Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Propofol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1997

Pretreatment with topical 60% lidocaine tape reduces pain on injection of propofol.

UNLABELLED: We determined whether pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol. In a randomized, double-blind trial, 90 patients were allocated to one of three groups: pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline (Group A); pretreatment with 60% lidocaine tape and a premixed solution of propofol and normal saline (Group B); or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg (Group C). The incidences of pain in Groups A, B, and C were 86.7%, 33.4%, and 20%, respectively. Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups. Pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol. IMPLICATIONS: Pretreatment with topical 60% lidocaine tape reduces the pain associated with injection of propofol, a frequently used intravenous anesthetic. This approach should increase patient comfort during induction of anesthesia.

Administration, Cutaneous↗
PubMed1997

Propofol attenuates ischemia-reperfusion injury in the isolated rat heart.

UNLABELLED: The purpose of this study was to examine the direct effects of propofol on ischemia-reperfusion injury using an isolated Langendorff rat heart preparation. Hearts were perfused with Krebs-Henseleit (K-H) solution (control); intralipid; or 10, 30, and 100 microM propofol. Hearts were rendered globally ischemic for 25 min, then reperfusion was begun with K-H solution for 30 min. Treatment with 100 microM propofol delayed the onset of contracture during ischemia compared with control or intralipid treatments (6.4 +/- 2.1 vs 4.4 +/- 1.4 or 4.1 +/- 0.7 min, respectively; P < 0.05). During reperfusion, 100 microM propofol increased coronary flow and reduced lactate dehydrogenase release compared with control or intralipid treatments. After 30 min of reperfusion, left ventricular developed pressure (LVDP) returned to 55 and 76 mm Hg in the 30 and 100 microM propofol-treated groups, respectively, whereas LVDP was 39 mm Hg in the control group. The hearts treated with 100 microM propofol showed significantly lower left ventricular end-diastolic pressure compared with the control or intralipid groups 30 min after reperfusion (29 +/- 13 vs 48 +/- 5 or 48 +/- 11 mm Hg, respectively; P < 0.05). In histological evaluation, control and intralipid hearts had increased injury severity scores compared with hearts treated with 100 microM propofol (1.8 +/- 0.9 and 1.7 +/- 0.8 vs 1.0 +/- 0.7, respectively; P < 0.05). In conclusion, we suggest that propofol administered before and during global myocardial ischemia has cardioprotective effects on ischemia-reperfusion injury. IMPLICATIONS: It is important to protect the heart from injury by ischemia and reperfusion. The current study demonstrates that in the isolated rat heart, propofol attenuates mechanical, biochemical, and histological changes causes by ischemia and reperfusion.

Anesthetics, Intravenous↗
PubMed1998

Propofol improves functional and metabolic recovery in ischemic reperfused isolated rat hearts.

UNLABELLED: Propofol attenuates mechanical dysfunction, metabolic derangement, and lipid peroxidation by exogenous administration of H2O2 in the Langendorff rat heart. In this study, we examined the effects of propofol on mechanical and metabolic changes, as well as on lipid peroxidation induced by ischemia-reperfusion, in isolated, working rat hearts. Rat hearts (in control-modified Krebs-Henseleit bicarbonate buffer) were treated with two doses (25 microM and 50 microM) of propofol in an intralipid vehicle. In the first protocol, propofol was administered during the preischemic and reperfusion period, whereas in the second, it was only administered during the reperfusion period. Ischemia (15 min) decreased peak aortic pressure (PAOP), heart rate (HR), rate-pressure product (RPP), coronary flow (CF), and tissue concentrations of adenosine triphosphate (ATP) and creatine phosphate. After postischemic reperfusion (20 min), the CF and tissue concentration of ATP recovered incompletely; however, PAOP, HR, and RPP did not. Ischemia-reperfusion also increased the tissue concentration of malondialdehyde (MDA). In both protocols, both doses of propofol enhanced recovery of PAOP, HR, RPP, CF, and tissue concentration of ATP during reperfusion, and inhibited the tissue accumulation of MDA. These results indicate that propofol improves recovery of mechanical function and the energy state in ischemic reperfused isolated rat hearts, and the mechanism may involve the reduction of lipid peroxidation during postischemic reperfusion. IMPLICATIONS: We evaluated the possible cardioprotective effects of propofol in isolated, working rat hearts subjected to 15-min ischemia, followed by 20-min reperfusion. We observed that propofol attenuated mechanical dysfunction, metabolic derangement, and lipid peroxidation during reperfusion. This latter finding seems to be one mechanism for cardioprotective effects of propofol.

