Plasma Propofol Research Articles

Pharmacokinetics of propofol in patients undergoing total hip replacement

The aim of the study was to investigate the effects of acute hypervolemic hemodilution (HHD) on the pharmacokinetics of propofol in patients undergoing total hip replacement. A total of 16 patients undergoing elective surgery for total hip replacement under general anesthesia in combination with epidural analgesia were randomly assigned to 2 groups: the control group (n = 8) or the HHD group (n = 8). All patients in both groups received lactated Ringer's solution before induction of general anesthesia. In the control group the conventional fluid replacement protocol was used. In the HHD group 4% succinylated gelatin was infused at the rate of 20ml•kg(-1)BW•h(-1 )with a targeted hematocrit of 30. Anesthesia was induced with midazolam 0.04mg•kg(-1), fentanyl 4µg•kg(-1) and propofol 1.5mg•kg(-1). Tracheal intubation was facilitated by infusion of succinylcholine 2mg•kg(-1). Anesthesia was maintained with isoflurane, fentanyl, vecuronium and epidural analgesia. Electrocardiogram (ECG), blood pressure (BP), blood oxygen saturation (SpO(2)), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) and central venous pressure (CVP) were monitored continuously. Blood samples were taken at 1, 2, 4, 6, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300 and 360min after propofol administration to determine plasma concentrations of propofol by high performance liquid chromatography (HPLC). Plasma propofol concentrations were significantly lower in the HHD group than in the control group at 1, 2, 4, 6 and 10min after propofol administration (p < 0.01) while there were no significant differences in plasma propofol levels 15-360min after administration of propofol (p > 0.05). In the HHD group the volume of distribution of the central compartment (V(C)) increased significantly, elimination half-life (T(1/2) (γ)) was significantly prolonged, the elimination rate constant (K(10)) and the whole-body clearance (CL) were significantly decreased compared with the control group (p < 0.01 or 0.05). There were no significant differences of the half-life of the fast distribution phase (T(1/2) (α)), half-life of the slower distribution phase (T(1/2) (β)), K(12), K(21), K(13), K(31) and the area under the curve (AUC) (p > 0.05). The pharmacokinetic profile of propofol is best described by a three-compartment model in both groups using minimal Akaike information criteria (AIC). Acute HHD increases V(C), prolongs the T(1/2) (γ), and decreases K(10) and CL, which suggests that care must be taken when propofol is used in patients undergoing HHD. The induction dose should be increased, but the maintenance dose should be decreased. The time to emergency from anesthesia will likely be prolonged, especially in patients receiving prolonged continuous infusions.

Pharmacokinetics of propofol when combined with remifentanil in patients with liver cirrhosis

Objective To investigate the pharmacokinetics of propofol when combined with remifentanil in patients with liver cirrhosis.Methods Ten patients (5 males, 5 females) with liver cirrhosis scheduled for endoscopic esophageal varix ligation (test group) and 10 cases (5 males, 5 females) with normal liver function scheduled for gastroscopy (control group), aged 18-55 yr, weighing 40-75 kg, were studied. The patients were unpremedicated. All the patients received iv injection of propofol 1.5 mg/kg and remifentanil 0.5 μg/kg, and 5 min later propofol 0.5 mg/kg and remifentanil 0.2 μg/kg was given again. Blood samples were taken from radial artery before administration and at 2, 5, 10, 15, 20, 30, 45, 60, 80 and 120 min after administration for determination of the plasma propofol concentration using gas chromatography-mass spectrography. The pharmacokinetic parameters were calculated using DAS 2.0 software.Results The pharmacokinetics of propofol was best described by a three-compartment open model. There was no significant difference in the distribution half-life, elimination halflife , terminal half-life, area under the curve and transfer rate constant between the two groups ( P ＞ 0.05) . The apparent volume of distribution of propofol and clearance were significantly increased in test group compared with control group (P ＜0.01) .Conclusion When propofol combined with remifentanil is used in patients with liver cirrhosis, the apparent volume of distribution of propofol and clearance are significantly increased, while no changes in the other pharmacokinetic parameters are found. Key words: Propofol; Piperidines; liver cirrhosis; Pharmacokinetics

