoscopy with a decrease in haemoglobin content of at least 2g/dl, mesenteric ischaemia or infarction, cholecystitis, pancreatitis, hepatic failure confirmed by clinical and laboratory data, pseudomembranous colitis and duodenal ulcer perforation.

STATISTICAL ANALYSIS 
The association of pre-operative, intra-operative and postoperative variables with post-operative gastrointestinal complications was investigated with univariate analysis. The following factors, reported as predictors of gastrointestinal complications by other investigators, were also included in the analysis: age at operation, sex, previous myocardial infarction, congestive heart failure, diabetes, hypertension, number of grafts, peripheral vascular disease, and chronic obstructive pulmonary disease. Because continuous data did not show a Gaussian distribution, they were analysed by the Mann-Whitney test. Categoric data comparison was made by the 
X ² test. Data  are expressed as median with minimalmaximal values or number (percentage) of patients. Statistical significance was confirmed with a probability error of less than 5 %( p<0.05). All calculations were performed with GraphPad Instat Version 3.00(GraphPad Software San Diego, CA, USA). Factors that turned out to be predictors of gastrointestinal complications at univariate analysis were then included in a stepwise logistic multivariate regression model to ascertain their independent role. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were calculated.

RESULTS
Of the 500 patients who underwent coronary artery surgery for the first time during an 18-month period, 18(3.2%) developed gastrointestinal complications during their post-operative hospital stay. The mortality rate for 482 patients who did not develop gastrointestinal complications was 1.65 %( n=8). Of the 18 patients with gastrointestinal complications, 9(50%) died (p <0.0001). Pre-operative and intra-operative data are shown in Tables 1 and 2, respectively. The off- pump and on-pump groups were identical in terms of demographic and surgical data, including number of distal anastomosis and risk stratification. The Parsonnet score for on-pump group was 7.5±7.1, compared with 7.4±7.2 for offpump group (p<0.7).

The incidence of gastrointestinal complications in the two cohorts of patients is presented in Tables 3 and 4. The overall incidence of gastrointestinal complications in the selected population was 4 %( n=12), with 11 patients in the on-pump group and one patient in the off-pump group (p<0.0001); 9(6%) patients in the on-pump group and none in the off-pump group died. As shown in Table 1, the most significant risk factors for the development of post-operative gastrointestinal complications were renal insufficiency, emergency surgery, and left ventricular ejection fraction<50%. Patients who developed gastrointestinal complications had significantly prolonged periods of both CPB (192.4± 83.2 vs 112.1±49.6 minutes, p<0.0001) and aortic cross clamping (105.3±45.6 vs 68.2± 35.6 minutes, p<0.0001). As listed in Table 5, patients with low cardiac output, new onset AF, post-operative need for vasopressor support, post-operative blood loss, and those needing redo thoracotomy within the first post-operative day had an increased incidence of gastrointestinal complications. Results from the univariate analysis for the association of each risk factor with post-operative gastrointestinal complications are shown in Table 6. The use of CPB with cardioplegic arrest, renal insufficiency, emergency surgery, left ventricular ejection fraction<50%, low cardiac output, need for inotropic support, new onset AF, post-operative blood loss, and redo thoracotomy<24hr were all predictors of gastrointestinal complications after myocardial revascularization. However, stepwise multivariate regression analysis indicated the use of CPB inclusive of cardioplegic arrest as the only independent predictor of post-operative gastrointestinal complications (Odds Ratio 7.4;Confidence Interval 3.4 to 17.9).

DISCUSSION
Despite intensive therapeutic efforts, the incidence and mortality of gastrointestinal complications after cardiac surgery employing CPB have not decreased during the last two decades.¹⁷ In our study, the overall incidence of post-operative gastrointestinal complications was 3.2%, which conforms to the low incidence demonstrated by other investigators. Once a gastrointestinal complication occurs, however, the mortality ranges from 13.5% to 72.0%. ^1-3,17 In particular, patients with gastric bleeding or cholecystitis are most likely to survive, whereas almost every patient with mesenteric ischaemia dies.^18,19 Many pre-operative and postoperative factors have been suggested to increase the incidence of post-operative gastrointestinal complications after conventional CABG such as age greater than 70 years, need for blood transfusion, re-operation, triple vessel disease, NYHA class IV, duration of CPB, peripheral vascular disease, congestive heart failure and inotropic support, prolonged ventilation and a positive history of peptic ulcer disease.^12,20 Strategies directed toward reduction of postoperative gastrointestinal complications have focused on early detection by frequent determination of serum lactate levels in patients at increased risk for gastrointestinal complications, use of H2-receptor antagonists and proton pump inhibitors and use of phosphodiesterase inhibitors rather than catecholamines  for inotropic support with conflicting results.^17,21,22 However, little is known about intra-operative mechanisms through which the incidence of postoperative gastrointestinal complications could be reduced. 

Recently, there has been a renewed interest in performing CABG on the beating heart.^13-15 Several studies have reported improved myocardial and renal protection, minimal inflammatory response, excellent patency rates of grafts and decreased costs.^{13, 23-28}

Whereas the above studies, by comparing conventional CABG with beating heart coronary surgery, have proved that beating heart surgery is associated with reduced post-operative complications, no comparative study for determining the incidence of gastrointestinal complications after conventional and beating heart coronary surgery has so far been done.

To the best of our knowledge, the present study is the first, prospective  randomised study to investigate factors such as CPB and associated techniques as determinants of post-operative gastrointestinal complications in similar cohorts of patients undergoing CABG with or without CPB through median sternotomy.

The main finding of the study is that CPB inclusive of cardioplegic arrest is the main independent predictor for the development of post-operative gastrointestinal complications, the risk being seven times higher in the on-pump compared with the off-pump group.This could be related to the period of visceral ischaemia or to the inflammatory response after CPB itself, and the adverse effects of cardioplegia. Cardiac surgery on CPB is associated with a low flow state with subsequent hypoperfusion of end organs. Peri-operative hypotension, hypovolaemia, prolonged CPB time, use of vasoconstrictors and post-operative arrhythmias all aggravate this end organ hypoperfusion and could well explain the  relatively high number of gastrointestinal complications in the conventional surgery group (7.3%), as well as the need for postoperative inotropic requirements in the on-pump group.

In keeping with the findings of Zacharias et al (2000), Byhahn et al (2001) and Yilmaz et al (1996), the univariate analysis of the present study showed that renal insufficiency, emergency surgery, the need for post-operative inotropic support, post-operative cardiac index less than 2.0L/min/m2, post-operative blood loss, redo thoracotomy<24 hr, and new onset AF were all predictors of development of post-operative gastrointestinal complications. ^18,17,20 Our study also revealed preoperative-left ventricular ejection fraction <50% as a predictor of post-operative gastrointestinal complications. However, when these factors were included in a stepwise logistic multivariate regression model, they did not appear to have an independent role.

In contrast with previous reports, this study failed to demonstrate advanced age as an independent predictor of post-operative gastrointestinal complications, although overall a higher percentage of gastrointestinal complications were observed in older patients.^12,20 The limitation of the present study is the relatively small size of cohorts of patients.

CONCLUSIONS
This prospective, randomised study clearly shows CPB inclusive of cardioplegic arrest as the main independent predictor of postoperative gastrointestinal complications in patients undergoing CABG. The minimal incidence of gastrointestinal complications in the off-pump group satisfies the modern demand of further improvements in peri-operative patient management, reduction of costs and resources while maintaining quality of care, and patient satisfaction.

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Copyright: 9 May 2003