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Effect of propofol on ropivacaine metabolism in human liver microsomes.

A combination of the general anesthetic propofol and epidural anesthesia with a local anesthetic is widely used. The metabolism of ropivacaine and that of lidocaine are mediated by similar P450 isoforms. Previously, propofol was found to inhibit the metabolism of lidocaine in vitro. Here we investigated whether propofol inhibits the metabolism of ropivacaine using human liver microsomes in vitro. Ropivacaine (6.0 micromol.l(-1)) as the substrate and propofol (1-100 micromol.l(-1)) were reacted together using human microsomes. The concentrations of ropivacaine and its major metabolite 2',6'-pipecoloxylidide (PPX) were measured using high-performance liquid chromatography. The metabolic activity of ropivacaine was reflected in the production of PPX. The inhibitory effects of propofol on ropivacaine metabolism were observed to be dose-dependent. The IC50 of propofol was 34.9 micromol.l(-1). Propofol shows a competitive inhibitory effect on the metabolism of ropivacaine (i.e., PPX production mediated by CYP3A4) in human CYP systems in vitro.

Amides↗

Combined effects of propofol and mild hypothermia on cerebral metabolism and blood flow in rhesus monkey: a positron emission tomography study.

PURPOSE: Propofol reduces the cerebral metabolic rate for oxygen (CMRO2), regional CMRO2 (rCMRO2), cerebral blood flow (CBF), and regional CBF (rCBF), but maintains the coupling of cerebral metabolism and blood flow. Under mild to moderate hypothermia, the coupling is maintained, while rCBF is reduced, but no direct measurement of rCMRO2 has yet been reported. This study aimed to evaluate the effects of propofol under normothermic and mild hypothermic temperatures upon rCMRO2, rCBF, and their regional coupling, through direct measurement by positron emission tomography. METHODS: Rhesus monkeys were anesthetized with 65% nitrous oxide and propofol. Then rCBF and rCMRO2 were measured under four sets of conditions: infusion of a low-propofol dose (12 mg.kg(-1) x h(-1)) at normothermic temperatures (38 degrees C), a high dose (25 mg x kg(-1) x h(-1)) at normothermic temperatures, a low dose under mild hypothermia (35 degrees C), and a high dose under mild hypothermia. The ratio of rCBF/rCMRO(2) was calculated from these data. RESULTS: Reductions in CMRO2 and rCMRO2 in most regions were associated with two factors: the higher propofol dose and the induction of hypothermia, but there was no interaction between these factors. Concerning blood flow, no significant reduction was observed, except for CBF by the induction of hypothermia. The ratio of rCBF/rCMRO2 was constant in this study setting. CONCLUSION: During propofol anesthesia, it is possible to reduce cerebral metabolism throughout the entire brain as well as in any brain region by increasing the propofol dose or inducing hypothermia. The concurrent use of these two interventions has an additive effect on metabolism, and can be considered as safe, as their combination does not impair the coupling of cerebral metabolism and blood flow.

Anesthetics, Intravenous↗

Modulation of ventral pallidal dopamine and glutamate release by the intravenous anesthetic propofol studied by in vivo microdialysis.

The intravenous anesthetic propofol is reported to have various psychological side effects as hallucinations, sexual disinhibition, or euphoria. Hedonic and rewarding states like these are modulated by the dopaminergic system in the nucleus accumbens, prefrontal cortex and also in the ventral pallidum and by the glutamatergic system in the neocortex and limbic system. In the present study, propofol was administered either alone or in combination with the GABAA receptor antagonist bicuculline via reverse microdialysis into the ventral pallidum of freely moving rats. Dialysis fractions were taken every 20 min and analyzed for dopamine and glutamate using high performance liquid chromatography. Application of propofol decreased dopamine levels in the ventral pallidum. This effect seems to be mainly mediated through GABAA receptors, since it was compensated by the GABAA receptor antagonist bicuculline. Propofol and propofol plus bicuculline exerted no effect on glutamate release in this brain region. The reduced dopamine release in ventral pallidum was most probably mediated through a GABAergic feedback loop from the ventral pallidum via the nucleus accumbens to the dopaminergic neurons of the ventral tegmental area or by long loop feedback. As an increase but not a decrease of dopamine release in the ventral pallidum is involved in hedonic and rewarding properties, similar symptoms induced by propofol seem to be unrelated to an action of propofol in the ventral pallidum.

