|Year : 2012 | Volume
| Issue : 2 | Page : 35-41
The impact of continuous retrograde cardioplegia compared with intermittent antegrade cardioplegia on left and right ventricular functions during coronary artery grafting in patients with left ventricular dysfunction ( transesophageal echocardiography examination and electron microscopic evaluation)
Maged S. Abdallah1, Osama M. Assad1, Mohamed A. Khalil1, Ali Moktar1, Mohamed Sewielam2, Ibrahim S. Ibrahim3
1 Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
3 Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||03-Sep-2012|
|Date of Acceptance||05-Oct-2012|
|Date of Web Publication||30-Jun-2014|
Maged S. Abdallah
MD, Department of Anesthesia, Faculty of Medicine, Cairo University, 11431 Cairo
Source of Support: None, Conflict of Interest: None
During coronary artery bypass grafting (CABG), both the quality of myocardial protection and the preoperative myocardial status directly influence the postoperative cardiac outcome, recovery, and complications. The aim of this study was to compare the protective effects of continuous retrograde cold blood cardioplegia with intermittent antegrade cold blood cardioplegia at systemic normothermia on left ventricular (LV) and right ventricular (RV) systolic and diastolic functions in patients with poor myocardial contractility, who underwent CABG surgery, in terms of the intraoperative course and the postoperative clinical outcome.
Patients and methods
Patients were randomly divided into two equal groups (20 patients each) according to the myocardial protection technique: antegrade group: intermittent antegrade cold blood cardioplegia and retrograde group: continuous retrograde cold blood cardioplegia. In the antegrade group, warm cardioplegia was administered through an aortic root catheter with infusion pressure not exceeding 150 mmHg. The initial dose used was 10 ml/kg, followed by 5 ml/kg every 30 min afterwards. In the retrograde group, cardioplegia was administered through a coronary sinus cannula at the same volume and composition, but with pressure not exceeding 40 mmHg and was continuously infused. Systemic temperature was allowed to drift to 35πC. Hemodynamic parameters were recorded after induction of anesthesia, after weaning from bypass, and before transportation to ICU. Transesophageal echocardiography examination (for the assessment of RV and LV systolic and diastolic functions) was carried out at the same time points. Cardiac enzymes and serum lactate were measured after induction, after weaning from bypass, and 8 h postoperatively. Clinical outcomes in terms of the use of postoperative inotropic support or the need for defibrillation or pacing were recorded. Electron microscopic evaluation of RV and LV biopsies was carried out using a semiquantitative method with scoring from 0 (apparently normal) to 3 (severely damaged).
Electron microscopic evaluation of LV and RV myocardial biopsies indicated significantly less cellular edema, mitochondrial degeneration, and myofibrillar damage in the retrograde group as compared with the antegrade group. Echo data showed no statistically significant difference between the antegrade group and the retrograde group. The need for vasodilators or inotropes and weaning time were significantly lower in the retrograde group.
We conclude that retrograde cold blood cardioplegia provided myocardial protection and even early recovery of myocardium after CABG surgery.
Keywords: antegrade, coronary artery bypass grafting, retrograde cardioplegia, ventricular functions
|How to cite this article:|
Abdallah MS, Assad OM, Khalil MA, Moktar A, Sewielam M, Ibrahim IS. The impact of continuous retrograde cardioplegia compared with intermittent antegrade cardioplegia on left and right ventricular functions during coronary artery grafting in patients with left ventricular dysfunction ( transesophageal echocardiography examination and electron microscopic evaluation). Egypt J Cardiothorac Anesth 2012;6:35-41
|How to cite this URL:|
Abdallah MS, Assad OM, Khalil MA, Moktar A, Sewielam M, Ibrahim IS. The impact of continuous retrograde cardioplegia compared with intermittent antegrade cardioplegia on left and right ventricular functions during coronary artery grafting in patients with left ventricular dysfunction ( transesophageal echocardiography examination and electron microscopic evaluation). Egypt J Cardiothorac Anesth [serial online] 2012 [cited 2020 May 27];6:35-41. Available from: http://www.ejca.eg.net/text.asp?2012/6/2/35/135552
| Introduction|| |
Multiple techniques have been used for myocardial protection during the surgical requirement for elective global ischemia since the start of cardiac surgery in the 1950s. In 1955, Melrose et al. 1 first used potassium citrate cardioplegia. However, this was associated with a high rate of myocardial injury 2. Evidences from research suggest that myocardial injury was related to the high concentration and tonicity of potassium. Thus, formulations with a much lower potassium content were developed 3. These solutions have been used widely until the 1980s, when blood-based potassium solutions were found to provide better myocardial protection 4,5.