Effect of remifentanil on plasma propofol concentration and bispectral index during propofol anaesthesia

BackgroundPropofol and remifentanil are commonly administered together in clinical anaesthesia, but the effect of remifentanil on the plasma concentration of propofol has yet to be established. The aim of the present study was to investigate the effect of remifentanil on plasma propofol concentrations (Cp) in the absence of surgical stimulation. MethodsThirty-eight patients undergoing elective gynaecologic surgery were randomly assigned to receive one of the three remifentanil doses (0, 0.5, or 1.0 µg kg−1 min−1). Anaesthesia was induced by a target-controlled infusion of propofol. After tracheal intubation, saline or remifentanil infusion was administered for 15 min. Mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded and cardiac index (CI), blood volume, and indocyanine green disappearance ratio (K-ICG) were measured using a dye densitogram analyser before and 15 min after saline or remifentanil infusion. Cp was measured using high-performance liquid chromatography. ResultsHR, K-ICG, and BIS were significantly decreased in the remifentanil 0 µg kg−1 min−1 group. The decrease in MAP, HR, CI, and K-ICG was significantly lower in the remifentanil 0.5 and 1.0 µg kg−1 min−1 groups compared with the remifentanil 0 µg kg−1 min−1 group. Cp was significantly increased after remifentanil administration, but this had no influence on BIS. ConclusionsRemifentanil reduced the CI and increased the Cp, which may be related to a decrease in the K-ICG, but had no significant effect on the BIS.

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats. Study designProspective, randomized, crossover experimental study. AnimalsSix goats, three does and three wethers. MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg−1 followed by a constant rate infusion (CRI) of 0.05 mg kg−1 minute−1 (treatment LPROP); bolus of 1.0 mg kg−1 followed by a CRI of 0.1 mg kg−1 minute−1 (treatment MPROP), bolus of 2.0 mg kg−1 followed by a CRI of 0.2 mg kg−1 minute−1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance). ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory. Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.

Drug Metabolism within the Brain Changes Drug Response: Selective Manipulation of Brain CYP2B Alters Propofol Effects

Drug-metabolizing cytochrome P450 (CYPs) enzymes are expressed in the liver, as well as in extrahepatic tissues such as the brain. Here we show for the first time that drug metabolism by a CYP within the brain, illustrated using CYP2B and the anesthetic propofol (2, 6-diisopropylphenol, Diprivan), can meaningfully alter the pharmacological response to a CNS acting drug. CYP2B is expressed in the brains of animals and humans, and this CYP isoform is able to metabolize centrally acting substrates such as propofol, ecstasy, and serotonin. Rats were given intracerebroventricularly (i.c.v.) injections of vehicle, C8-xanthate, or 8-methoxypsoralen (CYP2B mechanism-based inhibitors) and then tested for sleep time following propofol (80 mg/kg intraperitoneally). Both inhibitors significantly increased sleep-time (1.8- to 2-fold) and brain propofol levels, while having no effect on plasma propofol levels. Seven days of nicotine treatment can induce the expression of brain, but not hepatic, CYP2B, and this induction reduced propofol sleep times by 2.5-fold. This reduction was reversed in a dose-dependent manner by i.c.v. injections of inhibitor. Sleep times correlated with brain (r=0.76, P=0.0009), but not plasma (r=0.24, P=0.39) propofol concentrations. Inhibitor treatments increased brain, but not plasma, propofol levels, and had no effect on hepatic enzyme activity. These data indicate that brain CYP2B can metabolize neuroactive substrates (eg, propofol) and can alter their pharmacological response. This has wider implications for localized CYP-mediated metabolism of drugs, neurotransmitters, and neurotoxins within the brain by this highly variable enzyme family and other CYP subfamilies expressed in the brain.

