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PubMed1996

Propofol induces dilation and inhibits constriction in guinea pig basilar arteries.

The present study investigated the direct action of propofol on guinea pig basilar arterial rings and the possible underlying mechanisms. Arterial rings, with and without endothelium, were mounted in an organ bath and connected to an isometric tension recording system. The effects of propofol (0.63-20 micrograms/mL) were compared with those of Intralipid (n = 13) after equilibration and precontraction by 5-hydroxytryptamine (5-HT). In another group (n = 8), after pretreatment with either propofol (5 micrograms/mL) or Intralipid, a contraction by 35 mM KCl was obtained and compared. Another group (n = 12) were incubated in Ca(2+)-free Krebs buffer and after depolarization by 45 mM KCl, a dose-response curve to CaCl2 was obtained to compare the effect of propofol (5 micrograms/mL) and Intralipid on the influx of Ca2+. Finally, in Ca(2+)-free Krebs buffer, the effect of Intralipid or propofol on 5-HT-evoked contractions (n = 6) were assessed. Propofol caused significant dilation with or without endothelium present, inhibited KCl-induced contraction, and significantly lowered the dose-response curve for CaCl2. In Ca(2+)-free Krebs buffer, propofol significantly inhibited 5-HT-evoked contraction, which is dependent on intracellular Ca(2+)-release. In conclusion, propofol inhibited vaso-constriction and induced vasodilation by mechanisms consistent with reduced extracellular calcium influx and suppressed intracellular calcium release.

Anesthetics↗
PubMed1996

Awakening, clinical recovery, and psychomotor effects after desflurane and propofol anesthesia.

We compared postanesthetic and residual recovery of desflurane versus propofol anesthesia. Twenty volunteers were anesthetized for 1 h at 1-wk intervals with either propofol (induction) plus desflurane (1.25 minimum alveolar anesthetic concentration) in O2 (PD), propofol plus desflurane in N2O-O2 (PDN), propofol plus propofol infusion with N2O-O2 (PPN), or desflurane (induction) plus desflurane in O2 (DD). Awakening and clinical recovery were measured. Psychomotor skills (attention, coordination, reactive skills, and memory) were tested before and 1,3,5, and 7 h after anesthesia. Awakening was fastest in Group PDN. At 1 h after anesthesia, the subjects given desflurane for maintenance (PD, PDN, and DD) performed significantly (P < 0.05-0.01) better in several psychomotor tests compared with those whose anesthesia was maintained with propofol (PPN). However, subjects met criteria for home readiness as fast after PPN as after PDN anesthesia (mean times +/- SE until fitness for discharge were 126 +/- 20, 81 +/- 14, 70 +/- 7, and 106 +/- 14 min after PD, PDN, PPN, and DD, respectively). Awakening and early psychomotor recovery for as long as 1 h after anesthesia is faster after desflurane than after propofol, but there was no difference in time to home readiness or in residual effects thereafter between propofol and desflurane with N2O in O2.

Adult↗
PubMed1996

Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling.

As a highly lipophilic drug, propofol may interact with lipophilic domains in addition to its likely primary site of action on the gamma-aminobutyrateA) (GABA(A)) receptor. Likely candidates for such interaction are the G protein-coupled membrane receptors for lipid intercellular mediators. The phospholipid lysophosphatidate (LP) has attracted attention as such a signaling molecule. It has a variety of biological actions, including vasoconstriction. We therefore studied the interaction between propofol and the LP receptor. Intracellular Ca2+ release in response to LP was assessed by measuring C1- flux through Ca(2+)-activated C1- channels in Xenopus oocytes. The average charge movement in response to LP 10(-7)M was 2.0 +/- 0.2 microCoulombs. Propofol in Intralipid (0.01%) dose-dependently inhibited LP signaling (50% inhibitory concentration [IC50] 5.38 microM). Propofol 28 microM inhibited LP signaling by 81%. Intralipid (0.01%) was without effect. To ascertain that intracellular signaling pathways and the Ca(2+)-activated C1- channel were not affected by propofol, we tested the effects of propofol (5.6 microM) on currents induced by methylcholine (10(-7)M) in oocytes expressing the m1 muscarinic acetylcholine receptor. No inhibition was observed. As both receptors share the same intracellular signaling pathway, we conclude that clinically relevant concentrations of propofol most likely inhibit the LP receptor or its G protein. Inhibition of LP signaling may explain some of propofol's vasodilating actions.

