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PubMed1996

Inhibition by propofol of [3H]-batrachotoxinin-A 20-alpha-benzoate binding to voltage-dependent sodium channels in rat cortical synaptosomes.

1. Propofol (2,6 di-isopropylphenol), an intravenous general anaesthetic, blocks voltage-dependent Na+ channels (Na+ channels). In this study the interaction between propofol and Na+ channels was analysed by examining its effects on neurotoxin binding to various receptor sites of the Na+ channel in rat cerebrocortical synaptosomes. 2. Propofol (10-200 microM) exhibited concentration-dependent inhibition of equilibrium binding of [3H]-batrachotoxinin-A 20-alpha-benzoate ([3H]-BTX-B) to receptor site 2 of the Na+ channel (mean IC50 = 26 microM; 6.5 microM free). Scatchard analysis revealed that propofol significantly increased the KD without affecting the Bmax for [3H]-BTX-B binding. 3. Kinetic studies of [3H]-BTX-B binding in the presence of various concentrations (25-200 microM) of propofol showed no significant changes in the association rate of [3H]-BTX-B. However, propofol at 200 microM significantly increased the rate of dissociation of [3H]-BTX-B, consistent with an indirect allosteric competitive mechanism of inhibition. 4. [3H]-saxitoxin binding to receptor site 1 and [3H]-brevetoxin-3 binding to receptor site 5 of the Na+ channel were not inhibited by propofol (10-200 microM). 5. Propofol (10-100 microM) exhibited concentration-dependent inhibition of veratridine-evoked Na+ influx either in the absence or presence of scorpion toxin with IC50 values of 46 microM (8.8 microM free) and 44 microM (8.5 microM free), respectively. 6. These results suggest that propofol inhibits voltage-dependent Na+ channels due to a preferential interaction with the inactivated state of the channel. Blockade of Na+ channels by propofol, which is known to inhibit glutamate release from synaptosomes, may contribute to its anaesthetic, anticonvulsant and neuroprotective properties.

Anesthetics, Intravenous↗
PubMed1998

Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings.

PURPOSE: We compared propofol with high-dose barbiturates in the treatment of refractory status epilepticus (RSE) and propose a protocol for the administration of propofol in RSE in adults, correlating propofol's effect with plasma levels. METHODS: Sixteen patients with RSE were included; 8 were treated primarily with high-dose barbiturates and 8 were treated primarily with propofol. RESULTS: Both groups of patients had multiple medical problems and a subsequent high mortality. A smaller but not statistically significant fraction of patients had their seizures controlled with propofol (63%) than with high-dose barbiturate therapy (82%). The time from initiation of high-dose barbiturate therapy to attainment of control of RSE was longer (123 min) than the time to attainment of seizure control in the group receiving propofol (2.6 min, p = 0.002). Plasma concentrations of propofol associated with control of SE were 14 microM +/- 4 (2.5 microg/ml). Recurrent seizures were common when propofol infusions were suddenly discontinued but not when the infusions were gradually tapered. CONCLUSIONS: If used appropriately, propofol infusions can effectively and quickly terminate many but not all episodes of RSE. Propofol is a promising agent for use in treating RSE, but more studies are required to determine its true value in comparison with other agents.

Adult↗
PubMedDate not supplied

The effects of consecutive day propofol anesthesia on feline red blood cells.

This study investigated the potential for multiple exposures of propofol to induce oxidative injury, in the form of Heinz body production, to feline red blood cells. Anesthesia was induced in six healthy cats with propofol (6 mg/kg, intravenous [IV]) and maintained for 30 minutes with a propofol infusion (0.20 to 0.30 mg/kg/min, IV). The initial protocol was designed for each cat to receive 10 consecutive days of propofol anesthesia. All cats spontaneously breathed room air. Heart rate, respiratory rate, and indirect blood pressure were measured and recorded before and during anesthesia. Time to complete recovery after each infusion was measured and recorded. Heinz body analysis was performed before and after each day of propofol anesthesia. Based on predetermined criteria for discontinuing daily infusions, the mean number of consecutive days of propofol anesthesia was six and propofol administration did not continue beyond 7 days in any cat. Heart rate, respiratory rate, and indirect blood pressure did not change significantly during propofol anesthesia compared with awake values. Following the third consecutive day of propofol anesthesia, there was a significant increase from baseline in the mean percentage of Heinz bodies. Hemolysis was not detected in any cat. Recovery time significantly increased after the second consecutive day of propofol anesthesia compared with the first day. Five of six cats developed generalized malaise, anorexia, and diarrhea on day 5, 6, or 7, and two cats developed facial edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMedDate not supplied

Detomidine-butorphanol-propofol for carotid artery translocation and castration or ovariectomy in goats.

