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PubMed1999

Inhibitory effects of propofol on acetylcholine-induced, endothelium-dependent relaxation and prostacyclin synthesis in rabbit mesenteric resistance arteries.

BACKGROUND: Propofol (2,6-diisopropylphenol) modulates endothelium-dependent relaxation in some arterial preparations. The effect of propofol on endothelium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified. METHODS: The effect of propofol was examined on acetylcholine-induced membrane potential changes in the presence of N(G)-nitro-L-arginine (L-NOARG) in endothelium-intact rabbit mesenteric resistance arteries in vitro. The effects of propofol were also examined on the endothelium-dependent relaxation and prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine. The effect of propofol on the relaxation induced by a prostacyclin analogue was examined in strips treated with L-NOARG and diclofenac. RESULTS: Acetylcholine produced an initial and a slow membrane hyperpolarization. Propofol, 10 microM, and diclofenac each inhibited the acetylcholine-induced slow hyperpolarization, but not the initial hyperpolarization. Acetylcholine produced an endothelium-dependent relaxation that was significantly inhibited by propofol, 10 microM, and diclofenac. Propofol, 10 microM, greatly inhibited the acetylcholine-induced synthesis of prostacyclin, as did diclofenac. Propofol, 10 microM, had no effect on the relaxation induced by a prostacyclin analog. CONCLUSIONS: In rabbit mesenteric resistance arteries, propofol inhibits the synthesis of prostacyclin and thus attenuates acetylcholine-induced, endothelium-dependent responses. Our results may help to explain why some actions seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.

Acetylcholine↗
PubMed2001

Efficacy of propofol to prevent bronchoconstriction: effects of preservative.

BACKGROUND: The authors previously showed that propofol attenuates bronchoconstriction. Recently, a newer formulation of propofol with metabisulfite preservative has been introduced. metabisulfite causes airway narrowing in asthmatics. Therefore, we tested whether the preservative metabisulfite abolishes the ability of propofol to attenuate bronchoconstriction. The authors used a sheep model in which anesthetic agents could be directly administered to the airways via the bronchial artery. METHODS: After Internal Review Board approval, seven sheep were anesthetized (pentobarbital 20 mg x kg(-1) x h(-1)) and paralyzed (pancuronium 2 mg), and the lungs were ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, propofol with and without metabisulfite, lidocaine (5 mg/ml), or metabisulfite alone (0.125 mg/ml) was infused into the bronchial artery at a rate of 0.06, 0.2, or 0.6 ml/min. After 10 min, airway resistance (Raw) was measured before and after vagal nerve stimulation (30 Hz, 30-ms duration at 30 V for 9 s.) and methacholine challenge (2 microg/ml at 2 ml/min in the bronchial artery). Data were expressed as a percent of maximal response and analyzed by analysis of variance with correction and with significance accepted at P < or = 0.05. RESULTS: Raw at baseline was not significantly different among the four drugs (P = 0.87). Infusion of lidocaine and propofol without metabisulfite into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction (P = 0.001). Propofol with metabisulfite had no effect on vagal nerve stimulation-induced bronchoconstriction (P = 0.40). There was a significant difference in the ability of propofol without metabisulfite compared with propofol with metabisulfite to attenuate vagal nerve stimulation-induced (P = 0.0001) and methacholine-induced bronchoconstriction (P = 0.0001). CONCLUSION: Propofol without metabisulfite and lidocaine attenuated vagal nerve stimulation-induced bronchoconstriction in a dose-dependent fashion. Propofol without metabisulfite also decreased direct airway smooth muscle constriction. The preservative used for propofol can have a dramatic effect on its ability to attenuate bronchoconstriction.

Anesthetics, Intravenous↗
PubMed2003

Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index.

BACKGROUND: Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. METHODS: The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error. RESULTS: A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction). CONCLUSIONS: These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.

