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Completed

NCT Number: NCT01267487

Clinical Trial Comparing Heparin and Protamine Fixed and Titrated Doses in Cardiac Surgery With Cardiopulmonary Bypass

There are currently several schemes described for anticoagulation with heparin and its reversal with protamine during cardiac surgery with CPB. The oldest, and most used in our routine environment, is the scheme of fixed doses, in which a bolus dose of heparin at the start of CPB is established in IU/kg of body weight and the dose of protamine at the end of CPB is calculated based on the initial dose of heparin administered.

These schemes do not take into account the variability inter-patients and can result in overdose or sub-doses of one or both drugs.

The titration schedule of doses of heparin and protamine through the principle of dose-response curve of Bull promotes individualization of dosage according to the response of each patient. This scheme has been associated with an effective reversal of the effect of heparin after CPB and with reduction of post-operatory bleeding and transfusion.

The restoration of a state of anticoagulation by heparin after its reversal by protamine is called "rebound effect". It is a phenomenon explained by the recirculation of heparin stored in the reticulum-endothelial system and connective tissue, or by free residual concentration of heparin after clearance of protamine. This effect may be present for more than 6 hours of post-operatory and may contribute to increase post-operatory bleeding.

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Key information

Conditions

Cardiac Surgery Anticoagulation Cardiopulmonary Bypass

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90620-001, Brazil

About this study

The objectives were, primarily, to compare intraoperative fixed versus titrated doses of heparin and protamine in cardiac surgeries with CPB regarding blood loss and transfusion requirements during the first 24 post-operative (PO) hours.

Secondarily, the investigators compared continuous infusion of small doses of protamine (25mg/hour) and placebo during the first 6 PO hours to neutralize heparin rebound effect. The investigators measured KTTP and fibrinogen levels during the first 24 PO hours and also the difference in blood loss and transfusion requirements between the groups.

The study included patients from 18 to 75 years-old submitted to Cardiac surgeries with Cardiopulmonary Bypass.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients submitted to an Elective Cardiac Surgery with Cardiopulmonary Bypass
  • Age 18 to 75 years-old

Exclusion criteria

  • Hematocrit < 30
  • INR > 1,3
  • Platelets < 100,000
  • Altered KTTP
  • Receiving Non-fractioned Heparin or Low-Molecular Weight Heparin
  • Renal Insufficiency or Creatinine > 2,0
  • Liver Failure or altered ALT/AST
  • Von Willebrands'disease, Haemophilia, sepsis
  • Use in the past 7 days of antiplatelet-therapy(Ticlopidine or Clopidogrel)

Treatment and study plan

Heparin fixed doses

Drug

Fixed doses of 400 units/ kg of patient's body weight before CPB to achieve an ACT > 480 sec. Supplemental doses of 50mg of heparin if ACT <480 sec during CPB.

Reversal doses of protamine in a 1:1 ratio (1mg of protamine for every mg of heparin administered), plus 0.8mg/kg of protamine at the end of the surgery.

PO continuous infusion of Protamine

Drug

25mg/hour in IV continuous infusion during first 6 PO hours

Heparin and protamine titration

Drug

Titrated doses of heparin during CPB were manually calculated using Bull´s dose-response curve, which was based in periodic assessment of Activated-Coagulation Times (ACT)- baseline ACT, after 2mg/kg of heparin at cannulation and every 15 to 30 minutes during CPB.

Reversal doses of protamine were calculated as a 1:1 ratio of the actual estimated heparin concentration (in mg/kg) at the end of CPB, using the Bull´s dose response curve.

Primary outcomes

  1. Mediastinal blood drainage (ml)

    Time frame: First 24 PO hours

    The mediastinal blood drainage was measured hourly during the first 6 post-operatory (PO) hours, and every 6 hours from the 7th to 24th PO hours.

Secondary outcomes

  1. Transfusion of blood components

    Time frame: First 24 PO hours

    We measured the incidence(%) of transfusion of Packed Red Blood Cells, Plasma or Platelet during first 24 PO hours

Sponsors and collaborators

Lead sponsor

SANE-Society of Anesthesiology

Other

Collaborators

  • Fundação Universitária de Cardiologia (University Foundation of Cardiology)
  • Instituto de Cardiologia do Rio Grande do Sul

Registry information

Official study title

Phase 4 Study of Fixed-dose and Titration Schemes of Heparin and Protamine in Cardiopulmonary Bypass Cardiac Surgeries : Evaluation of Post-operatory Blood Loss and Transfusion Requirements

Important dates

Study start
2009
Primary completion
2010
Study completion
2010
First posted
Dec 28, 2010
Registry last updated
Dec 28, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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