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PubMed1998

Propofol concentrations in whole blood: influence of anticoagulants and storage time.

Blood samples for propofol determination are collected with oxalate, heparin and EDTA, but we have not found any study comparing the influence of those anticoagulants on propofol concentrations. This study was carried out on 50 samples from patients taking propofol for anesthesia or cerebral protection. First, 26 samples were simultaneously collected into tubes containing lithium heparin or sodium fluoride potassium oxalate as anticoagulant. In a second investigation, 24 samples were simultaneously collected into tubes containing heparin or EDTA. Propofol was assayed by HPLC 2 days after sampling and 2 weeks later. In the first assay, propofol concentration in samples collected with heparin were similar to those collected with oxalate (3.65 +/- 3.50 vs. 3.62 +/- 3.49 mg/l, ns) or EDTA (3.89 +/- 2.58 vs. 3.84 +/- 2.67 mg/L, ns). After storing for 2 weeks at 4 degrees C, propofol concentrations were slightly but insignificantly higher than in the first assay in samples collected with heparin (3.58 +/- 3.24 vs. 3.40 +/- 2.92 mg/l, ns), slightly higher in samples with oxalate (3.86 +/- 3.49 vs. 3.62 +/- 3.49 mg/l, p = 0.06), and slightly but significantly lower in samples with EDTA (3.63 +/- 2.67 vs. 3.84 +/- 2.67 mg/l, p < 0.05). It is concluded that the three anticoagulants used in this study seem to be suitable for determination of propofol concentration in whole blood, and that the stability of propofol concentration when samples are stored at 4 degrees C for up 2 weeks is acceptable.

Anticoagulants↗
PubMed1993

Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis.

The purpose of this study was to evaluate and compare the clinical effects, safety, and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU. Eighty-eight critically ill patients were studied and randomly allocated to receive short-term (less than 24 h), medium-term (24 h to 7 days), and prolonged (more than 7 days) continuous sedation with propofol (n = 46) or midazolam (n = 42). Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam. Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level (grade 2, 3, 4, or 5 on the Ramsay scale) of 93 percent, compared with 82 percent (p < 0.05) in the group receiving midazolam. Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation. Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those sedated with midazolam (p < 0.05). Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups (r = 0.98, 0.88, and 0.92, respectively), while this correlation was not observed in the midazolam-treated group. In the subgroup with sedation of less than 24 h, propofol provided a cost savings of approximately 2,000 pesetas (pts) per patient, due to shorter stays in the ICU. We conclude that propofol is a sedative agent with the same safety, higher clinical effectiveness, and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients.

Aged↗
PubMed2003

Comparison of propofol and sevoflurane for laryngeal mask airway insertion.

In this study, we compared haemodynamic changes, laryngeal mask airway (LMA) insertion time, and complications in patients anesthetized by inhalation of sevoflurane with those of intravenous induction with propofol. One hundred patients, aged between 20-40 years were enrolled in this study. Group 1 received propofol (2.5 mg/kg i.v.) and group 2 received sevoflurane (6%+50% N2O+50% O2) by inhalation using the tidal volume technique. LMA insertion time was found to be significantly longer in sevoflurane group than in propofol group. Mean arterial blood pressure was significantly lower within each group after induction in comparison to before induction values. In both groups, the LMA was successfully inserted in all patients. The quality of anaesthesia according to patients was significantly higher in the propofol group (80%) than in sevoflurane group (30%). Odor perception was significantly higher in sevoflurane group (84%) than in propofol group (38%). Apnoea was significantly higher in propofol group (40%) than in sevoflurane group (0%). Sevoflurane is an alternative to propofol for induction of anaesthesia and has a lower incidence of apnoea. Other complication rates are not higher than which propofol but the longer duration of induction time is a disadvantage.

Adult↗
PubMed1997

A cost analysis of alfentanil+propofol vs morphine+midazolam for the sedation of critically ill patients.