Adult↗
PubMed2003

Propofol and sufentanil titration with the bispectral index to provide anesthesia for coronary artery surgery.

BACKGROUND: To provide anesthesia for cardiac surgery, hypnotics and opioids are frequently titrated on variables such as mean arterial pressure and heart rate. In this study conducted in patients scheduled to undergo coronary artery bypass grafting, propofol and sufentanil, both administered by computer-controlled infusion, were titrated on the Bispectral Index (BIS) values using a predefined algorithm. METHODS: After written informed consent, 110 patients, 95 men and 15 women aged 61 (9) yr [mean (SD)], were randomly allocated to receive predicted sufentanil effect site concentrations (Ce) of 0.5, 0.75, 1, 1.25, and 1.5 ng/ml, decreased by a third after sternotomy (groups 1-5). Target induction propofol concentration was 1.5 microg/ml and subsequently adjusted on BIS values. The following parameters were recorded: BIS values, predicted propofol Ce, the number of changes of propofol target, mean arterial pressure, heart rate, the number of bolus injection and doses of vasoconstrictor and vasodilator drugs, time to tracheal extubation, postoperative awareness and satisfaction scores, and cumulative morphine doses for the first postoperative day. RESULTS: One patient randomized to group 1 required 0.75 ng/ml sufentanil Ce instead of 0.5 ng/ml for increased BIS values on tracheal intubation. BIS values were similar in the five groups. The predicted propofol Ce values were different (P < 0.05; analysis of variance) among the five groups: 1.59 (0.47) to 1.23 (0.25) microg/ml in group 1 and group 4, respectively. Significantly fewer changes of propofol target were required in group 4 as compared to group 1. There were no differences among the five groups for mean arterial pressure, heart rate, time to tracheal extubation, awareness, satisfaction scores, and morphine requirements. CONCLUSION: These results suggest the BIS, as part of an algorithm that uses both the absolute BIS value and its increase following tracheal intubation, can be used to effectively titrate both propofol and sufentanil. A predicted sufentanil Ce of 1.25 ng/ml before and 0.8 ng/ml after sternotomy was associated with the lowest predicted propofol Ce and fewer changes of propofol target. Lower sufentanil concentrations required higher propofol concentrations and more frequent changes of the target propofol concentration and were associated with similar hemodynamic tolerance.

Adolescent↗
PubMed2004

Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.

BACKGROUND: Propofol is neuroprotective when administered immediately after stroke. The therapeutic window, duration of administration, and antioxidant mechanisms of propofol in neuroprotection are not known. The effects of propofol after stroke were examined in the conscious animal. The authors have previously shown that light propofol anesthesia (25 mg x kg(-1) x h(-1)) for a period of 4 h, even if delayed 1 h after the onset of ischemia, decreases infarct volume 3 days after the stroke. METHODS: Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor, endothelin (6 pmol in 3 microl) into the striatum. Propofol treatment after ischemia was delayed up to 4 h, and the infusion period shortened from 4 h to 1 h. Infarct volume was assessed 3 or 21 days after the stroke. Neurologic outcome was evaluated on days 14-21 after ischemia. Tissue ascorbate and glutathione concentrations were evaluated at 4 h and 3 days after ischemia. RESULTS: Infarct volumes were reduced 3 days after ischemia when propofol treatment (25 mg x kg(-1) x h(-1)) was delayed for 2 h (0.5+/-0.3 mm3) but not 4 h (2.0+/-0.9 mm3), compared with intralipid controls (2.4 +/- 0.7 mm3). The propofol infusion period of 3 h but not 1 h reduced infarct volume. Propofol treatment did not reduce infarct volume 21 days after the stroke, although motor function improvements (Montoya staircase test) were observed 14-21 days after the stroke. Propofol neuroprotection was independent of tissue ascorbate and glutathione concentrations. CONCLUSIONS: Concurrent or delayed administration of propofol is neuroprotective 3 days after ischemia. Although there were no differences in infarct volume 21 days after ischemia, propofol-treated animals had functional improvements at this time.

