This study aimed to establish a new propofol target-controlled infusion (TCI) model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol (10 mg/kg) was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using WinNonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index (NI) versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/mL, while 12.52±0.69 μg/mL at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant (ke0) was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/mL (95% CI, 10.25-13.67). Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.
Anesthetics, Intravenous ; blood ; pharmacokinetics ; Animals ; Drug Monitoring ; Infusions, Intravenous ; Models, Statistical ; Propofol ; blood ; pharmacokinetics ; Rabbits ; Software

OBJECTIVE: A rapid and selective method has been developed for the determination of propofol in blood by gas chromatography-mass spectrometry (GC-MS). METHODS: The blood was extrasted with the solution of internal standard, the extracted residue was analyzed by gas chromatography-mass spectrometry using selected-ion monitoring mode. RESULTS: The linear range was 0.1-10 microg/mL. The coefficient(R2) was 0.993 1. The detection limit was 0.05 microg/mL. CONCLUSION The method is simple and rapid, offering superior sensitivity and selectivity for propofol. The method can be used successfully during clinical and forensic toxicology.
Anesthetics, Intravenous/blood* ; Gas Chromatography-Mass Spectrometry/methods* ; Humans ; Propofol/blood* ; Reproducibility of Results ; Sensitivity and Specificity

To evaluate the cardiovascular effect of lidocaine and serum electrolytes during inhalational or intravenous anesthesia, thirty-two healthy patients were randomly divided into three groups and measured systolic pressure, diastolic pressure, mean pressure, heart rate and serum K+ and Na+ level were measured at 30 sec, l, 3, 6, 12 minutes after intravenous injection of lidocaine(1.5 mg/kg) during halothane-N2O-O2 or enflurane-N2O-O2 or diazepam-N2O-O2 anesthesia. In all 3 groups, the values of hemodynamic and serum electrolytes were not changed by 2% lidocaine. These results indicate that intravenous injection of lidocaine(1.5 mg/kg) to prevent undesirable reflexes and to prevent intracranial hypertension is a safe method without depression of hemodynamics.
Anesthesia* ; Anesthesia, Intravenous ; Anesthetics ; Anesthetics, Local ; Blood Pressure ; Depression ; Diazepam* ; Electrolytes ; Enflurane* ; Halothane* ; Heart Rate ; Hemodynamics ; Humans ; Injections, Intravenous ; Intracranial Hypertension ; Lidocaine* ; Reflex

Backgrounds : There were many trials for the prevention of pain induced by the intravenous injection of propofol. However, any previous preventive techniques have not been completely satisfactory. The aim of this study was to compare the use of propofol pretreated with ketamine and lidocaine for the reduction of pain during the injection of propofol. METHODS: Patients in the lidocaine pretreated group(n=25) received lidocaine 40 mg, followed one minute later by propofol(2 mg/kg). Patients in the ketamine pretreated group(n=25) had a BP cuff inflated to 50 mmHg above their,s own systolic pressure and received ketamine 20 mg and the cuff was released one minute later, followed by the injection of propofol(2 mg/kg). Pain on injection of propofol was assessed verbally into none, mild, moderate and severe by the same observer. Blood pressure and heart rate before pretreatment injection and one minute after propofol injection were recorded. Any untoward effects of drugs were recorded. RESULTS: There was a significant reduction in the incidence and severity of pain in the ketamine pretreated group. Only 7 patients(28%) in the ketamine group experienced pain as compared to 18 patients (72%) in the lidocaine pretreated group. Systolic pressure at one minute after propofol injection was significantly reduced in the lidocaine pretreated group. In the ketamine pretreated group systolic pressure at one minute after propofol injection was not reduced. No post-operative hallucinations or bad dreams were reported in any patients. CONCLUSIONS: Prior to propofol intravenous injection, pretreatment with ketamine 40 mg after inflation of a BP cuff 50 mmHg above systolic pressure significantly reduces vascular pain without complications compare to pretreated with lidocaine 40 mg.
Anesthetics ; Blood Pressure ; Dreams ; Hallucinations ; Heart Rate ; Humans ; Incidence ; Inflation, Economic ; Injections, Intravenous ; Ketamine* ; Lidocaine* ; Propofol*

PURPOSE: To compare pain levels in cataract surgery under topical anesthesia only and topical anesthesia under monitored anesthesia care. METHODS: We recruited 243 patients who were scheduled to undergo cataract surgery under topical anesthesia only or topical anesthesia with monitored anesthesia care (MAC) using fentanyl and midazolam. Anesthesia methods were selected based on the patient's preference. All patients completed an anxiety and information scale survey preoperatively. Vital signs during the operations were recorded. A 0-to-10 visual analog scale pain score survey was conducted immediately and at 2 hours, 6 hours, and 1 day after surgery. RESULTS: Of the 237 patients who completed the study, 183 patients selected topical anesthesia, and 54 patients selected MAC. Mean pain scores according to the aforementioned time points after surgery were 0.50, 0.58, 0.29, and 0.12 in the topical anesthesia group, and 0.22, 0.16, 0.06, and 0.09 in the MAC group, respectively. The differences in pain score between the two groups was statistically significant at 2 hours (p = 0.019) and 6 hours (p = 0.040) after surgery. The mean patient anxiety score for anesthesia was 10.50 in the topical anesthesia group and 11.41 in the MAC group (p = 0.280). Mean systolic blood pressure at the start of surgery was 140.6 mm Hg in the topical anesthesia group, and 158.2 mmHg in the MAC group. CONCLUSIONS: Monitored anesthesia care consistently resulted in less pain throughout the post-operative period. However, transient systolic blood pressure should be carefully monitored for a rise related to intravenous anesthetics.
Anesthesia* ; Anesthetics, Intravenous ; Anxiety ; Blood Pressure ; Cataract* ; Fentanyl ; Humans ; Midazolam ; Visual Analog Scale ; Vital Signs

OBJECTIVETo investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs.

METHODSTwelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC).

RESULTSThe plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05).

CONCLUSIONSIn both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.

Anesthetics, Intravenous ; pharmacokinetics ; Animals ; Brain ; metabolism ; Dogs ; Female ; Male ; Propofol ; blood ; pharmacokinetics ; gamma-Aminobutyric Acid ; metabolism

BACKGROUND: Somatosensory evoked potential (SSEP) has been used to help minimize neurologic morbidity during spinal surgery. But, SSEP is affected by various factors, namely technical errors, anesthetics and physiologic aspects (systemic blood pressure, temperature, blood gas tensions). We experienced 40 cases of spinal surgery done with total intravenous anesthesia under SSEP monitoring. We reviewed these cases with the availability of total intravenous anesthesia during SSEP monitoring. METHODS: Forty patients, ASA class I-II, free of neurologic disease and scheduled for elective spinal surgery were randomly selected for the study. All of the operations were performed under general anesthesia employing the method of total intravenous anesthesia with propofol and fentanyl, and monitored by SSEP. We recorded latency and amplitude of SSEP in the pre-induction, post-induction, during-instrument insertion and post-distraction periods. RESULTS: There were no statistical differences in latencies among pre-induction, post-induction, screw insertion and post-distraction period. The amplitude of the post-induction period was statistically higher than pre-induction period (p<0.05), but there were no differences in other periods. None of cases showed abnormal findings (i.e., delay of latency over 10% or decrease of amplitude over 50%). CONCLUSIONS: SSEP monitoring may be helpful in identifying potentially neurologically threatening surgical maneuvers during spinal surgery. To achieve better outcomes, we should consider the effects of various factors on SSEP. Total intravenous anesthesia may be useful method, which has lifter influence on SSEP monitoring.
Anesthesia, General ; Anesthesia, Intravenous* ; Anesthetics ; Blood Pressure ; Evoked Potentials* ; Evoked Potentials, Somatosensory ; Fentanyl ; Humans ; Propofol

BACKGROUND: Using rotational thromboelastometry (ROTEM) analysis, we investigated the difference in blood hemostasis, based on the primary anesthetic agents used during general anesthesia. METHODS: Sixty-six adult patients scheduled for elective ophthalmic surgery under general anesthesia were evaluated with regard to changes in each parameter in INTEM, EXTEM, and FIBTEM analyses. The patients received intravenous anesthesia with propofol and remifentanil (TIVA group) or inhalation anesthesia with sevoflurane (SEVO group). The ROTEM tests were performed 10 min before starting anesthesia and 1 h after finishing anesthesia. The INTEM and EXTEM analyses included the clotting time (CT), clot firmness time (CFT), alpha angle (alpha), and maximum clot firmness (MCF). The FIBTEM analyzed only MCF. Maximum clot elasticity (MCE) was calculated by (MCF x 100) / (100 - MCF). The platelet component of clot strength was calculated as follows: MCE(platelet) = MCE(EXTEM) - MCE(FIBTEM). RESULTS: The preoperative and postoperative parameters (CT, CFT, alpha, and MCF) in the INTEM, EXTEM, and FIBTEM analyses were not significantly different between the two groups. The MCE(platelet) also did not show a significant difference. CONCLUSIONS: Presuming that the ophthalmic surgery had a minimal traumatic effect, we conclude that both anesthetic agents cause negligible changes in ROTEM analyses postoperatively.
Adult ; Anesthesia ; Anesthesia, General ; Anesthesia, Inhalation ; Anesthesia, Intravenous ; Anesthetics ; Blood Platelets ; Elasticity ; Hemostasis* ; Humans ; Propofol* ; Thrombelastography

Propofol is a new, rapidly effective, short-acting intravenous sedative-hypnotic agent that can be used for induction and maintenance of general anesthesia. This study was performed to evaluate the efficacy and safety of domestic product Pofol in comparison with Diprivan for the management of total intravenous general anesthesia by double blind method. This study was approved by the Clinical Research Committee of SNUH. Test drugs were administered in a double-blinded fashion for the anesthesia. Seventy-four patients(aged 18-60 yr, operation time below two hours) were induced anesthesia with bolus injection of 2 mg/kg of test drug for 20 seconds and then anesthesia was maintained with continuous infusion method by syringe pump. Infusion dose of test drug during maintenance of anesthesia was controlled to maintain the systolic blood pressure measured at ward +/-20%. To evaluate the efficacy of drug, induction dose, mean maintenance dose, time to loss of conciousness after injection of induction dose and awakening time were measured or calculated. To evaluate the safety of drug, pain after injection of drug, recovery condition of patients and adverse events or side effects were recorded. Changes of blood pressure and heart rate were measured and arterial blood gas was also analyzed during perianesthetic period. There were no statistically significant differences in sex, age, weight, duration of anesthesia and ASA physical status distribution between Pofol group(P) and Diprivan group(D). There were no differences in induction dose and mean maintenance dose between P and D (mean+SD, 121+/-25 mg and 0.213+/-0.064 mg/kg/min vs 125+/-27 mg and 0.233+/-0.058 mg/kg/min, respectively). Time to loss of conciousness, time to response and time to orientation after cessation of drug were 14+/-19 sec, 10 min 2 sec+/-5 min 39 sec, 17 min 16 sec+/-9 min 43 sec for P and 14+/-26 sec, 12 min 52 sec+/-8 min 42 sec, 22 min 47 sec+/-14 min 17 sec for D. But there were no statistically differences between P and D, respectively. The incidence of pain after injection was 65.7% for P and 52.7% for D. Recovery from anesthesia was assessed as smooth in 82.9% for P and 91.7% for D. Adverse events during induction were recorded in four patients (apnea(1), opisthotonus(2) and hypotension(1)) for P and in two patients (apnea(1), bradycardia(l)) for D. The number of patients showed adverse events during maintenance of anesthesia and postanesthesia recovery period were same to P and D as 8 patients. Even though the characters of adverse events to P and D were different, the incidence rate was not different between two drugs. These adverse events were resolved without any specific treatment. In conclusion, there were no differences in efficacy and safety between Pofol and Diprivan.
Anesthesia ; Anesthesia, General ; Anesthetics, Intravenous* ; Blood Pressure ; Double-Blind Method ; Heart Rate ; Humans ; Incidence ; Propofol ; Syringes

BACKGROUND: More remifentanil and less propofol may speed up the early recovery from anesthesia. This study evaluated the hemodynamic response and recovery profile of high-dose remifentanil/lowdose propofol anesthesia, compared with low-dose remifentanil/highdose propofol anesthesia for lower abdominal surgery. METHODS: Sixty women undergoing lower abdominal surgery were randomly assigned to either groups H or L. Anesthesia was maintained with remifentanil 0.5 micro/kg/min and propofol 4 mg/kg/h in group H, or with remifentanil 0.25 micro/kg/min and propofol 8 mg/kg/h in group L. The heart rate, blood pressure, and EEG bispectral index (BIS) score were recorded. At the end of surgery, the anesthetic agents were discontinued, and the early emergence, recovery, and side effects were assessed. RESULTS: In both groups, the heart rate and systolic blood pressure were decreased over time compared with the preanesthetic baseline values (P < 0.05) but there were no differences between the two groups. The frequency of hemodynamic events (hypertension, hypotension, and bradycardia) and their rescue drugs were similar in the two groups. The BIS scores were lower during anesthesia in group L than in group H (P < 0.05). The time to spontaneous ventilation, eye opening on verbal command, extubation, orientation, and full recovery were faster in group H than in group L (P < 0.05). The incidences of side effects were similar in both groups. CONCLUSIONS: In lower abdominal surgery, high-dose remifentanil/ low-dose propofol anesthesia offers faster recovery than low-dose remifentanil/high-dose propofol anesthesia. However, there were no differences in the hemodynamic changes and side effects between the groups.
Anesthesia ; Anesthesia, Intravenous* ; Anesthetics ; Blood Pressure ; Electroencephalography ; Female ; Heart Rate ; Hemodynamics ; Humans ; Hypotension ; Incidence ; Propofol* ; Ventilation