OBJECTIVE: To determine the safety and efficacy of propofol, after detomidine-butorphanol premedication, for induction and anesthetic maintenance for carotid artery translocation and castration or ovariectomy in goats. STUDY DESIGN: Case series. ANIMALS: Nine 4-month-old Spanish goats (17.1 +/- 2.6 kg) were used to evaluate propofol anesthesia for carotid artery translocation and castration or ovariectomy. METHODS: Goats were premedicated with detomidine (10 micrograms/kg intramuscularly [i.m.]) and butorphanol (0.1 mg/kg i.m.) and induced with an initial bolus of propofol (3 to 4 mg/kg intravenously [i.v.]). If necessary for intubation, additional propofol was given in 5-mg (i.v.) increments. Propofol infusion (0.3 mg/kg/min i.v.) was used to maintain anesthesia, and oxygen was insufflated (5 L/min). The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by movement, muscle relaxation, ocular signs, response to surgery, and cardiopulmonary responses. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, heart rate (HR), ECG, respiratory rate (RR), SpO2, and rectal temperature (T) were recorded every 5 minutes postinduction; arterial blood gas samples were collected every 15 minutes. Normally distributed data are represented as mean +/- SD; other data are medians (range). RESULTS: Propofol (4.3 +/- 0.9 mg/kg/min i.v.) produced smooth, rapid (15.2 +/- 6 sec) sternal recumbency. Propofol infusion (0.52 +/- 0.11 mg/kg/min i.v.) maintained anesthesia. Mean anesthesia time was 83 +/- 15 minutes. Muscle relaxation was good; eye signs indicated surgical anesthesia; two goats moved before surgery began; one goat moved twice during laparotomy. Means are reported over the course of the data collection period. Means during the anesthesia for pHa (arterial PH), PaCO2, PaO2, HCO3-, and BE (base excess) ranged from 7.233 +/- 0.067 to 7.319 +/- 0.026, 54.1 +/- 4.6 to 65.3 +/- 12.0 mm Hg, 133.1 +/- 45.4 to 183.8 +/- 75.1 mm Hg, 26.9 +/- 2.6 to 28.2 +/- 2.1 mEq/L, and -0.8 +/- 2.9 to 1.4 +/- 2.2 mEq/L. Means over time for MAP were 53 +/- 12 to 85 +/- 21 mm Hg. Mean HR varied over time from 81 +/- 6 to 91 +/- 11 beats/minute; mean RR, from 9 +/- 8 to 15 +/- 5 breaths/minute; SpO2 from 97 +/- 3% to 98 +/- 3%; mean T, from 36.0 +/- 0.6 degrees C to 39.1 +/- 0.7 degrees C. Over time, SpO2 and SaO2 did not change significantly; HR, RR, T, and PaCO2 decreased significantly; SAP, DAP, MAP, pHa, PaO2, and BE increased significantly. HCO3- concentrations increased significantly, peaking at 45 minutes. Recoveries were smooth and rapid; the time from the end of propofol infusion to extubation was 7.3 +/- 3 minutes, to sternal was 9.2 +/- 5 minutes, and to standing was 17.7 +/- 4 minutes. Median number of attempts to stand was two (range of one to four). Postoperative pain was mild to moderate. CONCLUSIONS: Detomidine-butorphanol-propofol provided good anesthesia for carotid artery translocation and neutering in goats. CLINICAL RELEVANCE: Detomidine-butorphanol-propofol anesthesia with oxygen insufflation may be safely used for surgical intervention in healthy goats.