Anesthetics, Intravenous↗

Rapid measurement of blood propofol levels: a proof of concept study.

OBJECTIVE: Despite many advantages over traditional volatile anaesthetic techniques, propofol total intravenous anaesthesia (TIVA) makes up a small percentage of general anaesthetics administered. One of the reasons for this is the absence of a clinically useful method for measuring blood propofol concentrations. We have designed and tested a prototype system for rapidly measuring blood plasma levels of propofol using solid phase extraction (SPE) methodology, coupled with colorimetric and spectrometric techniques. METHODS: Multiple venous blood samples were taken from 17 subjects during induction of anaesthesia with propofol. Samples were analysed in duplicate on both the prototype system and using High Performance Liquid Chromatography (HPLC). The prototype monitor response was calibrated against known methanol-based propofol standards and an estimate of the plasma concentration of propofol derived from regression analysis of the standard responses. RESULTS: Bland Altman analysis from a total of 87 samples gave 95% limits of agreement between the two methods of -0.34 to 0.42 microg mL(-1) (with no significant bias). The mean absolute prediction error was 8.9(7.5)%. The run time per sample on the prototype system was 4.5 min, including sample preparation. CONCLUSION: The results show that this methodology may be suitable for rapid and accurate clinical monitoring of propofol levels during general anaesthesia.

Anesthesia, General↗

Smooth muscle relaxant effects of propofol and ketamine in isolated guinea-pig trachea.

The effects of anesthetics on airway smooth muscle tone are important in the management of patients with asthma. In the present study we evaluated the effect of propofol and ketamine on isolated guinea-pig tracheal preparations mounted for recording isometric contractile force. In a concentration-dependent way both drugs produced 100% relaxation irrespective of whether tracheal tone was spontaneous or induced by carbachol, histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. The relaxant potency of propofol was dependent of the formulation of the drug used. Propofol showed an about 3 times higher potency when solubilized with hydroxypropyl-beta-cyclodextrin compared with an oil-in-water emulsion of the drug (Diprivan). Propofol had the greatest potency on tracheal preparations with spontaneous tone (EC50 = 4.0 +/- 0.9 microM). Ketamine preferentially relaxed contractions elicited by carbachol (EC50 = 120.8 +/- 5.2 microM) and had a lower potency than propofol when tone was spontaneous or induced by other tracheal spasmogens. Since propofol was a more effective tracheal relaxant in vitro than ketamine, the possibility that propofol, like ketamine, may inhibit bronchoconstriction during anesthesia should be studied further.

Animals↗

Propofol infusion technique for outpatient general anesthesia.

PURPOSE: The purpose was to evaluate the suitability of a continuous propofol infusion in combination with alfentanil for outpatient general anesthesia in an oral and maxillofacial surgery practice. MATERIALS AND METHODS: Twenty-seven ASA 1 patients were selected to undergo oral and maxillofacial surgery outpatient procedures of short duration. Induction of anesthesia was accomplished with 1 mg/kg intravenous (i.v.) propofol and 10 micrograms/kg i.v. alfentanil. Local anesthesia was administered. General anesthesia was maintained with a continuous infusion of 150 micrograms/kg/min of propofol. Various physical and psychomotor responses were recorded during induction, maintenance, emergence, and recovery. RESULTS: Anesthesia was successfully induced in all patients with single, slowly titrated, bolus doses of 1 mg/kg of propofol and 10 micrograms/kg of alfentanil. Induction of general anesthesia occurred in less than 1 minute in all cases and no excitatory phenomena, tremor, or hypertonus were observed. Maintenance of anesthesia was adequately accomplished and cardiovascular parameters remained within acceptable limits throughout the procedure. The average length of surgery was 22 minutes. Movement to surgical stimulus was minimal and easily managed with additional local anesthetic and/or a 10-mg bolus of propofol. Time to eye opening was approximately 5 minutes from the discontinuation of the propofol infusion. No emergence phenomena were observed. All patients were ready for discharge with baseline psychomotor activity within 30 minutes following the end of the procedure. The average total dose of propofol was 350 mg and the average dose of alfentanil was 750 micrograms. CONCLUSION: This anesthetic technique has numerous advantages with minimal side effects, and should be considered for routine use for outpatient general anesthesia in oral and maxillofacial surgery.

Adolescent↗

The differential cost of anesthesia and recovery with propofol-nitrous oxide anesthesia versus thiopental sodium-isoflurane-nitrous oxide anesthesia.