Effects of propofol on the minimum alveolar concentration of sevoflurane for immobility at skin incision in adult patients

Study Objective To determine the effect of propofol on skin incision at target plasma concentrations of one to 6 μg/mL on the minimum alveolar concentration (MAC) of sevoflurane. Design Prospective, randomized, single-blinded study. Setting Operating room of a university hospital. Patients 122 adult, ASA physical status I and II patients with cholecystitis and gastric cancer, presenting for elective abdominal surgery. Interventions Each group received propofol at different target-controlled plasma concentrations of 0, 1, 2, 3, 4, 5 and 6 μg/mL, respectively. The end-tidal concentration of sevoflurane was stable at a predetermined value for at least 15 minutes. Skin incision was performed after return of neuromuscular function. Measurements Patients were observed for gross purposeful movement for one minute after skin incision. Heart rate and mean arterial pressure were recorded before induction of anesthesia, before incision, and after incision. Main Results The MAC of sevoflurane when used alone was 2.2% ± 0.11%. Propofol decreased the MAC of sevoflurane by 12.3% at one μg/mL, 30.5% at two μg/mL, 35% at three μg/mL, 46.8% at 4 μg/mL, 57.7% at 5 μg/mL, and 72.7% at 6 μg/mL. The linear regression equation of the interaction between sevoflurane and propofol was Y = 2.1679 – 0.256 X, R 2 = 0.9407, where X = plasma propofol concentration, Y = sevoflurane concentration, and R 2 = correlation coefficient. Conclusions Propofol decreases the MAC of sevoflurane in a concentration-dependent manner in adult patients.

Effects of cerebral hypoperfusion on bispectral index: A randomised, controlled animal experiment during haemorrhagic shock

Background The aim of this porcine haemorrhagic shock model was to investigate the changes of bispectral index (BIS) after slow and fast recovery of cerebral perfusion, and its correlation with plasma propofol concentrations. Methods After Animal Investigational Committee approval, 16 pigs during propofol anaesthesia underwent a liver trauma with severe hypotension, and were randomly assigned to receive therapy for either slow recovery (fluid resuscitation; slow group; n = 8) or fast recovery of cerebral perfusion (vasopressor combined with hypertonic-saline-starch; fast group; n = 8), respectively. Cerebral perfusion pressure (CPP = MAP − ICP), cerebral tissue oxygenation index (TOI), BIS, and plasma concentrations of propofol and haemoglobin were measured at baseline (Pre-shock), haemodynamic decompensation (Shock), and 5 (Therapy) and 30 min (End) after therapy, respectively. Results CPP, TOI, and BIS decreased significantly during shock (pre-shock vs. shock, fast: CPP: 65 ± 14 vs. 15 ± 4 mm Hg; TOI: 64 ± 6 vs. 47 ± 7%; BIS 60 ± 5 vs. 9 ± 10; slow: CPP: 60 ± 12 vs. 13 ± 7 mm Hg; TOI: 68 ± 7 vs. 49 ± 7%; BIS 63 ± 5 vs. 13 ± 12; P < 0.05). In the fast group, CPP, TOI, and BIS increased after therapy compared to the slow group (Therapy, fast: CPP: 47 ± 15 mm Hg, TOI: 61 ± 7%, BIS: 47 ± 21; slow: CPP: 18 ± 9 mm Hg, TOI: 51 ± 5%, BIS: 21 ± 19; P < 0.05). Propofol and haemoglobin concentrations were comparable between groups throughout the resuscitation phase. Conclusions In a haemorrhagic shock scenario, therapies with different impact on cerebral perfusion resulted in differing changes of BIS values, while plasma propofol and haemoglobin concentrations were comparable during the resuscitation phase; this suggests that BIS may also have reflected changes of cerebral perfusion.

