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CUSTODIOL
Cardioplegia with unique benefits

  • Cardioplegia: Professor Bretschneider broadened the definition of “cardioplegia” to be a synonym for “myocardial protection”. The histidine-tryptophan-ketoglutarate solution (HTK) CUSTODIOL, has been originally designed in order to provide a good myocardial protection
  • One of the two well-documented methods of cardioplegia: Professor Bretschneider’s and Professor Buckberg’s principles of cardioplegia are the only techniques, which offer a proven track record of published clinical studies
  • Nondepolarizing cardiac arrest: The low-to-moderate content of electrolytes (“intracellular”-type cardioplegic solution, 15mM sodium) mean less cellular stress during cold ischemia, especially since the cell membranes are protected by tryptophan
  • A single/initial application applied over the period of 6-8 minutes is sufficient for up to 180 minutes of myocardial ischemia
  • Superior energetic protection (ATP): Energy substrates and high buffering capacity offer the basis for both anaerobic energy supply during ischemia and full return to function upon reperfusion

Comparison of cardioplegic concepts

CUSTODIOL Blood-based
Composition K+ low, Na+ low K+ high, Na+ low
Incidence of ventricular
Arrhythmia1)
33% 72%
Spontaneous
Defibrillation1),2),4)
90% 26%
Oedema formation3) 27% 54%
Mortality rate4) 1% NN
Cross clamp
period without repeat
cardioplegia4),5)
120-180 minutes Repeated doses of cardioplegia (<20min)
Transplantation yes no

1) Hachida M, Nonoyama M, Bonkohara Y, Hanayama N, Saitou S, Maeda T, Ohkado A, Lu H, Koyanagi H. Clinical assessment of prolonged myocardial preservation for patients with a severely dilated heart. Ann Thorac Surg.  1997 Jul;64(1):59-63.

2) Sakata J, Morishita K, Ito T, Koshino T, Kazui T, Abe T. Comparison of clinical outcome between histidine-triptophan-ketoglutalate solution and cold blood cardioplegic solution in mitral valve replacement. J Card Surg. 1998 Jan;13(1):43-7.

3) Kim S, Lee YS, Woo JS, Sung SH, Choi PJ, Cho GJ, Bang JH, Roh MR, Histidinetryptophan-ketoglutarate Versus Blood Cardioplegic Solutions: A Prospective, Myocardial Ultrastructural Study. Korean J Thorac Cardiovasc Surg 2007;40:8-16

4) Misfeld M, Davierwala P. Crystalloid-based cardioplegia for minimally invasive cardiac surgery. Semin Thorac Cardiovasc Surg. 2012 Winter;24(4):305-7.

5) Matzelle SJ, Murphy MJ, Weightman WM, Gibbs NM, Edelman JJ, Passage J. Minimally invasive mitral valve surgery using single dose antegrade Custodiol cardioplegia. Heart Lung Circ. 2014 Sep;23(9):863-8.


CUSTODIOL
Cardioplegia for all situations

  • Protection even in the case of coronary heart disease (CHD): excellent equilibration of the extracellular space provides a full protection of the whole heart
  • Recommended solution for highly complex procedures: the preferred solution for minimally invasive surgery (MICS), neonates (ASO), redo-, and combined operations
  • Excellent preservation of bypass grafts: during coronary artery bypass grafting (CABG) CUSTODIOL can be used for the storage of blood vessels
  • Safety for the young heart: less risk of damage to the tunica intima of neonatal hearts, because no intermittent reperfusions are required for over 2 hours
  • Excellent recovery of the young heart: gentle and fast post-ischemic recovery of the neonatal myocardium

CUSTODIOL
Heart transplantation (HTx)

  • The proper mixture to combat cold ischemia/reperfusion injuries:originally designed for cardioplegia. Same physiological principles apply to the long-term preservation of the graft (cardioplegia = myocardial protection)
  • Standard in HTx:only three preservation solutions are clinically accepted (HTK, UW, Celsior)
  • Used in tens of thousands of cases:a single German HTx centre transplanted over 1200 organs successfully (within 15 years)

