Introduction:
Cardiopulmonary bypass is an integral component used in the majority of cardiac surgeries. The instigation and maintenance of cardiopulmonary bypass requires the administration of an anticoagulant, and this is routinely in the form of heparin due to its predictable and favourable pharmacology. One of the important aspects of heparin’s pharmacology is the presence of a known and relatively safe reversal agent in the form of protamine. Protamine is routinely used after weaning patients from cardiopulmonary bypass, to reverse heparin’s anticoagulant effect and therefore reduce the risk of post-operative bleeding.
Postoperative bleeding remains a significant risk after cardiac surgery with a national prevalence of 2.6% (1). Blood transfusion is therefore often required in the postoperative period. There are a number of studies showing that red blood cell transfusion has a significant detrimental impact on both short- and long-term outcomes (2, 3), therefore reducing the transfusion requirements for patients is paramount.
Bleeding after coronary artery bypass grafting (CABG) is often multifactorial, and risk factors include patient demographics and comorbidities, perioperative pharmacology and technical factors (4). One factor which has been theorised to contribute to postoperative bleeding is that of heparin rebound, with a prevalence of up to 52% (5). In heparin rebound, previously bound or incompletely neutralised heparin leads to anticoagulation in the early postoperative period despite seemingly adequate neutralisation initially with protamine intraoperatively. It is theorised that there are a number of different factors which combine leading to heparin rebound, these include the release of extra-circulatory deposits of heparin postoperatively (6) and the binding of heparin to intravascular proteins leading to incomplete neutralisation by the initial dose of protamine (7). Due to increased knowledge of the heparin rebound phenomenon many centres now routinely use thromboelastography with pre- and post-heparinase levels, in those patients bleeding excessively postoperatively, to identify the patients who may require further protamine in intensive care (8).
Administration of protamine however does not come without risk. One side effect of overzealous protamine administration is its anticoagulant effect at high doses, an effect which has shown in randomised controlled data post-cardiac surgery (9). In addition, protamine has been shown to cause significant and sometimes profound vasoplegia with a reduction in systemic blood pressure, along with pulmonary hypertension with an increase in pressures of up to 9.9 mmHg (10).
In our centre a number of cardiac surgeons utilise postoperative low dose protamine infusions with the aim of reducing heparin rebound and the potential postoperative bleeding along with the morbidity and mortality associated with this. Other surgeons in our centre do not use the infusion due to current poor-quality evidence for its use and potential side-effects of protamine over administration.
Our aim was to study whether the use of a four-hour, low dose protamine infusion in intensive care would reduce post-operative bleeding and transfusion requirements. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Anonymised data were obtained from the institutional database normally utilised for patient care and therefore the need for informed consent was waived by the institutional Medical Ethical Committee. Baseline, and outcome data were prospectively collected, validated and entered into the database, which was analysed retrospectively.
Many studies focused in calculating heparin dose according to ideal body weight (not actual body weight) especially for those with high body mass index. (11, 12, 13), in which heparin dose was sufficient when adjusted to ideal or lean body weight. Moreover, Mya S. Baker et al concluded that some overweight and obese patients presenting for cardiac surgery may require as much as 25% less heparin and subsequently protamine than previously thought (12). So, we also studied the effect of protamine infusion in patients with high BMI as we thought that heparin might be is overdosed in those patients. In this study we also tried to study if we could achieve better outcome in obese patients with protamine infusion as many authors believed that the heparin dose calculated for these patients based on actual body weight was likely to be more and thereby increasing chances of Heparin rebound and bleeding(11-13)