Changes in plasma orexin A during propofol–fentanyl anaesthesia in patients undergoing eye surgery

BackgroundCentral orexinergic and noradrenergic neurones are involved in the control of sleep and wakefulness. In addition, previous reports suggest that both neurones may have an important role to play in general anaesthesia. In the present study, we have determined whether general anaesthesia would affect plasma orexin A (OXA) and norepinephrine concentrations. MethodsTwenty-two patients undergoing elective ophthalmic surgery under general anaesthesia with propofol, fentanyl, and vecuronium were studied. Arterial blood was collected before and 1 and 2 h after induction of anaesthesia and at emergence to measure plasma OXA, propofol, norepinephrine, and epinephrine concentrations. During anaesthesia, the propofol infusion rate was changed to maintain the bispectral index between 40 and 50. ResultsPlasma OXA and norepinephrine did not change during anaesthesia but significantly increased after emergence compared with pre-anaesthesia [from 19.9 (sd 3.2) to 28.3 (4.3) pM, P<0.01, and from 1351 (146) to 1798 (251) pM, P<0.05, respectively]. Plasma epinephrine did not change. There was a significant correlation between plasma OXA and norepinephrine (P<0.05) and also between plasma propofol and OXA (P<0.05) and norepinephrine (P<0.01). ConclusionsWe found that plasma OXA and norepinephrine significantly increased during emergence from propofol–fentanyl anaesthesia.

The antinociceptive effect of esmolol

Esmolol is the first intravenous, short-acting, titratable β-blocker available for use in critical care and surgical settings [1]. Esmolol is thought to be a "jack of all trades" among drugs used in anesthesia because it prevents and treats cardiovascular responses due to perioperative stimuli.

A comparison between target-controlled and manually controlled propofol infusions in patients undergoing routine surgical procedures

Previous studies have shown that target-controlled infusion (TCI) was associated with increased propofol consumption as compared with manually controlled infusion (MCI). However, most studies lacked an objective measurement of anaesthetic depth. We compared TCI and MCI with regard to propofol dose requirement while monitoring depth of anaesthesia with bispectral index (BIS) and midlatency auditory-evoked potentials (MLAEPs). Fifty ASA 1 or 2 patients undergoing elective ENT surgery were randomly allocated to the TCI group (n = 25)or the MCI group (n = 25). BIS, MLAEPs, haemodynamic parameters and propofol plasma concentration were determined at various stages before, during and after anaesthesia. During anaesthesia, BIS values were always maintained between 40 and 60. Anaesthesia significantly increased latency of Pa and Nb compared with when patients were awake (P < 0.01). After extubation, the latency of Pa and Nb significantly decreased and basically returned to baseline level. BIS and latency of both Pa and Nb did not differ between groups.Also, the propofol induction dose (mean WSD: TCI, 2.09 +/- 0.36 mg kg(-1); MCI, 2.06 +/- 0.16 mg kg(-1) and total dose (TCI, 5.57 +/- 0.96 mg kg(-1) h(-1); MCI, 5.79 +/- 0.87 mg kg(-1) h(-1) and measured plasma propofol concentration during anaesthesia did not differ between groups. At 15 min after intubation, the mean predicted plasma concentration (2.2 +/- 0.2 microg ml(-1)) differed significantly from the measured plasma concentration (2.8 +/- 1.2 microg ml(-1)). No correlation was observed between predicted and measured propofol plasma concentrations.