Adenine Nucleotides↗
PubMed1998

Left ventricular systolic and diastolic function is unaltered during propofol infusion in newborn swine.

UNLABELLED: Propofol is a cardiac depressant with minimal diastolic effects in the adult myocardium. Cardiac effects of propofol in the newborn are unknown. We examined hemodynamic variables and systolic and diastolic left ventricular function in 12 newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and 30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior dimension, determined by sonomicrometry, were continuously monitored. Mean arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP) were determined at every infusion. Systolic function was assessed by the maximal pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure-dimension relationship (ESP-D), and by the preload recruitable stroke work index (PRSWI). Diastolic function was assessed by relaxation indices, the minimal pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and by a stiffness index, the slope of the EDP-D relationship. MAP decreased approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with propofol, with no dose effect. HR and LVEDP were unchanged from control. Both dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged. Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1) infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to 0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this profile, propofol may be useful for the newborn requiring anesthesia. IMPLICATIONS: Most anesthetics depress heart function in the newborn. We examined both heart contraction and relaxation during anesthesia with propofol in newborn pigs. Propofol had minimal influence on heart function in this model at the doses studied. This may therefore be a useful anesthetic to test in the newborn human.

Anesthetics, Intravenous↗
PubMed1998

The effects of propofol on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass.

UNLABELLED: We investigated the effects of burst-suppression doses of propofol on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and dynamic autoregulation in 20 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with stable hypothermia (32 degrees C) in fentanyl-anesthetized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Dynamic autoregulation was tested by stepwise changes in mean arterial pressure (MAP) within a range of 40-80 mm Hg by sodium nitroprusside and phenylephrine before (control) and during propofol infusion, with a stable plasma concentration (approximately 9 microg/mL). Propofol induced a 35% decrease in CBFV (P < 0.0001) and a 10% decrease in COE (P < 0.05) compared with control. The slopes of the curves relating CBFV and COE to cerebral perfusion pressure (CPP = MAP - JVP) were less pronounced with propofol (P < 0.01 and P < 0.05, respectively). We conclude that propofol decreases CBFV and improves dynamic autoregulation during moderate hypothermic CPB. Furthermore, during propofol infusion, cerebral blood flow was in excess relative to oxygen demand, as indicated by the decrease in COE. IMPLICATIONS: In this study, we evaluated the effects of propofol on continuously measured cerebral blood flow velocity (CBFV) and cerebral oxygen extraction as a function of perfusion pressure. Propofol induced 35% and 10% decreases in CBFV and cerebral oxygen extraction, respectively. The slope of the curve relating cerebral perfusion pressure to CBFV decreased with propofol.

Aged↗
PubMed1998

The effect of rate of administration on brain concentrations of propofol in sheep.

