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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 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.

Background: The purpose of this study was to evaluate the effect of ephedrine and phenylephrine on propofol concentrations and bispectral index during propofol anesthesia., Methods: General anaesthesia was induced with propofol and was maintained with propofol (4 mg kg-1 h-1) and fentanyl. Vecuronium was used to facilitate the artificial ventilation of the lungs. Patients with systolic blood pressure > 90 mmHg were defined as the control group (n = 16). Patients who had to be treated for larger decreases in arterial blood pressure (systolic blood pressure 60, whereas no patient in the control or phenylephrine groups had bispectral index >60. There were no significant differences in propofol concentrations or cardiac output relative to baseline at 3 or 10 min after the administration of ephedrine or phenylephrine., Conclusions: Ephedrine increases bispectral index values without decreasing propofol concentrations during general anesthesia.

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.

Background: During normothermic cardiopulmonary bypass (CPB), the effect on propofol pharmacokinetics of changes in its binding to plasma proteins is consistent with the predictions of the well-stirred model of hepatic elimination for nonrestrictively cleared drug. However, whether changes in binding lead to clinically significant changes in the drug effect remains unclear. The purpose of this study was to assess changes in the drug effect of propofol in response to altered plasma binding using quantitative EEG measurements., Methods: Thirty patients undergoing cardiac surgery were assigned randomly to receive propofol infusions at 4 (Group P-4) or 6 (Group P-6) mg kg(-1) h(-1) during surgery. The concentration of propofol in blood samples, collected from the radial artery at predetermined intervals, was determined by HPLC. The unbound fraction of drug in plasma was estimated using equilibrium dialysis. Bispectral index (BIS) and burst suppression ratio (BSR) were measured at the time blood samples were collected., Results: The total concentration of propofol in blood was unchanged during CPB relative to the pre-CPB value in both groups. However, the fraction of unbound propofol in blood increased by 2-fold during CPB. While BIS values were unchanged during CPB in Group P-4, there was a slight, but significant, decrease in Group P-6. In both groups, BSR significantly increased during CPB. BIS values showed a weak correlation with the concentration of unbound propofol (r(2)=0.19, P<0.001). BSR showed a moderate correlation with the concentration of unbound propofol (r(2)=0.56, P<0.001)., Conclusions: The anaesthetic effect of propofol significantly increased during CPB without any alteration in the total drug concentration. The enhanced efficacy may be caused by a reduction in plasma binding of the drug.

The purpose of this study was to assess the effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion (TCI) system. Thirteen patients undergoing gynecologic laparoscopy (intraabdominal pressure of 10 mmHg) were enrolled in this study. Anesthesia was induced with vecuronium 0.1 mg.kg(-1) and propofol, then maintained by 60% nitrous oxide and sevoflurane in oxygen and a constant infusion of propofol. Propofol was administered to all subjects by means of a target-controlled infusion to achieve propofol plasma concentration at 6.0 microg.ml(-1) at intubation and 2.0 microg.ml(-1) after intubation. Before and during laparoscopy, plasma propofol concentration was determined using high-performance liquid chromatograhy. Cardiac output (CO) and effective liver blood flow (LBF) were also measured using indocyanine green as an indicator. Before and during pneumoperitoneum, there were no significant differences in propofol concentrations between each point. Propofol concentrations were well achieved to predicted concentrations administered by the TCI system during gynecologic laparoscopy under propofol and sevoflurane anesthesia.

Background: Propofol is used during living-related donor liver transplantation because its metabolism is not greatly affected by liver failure. However, the pharmacokinetics of propofol during liver transplantation have not been fully defined. The purpose of this study was to evaluate the apparent systemic clearance of propofol during the dissection, anhepatic and reperfusion phases of living-related donor liver transplantation, and to estimate the role of the small intestine and lung as extrahepatic sites for propofol disposition., Methods: Ten patients scheduled for living-related donor liver transplantation were enrolled in the study. Anaesthesia was induced with vecuronium 0.1 mg kg(-1) and propofol 2 mg kg(-1), and then maintained by 60% air, 0.5-1.5% isoflurane in oxygen and a constant infusion of propofol at 2 mg kg(-1) h(-1). Apparent systemic clearance during the dissection, anhepatic and reperfusion phases was calculated from the pseudo-steady-state concentration for each phase. Disposition in the small intestine was determined by measuring arteriovenous blood concentration in 10 liver transplantation donors. Pulmonary disposition was determined by measuring the arteriovenous blood concentration in 10 recipients during the anhepatic phase. The data are expressed as mean (sd)., Results: Apparent systemic clearances in the dissection, anhepatic and reperfusion phases were 1.89 (sd 0.48) litre min(-1), 1.08 (0.25) litre min(-1) and 1.53 (0.51) litre min(-1), respectively. The concentration of propofol in the portal vein was lower than in the radial artery. The intestinal extraction ratio calculated from the concentration in the radial artery and portal vein was 0.24 (0.12). There were no significant differences in propofol concentrations between the radial and pulmonary arteries., Conclusion: Apparent systemic clearance was decreased by approximately 42 (10)% during the anhepatic phase compared with the dissection phase. After reperfusion, liver allografts rapidly began to metabolize propofol. The small intestine also participates in the metabolism of propofol.

It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short-acting beta-1-adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control and landiolol group. Induction of anesthesia commenced 10 min after the infusion of 0.9% saline or landiolol, using a Diprifusor set to achieve propofol plasma concentration of 6.0 microg/mL. Induction of anesthesia was defined as the first lack of response to command. Propofol dose was 2.22+/- 0.21 mg/kg for the control group and 1.79+/- 0.28 mg/kg for the landiolol group (P<0.0001). The quantity of propofol required for the induction of anesthesia was reduced by the administration of landiolol.

Purpose: It is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia., Methods: 12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography., Results: At one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98 L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1) to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P < 0.0001)., Conclusions: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.

Background: Extrahepatic clearance of propofol has been suggested because its total body clearance exceeds hepatic blood flow. However, it remains uncertain which organs are involved in the extrahepatic clearance of propofol. In vitro studies suggest that the kidneys contribute to the clearance of this drug. The purpose of this study was to confirm whether human kidneys participate in propofol disposition in vivo., Methods: Ten patients scheduled to undergo nephrectomy were enrolled in this study. Renal blood flow was measured using para-aminohippurate. Anesthesia was induced with vecuronium (0.1 mg/kg) and propofol (2 mg/kg) and then maintained with nitrous oxide (60%), sevoflurane (1 approximately 2%) in oxygen, and an infusion of propofol (2 mg . kg . h). Radial arterial blood for propofol and para-aminohippurate analysis was collected from a cannula inserted in the radial artery. The renal venous sample and the radial arterial sample were obtained at the same time after the steady state of propofol was established., Results: The renal extraction ratio of propofol was 0.58 +/- 0.15 (mean +/- SD). The renal clearance of propofol was 0.41 +/- 0.15 l/min (mean +/- SD), or 27 +/- 9.9% (mean +/- SD) of total body clearance., Conclusion: Human kidneys play an important role in the elimination of propofol.

The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 +/- 0.82 mg kg(-1) h(-1) (mean +/- SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 +/- 0.24 microg ml(-1) and 1.83 +/- 0.54 l min(-1) (mean +/- SD, n =7), respectively.