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Clinical Outcomes of Del Nido Cardioplegia and St Thomas Blood Cardioplegia in Neonatal congenital Heart Surgery

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Objectives: Cardioplegia is essential for adequate myocardial protection. There continues to remain ambiguity regarding the ideal cardioplegia for adequate myocardial protection in congenital heart surgery. This study compares clinical outcomes using St Thomas II solution and Del Nido cardioplegia in neonates undergoing cardiac surgery. Methods: All neonates (<30 days) from 2011 to 2017 who underwent surgery requiring cardioplegic arrest were analyzed retrospectively. We divided the cohort into two groups depending on cardioplegia received, as group A (Blood cardioplegia with St Thomas II solution, n = 56) and group B (Del Nido cardioplegia, n = 48). Various demographic, intraoperative, early postoperative, and discharge variables were analyzed. Results: Two groups were similar in age, gender, pre-operative diagnosis, and risk category. Cardiopulmonary bypass (CPB) time (P = 0.002), aortic cross-clamp (ACC) time (P = 0.018), and the number of doses of cardioplegia (P < 0.001) were significantly lower with Del Nido group. Though vasoactive inotropic score (VIS) (P = 0.036) was high during the first 24 h in the immediate postoperative period in group A, there was no difference in early mortality among both groups (P = 0.749). Both groups did not show significant differences related to various postoperative and discharge variables. Conclusion: When compared to St. Thomas solution, the use of Del Nido cardioplegia solution in neonates is associated with a significant decrease in CPB and ACC times and VIS in the first 24 h after surgery. The choice of cardioplegia (St Thomas/Del Nido) in neonates does not affect early mortality and early postoperative clinical outcomes.
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54 © 2022 Annals of Cardiac Anaesthesia | Published by Wolters Kluwer - Medknow
Clinical Outcomes of Del Nido Cardioplegia and St Thomas
Blood Cardioplegia in Neonatal congenital Heart Surgery
Sameer Mohammed, Sabarinath Menon, Shrinivas V. Gadhinglajkar1, Sudip D. Baruah, Soumya V. Ramanan,
Arun Gopalakrishnan K2, Suneel P R1, Baiju S. Dharan
Departments of Cardiovascular and Thoracic Surgery, 1Cardiovascular and Thoracic Anesthesia, and 2Cardiology, Sree Chitra Tirunal
Instute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
Original Article
INTRODUCTION
The majority of congenital heart surgeries involve
diastolic cardiac arrest as one of the strategies to maintain
adequate myocardial protection.[1] Hence, cardioplegia
forms the prime basis to perform the surgical repair. The
development of cardioplegia was a signicant milestone
in the history of cardiac surgery. Since the development
of potassium citrate solution by Melrose et al.,[2] numerous
cardioplegia solutions have been developed and used in
various centers worldwide.
Among various types of cardioplegia solutions, blood
cardioplegia with St Thomas II and Del Nido cardioplegia
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DOI:
10.4103/aca.aca_220_20
ABSTRACT
Objectives: Cardioplegia is essential for adequate myocardial protection. There continues to remain ambiguity regarding the ideal cardioplegia
for adequate myocardial protection in congenital heart surgery. This study compares clinical outcomes using St Thomas II solution and Del Nido
cardioplegia in neonates undergoing cardiac surgery.
Methods: All neonates (<30 days) from 2011 to 2017 who underwent surgery requiring cardioplegic arrest were analyzed retrospectively.
We divided the cohort into two groups depending on cardioplegia received, as group A (Blood cardioplegia with St Thomas II solution,
n
= 56)
and group B (Del Nido cardioplegia,
n
= 48). Various demographic, intraoperative, early postoperative, and discharge variables were analyzed.
Results: Two groups were similar in age, gender, pre‑operative diagnosis, and risk categor y. Cardiopulmonary bypass (CPB) time (
P
= 0.002),
aortic cross‑clamp (ACC) time (
P
= 0.018), and the number of doses of cardioplegia (
P
< 0.001) were significantly lower with Del Nido group.
Though vasoactive inotropic score (VIS) (
P
= 0.036) was high during the first 24 h in the immediate postoperative period in group A, there was
no difference in early mortality among both groups (
P
= 0.749). Both groups did not show significant differences related to various postoperative
and discharge variables.
Conclusion: When compared to St. Thomas solution, the use of Del Nido cardioplegia solution in neonates is associated with a significant
decrease in CPB and ACC times and VIS in the first 24 h after surgery. The choice of cardioplegia (St Thomas/Del Nido) in neonates does not
affect early mortality and early postoperative clinical outcomes.
Keywords: Clinical outcomes, Del Nido cardioplegia, neonatal congenital heart surgery, St Thomas blood cardioplegia,
vasoactive ionotropic score
How to cite this article: Mohammed S, Menon S, Gadhinglajkar SV,
Baruah SD, Ramanan SV, Gopalakrishnan KA, et al. Clinical outcomes of Del
Nido cardioplegia and St Thomas blood cardioplegia in neonatal congenital
heart surgery. Ann Card Anaesth 2022;25:54-60.
This is an open access journal, and arcles are distributed under the terms of the Creave
Commons Aribuon‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
is given and the new creaons are licensed under the idencal terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
Address for correspondence: Dr. Sabarinath Menon, Department of Cardiovascular and Thoracic Surgery, Sree Chitra Tirunal Instute for Medical Sciences
and Technology, Thiruvananthapuram, Kerala ‑ 695 011, India.
E‑mail: sabarinath.menon@gmail.com
Submied: 01‑Sep‑2020 Revised: 29‑Apr‑2021 Accepted: 10‑May‑2021 Published: 21‑Jan‑2022
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Mohammed, et al.: Comparison of outcomes of cardioplegia in neonatal cardiac surgery
Annals of Cardiac Anaesthesia | Volume 25 | Issue 1 | January-March 2022 55
of our institution. The study is retrospective by design,
and data is collected from the institutional database and
the medical records department. All neonates (<30 days)
who underwent congenital heart surgery from 2011
to 2017, requiring cardiopulmonary bypass (CPB) and
cardioplegic arrest, were included. Those who underwent
surgery without CPB or where a cardioplegic arrest was
not required were excluded from the study.