UNLABELLED: A marked reduction in the dose of propofol required to achieve the onset of anesthesia with slower administration rates has previously been reported, but the mechanism of this phenomenon is unclear. We used a chronically instrumented sheep preparation to examine the effects of different administration rates of propofol on its distribution in the brain using mass balance principles to calculate brain concentrations. The administration of 100 mg of propofol i.v. at rates of 200, 50, and 20 mg/min had minimal effect on both the peak brain concentrations of propofol and the total amount of drug entering the brain. The more rapid administration rates increased the rate of uptake into the brain but resulted in large increases in peak arterial blood propofol concentrations. These faster administration rates have previously been associated with high arterial propofol concentrations and an increased risk of hypotension. Simulation of titration to an end point revealed that the dose sparing previously reported at induction with slow administration rates relates only to improved titration to effect, and does not result in more anesthesia for a given dose. Therefore, we conclude that the administration of propofol over 2 min provides a reasonable rate of induction and improved titration to effect, yet avoids excessively high arterial concentrations. IMPLICATIONS: Alterations in the rate of administration of propofol in sheep have been shown to have little effect on the quantity of propofol delivered to the brain. At induction of anesthesia, administration rates of approximately 50 mg/min seem likely to provide improved titration to effect without excessively prolonging induction.

Anesthesia, Intravenous↗
PubMed1999

Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients.

UNLABELLED: Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-thiopental synergy, as demonstrated with midazolam-thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. IMPLICATIONS: The propofol-thiopental hypnotic interaction is additive.

Adolescent↗
PubMed1999

The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway.

UNLABELLED: To determine the target plasma concentration of propofol required to place either a laryngeal mask airway (LMA) or a cuffed oropharyngeal airway (COPA), we started a continuous target-controlled infusion of propofol in 60 ASA physical status I or II unpremedicated patients scheduled for minor orthopedic surgery with peripheral nerve block. The target plasma concentration of propofol was initially set at 2 microg/mL. When the effect-site calculated concentration of propofol was equal to the plasma concentration according to the computer simulation, the target plasma concentration was increased by 0.5-microg/mL steps until successful placement of either the LMA (n = 30) or the COPA (n = 30). The mean target plasma concentration of propofol required to place a LMA was 4.3 +/- 0.8 microg/mL compared with 3.2 +/- 0.6 microg/mL to place a COPA (P < 0.001). To successfully place the airways in 95% of patients, the target plasma concentration of propofol had to be increased up to 4 microg/mL for the COPA and 6 microg/mL for the LMA. We conclude that placing a LMA in healthy, unpremedicated patients requires target plasma concentrations of propofol higher than those required for placing a COPA. IMPLICATIONS: We evaluated the use of target-controlled infusion of propofol to place extratracheal airways in this prospective, randomized study and demonstrated that the target plasma concentration of propofol required to successfully place a laryngeal mask in >95% of healthy, unpremedicated patients is 6 microg/mL, compared with 4 microg/mL to place a cuffed oropharyngeal airway.

Adolescent↗
PubMed1999

Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness.

UNLABELLED: Propofol (iv) depresses cardiovascular function in both humans and animals. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that this effect of propofol results in part from an antagonism of adrenergic control of the heart. Experiments examined effects of propofol on: 1) [3H]CGP12177 (a beta-adrenoceptor antagonist) binding in rat myocardial membranes; and 2) the inotropic and chronotropic actions of isoproterenol in rat left atrial muscle and right atria, respectively. Propofol (25-200 microM) increased the apparent dissociation constant for [3H]CGP12177 without affecting binding site density. Similarly, 200 microM propofol increased the 50% effective concentration values for the dose-dependent positive chronotropic and inotropic actions of isoproterenol in right and left atria, and depressed the maximum increase in spontaneous rate elicited by this beta-adrenoceptor agonist. Other experiments demonstrated that propofol does not alter muscarinic receptor binding as monitored using [3H]quinuclidi-nylbenzilate. In conclusion, these results indicate that propofol can decrease cardiac beta-adrenoceptor responsiveness; however, the concentrations of propofol required suggest that this action contributes to the cardiovascular depression produced by this anesthetic only during large-dose bolus injection. IMPLICATIONS: Experiments in membranes and cardiac preparations isolated from rat heart demonstrate that relatively high concentrations of propofol (25-200 microM) are required to antagonize beta-adrenoceptor binding and tissue responsiveness.

