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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 11
| Issue : 1 | Page : 46-51 |
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Comparison of postoperative outcomes of milrinone versus dobutamine in tetralogy of Fallot with transannular patch
Ishan Gohil, Herin Patel, Devvrat Desai, Jignesh Kothari
Department of Cardio Vascular and Thoracic Surgery, U. N. Mehta Institute of Cardiology and Research Centre, (Affiliated to B. J. Medical College), New Civil Hospital Campus, Ahmedabad, Gujarat, India
| Date of Submission | 31-Jan-2023 |
| Date of Decision | 02-Mar-2023 |
| Date of Acceptance | 04-Mar-2023 |
| Date of Web Publication | 12-Apr-2023 |
Correspondence Address:
Jignesh Kothari
Department of Cardio Vascular and Thoracic Surgery, U. N. Mehta Institute of Cardiology and Research Centre, (Affiliated to B. J. Medical College), New Civil Hospital Campus, Ahmedabad, Gujarat
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/heartindia.heartindia_10_23
Background: Since the original description of TOF, its management modalities are continuously evolving. Present modality includes complete correction of the pathology by intra-cardiac repair with or without using transannular patch. Various finer aspects of intraoperative and postoperative management of the TOF repair are still evolving.
Aims and Objectives: In this single centre study we are aiming to compare short term outcomes in patients of tof operated with transannular patch repair treated postoperatively with dobutamine vs milrinone.
Materials and Methods: Total 100 patients undergoing TOF repair with transannular patch were grouped with respect to the inotropes used. One group who received milrinone and other who received dobutamine. Postoperative outcomes depending upon the need of other inotropic support, duration of ventilatory support, icu stay , inotropic support , hospital stay , morbidity and mortality are compared between the groups.
Observations: No significant difference was seen in both groups for mean ventilation time, duration of icu and hospital stay. Only parameter which was significant was increase in usage of adjuvant inotropic support in milrinone group which were depicted in terms of increased VIS ( Vasoactive inotrope score). Almost equal incidence of adverse events were noted in both the groups.
Conclusion: Milrinone and dobutamine are fairly comparable to each other in cases of TOF repair with transannular patch. Dobutamine being a cheaper alternative have a better scope in developing countries like India.
Keywords: Tetralogy of Fallot, transannular patch, ventricle septal defect, milrinone, dobutamine , milrinone versus dobutamine
How to cite this article:
Gohil I, Patel H, Desai D, Kothari J. Comparison of postoperative outcomes of milrinone versus dobutamine in tetralogy of Fallot with transannular patch. Heart India 2023;11:46-51 |
How to cite this URL:
Gohil I, Patel H, Desai D, Kothari J. Comparison of postoperative outcomes of milrinone versus dobutamine in tetralogy of Fallot with transannular patch. Heart India [serial online] 2023 [cited 2023 May 28];11:46-51. Available from: https://www.heartindia.net/text.asp?2023/11/1/46/374099 |
| Introduction | |  |
Tetralogy of Fallot (TOF) is one of the common cyanotic congenital heart diseases. Of all infants born with congenital heart disease, 3%–5% have TOF. Significant advances have been made in the surgical repair of this defect with 90% of patients now surviving to adulthood.[1] Many structural and functional abnormalities are encountered frequently after TOF repair. Partial or complete removal of pulmonary valve tissue, infundibulectomy scar, resection of right ventricle (RV)/infundibular muscle tissue, right atriotomy, and ventricular septal defect (VSD) patch are inherent structural abnormalities after TOF repair.
