Myocardial protection in pediatric cardiac surgery – deep look to the most often used cardioplegic solutions

Full article

https://doi.org/10.53453/ms.2024.3.3

Myocardial protection in pediatric cardiac surgery: deep look to the

most often used cardioplegic solutions

Mamedov Arslan

, Rumbinaitė Eglė

, Jakuška Povilas

, Verikas Dovydas

2,3

, Žūkaitė Gabrielė

, Benetis

Rimantas

, Stankevičius Edgaras

5,6

Lithuanian University of Health Sciences, Clinical Department of Cardiac, Thoracic and Vascular Surgery, Kaunas,

Lithuania

Lithuanian University of Health Sciences, Clinical Department of Cardiology, Kaunas, Lithuania

Laboratory for Automation of Cardiovascular Investigation, Institute of Cardiology, Lithuanian University of Health

Sciences, Kaunas, Lithuania

Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania

Preclinical Research Laboratory for Medicinal Products, Institute of Cardiology, Lithuanian University of Health

Sciences, Kaunas, Lithuania

Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Medical Academy, Kaunas,

Lithuania

Abstract

Background:Cardioplegic arrest is a crucial strategy for myocardial protection in pediatric cardiac surgery. The

selection of an optimal cardioplegic solution remains a topic of debate, given the unique physiology of pediatric heart

muscle and the diverse range of available solutions. This comprehensive review aims to evaluate and synthesize

existing evidence on the effectiveness of different cardioplegic solutions in pediatric myocardial protection.

Methods. A comprehensive literature search was conducted to identify randomized control trials, prospective

observational studies, and retrospective analyses focusing on myocardial protection methods in pediatric open-heart

surgery. The review encompasses studies involving the four main types of cardioplegia: blood cardioplegia (BCP),

St. Thomas (STH) cardioplegia, del Nido (DNC) cardioplegia, and Histidine-tryptophan-ketoglutarate (HTK)

cardioplegia.

Results. The literature review includes 3,465 pediatric patients from various studies, with a focus on myocardial injury

markers, metabolic outcomes, intraoperative variables, and postoperative outcomes associated with different

cardioplegic solutions. Results indicate that DNC may offer benefits in terms of myocardial injury and intraoperative

variables, but there is a lack of significant differences in mortality among the four commonly used cardioplegic

solutions.

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

Medical Sciences 2024 Vol. 12 (2), p. 15-30, https://doi.org/10.53453/ms.2024.3.3

Conclusion. While current evidence does not demonstrate significant mortality benefits among the four cardioplegic

solutions in pediatric cardiac surgery, DNC shows promise in mitigating myocardial injury and influencing

intraoperative variables. However, the need for well-designed multicenter randomized controlled trials remains to

establish clear evidence for myocardial protection in pediatric cardiac surgery.

Keywords: pediatric cardiac surgery; cardioplegia, blood cardioplegia, crystalloid cardioplegia, del Nido

cardioplegia, Histidine-tryptophan-ketoglutarate cardioplegia, St. Thomas cardioplegia.

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

1. Introduction

Cardioplegic arrest is a commonly employed strategy

for myocardial protection 1. Initially, cardioplegia

for infant and pediatric patients followed the same

principles as that used for adults, with adjustments

made for volume, flow, and pressure 1, 2. Presently,

cardioplegic solutions used in pediatric clinical

practice are categorized based on various parameters

such as temperature (cold, tepid or warm),

composition (crystalloid or blood), delivery method

(anterograde, retrograde or combined), and substances

contained within the solution (e.g., glucose with

insulin) 3, 4. These cardioplegic solutions can also

be divided into two primary groups: those based on

extracellular components with high levels of

potassium, magnesium and bicarbonate, and those

based on intracellular electrolytes 5. Despite the

wide range of available cardioplegic solutions, there is

an ongoing debate regarding the most effective option

for pediatric myocardial protection.