The study population consisted of two groups based
on the type of cardioplegia solution administered.
Group A – patients who received blood cardioplegia with
St. Thomas II solution and Group B – patients who received
Del Nido cardioplegia solution [Table 1]. There was no age
bias, as the study population includes only neonates.
Surgical procedure and cardioplegia protocol
All operations were performed by three senior surgeons,
with expertise in neonatal cardiac surgery to avoid operator
bias. The same perfusion team has handled all the above
neonatal surgeries. There was no change in anesthesia and
perfusion protocol during the study period. All operations
were performed by primary median sternotomy, systemic
hypothermia, cardioplegic myocardial protection with
topical ice‑cold saline cooling. There were no signicant
changes in inotrope and postoperative management
strategies among both groups in the intraoperative and
postoperative periods.
At our institute, St Thomas II cardioplegia was used until
2014. Since outcomes following Del Nido cardioplegia
were promising, we changed our approach to myocardial
protection to Del Nido cardioplegia since 2014. All three
surgeons changed the approach at the same time.
We prepared the St Thomas II cardioplegia as four parts
of blood taken from the arterial outlet with one part of the
Ringer’s lactate solution to which St. Thomas type 2 solution
is added. Two strengths of the solution‑‑‑high strength for
initiation dose and low strength for maintenance dose were
are the most commonly used in neonatal cardiac
operations. Blood cardioplegia with St Thomas II solution
is an extracellular cardioplegia with high potassium
concentration, which acts predominantly by depolarizing
the cell membrane. This method of arrest involves
perfusing repetitive dosing of cardioplegia once every
20‑‑30 min. Repetitive dosing may interrupt the operation
and may result in inadequate myocardial protection if the
timing of cardioplegia is not appropriately followed.
The neonatal heart prefers single dose cardioplegia in
various experimental studies.[3,4] Pedro Del Nido et al.
at the University of Pittsburgh[5] developed a single
dose cardioplegia, which provides adequate myocardial
protection for more extended periods as compared
to conventional cardioplegia techniques. Del Nido
cardioplegia, a crystalloid based extracellular cardioplegia
solution, predominantly exerts its effect by depolarizing
the cell membrane. Though the potassium concentration
is lower compared to St. Thomas solution, its action
is prolonged because of magnesium and lignocaine as
additives. Lignocaine is a sodium channel blocker that
increases the myocyte refractory period. Further, it also
prevents the negative effect of hyperkalemic depolarized
arrest through its repolarizing effect. Both these additives
have also been proven to improve myocardial recovery.
The needs of an immature myocardium and its response to
ischemia remain contradictory. Immature myocardium of
neonates is known to be more tolerant to ischemia[6,7] and
their needs to achieve cardioplegic arrest differs from the
adult heart in some studies.[8] This tolerance of immature
myocardium to ischemia is enhanced in the presence of
hypothermia.[9] Whereas, few studies have demonstrated it
to be less tolerant to ischemia.[10] Furthermore, the dosing
interval of cardioplegia in immature myocardium also
remains contradictory, with few studies favoring single‑dose
and few in favor of multidose strategies.[11] Hence the
choice of cardioplegia, the dosing strategies may result in
variable clinical outcomes in neonates.
Since there remains ambiguity regarding the optimum
cardioplegic solution for adequate myocardial protection
in neonates, we compared our experience of using either
blood cardioplegia with St Thomas II solution or Del Nido
cardioplegia in neonates undergoing cardiac surgery.
MATERIALS AND METHODS
The study protocol was reviewed and approved by
the technical advisory committee (SCT/IEC/1326/
DECEMBER‑2018) and the Institutional Ethics Committee
Table 1: Composition of cardioplegia solutions
Group A Group B
Blood Cardioplegia in St.
Thomas solution
Del Nido cardioplegia
Blood: Crystalloid 4: 1 Blood: Crystalloid 1: 4
Ringer’s lactate 320 ml Plasmalyte‑A 500 ml
Mannitol 20 ml KCl (2 meq/ml) 6.5 ml
Bicarbonate 20 ml NaHCO36.5 ml
St. Thomas solution 40 ml
KCl 16 mmol
MgCl2 16 mmol
Procaine 1 mmol
Lidocaine 2% 3.25 ml
Mannitol 8.15 ml
MgSO4 50% 2 ml
KCl – Potassium chloride, MgCl2 – Magnesium chloride,
MgSO4 – Magnesium Sulfate, NaHCO3 – Sodium bicarbonate
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Mohammed, et al.: Comparison of outcomes of cardioplegia in neonatal cardiac surgery
56 Annals of Cardiac Anaesthesia | Volume 25 | Issue 1 | January-March 2022
prepared. Cardioplegia is delivered through a cardioplegia
delivery system at 6‑‑8°C at a dose of 20 ml/kg for
initiation and 10 ml/kg for maintenance once every 30 min.
We prepared Del Nido cardioplegia with one part of
blood and four parts of the crystalloid (Plasmalyte A)
solution [Table 1], which was delivered at 6‑‑8°C. Cardioplegia
is delivered at a dose of 20‑‑30 ml/kg for induction and
10 ml/kg for maintenance of cardiac arrest once every
90‑‑120 min. depending on the duration of the procedure
or return of cardiac activity. In both the groups, cardioplegia
was delivered through aortic root by antegrade approach.
Common congenital anomalies included the
Dextro‑Transposition of Great Arteries (D‑TGA)
and obstructed total anomalous pulmonary venous
connection (TAPVC). The intraoperative and postoperative
variables like Cardiopulmonary bypass (CPB) time, Aortic
cross‑clamp (ACC) time, the number of cardioplegia doses,
post‑CPB and postoperative (within rst 24 h) arrhythmias,
postoperative blood transfusion, vasoactive inotropic
score (VIS) within rst 48 h were collected from intensive
care unit charts.
Postoperative outcomes assessed were low cardiac output
syndrome (LCOS) in the rst 24 h, the number of ventilatory
hours, ICU stay, the total duration of hospital stay, and
renal dysfunction. Left ventricular function was assessed
by echocardiography before discharge. We dened early
mortality as death within 30 days of operation. LCOS was
dened as the presence of oliguria of less than 1 ml/kg/h
or anuria with a rising trend of lactate level and an increase
in inotropic score in the rst 24 h. Though cardiac index,
inammatory markers, and markers of myocardial injury like
troponin levels are better indicators of low cardiac output in
the immediate postoperative period, these variables were not
studied as we routinely do not measure these at our institution.
