Continuous or intermittant retrograde cardioplegia during coronary bypass: A propensity score adjusted comparison

Abstract

Introduction

Continuous retrograde cardioplegia worsens surgeon’s vision while performing distal anastomosis in coronary artery bypass grafting operations. We investigated whether intermittent retrograde cardioplegia, which provides a bloodless surgical field by interrupting cardioplegia flow during distal anastomosis, poses a disadvantage in terms of myocardial protection.

Methods

This retrospective study was conducted in two different heart centres between January 2013 and July 2023. A total of 234 patients who underwent ≥2 target vessel revascularization under cardiopulmonary bypass were examined. Isothermic, potassium-enriched blood cardioplegia was used and induction was performed antegrade in all patients. In addition to antegrade, we routinely gave retrograde cardioplegia. Retrograde cardioplegia was applied continuously with the force of gravity in the continuous group (n = 167), and intermittently with pressure in the intermittent group (n = 167).

Results

The volume of cardioplegia solution administered was significantly higher in the intermittent group compared to the continuous group (4070 ± 760 mL vs 3190 ± 575 mL; p = 0.001). However, no significant differences were observed between the groups regarding postoperative clinical outcomes or early mortality rates.

Conclusions

Intermittent retrograde cardioplegia offers superior operative conditions by ensuring a bloodless surgical field and improved procedural comfort, while maintaining equivalent efficacy in myocardial protection compared with the continuous method.

Keywords

retrograde cardioplegia coronary artery bypass grafting myocardial protection

Introduction

Cardioplegia aims to preserve myocardial function while providing a bloodless and immobile operation field to facilitate a surgery. Various cardioplegia methods differ in temperature, content, route of administration, and perfusion style. However, no clear consensus exists regarding the superiority of one method over another. This lack of agreement is evident internationally, regionally, and even among teams and physicians within the same hospital.¹ Cardioplegia is used to induce and maintain cardiac arrest. Retrograde perfusion of the coronary circulation is also possible, since the heart vessels do not have valves.² Clinical studies have shown that switching from antegrade to retrograde perfusion increases oxygen consumption and lactate washout. This indicates that each technique perfuses distinct myocardial regions. Therefore, the use of both antegrade and retrograde perfusion is recommended. During the induction phase, retrograde cardioplegia allows slower induction of cardiac arrest. This is not a desired situation. Therefore, it is reasonable to initiate cardiac arrest with the antegrade route and continue it with the retrograde route in order to conserve energy stores.³ While antegrade route ensures sufficient delivery of cardioplegia solution, retrograde route allows delivery of the cardioplegic solution beyond the occluded or critically stenotic coronary arteries. Additional retrograde perfusion also improves subendocardial perfusion.

Retrograde cardioplegia can be delivered continuously or intermittently. The former is considered safer for many surgeons and has been used widely although back flow to surgical site makes anastomose difficult to perform.³ Although the latter is superior in terms of surgical comfort, there is concern that it may be disadvantageous in terms of myocardial protection.

In this retrospective study, we compared continuous and intermittent retrograde cardioplegia techniques during the maintenance period of cardiac arrest in isolated coronary artery bypass grafting operations. Demonstrating comparable myocardial protection between the intermittent and continuous techniques would support the more widespread use of the intermittent technique, which already has the advantage of surgical comfort, by overcoming safety concerns.

Methods

Study population

The study included all 877 patients who underwent isolated two-or-more vessel coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB) by an experienced surgeon at two heart centers between January 2013 and July 2023. We routinely use retrograde cardioplegia in addition to antegrade in two or more bypasses. We used continuous retrograde cardioplegia between January 2013 and October 2017. İntermittent retrograde cardioplegia was adopted as institutional practice after 2017. Retrograde cardioplegia was administered continuously by gravity in the continuous group (n = 307) and intermittently under pressure between anastomoses in the intermittent group (n = 570). Some patient data were missing; after exclusion, the groups comprised 197 and 393 patients, respectively. Following one-to-one propensity score matching, unmatched cases were excluded, resulting in two comparable groups of 167 patients each. These groups were then analyzed retrospectively. The study protocol was approved by the Local Ethics Board.