Adrenergic beta-Agonists↗
PubMed1999

Fentanyl pretreatment does not impair the reliability of an epinephrine-containing test dose during propofol-nitrous oxide anesthesia.

UNLABELLED: We designed this study to determine the hemodynamic responses to and the efficacy of a simulated IV test dose during propofol anesthesia based on the conventional heart rate (HR; positive if increase > or =20 bpm), the modified HR (positive if increase > or =10 bpm), and the systolic blood pressure (SBP; positive if increase > or =15 mm Hg) criteria. Eighty healthy patients were randomized to receive 2 mg/kgpropofol or propofol plus fentanyl (100 microg) at the induction of anesthesia (n = 40 each). After endotracheal intubation, anesthesia in both groups was maintained with propofol 8 mg x kg(-1) x h(-1) and 67% nitrous oxide in oxygen. Each group of patients was further divided into a test dose group receiving 1.5% lidocaine 3 mL plus epinephrine 15 microg (1:200,000) or a saline group (n = 20 each) receiving 3 mL of isotonic sodium chloride solution i.v. HR and SBP were monitored for 4 min after the i.v. injection of the study drug. The i.v. injection of the test dose produced a HR increase > or =20 bpm in 20 and 17 patients in the propofol and propofol-fentanyl groups, respectively, whereas all patients receiving the test dose and none receiving saline had HR increases > or =10 bpm. Therefore, in the propofol-fentanyl group, sensitivity, specificity, positive predictive value, and negative predictive value were 85%, 100%, 100%, and 87% according to the conventional HR criterion, and all were 100% according to the modified HR criterion. In the propofol group, 100% efficacy was obtained based on both HR criteria. However, all patients receiving the test dose and none receiving saline developed a SBP increase > or =15 mm Hg, resulting in 100% efficacy based on the conventional SBP criterion in both groups. Our results indicate that both the modified HR criterion and the SBP criterion are clinically applicable during propofol anesthesia with or without supplemental fentanyl. IMPLICATIONS: To determine whether an epidural catheter is in a blood vessel, an epidural test dose containing 15 microg of epinephrine is used. We found that, during propofol anesthesia with or without fentanyl, a heart rate increase > or =10 bpm and a systolic blood pressure increase > or =15 mm Hg are reliable indicators for detecting accidental intravascular injection.

Adrenergic alpha-Agonists↗
PubMed2000

Propofol inhibits Ca(2+) transients but not contraction in intact beating guinea pig hearts.

UNLABELLED: We investigated whether propofol inhibits Ca(2+) transients and left ventricular pressure (LVP) in intact beating guinea pig hearts at clinical concentrations and whether an inhibition of Ca(2+) transients by propofol results from an impairment of sarcolemmal or of sarcoplasmic reticulum (SR) function. By using a Langendorff's preparation, transmural left ventricular phasic intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by the fluorescence ratio of indo-1 emission at 385 nm and 456 nm and was calibrated to Ca(2+) transients (in nM). The Ca(2+) transients during each contraction were defined as available [Ca(2+)](i). Sixty hearts were perfused with modified Krebs-Ringer's solution containing lipid vehicle and propofol (1 and 10 microM) in the absence and presence of ryanodine, thapsigargin, and nifedipine, while developed LVP and available [Ca(2+)](i) were recorded. Propofol (10 microM) decreased available [Ca(2+)](i) by 11.0% +/- 1.3% without decreasing developed LVP (% of control, P < 0.05). Propofol (10 microM) caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i). Propofol (10 microM) with nifedipine (1 microM), but not with ryanodine (1 microM) or thapsigargin (1 microM), decreased available [Ca(2+)](i) by 15.5% +/- 1.7% (P < 0.05). Propofol decreases available [Ca(2+)](i) without decreasing cardiac contraction, and it enhances myofilament Ca(2+) sensitivity in intact beating hearts at clinical concentrations. The inhibition of available [Ca(2+)](i) by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum Ca(2+) handling rather than the sarcolemmal L-type Ca(2+) current. IMPLICATIONS: This is the first study of the effects of propofol on intracellular Ca(2+) concentration and myofilament Ca(2+) sensitivity under physiologic conditions in intact isolated beating guinea pig hearts.