Animals↗
PubMed2004

Determination of the pharmacodynamic interaction of propofol and remifentanil during esophagogastroduodenoscopy in children.

BACKGROUND: Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 microg/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients. METHODS: The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol. RESULTS: There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with remifentanil. CONCLUSION: A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces the concentration of propofol required for adequate anesthesia for esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil infusion yields minimal additional decrease in propofol concentration and may increase the risk of side effects.

Child↗
PubMed2005

Effect of propofol on carotid body chemosensitivity and cholinergic chemotransduction.

BACKGROUND: Propofol decreases the acute hypoxic ventilatory response in humans and depresses in vivo carotid body chemosensitivity. The mechanisms behind this impaired oxygen sensing and signaling are not understood. Cholinergic transmission is involved in oxygen signaling, and because general anesthetics such as propofol have affinity to neuronal nicotinic acetylcholine receptors, the authors hypothesized that propofol depresses carotid body chemosensitivity and cholinergic signaling. METHODS: An isolated rabbit carotid body preparation was used. Chemoreceptor activity was recorded from the whole carotid sinus nerve. The effect of propofol on carotid body chemosensitivity was tested at three different degrees of PO2 reduction. Nicotine-induced chemoreceptor response was evaluated using bolus doses of nicotine given before and after propofol 10-500 microM. The contribution of the gamma-aminobutyric acid A receptor complex was tested by addition of gamma-aminobutyric acid A receptor antagonists. RESULTS: Propofol reduced carotid body chemosensitivity; the magnitude of depression was dependent on the reduction in PO2. Furthermore, propofol caused a concentration-dependent (10-500 microM) depression of nicotine-induced chemoreceptor response, with a 50% inhibitory concentration (propofol) of 40 microM. Bicuculline in combination with propofol did not have any additional effect, whereas addition of picrotoxin gave a slightly more pronounced inhibition. CONCLUSIONS: It is concluded that propofol impairs carotid body chemosensitivity, the magnitude of depression being dependent on the severity of PO2 reduction, and that propofol causes a concentration-dependent block of cholinergic chemotransduction via the carotid sinus nerve, whereas it seems unlikely that an activation of the gamma-aminobutyric acid A receptor complex is involved in this interaction.

Anesthetics, Intravenous↗
PubMed2005

Experimental conditions are important determinants of cardiac inotropic effects of propofol.

BACKGROUND: The rationale for this study is that the depressant effect of propofol on cardiac function in vitro is highly variable but may be explained by differences in the temperature and stimulation frequency used for the study. Both temperature and stimulation frequency are known to modulate cellular mechanisms that regulate intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in cardiac muscle. The authors hypothesized that temperature and stimulation frequency play a major role in determining propofol-induced alterations in [Ca2+]i and contraction in individual, electrically stimulated cardiomyocytes and the function of isolated perfused hearts. METHODS: Freshly isolated myocytes were obtained from adult rat hearts, loaded with fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte shortening were simultaneously measured in individual cells at 28 degrees or 37 degrees C at various stimulation frequencies (0.3, 0.5, 1, 2, and 3 Hz) with and without propofol. Langendorff perfused hearts paced at 180 or 330 beats/min were used to assess the effects of propofol on overall cardiac function. RESULTS: At 28 degrees C (hypothermic) and, to a lesser extent, at 37 degrees C (normothermic), increasing stimulation frequency increased peak shortening and [Ca2+]i. Times to peak shortening and rate of relengthening were more prolonged at 28 degrees C compared with 37 degrees C at low stimulation frequencies (0.3 Hz), whereas the same conditions for [Ca2+]i were not altered by temperature. At 0.3 Hz and 28 degrees C, propofol caused a dose-dependent decrease in peak shortening and peak [Ca2+]i. These changes were greater at 28 degrees C compared with 37 degrees C and involved activation of protein kinase C. At a frequency of 2 Hz, there was a rightward shift in the dose-response relation for propofol on [Ca2+]i and shortening at both 37 degrees and 28 degrees C compared with that observed at 0.3 Hz. In Langendorff perfused hearts paced at 330 beats/min, clinically relevant concentrations of propofol decreased left ventricular developed pressure, with the effect being less at 28 degrees C compared with 37 degrees C. In contrast, only a supraclinical concentration of propofol decreased left ventricular developed pressure at 28 degrees C at either stimulation frequency. CONCLUSION: These results demonstrate that temperature and stimulation frequency alter the inhibitory effect of propofol on cardiomyocyte [Ca2+]i and contraction. In isolated cardiomyocytes, the inhibitory effects of propofol are more pronounced during hypothermia and at higher stimulation frequencies and involve activation of protein kinase C. In Langendorff perfused hearts at constant heart rate, the inhibitory effects of propofol at clinically relevant concentrations are more pronounced during normothermic conditions.