Surgical procedures

Median sternotomy was performed in all patients. Left internal mammary artery (LIMA) graft was harvested for the anterior descending (LAD) artery, and saphenous vein graft was used for the remaining target vessels. Arterial cannulation was performed through the distal ascending aorta and two-stage venous cannulation of the right atrium. A multiple perfusion adapter with vent-line (California Medical Laboratories) was used for the delivery of the cardioplegia solution. A retrograde cannula (California Medical laboratories) was inserted into the coronary sinus with a manually inflating balloon. The pressure of the tip of the retrograde cardioplegia cannula was monitored. As standard institutional protocol, hematocrit was maintained between 23% and 25%, esophageal temperature between 28 and 30°C, pump flow between 2.2 and 2.4 L/min/m², and mean arterial pressure between 50 and 60 mmHg during CPB.

Tepid, isothermic (The condition where the patient, cardioplegic solution, and systemic blood are at equal temperature), potassium-enriched blood was administered for myocardial protection in all patients. The hematocrit of the blood in the cardioplegic circuit and systemic blood was also the same. The blood was delivered through the arterial line into the cardioplegia bag by a pump in a close system. Blood cardioplegia was prepared using potassium, magnesium, and bicarbonate (induction: 30 mEq potassium, 12 mEq magnesium, 10 mEq sodium bicarbonate per 1000 mL blood). Potassium and sodium bicarbonate content of the maintenance solutions was decreased by 50%.

Half of the induction solution was delivered through aortic root with a pressure of 80 to 90 mmHg. After diastolic arrest was achieved, the remaining half of the induction solution was administered through the coronary sinus and retrograde cardioplegia was initiated.

In the continuous group, cardioplegia was administered by gravity from a bag suspended 1 m above the patient throughout the operation, as standard institutional protocol. Coronary sinus pressures varied between 12 and 27 mmHg depending on factors such as the bag’s fill status and the heart’s position, but were most often around 20–23 mmHg.

In the interrupted group, cardioplegia was not administered during distal anastomoses. In this group, the bag was pressurized to deliver a similar volume of cardioplegia solution to that in the continuous group. Coronary sinus pressure was generally maintained at levels of 28–32 mmHg, with care not to exceed 40 mmHg, as this could lead to myocardial edema or rupture. While giving cardioplegia, the heart was left in a neutral position and no manipulation or compression was applied to the heart.

It has been reported that the left side of the heart generally receives more retrograde cardioplegia than the right side due to venous anatomy.² To avoid risking the right heart, we administered another dose of antegrade cardioplegia to all patients after the distal anastomoses were completed. We then performed the proximal anastomoses and removed the cross-clamp.

Perioperative myocardial infarction was defined as the appearance of new or persistent Q waves or disappearance of R waves on the electrocardiogram. Low cardiac output syndrome was defined as hemodynamic instability requiring postoperative mechanical circulatory support and/or two or more inotropic support for longer than 24 h.⁴

Statistical analysis

Categorical variables were expressed as frequencies and compared using Fisher’s exact and Chi-squared tests. Continuous variables were expressed as mean ± standard deviation and compared using the independent sample t-test. A p value < 0.05 was considered to be statistically significant.

Propensity-score matching was performed to correct the imbalance between the groups. A propensity-score was generated for each patient in the standard fashion by performing binary logistic regression with the usage of basaline charesteric of patients and number distal anastomosis. Once generated, patients were matched one-to-one on their propensity-score with a fixed caliper width of 0.02.

Results

The groups were compared in terms of age, gender, ejection fraction, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, smoking, peripheral artery disease, unstable angina pectoris, previous myocardial infarction, and left main coronary disease. There was no significant difference between the two groups in terms of other preoperative characteristics (Table 1).

Table 1.

Baseline characteristics of patients.