Actin Cytoskeleton↗
PubMed2001

The determinants of propofol induction of anesthesia dose.

UNLABELLED: Recently it was reported that the pharmacokinetics of propofol are modified by changes in cardiac output. The objective of this study was to evaluate the effects of cardiac output and other factors on the hypnotic dose of propofol. One-hundred surgical patients were administered indocyanine green immediately before the induction of anesthesia to measure their cardiac outputs and blood volumes. Propofol (250 microg. kg(-1). min(-1)) was infused IV for 8 min, and the hypnotic dose of propofol and the time to hypnosis were recorded. The plasma concentration of propofol immediately after 2 mg/kg infusion was measured. Multiple regression analysis showed that, in addition to age and weight, cardiac output was a small but significant factor for predicting the hypnotic dose of propofol (R(2) = 0.468, P < 0.001), the time to hypnosis (R(2) = 0.454, P < 0.001), and the plasma concentration of propofol (R(2) = 0.248, P < 0.01). Cardiac output, age, and weight showed similar partial coefficients for the hypnotic dose (0.128, 0.137, and 0.140, respectively). IMPLICATIONS: This study demonstrates a significant relationship between cardiac output and the hypnotic dose of propofol. We suggest that anesthesiologists should include cardiac output, as well as age and weight, in calculating the induction dose of propofol.

Adolescent↗
PubMed2001

The effects of uterine and umbilical blood flows on the transfer of propofol across the human placenta during in vitro perfusion.

UNLABELLED: The safety of using propofol in parturients is controversial, and little information is available on the factors that influence the placental transfer of propofol. In this study, we investigated the effects of uterine and umbilical blood flows on the placental transfer of propofol by using the dually perfused human placental cotyledon. Placental transfer was evaluated on the basis of the placental clearances at various uterine and umbilical flow rates. The placental transfer of propofol was significantly facilitated by the increased uterine flow rates over the range from 7.5 to 25 mL/min. The placental clearances of propofol were also dependent on the umbilical flow rates over the range from 0.5 to 4.0 mL/min. In contrast, the placental transfer of antipyrine was flow dependent when the umbilical flow rate was <2.0 mL/min and became permeability limited when it was >2.0 mL/min. No differences in either maternal or fetal venous concentrations of propofol were observed as umbilical flow rates varied from 0.5 to 4.0 mL/min, suggesting that an equilibration across the placenta occurs at low flow rates. These results indicate that fetal uptake of propofol can be profoundly altered by the changes in both uterine and umbilical blood flows observed in various pathophysiologic conditions and that lipid solubility greatly influences placental transfer of drugs. IMPLICATIONS: Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.

Adult↗
PubMed2001

Propofol protection of sodium-hydrogen exchange activity sustains glutamate uptake during oxidative stress.