During coronary artery bypass grafting (CABG), both the quality of myocardial protection and the preoperative myocardial status directly influence the postoperative cardiac outcome, recovery, and complications. The two strategies of antegrade cold blood cardioplegia (ACBC) and retrograde cold blood cardioplegia (RCBC) were commonly compared for myocardial protection during CABG 6. Some studies have showed the advantages of RCBC over ACBC in myocardial protection 6,7. Therefore, RCBC becomes a unique choice for myocardial protection in special complex cases 8. Patients with severe and diffuse coronary artery disease (CAD) potentially require a more prolonged elective ischemia. Hence, an improved myocardial protection would be beneficial. Some studies on CAD patients have reported better myocardial outcomes with RCBC 9.
The aim of this study was to compare the protective effects of continuous retrograde cold blood cardioplegia with intermittent antegrade warm blood cardioplegia at systemic normothermia on left ventricular (LV) and right ventricular (RV) systolic and diastolic functions in patients with poor myocardial contractility, who underwent CABG surgery, in terms of the intraoperative course and the postoperative clinical outcome.
| Patients and methods|| |
Patient population and study design
This prospective, randomized, double-blind study was carried out on 40 adult patients who underwent CABG surgery between January 2009 and December 2011, after approval from the ethics and research committee and obtaining informed consent. These procedures were carried out at the Department of Cardiac Surgery, Kasr El Aini Teaching Hospital, Cairo University. The conduct of the operation was not standardized, but was left to the discretion of the individual surgeon.
Patients were randomly divided into two equal groups (20 patients each) using a random numbers table according to the myocardial protection technique, antegrade group: intermittent antegrade warm blood cardioplegia and retrograde group: continuous retrograde cold blood cardioplegia. Inclusion criteria were as follows: age between 18 and 60 years and LV ejection fraction between 30 and 45%. Patients were excluded if they had a history of sustained ventricular tachycardia, left main stem CAD, hemodynamic instability, poorly controlled diabetes mellitus, cerebrovascular disease, serum creatinine concentration greater than 2 mg/dl, past or concomitant valve surgery, emergency operation, redo surgery, or cardiopulmonary bypass (CPB) time greater than 120 min.
Anesthesia and surgical techniques
Two hours preoperative midazolam 7.5 mg with morphine 0.15 mg/kg intramuscularly were given. In the operation room OR, the standard monitors were attached to the patients. All patients were induced with midazolam (0.1 mg/kg), propofol (0.5–1 mg/kg), fentanyl (3–5 µg/kg), and pancuronium (0.1 mg/kg). Anesthesia was maintained with an inspired volume percent of isoflurane 0.5-1.5% in oxygen, and repeated boluses of pancuronium (0.02 mg/kg) and fentanyl (1 mcg/kg) were administered as required. Ventilator parameters were adjusted to maintain PaCO2 between 35 and 45 mmHg. During CPB, anesthesia was maintained using a propofol infusion at a rate of 3 mg/kg/h.
Heparin sulfate (400 IU/kg) was administered before CPB and supplemented as required to maintain an activated clotting time of not less than 400 s. CPB was carried out with a roller pump (STOCKERT S3; Sorin Group, Deutschland GmbH, München, Germany) using a membrane oxygenator (Medtronic, USA) and a 40-µm arterial line filter with nonpulsatile perfusion (at a flow rate of 2.4 l/min/m2).
CPB was instituted with ascending aortic cannulation; venous return was through a single two-stage cannula placed through the right atrial appendage. Blood cardioplegia was prepared with equal volumes of isotonic saline and blood (1 : 1). The final composition contained 30 mEq/l of potassium, 1 g/l of magnesium sulfate, 100 mg/l of lignocaine, and 10 mEq/l of sodium bicarbonate. In the antegrade group, cardioplegia was administered through a 12 Fr aortic root catheter with an infusion pressure not exceeding 150 mmHg. The initial dose used was 10 ml/kg, followed by 5 ml/kg every 20–30 min afterwards. In the retrograde group, the same volume and composition was used, but with pressure not exceeding 40 mmHg and was continuously infused and administered through a 14 Fr coronary sinus cannula placed, with transesophageal echocardiography (TEE) guidance, through a purse string in the wall of the right atrium through the coronary sinus. Systemic temperature was allowed to drift to 35°C.