Statistical analysis
All collected data paired among both groups and analyzed
using SPSS software (SPSS Inc, Chicago, Illinois, USA) and
data are represented as mean with standard deviation or
median with an interquartile range as appropriate. Further
variables were assessed using the Student’s t‑test, Fischer’s
exact t‑test, and Mann‑‑Whitney test for signicance.
A P value of less than 0.05 is considered as statistically
signicant.
RESULTS
A total of 104 neonates underwent congenital heart
operations under CPB and cardioplegic arrest from
2011 to 2017. 56 neonates received blood cardioplegia
with St Thomas II solution (Group A), and 48 neonates
received Del Nido cardioplegia (Group B). Three neonates
with TAPVC had heterotaxy syndrome. Demographic
characteristics between Groups A and B are depicted
in Table 2. Cardiopulmonary bypass time (Group A
219 ± 51 min vs. Group B 184 ± 60 min, P = 0.002) and
ACC (Group A 122 ± 33 min vs. Group B 106 ± 36 min,
P = 0.018) times were signicantly lower in group B as
compared to group A as shown in Figure 1.
A variable which has shown its applicability in predicting
mortality and morbidity in postoperative setting is the
vasoactive inotropic score (VIS). On comparison of VIS
for the rst 24 h and the subsequent 24 h, VIS during
the rst 24 h (St. Thomas group A 10, IQR 7.5‑‑10;
Del Nido group ‑ B 7.5, IQR 5‑‑10) was found to be
signicantly lower in neonates operated with Del Nido
cardioplegia. Whereas there appears to be a clinically
signicant reduction of inotropic support in group A in
the next 24 h. However, this reduction was not observed
in group B. Hence, VIS in both the groups was similar in
the subsequent 24 h and did not maintain this signicant
difference.
Though blood transfusion requirement was higher during
the first 24 h in group B, there exists no significant
difference among both groups. Similarly, no signicant
difference was observed in the incidence of LCOS and
postoperative renal dysfunction (serum creatinine levels)
among both groups. There was no signicant difference
between the two groups for the number of ventilatory
hours, ICU stay, and hospital stay [Table 3]. The incidence
of postoperative arrhythmias is less in group B, but we did
not observe a statistically signicant difference.
Early mortality in this study was 10.4% (10), of which six
are from group A and four from group B. Even though
Figure 1: Comparison of CPB and ACC time (min) among both groups.
ACC – Aortic cross clamp, CPB – Cardio pulmonary bypass
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Mohammed, et al.: Comparison of outcomes of cardioplegia in neonatal cardiac surgery
Annals of Cardiac Anaesthesia | Volume 25 | Issue 1 | January-March 2022 57
number of deaths in group B are less than group A, there
was no statistically signicant difference. The survival trend
among both groups is shown in Figure 2. Subgroup analysis
based on the diagnosis of D‑TGA and obstructed TAPVC
did not reveal any significant difference in mortality
between the two groups. A detailed description of mortality
is included in Supplementary Table 1.
Of six deaths in group A, three patients had heterotaxy
syndrome with obstructed TAPVC and duct dependent
pulmonary circulation. They presented with severe acidosis,
desaturation, and maintained on prostaglandin infusion.
One patient developed sepsis with occult gastrointestinal
bleed following arterial switch procedure. Of the four
mortality in group B, one patient had HLHS and underwent
stage 1 Norwood with Sano shunt. This patient required
Extracorporeal membrane oxygenation (ECMO) support
Table 2: Demographic characteristics of both groups
Variable Group A
(n=56, 53.8%)
Group B
(n=48, 46.2%)
Total
(n=104)
P*
Age (in days), mean (SD) 17.8 (7.6) 17 (9) 17.4 (8.4) 0.627
Male, n (%) 46 (82.1) 39 (81.3) 85 (81.7) 1.00
BSA (m2), mean (SD) 0.19 (0.02) 0.19 (0.02) 0.19 (0.02) 0.29
Pre‑operative Diagnosis, n (%)
D‑TGA 38 (67.9) 32 (66.7) 70 (67.3)
Obstructed TAPVC 15 (26.8) 15 (31.3) 30 (28.8)
Heterotaxy with obstructed TAPVC 3 (5.4) 3 (2.9)
HLHS 1 (2.1) 1 (1)
RACHS category, n (%)
RACHS 3 31 (55.4) 29 (60.4) 60 (57.7)
RACHS 4 25 (44.6) 18 (37.5) 43 (41.3)
RACHS 5 0 1 (2.1) 1 (1)
Group A – Blood Cardioplegia with St. Thomas solution, Group B – Del Nido cardioplegia. BSA – Body Surface area, D-TGA: D – Transposition
of Great Arteries, HLHS – Hypoplastic Left heart Syndrome, RACHS – Risk Adjusted Congenital Heart Surgery, SD – Standard deviation,
TAPVC – Total Anomalous Pulmonary Venous Connection. *Student’s t-test
Table 3: Comparison analysis of various intra-operative and post-operative variables among two groups
Variable Group A
(n=56, 53.8%)
Group B
(n=48, 46.2%)
Total
(n=104)
P*
Cardio pulmonary bypass (CPB) time (min), mean (SD) 219.23 (51.3) 184.7 (60) 203.29 (57.87) 0.002
Aortic cross clamp (ACC) time (min), mean (SD) 122.29 (33.3) 106.02 (35.9) 114.78 (35.31) 0.018
Number of doses of cardioplegia, median (IQR) 3 (3‑4) 1 (1‑2) 2 (2‑3) <0.001
Priming Volume (ml), mean (SD) 306.95 (55.78) 319.52 (49.18) 312.75 (52.96) 0.229
Post‑op blood transfusion during first 24 hrs. (ml), median (IQR) 30 (2.5‑40) 30 (14.75‑58.75) 30 (10‑50) 0.185
Vasoactive inotropic score (VIS) first 24 hrs., median (IQR) 10 (7.5‑15) 7.5 (5‑12.5) 9 (6.62‑13.37) 0.036
Vasoactive inotropic score (VIS) next 24 hrs., median (IQR) 9 (5‑10) 7.5 (5‑10) 7.5 (5‑10) 0.592
Mechanical ventilation (hrs.), Median (IQR) 91 (66.25‑117) 89 (68‑129) 90 (67.25‑119.75) 0.876
Mean ICU stay (days), Median (IQR) 9.5 (8‑13.75) 10.5 (7‑14.75) 10 (7‑14) 0.749
Hospital stay (days), Median (IQR) 14 (12‑21) 14 (10‑18.75) 14 (11‑20) 0.310
Post‑op Arrhythmias, n (%) 9 (16.1) 8 (16.7) 17 (16.3) 1
Defibrillation, n (%) 3 (5.4) 0 3 (2.9) 0.247
Low cardiac output syndrome, n (%) 23 (41.1) 17 (35.4) 40 (38.5) 0.686
Post‑op creatinine (mg/dl), mean (SD) 0.76 (0.4) 0.85 (0.31) 0.8 (0.36) 0 .17 6
Post‑op platelet count (L/c.mm), mean (SD) 1.15 (0.59) 1.33 (0.67) 1.23 (0.63) 0.134
30‑day mortality, n (%) 6 (10.7) 4 (8.3) 10 (9.6) 0.749