Morphine + midazolam and alfentanil + propofol are regimens offering well tolerated and effective sedation for critically ill patients. However, morphine + midazolam is associated with accumulation in these patients, resulting in prolonged recovery characteristics. Alfentanil+propofol, although more expensive, has a shorter elimination half-life, is not associated with accumulation problems and results in a rapid recovery. This study compared sedation quality, patient recovery characteristics and the cost of alfentanil + propofol and morphine + midazolam for sedating critically ill patients in the intensive care setting. 26 patients were randomly allocated to receive sedation with alfentanil + propofol (n = 17) or morphine + midazolam (n = 9). Outcome measures were the times until extubation, intensive care unit (ICU) transfer and final hospital discharge. Cost analysis assessed both drug-related costs, including drug acquisition and administration, and non-drug-related costs, including bed occupancy. Age, gender, diagnosis, Acute Physiological and Chronic Health Evaluation (APACHE) II scores and sedation quality did not differ significantly between groups. The times to extubation and until patients were fit for transfer from ICU were significantly shorter for patients sedated with alfentanil + propofol than for those sedated with morphine + midazolam. The total costs (at the time of the study Pounds 1 was equivalent to $US1.59) for ICU hospital stay per patient for alfentanil + propofol and morphine + midazolam were 3063 Pounds and 9511 Pounds, respectively, because the shorter recovery characteristics of alfentanil + propofol led to a reduction in ICU stay. Corresponding costss for total hospital stay were 6063 Pounds and 13735 Pounds, respectively. In conclusion, alfentanil + propofol has a better pharmacoeconomic profile than morphine + midazolam for sedating critically ill patients in the ICU setting.

Adolescent↗
PubMed2003

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in cats.

OBJECTIVE: To compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with propofol (loading dose, 6.6 mg/kg; constant rate infusion [CRI], 0.22 mg/kg/min) and instrumented for blood collection and measurement of blood pressures and cardiac output. Cats were maintained at this CRI for a further 60 minutes, and blood samples and measurements were taken. A noxious stimulus was applied for 5 minutes, and blood samples and measurements were obtained. Propofol concentration was decreased to 0.14 mg/kg/min, and ketamine (loading dose, 2 mg/kg; CRI, 23 microg/kg/min) was administered. After a further 60 minutes, blood samples and measurements were taken. A second 5-minute noxious stimulus was applied, and blood samples and measurements were obtained. RESULTS: Mean arterial pressure, central venous pressure, pulmonary arterial occlusion pressure, stroke index, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, partial pressure of oxygen in mixed venous blood, pH of arterial blood, PaCO2, arterial bicarbonate concentration, and base deficit values collected during propofol were not changed by the addition of ketamine and reduction of propofol. Compared with propofol, ketamine and reduction of propofol significantly increased mean pulmonary arterial pressure and venous admixture and significantly decreased PaO2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by CRI for maintenance of anesthesia induced stable hemodynamics and could prove to be clinically useful in cats.

Anesthesia↗
PubMed2003

Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes.

AIM: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 % of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drug-drug interaction. METHODS: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery. Primary incubated hepatocytes were treated with 0, 0.01, 0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis. RESULTS: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1 mM) showed no inhibitory effect on the cellular protein expression of P450 3A4. CONCLUSION: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression. propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Inhibition of bacterial growth by different mixtures of propofol and thiopentone.

Propofol is, as a result of its formulation, an ideal bacterial and yeast culture medium. An outbreak of sepsis in humans and an increase in wound infections in dogs has been ascribed to the use of propofol. It has been previously reported that a 1:1 mixture of propofol and thiopentone has bactericidal properties. This study was undertaken to determine if further serial mixtures of propofol and thiopentone maintained the bactericidal properties. Mixtures of 1:1 (solution A), 5:1 (solution B), 10:1 (solution C), 50:1 (solution D) and 100:1 (solution E) of 1% propofol to 2.5 % thiopentone, 2.5% thiopentone (solution T), 1% propofol (solution P) and saline (solution S) were prepared and inoculated with between 10(5) and 10(6) colony-forming units of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. A sample was withdrawn from each solution at 0, 1, 6, 12, 48 and 120 hours after inoculation and a bacterial count was performed. This study showed that thiopentone and solution A behaved in similar fashion by inhibiting bacterial growth and was bactericidal after 48 hours. Solution B was not bactericidal against S. aureus and C. albicans. Propofol and solutions D and E all supported growth of all the organisms tested. These data indicate that mixtures of propofol and thiopentone at a ratio less than 1:1 do not maintain the bactericidal properties.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Pharmacokinetic evaluation of a computerized target-controlled infusion system: application to propofol in orthopedic surgery].