Pulmonary regurgitation, tricuspid regurgitation (TR), and various collaterals eventually increase volume overload over RV and lead to decrease in its efficiency and eventual RV failure.[2] Infundibular hypertrophy has to be respected as to relieve the RV outflow tract (RVOT) obstruction. This resection and valvular regurgitation contribute to the RV dysfunction and eventually biventricular dysfunction in every patient undergoing this surgery and thus the use of inotropes is obligatory while weaning of cardiopulmonary bypass (CPB) and in the immediate postoperative period. Dobutamine was used in this situation since the advent of surgery particularly due to its effect on inotropy, chronotropy, and decrease of systemic vascular resistance (SVR).[3] Later on, milrinone was discovered to have a similar but stronger effect and was used instead in many centers.[4] Milrinone has added advantage of its effect on pulmonary vascular resistance, this may be the reason it is the preferred drug in many of the centers. Since then the efficacy of both of these drugs are compared in a variety of situations,[3] but specifically in patients of transannular patch (TAP) repair in TOF in terms of hospital stay and morbidity is not yet established which is tried to achieve in this study.
| Patient and Methods | | |
Study population
As a part of retrospective analysis, a total of 100 patients were chosen who underwent TOF repair with TAP in UNMICRC. The criteria were such that half of the patients had received dobutamine and half milrinone as part of intraoperative and postoperative inotrope. Thus, 50 patients received dobutamine and 50 received milrinone inotrope.
TOF with pulmonary atresia, absent pulmonary valve, associated with other congenital heart diseases, undergoing RVOT patch redo cases, emergency cases, and other cases with TOF physiology – atrioventricular conduction disorder were excluded from the study.
Evaluation
Preoperative parameters
Preoperative assessment was done using modalities such as electrocardiogram, X-ray, and two-dimensional (2D) echocardiography (ECHO), and if in doubt, computed tomography angiography was done after discussion with the cardiologist to determine the adequacy of pulmonary artery for one-staged repair using TAP. In preoperative 2D ECHO, the main parameters to be seen are the presence of RVOT infundibular stenosis and gradient across it, pulmonary annulus (PA) annulus, right pulmonary artery (RPA) and left pulmonary artery (LPA) size and its Z-score, the presence and degree of mitral regurgitation or TR, and ejection fraction. Intraoperatively, cross-clamp and CPB time were noted.
Intraoperative techniques and evaluation
Surgical procedure for TOF correction with TAP involves aortic and bicaval cannulation with St. Thomas II Cardioplegia solution. Trans Right atrium (RA) VSD closure was done with polytetrafluoroethylene patch with continuous and interrupted suturing technique. RVOT and pulmonary valve opened and infundibular resection was done. Proper-sized Hegar dilators passed through RVOT, main pulmonary artery, RPA, and LPA. If required, pulmonary valvotomy is done with knife. If Z-score is less than minus 2, then augmentation is done. RVOT and opened pulmonary vein closure were done using fresh untreated pericardial patches such that the patch crosses over the pulmonary valve annulus.
On completion of the procedure, RV pressure/left ventricularand central venous pressure were noted intraoperatively. Adynamic gradient of <40 mmHg across RVOT was accepted and if found more would be amenable for further RVOT resection by going on CPB.
Patients will be provided either dobutamine or milrinone, which will be started while weaning of CPB. Milrinone was given 0.5 μg/kg loading dose, followed by 0.05 μg/kg/min infusion. If dobutamine is to be started then, no loading is necessary and the infusion is started at 0.5 μg/kg/min. These will be continued along with other inotropes in the early postoperative period and weaning is initiated once the cardiac condition is stabilized.
Postoperative assessment
Among the objective components, mechanical ventilation hours, total inotropic support in hours, intensive care unit (ICU) stay in hours, drain output, and total hospital stay. Follow-up postoperative ECHO was done in the immediate postoperative period within 24 h of surgery, on 7th postoperative day (POD), and in 4th week.
In this study, we use vasoactive-inotrope score (VIS) as a marker of inotropic burden for two reasons, first, to know the net effect of the inotropic action provided by milrinone and dobutamine in either of the group and second, to eliminate the bias of the confounding different inotropes which are there along with milrinone and dobutamine and to maintain the uniformity.
Wernovsky IS = dopamine dose (μg/kg/min)
+ dobutamine dose (μg/kg/min)
+100 × epinephrine dose (μg/kg/min)
VIS = IS + 10 × milrinone dose (μg/kg/min)
+10,000 × vasopressin dose (U/kg/min)
+100 × norepinephrine dose (μg/kg/min)
As in this study, we are comparing the difference in the outcome of patients who were on milrinone versus patients who were on dobutamine we have all the patients undergoing transthoracic echocardiographic analysis and pointing out specific aspects of RV dysfunction as per the proforma.