Anesthetics, Intravenous↗
PubMed2005

Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain.

AIMS: The principal site for the metabolism of propofol is the liver. However, the total body clearance of propofol is greater than the generally accepted hepatic blood flow. In this study, we determined the elimination of propofol in the liver, lungs, brain and kidneys by measuring the arterial-venous blood concentration at steady state in patients undergoing cardiac surgery. METHODS: After induction of anaesthesia, propofol was infused continuously during surgery. For measurement of propofol concentration, blood samples were collected from the radial and pulmonary artery at predetermined intervals. In addition, blood samples from hepatic and internal jugular vein were collected at the same times in 19 patients in whom a hepatic venous catheter was fitted and the other six in whom an internal jugular venous catheter was fitted, respectively. In six out of 19 patients fitted with a hepatic venous catheter, blood samples from the radial artery and the renal vein were also collected at the same time, when the catheter was inserted into the right renal vein before insertion into the hepatic vein. RESULTS: Hepatic clearance of propofol was approximately 60% of total body clearance. The hepatic extraction ratio of propofol was 0.87 +/- 0.09. There was no significant difference in the concentration of propofol between the radial, pulmonary arteries and internal jugular vein. However, a high level of propofol extraction in the kidneys was observed--the renal extraction ratio being 0.70 +/- 0.13. CONCLUSIONS: We have demonstrated substantial renal extraction of propofol in human. Metabolic clearance of propofol by the kidneys accounts for almost one-third of total body clearance and may be the major contributor to the extrahepatic elimination of this drug.

Adult↗
PubMedDate not supplied

Electrophysiological effects of propofol on the normal cardiac conduction system.

To determine the electrophysiological effects of propofol and to explain the potential mechanism(s) whereby it causes bradyarrhythmias, 10 closed-chest pigs weighing 20-25 kg were studied. Each animal was premedicated by intramuscular administration of ketamine hydrochloride, intubated, and mechanically ventilated. Femoral arterial and venous catheters were placed, and a comprehensive electrophysiologic evaluation was performed at baseline and after two doses (1 mg/kg i.v. bolus and 0.1 mg/kg/min infusion and an extra 1- mg/kg i.v. bolus and 0.2 mg/kg/min infusion) of propofol. The electrophysiological effects obtained on low-and high-dose propofol were compared to baseline values. Propofol caused a dose-related decrease in sinus cycle length (baseline 565 +/- 36 ms, low-dose propofol 541 +/- 28, high-dose propofol 527 +/- 26 ms; p < 0.05), a prolongation of the corrected sinus node recovery time (baseline 119 +/- 35 ms, low-dose propofol 126 +/- 32, high-dose propofol 130 +/- 30 ms; p < 0.01), and an increase in the His-ventricular interval (baseline 33 +/- 4 ms, low-dose propofol 36 +/- 4, high-dose propofol 40 +/- 3 ms; p < 0.005). All other electrophysiological parameters remained unchanged, and there were no cases of spontaneous atrioventricular block or sinus pauses. We conclude that propofol causes dose-related depression of sinus node and His-Purkinje system functions, but has no effect on the atrioventricular node function and on the conduction properties of atrial and ventricular tissues in normal pig hearts.

