Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery
Condition: Congenital Heart Disease
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Interventional
Phase: Phase 2

Summary: 
      Cardioplegic arrest is an essential part of cardiac surgery which aims to allow myocardial
      preservation and minimise myocardial swelling ,while providing a motionless and bloodless
      field ,.Blood cardioplegia has proven its efficacy for several decades and surgeons are still
      preferring to use it for myocardial protection of paediatric cardiac surgery ,although it is
      thought to be more time consuming since it is given with interrupted doses, . Even when
      advancement has came along the field of myocardial protection and cardioplegia solutions with
      the introduction of Bretschneider Histidine-Tryptophan-Ketoglutarate solution ,custodiol ,in
      1970 ,which is given as a single dose and believed to be convenient, simple to deliver , and
      less time consuming . Many Surgeons haven't change their practice possibly due to paucity of
      studies comparing cardioplegia solutions in paediatric cardiac surgery and conflicting
      reports regarding the superiority of different cardioplegia solution.The investigators aim to
      provide evidence that will help paediatric cardiac surgeons to choose the optimal solution
      for their practice .
    

Detailed description: 
      Hypothesis :

      Custodial is not inferior to blood cardioplegia in myocardial protection in paediatric
      cardiac surgery ..

      Methodology :

      Study design :

      Randomized controlled trial

      Data collection:

      All demographic data ,diagnosis ,procedure(type.CPB time ,crossclamp time) , surgeon and
      hospital course details .

      Computer generated randomisation into two groups based on cardioplegia solution .

      if randomised to blood patient will receive blood cardioplegia, delivered by microplegia
      delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be
      35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15
      °C, while maintaining a perfusion pressure of 100-125 mmHg.

      if randomised to custodial patient will receive single dose of HTK custodiol cardioplegia. at
      temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to
      1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg
      until the heart is arrested..

      Blinding :

      Surgeons will know the type of cardioplegia in the OR while other assessor will be blinded .

      Sample size calculated with an online calculator based on α error of 0.05 and β error of 0.2
      to detect an absolute risk difference of 15% in composite end point between the two groups
      yielded 137 in each arm ,The results will be presented as mean (SD), median (interquartile
      range), or proportion . Using relative risk and log rank for statistical analysis .A P value
      of less than 0.05 will be considered statistically significant. Statistical analyses will be
      carried out using the SPSS .

      Safety monitoring and interim results :

      Both cardioplegia solutions are already in use and FDA approved there is no safety concerns
      at the time being . However , an interim analysis will be carried on every 6 months and the
      principal investigator will decide weather to stop or carry on if any major discrepancies in
      outcomes

      literature review : After an extensive literature review the investigators found only one
      randomised trial by elmorsy et al , which concluded that A single dose of an HTK cardioplegic
      solution provides better myocardial and cerebral protection than repeated doses of oxygenated
      blood cardioplegia during pediatric congenital cardiac surgery.

      On the other hand there was another retrospective report by bojan et al, found that The use
      of Custodiol cardioplegia in neonates undergoing ASO was associated with a larger troponin
      release when compared with warm blood cardioplegia,p <0.001 suggesting poor myocardial
      protection.

      koruon et al, done a tissue level comparison between htk and conventional crystalloid
      cardioplegia and their statistical analysis revealed no significant difference between the
      two groups regarding the clinical variables, apoptotic indices and proliferation indices.

      Liu j et al ,did a retrospective study comparing custodiol to St. Thomas crystalloid
      cardioplegia which concluded That HTK group had shorter cross-clamping time and more frequent
      spontaneous defibrillation than St. Thomas group.

      Also an animal study by Chen Y et al, on piglets that were randomised to either a single dose
      of HTK or multidose cold blood cardioplegia .. No significant differences were noted in the
      myocardial lactate content, ATP content, and histopathological score between both groups .

      Finally a retrospective report by E Qulisy et al concluded that Custodiol cardioplegia is
      associated with less myocardial protection and higher adverse outcomes compared to blood
      cardioplegia in pediatric age group undergoing cardiac surgery.
    

Intervention name(s): Custodiol Solution; Blood cardioplegia
Intervention type(s): Drug; Drug
Intervention description(s): After cross clamping patient will receive single dose of HTK custodiol cardioplegia. at temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to 1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg until the heart is arrested.; After cross clamping patient will receive blood cardioplegia, delivered by microplegia delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be 35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15 °C, while maintaining a perfusion pressure of 100-125 mmHg.
Other intervention name(s): htk
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomisation :
Computer generated randomisation into two groups based on cardioplegia solution .
if randomised to blood patient will receive blood cardioplegia, delivered by microplegia delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be 35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15 °C, while maintaining a perfusion pressure of 100-125 mmHg.
if randomised to custodial patient will receive single dose of HTK custodiol cardioplegia. at temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to 1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg until the heart is arrested.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: cardioplegia; myocardial protection; custodiol; htk