Influence of atropine on the dose requirements of propofol in humans.

OBJECTIVE: The purpose of this study was to evaluate the effect of atropine on the dose requirement of propofol for induction of anesthesia and propofol concentrations during continuous infusion. METHODS: Study 1: Forty patients were randomly allocated to the control or atropine groups. Induction of anesthesia commenced 3 min following the administration of 0.9% saline or atropine (0.01 mg kg(-1)), using a Diprifuser set to achieve propofol concentration of 6.0 microg mL(-1). The primary end point was the propofol dose per kg at the moment of loss of response to a command. Study 2: Fifteen patients undergoing elective surgery were enrolled. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 2.0 microg mL(-1) after intubation. Before and after administration of atropine (0.01 mg kg(-1)), cardiac output (CO) was measured using indocyanine green as an indicator and blood propofol concentration was determined using high-performance liquid chromatography. RESULTS: Study 1: The propofol dose for each group was 2.22+/-0.21 mg kg(-1) for control group and 2.45+/-0.28 mg kg(-1) for atropine, respectively (p=0.014). Study 2: After the administration of atropine, CO was significantly increased from 4.28+/-0.83 to 5.76+/-1.55 l min(-1) (p<0.0001). Propofol concentration was significantly decreased from 2.12+/-0.28 to 1.69+/-0.27 microg mL(-1) (p<0.0001). CONCLUSIONS: Following the administration of atropine, the propofol requirements for the induction of anesthesia were increased and propofol concentrations were decreased during continuous infusion by the administration of atropine.

The effect of positive end-expiratory pressure ventilation on propofol concentrations during general anesthesia in humans.

The present study investigated the effects of positive end-expiratory pressure (PEEP) on propofol concentrations in humans. Eleven patients undergoing elective surgery were enrolled in this study. Anesthesia was induced with propofol, then maintained using 60% nitrous oxide in oxygen, fentanyl 10-20 microg/kg and continuous infusion of propofol. Vecuronium was used to facilitate the artificial ventilation of the lungs. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration of 6.0 microg/mL at intubation and 2.0 microg/mL after intubation. Before, during and after PEEP level of 10 cmH(2)O, cardiac output (CO) and effective liver blood flow (LBF) was measured using indocyanine green as an indicator and blood propofol concentration was determined using high-performance liquid chromatography. Data are expressed as median and range. After PEEP of 10 cmH(2)O was applied, CO and effective LBF was significantly decreased from 5.5 (3.8-6.8) L/min to 4.5 (3.2-5.8) L/min (P < 0.05), 0.78 (0.65-1.21) L/min to 0.65 (0.50-0.89) L/min (P < 0.05), respectively. Propofol concentration was significantly increased from 2.21 (1.46-2.63) microg/mL to 2.45(1.79-2.89) microg/mL (P < 0.05). These data indicate that propofol concentrations can be increased by PEEP, suggesting the possibility of overdosing following PEEP.

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 microg 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 microg ml-1 to 0.17+/-0.041 microg 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.