PaMo 2.0, a type of software, includes a pharmacokinetic model for propofol in the adult. It allows both administration and monitoring of propofol target-controlled infusions. In order to evaluate PaMo 2.0, a prospective clinical trial compared, at defined infusion times, predicted and measured plasma propofol concentrations, in 28 patients programmed for hip-replacement surgery. A propofol plasma determination technique had first been validated, including high performance liquid chromatography with fluorescence detection. A statistical analysis based on correlation (r = 0.73), inaccuracy = 29.18 per cent, bias = 11.67 per cent, wobble = 19.15 per cent, and divergence = -0.06 per cent/min calculation, related to this system, has been carried out. PaMo 2.0 under-estimated plasma propofol concentrations. The convergence between predicted and measured propofol concentrations was good and not modified in respect of infusion time. This infusion system is suitable for propofol administration, but the integration of Bayesian pharmacokinetic models would greatly improve propofol plasma concentration estimation and regimen adaptation to each patient.

Adult↗
PubMed1999

[Intravenous anesthesia with propofol in intracranial surgery].

OBJECTIVES: To analyze the repercussions of intravenous anesthesia with propofol as the single hypnotic drug on intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and also to study the time until recovery from anesthesia and to tracheal extubation as well as intraoperative hemodynamic changes in patients undergoing surgery to remove a supratentorial brain tumor. PATIENTS AND METHODS: Twenty-three ASA I/II patients scheduled for exeresis of a supratentorial brain tumor were studied. A fiberoptic sensor placed in direct contact with the dura mater was used to measure ICP. Anesthetic induction was achieved with propofol (2 mg/kg). Propofol (12 and 9 mg/kg/h for 10 min and 6 mg/kg/h throughout the rest of the operation) was used for maintenance. Mean arterial pressure (MAP), heart rate (HR), ICP and CPP were recorded at baseline and 1, 2, 3 and 4 min after induction, during laryngoscopy and tracheal intubation; 1, 3, 5, 10, 15 and 20 min after tracheal intubation (L + 1, L + 3, L + 5, L + 10, L + 15, L + 20), upon placement of a craniostat; upon skin incision; upon withdrawal of propofol perfusion; and during extubation. The following variables were recorded after awakening: time until eye opening after receiving a verbal command, time until extubation and time until orientation. Analysis of variance for repeated measures (ANOVA) was performed on the results. RESULTS: MAP decreased significantly from baseline at the following times: during the post-induction period, upon placement of the craniostat, upon skin incision and when the propofol infusion was switched off. HR increased significantly during laryngoscopy and at the following moments: intubation, post intubation (L + 1, L + 3, L + 5), craniostat placement, and extubation. ICP was lower throughout the surgical period except during laryngoscopy, when this variable increased significantly. CPP decreased significantly after induction and returned to baseline after intubation. CPP was significantly higher after surgery. Recovery times after weaning from propofol infusion until eye opening in response to an order and until orientation were 13 +/- 3 and 22 +/- 4 min, respectively. The mean interval between withdrawal of propofol until extubation was 18 min. CONCLUSIONS: Intravenous anesthesia with propofol in intracranial surgery (supratentorial tumors) affords hemodynamic stability and lowers ICP except during laryngoscopy. Early recovery from anesthesia allows for neurological assessment and vigilance during the immediate postoperative period.

Adult↗
PubMed1999

Propofol hydroxylation by dog liver microsomes: assay development and dog breed differences.

Pharmacokinetic studies indicate that clearance of propofol, an anesthetic agent, is slower in greyhounds compared with other dog breeds. Biotransformation of propofol to 2,6-diisopropyl-1,4-quinol (4-hydroxypropofol) by cytochrome P-450 in the liver is proposed as a critical initial step in the elimination of this drug in dogs. Breed differences in the activity of this enzyme could therefore explain pharmacokinetic differences. An in vitro propofol hydroxylase assay was developed and then used to compare enzyme activities in liver microsomes from male greyhound, beagle, and mixed-breed dogs (five each). HPLC of incubate identified only one NADPH-dependent metabolite, which had a chromatographic retention time and UV absorbance, fluorescence, and mass spectra that were identical with authentic 4-hydroxypropofol standard. HPLC with fluorescence detection provided a highly sensitive quantitation method for 4-hydroxypropofol with a quantitation limit of 8 ng/ml using optimized excitation/emission wavelengths (288 nm/330 nm, respectively). Estimates of apparent K(m) and V(max) for propofol hydroxylation by microsomes from a male beagle dog were 7.3 microM and 3.8 nmol/mg/min, respectively. At a substrate concentration of 20 microM, propofol hydroxylase activity was significantly lower (p =.032) in greyhound microsomes (1.7 +/- 0.4 nmol/mg/min) compared with beagle microsomes (5.1 +/- 1.3 nmol/mg/min) but was not statistically different (p =.42) compared with mixed-breed microsomes (3.1 +/- 1.2 nmol/mg/min). These results indicate that there are breed differences in propofol hydroxylase activity and that deficient hydroxylation of propofol by one or more hepatic cytochrome P-450 isoforms may contribute to slow pharmacokinetic clearance of propofol by greyhounds.