Placental transfer and neonatal effects of propofol for cesarean section

Objective To investigate the placental transfer and neonatal effects of propefol for cesarean section. Methods Sixty ASA Ⅰ or Ⅱ parturicnts at full term, aged 23-31 yr, weighing 59-98 kg, height 156-169 cm, undergoing elective cesarean section under general anesthesia, were randomly divided into 2 groups (n = 30 each): general anesthesia group (group G) and epidural anesthesia group (group E). Group G received iv injection of propofol 2 mg/kg and sueeinyleholine 2 mg/kg to facilitate tracheal intubation. Blood samples of 5 ml were drawn from umbilical vein (UV) and artery (UA), and maternal artery (MA) after ligation of the umbilical cords respectively for determination of plasma propofol concentrations (CUV, CUA and CMA) by HPLC. Epidural anesthesia was performed at L1,2 interspace, 2% lidocaine 11-17 ml was administered and the upper spread of sensory block reached T6-8. HB, SpO2 and MAP were recorded after the parturients had settled down for 5 min in the operating room (T0), at skin incision (T1), after delivery of the baby (T2), and at the end of operation (T3) in both groups. The delivery time (duration between uterus incision and delivery of the baby), duration between the end of administration and clamping of UA and UV, and Apgar score at 1 and 5 min after delivery were also recorded. Results The duration between the end of administration and clamping of UA and UV was significantly shorter in group G than in group E (P 0.05). No neonatal respiratory depression in both groups and no intraoperative awareness in group G occurred. The plasma concentrations of propofol were (1.4±0.4), (0.86±0.25) and (0.70±0.22) μg/ml in maternal arterial, and umbilical venous and arterial blood samples respectively. CUV/CMA and CUA/CUV were 0.61±0.11 and 0.80± 0.10 respectively. Conclusion The anesthetic efficacy of propofol 2 mg/kg was satisfactory for cesarean section, and it has no adverse effects on the newborn although the metabolism is slow after easy placental transfer. Key words: Propofol; Cesarean section; Infant, newborn; Placenta

Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane

To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.

Skin impedance correlates to sedation grade, plasma propofol concentrations and bispectral index during a target-controlled infusion of propofol

Sympathetic activity, measured as changes in electrical skin impedance, may be used to assess the adequacy of general anaesthesia. The aim of this prospective study was to evaluate electrical skin impedance in comparison with bispectral index values and the Observer's Assessment of Alertness and Sedation (OAAS) scale during propofol infusion. Electrical skin impedance was measured with an electrosympathicograph. In 22 patients and eight healthy volunteers, anaesthesia was induced and maintained with propofol that was administered via a target-controlled infusion pump at increasing plasma concentrations. Bispectral index, electrosympathicograph and OAAS values were compared at six successive predicted target plasma concentrations (T 1-6: 0, 1.3, 1.7, 2.0, 2.4 and 2.8 microg ml(-1)). The changes in the electrical skin impedance measured with the assistance of the electrosympathicograph correlated with the changes in bispectral index values at each measurement time point and during the whole course (P < 0.0001), with the target plasma propofol concentrations (P < 0.0001), and with the OAAS scale (P < 0.0001). The observed correlations between electrical skin impedance, predicted plasma concentrations of propofol and OAAS scale appear to justify further investigation of skin impedance as a depth of anaesthesia monitor.

Effects of Cardiopulmonary Bypass on Propofol Pharmacokinetics and Bispectral Index During Coronary Surgery

PURPOSECardiopulmonary bypass is known to alter propofol pharmacokinetics in patients undergoing cardiac surgery. However, few studies have evaluated the impact of these alterations on postoperative pharmacodynamics. This study was designed to test the hypothesis that changes in propofol pharmacokinetics increase hypnotic effects after cardiopulmonary bypass.METHODSTwenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypass graft (group, n=10) coronary artery bypass grafts were anesthetized with sufentanil and a propofol target controlled infusion (2.0 μg/mL). Depth of hypnosis was monitored using the bispectral index. Blood samples were collected from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma propofol concentrations were measured using high-performance liquid chromatography, followed by a non-compartmental propofol pharmacokinetic analysis. Data were analyzed using ANOVA, considering p<0.05 as significant.RESULTSAfter cardiopulmonary bypass, despite similar plasma propofol concentrations in both groups, bispectral index values were lower in the on-pump coronary artery bypass graft group. Time to extubation after the end of propofol infusion was greater in the on-pump coronary artery bypass graft group (334 ± 117 vs. 216 ± 85 min, p = 0.04). Patients undergoing cardiopulmonary bypass had shorter biological (1.82 ± 0.5 vs. 3.67 ± 1.15h, p < 0.01) and terminal elimination (6.27 ± 1.29 vs. 10.5h ± 2.18, p < 0.01) half-life values, as well as higher total plasma clearance (28.36 ± 11.40 vs.18.29 ± 7.67 mL/kg/min, p = 0.03), compared to patients in the off-pump coronary artery bypass graft group.CONCLUSIONAside from the increased sensitivity of the brain to anesthetics after cardiopulmonary bypass, changes in propofol pharmacokinetics may contribute to its central nervous system effects.

Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children

Propofol is a sedative-hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration-response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD. A total of 24 children undergoing EGD, ages 3-10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 microg x kg(-1) given over 10 min as well as a continuous infusion of propofol delivered by a computer-assisted target-controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 microg x ml(-1) (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC50 for anesthesia). The EC50 +/- SE values in the control and DEX groups were 3.7 +/- 0.4 microg x ml(-1) and 3.5 +/- 0.2 microg x ml(-1), respectively. There was no significant shift in the propofol concentration-response curve in the presence of dexmedetomidine. The EC50 of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 microg x kg(-1) given over 10 min.

Predicted and Measured Plasma Propofol Concentration and Bispectral Index During Deep Sedation in Patients With Impaired Left Ventricular Function

To evaluate the ability of the Schnider pharmacokinetic model to predict plasma propofol concentration during target-controlled propofol infusion in patients with impaired left ventricular function and to investigate the predictive value of the bispectral index (BIS) to indicate deep sedation in this patient group. Prospective, observational study. Thirty-four patients (mean left ventricular ejection fraction 31% +/- 9%) undergoing the implantation of a cardioverter-defibrillator during deep sedation. None. Predicted and measured propofol plasma concentrations and BIS were assessed during steady-state conditions with the propofol infusion rate constant for at least 20 minutes. The plasma propofol concentration was significantly underestimated by the pharmacokinetic model used (mean percentage prediction error 37% +/- 49%). The 50% probability of deep sedation was calculated at a predicted propofol concentration of 2.09 (95% confidence interval [CI], 2.04-2.14) mug/mL and at a measured propofol concentration of 2.70 (95% CI, 2.62-2.78) mug/mL. BIS values showed a marked variability among individuals during deep sedation (5th-95th percentiles: 25-81). The pharmacokinetic model used markedly underestimated propofol plasma levels in the patient group studied. The large variability among patients suggests that BIS monitoring is not suitable for indicating an exact endpoint corresponding to deep sedation.

The Relationship Between Bispectral Index and Propofol During Target-Controlled Infusion Anesthesia: A Comparative Study Between Children and Young Adults

In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol. Forty-five prepubertal subjects (children) and 45 postpubertal subjects (adults) were studied. All patients were anesthetized with TCI of propofol, based on the Kataria et al.'s model for children and on the Schnider et al.'s model for adults. All data from the BIS and the TCI system were continuously recorded using Rugloop software. Remifentanil was continuously administered throughout the study (0.25 microg x kg(-1) x min(-1)). In all patients, after the end of surgery, a 12-min period with a stable target plasma concentration (Ct) of propofol, randomly assigned at 2, 3, 4, 5, and 6 microg/mL, was performed. In addition, in most of the patients, another 12-min period was performed during which the BIS was targeted at 50 +/- 5. After each 12-min steady-state period, the Ct and BIS were noted and the plasma concentration of propofol was measured (Cm). The Ct and Cm corresponding to half maximal effect (BIS(50)) was determined by the Hill equation, and by targeting BIS at 50. In children, as in adults, BIS values were highly correlated with the corresponding Ct or Cm of propofol following classical E(max) dose-response curves. The ECt(50) and the ECm(50), derived from the dose-response curves, were higher in children than in adults: ECm(50): 4.0 (3.6-4.5) microg/mL vs 3.3 (3.0-3.7) microg/mL [mean (95% CI)], P < 0.001; as well were the Ct and Cm clinically obtained when BIS was targeted at 50 (Cm(50): 4.3 +/- 1.1 microg/mL vs 3.4 +/- 1.2 microg/mL, (mean +/- SD) P < 0.05, children versus adults). Cm was generally under-estimated by the Ct, and the bias was higher in children than in adults: 2.6 +/- 2.6 microg/mL vs 1.7 +/- 1.6 microg/mL (P = 0.05). The good relationship between propofol and BIS demonstrated in children as in adults suggested a slightly lower sensitivity to propofol in children. As the predictability of plasma propofol concentrations with the classical pharmacokinetic/pharmacodynamic models is limited in children, a cerebral pharmacodynamic feedback, such as BIS, may be useful in this population.