Myocardial protection during MICS

A single dose of antegrade CUSTODIOL crystalloid cardioplegia is a safe and effective strategy to protect the myocardium during Minimal Invasive Valve Surgery6)

Operative data Evaluation
In-hospital mortality 0%
ICU stay Short
Myocardial cytonecrosis enzymes (CK-MB, Lactate) No significant increase was found
Inotropic support >24 h Mild-to-moderate postoperative support
Neurologic complications Only one patient (not related to HTK)
Occurrence of renal complications Very low
Incidence of AF (postoperative atrial fibrillation) Low
Overall clinical outcomes Excellent

After aortic occlusion, one single dose of CUSTODIOL solution is delivered for a period of 6 to 8 minutes (20-25mL/kg) into the aortic root with a perfusion pressure (aortic root pressure) of 40 to 60mmHg. No additional cardioplegic doses are required Hemodilution after a large volume of cardioplegia infusion is an important point. To maintain a stable hemoconcentration during the perioperative period, a careful ultrafiltration during extracorporeal circulation as well as a strict use of diuretic drugs in intensive care and ward units was used. This approach enabled the authors to use a minimal amount of blood transfusion during the postoperative course

6) Savini C, Murana G, Di Eusanio M, Suarez SM, Jafrancesco G, Castrovinci S, Castelli A, Di Bartolomeo R. Safety of single-dose histidine-tryptophan-ketoglutarate cardioplegia during minimally invasive mitral valve surgery. Innovations (Phila). 2014 Nov-Dec;9(6):416-20.


Myocardial protection of the young heart

The usage of CUSTODIOL helps minimizing the frequency of interruptions of the surgical procedure7)

CUSTODIOL Blood group
Number of doses given 1 5
Cardiopulmonary bypass time (min) 160 188
Aortic cross-clamp time (min) 93 112
Mortality at 30 d (%) 0 2.3
Total hospital stay 23 25

Blood and metabolic outcomes were equal. Typically, in the CUSTODIOL group, TnI level had a peak in the early hours after CPB with a rapid decrease within the first 24 hours CUSTODIOL was infused anterograde according to the following protocol: temperature 5 to 8°C; 1ml of solution per minute and per gram estimated heart weight (infant ≈ 0.6% of bodyweight); and perfusion pressure initially 80 to 90mmHg, after cardiac arrest 30 to 40mmHg for 6 minutes. The right atrium was opened and the cardioplegia was completely aspirated outside the bypass circuit to avoid hemodilution 

7) Giordano R, Arcieri L, Cantinotti M, Pak V, Poli V, Maizza A, Melo M, Assanta N, Moschetti R, Murzi B. Custodiol Solution and Cold Blood Cardioplegia in Arterial Switch Operation: Retrospective Analysis in a Single Center. Thorac Cardiovasc Surg.  2016 Jan;64(1):53-8.


Myocardial protection during transplantation

Efficacy confirmed in more than 1290 Heart Transplant Recipients 8)

Cold Ischemia Time (CIT)
Median 194.4 min
Standard deviation ±40.4 min
30-day mortality
Overall 9%
CIT > 240 min 13%

Data recorded between 1989 and early 2004 at a single transplant centre (Bad Oeynhausen, Germany) where the greatest number of heart transplants in the world were performed during that time. These data represent the entire experience of the centre, with no cases excluded.

Donor heart procurement was performed as follows: At the time of explantation, 50ml/kg body weight of CUSTODIOL was used for flushing and the heart was stored in 1000ml of CUSTODIOL. Following cross-clamping of the ascending aorta, the perfusion pressure of CUSTODIOL was maintained at 60mmHg initially, and maintained at 40mmHg for a period of 7 minutes after cardiac arrest. This follows a perfusion rate of 1ml/min per gram of heart weight, up to a total amount of 3000 to 4000ml used for adults

8) Tjang YS, van der Heijden GJ, Tenderich G, Grobbee DE, Körfer R. Survival analysis in heart transplantation: results from an analysis of 1290 cases in a single center. Eur J Cardiothorac Surg. 2008 May;33(5):856-61