Duration of mechanical ventilation, duration of inotropic support, and duration of ICU stay were noted in every patient. Repeat transthoracic echocardiogram (TTE) was done on POD7 and the function of heart was assessed and compared with the previous ECHO.
Any specific complication in the postoperative period, namely low cardiac output syndrome (LCOS), reintubation, septicemia, RV dysfunction, wound infection, or mortality, is noted.
| Results | | |
In demographics, we can see slightly male preponderance with 68 males and 32 females [Table 1].
Majority of the patients (76%) had SpO2 between 70% and 90% [Table 2].
All the patients had PA annulus Z-score of Less than -3 hence were candidates of TAP.
In preoperative echo evaluation, the majority of the patients (96%) had RVOT Gmax of more than 50 mmHg.
Infundibular spasm was present in all cases with varied degrees of stenosis across the RVOT ranging the RVOT Gmax from 36 mmHg to 94 mmHg [Table 3].
These above factors were uniformly distributed in both groups.
Intraoperatively, timing of CPB and the cross-clamp time was noted in all patients of both groups, and the average of both groups was noted and P value was more than 0.05 deeming it to be nonsignificant [Table 4].
In the ICU, ventilation duration, inotropic duration, ICU stay in hours, and mean hospital stay in day are noted in every patient in both groups.
The mean and P value of each category are noted in [Table 5].
To know the cumulative effect of these inotropes inpatient, VIS was calculated in patients of both groups and the mean VIS score was noted [Table 6].
P value of VIS is 0.0001 which makes it extremely significant and hence it means the overall burden of inotropes is significantly increased in patients with milrinone as compared with patients who had dobutamine as the chief inotrope as adrenaline and noradrenaline is used in the majority of the cases with milrinone as compared to the rare need of the same in patients receiving dobutamine.
All the adverse events in the patient were noted and classified in accordance to the groups created. Most common complication was LCOS, followed by septicemia, wound infection, and RV failure. There was one case of postoperative chylothorax, and there was no mortality in our study [Table 7].
Even on the categorization of the patients into milrinone and dobutamine, the complications are almost of the same frequency but due to the low frequency of both the statistical significance cannot be commented upon.
| Discussion | | |
TOF is not a disease with absolute single morphology but a whole spectrum of variations in different components of heart morphology. Each point of this spectrum gives rise to a different physiology in heart, depending on it the patients symptoms present. Only thing constant about this disease is the majority of cases are symptomatic by end of 1st year of their life due to poor pulmonary blood flow.
Many attempts have been made for the surgical treatment of TOF. The very first attempt of treating a case of TOF was done by Blalock and Taussing[5] in 1945 by doing a palliative subclavian to pulmonary artery shunt. It was done in view to increase the pulmonary blood flow and hence increase the proportion of saturated blood in cardiac output. This was followed by different types of shunts leading to an increase in pulmonary flow, namely, Potts[6] and Waterston-Cooleys shunt.[7] All of these were at the end palliative shunts which did not alter the core anatomy of the lesion but would buy time for further management strategies.
TOF was first successfully repaired by Lillehei et al.[8] at the University of Minnesota in 1954 using controlled cross-circulation with another person serving as oxygenator. The first successful repair of Tetrology of Fallot (TF) using a pump-oxygenator was done by Kirklin et al.[9] at the Mayo Clinic in 1955. These small steps in the evolution of TOF repair have lead us to the stage where we are today which is the single-stage intracardiac repair of TOF.
It is proved beyond doubt that irrespective of any case from the entire spectrum, the best method of correction of TOF is complete anatomical correction with the intracardiac repair of the individual problems, namely infundibular and/or pulmonary stenosis and VSD, the rest are been taken care of automatically. A clear majority of the patients who undergo TAP repair have free Pulmonary regurgitation (PR) in the postoperative period. This PR directly impacts the Right ventricular end diastolic volume (RVEDV) and thus the function of RV.