Anesthetics, Intravenous↗
PubMed2005

Propofol specifically inhibits mitochondrial membrane potential but not complex I NADH dehydrogenase activity, thus reducing cellular ATP biosynthesis and migration of macrophages.

Propofol is a widely used intravenous anesthetic agent. Our previous study showed that a therapeutic concentration of propofol can modulate macrophage functions. Mitochondria play critical roles in the maintenance of macrophage activities. This study attempted to evaluate further the effects of mitochondria on the propofol-induced suppression of macrophage functions using mouse macrophage-like Raw 264.7 cells as the experimental model. Macrophages were exposed to a clinically relevant concentration of propofol for 1, 6, and 24 h. Analysis by the Trypan blue exclusion method revealed that propofol was not cytotoxic to macrophages. Exposure of macrophages to propofol did not affect mitochondrial NADH dehydrogenase activity of complex I. However, analysis of flow cytometry showed that propofol significantly decreased the mitochondrial membrane potential of macrophages. Cellular levels of ATP in macrophages were significantly reduced after propofol administration. In parallel with the dysfunction of mitochondria, the chemotactic analysis showed that exposure to propofol significantly inhibited the migration of macrophages. This study shows that a therapeutic concentration of propofol can specifically reduce the mitochondrial membrane potential, but there is no such effect on complex I NADH dehydrogenase activity. Modulation of the mitochondrial membrane potential may decrease the biosynthesis of cellular ATP and thus reduce the chemotactic activity of macrophages. This study provides in vitro data to validate mitochondrial dysfunction as a possible critical cause for propofol-induced immunosuppression of macrophage functions.

Adenosine Triphosphate↗
PubMed1992

Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts.

The authors examined direct myocardial and coronary vascular responses to the anesthetic induction agents etomidate, ketamine, midazolam, propofol, and thiopental and compared their effects on attenuating autoregulation of coronary flow as assessed by changes in oxygen supply/demand relationships. Spontaneous heart rate, atrioventricular conduction time during atrial pacing, left ventricular pressure (LVP), coronary flow (CF), percent oxygen extraction, oxygen delivery, and myocardial oxygen consumption (MVo2) were examined in 55 isolated guinea pig hearts divided into five groups of 11 each. Hearts were perfused at constant pressure with one of the drugs administered at steady-state concentrations increasing from 0.5 microM to 1 mM. Adenosine was given to test maximal CF. At concentrations below 10 microM no significant changes were observed; beyond 50 microM for midazolam, etomidate, and propofol, and 100 microM for thiopental and ketamine, each agent caused progressive but differential decreases in heart rate, atrioventricular conduction time (leading to atrioventricular dissociation), LVP, +dLVP/dtmax, percent oxygen extraction, and MVo2. The concentrations (microM) at which +dLVP/dtmax was reduced by 50% were as follows: etomidate, 82 +/- 2 (mean +/- SEM); propofol, 91 +/- 4; midazolam, 105 +/- 8; thiopental, 156 +/- 11; and ketamine, 323 +/- 7; the rank order of potency was etomidate = propofol = midazolam greater than thiopental greater than ketamine; results were similar for LVP. At the 100 microM concentration, CF was decreased 11% +/- 2% by ketamine and 5% +/- 3% by thiopental but was increased 17% +/- 6% by etomidate, 21% +/- 5% by midazolam, and near maximally to 57% +/- 10% by propofol; MVo2 was decreased 8% +/- 4% by thiopental, 10% +/- 5% by ketamine, 19% +/- 5% by midazolam, 29% +/- 7% by etomidate, and 37% +/- 5% by propofol; oxygen delivery/MVo2 was unchanged by thiopental and ketamine but was increased 62% +/- 7% by midazolam, 71% +/- 9% by etomidate, and 150% +/- 15% by propofol. Between 100 microM and 1 mM, thiopental and ketamine did not increase CF but decreased MVo2 and percent oxygen extraction, whereas propofol maximally increased CF and decreased MVo2 and midazolam and etomidate had intermediate effects. These results indicate that on a molar basis, propofol, and less so midazolam and etomidate, depress cardiac function moderately more than thiopental and ketamine, and that propofol markedly attenuates autoregulation by causing coronary vasodilation. With doses used to induce anesthesia, propofol and thiopental appear to depress cardiac function more than ketamine or etomidate.