Anesthetics, Intravenous↗
PubMed1997

Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol-induced sedation.

The bispectral (BIS) index and 95% spectral edge frequency (SEF) of the electroencephalograph (EEG) have been used to study the anesthetic and sedative effects of intravenously (i.v.) administered drugs. This prospective study was designed to evaluate the effectiveness of the BIS index and 95% SEF for assessing the level of propofol-induced sedation and amnesia during regional anesthesia. Ten consenting adult patients undergoing surgery with regional anesthesia were administered propofol in increments of 10-20 mg i.v., every 5-10 min until they became unresponsive to tactile stimulation (i.e., mild prodding or shaking). The BIS index and 95% SEF were continuously recorded from a bifrontal montage (Fp1-Cz and Fp2-Cz) using the Aspect B500 monitor. The depth of sedation was assessed clinically at 5- to 10-min intervals using the observer's assessment of alertness/sedation (OAA/S) scale, with 1 = no response to tactile stimulation to 5 = wide awake. Each patient was shown a picture of an animal (cat) prior to administration of an initial dose of propofol, 40 mg i.v.. Subsequently, patients were administered intermittent bolus doses of propofol, 10-20 mg i.v., and shown different pictures upon achieving OAA/S scores of 4, 3, and 2 during the onset of and recovery from propofol-induced sedation. Picture recall was tested upon arrival of the patient in the postanesthesia care unit (PACU). Of the two EEG variables studied, the BIS index exhibited a better correlation with the OAA/S scores during both the onset (Spearman's rho = 0.744) and recovery (Spearman's rho = 0.705) phases of propofol-induced sedation. With the increasing depth of sedation, there was a progressive decrease in the BIS index (OAA/S score of 5, BIS = 94.5 +/- 2.9; 4, 93.3 +/- 3.3; 3, 89 +/- 6.1; 2, 80.1 +/- 8.7; 1, 75.6 +/- 7.5; mean +/- SD). Conversely, there was a progressive increase in the BIS value during recovery from propofol sedation (OAA/S score of 1, BIS = 75.6 +/- 7.5; 2, 82.4 +/- 10.5; 3, 84.9 +/- 5.9; 4, 93.8 +/- 0.8). Although the changes in the 95% SEF values were less consistent during the onset phase, this EEG variable increased from 16.4 +/- 5.0 to 19.3 +/- 5.6 as the OAA/S score increased from 1 to 4 during the recovery phase. Patient recall of the intraoperative pictures decreased with increasing depth of sedation and decreasing BIS values (OAA/S:% BIS:% recall = 5:94.5 +/- 2.9:100%; 4:93.4 +/- 3:63%; 3:87.3 +/- 6.1:40%; 2:80.8 +/- 8.3:0%; 1:75.6 +/- 7.5:0%). The BIS index appears to be a useful variable for assessing the depth of propofol-induced sedation. Increasing depth of sedation was associated with a significant decrease in intraoperative picture recall.

Adult↗
PubMed1997

The arterial blood propofol concentration preventing movement in 50% of healthy women after skin incision.

To target appropriate drug concentrations and to facilitate comparisons between drugs, the potency of propofol must be firmly established. We therefore determined the arterial blood propofol concentration preventing movement in 50% of patients after skin incision and the ability of arterial blood pressure and heart rate to predict movement after incision. Fifteen healthy women scheduled for breast surgery were randomly assigned to computer-targeted propofol blood concentrations. No other drugs were administered. Fifteen minutes after starting the propofol infusion, a 5-cm skin incision was made. Patients were observed for gross purposeful movement for 1 min. Arterial blood was sampled for propofol to confirm steady-state blood concentrations. Arterial blood pressure and heart rate were measured noninvasively. Logistic regression was used to calculate the propofol blood concentrations and arterial blood pressures at which 50% and 95% of patients did not move after skin incision (CP50 and CP95, MABP50 and MABP95, respectively). The CP50 and CP95 values for propofol were 14.3 +/- 1.6 microg/mL (mean +/- SE) and 20.6 microg/mL, respectively. The MABP50 and MABP95 values were 63 +/- 4 mm Hg and 43 mm Hg, respectively. Heart rate did not differ significantly in patients who moved and who did not move. Propofol blood concentrations required to prevent movement in most patients resulted in significant arterial hypotension.

