Disposition and pharmacodynamics of propofol during isovolaemic haemorrhage followed by crystalloid resuscitation in humans

Aims The purpose of this study was to estimate the changes in unbound propofol concentration and pharmacodynamics of propofol during isovolaemic haemorrhage followed by crystalloid resuscitation. Methods Ten patients undergoing measure elective surgery were enrolled in this study. Anaesthesia was maintained by 60% nitrous oxide in oxygen, fentanyl 10–20 µg kg−1 and an infusion of propofol at 8 mg kg−1 h−1 until the end of the operation. Radial arterial samples were collected for measurement of propofol concentration just before the start of the operation, and at the point when blood loss was > 10 ml kg−1, 20 ml kg−1 and 30 ml kg−1. Cardiac output (CO), haemoglobin values and plasma concentrations of albumin were also determined. Patients were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure (± 20% of prehaemorrhage). Bispectral index (BIS) was measured continuously. Results Mean blood pressure, heart rate and CO were well maintained during the operation in all patients. Haemoglobin values and plasma albumin concentrations decreased significantly during surgery. There were no significant differences in total propofol concentrations across the time points. The unbound propofol concentration was increased from 0.10 ± 0.040 µg ml−1 to 0.17 ± 0.041 µg ml−1 after the haemorrhage of 30 ml kg−1 (P < 0.05). BIS was significantly decreased from 47 ± 5.9 to 39 ± 3.7 (P < 0.05) after the haemorrhage of 30 ml kg−1. Conclusions The hypnotic potency of propofol is increased during isovolaemic haemorrhage in crystalloid resuscitated patients even if CO is maintained.