Distal anastomoses were constructed during a single period of aortic cross-clamping. Before removal of the aortic cross clamp, 500 ml of warm blood hot shots were infused in both groups. The proximal anastomoses were constructed using a partial occlusion clamp. After separation from CPB and removal of the aortic cannula, heparin activity was neutralized with protamine sulfate.
A TEE probe (Vivid pro 3; General Electric, Horten, Norway) was inserted after induction of anesthesia. Assessment of RV and LV functions was carried out using a mid-esophageal four-chamber view, a mid-esophageal RV inflow–outflow view, a transgastric mid-papillary short axis view, and a deep transgastric view. Assessment of RV systolic function was carried out using (a) right ventricular fractional area change (RV-FAC=[100×(RVEDA−RVESA)/RVEDA]), measured from the four-chamber view, and (b) tricuspid annular plane systolic excursion (TAPSE), measured from the four-chamber view. Assessment of RV diastolic function was carried out using Doppler trans-tricuspide flow velocities (E/A wave ratios). Assessment of LV systolic function was carried out using fractional area change (LV-FAC) and assessment of LV diastolic function was carried out using Doppler trans-mitral flow velocities (E/A wave ratios using a mid-esophageal five-chamber view).
Before the aortic cross clamp is applied (preischemia) and 15 min after declamping the aorta and reperfusion, biopsies for transmission electron microscopy (TEM) were taken from the RV and LV myocardium. Samples were immediately fixed in buffered glutaraldehyde (pH 7.3) for 24 h at 4°C and were postfixed in 1% osmic acid for 1 h. The samples were then washed in phosphate buffer and dehydrated in ascending grades of alcohol, and then embedded in Embed B12 capsules. The capsules were sectioned at 80 nm thickness, sections were placed on copper grids, stained with a saturated solution of uranyl acetate and lead citrate, and finally examined using TEM JEM-1010 (JEOL Ltd, Tokyo, Japan).
The results were assessed consideringthe following:
- Hemodynamic parameters (blood pressure, central venous pressure, and heart rate) were recorded after induction of anesthesia, after weaning from bypass, and before transportation to the ICU.
- TEE examination (for the assessment of RV and LV systolic and diastolic functions) was carried out at the same time points as for hemodynamics.
- ECG monitoring for identification of rhythm, occurrence of arrhythmias after coming off bypass, development of new Q wave, or ischemic ECG changes.
- Laboratory parameters – cardiac enzymes (CK-MB and troponin I) and serum lactate were measured after induction, after weaning from bypass, and 8 h postoperatively.
- Clinical outcomes in terms of the use of postoperative inotropic support or an intra-aortic balloon pump, the need for defibrillation or pacing, ICU stays (days), in-hospital stay (days), and deaths (up to 30 days postoperatively).
- Electron microscopic evaluation of RV and LV biopsies using the semiquantitative method with scoring from 0 (apparently normal) to 3 (severely damaged). The ultrastructural changes assessed included cellular edema, intercellular junctions, mitochondria, nuclei, and myofibrils.
Sample size was calculated before the study on the basis of an α error of 0.05 and a β error of 0.1 to detect 25% differences in ventricular functions between the two groups and it was found to be 17 patients in each group. To compensate for dropouts, 20 patients were enrolled in each group. Data were first tested for normality using the Kolmogorov–Smirnov test. Normally distributed continuous data were analyzed using Student’s t-test. Non-normally distributed continuous and ordinal data were analyzed using the Mann–Whitney U-test. Categorical data were analyzed using the χ2 or Fisher’s exact test as appropriate. The results are presented as mean (SD), median (interquartile range), or number of patients as appropriate. A P-value less than 0.05 was considered statistically significant. Statistical analyses were carried out using the SPSS for Windows, version 17 (SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Forty patients were enrolled and completed the study. There were no statistically significant differences in demographic data, preoperative ejection fraction, number of diseased vessels, and preoperative New York Heart Association (NYHA) functional class among the two groups studied [Table 1].
Hemodynamic parameters showed no statistically significant difference between the two groups [Table 2].
The study groups were comparable with respect to aortic cross clamp time, CPB time, volume of cardioplegic solution infused, and number of grafts. Comparable results were also found in both groups with respect to the length of ICU stay and hospital stay [Table 3]. Intraoperative defibrillation, the frequency of initial normal sinus rhythm, and the need for temporary pacing did not differ significantly between the two groups. Three of 40 patients in the groups presented with new Q waves on postoperative ECGs. Two hospital deaths (30 days follow-up, one from each group) were noted (5%). The cause of death of both patients was acute myocardial infarction and cardiogenic shock [Table 3].