The physiology of pediatric heart muscle differs

significantly from that of the adult myocardium. There

have been contrasting descriptions of the immature

heart, with some studies suggesting it is more tolerant

to ischemia 6-8, while others indicate it is less

tolerant 9, 10. This disparity may be attributed to the

potential impact of the cardioplegia solution on the

efficacy of myocardial protection, rather than solely

relying on the physiology of the neonatal heart 11.

Another crucial factor is the increased calcium

sensitivity is increased, and reduced ability to

scavenge free radicals in the immature heart, which

heightens the risk of ischemic injury 6-8.

Furthermore, the immature hearts demonstrates a

preference for utilizing glucose as a substrate and

accumulates glycogen, potentially increasing its

resistance to ischemic damage 6-8.

Myocardial protection becomes particularly

challenging in certain cases, such as lengthy and

complex procedures or pediatric patients with

preoperative damaged myocardium 12. In such

situations, the selection of an optimal cardioplegic

solution poses more questions than answers.

Experimental studies have demonstrated a preference

for single-dose cardioplegia in neonatal hearts 13,

others have found no significant difference when

compared to multidose approaches 14. It is worth

noting that there is significant heterogenity in practice

of cardioplegia in pediatric cardiac surgery, as

highlighted by a recent survey perfomed in United

Kingdom and Ireland 15.

2. Materials and methods

2.1 Literature search strategy

A comprehensive literature search was conducted

using various databases, including PubMed, SCOPUS,

Embase, Cochrane database, Google scholar and Ovid.

The aim was to identify randomised control trials,

prospective observational studies, and retrospective

analyses that discussed the utilization of myocardial

protection methods during pediatric open-heart

surgery. The search utilized specific keywords such as

‘pediatric cardiac surgery; cardioplegia, blood

cardioplegia, crystalloid cardioplegia, del Nido

cardioplegia, Histidine-tryptophan-ketoglutarate

cardioplegia, St. Thomas cardioplegia’. These

keywords were used both individually and in

combination, including Medical Subject Headings

terms, to maximise the scope of literature findings. In

instances where a paper covered multiple aspects of

the myocardial protection, the results were divided and

relevant information was included in the respective

sections of this review. Only articles written in English

were included. Eligible studies for this comprehensive

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review consisted of pediatric patients undergoing

cardiac surgery, involving at least one of the four types

of cardioplegia: DN, BC, HTK or St. Thomas.

2.2 Cardioplegic solutions most often used in

pediatric cardiac surgery

The original extracellular cardioplegic solution

developed by Hearse and colleagues in the early 1970s

was known as St. Thomas's Hospital solution No. 1

(STH1) 16. Over time, this solution underwent

refinement and evolved into Plegisol or St. Thomas’s

Hospital solution No. 2 (STH2) which has become the

most widely used crystalloid cardioplegic solution

worldwide 17. One of the main differences between

STH1 and STH2 is the inclusion of procaine

hydrochloride in STH1, which acts as a membrane

stabilizer with known cardioplegic effects 16.

Consequently, patients who receive STH1 may

experience fewer reperfusion-induced arrhythmias

18. Due to the high concentrations of potassium and

magnesium concentration in St. Thomas‘s (STH)

cardioplegic solution, it induces rapid cardiac arrest

19. As a result, repeated perfusion is required during

ischemia, typically administered every 20-40 minutes

20. It is important to note that STH cardioplegia also

leads to increased cellular oedema and can damage

endothelial function 16.

The Histidine-tryptophan-ketoglutarate (HTK)

solution was initially introduced in early 1970s by

Hans Jürgen Bretschneider 21. This crystalloid,

intracellular solution with low sodium concentration

of 15 mmol/L and extracellular potassium of

9 mmol/L, providing up to 3 hours of myocardial

protection with a single dose 21-23. The reduced

sodium level in the extracellular space inhibits the fast

inward current and achieves cardiac arrest in diastole.

Histidine acts as buffer, supportting anaerobic

glycolysis and preventing acidosis 21, 22.

Ketoglurate, an intermediate in the Krebs cycle,

enhances ATP production during reperfusion. It also

is regulates cell membrane function, reduces

reperfusion injury, and decrease edema 24.

However, caution should be exercised when using

HTK solution because of its low sodium content,

which can effect extracellular sodium levels 25, 26.