Analgesics↗
PubMed2005

Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study.

OBJECTIVES: Adequate patient sedation is mandatory for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In this respect it is known that the short-acting anesthetic propofol offers certain potential advantages for sedation during ERCP, but there are no controlled studies concerning the feasibility and safety of propofol sedation in elderly, high-risk patients. METHODS: One hundred and fifty consecutive patients aged >or=80 yr with high comorbidity (ASA score >or=III: 91 %), randomly received midazolam plus meperidine (n = 75) or propofol alone (n = 75) for sedation during ERCP. Vital signs were continuously monitored and procedure-related parameters, recovery time, and quality as well as patients' cooperation and tolerance of the procedure were assessed. RESULTS: Clinically relevant changes in vital signs were observed at comparable frequencies with a temporary oxygen desaturation (<90%) occurring in eight patients in the propofol-group and seven patients receiving midazolam/meperidine (n.s.). Hypotension was documented in two patients in the propofol group and one patient receiving midazolam/meperidine. Propofol provided a significantly better patient cooperation than midazolam/meperidine (p < 0.01), but the procedure tolerability was rated nearly the same by both groups. Mean recovery time was significantly shorter in the propofol group (22 +/- 7 min vs 31 +/- 8 min for midazolam/meperidine (p < 0.01)) while the recovery score was significantly higher under propofol (8.3 +/- 1.2 vs 6.1 +/- 1.1(p < 0.01)). During recovery a significant lower number of desaturation events (<90%) were observed in the propofol group (12%) than in the midazolam/meperidine group (26%, p < 0.01). CONCLUSION: Under careful monitoring the use of propofol for sedation during ERCP is superior to midazolam/meperidine even in high-risk octogenarians.

Aged↗
PubMed2003

Site of action of the general anesthetic propofol in muscarinic M1 receptor-mediated signal transduction.

Although a potential target site of general anesthetics is primarily the GABA A receptor, a chloride ion channel, a previous study suggested that the intravenous general anesthetic propofol attenuates the M1 muscarinic acetylcholine receptor (M1 receptor)-mediated signal transduction. In the present study, we examined the target site of propofol in M1 receptor-mediated signal transduction. Two-electrode voltage-clamp method was used in Xenopus oocytes expressing both M1 receptors and associated G protein alpha subunits (Gqalpha). Propofol inhibited M1 receptor-mediated signal transduction in a dose-dependent manner (IC50 = 50 nM). Injection of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) into oocytes overexpressing Gqalpha was used to investigate direct effects of propofol on G protein coupled with the M1 receptor. Propofol did not affect activation of Gqalpha-mediated signal transduction with the intracellular injection of GTPgammaS. We also studied effects of propofol on l-[N-methyl-3H]scopolamine methyl chloride ([3H]NMS) binding and M1 receptor-mediated signal transduction in mammalian cells expressing M1 receptor. Propofol inhibited the M1 receptor-mediated signal transduction but did not inhibit binding of [3H]NMS. Effects of propofol on Gs- and Gi/o-coupled signal transduction were investigated, using oocytes expressing the beta2 adrenoceptor (beta2 receptor)/cystic fibrosis transmembrane conductance regulator or oocytes expressing the M2 muscarinic acetylcholine receptor (M2 receptor)/Kir3.1 (a member of G protein-gated inwardly rectifying K(+) channels). Neither beta2 receptor-mediated nor M2 receptor-mediated signal transduction was inhibited by a relatively high concentration of propofol (50 microM). These results indicate that propofol inhibits M1 receptor-mediated signal transduction by selectively disrupting interaction between the receptor and associated G protein.

Acetylcholine↗
PubMed2006

Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons: implications for anticonvulsant activity.