STUDY OBJECTIVE: To assess the recovery room profile of propofol in outpatient anesthesia and to compare it to the profile of a standard technique. DESIGN: A comparative, randomized, double-blind, third-party open study. SETTING: Ambulatory Surgery Center at The Emory Clinic. PATIENTS: Ninety-nine ASA physical status I, II, or III nonpregnant female patients who had been diagnosed as needing breast biopsies. INTERVENTIONS: All patients were given 1 microgram/kg of fentanyl prior to induction. Those in the propofol group were induced with 2.0 to 2.5 mg/kg of propofol and maintained with a 100 to 200 microgram/kg/min infusion of propofol with nitrous oxide (N2O) in oxygen (O2). In the thiopental sodium-isoflurane group, patients were induced with 4.0 to 5.0 mg/kg of thiopental sodium and maintained with isoflurane and N2O in O2. MEASUREMENTS AND MAIN RESULTS: Recovery from anesthesia was assessed by an evaluator who was unaware of the anesthetic technique used for each patient. Immediate recovery time was measured in terms of awakening, response to verbal command, and orientation to time and place. A brief postoperative follow-up questionnaire was completed to assess the patients' subjective feelings regarding their ability to eat, concentrate, and resume normal activities. In the thiopental sodium-isoflurane group, 15 of 50 patients (30%) had nausea and vomiting, but in the propofol group, only 4 of 49 patients (8.1%) had nausea and vomiting (p less than 0.01). The latter group resumed normal activity (i.e., reading and watching television) 7.93 +/- 0.76 hours postanesthesia, whereas the thiopental sodium-isoflurane group resumed normal activity 17.02 +/- 1.21 hours postanesthesia (p less than 0.001). Patients in the propofol group returned to work in an average of 1.5 +/- 0.09 days, compared with 2.0 +/- 0.09 days for the thiopental sodium-isoflurane group (p less than 0.001). CONCLUSIONS: The propofol group needed less nursing care and returned to more productive activity earlier than did the thiopental sodium-isoflurane group.

Ambulatory Surgical Procedures↗

Propofol versus midazolam for monitored sedation: a comparison of intraoperative and recovery parameters.

STUDY OBJECTIVE: To compare intraoperative and recovery parameters in patients who received either propofol infusion (PI), propofol bolus (PB), or midazolam bolus (MZ) for sedation. DESIGN: Randomized clinical study. SETTING: Medical/surgical patients in a specialized hospital. PATIENTS: Ninety patients, aged 18 to 85 years, scheduled for central venous access for chemotherapy and/or total parenteral nutrition. INTERVENTIONS: In 30 patients, sedation was induced with MZ 0.02 mg/kg intravenously (i.v.), repeated every 2 to 3 minutes to achieve a sedation level of 3 (eyes closed, responds to verbal stimulus) (SL3). Maintenance was with MZ 0.005 mg/kg i.v. repeated as necessary to maintain SL3. In both propofol groups (30 patients each), induction of sedation was with a bolus of propofol 0.75 to 1.0 mg/kg i.v. Maintenance in the PB group was with propofol 0.25 mg/kg IV, repeated as necessary to maintain SL3. Maintenance in the PI group was with propofol 2 to 4 mg/kg/hr or 33 to 66 micrograms/kg/min to maintain SL3. MEASUREMENTS AND MAIN RESULTS: Blood pressure, heart rate, respiratory rate, oxygen saturation, and sedation level were monitored each minute for 5 minutes and then at 5-minute intervals during the procedure. A right atrial blood sample was taken for pH and partial pressure of carbon dioxide at maximum sedation. Adequate sedation was achieved in all three groups. The time to reach SL3 was significantly shorter in the PB group than in the PI and MZ groups (p < 0.05 and p < 0.01, respectively). Cardiovascular and respiratory parameters were remarkably stable. Immediate recovery, as judged by spontaneous eye opening, response to commands, and ability to state date of birth, was significantly shorter in both the PB and PI groups than in the MZ group (p < 0.0001). Intermediate recovery, as measured by sedation score at recovery entry, Aldrete score, and time to standing, was slower in the MZ group (p < 0.05 for the MZ group vs. the PB and PI groups for sedation score and Aldrete score; p < 0.05 for the MZ group vs. the PI group in time to standing). Psychomotor recovery, judged by digit symbol substitution tests, was significantly faster in the PB and PI groups (p < 0.05 vs. the MZ group). Amnesia, measured by picture recall, was significantly greater in the MZ group than in the PI and PB groups (p < 0.05). Mood changes were measured on a visual analog scale. All groups showed improvement. Nausea, headache, dizziness, blurred vision, appetite, tension, pain, depression, drowsiness, and ability to concentrate were evaluated in the preoperative and postoperative periods. The frequency did not differ significantly between groups due to confounding factors such as postoperative chemotherapy and premedicant drugs. CONCLUSION: The PI, PB, and MZ groups all gave excellent sedation for patients undergoing surgical procedures with local anesthesia. Amnesia was greatest with midazolam, and recovery was more rapid with propofol.