In 1990, researchers at the University of Pittsburg

developed a long-acting cardioplegia solution

specifically designed for pediatric patients, known as

del Nido cardioplegia (DNC) 27. The inclusion of

polarizing agents like lidocaine aims to slow down the

energy consumption. Additionally, the presence of

calcium-competing ions like magnesium in optimum

concentration is believed to prevent intracellular

calcium accumulation, thus reducing cell injury. The

prolonged action of DNC is advantageous in

minimizing the detrimental effects of repeated

doses of cardioplegia 28. DNC is an extracellular

solution that allows for uninterrupted surgery through

a single dosing of cardioplegia. This contributes to

reduced surgical times, minimized fluctuations in

blood glucose levels, and easier management of

glycaemic control 29, 30. DNC also aids in reducing

myocardial oedema, preserving high-energy

phosphates and promoting anaerobic glycolysis 30.

3. Results

The initial literature search yielded 1,389 potentially

relevant records. Following the screening of titles and

abstracts, 141 reports were selected for full-text

evaluation. Ultimately, three meta-analysis of

randomized clinical studies, consisting of 5 studies 4,

12 studies 46, and 10 studies 51, along with 19

clinical studies 28-45, 47, met predetermined search

criteria and were included in this comprehensive

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review. In total, the analysis encompassed 3,465

pediatric patients who underwent cardiac surgery

utilizing various types of cardioplegia.

Changes in cardiac troponin I level (cTnI)

(myocardial injury marker) after cardiac surgery.

Table 1 presents studies comparing levels of cTnI after

different types of cardioplegia. In studies comparing

blood cardioplegia (BCP) and cristaloid cardioplegia

(STH) 4,31 no significant differences were found in

postoperatively cTnI release at 4-6 hours, 12 hours,

and 24 hours. A meta-analysis 51, which included 10

eligible studies directly comparing BCP to STH, also

showed no significant difference between the two

groups, except for significantly lower cTnI levels at 4

hours postoperatively in the BCP group 51.

In a study comparing HTK cardioplegia and cold BCP,

it was found that cTnI concentrations were higher in

the cold BCP group from postoperative hours 1 to 72

32. Another study by Dolcino et al 33 investigated

neonates undergoing arterial switch operation with

either HTK cardioplegia or warm BCP, and it showed

that postoperative troponin concentrations were higher

in the HTK group 33. Studies comparing DNC and

BCP 34, 35 concluded that DNC provides lower

postoperative troponin I concentration compared to

the BCP group. In the study conducted by Panigrahi et

al 36 although no significant difference was

observed regarding cTnI levels between the two

groups, a tendency of greater amount of cTnI release

noticed at 12 hours in the BCP group. Two studies 37,

38 comparing HTK cardioplegia and DNC showed

that DNC was associated with less release of cTnI.

Data regarding myocardial metabolism is limited and

is derived from few studies (table 2) which evaluated

lactate levels after cardiopulmonary bypass (CPB).

According to meta-analysis 4, lactate levels after

CPB were significantly lower in the BCP group

compared to the CCP group. In the study conducted by

Gholampour Dehaki M et al 37 which compared

DNC with HTK cardioplegia, lactate levels were

significantly higher among patients who received

HTK cardioplegia 37.

Cardioplegic solutions effects to myocardial energy

marker - ATP level. In the meta-analysis conducted

by Mylonas et al. 51, no significant difference

between in ATP levels was found between the two

groups (BCP vs CCP).

Intraoperative outcomes when using different

cardioplegia solutions

Inotropic status after CPB. In a study by Talwar et

al. [28], which compared DNC and HTK cardioplegia,

DNC was associated with lower inotropic scores

compared to HTK cardioplegia. The inotropic score

was evaluated at the end of the first 24 hours, after 48

hours, and after 72 hours. Three studies 32,34,36

compared DNC with BCP and concluded that DNC

provides lower inotrope scores at 24 hours and at 48

hours 32. In one study 40, HTK cardioplegia was

compared with BCP, and the inotrope score was found

to be lower in HTK group. A study comparing DNC

vs STH cardioplegia with 220 patiens did not find a

significant difference in terms of inotropic score 41.