Adenosine↗
PubMed1994

Propofol for ambulatory gynecologic laparoscopy: does omission of nitrous oxide alter postoperative emetic sequelae and recovery?

The role of nitrous oxide in postoperative emesis is controversial. This prospective randomized study was performed to compare the emetic sequelae and quality of recovery between a group of patients anesthetized with propofol alone and a group anesthetized with propofol plus nitrous oxide. Seventy patients, ASA grade I or II, scheduled for ambulatory gynecologic laparoscopy under general anesthesia were included. Most factors which could influence the incidence of postoperative emesis were controlled. The overall incidence of emetic sequelae during the first 24 h postoperatively was 25% in the group anesthetized with propofol alone versus 29% for the group anesthetized with propofol and nitrous oxide. The incidence of emetic sequelae requiring therapeutic intervention was 13% and 6%, respectively. This difference was not statistically significant. The group of patients who received propofol alone required an average propofol dose of 221.5 +/- 71.9 micrograms.kg-1.min-1 to maintain anesthesia compared with 162.5 +/- 43.9 micrograms.kg-1.min-1 for the group receiving propofol plus nitrous oxide (P < 0.001). The time from discontinuation of propofol to eye-opening and orientation was significantly longer in patients anesthetized with propofol alone. Otherwise, the recovery variables were comparable between the two groups. We conclude that supplementing propofol with nitrous oxide in patients undergoing ambulatory laparoscopy reduces the requirements of propofol, expedites immediate recovery (emergence), and does not increase the incidence of postoperative emesis. This tends to confirm that there is no clinical advantage to omitting nitrous oxide.

Adult↗
PubMed2003

Propofol decreases reperfusion-induced arrhythmias in a model of "border zone" between normal and ischemic-reperfused guinea pig myocardium.

UNLABELLED: We examined the effect of propofol on the main mechanisms involved in ischemia/reperfusion-induced arrhythmias (i.e., spontaneous arrhythmias, conduction blocks, and dispersion of repolarization) in vitro. In a double-chamber bath, guinea pig right ventricular muscle strips were subjected to 30 min of simulated ischemia followed by 30 min of reperfusion (altered zone; AZ) and to standard conditions (normal zone; NZ). Action potential (AP) parameters were recorded in the NZ and AZ. We studied the effects of Intralipid(R) and of propofol at 10(-6), 10(-5), and 2 x 10(-5) M on the occurrence of spontaneous sustained arrhythmias, conduction blocks, and the dispersion of repolarization. In NZ, Intralipid and propofol did not significantly modify the AP parameters. Propofol, but not Intralipid, lessened the ischemia-induced decrease in AP duration (APD) at 90% of repolarization (APD(90)) and attenuated the APD dispersion around the "border zone." Propofol did not modify the occurrence of ischemia-induced arrhythmias. Propofol 10(-6) M, but not Intralipid or propofol at 10(-5) and 2 x 10(-5) M, decreased the occurrence of ischemia-induced conduction blocks. Propofol decreased the occurrence of reperfusion-induced spontaneous sustained arrhythmias. We conclude that, in vitro, propofol attenuated the ischemia-induced APD(90) dispersion around the "border zone" and decreased the occurrence of spontaneous arrhythmias related to myocardial reperfusion injury. IMPLICATIONS: In isolated guinea pig ventricular myocardium propofol, but not Intralipid(R), attenuated the ischemia-induced shortening of action potential and, thus, the dispersion of repolarization and decreased the occurrence of spontaneous ventricular arrhythmia related to reperfusion injury. This result may be important for propofol-based anesthesia in patients at high risk for intraoperative ischemia.

