Calcium Administration in Cardiac Surgery

Study Overview
=================
Brief Summary
-----------------
Termination of cardiopulmonary bypass is a critical step in any cardiac surgical procedure and requires a thorough planning. Debate about rationale of calcium administration during weaning of cardiopulmonary bypass has been conducted for several decades; however, a consensus has not been yet reached. Perioperative hypocalcemia can develop because of haemodilution or calcium binding from heparin, albumin and citrate. Perioperative hypocalcemia is often complicated by development of arrhythmias, especially QT interval prolongation. Furthermore, low content of calcium can lead to vascular tone disorders, violation of neuromuscular transmission, altered hemostasis and heart failure, resistant to inotropic agents, especially in patients with concomitant cardiomyopathy. On the other hand, hypercalcaemia is a dangerous complication in cardiac surgery. Among the fatal, but rather rare complications, there are acute pancreatitis and the phenomenon of the stone heart, which is essentially a reperfusion injury of the myocardium caused by rapid calcium overload. Hypercalcaemia can also trigger rhythm disturbances, hypertension, increase systemic vascular resistance, reduce diastolic compliance and impair relaxation of the myocardium due to excessive calcium intake into the cardiomyocytes, cause coronary vasospasm and aggravate ischaemic myocardial damage, impair arterial graft blood flow during aortocoronary and mammary coronary bypass surgery. To date, there is a lack of data indicating clinical efficacy of calcium administration before separation from CPB. Therefore, we designed this randomized controlled trial to test the hypothesis whether calcium administration at termination of CPB will reduce the need for inotropic support at the end of surgery.

Official Title
-----------------
Calcium Administration in Patients Undergoing Cardiac Surgery Under Cardiopulmonary Bypass (ICARUS Trial): Prospective Randomized, Double-blind Placebo-controlled Superiority Trial

Conditions
-----------------
Cardiac Surgery, Cardiopulmonary Bypass

Intervention / Treatment
-----------------
* Drug: Calcium Chloride
* Drug: 0.9% Sodium Chloride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: surgery under cardiopulmonary bypass valve or valve surgery + CABG age > 18 years signed informed consent Exclusion Criteria: emergency surgery isolated aortic valve repair/replacement planned (before surgery) blood transfusion redo surgery known allergy to the study drug pregnancy current enrollment into another RCT (in the last 30 days) previous enrollment and randomization to ICARUS trial liver cirrhosis (Child B or C) transfusion during CPB hypo- or hyperparathyreosis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcium chloride<br>Participants randomly assigned to the experimental group will receive 15 mg/kg of calcium chloride (bolus) intravenously during separation from cardiopulmonary bypass | Drug: Calcium Chloride<br>* Calcium Chloride<br>|
| Placebo Comparator: 0,9% Sodium Chloride<br>Participants randomly assigned to the placebo group will receive equivalent amount of placebo intravenously during separation from cardiopulmonary bypass | Drug: 0.9% Sodium Chloride<br>* 0.9% Sodium Chloride<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inotropic support | Number of patients requiring inotropic support before transfer to intensive care unit | Intraoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of inotropic support after surgery | Duration of infusion of any vasoinotropic agent at any dose | 30 days after surgery | 
| Vasoactive-inotropic score | Vasoactive-inotropic score will be measured on the morning of postoperative day 1. The inotropic score will be calculated using the following formula: Dobutamine dose (in mcg/kg/min) + Dopamine dose (in mcg/kg/min) + Enoximone dose (in mcg/kg/min) + [Epinephrine dose (in mcg/kg/min) x 100] + [Norepinephrine dose (in mcg/kg/min) x 100]. | Postoperative day 1 | 
| Plasma Ca2+ concentration before and after drug administration |  | Intraoperatively | 
| Time spent in theatre after cardiopulmonary bypass |  | Intraoperatively | 
| Duration of ventilation |  | Up to 30 day after randomization | 
| Duration of intensive care unit stay |  | Up to 30 day after randomization | 
| Myocardial infarction | Number of patients who develop myocardial infarction | Up to 30 day after randomization | 
| Atrial fibrillation | Number of patients who develop postoperative atrial fibrillation | Up to 30 day after randomization | 
| Type 1 and type 2 neurological complications | Number of patients who develop type 1 and type 2 develop myocardial infarction | Up to 30 day after randomization | 
| Postoperative blood loss | Postoperative blood (ml/kg) loss will be measured on the morning of postoperative day 1 | Postoperative day 1 | 
| Need for blood transfusion after surgery | Number of patients who will need transfuion of any blood products (red cells, fresh frozen plasma, cryoprecipitate) | Up to 30 day after randomization | 
| Intraoperative myocardial ischemia | The presence of intraoperative myocardial ischemia will be defined during continuous intraoperative ECG monitoring after calcium chloride or placebo administration | Intraoperatively | 
| Myocardial ischaemia on ECG after arrival to ICU | Number of patients who develop myocardial ischemia | Postoperative day 1 | 
| Concentration of alpha-amylase after surgery |  | Postoperative day 1 | 
| Internal mammary artery vascular resistance (if available) | Will be defined by intraoperative graft flow measurements | Intraoperatively | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inotropic support, calcium chloride, cardiopulmonary bypass, cardiac surgery