Anesthetics, Intravenous↗
PubMed1999

[Effects of endothelin antagonists on isolated perfused murine livers in the early phase of warm ischemia-reperfusion injury under propofol anesthesia].

We investigated the effects of selective and non-selective endothelin (ET) antagonists on warm ischemia-reperfusion injury of the early phase in the murine liver under propofol anesthesia. We examined portal pressures, O2 consumptions and liver enzymes to estimate injuries using perfused isolated murine liver model. Experiment 1: we compared the perfusate only group, the soy oil (as vehicle) group, and the propofol group without ischemic loading to determine whether propofol and its vehicles themselves have any effect. Experiment 2: we determined the effects of ET antagonists on reperfusion injury after warm ischemia of 40 minute's cutoff of perfusate under propofol anesthesia and compared five groups up to 90 min after reperfusion; the propofol only group (control; 4 mg.l-1), the BQ-485 group (20 microM), the BQ-788 group (50 microM), the bosentan group (40 microM), and the BQ-485 + BQ-788 group. The soy oil group showed significantly more liver damage, and the propofol group showed no damage. In addition, propofol did not alter the effect of ET antagonists on reperfusion injury. Clinical dose of propofol did not seem to alter the effects of ET antagonists on the murine liver in the early phase of ischemia-reperfusion injury.

Anesthesia, Intravenous↗
PubMed2000

[Decrease in serum propofol concentrations after acute autologous blood letting].

A change in serum propofol concentrations associated with acute autologous blood letting during anesthesia was investigated in seven scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with infusion of propofol 6 mg.kg-1.hr-1 at a constant rate. After achieving a stable anesthesia, about 10 g.kg-1 of autologous blood was withdrawn in about 15 minutes and 20 ml.kg-1 of acetated Ringer's solution was infused to manage the hypotension caused by withdrawal. A blood sample each 4 ml was taken before and 0, 5, 15, 30 minutes after blood withdrawing. Another 7 patients were anesthetized with the same procedure without blood letting to distinguishing the effect of blood letting from rapid infusion therapy of crystalloid. Assay of serum concentration of propofol was performed with HPLC-spectrofluorometry. Concentrations of propofol were significantly decreased from 2.8 micrograms.ml-1 to 2.3 micrograms.ml-1 just after blood letting, and remained at 2.3 micrograms.ml-1 after 30 minutes from letting. Rapid infusion therapy also decreased the concentrations of propofol from 2.4 micrograms.ml-1 to 1.7 micrograms.ml-1. Continuous infusions of propofol may become a major method of general anesthesia with target controlled infusion techniques (TCI) in clinical settings for the accuracy and reliability of prediction of blood concentrations. However, this study demonstrated unexpected decreases of concentration of propofol during acute autologous blood letting similar to surgical mass bleeding, which might be mainly caused by rapid infusion therapy. The rate of infusion of anesthetic should be readjusted to counteract the effect of acute blood loss or volume replacement.

Adult↗
PubMed2000

Probing for nasolacrimal duct obstruction with intravenous propofol sedation.

BACKGROUND: Nasolacrimal duct obstruction occurs in 5% to 6% of neonates. Many studies advocate the probing of nasolacrimal duct obstruction under general inhalational anesthesia in patients at a late age (12 to 13 months) because a high percentage will resolve spontaneously. Others support early surgical intervention in patients aged younger than 6 to 9 months without anesthesia. We present late nasolacrimal duct probing under intravenous propofol sedation as an alternative approach to the treatment of nasolacrimal duct obstruction with a decrease in cost and time compared with probing under general inhalational anesthesia. METHODS: We made a retrospective review of patient charts of children who underwent nasolacrimal duct probing with intravenous propofol sedation from April 1996 to September 1997. Procedure time and cost of procedure were compared for patients who had probings under propofol sedation to patients who had probings under general anesthesia. RESULTS: A total of 22 patients (31 eyes) underwent nasolacrimal duct probing with propofol sedation; the patients' ages ranged from 11.5 to 39 months (average age, 17.8 months). Twenty-six (84%) of 31 eyes had resolution of the symptoms. The average total time for procedure under propofol sedation was 10.5 minutes, compared with 43.6 minutes under general inhalational anesthesia. The average total recovery time under propofol sedation was 13.6 minutes, compared with 121.1 minutes with general inhalational anesthesia. The cost of probing under propofol sedation was one third less than the cost of probing under general inhalational anesthesia. DISCUSSION: Late probing for nasolacrimal duct obstruction under intravenous propofol sedation is comparable in efficacy to late probing under general inhalational anesthesia with a shorter time for the procedure and decreased expense.