Additionally, one study 2 analyzed the outcomes

between three groups - HTK, cold BCP and STH

cardioplegia. It showed that patients who were given

HTK solution required a greater need of inotropic

support (P < 0.05) 2. Summarized data on inotropic

status after CPB is presented in Table 3.

Total volume of cardioplegia. Data comes from two

studies 34, 42 which showed that using DNC was

associated with lower total volume of cardioplegia (P

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< 0.001) 34 (331.67±188.07 vs. 458.67±226.62,

P=0.022) 42.

Shorter CPB and cross clamp time. Comparing

DNC vs BCP 34,42 it was showed that cardiac arrest

with DNC was associated with reduced CPB and cross

clamp times (P = 0.006 and P = 0.001, respectively)

34. While other two studies 35,41 found no

significant difference regarding CPB and aortic cross-

clamp time comparing the same two cardioplegic

solutions (P= 0.24). Dolcino et al 33 in their study

showed that single-dose HTK may be inadequate for

prolonged cross-clamping durations.

Intensive care unit (ICU) stay and hospital stay.

According to the meta-analysis [4], which included

five studies with a total of 323 patients, there was no

significant difference in the length of ICU stay

between the BCP and CCP groups. This finding was

also confirmed by Mylonas et al. [51] in their meta-

analysis, which indicated no significant difference in

ICU stay and hospital stay between BCP and CCP

groups. In the studies comparing DNC and HTK [28,

37], it was found that DNC was associated with shorter

ICU and hospital stay compared to HTK. However,

the last meta-analysis [46] did not find significant

differences in ICU stay or hospital stay among the four

types of cardioplegia (DNC, BCP, HTK, and STH).

Additionally, a pairwise meta-analysis of one trial

with 101 patients showed that HTK was associated

with significantly shorter ICU and hospital stay

compared to STH [46]. Summarized data on ICU and

hospital stay for different cardioplegic solutions can be

found in Table 4.

Low cardiac output syndrome (LCOS). In a

retrospective single-centre study 43 involving 1,129

pediatric patients BCP compared to CCP. It was

showed that BCP has potential advantages in reducing

the incidence of LCOS 43. Another study comparing

DNC vs STH cardioplegia 44 found that DNC was

associated with a lower occurrence of LCOS

compared to patients who received the standard

myocardial protection using a modified STH solution.

Additionally, Ebtehal A. Quilsy and colleagues 45

investigated the efficiency of HTK cardioplegia

compared to cold BCP and found that HTK was

associated with a higher risk of LCOS. Summarized

data on LCOS after CPB is presented in table 5.

Resumption of sinus rhythm and postoperative

arrythmias. In a comparative study 36 between

DNC and BCP, it was found that DNC leads to a faster

resumption of spontaneous regular cardiac rhythm (P

< 0.0001). Ebtehal A. Quilsy and colleagues 45

examined the efficiency of HTK cardioplegia in

comparison with cold BCP. HTK was associated with

higher, higher occurrence of postoperative

arrhythmias (20% vs 17%).

Postoperative outcomes. The largest mortality data is

derived from meta-analysis 51 which found no

difference in 30-day mortality when comparing BCP

with CCP (OR 1.11, 95% CI 0.43-2.88). In the latest

meta-analysis 46 with 1,634 children from 12

studies, outcomes after four types of cardioplegia

(DNC, BCP, HTK and STH) were compared and no

significant differences in endpoints were observed

among the four types of cardioplegia. Floh et al 47 in

a retrospective study involving 1534 patients,

comparing DNC to BCP, similar mortality rates were

found in both groups.