The need for vasodilators and/or the use of inotropes were significantly lower in the retrograde group (P=0.002) [Table 3]. Again, there was a statistically significant difference in the time of weaning from bypass in the antegrade group (longer time) compared with the retrograde group (P=0.004) [Table 3].Intraoperatively, however, patients who received retrograde cardioplegia had significantly longer cross-clamp and CPB times as they received more grafts per patient. Despite this, they had significantly less inotropic use and a reduced weaning time from bypass.
There were no statistically significant differences between the two groups with respect to serum lactate and CK-MB levels. With respect to troponin levels, lower levels were found in the retrograde group in comparison with the antegrade group, but did not reach significant levels [Table 4].
Electron microscopic evaluation of LV myocardial biopsies indicated significantly less (P<0.05) cellular edema, mitochondrial degeneration, and myofibrillar damage in the retrograde group as compared with the antegrade group. However, there was no significant change in the ultrastructure of the cellular junction among the two groups [Table 5].
Electron microscopic evaluation of RV myocardial biopsies indicated significantly less (P<0.05) myofibrillar damage in the retrograde group as compared with the antegrade group, whereas the other electron microscopic parameters in terms of cellular edema, intercellular junctions, and mitochondria showed no significant change among the two groups (P>0.05) [Table 6].
Echo data: all the transoesophageal echo results appeared to be better in the retrograde group compared with the antegrade group, but no statistically significant differences were found between both groups [Table 7] and [Table 8].
| Discussion|| |
In the present study, we examined the effect of two different infusion techniques of cardioplegia on RV and LV functions in ischemic patients with LV dysfunction who underwent CABG surgery. The main results were as follows: (a) electron microscopic studies showed significantly less LV and RV myocardial damage in the retrograde cardioplegia group when compared with the antegrade cardioplegia group, indicating better myocardial protection. This protection seems to be less in the RV myocardial biopsies in comparison with the LV as retrograde cardioplegia showed less myofibrillar damage than antegrade cardioplegia, whereas cellular edema, intercellular junctions, and mitochondrial changes were almost the same in the two groups for the right ventricle, (b) the need for inotropes and vasodilators was significantly lower in the retrograde group, and (c) there was a significant difference in the time of weaning from bypass in favor of the retrograde group when compared with the antegrade group.
The results of the current study showed that better myocardial protection (in terms of clinical outcome, the need for inotropes, and weaning time) and less myocardial damage (as proved by electron microscopic features) were provided by retrograde cardioplegia. However, retrograde cardioplegia was found to be less protective to the right side of the heart as shown by TEM.
Several studies in the past on the efficacy of myocardial protection by retrograde cardioplegia through the coronary sinus found that it to be better than antegrade cardioplegia in terms of easier restoration of ventricular function, better postbypass hemodynamics, and less need for postoperative inotropic support, but there was no significant difference in the long-term outcome 10–12. In contrast, conflicting results were found for RV myocardial protection by retrograde when compared with antegrade cardioplegia in CABG patients. Some studies have reported that retrograde cardioplegia does not adequately protect the myocardium of the right ventricle or the posterior part of interventricular septum 13,14. However, other studies have rejected this hypothesis, claiming the reverse, and showed efficient RV myocardial protection by the retrograde cardioplegia, even better than that provided by ACBC 15. A third reasonable assumption was concluded by some studies that neither antegrade nor RCBC alone can adequately protect RV myocardium during CABG procedures and suggested a combination of both 16,17.
In our study, although there was early recovery and less use of inotropes, there were better echo results (FAC,TAPSE, E/A ratio) of the right and left ventricle in favor of retrograde cardioplegia, but it did not reach statistical significance. The same was noted for laboratory investigations (lactates and troponin).
The study by Nirupama et al. 18 showed that retrograde cardioplegia alone without adjuvant antegrade cardioplegia can be safely and effectively used in all valve operations and in combination with procedures with coronary or ascending aortic aneurysm. It has obvious advantages in the presence of aortic insufficiency. Low operative mortality, absence of perioperative myocardial infarction, and low, acceptable prevalence of ventricular arrhythmias/conduction disturbances, and hemodynamic instability requiring inotropic support in the immediate perioperative period are the clinical markers indicative of adequate myocardial protection. The clinical outcome of the exclusive use of retrograde cardioplegia in all valve operations is encouraging. It is close to that of our study, but we applied it in CABG surgery.