Adult↗
PubMed1997

Pharmacokinetics and pharmacodynamics of propofol in a new solvent.

UNLABELLED: Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation. IMPLICATIONS: Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.

Adult↗
PubMed1998

Propofol concentration required for endotracheal intubation with a laryngoscope or fiberscope and its interaction with fentanyl.

UNLABELLED: The administration of fentanyl with propofol reduces the blood concentration of propofol required to achieve adequate anesthesia for tracheal intubation. However, different intubation procedures have variable intensities of noxious stimulation and may require different levels of anesthesia. The goal of this study was to determine the propofol blood concentration at which 50% of patients did not respond to stimulation (Cp50) for laryngoscopy, intubation with a laryngoscope, insertion of a slotted oral-pharyngeal airway (Ovassapian airway), and intubation with a fiberscope when administered in conjunction with fentanyl. Patients undergoing elective surgery were given varying amounts of propofol or propofol with fentanyl, and their responses to the four procedures listed above were assessed. These experiments demonstrated that the propofol concentration required for intubation with a laryngoscope was similar to that for intubation with a fiberscope, and that the required level was reduced by fentanyl. Hemodynamic responses to intubation were lower with a fiberscope than with a laryngoscope. We conclude that almost the same concentrations of propofol or fentanyl are necessary for suppressing both of the somatic responses to tracheal intubation with a fiberscope or a laryngoscope. Hemodynamic responses were attenuated more during intubation with a fiberscope. IMPLICATIONS: The propofol blood concentrations at which 50% of patients did not respond to stimulation for laryngoscopy, tracheal intubation with a laryngoscope, and tracheal intubation with a fiberscope were 10.9, 19.6, and 19.9 microg/mL, respectively. These were reduced by fentanyl. Hemodynamic responses to intubation were less with a fiberscope than with a laryngoscope.

Adult↗
PubMed1998

Comparison of desflurane with isoflurane or propofol in spontaneously breathing ambulatory patients.

UNLABELLED: Desflurane is a potentially useful anesthetic for ambulatory surgery, but it has had limited evaluation in spontaneously breathing patients. After the induction of anesthesia with propofol and laryngeal mask insertion, 90 patients were randomized to receive isoflurane (0.25%-1%), propofol (50-200 microg x kg(-1) x min(-1)), or desflurane (1.4%-6%) for anesthetic maintenance. Respiratory complications were uncommon; only six patients coughed (three who received isoflurane, one who received propofol, and two who received desflurane), and no anesthetic produced significant respiratory depression. Purposeful movement was significantly more common with propofol (19 patients; 63%) compared with isoflurane (7 patients; 23%) or desflurane (2 patients; 6.7%), but no patient had recall. Emergence times were similar in the isoflurane, propofol, and desflurane groups (5.1 +/- 2.3, 5.6 +/- 3.1, and 4.4 +/- 1.4 min, respectively). Later recovery end points and pain and sedation visual analog scale scores did not differ among groups. Overall, 85 patients (94%) were free from postoperative nausea and vomiting. Desflurane produced few respiratory complications in spontaneously breathing ambulatory patients but offered no improvement in emergence or recovery compared with isoflurane. Propofol also did not reduce recovery times or side effects; however, it was more difficult to maintain an adequate depth of anesthesia. We conclude that neither desflurane nor propofol offered any major advantages over the older anesthetic, isoflurane, under the conditions of our study. IMPLICATIONS: The new inhaled anesthetic desflurane is acceptable in spontaneously breathing outpatients despite its known ability to irritate the airway. The i.v. anesthetic propofol was associated with more patient movement (without awareness) during surgery. Neither anesthetic conferred any clinically significant advantages over the older inhaled drug, isoflurane.

Adult↗
PubMed1999

Comparison of sevoflurane with propofol for laryngeal mask airway insertion in adults.

