Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in CABG
Condition: Cardioplegia Solution Adverse Reaction
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background: In cardiac surgery, myocardial protection is mandatory during cross clamp time
      followed by reperfusion. Use of cardioplegic solutions preserves myocardial energy stores,
      hindering electrolyte disturbances and acidosis during periods of myocardial ischemia. This
      study was designed to compare the efficacy and safety of Histidine-tryptophan-ketoglutarate
      (HTK) solution versus blood cardioplegia in coronary artery bypass graft surgery.

      Methods: Three hundred and twenty patients were randomized into
      Histidine-tryptophan-ketoglutarate (HTK) group and blood cardioplegia group. Ventilation
      time, total bypass time, cross clamp time, length of ICU or hospital stay and the early
      postoperative outcomes were analysed.
    

Detailed description: 
      The Ethics Committee of Ain Shams university approved this randomized prospective
      double-blinded controlled parallel group study to be held in Cardiothoracic Academy for three
      months from December 2019 to April 2020. The study was conducted on three hundred and twenty
      older patients aged from 60-80 years old posted for elective coronary artery bypass grafting
      (CABG). Written informed consents were signed by all patients. Exclusion criteria included
      (1) patients with Unstable angina (class III or IV); (2) Poor left ventricular function (LVEF
      <40%) ;(3) Patient with acute myocardial infarction; (4) Previous CABG; (5) Previous renal
      failure; (6) Preoperative Aortic valve or Mitral valve disease requiring replacement ;(7)
      Urgent CABG operation.

      A detailed medical history, including medications used, symptoms and risk factors for
      ischemic heart disease (smoking, DM, hypertension), NYHA classification and full
      investigations were assessed on the night of the surgical procedure. Anesthesia management
      was standardized for all patients. Premedication with midazolam was limited to a maximum of
      0.05 mg/kg. Anesthesia was done with 12 μg/kg fentanyl, 5-7 mg/kg thiopental sodium, and 0.15
      mg/kg pancuronium and was maintained with 1-2.0% isoflurane. Heart rate and blood pressure
      were maintained within 20% of the baseline values. Anticoagulation was achieved with heparin
      300 U/kg administered into the right atrium to maintain an activated clotting time above 480
      s. Cardiopulmonary bypass (CPB) was established by non-occlusive roller pumps, membrane
      oxygenators and arterial line filtration. The CPB circuit was primed with 1.8 l lactated
      Ringer's solution and 50 ml of 20% mannitol. Management of CPB included systemic hypothermia
      during aortic cross-clamping, targeted mean perfusion pressure between 60 and 80 mmHg, and
      pump flow rates of 2.2 l/min/m2.Intraoperatively the patients were monitored using ECG, pulse
      oximetry, Invasive blood pressure monitoring, arterial blood gases, central venous line
      catheter and temperature probe. Surgical approach was performed by median sternotomy.

      Patients were randomly allocated into 2 groups either HTK group and blood cardioplegia group
      according to a computer-generated randomization code, with allocation ratio 1:1. Opaque
      sealed envelopes were prepared according to the randomization schedule, and were opened by a
      clinician not involved in any part of the study.

      In the HTK group, patients received 30 ml/kg of HTK cardioplegic solution at 4°C through an
      antegrade fashion at an initial perfusion pressure of 80-100 mmHg. In blood cardioplegia
      group, patients received one liter of blood cardioplegia was given with the antegrade route
      at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins. The study
      medications were calculated and prepared by ICU residents who were not a part of the research
      team. To ensure blinding of study drug administration, the medication vials were kept in
      opaque bags. Trial bags were blinded and marked with a unique number. The allocation of trial
      drugs was determined by the web-based randomization system by the allocation of the bag
      number. The end-point assessor of the outcomes was blinded to the study drugs.

      Before separation from CPB, patients were rewarmed to 36-37°C. After separation from CPB,
      heparin was neutralized with protamine sulfate 1 mg/100 U heparin to reach an activated
      clotting time within 10% of baseline. All patients were then transferred to the ICU after
      surgery.

      The primary end-point of the study included early postoperative outcomes including cardiac
      enzymes preoperatively, 8 & 24 hour post-operatively, 30-day mortality, wall motion
      abnormalities and pericardial effusion. The secondary end-points included ventilation time,
      cross clamp and total bypass time, length of ICU stay, length of hospital stay, need for
      inotropic support, 30-day readmission, the incidence of late postoperative complications as
      renal dysfunction.
    

Intervention name(s): HTK cardioplegic solution; blood cardioplegia
Intervention type(s): Drug; Drug
Intervention description(s): 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg; one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins
Other intervention name(s): Histidine-tryptophan-ketoglutarate solution
Intervention MeSH terms: Cardioplegic Solutions; Tryptophan; Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment