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Inhibition of the neutrophil oxidative response by propofol: preserved in vivo function despite in vitro inhibition.

BACKGROUND AND OBJECTIVE: Propofol has been shown to inhibit a variety of functions of neutrophils in vitro, but there is a lack of in vivo data. To analyse the effects of propofol on neutrophil function in vivo we chose to investigate cataract surgery since it represents a small surgical procedure with minimal immunomodulatory effects induced by surgery. We sought to analyse any immunosuppressive effects of propofol after short-term administration in vivo in comparison to local anaesthesia as well as to in vitro effects of propofol. METHODS: The study was designed as an open randomized trial enrolling 20 patients undergoing general or local anaesthesia. The neutrophil oxidative response and propofol plasma concentration were assessed prior, during and after anaesthesia. Neutrophil function was determined flow cytometrically based on dihydrorhodamine 123 oxidation. RESULTS: Propofol concentrations which yielded a marked suppression in vitro did not alter the neutrophil oxidative response during cataract surgery in vivo. However, after local anaesthesia the neutrophil oxidative response declined to 37%, compared to the control response prior to anaesthesia. CONCLUSIONS: Although we could detect the well established suppression of neutrophil function by propofol in vitro it was not evident in vivo. This may be due to compensating effects on neutrophil function during surgery in vivo. The decline in the neutrophil oxidative response in the local anaesthesia group might be due to increased stress and catecholamine concentrations or a direct interaction of local anaesthetics with neutrophil intracellular signalling.

Adult↗

Melatonin premedication and the induction dose of propofol.

BACKGROUND AND OBJECTIVES: Melatonin (N-acetyl-5-methoxytryptamine) is the main indolamine secreted by the pineal gland. Many studies showed that premedication with melatonin is associated with preoperative anxiolysis and sedation without impairment of cognitive and psychomotor skills and without prolonging recovery. We hypothesized that melatonin decreases the amount of propofol required to produce an adequate depth of hypnosis at induction time. METHODS: After approval from the research committee of the anaesthesia department, informed written consent was taken from 45 adult patients undergoing different surgical procedures. They were allocated randomly into three groups according to the premedication. At 100 min preoperatively, premedication was given in the form of oral melatonin 3 mg (M3 group), oral melatonin 5 mg (M5 group) or no premedication (P group). After preoxygenation an anaesthesiologist who was blinded to the premedication injected propofol 10 mg over 5 s every 15 s until the bispectral index (BIS) score fell to 45. The total dose of propofol required to achieve a BIS score of 45 was recorded. Response to verbal commands and eyelash reflex was evaluated and correlated to the BIS score and propofol dosage. When a BIS score of 45 was reached, tracheal intubation was accomplished after administration of a narcotic and muscle relaxant. RESULTS: The mean (standard devitation (SD)) induction dose of propofol producing a BIS score of 45 was 134 (25) mg in the placebo group vs. 115 (19.5) and 114 (20.9) mg in the M3 and M5 groups, respectively (P < 0.05). The propofol dose required to achieve loss of eyelash reflex and loss of response to verbal commands was more in the placebo group. Anxiety score as assessed by visual analogue scale (VAS) scored more in the placebo group than both melatonin groups. Time spent in the recovery room did not differ between the three groups. CONCLUSION: Melatonin premedication, in an oral dose of either 3 or 5 mg, reduced the required dose of propofol to achieve a BIS score of 45, reflecting a sufficient level of hypnosis for tracheal intubation without prolongation of postoperative recovery room stay.

Adolescent↗

Concentration-EEG effect relationship of propofol in rats.

Propofol is a unique highly lipid-soluble anesthetic that is formulated in a fat emulsion (Diprivan) for intravenous (i.v.) use. It has the desirable properties of rapid onset and offset of effect following rapid i.v. administration and minimal accumulation on long-term administration. Based on physicochemical properties and preliminary brain solubility data, propofol should have an extended effect-site turnover and a resulting prolonged effect. However, a preliminary study in humans has reported a rapid blood-brain equilibration half-time (T1/2 kE0) of only 2.9 min. We used a chronically instrumented rat model to examine the unique disposition and electroencephalographic (EEG) pharmacodynamics of propofol. Although the pharmacokinetics were variable, there was low interindividual variability in the concentration-EEG effect relationship. The duration of EEG sleep was 26 (+/- 44% CV) min following 11-15 mg/kg doses of propofol. The T1/2 kE0 was 1.7 (+/- 32%) min. Apparent effect-site concentrations of 0.5-1 microg/mL were required to maintain sleep in rats. Like other general anesthetics, the concentration-EEG effect relationship of propofol is biphasic. At a propofol concentration of 0.6 (+/- 35%) microg/mL, the number of EEG waves/s was maximal at 175% of baseline awake state. Further increases in the concentration of propofol depressed EEG activity until complete suppression occurred at 7 (+/- 22%) microg/mL.

Anesthetics, Intravenous↗

Correlation beween AAI-index and the BIS-index during propofol hypnosis: a clinical study.

OBJECTIVE: To determine the degree of linearity and correlation between the anaesthetic depth indices BIS and AAI over a wide range of hypnotic depth using propofol. METHODS: 20 ASA I patients were studied during propofol induction. Co-induction with 0.05 mg fentanyl and 30 mg propofol iv before initiation of the study. Thereafter repeated doses of propofol 0.5 mg/kg iv. every minute until BIS < 30. Loss of responsiveness to verbal command was determined by repeated loud commands to the patient. BIS (Aspect 2000 XP, BIS algorithm 4.0, system rev. 3.12, Aspect Medical Systems; Natick, MA, U.S.A.) and AAI-index (A-Line Auditory Evoked Potential Monitor, version 1.4, Danmeter A/S; Odense, Denmark) were determined simultaneously (n = 15). BIS alone without acoustical stimulation was studied in a control group (n = 5). MAIN RESULTS: Both indices decreased with increasing dose, and there was a high correlation between the two (r2 = 0.82). The indices showed however different values and while BIS were quite linear, the AAI-index had a more on-offb ehaviour. CONCLUSION: The AAI-index correlates with the BIS-index during propofol hypnosis in the absence of surgical stimulation. Neither the BIS-index, heart rate, nor systemic blood pressure were influenced by the acoustical stimulation from the A-line monitor. Both indices decreased in relation to increasing doses of propofol, but the AAI-index was lower both before becoming unconscious, during transition to unconsciousness, and during the deeper levels of sedation. The AAI-index lacks linearity at both very low and higher levels of propofol sedation with a nearly on-off behaviour for wakefulness vs hypnosis.

Adult↗

In vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph technique.

BACKGROUND: To investigate the in vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph (TEG) technique. METHODS: The blood samples, obtained from 14 healthy volunteers, were divided into two groups: propofol (n = 7) and intralipid (n = 7), and 360 microliters volumes of whole blood were incubated with 2 microliters of 1% propofol and with its solvent intralipid, respectively. The incubated sample was then used for TEG measurements. RESULTS: The maximum amplitude (MA), which reflects coagulability, in the intralipid group significantly increased by about 7% and 16% compared to the control and propofol groups, respectively (P < 0.05), whereas the MA in the propofol group did not change. The fibrinolytic rate (FR) in the propofol group significantly increased by about 170% and 210% compared to the control and intralipid groups, respectively (P < 0.05), whereas the FR in the intralipid group did not change. CONCLUSIONS: Propofol, per se, has at the concentration of 55.6 micrograms.ml-1 an in vitro accelerative effect on blood fibrinolysis detected by TEG.

Anesthetics, Intravenous↗

Effects of propofol on isolated human pial arteries.

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.

Adolescent↗

No genotoxic effect of propofol in chinese hamster ovary cells: analysis by sister chromatid exchanges.

BACKGROUND: In spite of its high placental transfer, propofol is frequently used in general anesthesia and sedation during obstetric and gynecological surgery such as in vitro fertilization. This study investigated whether or not propofol has a genotoxic potential by the sister chromatid exchange assay in vitro. METHODS: Sister chromatid exchanges induced after exposure to propofol were measured in Chinese hamster ovary cells with and without metabolic activation. After propofol (0.2-20 microg ml(-1)) diluted dimethyl sulfoxide was applied for 2 h with or without S9 mix, the cells having been incubated for two metaphases (34 h) in the presence of 5'-bromo-2-deoxyuridine. N-nitrosodimethylamine and mitomycin C were used as positive controls with and without metabolic activation. The chromosomes were stained with the fluorescence plus Giemsa method, and then sister chromatid exchanges in 50 cells were counted for each concentration. RESULTS: Although increasing concentrations of propofol inhibited cell proliferation, no concentrations of propofol used in this study increased the sister chromatid exchange values, with and without metabolic activation. CONCLUSION: It was concluded that there was no indication, from the sister chromatid exchange assay in mammalian cells, of a genotoxic effect of propofol and its metabolites.

Anesthetics, Intravenous↗

Does discontinuation of desflurane at the time of neostigmine administration speed recovery from cisatracurium block compared to that with a propofol-based technique?

BACKGROUND: Volatile anaesthetics are known to influence the effect of neostigmine as an antagonist of neuromuscular block. The aim of the present study was to investigate whether discontinuation of desflurane at the time of neostigmine administration shortens reversal time from cisatracurium block, compared to that with a propofol-based anaesthesia. METHODS: Ten volunteers were studied twice. For one study, anaesthesia was induced with alfentanil and propofol and maintained with nitrous oxide 70% and propofol 150 microg. kg-1. min-1. For the other study, experimental conditions were replicated except that desflurane 6% was administered and the dose of propofol was only 50 microg. kg-1. min-1. The evoked mechanical response of the adductor pollicis to train-of-four (TOF) stimulation was recorded. Neuromuscular block was induced with cisatracurium 0.2 mg. kg-1. When the magnitude of the first TOF response (T1) had recovered to 10%, the block was antagonized with neostigmine 70 microg. kg-1. At this time, propofol was decreased to 50 microg. kg-1. min-1, or the desflurane was discontinued. RESULTS: There were no significant differences between the two techniques of anaesthesia in the rate of neostigmine-induced recovery of the TOF ratio. The times (mean+/-SD) to achieve TOF ratios of 0.7, 0.8, and 0.9 were (propofol first, desflurane second) 6.1+/-2.2 and 6.5+/-1.6 min; 10.4+/-4.2 and 9.6+/-2.7 min; 17.1+/-6.9 and 21.0+/-13.0 min, respectively. CONCLUSION: Discontinuing desflurane does not speed neostigmine-induced recovery from cisatracurium neuromuscular block, when compared to that during propofol-based anaesthesia.

Adult↗

Pain on injection of propofol with or without infusion of carrier fluid.

BACKGROUND: Propofol, a popular intravenous (iv) anaesthetic induction agent for brief cases or day surgery, is associated with smooth induction, pleasant sleep, rapid recovery and little postoperative nausea. A major disadvantage is pain at the site of injection. The aim of the present study was to examine the influence of simultaneous iv infusion of carrier fluid on propofol-induced local pain. METHODS: Thirty patients, scheduled for ear-nose-throat or plastic surgery under general anaesthesia, were randomly allocated into two groups. Each patient had two 2 ml iv bolus injections of propofol given at two minutes' interval. In group I (n=15) the first bolus injection was given with no iv carrier fluid and the second one given with a 10 ml iv carrier fluid infused over 10 s. Correspondingly, the patients in group II (n=15) had their first injection with and their second one without the iv carrier fluid. Following each injection of propofol the patients were asked by a blinded investigator to score their pain on a 10-point visual analogue scale, and to report the appearance, maximum and disappearance of pain. After the second assessment of pain, general anaesthesia was induced with more propofol. RESULTS: Pain intensity at the site of propofol injection was found not to be influenced by simultaneous iv infusion of carrier fluid. CONCLUSION: It seems, from the results obtained here, that simultaneous iv infusion of carrier fluid has no particular effect on local pain following iv administration of propofol.

Adult↗

High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.

BACKGROUND: Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS: Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS: Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. CONCLUSIONS: These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

Anesthetics, Intravenous↗

Dose-response relationship of propofol on mid-latency auditory evoked potentials (MLAEP) in cardiac surgery.

BACKGROUND: Propofol-sufentanil anaesthesia has become popular during cardiac surgery for its titrability and short recovery time. Avoidance of awareness is a major goal during cardiac surgery. We therefore investigated the dose-response relationship of propofol and cortical responses (mid-latency auditory evoked potentials, MLAEP). METHODS: One hundred patients undergoing cardiac surgery were investigated. Basic anaesthesia was performed with sufentanil (4.5 microg kg(-1) h(-1)) / flunitrazepam (9 microg kg(-1) h(-1)) infusion (control group); the other groups received in addition a loading dose of propofol 2 mg kg(-1) and a maintainance infusion of 1-3.5 mg kg(-1) h(-1). MLAEP were evaluated by using Pa/Nb-amplitudes and Nb-latencies. Haemodynamics were monitored by ECG, arterial blood pressure and cardiac function with pulmonary artery catheterization. RESULTS: In the control group, median amplitude of MLAEP decreased by 50% with a wide range, but were detectable in >90% of patients throughout surgery. Propofol suppressed amplitude Pa/Nb of MLAEP dose dependently. With 3.5 mg kg(-1) h(-1) amplitudes disappeared in >40% of patients throughout cardiac surgery. Median Nb-latencies increased in the control group from 44 to a range from 50 to 60 ms. In groups with propofol >2 mg kg(-1) h(-1), Nb-latencies, detectable in the patients without complete suppression of MLAEP, increased to median 60 ms. Haemodynamic parameters and cardiac function did not differ among the groups. The use of vasopressors was not increased even with the highest propofol dose used. CONCLUSION: The dose-response effect of propofol on auditory evoked potentials reveals that combining a loading dose of 2 mg kg-1 with a consecutive infusion of 3.5 mg kg(-1) h(-1) significantly suppresses MLAEP during cardiac surgery. Thus, auditory information may not be processed and awareness with recall becomes unlikely.

Adolescent↗

Superior prolonged antiemetic prophylaxis with a four-drug multimodal regimen - comparison with propofol or placebo.

BACKGROUND: The purpose of this study was to compare the effects of a low-dose propofol infusion with a four-drug multimodal regimen for prophylaxis of postoperative nausea and vomiting (PONV). METHODS: : PONV was studied in two patient groups with a known high incidence. Through a stratified randomization, 60 patients undergoing breast surgery and 120 patients undergoing abdominal surgery were randomized to three groups of equal size: the propofol group (P), the multidrug group (M) and the control group (C). All patients received general anesthesia, induction with propofol and maintenance with sevoflurane. After induction, patients in the P group received a continuous infusion of propofol 1 mg/kg/h during the operation and the first 4 postoperative h. Patients in the M group received dexamethasone 4 mg and three antiemetics, ondansetron 4 mg, droperidol 1.25 mg and metoclopramide 10 mg i.v. In the control group no prophylaxis was given. Nausea and pain were evaluated by incidence and a visual analog scale (0-10 cm). All emetic episodes were noted by the staff during the first 4 h and by the patients during the next 20 h. RESULTS: The overall incidence of PONV during the first 24 h postoperatively was significantly lower in the M group (24%) than in the P group (49%) (P<0.01) or the C group (70%) (P<0.001). The incidence of PONV increased significantly both in patients undergoing breast surgery and abdominal surgery after termination of propofol. The number of patients who vomited was significantly lower in the M group, both in breast surgery patients (5%) and abdominal surgery patients (3%) compared to patients in the propofol groups (breast 16% NS; abdominal 29%, P<0.05) and in the control groups (breast 37%, P<0.01; abdominal 29%, P<0.01). CONCLUSION: The incidence of PONV is very high in patients undergoing breast and abdominal surgery. In the present study antiemetic prophylaxis with a combination of droperidol, ondansetron, metoclopramide and dexamethasone was more effective in preventing PONV, especially vomiting, than a postoperative low-dose infusion of propofol, which had a short lasting effect.