Group A – Blood cardioplegia with St. Thomas solution, Group B – Del Nido cardioplegia solution. ICU – Intensive care Unit, IQR – Inter Quartile
Range, SD – Standard Deviation. *Student’s t-test, Fischer’s exact t-test, Mann-Whitney test
Figure 2: Kaplan-Meier curve showing survival trend in both groups
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Mohammed, et al.: Comparison of outcomes of cardioplegia in neonatal cardiac surgery
58 Annals of Cardiac Anaesthesia | Volume 25 | Issue 1 | January-March 2022
in the postoperative period, and we could not wean off
ECMO. Another neonate who had D‑TGA with an
interrupted aortic arch continued to remain in severe low
cardiac output in the postoperative period, and we could
not institute ECMO.
Comment
Over the decades, various strategies have developed for safe
and effective myocardial protection.[5] Cardioplegia forms
the cornerstone of myocardial preservation. Pediatric
immature myocardium is structurally, physiologically, and
metabolically different from the mature adult heart, and
many researchers have focused attention on developing
the best myocardial protection for pediatric congenital
heart surgeries.[1,12,13] Even though signicant advances in
cardioplegia strategies resulted in improved outcomes, new
methods continue to emerge,[14] indicating a continuous
quest to identify an ideal cardioplegic solution to achieve
the best results.
Multiple cardioplegic solutions were developed to protect
immature myocardium without causing signicant metabolic
changes by focusing on specic intracellular processes.[15‑18]
Elaborative animal and experimental studies have targeted
various biochemical and molecular mechanisms during the
ischemic period of surgery, contributing to progress in this
eld. Despite this progress, there is still no consensus on
the best cardioplegic strategy.[4,19,20]
Expert pediatric cardiac surgical centers worldwide
continue to use various solutions depending on their
experience and outcome over the years. Introduction of
Del Nido cardioplegia developed by Pedro Del Nido et al.
in the early 1990s has led to a change in the practice of
cardioplegic arrest in many centers.[5] Though Del Nido
solution has the potential benet of arresting heart for a
prolonged period with reduced arrhythmogenic potential
because of its lignocaine and magnesium as content, the use
of Del Nido solution for cardioplegia is still not universal.[21]
Studies have shown St. Thomas II cardioplegia as being
both effective and ineffective for neonatal hearts.[4,10,13] Initial
experimental animal studies were inconclusive, as neonatal
hearts preferred single dose cardioplegia in some studies, while
no difference was observed with multidose cardioplegia in
other studies.[3,6] Better myocardial protection can be achieved
postoperatively by reducing energy consumption during
ischemia, which can be attained by a decrease in myocardial
excitability and intracellular calcium ion concentration.[21]
There are few retrospective studies and one randomized
controlled trial comparing the Del Nido solution’s
effectiveness to others in the pediatric population, and
none specifically studied among neonatal hearts.[22,23]
Retrospective studies on the infants have shown similar
clinical outcomes in both groups without proven
superiority over other.[11,23] This study compares the use
of St Thomas II solution to Del Nido solution exclusively
among neonates undergoing complex procedures, as they
represent the most immature form of the myocardium,
eliminating differential maturity of different hearts as age
advances.
Charette et al.[11] showed Del Nido solution to be safer
for prolonged periods, with no signicant impact on
postoperative outcomes. A recent study by Lenoir et al.[24]
compared Del Nido versus blood cardioplegia in adult
aortic surgery and found interesting results on prolonged
periods of cardioplegic arrest. In their study, patients with
myocardial ischemia for more than 180 min. were found to
have higher median creatine kinase MB isotype in Del Nido
group. Hence, they concluded that Del Nido cardioplegia
solution might be associated with increased myocardial
injury, especially during prolonged ischemia times, however,
this did not translate into clinical outcomes in their study.
Pourmoghadam et al.[23] compared Del Nido solution with
non‑Del Nido solution in infantile and neonatal hearts
with similar clinical outcomes. The use of the Del Nido
solution was, however, associated with the advantage
of less interruption of operation and lower volume of
cardioplegia. There was no signicant superiority in terms
of postoperative clinical outcomes or early morbidity and
mortality in either cardioplegia strategies.
Though CPB and ACC times are signicantly lower in
neonates who received Del Nido cardioplegia as they
receive less frequent dosing (Prolonged action), these
cannot be attributed entirely to lesser interruption of
operation to administer cardioplegia alone but can also be
related to probable “learning curve effect.”
We observed similar results in other studies comparing
these cardioplegia strategies. Even the dosing volume was
lower in the Del Nido group. In this study, we repeated the
Del Nido solution at intervals of 90 min. This duration was
similar to Charette et al.[11] and higher than Pourmoghadam
et al.[23] (60 min.). We did not observe the return of activity
during this period or increased incidence of ventricular
arrhythmias during recovery. We presume that myocardial
protection was maintained during these prolonged intervals,
though there was no quantitative evidence to support the
same as we do not routinely perform troponin levels
during operation. Transesophageal echocardiography is not
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Mohammed, et al.: Comparison of outcomes of cardioplegia in neonatal cardiac surgery
Annals of Cardiac Anaesthesia | Volume 25 | Issue 1 | January-March 2022 59
routinely performed for neonates, whereas epicardial echo
performed did not reveal signicant ventricular dysfunction
or other gross abnormalities.