Anesthesia, Intravenous↗
PubMed1998

Effects of propofol on a Ca2+-activated CI- current in rabbit ventricular myocytes.

Propofol is a widely used intravenous anesthetic, which is known to affect cardiac functions. Cardiac effects may be caused by direct actions on ion channels of the heart. While effects of propofol on several ion channels have been studied at the whole cell and single-channel levels, its effects, if any, on anion currents have yet to be examined. Effects of propofol on Ca2+-activated Cl- current (I(Cl(Ca))) were investigated in single myocytes isolated from rabbit ventricles by the whole-cell patch clamp technique at 36 degrees C. I(Cl(Ca)) was activated by perfusing internal solutions with 0.1 microM free Ca2+ in the absence and presence of 10 mM internal Na+, eliciting I(Ca)-dependent and -independent component, respectively. By the application of propofol (0.1-300 microM), I(Ca)-independent I(Cl(Ca)) was strongly inhibited in a dose-dependent manner with an IC50 of about 5 microM. The blocking effects of propofol were voltage independent. On the other hand, the I(Ca)-dependent component of I(Cl(Ca)) was little affected by propofol at concentrations of up to 50 microM. The outward Na+/Ca2+ exchanger current was also blocked by application of 5 microM propofol. We conclude that propofol inhibits cardiac I(Cl(Ca)) in rabbit ventricular myocytes, mainly the I(Ca)-independent component, at therapeutic concentrations. The inhibition may be due to block of a reverse mode of Na+/Ca2+ exchange current.

Action Potentials↗
PubMed2001

[Propofol Concentration during Maintenance of and Emergence from Propofol/Epidural Anesthesia: Comparison between Younger and Elderly Patient].

To investigate the influence of patient age on the sensitivity to propofol, we measured blood propofol concentrations in ten elderly (over 70 years of age) and ten younger (under 60 years of age) patients undergoing elective abdominal surgery during propofol/epidural anesthesia. Bispectral index (BIS) was continuously recorded for monitoring anesthetic effect, and the infusion rate of propofol was controlled to keep BIS at 50 after the induction of anesthesia with propofol. At steady-state before skin incision, propofol concentrations to maintain BIS at 50 in younger and elderly patients were 4.3 +/- 1.6 micrograms.ml-1 and 3.2 +/- 1.3 micrograms.ml-1, respectively, and there was no significant difference. Mean blood propofol concentrations were 4.0 +/- 1.5 micrograms.ml-1 for the younger group and 3.2 +/- 1.7 micrograms.ml-1 for the elderly group at the end of surgery immediately before discontinuation of propofol, and they were 1.9 +/- 0.7 micrograms.ml-1 (BIS = 86 +/- 7) for the younger group and 1.5 +/- 0.8 micrograms.ml-1 (BIS = 84 +/- 3) for the elderly group at the time of eye opening with no significant difference. We found appreciable individual variations in the propofol concentrations both in younger and elderly patients in this study.

Abdomen↗
PubMed1999

Additive potentiation by co-application of propofol and sevoflurane on GABA-induced chloride current in cultured neurons from rat dorsal root ganglia.

OBJECTIVE: To investigate the effects of various concentrations of sevoflurane and propofol and a combination of the two agents on chloride current induced by bath utilization of 3 x 10(-6) mol/L gamma-aminobutyric acid (GABA) in the rat dorsal root ganglia neurons maintained in primary culture. METHODS: Sensory neurons from rat dorsal root ganglia were dissociated and cultured. The whole-cell patch clamp technique was used to record chloride current. All drugs were applied with a rapid perfusion system, named "Y-tube" method. RESULTS: The peak chloride current amplitude was induced by 3 x 10(-6) mol/L GABA with substantially increasing of both sevoflurane and propofol. Additionally, desensitization of IGABA induced by either propofol or sevoflurane was not observed. We examined actions of various concentrations of propofol (3 x 10(-7), 1 x 10(-6), 3 x 10(-6) mol/L), sevoflurane (7 x 10(-4) mol/L) and their combination at concentrations relevant to clinical anesthesia on IGABA propofol (3 x 10(-7), 1 x 10(-6), 3 x 10(-6) mol/L) produced a concentration-dependent increase in the response to 3 x 10(-6) mol/L GABA on IGABA. When combined with 7 x 10(-4) mol/L sevoflurane, the potentiation of response to GABA obtained with various concentrations of propofol was not different from a theoretical additive response (P > 0.05). CONCLUSIONS: Either sevoflurane or propofol and their combination at clinically relevant concentrations potentiate the GABA-induced chloride current, which may at least partially contribute to the anesthetic mechanism. Additive interaction obtained with a co-application of propofol and sevoflurane may provide an evidence for a clinical combination of these two anesthetic agents.