UNLABELLED: We investigated the role of intracellular pH in protection by propofol of glutamate uptake during oxidative stress. Exposure of primary astrocyte cultures to tert-butylhydroperoxide (t-BOOH, 300 microM) decreased the initial rate of Na-dependent glutamate uptake. Either propofol or alpha-tocopherol, administered 30 min after t-BOOH, attenuated this transport inhibition. These lipophilic antioxidants protected glutamate uptake whether the medium contained 25 mM bicarbonate or was nominally bicarbonate-free. t-BOOH also inhibited Na/H exchanger isoform 1 (NHE1) activation by intracellular protons and propofol prevented this inhibition. Blockade of NHE1 by the potent antagonist, 5-(N-ethyl-N-isopropyl) amiloride (1 microM), abolished the protective effects of small concentrations of propofol (1 microM) and alpha-tocopherol (40 microM) on glutamate uptake during oxidative stress in bicarbonate-free medium. 5-(N-ethyl-N-isopropyl) amiloride had no effect on antioxidant rescue of glutamate transport in medium containing 25 mM bicarbonate. These results indicate that regulation of intracellular pH may contribute to neuroprotection by propofol and other lipophilic antioxidants. Propofol concentrations that are associated with anesthesia and neuroprotection may prevent intracellular acidification during oxidative stress by preserving the NHE1 response to cytosolic protons. However, if intracellular acidification occurs nonetheless, then propofol protection of glutamate uptake activity becomes less effective and the extracellular glutamate concentration may increase to neurotoxic levels. IMPLICATIONS: Anesthetic concentrations of propofol maintain the capacity of brain cells to extrude protons during oxidative stress. However, if intracellular acidification occurs nonetheless, then propofol's protection of glutamate clearance mechanisms from oxidative damage becomes attenuated, and extracellular glutamate concentration may increase to neurotoxic levels.

Amiloride↗
PubMed2002

The effects of propofol on neural and endothelial control of in situ rat mesenteric vascular smooth muscle transmembrane potentials.

UNLABELLED: We indirectly assessed the in vivo effect of propofol on sympathetic neural and endothelial control of vascular smooth muscle (VSM) tone in Sprague-Dawley rats by measurement of in situ responses of VSM transmembrane potential (E(m)) in intact, small mesenteric arteries and veins superfused with physiologic salt solution. Measurements were made before, during, and after propofol infusion (10 and 30 mg x kg(-1) x h(-1)) in sympathetically innervated and locally denervated vessels. Propofol's effect on E(m) response to superfusion with acetylcholine (ACh), in physiologic salt solution also containing NG-nitro-L-arginine-methyl-ester and indomethacin, was determined in innervated vessels. At 30 mg x kg(-1) x h(-1), propofol caused greater arterial VSM hyperpolarization in innervated compared with denervated vessels (4.8 +/- 2.0 mV versus 2.8 +/- 1.5 mV, respectively). ACh hyperpolarized arterial, but not venous, VSM (e.g., 11.7 +/- 2.4 mV at 10(-4) M). ACh-induced hyperpolarization was eliminated by 30 mg x kg(-1) x h(-1) propofol. Assuming a close inverse correlation between magnitude of VSM E(m) and contractile force, these results suggest that propofol attenuates both sympathetic neural and nonneural regulation of VSM tone. They also suggest that propofol and ACh may act competitively in the second messenger cascade regulating VSM K+ channel activity in mesenteric resistance arteries. IMPLICATIONS: Vascular smooth muscle (VSM) contractile force responses to the IV anesthetic, propofol, were indirectly assessed by VSM membrane potential changes to clarify the mechanisms underlying attenuation of peripheral vascular control of arterial blood pressure. Results indicate that propofol-induced VSM membrane hyperpolarization and coupled reduction of VSM contractile force underlie such attenuation.

Acetylcholine↗
PubMed2002

Changes of propofol concentration in cerebrospinal fluid during continuous infusion.

UNLABELLED: We studied the changes in the propofol concentration in the cerebrospinal fluid (CSF) in 14 patients, undergoing elective intracranial procedures, who were anesthetized with propofol administered by target-controlled infusion. During anesthesia, fentanyl and cisatracurium were administered as required. After intubation of the trachea, the lungs of the patients were ventilated to normocapnia with an oxygen-air mixture (FIO(2) = 0.33). Arterial blood and CSF samples (from an intraventricular drain) were collected between 90-180 min after the induction of anesthesia. Blood propofol concentrations were stable, between 5.0 +/- 1.89 and 4.5 +/- 1.7 microg/mL (mean +/- SD). There was a significant decrease in the CSF propofol concentration, from 52.2 +/- 35.01 ng/mL at 90 min to 28.6 +/- 21.9 ng/mL at 150 min (P < 0.05). The CSF propofol concentration at 180 min (21.4 +/- 14.0 ng/mL) was not significantly different from the concentration at 150 min. Some possible reasons for this decrease after commencing continuous intraventricular drainage are discussed. IMPLICATIONS: Propofol concentrations in the cerebrospinal fluid in neurosurgical patients Propofol concentration in cerebrospinal fluid of investigated patients decreased significantly after starting intraventricular drainage, despite relatively steady blood propofol concentrations. These results supplement the limited information about propofol pharmacokinetics in the human central nervous system.