The incidence of LCOS was more in group A (St Thomas
II) than in group B (Del Nido), although not statistically
signicant. The randomized trial by Talwar et al.[22] has
shown better preservation of myobrillar architecture
and preservation of cardiac indices with the Del Nido
solution. Their study population involved older children
who underwent elective surgeries for ventricular septal
defects and Tetralogy of Fallot. Pediatric myocardium in
their group is more mature than neonatal myocardium,
and surgeries are less complex requiring lesser CPB times.
Our study demonstrated that the mean vasoactive inotropic
scores (VIS) in neonates of group A during the rst 24 h
were higher as compared to group B, and it is statistically
signicant. These ndings are consistent with the results of
Pourmoghadam et al.[23] Whereas vasoactive scores assessed for
the subsequent 24 h did not reveal any difference. The higher
VIS score in group A neonates probably suggests a higher
degree of myocardial depression, which gradually resolved over
the next 48 h of operation. The incidence of postoperative
arrhythmias is higher in group A and comparable to group B.
This protective effect might be because of lignocaine (increases
the myocyte refractory period) in group B neonates.[25] Although
the myocardial function is depressed more in group A than
group B in the immediate postoperative period, the incidence
of early mortality is similar in both groups.[26,27]
Even though early postoperative clinical parameters (rst
24 h) were unfavorable in group A, late postoperative clinical
outcomes were similar in both groups without signicant
differences. Mean ventilatory days did not differ signicantly
among both groups. Besides, the length of ICU stay and
total hospital stay were similar in both groups. These
ndings are consistent with the nal clinical outcomes of
Pourmoghadam et al,[23] whereas in contrast with ndings
of trial by Talwar et al.[22] These contrast ndings could
have been due to different sets of cohorts, including older
children and complexity of operating condition (RACHS
2 & 3), whereas similar ndings could have been possible
because of a similar patient population. Though there
was no signicant difference among both groups in late
outcomes regarding cardioplegia strategy, it is difcult to
conclude the effect of cardioplegia solution on outcomes.
CONCLUSIONS
Del Nido cardioplegia is associated with favorable
early (rst 24 h) clinical outcomes. Use of Del Nido
cardioplegia is associated with signicantly decreased
vasoactive inotropic score and decreased incidence of low
cardiac output only during the rst 24 h after surgery. After
the rst 24 h, postoperative clinical outcomes are similar
to both Del Nido and ST Thomas cardioplegia solution.
Limitations
This is a single‑center retrospective study. The small sample
size precludes sophisticated statistical analyses and may
lack the power to detect signicant differences in outcome.
The study is retrospective, objective analysis of myocardial
function by enzyme assays was not possible in this study.
However, if biomarkers for myocardial ischemia or injury
have been measured, it would have provided weightage to
our observations. As study groups were from two different
time periods, changes over time can have a “learning curve
effect” and act as a confounder for the variables measured.
Acknowledgments
We sincerely thank Mr. Manas Chacko for help in statistical
analysis. We express our gratitude to Mrs. Beegum Thaslim,
chief of clinical perfusion for providing expert advice in
drafting the article.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
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... There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively, P = 0.87. The total length of stay in the hospital was 14 (25-75th percentiles: [10][11][12][13][14][15][16][17][18][19] days in the CC group vs. 13 [10] days in the BC group, P = 0.85. The vasoactive inotropic score was not significantly different between the CC and BC groups; VIS was 5 (2.6-7.45) vs. 5 (2.6-7.5) in the CC vs. BC groups, respectively (P = 0.82). ...
... Studies comparing different cardioplegic solutions in pediatric cardiac surgery have used different endpoints on a small number of patients [10]; therefore, the results are variables, and conclusions about the optimal cardioplegic solution cannot be reached. Global practice varies widely, and new cardioplegic solutions have been introduced with variable outcomes [8,[11][12][13]. In this clinical trial, randomized patients to receive either Custodiol cardioplegia (n = 107) or blood cardioplegia (n = 119). ...
Article
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Background Blood-based cardioplegia is the standard myocardial protection strategy in pediatric cardiac surgery. Custadiol (histidine-tryptophan-ketoglutarate), an alternative, may have some advantages but is potentially less effective at myocardial protection. This study aimed to test whether custadiol is not inferior to blood-based cardioplegia in pediatric cardiac surgery. Methods The study was designed as a randomized controlled trial with a blinded outcome assessment. All pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegia, including neonates, were eligible. Emergency surgery was excluded. The primary outcome was a composite of death within 30 days, an ICU stay longer than 5 days, or arrhythmia requiring intervention. Secondary endpoints included total hospital stay, inotropic score, cardiac troponin levels, ventricular function, and extended survival postdischarge. The sample size was determined a priori for a noninferiority design with an expected primary outcome of 40% and a clinical significance difference of 20%. Results Between January 2018 and January 2021, 226 patients, divided into the Custodiol cardioplegia (CC) group (n = 107) and the blood cardioplegia (BC) group (n = 119), completed the study protocol. There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively (P = 0.87). The total length of stay in the hospital was 14 (Q2–Q3: 10–19) days in the CC group vs. 13 (10–21) days in the BC group (P = 0.85). The inotropic score was not significantly different between the CC and BC groups, 5 (2.6–7.45) vs. 5 (2.6–7.5), respectively (P = 0.82). The cardiac troponin level and ventricular function did not differ significantly between the two groups (P = 0.34 and P = 0.85, respectively). The median duration of follow-up was 32.75 (Q2–Q3: 18.73–41.53) months, and there was no difference in survival between the two groups (log-rank P = 0.55). Conclusions Custodial cardioplegia is not inferior to blood cardioplegia for myocardial protection in pediatric patients. Trial registration The trial was registered in Clinicaltrials.gov, and the ClinicalTrials.gov Identifier number is NCT03082716 Date: 17/03/2017
... Previous research suggests shorter aortic cross-clamp times, as well as reduced or similar levels of markers of myocardial injury, after del Nido compared to those in blood cardioplegia pediatric patients [66,73,74]. A recent cohort study from 2022 also confirmed the advantage of del Nido solution over ST blood cardioplegia in terms of the decrease in the aortic cross-clamp time and number of doses, but in neonates [75]. It should be highlighted that most studies proving the advantages of del Nido compared to blood cardioplegia were conducted on patients with a short cross-clamp period, while there is a lack of comparative analyses of these two cardioplegic strategies in patients subjected to prolonged ischemia. ...