Abdomen↗

Propofol infusion rate does not affect local pain on injection.

BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmö University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration.

Adolescent↗

The difference between sleep and anaesthesia is in the intracellular signal: propofol and GABA use different subtypes of the GABA(A) receptor beta subunit and vary in their interaction with actin.

BACKGROUND: Propofol is known to interact with the gamma-aminobutyric acidA (GABA(A)) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia. METHODS: To compare propofol and GABA, their interaction with the GABAA receptor beta subunit and actin were studied in three cellular fractions of cultured rat neurons using Western blot technique. RESULTS: Propofol tyrosine phosphorylated the GABA(A) receptor beta2 (MW 54 and 56 kDa) and beta3 (MW 57 kDa) subtypes. The increase was shown in both the cytoskeleton (beta2(54) and beta2(56) subtypes) and the cell membrane (beta2(54) and beta3 subtypes). Concurrently the 56 kDa beta2 subtype was reduced in the cytosol. Propofol, but not GABA, also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. Without extracellular calcium available, the amount of actin decreased in the cytoskeleton, but tyrosine phosphorylation was unchanged. GABA caused increased tyrosine phosphorylation of beta2(56) and beta3 subtypes in the membrane and both beta2 subtypes in the cytoskeleton but no cytosolic tyrosine phosphorylation. CONCLUSION: The difference between propofol and GABA at the GABA(A) receptor was shown to take place in the membrane, where the beta2(54) was increased by propofol and instead the beta2(56) subtype was increased by GABA. Only propofol also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. This interaction between the GABAA receptor and actin might explain the difference between anaesthesia and physiological neuronal inhibition.

Actins↗

Different benefit of bispectal index (BIS) in desflurane and propofol anesthesia.

BACKGROUND: Bispectal index (BIS) monitoring may reduce drug usage and hasten recovery in propofol and inhalation anesthesia. The faster emergence profile of desflurane may reduce the effect of BIS monitoring on recovery from desflurane compared with propofol. This study compared hypnotic drug usage, recovery, patient satisfaction and incidence of inadequate sedation in BIS monitored and nonmonitored women anesthetized with desflurane or propofol. METHODS: One hundred and sixty patients scheduled for elective gynecological surgery were randomly assigned to desflurane or propofol anesthesia with and without BIS monitoring. Fentanyl, vecuronium and remifentanil were administered according to clinical criteria. The BIS monitor was used in all patients, but the monitor screen was covered in the controls. A BIS level between 45 and 55 was targeted in the BIS monitored patients whereas depth of anesthesia was assessed by clinical criteria in the controls. RESULTS: The mean (SD) desflurane MAC-hours administered with and without BIS were 0.70 (0.15) and 0.76 (0.12), respectively, resulting in extubation times of 6.5 (4.1) and 8.3 (6.1) min. (NS). Bispectal index monitoring was associated with improved patient satisfaction, reduced postoperative nausea and antiemetic drug requirement, and fewer episodes with sustained BIS levels > 60. The mean (SD) propofol infusion rates were 6.0 (1.4) and 6.6 (0.9) mg kg(-1)h(-1) with and without the BIS monitor (P = 0.023), resulting in mean (SD) extubation times of 6.8 (4.6) and 10.5 min (5.9), respectively (P < 0.05). CONCLUSION: Bispectal index monitoring reduced propofol usage and hastened recovery after propofol anesthesia, whereas in desflurane anesthesia it was associated with improved patient satisfaction, probably because of decreased postoperative nausea and fewer episodes of inadequate hypnosis.