UNLABELLED: We performed a prospective, randomized, controlled trial to compare the quality and ease of laryngeal mask airway (LMA) insertion after either rapid inhaled sevoflurane or i.v. propofol induction of anesthesia. Seventy-six unpremedicated ASA physical status I or II patients were anesthetized with either a single vital capacity breath of sevoflurane 8% or i.v. propofol 3 mg/kg, which produced equally rapid loss of consciousness (40.5 +/- 13.9 vs 37.7 +/- 9.9 s; P > 0.05). The LMA was inserted more rapidly in patients in the propofol group (74 +/- 29 vs 127 +/- 35 s; P < 0.01) and required fewer attempts (1.2 vs 1.6; P < 0.05) than the sevoflurane group. There was a greater incidence of initially impossible mouth opening in the sevoflurane group (45% vs 21%; P < 0.05). Once mouth opening was possible, the degree of attenuation of laryngeal reflexes was similar. The overall incidence of complications related to LMA insertion, especially apnea (32% vs 0%; P < 0.01), was more frequent in the propofol group (82% vs 26%; P < 0.01). There were four failures of LMA insertion in the propofol group and none in the sevoflurane group. Both groups had stable hemodynamic profiles and good patient satisfaction. We conclude that sevoflurane vital capacity breath induction compares favorably with i.v. propofol induction for LMA insertion in adults. However, prolonged jaw tightness after the sevoflurane induction of anesthesia may delay LMA insertion. IMPLICATIONS: In this randomized, controlled trial, we compared the ease of insertion of the laryngeal mask airway in adults after induction of anesthesia with either a sevoflurane vital capacity breath technique or propofol i.v.. We conclude that sevoflurane compares favorably with propofol, although prolonged jaw tightness may delay laryngeal mask airway insertion.

Adult↗
PubMed1999

Propofol anesthesia enhances pressor response to ephedrine in patients given clonidine.

UNLABELLED: We studied the hemodynamic effects of ephedrine in patients with or without clonidine premedication during either isoflurane or propofol anesthesia. Forty adult patients were randomly assigned to one of two groups: 20 patients received famotidine 20 mg orally (control group) and 20 received clonidine 3 microg/kg and famotidine 20 mg orally (clonidine group). Within each group, 10 patients were then anesthetized with isoflurane and 10 with propofol. Hemodynamic measurements were taken at 1-min intervals for 10 min after a bolus injection of ephedrine 0.1 mg/kg. The magnitude of the maximal pressor response to ephedrine was no different whether patients without clonidine were anesthetized with isoflurane (increase 5+/-7 mm Hg) or propofol (3+/-9 mm Hg); however, this response was greater (P<0.05) with propofol (17+/-6 mm Hg) versus isoflurane (6+/-5 mm Hg) in patients given clonidine. The arterial blood pressure increase in clonidine-premedicated patients with propofol anesthesia was the largest among the four subgroups. The heart rate response to ephedrine was not significant in patients anesthetized with isoflurane and was small but significant in those anesthetized with propofol. The present results, together with previous studies on the effect of ephedrine in patients medicated with clonidine, suggest that the interaction between clonidine and ephedrine is modulated by the anesthetic used. IMPLICATIONS: We evaluated the pressor response to ephedrine during isoflurane or propofol anesthesia with or without clonidine premedication. Our study suggests that, in anesthetized patients premedicated with clonidine, decreases in blood pressure may be easier to reverse with ephedrine with some types of anesthesia (e.g., propofol) than with others (e.g., isoflurane).

Adult↗
PubMed1999

The relaxant effect of propofol on guinea pig tracheal muscle is independent of airway epithelial function and beta-adrenoceptor activity.

UNLABELLED: Airway epithelium and vascular endothelium modulate the tension of the underlying smooth muscle by releasing relaxing factors such as prostanoids and nitric oxide (NO). We investigated whether the relaxant effect of propofol on airway smooth muscle is dependent on airway epithelial function. Tracheal spirals of female guinea pigs were mounted in water-jacketed organ baths filled with Krebs-bicarbonate buffer aerated with 95% O2 and 5% CO2 at 37 degrees C. Changes in isometric tension of the specimens were measured with a force-displacement transducer and recorded with a polygraph. Propofol (10(-4) to 10(-3) M) inhibited carbachol (CCh)-, histamine (HA)-, or endothelin-1-induced contractions of the muscles in a dose-dependent manner. Neither mechanical removal of the epithelial layer, chemical inhibition of epithelial synthesis of prostanoids, nor NO affected the relaxant effect of propofol on CCh- or HA-induced tracheal contraction. Furthermore, the blockade of beta-adrenoceptors did not change the relaxant effect of propofol. These results indicate that the relaxant effect of propofol on the airway smooth muscle is independent of the epithelial function or beta-adrenoceptor activity. Propofol is an excellent anesthetic for patients with hyperreactive airways in which the epithelial layer is damaged. IMPLICATIONS: Airway epithelium, as well as vascular endothelium, plays an important role in modulating the baseline tone and reactivity of underlying smooth muscle. We investigated, in vitro, whether the relaxant effect of propofol on airway smooth muscle is dependent on airway epithelial function. We suggest that propofol relaxes airway smooth muscle independently of the epithelial function.

Anesthetics, Intravenous↗
PubMed1999

Propofol decreases diaphragmatic contractility in dogs.

UNLABELLED: Volatile anesthetics depress diaphragmatic muscle function; however, no data are available regarding the effect of propofol on diaphragmatic contractility. We therefore studied this effect in dogs. Pentobarbital-anesthetized animals were divided into three groups of 10 each. Group I received only maintenance fluid; Group II was infused with a subhypnotic dose of propofol (0.1-mg/kg initial dose plus 1.5-mg x kg(-1) x h(-1) maintenance dose); Group III was infused with an anesthetic dose of propofol (0.1-mg/kg initial dose plus 6.0-mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of propofol in Groups II and III, Pdi at low-frequency (20-Hz) stimulation decreased from the baseline values (P < 0.05), whereas Pdi at high-frequency (100-Hz) stimulation did not change. Compared with Group I, Pdi at 20-Hz stimulation decreased during propofol administration in Groups II and III (P < 0.05). The decrease in Pdi was more in Group III than in Group II (P < 0.05). We conclude that propofol is associated with a dose-related inhibitory effect on diaphragmatic contractility in dogs. IMPLICATIONS: Propofol is an effective IV anesthetic for the induction and maintenance of anesthesia. Subhypnotic and anesthetic doses of propofol decrease diaphragmatic contractility in dogs.

Anesthetics, Intravenous↗
PubMed2000

The effects of propofol with and without ketamine on human cerebral blood flow velocity and CO(2) response.

UNLABELLED: The combination of propofol and ketamine has been used for total IV anesthesia. This study was designed to clarify the effects of propofol-ketamine anesthesia on cerebral circulation by using transcranial Doppler ultrasonography. In Study 1, we examined the time course of time-mean middle cerebral artery blood flow velocity (Vmca) after ketamine (n = 10) or saline (n = 6) administration during propofol anesthesia. In Study 2, CO(2) responses were measured under the following conditions: awake (Group C, n = 7), propofol anesthesia (Group D, n = 7), and propofol-ketamine anesthesia (Group E, n = 8). Ketamine administration during propofol anesthesia administration did not affect Vmca, mean arterial pressure, or heart rate. Vmca under normocapnia in Groups D and E were 36 +/- 3 and 37 +/- 3 cm/s (mean +/- SE), respectively. The values were significantly lower than that of Group C (70 +/- 3 cm/s). The CO(2) response slopes of Groups D and E were significantly lower than that of Group C, although there was no significant difference between Groups D and E. These results suggest that ketamine does not influence Vmca or the cerebrovascular CO(2) response during propofol anesthesia administration, although the sample size in each group was small. IMPLICATIONS: Our study suggests that ketamine does not influence middle cerebral artery blood flow velocity or the cerebrovascular CO(2) response assessed by transcranial Doppler ultrasonography during propofol anesthesia administration in patients without neurological complications.

Adult↗
PubMed2000

Reversal of rapacuronium block during propofol versus sevoflurane anesthesia.

UNLABELLED: We studied the antagonism of rapacuronium with edrophonium-atropine during propofol- or sevoflurane- based anesthesia in 60 healthy outpatients. After the induction of anesthesia with standardized doses of propofol and fentanyl, rapacuronium 1.5 mg/kg was administered to facilitate tracheal intubation. Patients were randomized to receive either a propofol infusion (100 microg. kg(-1). min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular block was monitored by using electromyography at the wrist and reversed with edrophonium 1.0 mg/kg and atropine 0.015 mg/kg when the first twitch (T(1)) response of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. The clinical duration of action (i.e., time to 25% T(1) recovery) was similar during both propofol (13.1 +/- 3.6 min) and sevoflu-rane (13.7 +/- 4.4 min) anesthesia. The time from 25% T(1) recovery to TOF ratio of 0.8 was also similar with propofol (3.4 +/- 2.1 min) and sevoflurane (5.9 +/- 8.7 min) (P > 0.05). Although none of the patients in the propofol group required more than 9 min to achieve a TOF ratio of 0. 8, two patients receiving sevoflurane required 31 min and 37 min. Adequate antagonism of rapacuronium block with edrophonium can be achieved within 10 min during propofol anesthesia. However, more prolonged recovery may occur in the presence of sevoflurane. IMPLICATIONS: We studied the reversal of rapacuronium-induced block with edrophonium and found that the residual rapacuronium block can be readily antagonized during propofol-based anesthesia. However, reversal of rapacuronium appears to be less predictable during sevoflurane-based anesthesia.

Adolescent↗
PubMed2000

The combined effect of age and premedication on the propofol requirements for induction by target-controlled infusion.

In this prospective study, we evaluated the combined influence of age and premedication on propofol requirements for the induction of anesthesia and their hemodynamic effects using a target-controlled infusion. We studied 180 patients separated into three age groups: 20-39 yr, 40-59 yr, and more than 59 yr. In each age group, patients were randomly allocated to receive either no premedication (n = 20), fentanyl (2 microg/kg) (n = 20), or midazolam (0.03 mg/kg) plus fentanyl (2 microg/kg) (n = 20). The concentration of propofol targeted for the induction was 5 microg/mL, to be reached in 2 min. The dose, time, and predicted plasma concentration of propofol at hypnosis were measured. Baseline and postinduction heart rate and arterial blood pressure were registered. Computer simulation was used to calculate the effect site propofol concentration at hypnosis. The concentration of propofol, effect site propofol concentration, time, and induction dose and their hemodynamic effect were significantly different among groups with respect to age and premedication. The combined effect of the two factors was additive, but without significant interaction. The propofol requirements were significantly less in the midazolam-fentanyl groups, regardless of age, and among the premedicated patients older than 60 yr compared with the other age groups. We conclude that the combined effect of age and premedication on the requirements of propofol for the induction of anesthesia should be considered when the concentration is targeted with a target-controlled infusion system.

Adjuvants, Anesthesia↗
PubMed2000

Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for induction of anesthesia?

UNLABELLED: Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125 microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15 compared with $13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM) for the induction of outpatient anesthesia. IMPLICATIONS: Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM).

Ambulatory Care↗
PubMed2000

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis.

UNLABELLED: We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 microg/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r(2) = 0.76 and 0.93, respectively; P<0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47+/-0.13 microV, mean +/- SD) was significantly (P<0.002) larger than with monaural stimulation (0.35+/-0.11 microV). During unconsciousness, the amplitude was 0.09+/-0.09 microV with monaural and 0.06+/-0.04 microV with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 SE) for monaural and 1.00 (0.00 SE) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. IMPLICATIONS: We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.

Adolescent↗
PubMed2001

A comparison of patient-controlled sedation using either remifentanil or remifentanil-propofol for shock wave lithotripsy.

UNLABELLED: Patient-controlled sedation (PCS) has been used for extracorporeal shock wave lithotripsy (SWL) because it allows for rapid individualized titration of anesthetics. Because of its sedating effects, the addition of propofol to remifentanil may improve patient tolerance of SWL with PCS. One hundred twenty patients were randomly assigned to receive remifentanil 10 microg or remifentanil 10 microg plus propofol 5 mg for PCS with zero-lockout interval. Nine patients in the Remifentanil group and three patients in the Remifentanil-Propofol group required additional sedatives to complete their SWL (P = 0.128). Compared with the Remifentanil group, the Remifentanil-Propofol group required less remifentanil, had a decreased incidence of postoperative nausea and vomiting, and had a better overall satisfaction level. However, they had an increased incidence of transient apnea and oxygen desaturation. The incidence of apnea was 15% in the Remifentanil group and 52% in the Remifentanil-Propofol group (P < 0.001). All patients were able to move themselves to the stretcher at the end of SWL, and median time to home discharge was <70 min in both groups. Both remifentanil and remifentanil-propofol were useful for PCS during SWL. IMPLICATIONS: The addition of propofol to remifentanil improves patient satisfaction and decreases postoperative nausea and vomiting. However, it causes more respiratory depression than remifentanil alone. When remifentanil-propofol is used with patient-controlled sedation, appropriate monitoring and a minimum 1-2 min lockout interval is required.

Adolescent↗