Characteristics	Continuous group (n = 167)		Intermittent group (n = 167)
Characteristics	n (%)	Mean ± SD	n (%)	Mean ± SD
Age (year)		64.01 ± 19.74		64.05 ± 10.69	0.316
EF (%)		60.22 ± 10.69		59.05 ± 10.55	0.316
Sex, female	37 (22.2)		30 (18.0)		0.339
Hypertension	76 (45.5)		82 (49.1)		0.511
DM	39 (23.4)		38 (22.8)		0.897
COPD	41 (24.6)		39 (23.4)		0.798
PAD	8 (4.8)		10 (6.0)		0.628
Smoking	65 (49,6)		66 (50.4)		0.911
USAP	114 (68.3)		116 (69.5)		0.813
Previous MI	63 (37.7)		77 (46.1)		0.121
LMC	26 (15.6)		35 (21.0)		0.238

EF: ejection fraction; DM: diabetes mellitus; COPD: chronic obstructive pulmonary disease; PAD: peripheric artery disease; USAP: unstable angina pectoris; MI: myocardial infarction; LMC: left main coronary.

Intraoperative data are summarized in Table 2. The mean cardioplegia volume per patient was significantly higher in the intermittent group than the continuous group (4070 ± 760 vs 3190 ± 575 mL, respectively, p = 0.001). There was no difference between the groups in terms of mean cross-clamp time and total perfusion time (p = 0.166 and 0.250, respectively).

Table 2.

Intraoperative data of patients.

Variables	Continuous group (n = 167)	Intermittent group (n = 167)	p value
Number of distal anastomosis	3.33 ± 0.78	3.35 ± 0.77	0.332
ACC time (min)	104.03 ± 29.55	108.34 ± 26.85	0.166
CPB time (min)	136.99 ± 32.25	131.14 ± 31.90	0.250
Total cardioplegic volume (ml)	3190 ± 575	4070 ± 760	0.001
Max potassium (mEq/L)	5.28 ± 1.61	5.42 ± 1.19	0.079
Spontaneous sinus rhythm, n (%)	127 (76.0)	133 (79.6)	0.242

ACC: aortic cross-clamp; CBP: cardiopulmonary bypass.

The perioperative mortality was 3-fold lower in the intermittent group but was not statistically significant (1.8% vs 0.6%, p = 0.623). There was no significant difference between two groups regarding to the mean intubation time, length of intensive care unit and hospital stays. The incidence of atrial fibrillation were similar within the two groups. Mean Troponin T and CK-MB levels on the first postoperative day, as indicators of myocardial protection, showed no significant differences. Similarly, perioperative myocardial infarction, postoperative low cardiac output syndrome, inotropic support, and intra-aortic balloon pump usage did not differ significantly between the groups (Table 3).

Table 3.

Postoperative datas of patients.

Variables	Continuous group (n = 167)	Intermittent group (n = 167)	p value
Mortality, n (%)	3 (1.8)	1 (0.6)	0.623
Intubation period (h)	11.25 ± 8.65	10.70 ± 5.87	0.523
ICU stay (day)	2.11 ± 0.712	2.20 ± 0.555	0.171
Hospital stay (day)	6.53 ± 1.91	6.32 ± 2.86	0.383
CK-MB (u/L)^a	30.85 ± 14.55	32.51 ± 16.29	0.319
Troponin T (u/L)^a	1.1 ± 0.98	1.2 ± 0.72	0.182
Atrial fibrillation, n (%)	11 (6.6)	14 (8.4)	0.533
Perioperative MI	0 (0)	0 (0)	0.230
Intraaorticballoon, n (%)	1 (0.6)	0 (0)	0.318
Inotropic support, n (%)^b	10 (6.0)	14 (8.4)	0.397
Low cardiac output, n (%)	5 (3.0)	3 (1.8)	0.723

ICU: intensive care unit; CK-MB: creatine kinase muscle and brain; MI: myocardial infarction.

^aThe values of postoperative first days.

^bExcept low cardiac output syndrome.

Discussion

Retrograde cardioplegia can be delivered continuously or intermittently.³ However, it is still controversial which retrograde delivery technique provides the best results for the cardiac protection. In this retrospective, propensity score-matched study, no significant differences were observed between the two methods of retrograde cardioplegia. Given that intermittent cardioplegia provides a bloodless surgical field and enhances surgical comfort, its use appears reasonable and safe.