Although propofol is most commonly known for its general anesthetic properties, at subanesthetic doses, propofol has been effectively used to suppress seizures during refractory status epilepticus, a mechanism, in part, attributed to the inhibition of neuronal sodium channels. In this study, we have designed and synthesized two novel analogs of propofol, HS245 [2-(3-ethyl-4-hydroxy-5-isopropyl-phenyl)-3,3,3-trifluoro-2-hydroxy-propionamide] and HS357 [2-hydroxy-8-(4-hydroxy-3,5-diisopropyl-phenyl)-2-trifluoromethyl-octanoic acid amide], and determined their effects on sodium currents recorded from cultured hippocampal neurons. HS357 had greater affinity for the inactivated state of the sodium channel than propofol and HS245 (0.22 versus 0.74 and 1.2 microM, respectively) and exhibited the greatest ratio of affinity for the resting over the inactivated state. HS357 also demonstrated greater use-dependent block and delayed recovery from inactivation in comparison with propofol and HS245. Under current-clamp conditions, action potentials from hippocampal CA1 neurons in slices were evoked by current injection, or following perfusion with a zero Mg(2+)/7 mM K(+) artificial cerebrospinal fluid solution. Propofol and HS357 reduced the number of current-induced action potentials; however, HS357 caused a greater reduction in the number of spontaneous action potentials. Consistent with these electrophysiology studies, propofol and HS357 protected mice against acute seizures in the 6-Hz (22-mA) partial psychomotor model. Efficacious doses of propofol were associated with an impairment of motor coordination as assessed in the rotorod toxicity assay. In contrast, HS357 demonstrated a 2-fold greater protective index than propofol. Thus, propofol analogs represent an important structural class from which not only effective, but also safer, anti-convulsants may be developed.

Action Potentials↗
PubMed2004

Multiple actions of propofol on alphabetagamma and alphabetadelta GABAA receptors.

GABAA receptors are predominantly composed of alphabetagamma and alphabetadelta isoforms in the brain. It has been proposed that alphabetagamma receptors mediate phasic inhibition, whereas alphabetadelta receptors mediate tonic inhibition. Propofol (2,6-di-isopropylphenol), a widely used anesthetic drug, exerts its effect primarily by modulating GABAA receptors; however, the effects of propofol on the kinetic properties of alphabetagamma and alphabetadelta receptors are uncertain. We transfected human embryonic kidney (HEK293T) cells with cDNAs encoding rat alpha1, alpha6, beta3, gamma2L, or delta subunits and performed whole-cell patch-clamp recordings to explore this issue. Propofol (3 microM) increased GABA concentration-response curve maximal currents similarly for both alpha1beta3gamma2L and alpha6beta3gamma2L receptors, but propofol increased those for alpha1beta3delta and alpha6beta3delta receptors differently, the increase being greater for alpha1beta3delta than for alpha6beta3delta receptors. Propofol (10 microM) produced similar alterations in alpha1beta3gamma2L and alpha6beta3gamma2L receptor currents when using a preapplication protocol; peak currents were not altered, desensitization was reduced, and deactivation was prolonged. Propofol enhanced peak currents for both alpha1beta3delta and alpha6beta3delta receptors, but the enhancement was greater for alpha1beta3delta receptors. Desensitization of these two isoforms was not modified by propofol. Propofol did not alter the deactivation rate of alpha1beta3delta receptor currents but did slow deactivation of alpha6beta3delta receptor currents. The findings that propofol reduced desensitization and prolonged deactivation of gamma2L subunit-containing receptors and enhanced peak currents or prolonged deactivation of delta subunit-containing receptors suggest that propofol enhancement of both phasic and tonic inhibition may contribute to its anesthetic effect in the brain.

Cell Line↗
PubMed1992

Propofol is a 'safe' anaesthetic agent in malignant hyperthermia susceptible patients.

In this study we investigated in vitro and in vivo effects of propofol in malignant hyperthermia susceptible (MHS) patients in order to assess the safety of propofol infusion as a non-triggering anaesthetic technique for diagnostic and therapeutic procedures. In vitro, human MHS muscle samples were exposed to propofol and changes in (a) baseline tension and (b) contracture tension on exposure to halothane and caffeine were measured. In vivo, (a) anaesthesia was induced in ten muscle biopsy positive MHS patients with propofol 2.5 mg/kg and (b) anaesthesia was produced in five muscle biopsy positive MHS patients with infusions of propofol up to 10 mg/kg/hr. In vitro, human MHS muscle did not develop contractures with propofol alone. Propofol had no significant effect on contracture development in response to halothane and caffeine. In vivo, no evidence of an MH response was detected following induction or maintenance of anaesthesia with propofol. Our results and literature review are in agreement that propofol is a 'safe' induction and maintenance agent in MHS patients. Propofol can be used for muscle biopsy anaesthesia because it does not alter the sensitivity of diagnostic muscle biopsy testing.