Left and right ventricle functions. Gholampour

Dehaki M et al 37 conducted a study comparing the

effects of DNC and HTK on peri-operative clinical

outcomes in children with Tetralogy of Fallot. They

found no significant differences in left ventricular

ejection fraction (LV EF) after the surgery. Pérez-

Andreu et al 32 showed that LV EF was higher in the

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HTK group compared to cold BCP immediately after

the operation, at 24 hours and on the first day without

inotropic support. However, an experimental animal

study 13 found no difference in LV EF at 24 hours

post operation or at discharge. The pre-operative right

ventricle function, as measured by fractional area

change was also similar between BCP and HTK. In a

single-center 47, retrospective study which included

1,534 patients undergoing CPB, a significant rise in

right ventricular dysfunction was observed in DNC

group compared to conventional STH cardioplegia.

Summarized data on left and right ventricle functions

using different cardioplegic solutions are presented in

Table 6.

4. Discussion

This comprehensive review aimed to evaluate the

knowledge derived from the randomized and non-

randomized studies on myocardial injury, metabolism,

energy, intraoperative and postoperative outcomes

associated with the use of different cardioplegic

solutions in pediatric cardiac surgery. The assessment

of myocardial injury, as indicated by cTnI release,

focused mainly on the comparison between BCP and

CCP, with two meta-analyses involving a total of

8,034 patients showing no significant differences

between the two groups. However, there is limited

data available comparing HTK and BCP. One study

32 comparing HTK with cold BCP reported more

pronounced myocardial damage in the cold BCP

group, while another study 33 comparing HTK with

warm BCP reported higher troponin concentrations in

the HTK group. In comparisons between DNC and

BCP, two studies 34, 35 demonstrated lower

troponin concentrations in the DNC group. When

comparing HTK with DNC 28,37,38, DNC resulted

in lower troponin values in multiple studies. It is worth

noting that, in the adults, troponin levels at 72 hours

have been shown to be a reliable predictor of mid-term

mortality 48. However, there is limited evidence

available regarding cTnI measurements after 72 hours

specifically in the pediatric population.

In assessing myocardial metabolism through lactate

levels, the available data is limited and shows

contradictory results. A 2015 meta-analysis [4]

indicated that lactate levels are significantly lower in

the BCP group, but this finding was primarily

influenced by a single study. Another study by Busro

et al. [39] did not find a significant difference when

comparing BCP and CCP in terms of lactate levels.

However, Gholampour Dehaki et al. [37], comparing

DNC with CCP, reported significantly higher lactate

concentrations in the CCP group, suggesting poorer

myocardial metabolism in that group. It is important to

note that the available evidence on lactate levels and

myocardial metabolism is limited and further research

is needed to draw more conclusive findings.

In evaluating the impact of different cardioplegic

solutions on myocardial energy resources, several

studies have measured ATP levels during BCP and

CCP. A meta-analysis published in 2017 [51]

examined these data and found no significant

difference between the two groups in terms of ATP

levels. This suggests that both BCP and CCP are

comparable in their ability to maintain myocardial

energy resources as measured by ATP levels.

Intraoperative outcomes when using different

cardioplegic solutions.

There is limited available data regarding the need for

inotropic support when different cardioplegic

solutions are used. One study by Talwar et al. [28]

compared DNC with HTK and found that the DNC

group required less inotropic support. In the

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comparison between DNC and BCP, data from three

studies [32,34,36] favored DNC in terms of reducing

the need for inotropes during the first and second

postoperative days. However, a study by Elassal et al.

[41] comparing DNC and STH found no significant

difference in the inotrope status between the two

groups.

Regarding the duration of CPB and aortic cross-clamp

time, the findings from current studies are

contradictory. Two studies 34,42 indicated the

superiority of DNC over standard cardioplegia in

reducing CPB and aortic cross-clamp time, while two

other studies 35,41 found no significant difference

between the two cardioplegic solutions in terms of

these time parameters.

The length of stay in the ICU was primarily reported

based on the actual elapsed time rather than being

assessed against specific discharge criteria in the

available trials. Additionally, the trials focused on

short-term endpoints and did not evaluate long-term

functional outcomes 49. Two meta-analyses compa-

ring BCP with CCP did not find any significant

differences in ICU stay. However, when comparing

DNC with HTK, two studies reported a shorter

duration of ICU stay in the DNC group. Similarly, in

the comparisons of DNC with BCP, the DNC group

also had a shorter ICU duration according to studies

[35, 36, 41].