Clinical adaptation of a pharmacokinetic model of Propofol plasma concentrations in children

A previously published pharmacokinetic simulation suggested a simple manual infusion regimen to achieve propofol plasma concentrations of 3 microg.ml(-1). This study investigated if a simple variation in propofol infusion rates is able to achieve distinct propofol plasma concentrations and whether these are close to the propofol plasma concentrations predicted by the Kataria model. With Research Ethics Board approval and written parental consent, a total of 17 healthy children requiring general anaesthesia were enrolled. Following inhalational induction of anaesthesia, a propofol bolus of 5 mg.kg(-1) was given and anaesthesia maintained using an adaptation of the McFarlan continuous propofol infusion regimen to achieve three distinct depths of propofol anaesthesia. Weight and propofol infusion data were used to calculate simulated propofol concentrations using the Kataria dataset and the TIVA simulation program. The performance of the infusion regimen was assessed by calculating the median performance error, median absolute performance error, wobble, and divergence. Measured propofol concentrations were (mean +/- sd) 7.15 +/- 1.4, 4.3 +/- 0.85, and 2.85 +/- 0.53 microg.ml(-1) against simulation values of 6.6, 4.1, and 2.8 microg.ml(-1), respectively, at 30, 50, and 70 min using the Kataria dataset. These differences were not significant. Formal assessment of the infusion regimen's performance was acceptable. The manual propofol infusion regimen achieved three distinct depths of propofol anaesthesia. The manual infusion regimen produced higher plasma propofol concentrations than predicted during the early part of the infusion period but was more accurate for later time points.

The correlation between actual blood concentration of propofol and the difference of estimated lean body mass with actual lean body mass in target controlled infusion

Background: We evaluated the correlation between the difference of estimated lean body mass (LBME) with actual lean body mass (LBMA) and actual blood concentration of propofol, hemodynamic variables and Bispectral index (BIS) during target controlled infusion (TCI) of propofol in Korean female patients who would take total intravenous anesthesia (TIVA) using propofol-remifentanil combination. Methods: Eighty Korean women participated in this trial. Demographic data were collected and LBMA was measured using body mass analyzer. Target concentration of propofol was set at 6μg/ml during induction and 3μg/ml during maintenance. Hemodynamic variables and BIS were measured at 60 minutes after anesthetic induction. Peripheral blood sample was collected from a large forearm vein on the contralateral side of infusion for measurement of whole blood concentration of propofol at 60 minutes after anesthetic induction. Delta lean body mass (ΔLBM) was obtained by subtracting LBMA from LBME. Correlation analyses were done between ΔLBM and plasma propofol concentration, blood pressure, and BIS, respectively. Results: Blood concentrations of propofol were 1.9−6.9μg/ml. Mean plasma concentration of propofol was higher than target concentration. ΔLBM had a positive correlation with actual plasma propofol concentration. ΔLBM was not correlated with hemodynamic variables and BIS. Conclusions: TCI of propofol resulted in large variation in measured plasma concentration. We thought ΔLBM was one of interpatient variation factors of propofol plasma concentration during TCI. We found that TCI of propofol using Schnider model would result in higher blood concentration than target concentration in Korean women.

Variation of bispectral index under TIVA with propofol in a paediatric population

In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.