Douville et al. 19 compared the effects of retrograde and antegrade cardioplegia on RV performance in patients undergoing myocardial revascularization. A RV rapid-response thermistor catheter was used to measure RV parameters. The results showed equivalent parameters in both groups at all time intervals, except 30 min after bypass. The RV end-diastolic volume index was lower and the RV stroke volume index was higher in the retrograde group compared with the antegrade group, indicating better RV function with retrograde cardioplegia early after bypass. In our study, there are many differences from that of Douville; we used TEE and there were no differences between the two groups in FAC, TAPSE, and the E/A ratio. Moreover, our study was based on the use of blood rather than crystalloid cardioplegia.
However, there are many challenges in TEE assessment of the right side such as (a) the complex shape of the RV, (b) heavy apical trabeculations of the RV, which limits endocardial surface recognition, and (c) the marked load dependence of several indices of the RV function. We used Geometric indices, those that reflect the extent of contraction, such as RV-FAC and TAPSE.
RV-FAC is an index of RV systolic function that is easier to measure. RV-FAC represents the ratio of RV systolic area change to the end-diastolic area. It is measured in the four-chamber view and can be incorporated systematically into a basic Echo study. In nonsegmental disease, a good correlation has been reported between RV-FAC and RVEF, measured using MRI. A consensus from the American and European Societies of Echocardiography has determined the ranges in the evaluation of RV-FAC: normal values are between 32 and 60%, mildly abnormal between 25 and 31%, moderately abnormal between 18 and 24%, and severely abnormal below 17%.
TAPSE measures the longitudinal systolic motion of the free edge of the tricuspid valve annulus. Compared with RVEF and RV-FAC, TAPSE has the advantage of not being limited by RV endocardial border recognition. It may represent a reasonable index of global systolic function. We exclude RVEF as an index to be measured for the following disadvantage of being highly load dependent and may not always reflect ventricular contractility in volume-overloaded or pressure-overloaded states. An accurate assessment of RVEF using echocardiography also remains difficult because of the complex shape and heavy trabeculations of the RV. In terms of diastolic functions, trans-tricuspid flow velocity in the mid-esophageal four-chamber view was used.
Hamid et al. 20, in a more recent study, compared retrograde against ACBC–RCBC in a randomized clinical trial in patients with CABG, and they found that no significant difference was found between the two procedures on myocardial function and ejection fraction and also in patients with normal condition.
From another point of view, Bezon et al. 7 had found that continuous retrograde blood cardioplegia ensures prolonged aortic cross-clamping time without increasing the operative risk. The operative mortality was 8.3%. The mean predicted mortality of the population studied (EuroSCORE logistic method) was 8.4%±12 (range 0.87–76.15%), with a 95% confidence interval of 6.7–10%. The observed mortality was not different from the predicted mortality.
Similar findings were obtained in the study of Onorati et al. 21, who compared clinical, echocardiographic, and biochemical results in patients with left main stem disease (LMSD) treated with two different strategies of myocardial protection: antegrade or antegrade followed by retrograde. They found that postoperative recovery of the LV ejection fraction and the wall motion score index did not differ between the two groups, but troponin I was significantly higher in the antegrade group. They concluded that the combined route of intermittent blood cardioplegia allows better results in LMSD.
Bolcal et al. 22 evaluated the postoperative conduction disorders after CABG with respect to the antegrade blood cardioplegia and antegrade plus continuous retrograde cardioplegia delivery methods. They found that the perioperative occurrence of conduction disorders after CABG was decreased by antegrade-controlled and retrograde continuous combination cardioplegia. Again, Onorati et al. 23 compared two different strategies of myocardial protection in diabetics with LMSD. Although the major in-hospital end points did not differ with the strategy of cardioplegia administration, the combined route of intermittent blood cardioplegia yielded better biochemical and perioperative results in diabetics with LMSD.
The present study had a few limitations: first, complicated surgeries such as redo surgery or associated valve surgeries were not included; second, long-term morbidity and mortality are not included in the study.
Acute RV failure after cardiac surgery remains a major cause of morbidity and mortality. A comprehensive assessment of RV function may improve risk stratification and lead to early management of RV failure. Echocardiography is becoming a mainstay in the assessment of perioperative RV function.
| Conclusion|| |
We conclude that RCBC provides RV myocardial protection similar to that provided by antegrade cardioplegia, and even early recovery of myocardium and less use of inotropes in patients with ventricular dysfunction.
| References|| |
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]