Anesthetics, Inhalation↗
PubMed2001

The analgesic effects of subhypnotic doses of propofol in human volunteers with experimentally induced tourniquet pain.

This double-blind, placebo-controlled study was performed to determine whether subhypnotic doses of propofol have analgesic or sedative effects. Of 48 subjects randomly assigned to 1 of 4 bolus-infusion treatment groups, group 1 (n = 16) received propofol at 16 micrograms/kg per minute; group 2 (n = 16) received propofol at 32 micrograms/kg per minute; and group 3 (n = 8) received 10% intralipids at 16 micrograms/kg per minute; and group 4 (n = 8) received 20% intralipids at 32 micrograms/kg per minute. Following a bolus of the study drug, a maintenance infusion was started and continued throughout the study. Thirty minutes after the study drug began infusing, an Observer's Assessment of Alertness/Sedation Scale was completed, a tourniquet was inflated, and a maximum tourniquet tolerance time (TTT) was obtained. Pain was assessed every 5 minutes while the tourniquet was inflated and immediately before deflation using a 0 to 10 verbally administered numeric rating scale (NRS). No significant differences in TTT were noted between the 2 propofol groups. However, the TTT for both propofol groups differed significantly from the control group (intralipid groups combined) (P < .05). There was a statistically significant difference in the time it took the propofol groups to reach a NRS score of 8 or greater when compared with the control group (P < .05). Sedation scores differed significantly between the control and the propofol at 32 micrograms/kg per minute groups (P < .05). The results of this study suggest that propofol given at subhypnotic doses could serve as a valuable adjunct for acute postoperative pain management.

Adult↗
PubMed2002

Effect of propofol anaesthesia on the event-related potential mismatch negativity and the auditory-evoked potential N1.

BACKGROUND: Studies on the effects of anaesthesia on event-related potentials and long latency auditory-evoked potentials (AEP) are sparse. Both provide information on cortical processing and may have potential as monitors of awareness. We studied the effect of propofol on the event-related potential mismatch negativity (MMN) and the long-latency AEP NI. METHODS: Twenty-one patients received 1 microgram ml-1 stepped increases in the target concentration of propofol using Diprifusor until a maximum of 6 micrograms ml-1 was achieved or the patient had lost consciousness. Neurophysiological responses (MMN and N1) and the patients' level of consciousness were recorded before the administration of propofol and at a target effector site concentration of propofol of 1, 2, 3, 4, and 6 micrograms ml-1. Grand average evoked potentials were computed at baseline, before the administration of propofol (A); at the highest propofol concentration at which each patient was responsive (B); and at the concentration of propofol at which the patient became unconscious (C). RESULTS: Patients lost consciousness at different target concentrations of propofol, all being unresponsive by 4 micrograms ml-1. The response to the deviant stimuli used to elicit duration-shift MMN was significantly more negative than to the standard stimuli at A (mean difference 2.58 microV, P = 0.0011) but this difference was virtually abolished at point B, before the patients lost consciousness (mean difference 0.63 microV, P = ns). The amplitude of N1 evoked by standard stimuli was negative compared with electrical baseline at both point A (mean amplitude -3.81 microV, P < 0.001) and at point B (mean amplitude -2.2 microV, P = 0.002), but was no longer significantly different to baseline at point C (mean amplitude 0.51 microV, P = ns). The change in the mean amplitude of N1 from last awake (point B) to first unconscious (point C) was also significant (mean difference in amplitude 1.69 microV, P = 0.02). CONCLUSIONS: MMN is unlikely to be a clinically useful tool to detect awareness in surgical patients. In contrast, the loss of N1 may identify the transition from consciousness to unconsciousness and deserves further study.

Adult↗