Over time, many inotropes are used in weaning off CPB and the early postoperative period to overcome the effect of PR on RV. With the advent of newer inotropes, they gradually replace the older ones without proven by a randomized controlled trial or meta-analysis and at times purely out of excitement. Although it must be noted that there are multiple factors affecting the patient in smooth recovery in the early postoperative period which can be considered confounding factors in this case, all these factors affect the patients uniformly and hence not given individual unduly importance.
Comparing the postoperative TTE and the length of inotropes, mechanical ventilation and ICU stay required for the patient in both groups, it is evident that patients from both groups had no significant difference in these variants.
The VIS of both groups was statistically significantly different. Much more VIS was observed in the milrinone group than the dobutamine group, the reason being milrinone as a sole inotrope is used very rarely and majority of times, adrenaline and/or noradrenaline were accompanied along with it to improve the mean pressure. As opposed to it, dobutamine is rarely used in adjunct to inotrope thus making its VIS significantly less than the milrinone group. Less VIS is in direct correlation with long-term morbidity and mortality, especially in pediatric cardiac surgery patients. Hence, we can conclude that dobutamine is deemed safer as an alternative.
The complication rates of the two compared groups were showing no statistical significant differences.
Dr. George Mager et al.[10] compared milrinone as an alternative to dobutamine in patients with severe heart failure leading to the conclusion that in comparison with dobutamine sequentially administered milrinone showed more benefit and seemed to be the better medication for the treatment of severe heart failure with less side effects and tolerance. Here, a Swan-Ganz catheter was introduced and Pulmonary capillary wedge pressure and Pulmonary vascular resistance (PCWP and PVR) were looked for as indicators of recovery.
Even Dr. Robert o. Feneck et al.[11] compared dobutamine and milrinone in cardiac surgery patients suggesting both drugs are equally effective in pulmonary hypertension when compared using parameters such as cardiac index, PCWP, (PVRI) Pulmonary Vascular Resistance Index, mean arterial pressure (MAP), SVR, and heart rate (HR). However, when the reversal of hypotension and chronotropic response is required, dobutamine appears to be preferable. When more pronounced vasorelaxant effects and the avoidance of tachycardia are required, milrinone appears to be a better alternative.
Dorthe Viemose et al.[12] had a retrospective study conducted in over 10,000 cardiac surgery patients requiring CPB and the role of dobutamine and milrinone in the end-stage outcome of those patients. This study had perioperative morbidity and mortality along with the hospital stay as the chief determinants to know the outcome. These same parameters were used in our case as variants. In this study, it was concluded that milrinone increases all-cause mortality in early outcomes in such patients.
Sunny et al.[13] did a prospective study over 2 years of patients for comparison of ionotropic drugs such as levosimendan, milrinone, and dobutamine with outcomes of low cardiac output in cardiac surgeries performed with CPB. Here, MAP, HR, stroke volume, and in hospital stay were the key indices to be observed for the efficacy of the drug in low cardiac output state. It was concluded that dobutamine is as effective as levosimendan and more effective than milrinone in preventing postoperative low cardiac output state in such patients.
From the above discussion on literature, it is evident that though milrinone has been compared with dobutamine in various occasions in cardiac surgery but none of the drugs has established statistically significant more efficacious than other for the improvement of low cardiac output but it is the careful selection of the drug in patient to patient basis which helps in improvement of the outcome.
We can thus conclude that using milrinone or dobutamine does not make a significant difference in the immediate postoperative outcome of patients undergoing TOF repair with TAP. VIS is statistically significant in both groups thus indirectly leading to increased morbidity. It must also be noted that the cost and availability between the two drugs are significantly different, especially in developing countries and this grossly affects the implication of the above sentence.
In a developing country like India, more than 80% of health care are taken care by government hospitals. Furthermore, being a densely populated country, the patient load pertaining to each disease is quite more. Hence, the load of TOF being the most common cyanotic congenital heart disease whole global prevalence is 0.5/1000[14] live births can be estimated of. More expensive drugs such as milrinone should be spared for its other indications rather than using it in these cases as there is no significant benefit in these cases over dobutamine.