Adolescent↗
PubMed1994

Propofol and seizures.

It is now clear that "seizure activity", excitatory phenomena, and/or a disorder of muscle tone are potential complications of the use of propofol. Whether this "seizure activity" is primarily, secondarily, or not at all a cerebral cortical event is still to be elucidated. Clearly propofol does have anticonvulsant activity, and also clearly it can produce an involuntary movement disorder, in certain patients, under certain conditions. Propofol is not the first anaesthetic drug to be implicated in the causation of seizures or abnormal movements nor indeed the first to appear to have anti-convulsant and proconvulsant activity (e.g. Althesin). While propofol has undoubtedly proved a very useful drug, the problem of convulsive phenomena creates a degree of background concern about its use. More needs to be known about the mechanism of this complication and any risk factors involved in determining who may have a seizure after propofol. In the clinical setting, the reporting of seizures possibly related to propofol should include--medical history, including personal or family history of epilepsy and movement disorders; a history of previous anaesthetics and whether propofol was used; regular medications; use of drugs or alcohol; history of chemical dependency; emotional state prior to induction; presence of hyperventilation or fever; a description of the alleged seizure, including rate of administration of propofol and amount given, time of onset of seizure in relation to time of drug administration, speed of onset of signs, quality of the abnormal movements, part of body involved, duration, any indication of a postictal state, any cardiovascular changes which may have accompanied the seizure, and any other possible triggers for the reaction such as other drugs used, including premedication; post seizure investigations including temperature, blood sugar, electrolytes, arterial gas analysis, neurological examination, EEG and CT scan. These actions and these investigations concerning propofol should not be delayed. It would appear appropriate to recommend to patients who experience apparent convulsive phenomena after propofol that they not be re-exposed to the drug.

Adult↗
PubMed1994

Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties.

We examined the plasma concentrations and resultant clinical effects produced by four different propofol bolus infusion regimens in 98 healthy males undergoing elective urologic procedures under regional anesthesia. Patients were randomly assigned to one of four propofol dosage groups. In Groups 1-4, loading doses of propofol equal to 0.2, 0.4, 0.5, or 0.7 mg/kg intravenously, respectively, were followed by fixed-rate propofol infusions of 0.5, 1, 2, or 4 mg.kg-1.h-1, respectively, during the regional block procedure. Sedation (sleepiness) was assessed independently by the patient and a blinded observer using 100-mm visual analog scales. Intraoperative amnesia was assessed using picture recall. Sedation scores increased in a dose-dependent fashion (13 +/- 19, 21 +/- 19, 45 +/- 28, and 73 +/- 26 mm at 30 min in Groups 1-4, respectively). Within a given dosage group, sedation scores were stable during the maintenance infusion period. Mean plasma propofol concentrations increased with higher propofol infusion rates (0.16 +/- 0.3, 0.18 +/- 0.1, 0.47 +/- 0.2, and 1.1 +/- 0.8 microgram/mL at 30 min in Groups 1-4, respectively). However, significant variability was observed among individual patient sedation scores and plasma propofol concentrations. Anxiety scores decreased in all four propofol infusion groups during the maintenance period. Hemodynamic variables and hemoglobin oxygen saturation values were similar in all four treatment groups. Recovery from propofol's central effects was rapid after discontinuation of the propofol infusion, and the incidence of side effects was low. Recall of intraoperative events was more commonly observed in the lower-dosage groups (86%, 96%, 58%, and 13% of patients in Groups 1-4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors.