Adolescent↗

Which induction drug for cesarean section? A comparison of thiopental sodium, propofol, and midazolam.

STUDY OBJECTIVE: To determine maternal and neonatal effects of three different induction drugs (thiopental sodium, propofol, and midazolam) for cesarean section. DESIGN: Randomized, double-blind study. SETTING: Inpatient obstetric department at a general hospital. PATIENTS: 90 healthy patients undergoing elective cesarean section with general anesthesia. INTERVENTIONS: 3 groups of 30 patients each receiving thiopental 5 mg/kg, propofol 2.4 mg/kg, or midazolam 0.3 mg/kg for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Time to induce anesthesia, hemodynamic changes, depth of anesthesia, recovery after anesthesia, placental transfer, and neonatal outcome (Apgar and neurobehavioral examinations) were studied. In the thiopental and midazolam groups, systolic blood pressure and heart rate rose following endotracheal intubation and skin incision (p < 0.001 and p < 0.0025, respectively), while in the propofol group, there was significant hypotension after induction (p < 0.005). Electroencephalographic patterns showed a light depth of anesthesia with propofol and midazolam between anesthesia induction and delivery, confirmed by the presence of clinical signs of light anesthesia in 50% of propofol patients and 43% of midazolam patients. Time to induce anesthesia was longer with midazolam (p < 0.0001). Neonates in the midazolam and propofol groups had lower Apgar and neurobehavioral scores than those in the thiopental group. Umbilical artery to umbilical vein ratios were above 1 in the propofol and midazolam groups. CONCLUSION: Thiopental still remains the first-choice induction drug for cesarean section. The slow induction time with midazolam may put the mother at risk for pulmonary inhalation. A plane of anesthesia that may risk awareness and potential neonatal depression is the main drawback of the two newer induction drugs.

Adult↗

Compatibility of propofol, fentanyl, and vecuronium mixtures designed for potential use in anesthesia and patient transport.

STUDY OBJECTIVE: To determine whether propofol emulsion, fentanyl, and vecuronium remain compatible and stable when mixed in clinically appropriate concentrations. DESIGN: Seven separate in vitro experiments. Two different propofol-fentanyl-vecuronium mixtures were formulated. Regular assays of propofol, fentanyl, and vecuronium were performed during a 90-minute infusion period and also during storage of one of the mixtures for 30 days at 4 degrees C, 22 degrees C, and 30 degrees C. Initial and storage pH were determined, and assays of the three drugs were performed when pH of the mixtures was varied between 1.4 and 12.7. Emulsion stability was assessed by measuring immediate and delayed alterations in droplet charge (zeta potential) and size. Finally, samples of the stored mixtures were incubated in culture medium for one week. SETTING: Teaching hospital and university laboratories. MEASUREMENTS AND MAIN RESULTS: Concentrations of the three drugs remained unchanged during infusion. During storage, concentrations of all three drugs were stable for two weeks at 4 degrees C or 22 degrees C, and for several days at 30 degrees C. Initial pH of the two mixtures was 5.1 and 5.3, and pH of the stored mixture increased slowly after 8 days. When the pH of mixtures was greater than or equal to 5.6, concentrations of fentanyl and vecuronium were unstable, but the concentration of propofol remained unchanged. Despite a reduction in zeta potential, immediate droplet size was essentially unchanged. No microbial growth was detected in stored mixtures. CONCLUSION: The propofol, fentanyl, and vecuronium mixtures studied were compatible and stable immediately after mixing. Appropriate in vitro compatibility testing is recommended before clinical evaluation of propofol-opioid or propofol-opioid-muscle relaxant mixtures.