Action Potentials↗
PubMed2003

Propofol suppresses the cortical somatosensory evoked potential in rats.

UNLABELLED: The dose-response curve for the effect of volatile anesthetics on the somatosensory evoked potential (SEP) is well described, but for propofol, the large dose segment of the curve is undefined. We describe the effect of increasing plasma concentrations of propofol on cortical SEPs in 18 rats. After surgical preparation under ketamine anesthesia, a remifentanil infusion was begun at 2.5, 5, or 10 microg x kg(-1) x min(-1). After 20 min, the propofol infusion was initiated at 20 mg x kg(-1) x h(-1) and was increased to 40, 60, and 80 mg x kg(-1) x h(-1) at 20-min intervals. SEP was recorded before remifentanil infusion, before propofol infusion rate changes, and 30 min after discontinuing propofol infusion. In six additional rats, the plasma concentrations of propofol after each 20-min infusion were measured using gas chromatography. Remifentanil did not have a significant effect, but propofol significantly depressed the SEP amplitude and prolonged the latency at infusion rates of 40 mg x kg(-1) x h(-1) and more. Propofol's effect was dose-dependent, but even at 80 mg x kg(-1) x h(-1) with an estimated plasma concentration of 31.6 +/- 3.4 microg/mL (10.8 50% effective concentration), a measurable response was present in 44.5% of rats. These results suggest that even at large doses, propofol and remifentanil provide adequate conditions for SEP monitoring. IMPLICATIONS: Rats demonstrate dose-dependent somatosensory evoked potential (SEP) suppression with propofol but not with remifentanil. However, SEP suppression by 50% occurred only at large (1.5 EC(50)) concentrations of propofol, and a measurable SEP was present in 8 of 18 rats, even at 10.8 EC(50).

Analgesics, Opioid↗
PubMed2004

Amplification by hyperoxia of coronary vasodilation induced by propofol.

UNLABELLED: We tested the hypothesis that in vitro coronary and myocardial effects of propofol (10-300 microM) should be significantly modified in an isolated and erythrocyte-perfused rabbit heart model in the absence (PaO(2) = 137 +/- 16 mm Hg, n = 12) or in the presence (PaO(2) = 541 +/- 138 mm Hg, n = 12) of hyperoxia. The induction of hyperoxia provoked a significant coronary vasoconstriction (-13% +/- 7%). Propofol induced increased coronary vasodilation in the presence of hyperoxia. Because high oxygen tension has been reported to induce a coronary vasoconstriction mediated by the closure of adenosine triphosphate-sensitive potassium channels, we studied the effects of propofol in 2 additional groups of hearts (n = 6 in each group) pretreated by glibenclamide (0.6 microM) and cromakalim (0.5 microM) in the absence and presence of hyperoxia, respectively. The pretreatment by glibenclamide induced a coronary vasoconstriction (-16% +/- 7%) which did not affect propofol coronary vasodilation. The pretreatment by cromakalim abolished the amplification of propofol coronary vasodilation in the presence of hyperoxia. Propofol induced a significant decrease in myocardial performance for a concentration >100 micro M both in the absence and presence of hyperoxia. We conclude that propofol coronary vasodilation is amplified in the presence of hyperoxia. This phenomenon is not explained by the previous coronary vasoconstriction induced by glibenclamide. However, the pretreatment of hearts by cromakalim abolished the amplification of propofol coronary vasodilation in the presence of hyperoxia. The myocardial effects of propofol were not affected by the presence of hyperoxia. IMPLICATIONS: Propofol induced a coronary vasodilation that was amplified in the presence of hyperoxia. This phenomenon does not seem to be related to previous coronary vasoconstriction. The myocardial effects of propofol were not significantly modified in the presence of hyperoxia.