Article
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Introduction: Cardioplegia is a pharmacological approach essential for the protection of the heart from ischemia-reperfusion (I-R) injury. Over the years, numerous cardioplegic solutions have been developed, with each cardioplegic approach having its advantages and disadvantages. Cardioplegic solutions can be divided into crystalloid and blood cardioplegic solutions, and an experienced surgeon chooses the type of solution based on the individual needs of patients in order to provide optimal heart protection. Importantly, the pediatric immature myocardium is structurally, physiologically, and metabolically different from the adult heart, and consequently its needs to achieve cardioplegic arrest strongly differ. Therefore, the present review aimed to provide a summary of the cardioplegic solutions available to pediatric patients with a special focus on emphasizing differences in heart injury after various cardioplegic solutions, the dosing strategies, and regimens. Material and methods: The PubMed database was searched using the terms cardioplegia, I-R, and pediatric population, and studies that investigated the influence of cardioplegic strategies on markers of cardiac muscle damage were further analyzed in this review. Conclusions: A large body of evidence suggested more prominent benefits achieved with blood compared to those with crystalloid cardioplegia in pediatric myocardium preservation. However, standardized and uniform protocols have not been established so far, and an experienced surgeon chooses the type of cardioplegia solution based on the individual needs of patients, while the severity of myocardial damage strongly depends on the type and duration of the surgical procedure, overall patient condition, and presence of comorbidities, etc.
Article
Background Although recently it has been extended for use in adult cardiac surgery, del Nido cardioplegia was originally indicated for pediatric cardiac surgery. In this meta-analysis, we compare del Nido cardioplegia vs St. Thomas cardioplegia in pediatric and adult cardiac surgery.MethodsA comprehensive systematic literature review was performed to identify observational and randomized controlled trials (RCTs) comparing del Nido cardioplegia with St. Thomas cardioplegia. An analysis of both random and fixed effects was conducted. The measure of the effect was by the mean difference (MD) and the risk ratio (RR) with a 95% confidence interval (95% CI).ResultsA total of 1893 patients from 12 studies were included (5 RCTs and 7 observational studies). Compared to St. Thomas solution, del Nido cardioplegia was associated with a shorter aortic cross-clamp in adult cardiac surgery (RCT MD − 19.83, 95% CI − 21.89–17.78; observational − 5.85; 95% CI − 11.59, − 0.11 respectively), but no difference in pediatric cardiac surgery. Additionally, del Nido cardioplegia was associated with lower cardiopulmonary bypass time in both adults (observational, MD − 29.15; 95% CI − 31.76–26.55) and pediatric cardiac surgery (RCTs, MD − 7.15; 95% CI − 13.25–1.05). Defibrillation rates were also significantly lower with del Nido cardioplegia group in both adult (RR 0.35, 95% CI 0.24–0.50, I2 = 50%) and pediatric cardiac surgery (odds ratio (OR) 0.30, 95% CI 0.18–0.49, I2 = 92%).Conclusion In both adults and pediatric cardiac surgery, del Nido cardioplegia helps in lowering cardiopulmonary bypass duration, defibrillation rates, and hospital stay, compared to St. Thomas solution. Among adults, del Nido cardioplegia lessens the aortic cross clamp times with no difference observed in all-cause mortality, intensive care unit stay, or mechanical ventilation.
Article
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Background: The aim of this study was to evaluate outcome measures after the use of del Nido (dN) cardioplegia compared with conventional multidose high-potassium (non-dN) cardioplegia in neonates and infants. Methods: We retrospectively analyzed data in patients, aged younger than 1 year, undergoing cardiopulmonary bypass (CPB) from January 2012 to August 2015. We changed our cardioplegia protocol from non-dN to dN administered in a single or infrequently dosed strategy in September 2013. The outcomes of the dN group (n = 107) are compared with the non-dN group (n = 118). We analyzed variables for demographic, intraoperative, early postoperative, and discharge variables. Results: The two groups were similar in age, weight, height, CPB, and cross-clamp time; preoperative and postoperative echocardiographic systolic functions; first 24-hour postoperative urine output and inotropic score; length of stay; and mortality rate. The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) mortality category was significantly higher in the dN group (p = 0.03). The cardioplegia dosing interval was lower for the non-dN group (p < 0.001). The volume and doses of cardioplegia per patient were significantly higher in the non-dN group (p < 0.001). In a subanalysis, when the Norwood patients were excluded from both groups, the overall STAT mortality category difference was no longer significant. The demographic, early postoperative, and discharge variables still showed no significant difference when the two groups were compared. Conclusions: Similar outcomes can be achieved with less frequent interruption of the operation and lower volume of cardioplegia when using dN cardioplegia solution compared with conventional cardioplegia. The dN cardioplegia with extended ischemic interval can be used as an alternative strategy in the neonatal and infant population during cardiac operations.