Anesthesia↗

Propofol-fentanyl anesthesia: a comparison with isoflurane-fentanyl anesthesia in coronary artery bypass grafting and valve replacement surgery.

The hemodynamic effects of propofol-fentanyl and isoflurane-fentanyl anesthesia during the prebypass period were compared in 42 patients undergoing coronary artery bypass grafting (CABG) and 22 patients undergoing valve replacement (VR) for stenotic lesions. Anesthesia was induced with fentanyl, 25 micrograms/kg, and pancuronium, 0.1 mg/kg, and was maintained with a propofol infusion commenced at 4 mg/kg/h (range 1 to 10 mg/kg/h) or with isoflurane commenced at 1% (range 0 to 2%). Additional fentanyl, 7.5 micrograms/kg, was given before sternotomy. Hemodynamic measurements were made before induction of anesthesia and at various times in the prebypass period. In the VR group, there were no significant differences between the two anesthetics in any hemodynamic variables during the study. Significant decreases (P < 0.05) in mean arterial pressure (MAP 14%), left ventricular stroke work index (LVSWI 29%), and stroke volume index (SVI 24%) occurred after 15 minutes of propofol anesthesia in the CABG group. With isoflurane MAP was well maintained with reductions in LVSWI and SVI of 22% and 20%, respectively. Isoflurane was, however, associated with a significant increase in heart rate (HR) in the CABG group (P < 0.05), whereas no significant change in HR occurred in CABG or VR patients receiving propofol. With both techniques there were no significant changes in right-sided or left-sided filling pressures or in systemic vascular resistance index in the CABG or VR groups, except for a decrease in pulmonary artery occlusion pressure in the propofol VR group and isoflurane CABG group at the time of aortic cannulation. Propofol produced similar hemodynamic changes in the CABG and VR groups. Both anesthetic techniques caused myocardial depression and effectively controlled the autonomic responses to sternotomy in both groups. The study suggests that propofol-fentanyl anesthesia is an acceptable technique for CABG surgery and for VR in patients with stenotic valvular heart disease.

Adolescent↗

Propofol ameliorates liver dysfunction and inhibits aortic superoxide level in conscious rats with endotoxic shock.

Propofol, widely used as a sedative agent, is known to exert antioxidant and anti-inflammatory effects in vitro. We studied the effects of propofol on hemodynamics and the function of several organs in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (lipopolysaccharide) caused hypotension, vascular hyporeactivity and tachycardia as well as significant lung, liver and kidney damage. Hepatocellular damage caused by lipopolysaccharide for 6 h was significantly attenuated in the lipopolysaccharide+propofol group. Aortic superoxide anion (O(2)(radical)(-)) production, but not plasma nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level, was also suppressed by propofol in lipopolysaccharide-injected rats. Light microscopy showed that propofol attenuated the marked infiltration of neutrophils in liver tissues from lipopolysaccharide-injected rats. Moreover, the survival rate of the lipopolysaccharide+propofol group at 16 h was significantly increased when compared with that of the lipopolysaccharide group (53% vs. 12%). These results suggest that inhibition of aortic O(2)(radical)(-) production and amelioration of liver dysfunction contribute to the beneficial effect of propofol in conscious rats with endotoxic shock.

Animals↗

Propofol, an anesthetic possessing neuroprotective action against oxidative stress, promotes the process of cell death induced by H2O2 in rat thymocytes.

Propofol (2,6-diisopropylphenol) is a general anesthetic possessing a neuroprotective action against oxidative stress produced by H2O2. H2O2 induces an exposure of phosphatidylserine on outer surface of cell membranes, resulting in change in membrane phospholipid arrangement, in rat thymocytes. Since propofol is highly lipophilic, the agent is presumed to interact with membrane lipids and hence to modify the cell vulnerability to H2O2. Therefore, to test the possibility, we have examined the effect of propofol on rat thymocytes simultaneously incubated with H2O2. Although propofol (up to 30 microM) alone did not significantly affect the cell viability, the agent at 10 microM started to increase the population of dead cells in the presence of 3 mM H2O2 and the significant increase was observed at 30 microM. Propofol at clinically relevant concentrations (10-30 microM) facilitated the process of cell death induced by H2O2 in rat thymocytes. However, propofol protected rat brain neurons against the oxidative stress induced by H2O2 under same experimental condition. Therefore, the action of propofol may be dependent on the type of cells.

Anesthetics, Intravenous↗

Evaluation of new propofol aqueous solutions for intravenous anesthesia.