UNLABELLED: To elucidate the role of gamma-aminobutyric acid (GABA)(A) receptor complex and excitatory amino acid receptors (N-methyl-D-aspartate [NMDA] and non-NMDA receptors) in propofol-induced anesthesia, we examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol anesthesia in mice. All drugs were administered intraperitoneally. General anesthetic potencies were evaluated using a righting reflex assay. The GABA(A) receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diazepam and the NMDA receptor antagonist MK-801 augmented propofol anesthesia, but the non-NMDA receptor antagonist CNQX did not. In contrast, the GABA(A) receptor antagonist bicuculline antagonized propofol (200 mg/kg; 95% effective dose for loss of righting reflex) induced anesthesia. However, neither the benzodiazepine receptor antagonist flumazenil, the GABA synthesis inhibitor L-allylglycine, nor the NMDA receptor agonist NMDA reversed propofol anesthesia. Conversely, the non-NMDA receptor agonist kainate enhanced propofol anesthesia. These results suggest that propofol-induced anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors. IMPLICATIONS: We examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol-induced anesthesia in mice. The results suggest that propofol anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors.

Anesthesia, General↗
PubMed2003

The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients.

UNLABELLED: In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults. IMPLICATIONS: Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.

Adult↗
PubMed2004

Narcotrend index versus bispectral index as electroencephalogram measures of anesthetic drug effect during propofol anesthesia.

UNLABELLED: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) performs an automatic analysis of the electroencephalogram (EEG) during anesthesia based on a visual assessment of the raw EEG. Its newest software version 4.0 includes a dimensionless index that, similar to the bispectral index (BIS), ranges from 100 (awake) to 0. We compared the performance of Narcotrend index and BIS as EEG measures of anesthetic drug effect during propofol anesthesia. Eighteen adult patients scheduled for radical prostatectomy were investigated. An epidural catheter was placed in the lumbar space and electrodes for BIS (version XP; Aspect Medical Systems, Natick, MA) and Narcotrend were positioned as recommended by the manufacturers. Narcotrend index, BIS values, and propofol plasma and effect site concentrations as parallelly simulated by Rugloop software (Department of Anesthesia, Ghent University, Belgium) were automatically recorded in intervals of 5 s. Induction of anesthesia consisted of a fentanyl bolus and a propofol infusion. After endotracheal intubation, patients received 15 mL bupivacaine 0.5% epidurally, and 45 min later propofol dosages were subsequently increased and decreased twice. Simulated propofol effect site concentrations ranged from 2.0 +/- 0.4 microg/mL (smallest) to 6.3 +/- 1.3 microg/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (P(K)) the performance of the Narcotrend index (P(K) = 0.88 +/- 0.03) to predict propofol effect site concentrations was comparable to the BIS (P(K) = 0.85 +/- 0.04). Using the respective EEG index as a measure of drug effect the mean k(e0) was calculated as 0.20 +/- 0.05 min(-1) for Narcotrend index and 0.16 +/- 0.07 min(-1) for BIS. In the observed propofol concentration range Narcotrend index detected differences in EEG dynamics as well as BIS. IMPLICATIONS: This study in 18 adult patients undergoing radical prostatectomy describes the relationship between Narcotrend index and bispectral index versus predicted propofol effect compartment concentrations. In terms of prediction probability, the performance of the Narcotrend index and the bispectral index to predict propofol effect site concentrations was comparable.

Aged↗
PubMed2004

The anticonvulsant action of propofol on epileptiform activity in rat hippocampal slices.

We used extracellular electrophysiological recordings from the CA1 region in rat hippocampal slices to investigate the effects of propofol on the field excitatory postsynaptic potential (fEPSP), population spike, and epileptiform activity induced by a Mg(2+)-free condition. Propofol depressed the population spike, fEPSP, and epileptiform activity. Both aminophylline, a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine, an A(1) receptor antagonist, significantly reduced the effect of propofol on fEPSP amplitude. However, 3,7-dimethyl-1-propagylxanthine, an A(2) receptor antagonist, did not alter the effect of propofol on fEPSP amplitude. Picrotoxin, a specific chloride channel blocker, partly reduced the effect of propofol on epileptiform activity, but bicuculline, a competitive gamma-aminobutyric acid(A) receptor antagonist, failed to antagonize it. Aminophylline significantly reduced the action of propofol on the epileptiform activity. The anticonvulsant action of propofol was partly reduced by 8-cyclopentyl-1,3-dipropylxanthine, whereas 3,7-dimethyl-1-propagylxanthine failed to affect it. Adenosine depressed the amplitude of fEPSPs in a dose-dependent manner, and propofol enhanced this inhibition. The results demonstrated that, in rat hippocampal slices, propofol inhibits epileptiform activity. In addition, adenosine neuromodulation through the A(1) receptor may contribute to the anticonvulsant action of propofol.