LCOS is a common complication in children after

surgery and is a significant contributor to mortality

50. A retrospective study conducted at a single center

demonstrated that the BCP group had lower rates of

LCOS compared to CCP, highlighting the potential

advantages of BCP in reducing LCOS occurrence

[43]. Similarly, when comparing DNC with the

standard STH cardioplegia, a lower incidence of

LCOS was observed in the DNC group. Another study

conducted by Ebtehal A. Quilsy and colleagues

compared HTK cardioplegia with cold BCP and found

a higher probability of LCOS when HTK cardioplegia

was used [45]. These findings suggest that the choice

of cardioplegic solution may have an impact on the

occurrence of LCOS in pediatric cardiac surgery.

Postoperative outcomes when using different

cardioplegic solutions.

The most recent meta-analysis [46], which included

1,634 children from 12 randomized studies, suggests

that there are no significant differences in perio-

perative mortality among the four types of cardio-

plegia (DNC, BCP, HTK, and STH) in the pediatric

population. However, in adult patients, DNC may be

associated with lower perioperative mortality com-

pared to HTK or BCP. Regarding the assessment of

left ventricular systolic function before and after

surgery using different cardioplegic solutions, current

studies do not show significant differences.

In a larger retrospective study [47] involving 1,534

patients, it was found that the DNC group had better

postoperative right ventricular function compared to

conventional STH cardioplegia. However, it is impor-

tant to note that the current literature on cardioplegia

in children lacks late-phase trials, and the studies

conducted so far are of small size and use inconsistent

endpoints, providing limited evidence [49].

To thoroughly understand the benefit-risk profiles of

different types of cardioplegia in pediatric cardiac

surgery, large multicenter randomized studies are

needed. These studies will help provide more robust

and comprehensive evidence for guiding clinical

practice in the field of pediatric cardioplegia.

5. Conclusions

The available studies have not demonstrated any

significant mortality benefits comparing the four

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commonly used cardioplegic solutions (BCP, STH,

DNC and HTK) in pediatric cardiac surgery. However,

the use of DNC has shown significant benefits in terms

of myocardial injury and of other intraoperative

variables. Despite these findings, there remains a

substantial need for well-designed multicenter

randomized controlled trials to establish clear

evidence for myocardial protection in pediatric cardiac

surgery.

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Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

Table 1. Changes in cardiac troponin I level after cardiopulmonary bypass

Authors

Study type

Patient

number,

Type of

cardioplegia

used

P-value

at 4-6

hours

P-value

at 8

hours

P value

at 12

hours

P value

at 24

hours

P value

at 48

hours

P value

at 72

hours

When study

performed,

year

Fang et al. [4]

Meta-analysis

323

BCP vs CCP

P=0.09

P=0.53

P=0.12

2014

Romolo et al.

[31]

Randomized

clinical trial

BCP vs STH

2016-2017

Mylonas et al.

[51]

Meta-analysis

697

BCP vs STH

P=0.860

P=0.019

P=0.000

2017

Pérez-

Andreu et al.

[32]

Observational

Cold BCP vs

HTK

P=0.001

P<0.001

P=0.001

P=0.003

2010-2015;

2016-2018

Dolcino et al.

[33]

Observational

101

Warm BCP vs

HTK

P<0.001

2014-2016

Isildak et al.

[34]

Randomized

clinical trial

BCP vs DNC

P=0.091

P=0.045

P=0.315

2021

Haranal et al.

[35]

Randomized

clinical trial

100

BCP vs BSTH

(blood-based

STH)

P=0.629

2018-2019

Panigrahi et

al. [36]

Randomized

clinical trial

BCP vs DNC

P=0.873

P=0.180

P=0.780

2018

Dehaki et al.

[37]

Randomized

clinical trial

HTK vs DNC

P<0.001

2018

Tunçer et al.

[38]

Observational

HTK vs DNC

P=0.016

2017-2018

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

Table 2. Lactate levels after cardiopulmonary bypass

Table 3. Inotropic status after CPB.