ATP-Binding Cassette Transporters↗
PubMed2005

Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures.

The neuroprotective potency of anesthetics such as propofol compared to mild hypothermia remains undefined. Therefore, we determined whether propofol at two clinically relevant concentrations is as effective as mild hypothermia in preventing delayed neuron death in hippocampal slice cultures (HSC). Survival of neurons was assessed 2 and 3 days after 1 h oxygen and glucose deprivation (OGD) either at 37 degrees C (with or without 10 or 100 microM propofol) or at an average temperature of 35 degrees C during OGD (mild hypothermia). Cell death in CA1, CA3, and dentate neurons in each slice was measured with propidium iodide fluorescence. Mild hypothermia eliminated death in CA1, CA3, and dentate neurons but propofol protected dentate neurons only at a concentration of 10 microM; the more ischemia vulnerable CA1 and CA3 neurons were not protected by either 10 microM or 100 microM propofol. In slice cultures, the toxicity of 100 muM N-methyl-D-aspartate (NMDA), 500 microM glutamate, and 20 microM alpha-amino-5-methyl-4-isoxazole propionic acid (AMPA) was not reduced by 100 microM propofol. Because propofol neuroprotection may involve gamma-aminobutyric acid (GABA)-mediated indirect inhibition of glutamate receptors (GluRs), the effects of propofol on GluR activity (calcium influx induced by GluR agonists) were studied in CA1 neurons in HSC, in isolated CA1 neurons, and in cortical brain slices. Propofol (100 and 200 microM, approximate burst suppression concentrations) decreased glutamate-mediated [Ca2+]i increases (Delta[Ca2+]i) responses by 25%-35% in isolated CA1 neurons and reduced glutamate and NMDA Delta[Ca2+]i in acute and cultured hippocampal slices by 35%-50%. In both CA1 neurons and cortical slices, blocking GABAA receptors with picrotoxin reduced the inhibition of GluRs substantially. We conclude that mild hypothermia, but not propofol, protects CA1 and CA3 neurons in hippocampal slice cultures subjected to oxygen and glucose deprivation. Propofol was not neuroprotective at concentrations that reduce glutamate and NMDA receptor responses in cortical and hippocampal neurons.

Anesthetics, Intravenous↗
PubMed2005

A comparison of pain on intravenous injection between two preparations of propofol.

Propofol is frequently used for sedation, induction, and maintenance of anesthesia. It is, however, associated with pain on injection. Propofol-Lipuro has an oil phase that allows a larger proportion of propofol to be dissolved in it and, thereby, apparently reduces pain. However, studies investigating this have had methodological limitations. We devised a randomized, double-blind, crossover study comparing pain on injection between two preparations of propofol, Diprivan and Propofol-Lipuro, in subanesthetic doses. Sixty healthy patients received the drugs in random order via the same injection site separated by 10 min and a 0.9% saline flush. Pain was assessed using a verbal rating score (VRS) during and at 1-min time points after injection. Differences in VRS between the two propofol preparations at different time points in each patient were analyzed. In patients who were given Diprivan first followed by Propofol-Lipuro (group D-P), pain was significantly reduced with Propofol-Lipuro compared with Diprivan during initial injection (median difference in VRS = 2 [interquartile range 0-2], P = 0.002) and at 1 min (3 [0-4], P < 0.001). In patients who were given Propofol-Lipuro first followed by Diprivan (group P-D), no significant differences in VRS were shown. Propofol-Lipuro is associated with reduced injection pain compared with Diprivan and also seems to attenuate subsequent injection pain of Diprivan when administered first. The mechanism is unknown, but may be related to a reduction in the concentration of propofol in the aqueous phase.

Adult↗