One cannot ignore the fact that milrinone is a relatively recent drug which was made popular in this new century. However, surgeries related to TOF predate much before this era. It seems as if the enthusiasm of new drug culture has made milrinone as a frontline drug for cases such as these but it must be duly noted that as per our above study, both drugs are comparable to each other and dobutamine is as safer than milrinone in postoperative patients of TOF without much of adverse effects.
| Conclusion | | |
Based on above prospective one can fairly conclude that dobutamine and milrinone are both comparable to each other in patients of TOF operated with TAP. However, dobutamine being a cheaper drug is more preferable in developing countries like India and it should be extended to other countries as well. Thus, a change in mindset and change in the protocol should be given a thought.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Ethical approval
Institutional Ethics Committee approval has been taken before this publication.
Authors' contributions
Ishan Gohil: Concepts, Design; Clinical studies, Experimental studies; Herin Patel: Clinical studies, Experimental studies; Devvrat Desai: Design; Clinical studies; Jignesh Kothari: Concepts, Design; Clinical studies, Experimental studies.
| References | | |
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| 2. | Tverskaya MS, Mishnev OD, Raksha AP, Karpova VV, Sukhoparova VV, Izmailova NS, et al. Comparative pathomorphological study of contractile myocardium under conditions of increased left and right ventricular afterload. Bull Exp Biol Med 2004;138:616-20. |
| 3. | Roeleveld PP, de Klerk JC. The perspective of the intensivist on inotropes and postoperative care following pediatric heart surgery: An international survey and systematic review of the literature. World J Pediatr Congenit Heart Surg 2018;9:10-21. |
| 4. | Carmona MJ, Martins LM, Vane MF, Longo BA, Paredes LS, Malbouisson LM. Comparison of the effects of dobutamine and milrinone on hemodynamic parameters and oxygen supply in patients undergoing cardiac surgery with low cardiac output after anesthetic induction. Rev Bras Anestesiol 2010;60:237-46. |
| 5. | Blalock A, Taussig HB. Landmark article May 19, 1945: The surgical treatment of malformations of the heart in which there is pulmonary stenosis or pulmonary atresia. By Alfred Blalock and Helen B. Taussig.JAMA 1984;251:2123-38. |
| 6. | Potts WJ, Smith S, Gibson S. Anastomosis of the aorta to a pulmonary artery; certain types incongenital heart disease. J Am Med Assoc 1946;132:627-31. |
| 7. | Waterston DJ. Treatment of Fallot's tetralogy in children under 1 year of age. Rozhl Chir 1962;41:181-3. |
| 8. | Lillehei CW, Varco RL, Cohen M, Warden HE, Patton C, Moller JH.The first open-heart repairs of ventricular septal defect, atrioventricular communis, and tetralogy of Fallot using extracorporeal circulation by cross-circulation: A 30-year follow-up. Ann Thorac Surg 1986;41:4-21. |
| 9. | Kirklin JW, Dushane JW, Patrick RT, Donald DE, Hetzel PS, Harshbarger HG, et al. Intracardiac surgery with the aid of a mechanical pump-oxygenator system (gibbon type): Report of eight cases. Proc Staff Meet Mayo Clin 1955;30:201-6. |
| 10. | Mager G, Klocke RK, Kux A, Höpp HW, Hilger HH. Phosphodiesterase III inhibition or adrenoreceptor stimulation: Milrinone as an alternative to dobutamine in the treatment of severe heart failure. Am Heart J 1991;121:1974-83. |
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| 13. | Sunny MY, Karim HM, Saikia MK, Bhattacharyya P, Dey S. Comparison of levosimendan, milrinone and dobutamine in treating low cardiac output syndrome following valve replacement surgeries with cardiopulmonary bypass. Journal of clinical and diagnostic research: JCDR. 2016;10:UC05. |
| 14. | Shinebourne EA, Andersen RH. Fallot's tetralogy. In: Anderson RH, Baker E, Macartacy F, Right ML, Shinebourne EA, M Tynan, editors. Pediatric Cardiology. 2 nd ed. London: Terontec Churchll Livingstone; 2012. p. 1213-32. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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