Authors

Study type

Patient number,

Type of cardioplegia

used

P value

When study was performed

(year)

Fang et al 4

Meta-analysis

323

BCP vs CCP

P=0.03

2014

Gholampour Dehaki M et

al 37

Randomized

clinical trial

DNC vs HTK

P=0.001

2018

Authors

Study type

Patient

number,

Type of

cardioplegia

used

P-value

at 0

hours

P-value

at 24

hours

P value at

48 hours

P value

at 72

hours

P value at

96 hours

P-value at

120 hours

When study

performed,

year

Talvar et

al 28

Randomized

clinical trial

100

DNC vs HTK

P=0.021

P=0.036

P=0.026

P=0.008

2017-2018

Pérez-

Andreu

et al [32]

Observational

Cold BCP vs

HTK

P=0.001

P=0.006

P=0.059

P=0.285

P=0.658

P=0.924

2010-2015;

2016-2018

Isildak et

al [34]

Randomized

clinical trial

BCP vs DNC

P=0.058

P=0.032

P=0.005

P=0.136

2021

Panigrahi

et al [36]

Randomized

clinical trial

BCP vs DNC

P=0.040

P=0.030

P=0.610

P=0.350

2018

Bibevski

et al [40]

Observational

132

cold BCP vs

HTK

P<0.05

2007-201

Elassal et

al [41]

Observational

220

DNC vs STH

P=0.591

2011-2019

Hamed et

al [2]

Randomized

clinical trial

HTK vs cold

BCP vs STH

P<0.05

2015-2017

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

Table 4. Intensive care unit and hospital stay after CPB in pediatric patients.

Table 5. Low cardiac output syndrome (LCOS) after CPB using different cardioplegic solutions

Authors

Study type

Patient

number, n

Type of cardioplegia

used

ICU length of

stay, P value

Hospital length of

stay, P value

When study performed,

year

Fang et al 4

Meta-analysis

323

BCP vs CCP

P=0.25

2014

Mylonas et al [51]

Meta-analysis

697

BCP vs STH

P=0.002

P=0.060

2017

Talvar et al 28

Randomized

clinical trial

100

DNC vs HTK

P=0.05

P<0.001

2017-2018

Dehaki et al 37

Randomized

clinical trial

DNC vs HTK

P=0.02

2018

Tan et al [46]

Meta-analysis

101

HTK vs STH

2022

Authors

Study type

Patient

number, n

Type of cardioplegia

used

P value

When study performed,

year

Sobieraj et al [43]

Observational

1129

BCP vs CCP

P = 0.0017

2006-2012

Caneo et al [44]

Observational

500

DNC vs STH

P⩽ 0.05

2015-2019

Qulisy et al [45]

Observational

154

HTK vs cold BCP

P=0.14

2013-2014

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

Table 6. Left ventricle (LV) and right ventricle (RV) function after CPB when different cardioplegic solutions were used.

Autho

Study

type

Patie

num-

ber, n

Type of

cardiopleg

ia used

Pre-

operati

ve P-

value

(LV)

Intraoperati

ve P-value

(LV)

P-

value

after

the

surger

y (LV)

value

at 24

hours

(LV)

P value

the first

day

without

inotrop

support

(LV)

P value

dischar

ge (LV)

Intraoperati

ve P-value

(RV)

P value

of at

dischar

ge (RV)

When

study

performe

d, year

Dehaki

et al

37

Randomize

d clinical

trial

DNC vs

HTK

P=0.791

P=0.75

P=0.906

2018

Pérez-

Andre

u et al

[32]

Observation

Cold BCP

vs HTK

P=0.880

P=0.00

P=0.011

2010-

2015;

2016-

2018

Floh et

al [47]

Observation

1534

DNC vs

STH

P=0.90

P=0.43

<0.001

P<0.001

2013-

2016

Journal of Medical Sciences. 11 Mar, 2024 - Volume 12 | Issue 2. Electronic - ISSN: 2345-0592

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Myocardial protection in pediatric cardiac surgery – deep look to the most often used cardioplegic solutions