The aim of this study was to evaluate the potential of using three new aqueous formulations of propofol for intravenous (i.v.) anesthesia. The first formulation can be prepared by using hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as a solubilizer. Phase-solubility analysis showed a linear increase in the solubility of propofol to a maximum of 16.6 mg/ml in 30% (w/v) HP-gamma-CD. Moreover, phase-solubility studies demonstrated that 18% (w/v) HP-beta-CD or SBE-beta-CD and 24% HP-gamma-CD solutions, respectively, are required to dissolve 10mg of propofol in 1 ml of the vehicle; the corresponding solutions, however, are slightly hypertonic. Autoclaving the 10 mg/ml CD-based formulations for 15 min at 121 degrees C caused a change in pH which was more evident for the HP-beta-CD-based formulation while, in any case, no detectable fall in propofol concentration was observed. The second formulation herein evaluated is a co-solvent mixture (i.e., propylene glycol:water (1:1), v/v) which is able to dissolve 10 mg/ml of the anesthetic agent. However, although it is simple to prepare, the stability of this formulation is limited. The third aqueous formulation can be prepared by using the prolinate ester of propofol and its water-soluble derivative dissolved in water at equimolar concentration. The efficacy of all these formulations as i.v. anesthetic agents was assessed using a pharmacodynamic measure (onset and duration of loss of the righting reflex, LORR), and compared with that of the commercial propofol formulation (Diprivan, 10 mg/ml) in rats. It was found that minimizing the amount of cyclodextrin in all CD-based formulations, anesthetic effects comparable to those of propofol in Diprivan were still observed. Moreover, the prolinate ester constituted an effective i.v. anesthetic formulation with the same duration of action but with a longer induction time than Diprivan.

Anesthetics, Intravenous↗

Does propofol or caffeic acid phenethyl ester prevent lung injury after hindlimb ischaemia-reperfusion in ventilated rats?

BACKGROUND: To investigate the effects of propofol and caffeic acid phenethyl ester (CAPE) on prevention of lung injury as a remote organ after performing hindlimb ischaemia-reperfusion (IR) in a rat model. METHODS: The animals were divided randomly into one of four groups: sham, no IR (n = 8), control, IR, (n = 8), CAPE group, IR with CAPE, (n = 8), propofol group, IR with P, (n = 8). After the rats were anaesthetised, the animals in the CAPE group received CAPE of 10 micromol, in the propofol group received propofol 50 mg/kg, in the control group received a similar volume of saline solution by means of intraperitoneal injection 1 h before reperfusion. After 4 h of ischaemia the tourniquet was removed and the animals were released for reperfusion for 4 h thereafter. At the end of the reperfusion period, a median sternotomy was performed. A blood sample was obtained for plasma malondialdehyde (MDA). The lung tissues were also removed for MDA assays, myeloperoxidase (MPO) activity, and histopathological examination. RESULTS: Plasma and lung MDA levels, and lung MPO activity were significantly higher in the control group compared to the other groups (p < 0.0005). In the CAPE group, these were significantly lower compared to the control group (p < 0.0005). Also, propofol caused a marked reduction in the MDA levels and MPO activity compared with control group (p < 0.0005), with no significant difference compared to that of the sham group. Histopathologically, the scores resulted in a grade zero (8/8) in the sham group, 3 (3/8) or 4 (5/8) in the control group, 1 (2/8) or 2 (6/8) in the CAPE group, and 1 (3/8) or 2 (5/8) in the propofol group. CONCLUSION: Propofol and CAPE seem to be effective in protecting against lung injury caused by increased oxidative stress and neutrophil accumulation after hindlimb IR in a rat model.

Animals↗

The effects of alfentanil or remifentanil pretreatment on propofol injection pain.

STUDY OBJECTIVE: To compare the efficacy of alfentanil, remifentanil, and saline in minimizing the propofol injection pain. DESIGN: Randomized, double-blind study. SETTING: University hospital. PATIENTS: 175 ASA physical status I and II, adult female patients undergoing minor gynecological procedures with general anesthesia. INTERVENTIONS: Unpremedicated patients were randomly allocated to one of four groups. Patients received 2 mL (1 mg) of alfentanil (n=43), 2 mL of remifentanil 0.01 mg (n = 43), 2 mL of remifentanil 0.02 mg (n=45), or 2 mL of saline (n=44) 30 seconds prior to administration 5 mL of propofol 1%. MEASUREMENTS: Patients were asked whether they had pain due to propofol injection. Their pain scores were evaluated with a Visual Analogue Scale. In the Postanesthesia Care Unit, frequency of postoperative nausea, vomiting, hypotension, and flushing were all determined. MAIN RESULT: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group (p <0.05). When the alfentanil group was compared with the remifentanil groups, significant differences in pain relief associated with injection of propofol (p <0.001) were noted. Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p <0.001). CONCLUSIONS: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group. Remifentanil was effective in preventing propofol injection pain, and should be used at a dose of at least 0.02 mg for this purpose. Remifentanil may be an alternative drug for prevention of propofol injection pain.

