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)