Article
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There are a wide variety of reported techniques with few comparative trials and no current data available by which surgeons can compare their myopreservation strategies across the specialty. We therefore surveyed congenital heart surgeons to develop a profile of current practice. One hundred twenty-two members of the Congenital Heart Surgeons' Society were surveyed, and 56 responses were analyzed. The survey focused on cardioplegia formulations, dosage and administration, and perfusion strategies for four age groups: neonates, infants, children, and adolescents. All percentages are expressed as percentage of the entire reporting cohort (n = 56). Eighty-six percent of surgeons use blood-based cardioplegia versus crystalloid cardioplegia. Microplegia is used in 5%. Blood-based cardioplegia additives include del Nido (38%), customized solutions (32%), St. Thomas, Plegisol, or Baxter (11%), and microplegia (5%). Crystalloid cardioplegia types are Custodiol (7%), St. Thomas, Plegisol, or Baxter (5%), and customized solutions (2%). Cold (<10°C) cardioplegia is most common (93%), and "hot shots" are used in 21%. Moderate (26° to 30°C) hypothermic cardiopulmonary bypass is more common in neonates and infants compared with older children and adolescents. Antegrade administration is most common (89%). Longer intervals between cardioplegia doses were associated with surgeons using del Nido and Custodiol solutions, and these solutions were commonly administered with a single dose regardless of aortic cross-clamp time. Myocardial protection techniques still remained highly variable among congenital heart surgeons. This survey demonstrates that there is a perception that del Nido and Custodiol solutions can offer appropriate myocardial protection for longer intervals with decreased repeat dosing. An observational study correlating markers of postoperative myocardial performance with myocardial preservation strategies should be considered.
Article
Background Prior studies indicate that immature myocardium has a greater tolerance to ischemia. Prior studies from our laboratory have shown that impaired postischemic endothelial function was correlated with reduced ventricular contractility, and that coronary endothelium has an important role in ischemia and reperfusion injury in neonatal hearts. Methods We examined the differences of endothelial function as well as ventricular function between immature and mature hearts in isolated blood-perfused lamb and sheep hearts after 2 hours of 15°C cardioplegic ischemia. Three groups were defined according to age: neonatal (<1 week) hearts (n = 8), infant (1 month) hearts (n = 8), and adult (1 year) hearts (n = 6). Each of the three groups underwent a similar protocol including ischemic time, myocardial temperature, and cardioplegic solution. Based on earlier work, all had low perfusion pressures during the first 10 minutes of reperfusion. Thereafter the perfusion pressure was constant at 60 mm Hg in the neonatal hearts, 80 mm Hg in the infant hearts, and 100 mm Hg in the adult hearts to match the mean arterial pressure at each age in this species. Results At 30 minutes of reperfusion, the neonatal and infant hearts achieved significantly improved recovery of left ventricular systolic (maximum developed pressure and positive first time derivative of pressure, and volume normalized developed pressure and first time derivative of pressure) and diastolic (negative maximum first time derivative of pressure) functions and coronary blood flow. The postischemic endothelial function determined by the coronary vasodilator response to acetytlcholine was better in the neonatal and infant hearts compared with the adult hearts (p < 0.05). Conclusions These results show that the immature hearts had better recovery of endothelial function and coronary blood flow as well as ventricular function compared with adult hearts after hypothermic ischemia and reperfusion. These results combined with previous studies add further support to the concept that events in the coronary vascular bed play an important role in reperfusion injury in both immature and mature hearts.
Article
Objective: Del Nido cardioplegia solution offers prolonged cardiac protection with single-dose administration; this is particularly interesting for aortic root surgery. However, there is a scarcity of data supporting its safety in adults undergoing complex cardiac surgery, such as aortic root repair. We hypothesized that del Nido cardioplegia solution and blood cardioplegia solution provide equivalent safety during aortic root surgery. Methods: Between January 2015 and June 2018, 283 consecutive patients undergoing the Ross procedure (204) and valve-sparing operation (79) with del Nido cardioplegia solution or blood cardioplegia solution were 1:1 propensity matched (110 aortic root surgery), and outcomes were compared. Clinical patient characteristics and data were extracted from our local database for valve-sparing operations and for Ross procedures. Results: Preoperative characteristics were similar between del Nido cardioplegia solution and blood cardioplegia solution after propensity matching (mean age, 48.6 ± 1.5 years). Median postoperative creatine kinase MB isotype did not differ between del Nido cardioplegia solution and blood cardioplegia solution (48.9 [14.9-300] μg/L vs 51.2 [12.4-116] μg/L for blood cardioplegia solution [P = .1]), but there was a trend toward higher troponin T levels with del Nido cardioplegia solution (748 [221-5834] ng/L vs 710 [212-3332] ng/L for blood cardioplegia solution [P = .07]). In patients with myocardial ischemia longer than 180 minutes, median creatine kinase MB isotype was higher in del Nido cardioplegia solution (75.1 [59.3-300] μg/L than in blood cardioplegia solution 60.5 [16.5-116] μg/L [P = .01]). Aortic crossclamp and cardiopulmonary bypass times were shorter with del Nido cardioplegia solution (163 ± 5 vs 181 ± 5 minutes, P = .01 and 145 ± 4 vs 161 ± 4 minutes, respectively, P = .006). Return to spontaneous rhythm was more frequent in the del Nido cardioplegia solution group (52% [29/55] vs 27% [15/55], P = .006). There was no difference in inotropic or vasoactive agent use (P = .8). Postoperative left ventricle ejection fraction was similar (0.54 ± 0.09 vs 0.55 ± 0.08 for del Nido cardioplegia solution and blood cardioplegia solution, respectively; P = .4). There was no difference between groups for perioperative mortality and postoperative complications. Conclusions: Del Nido cardioplegia solution can be used as an alternative to blood cardioplegia solution in adults undergoing complex aortic root surgery, providing comparable clinical outcomes and improved surgical workflow. However, del Nido cardioplegia solution seems to be associated with increased myocardial injury, especially with extended myocardial ischemic times, but this finding did not translate into adverse clinical events. Caution is warranted in adopting this cardioplegic solution in aortic interventions requiring long ischemic times, and further study is required to establish its exact role in complex cardiac surgery.
Article
We conducted a prospective randomized trial to compare del Nido (DN) cardioplegia with conventional cold blood cardioplegia (St Thomas [STH]) in pediatric patients. We randomized 100 pediatric patients aged ≤12 years undergoing elective repair of ventricular septal defects and tetralogy of Fallot to the DN and the STH groups. In the DN group, a 20 mL/kg single dose was administered. In the STH group, a 30 mL/kg dose was administered, followed by repeated doses at 25- to 30-minute intervals. The primary outcome was cardiac index that was measured 4 times intra- and postoperatively. Troponin-I, interleukin-6, and tissue necrosis factor-alpha were measured. Myocardial biopsy was obtained to assess electron-microscopic ultrastructural changes. Cardiac indices were significantly higher in the DN group than in the STH group 2 hours after termination of cardiopulmonary bypass (P = 0.0006), after 6 hours (P = 0.0006), and after 24 hours (P ≤ 0.0001). On repeated measure regression analysis, the cardiac index was on an average 0.50 L/min/m(2) higher in the DN group than in the STH group at any time point (P = 0.002). Duration of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.01), and hospital stay (P = 0.0007) was significantly lower in the DN group. Patients in the DN group exhibited lower troponin-I release 24 hours following cardiopulmonary bypass (P = 0.021). Electron microscopic studies showed more myofibrillar disarray in the STH group (P = 0.02). Use of long-acting DN cardioplegia solution was associated with better preservation of cardiac index, lesser troponin-I release, and decreased morbidity. Ultrastructural changes showed better preservation of myofibrillar architecture.