Some authors argue that continuous delivery is the optimal choice because infusion time is more critical than dose, as oxygen utilization is over time in blood cardioplegia.³ It has also been shown that intermittent infusion can reduce the myocardial protective effects of cardioplegia, especially under normothermic conditions (37°C).^5,6 In case of intermittent or non-homogenous cardioplegic delivery, reducing the cardiac temperature from 37°C to 29°C may prevent ischemic injury.^7,8 In a recent article, it has been reported that if the cardioplegic delivery is not interrupted for more than 10 min, warm cardioplegia may result in the same short-term mortality as cold cardioplegia and even reduces adverse postoperative events and morbidity.⁹ These results indicate that prolonged interruption during intermittent cardioplegia may compromise myocardial protection under normothermic conditions, but this risk is negligible with hypothermic or tepid cardioplegia. As tepid cardioplegia was used in our patients, intermittent administration was considered safe and well-tolerated.

We have some concerns about homogenous and effective distribution of cardioplegia when used in a continuous fashion. Almost all studies have reported that continuous retrograde cardioplegia must often be interrupted to achieve a dry site for the creation of distal anastomoses. The situation is similar in valve patients. To ensure adequate surgical visibility, the infusion rate is kept very low and retrograde cardioplegia is interrupted from time to time.¹⁰ Also, manipulations during positioning the heart and compressions to maintain the final position restrict the delivery and reduce the total cardioplegic volume. The time period is very limited in which there is no compression to heart and the solution distributed freely. In accordance with the above result, Yılık et al.¹¹ reported that the total mean cardioplegic volume was 1950 ± 735 mL and 2280 ± 610 mL in patients receiving continuous and intermittent retrograde cardioplegia, respectively (p < 0.05). Intermittent cardioplegia delivered between the anastomoses offers a more effective distribution because the heart is free. In our study, the higher volume of cardiopegia given in the intermittent group may be explained by this situation. Another reason is that the cardioplegia solution can be administered with a higher flow rate by applying pressure in the intermittent group.

The coronary sinus pressure is of utmost importance during retrograde cardioplegia. The pressure must be maintained at a certain level for an effective delivery of the cardioplegic solution into the coronary vascular bed. Despite some concerns on the gravitational force in this regard, it has been reported that it can provide adequate flow-out in coronary arteries.^12,13 In another study, Huang et al.¹⁴ have indicated that increasing the coronary sinus perfusion pressure from 20 mmHg to 30 mmHg and to 40 mmHg thereafter, has no remarkable impact on the delivery of cardioplegic solution. Several studies investigating the optimal pressure for retrograde cardioplegia have revealed that a coronary sinus pressure of above 40 mmHg might contribute to the coronary sinus injury, as well as perivascular hemorrhage and myocardial edema.¹⁵ In our study, coronary sinus pressures ranged from 12 to 27 mmHg in the continuous group and between 25 and 40 mmHg in the intermittent group.

In the intermittent group, cardioplegia was paused during distal anastomosis, so a substantially longer cross-clamp time was anticipated; however, the mean increase was only 3 min. This suggests that anastomoses were performed more comfortable in the intermittent group. Indeed, the bloodless surgical field has enabled faster, safer and easier anastomoses. This slight prolongation of cross-clamp time did not result in an increase in cardiopulmonary bypass duration.

There were no significant differences between the groups in postoperative clinical results such as mortality, perioperative MI, postoperative low cardiac output syndrome, inotropic drug use, and intraaortic balloon pump support. These results support that concerns about the intermittent technique are unwarranted.

In the current study, the mean maximum potassium level was slightly higher in the intermittent group than in the continuous group, which can be explained by higher volumes of cardioplegic solution in these patients. However, it did not result in any complications when weaning from CPB.

Conclusion

In accordance with the principles of the procedure, pressurized intermittent delivery of retrograde blood cardioplegia facilitates distal anastomoses without adverse effect on myocardial protection. Therefore, we conclude that intermittent cardioplegia is a reasonable and practical option, as it provides a bloodless surgical field that facilitates operative comfort without compromising clinical outcomes.

Footnotes

ORCID iDs

Kemal Uzun

Muhammet Onur Hanedan

Hakan Kara

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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