Adult↗
PubMed2003

The effects of clonidine premedication on the blood pressure and tachycardiac responses to ephedrine in elderly and young patients during propofol anesthesia.

UNLABELLED: We studied the pressor and tachycardiac responses to ephedrine in elderly and young patients given either clonidine or midazolam during propofol anesthesia. In the first experiment, elderly (>60 yr) and young (20-45 yr) patients were randomly allocated to one of four groups according to age and premedicated regimens (n = 16 each; elderly-clonidine [EC], elderly-midazolam [EM], young-clonidine [YC], and young-midazolam [YM]). Under propofol anesthesia, ephedrine was injected, and hemodynamic measurements were made. In the second experiment, with clonidine premedication, elderly patients (n = 16) were given a reduced dose of propofol (EC-LP) and young patients (n = 16) were given an increased dose of propofol (YC-HP). Ephedrine was injected, and he- modynamic measurements were performed. The in-creases in mean blood pressure and heart rate were larger in the EC group than in the EM, YM, and EC-LP groups (P < 0.05). In the YC-HP group, the pressor response to ephedrine tended to be augmented as compared with the YC group but was not statistically significant. These results suggest that clonidine premedication augmented the pressor and tachycardiac responses to ephedrine, especially in elderly patients during a standard dose of propofol anesthesia, and that clonidine, age, and propofol could be involved in the augmentation of the blood pressure and tachycardiac responses to ephedrine. IMPLICATIONS: Clonidine premedication augments the pressor and tachycardiac responses to ephedrine in elderly patients during standard or large doses of propofol anesthesia but does not augment during small doses of propofol anesthesia. Clonidine, age, and propofol could be involved in the augmentation of the pressor and tachycardiac responses to ephedrine.

Adjuvants, Anesthesia↗
PubMed1992

Propofol and barbiturate depression of spinal nociceptive neurotransmission.

Barbiturates are often described as non-analgesic or even hyperalgesic agents; the newer intravenous anesthetic agent propofol is said to be non-analgesic. Both propofol and barbiturates occupy sites on the GABAA receptor. The present study was designed to compare the effects of propofol and barbiturates on nociceptive-related neurotransmission in neonatal rat spinal cord; to search for actions that might be hyperalgesic; and to determine the extent to which propofol depression of nociceptive neurotransmission is mediated by GABAA receptors. The monosynaptic reflex, a slow ventral root potential (slow VRP) and the dorsal root potential (DRP) were recorded from isolated neonatal (1-5 days old) superfused rat spinal cords in response to electrical stimulation of a lumbar dorsal root. The slow VRP and the DRP are related to nociception. Propofol (0.5-10 microM), pentobarbital (1-10 microM), and thiopental (1-10 microM) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABAA agonist muscimol (0.2-1 microM) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABAA antagonist bicuculline (1 microM). Propofol depressed the response evoked by direct application of substance P. The DRP is a GABAA-mediated depolarization of primary afferent nerve terminals that diminishes the effectiveness of nociceptive input. Propofol and thiopental increased electrically evoked DRP amplitude and increased the DRP evoked by application of muscimol. Both propofol and barbiturates thus depressed the nociceptive-related slow VRP and enhanced the antinociceptive DRP; their effective concentrations are at or close to the general anesthetic range for these agents. No anti-analgesic or hyperalgesic effect was observed. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