Article
There are many cardioplegia solutions currently in use for pediatric cardiopulmonary bypass (CPB). The most common being del Nido solution. Another common cardioplegia solution used for pediatric CPB is St. Thomas. In October 2014, Children's Mercy Kansas City changed from the use of modified St. Thomas to del Nido. This study compared rates of post cross-clamp fibrillation requiring defibrillation between del Nido solution and modified St. Thomas solution stratified by weight at Children's Mercy Kansas City. This retrospective study consisted of 394 patients who underwent cardiac surgery requiring cardioplegia between January 1, 2014 and July 31, 2015. The outcome measured was defibrillation upon cross-clamp removal. Statistical significance was determined using Fishers exact test with a two-sided significance level of .05. Incidence of defibrillation post cross-clamp removal was 4.4% in the del Nido group and 26.8% in the St. Thomas group (p < .0001). Analysis by weight stratifications displays a reduction in post cross-clamp defibrillation rates in groups using the del Nido solution. The 0- to 6-kg category had an incidence of fibrillation of 1.23% in the del Nido group and 17.5% in the St. Thomas group (p < .0003). The 6- to 15-kg category had an incidence of defibrillation of 1.82% in the del Nido group and 14% in the St. Thomas group (p < .0198). The 15- to 60-kg category had an incidence of defibrillation of 8.9% in the del Nido group and 61% in the St. Thomas group (p < .0001). The > 60-kg category had an incidence of defibrillation of 16.7% in the del Nido group and 63% in the St. Thomas group (p < .0623). This study demonstrates a 6-fold decrease in the overall rate of defibrillation post cross-clamp removal between St. Thomas and del Nido cardioplegia solutions. Analyses of weight stratifications demonstrate a decrease in the rate of defibrillation post crossclamp removal in all categories within the del Nido group.
Article
Background: Previous analyses of The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database have demonstrated a reduction over time of risk-adjusted operative mortality after coronary artery bypass grafting. The STS Congenital Heart Surgery Database (STS CHSD) was queried to assess multiinstitutional trends over time in discharge mortality and postoperative length of stay (PLOS). Methods: Since 2009, operations in the STS CHSD have been classified according to STAT (The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery) Congenital Heart Surgery Mortality Categories. The five STAT Mortality Categories were chosen to be optimal with respect to minimizing variation within categories and maximizing variation between categories. For this study, all index cardiac operations from 1998 to 2014, inclusive, were grouped by STAT Mortality Category (exclusions: patent ductus arteriosus ligation in patients weighing less than or equal to 2.5 kg and operations that could not be assigned to a STAT Mortality Category). End points were discharge mortality and PLOS in survivors for the entire period and for 4-year epochs. The Cochran-Armitage trend test was used to test the null hypothesis that the mortality was the same across epochs, by STAT Mortality Category. Results: The analysis encompassed 202,895 index operations at 118 centers. The number of centers participating in STS CHSD increased in each epoch. Overall discharge mortality was 3.4% (6,959 of 202,895) for 1998 to 2014 and 3.1% (2,308 of 75,337) for 2011 to 2014. Statistically significant improvement in discharge mortality was seen in STAT Mortality Categories 2, 3, 4, and 5 (p values for STAT Mortality Categories 1 through 5 are 0.060, <0.001, 0.015, <0.001, and <0.001, respectively). PLOS in survivors was relatively unchanged over the same time intervals. Sensitivity analyses reveal that the finding of declining risk-stratified rates of discharge mortality over time is not simply attributable to the addition of more centers to the cohort over time. Conclusions: This 16-year analysis of STS CHSD reveals declining discharge mortality over time, especially for more complex operations.
Chapter
The repair of most congenital intra-cardiac defects in neonates and infants requires a period of myocardial ischemia to provide satisfactory operating conditions for the conduct of the repair. Extensive efforts have been made to improve the preservation of the heart during these periods of surgically induced ischemia, but there is still a need for further improvements in this area. The majority of the experimental efforts have involved ‘mature’ heart models, but there are reasons to believe that myocardial ischemia may have different effects on the ‘immature’ heart from the ‘mature’ heart. Therefore different strategies for myocardial preservation might be desirable for the immature heart. This discussion will focus primarily on preservation of the ‘immature’ heart although it must be understood that the precise definition of the term ‘immature’ remains unclear. Further, the crossover point from ‘immature’ to ‘mature’ for the human species is unknown as well.
Article
The pediatric heart is smaller in size and the interstitial tissue contains more water and collagen when compared to the adult heart. This makes the absolute contractile mass of pediatric heart small [17,18]. At the cellular level, pediatric myocardial cells have a larger mass of non contractile elements and poorly developed sarcoplasmic reticulum and mitochondria that are fewer in number but have a higher cytochrome c activity [17,18]. Reduced amount of contractile elements and increased water and collagen contents partially explains the poor contractile response of the immature hearts to inotropes, their poor preload reserve and poor tolerance to afterload. However, the patients in the pediatric age group have normal coronary arteries and healthy myocardium as compared to adults who may have atherosclerotic coronary artery disease and subsequent myocardial scarring and dysfunction. This allows for relatively uniform distribution of cardioplegia by antegrade routes. Due to smaller body size, smaller hardware and prime solution volumes are required. There is relative abundance of PUFA (poly unsaturated fatty acids) in membranes of cellular and sub cellular organelles, providing additional sites of oxidative damage [19,20] and making the immature cyanotic heart more vulnerable to oxidative insult.