Adult↗

A novel mixture of propofol, alfentanil, and lidocaine for regional block with monitored anesthesia care in ophthalmic surgery.

STUDY OBJECTIVE: The purpose of this study is to determine the efficacy and safety of sedation/analgesia using a mixture of propofol, alfentanil, and lidocaine. DESIGN: A retrospective case review was undertaken. SETTING: This study took place at a university medical center. PATIENTS: Eighty-nine American Society of Anesthesiologists physical status 1, 2, and 3 adult patients undergoing ophthalmic surgery with regional block and monitored anesthesia care were studied. INTERVENTION: Six milliliters of propofol, 2 mL of alfentanil, and 2 mL of 2% lidocaine (6-2-2 mixture) were freshly mixed. The bolus dose was determined based on the patients' age: 5 microg/kg of alfentanil (and 0.3 mg/kg of propofol) for patients older than 75 years; the dose increased 1 mug/kg per 10-year decrease in age; and up to 9 microg/kg of alfentanil (0.54 mg/kg of propofol) for patients younger than 45 years. Regional block was performed at 1 minute after bolus completion. Blood pressure (BP), Sa(O2), electrocardiogram, capnography, clinical signs of sedation, responses to block, need for airway support, nausea and vomiting (N/V), pain due to propofol infusion, recall, and patient and surgeon satisfaction were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy-eight percent of patients achieved analgesia and sedation without adverse response to the block. Twelve percent achieved good analgesia and sedation with only eyebrow movement upon needle insertion. Twenty-seven percent had respiratory depression but were able to follow commands and maintain adequate ventilation. Two percent had brief apnea alleviated by chin lift or jaw thrust. None had pain because of propofol infusion or N/V. Before sedation, average systolic BP was significantly increased (P < 0.0001) compared with baseline. After sedation and block, systolic BP decreased 6% from baseline (P < 0.005). CONCLUSION: Adjusted for age and weight, the dose of the 6-2-2 mixture met the sedation requirements for most patients. With a low incidence of need for airway support, no pain during infusion, and no N/V, this novel mixture of propofol, alfentanil, and lidocaine provided adequate analgesia and sedation as well as hemodynamic stability for ophthalmic surgery under regional block.

Adult↗

Propofol anesthesia in children does not induce sister chromatid exchanges in lymphocytes.

BACKGROUND: Propofol is frequently used for general anesthesia in children although little is known about possible genotoxic effects in humans. We investigated the formation of sister chromatid exchanges (SCE) in metaphase chromosomes of T-lymphocytes of children as a marker for possible genotoxocity following total intravenous anesthesia with propofol for minor surgical procedures. METHODS: 40 children ASA classification I-III were included (ASA I n=34, ASA II n=5, ASA III n=1) in the study. Anesthesia was induced by propofol (3mg/kg) and alfentanil. Succinylcholine or rocuronium were administered for muscle relaxation. After tracheal intubation anesthesia was maintained by continuous propofol infusion at 12 mg/(kgh). Blood samples were drawn before induction and after termination of anesthesia. Following a 72 h cell culture period, 25 T-lymphocyte metaphases per blood sample for all children were analyzed for SCE frequencies. RESULTS: Total intravenous anesthesia with propofol on children did not influence SCE rates in metaphase chromosomes of T-lymphocytes. No SCE differences could be detected between blood samples before initiation and after termination of anesthesia (Wilcoxon signed rank test). Slightly elevated SCE rates were obtained in T-lymphocytes of girls compared to boys, but these differences did not reach statistical significance. CONCLUSIONS: Propofol anesthesia under the chosen conditions did not induce the formation of SCE in children in vivo. No genotoxic effect of a short term exposure to propofol during pediatric anesthesia had been observed.

Adolescent↗