Adult↗

Intravenous sedation for handicapped dental patients: a clinical trial of midazolam and propofol.

A double blind, cross-over study to compare intravenous sedation using continuous infusions of midazolam and propofol was carried out in 18 handicapped patients, aged between 5 and 26 years. Using a syringe pump (Ohmeda 9000) midazolam was delivered at 0.4 mg/kg/h with a bolus dose of 0.02 mg/kg and propofol was infused at 4.0 mg/kg/h with a bolus dose of 0.2 mg/kg. Sequential analysis showed that induction and recovery times were shorter with propofol (P < 0.05 and P < 0.01 respectively) and more work was performed over unit time (P < 0.05), with 15.7 units of work being completed per hour on patients under propofol sedation compared to 11.0 units under midazolam. The quality of sedation was assessed as better in patients receiving propofol; eight cases were abandoned under midazolam infusion due to failure of induction, uncontrolled movement and/or emotional outbursts compared with none under propofol. All parents/patients preferred propofol sedation, because recovery was faster and smoother.

Adolescent↗

Computer controlled infusion of propofol for conscious sedation in dental treatment.

OBJECTIVE: To assess a drug delivery system that can rapidly achieve and maintain a constant blood concentration of Propofol (2,6 di-isopropyl phenol) which, in subanaesthetic doses, is an effective intravenous sedative for treating anxious or handicapped patients in dentistry. DESIGN: The clinical use of a computer controlled infusion system to induce and maintain conscious sedation with propofol was prospectively studied. Based on a 3-compartment pharmacokinetic model, the system calculates the initial bolus dose and infusion rates to achieve a user-selected target blood concentration. SETTING: Amsterdam Center for Special Dental Care. SUBJECTS: 89 patients attending for dental treatment. RESULTS: Treatment could be performed within 2 minutes after the onset of the infusion. The median therapeutic target blood propofol concentration was 2.5 micrograms/ml and the median recovery time was 9 minutes. Transient oversedation (38 procedures) could easily be treated by decreasing the target concentration. No adverse cardiorespiratory effects resulted from propofol sedation. Venous blood propofol concentrations were measured in 25 anxious patients. The kinetic data set used in this study underestimated the distribution and elimination of propofol in our patients. CONCLUSIONS: Computer controlled infusion of propofol can provide satisfactory and safe conscious sedation in dental patients.

Adolescent↗

The differential effect of propofol on contractility of isolated myocardial trabeculae of rat and guinea-pig.

1. The effects of propofol on myocardial contractility were studied in rat, in which the contractile activation mainly depends on calcium derived from the sarcoplasmic reticulum (SR), and guinea-pig, in which transsarcolemmal influx of calcium plays a major role. 2. Intact and chemically skinned trabeculae from the right ventricle were studied. Intact trabeculae were electrically stimulated and force development during steady state and post rest contractions was measured. In saponin skinned trabeculae Ca(2+) uptake and release by the SR was studied. In Triton skinned trabeculae the influence of propofol on calcium sensitivity of the myofilaments was studied. 3. In intact rat trabeculae propofol in concentrations of 28, 112 and 280 microM did not change peak force development nor the pattern of post rest contraction. In guinea-pig trabeculae propofol significantly reduced peak force to respectively 64, 40 and 23% of control values and the post rest contractions were potentiated. In skinned trabeculae propofol did not affect Ca(2+) handling by the SR, nor did it change force production and Ca(2+) sensitivity of the myofilaments. 4. This study shows that, in contrast to rat, in guinea-pig propofol directly depresses myocardial contractility, probably by decreasing transsarcolemmal Ca(2+) influx. There is no significant influence of propofol on Ca(2+) handling by the SR, nor on the contractile proteins.

Anesthetics, Intravenous↗