Adenosine↗
PubMed2005

Selective phosphodiesterase 5 inhibition does not reduce propofol sedation requirements but affects speed of recovery and plasma cyclic guanosine 3',5'-monophosphate concentrations in healthy volunteers.

UNLABELLED: Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study. Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans. IMPLICATIONS: Plasma cyclic guanosine 3',5'-monophosphate (cyclic GMP) concentrations are reduced during propofol sedation. Selective phosphodiesterase 5 inhibition, however, does not reduce propofol sedation requirements or plasma cyclic GMP concentrations but affects speed of recovery in healthy volunteers.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Cerebrospinal fluid and plasma propofol concentration during total intravenous anaesthesia of patients undergoing elective intracranial tumor removal.

OBJECTIVE: The aim of this paper is to compare the propofol concentration in plasma and cerebrospinal fluid (CSF) in patients scheduled for intracranial tumor removal and anaesthetized using propofol as part of a total intravenous anaesthesia technique. METHODS: Twenty-seven patients (ASA I-II) scheduled for elective intracranial tumor removal were studied. Anesthesia was induced with 2 mg/kg propofol for 5 min and infused at 10 mg/(kg x h) for 5 min and then stopped. CSF and arterial blood were collected simultaneously before infusion of propofol and at different time points after infusion of propofol according to bispectral index (BIS) values. Concentrations of propofol in plasma and CSF were measured by HPLC with fluorescence detection. The correlation coefficient and regression equation between plasma and CSF concentration of propofol were worked out by linear simple regression. RESULTS: The propofol CSF concentration that we measured was 1.46% of the plasma concentration. The coefficient of relation between plasma and CSF concentration was 76.7%. CONCLUSIONS: The propofol CSF concentration was positively correlated with and much lower than the plasma concentration. Discrepancies may result from high plasma protein binding of propofol, intracranial pathology and sampling volume.

Adolescent↗
PubMed2002

Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs.

OBJECTIVE: To evaluate dose-sparing effects of medetomidine-midazolam (MM), acepromazine-butorphanol (AB), and midazolam-butorphanol (MB) on the induction dose of thiopental and propofol and to examine cardiopulmonary changes in dogs. ANIMALS: 23 healthy Beagles. PROCEDURE: Dogs were administered MM, AB, MB, or physiologic saline (0.9% NaCI) solution (PS) IM, and anesthesia was induced with thiopental or propofol. Cardiopulmonary measurements were obtained before and after administration of medication and 0, 5, 10, and 15 minutes after endotracheal intubation. RESULTS: Induction doses were reduced significantly by preanesthetic administration of MM, AB, and MB (thiopental, 20, 45, and 46% after administration of PS; propofol, 42, 58, and 74% after administration of PS, respectively). Recovery time in dogs administered MM-thiopental or MM-propofol and AB-propofol were significantly prolonged, compared with recovery time in dogs administered PS-thiopental or PS-propofol. Relatively large cardiovascular changes were induced by administration of MM, which were sustained even after the induction of anesthesia. Administration of AB and MB induced cardiovascular changes during and immediately after endotracheal intubation that were significantly decreased by induction with thiopental or propofol. However, mild hypotension developed with AB-propofol. Apnea was observed in dogs administered MM during induction of anesthesia, but most respiratory variables did not change significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Preanesthetic medication with MM greatly reduced the anesthesia induction dose of thiopental and propofol but caused noticeable cardiopulmonary changes. Preanesthetic medication with AB and MB moderately reduced the induction dose of thiopental and propofol and amelio rated cardiovascular changes induced by these anesthetics, although AB caused mild hypotension.

Acepromazine↗