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Propofol is a new intravenous anaesthetic agent chemically unrelated to barbiturate, steroid, imidazole, or eugenol agents. It is available as 1% solution in an aqueous solution of 10% soya bean oil, 2.25% glycerol and 1.2% purified egg phosphatide. The desirable features of the drug are rapid, clear emergence from anaesthesia, lack of cumulation, lack of effect on adrenal steroidogenesis, and has no adverse effect on liver and renal function. In emulsion form, it does not release histamine, nor has it been associated with anaphylactoid reactions. Although, it causes pain on injection, it infrequently results in phlebitis or thrombosis. It causes hypotension and respiratory depression during induction. The induction dose in healthy adults is 2-2.5 mg/kg. Older or debilitated individuals require less propofol for induction.
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PMID:Pharmacology of propofol. 202 66

Propofol (Diprivan), a modern intravenous hypnotic, produces a reduction in both cardiac index (CI) and mean arterial pressure (MAP). Ketamine (Ketanest), a potent analgesic, in contrast, causes an increase in MAP and CI. The aim of the present study was to investigate whether the combination of propofol and ketamine can give better hemodynamic stability during the induction and maintenance of general anesthesia than propofol used with fentanyl, whose cardiodepressant actions may cumulate. METHODS. For induction of general anesthesia 10 patients (ASA I and II) each received 3-5 boluses of propofol (0.5 mg.kg-1 during 35 s until predetermined level of anesthesia was reached (stage D2/E0 according to [20]) followed by a continuous propofol infusion (0.120 mg.kg-1.min). Fentanyl 0.1 mg was administered to each patient in group A for induction of anesthesia and again if evident pain was present. In group B ketamine was given following a pharmacokinetic model based on computer-simulated calculation. After an initial bolus of 38 mg injected within 2 min further doses of 42 mg, 35 mg, 32 mg and 28 mg ketamine were administered over 30 min at a time. Signs of evident pain were treated by means of supplementary doses of 0.5 mg.kg-1. RESULTS. In both groups a moderate drop of MAP was observed after the induction of general anesthesia. Two patients in each group showed a distinct decrease in MAP (-32%). The heart rate dropped slightly (-9%) in group A, but did not change in group B. Following intubation the MAP rose by less in group A (+8%) than in group B (+21%). After the beginning of the operation the group treated with propofol/fentanyl showed major hemodynamic changes; in particular, bradycardia with less than 40 bpm was observed in more patients than in the propofol/ketamine group. Postoperatively, fewer patients in group B required rescue doses of analgesics (1 of 10) than these in group A (7 of 10), though vigilance was better in group B. DISCUSSION. The dose of ketamine administered during the induction of general anesthesia may have been not high enough to neutralize the cardiodepressant effect of propofol. But during the maintenance of anesthesia there was in fact better hemodynamic stability in group B than in group A as a result of the neutralization of opposing actions. Fentanyl even intensified the fall in MAP after propofol. Patients in group B showed better vigilance as well as better pain relief postoperatively. The population of the fentanyl group was obviously more deeply sedated and analgesia was still inadequate. In our study general intravenous anesthesia with propofol and ketamine offered the advantages of better analgesia, a higher state of vigilance and the absence of respiratory depression during the postoperative phase compared with the combination of propofol and fentanyl.
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PMID:[The effect of propofol-ketamine anesthesia on hemodynamics and analgesia in comparison with propofol-fentanyl]. 207 45

The anaesthetic propofol was investigated in domestic pigeons (Columba livia). The agent was administrated intravenously, in one group of birds as an adjunct to ketamine hydrochloride, and careful monitoring was performed. The dose of 14 mg kg-1 of propofol was based on allometric scaling for its use as a sole agent. Propofol anaesthesia was characterised by smooth rapid induction and good muscle relaxation but was only of short duration, ranging from two to seven minutes, and seemed to cause a marked respiratory depression. Indeed, a very narrow safety margin for propofol was observed in pigeons when ventilation was not assisted. The agent may have applications in avian anaesthesia but these are likely to be limited.
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PMID:Preliminary studies on the use of propofol in the domestic pigeon (Columba livia). 226 24

The effect of the intravenous (i.v.) short-acting anesthetic propofol on baroreflex control of heart rate (HR) was examined in normotensive rats. Propofol was infused at a fixed rate of 9 mg/kg.h immediately after a bolus dose of 10 mg/kg. Blood pressure (BP) was maintained with a plasma substitute. Conscious rats were used for comparisons. Reflex HR response were recorded after i.v. doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by sigmoidal computerized curve-fitting. Propofol produced tachycardia at rest and atropine increased HR only moderately. In addition, a limitation in the bradycardiac response to artificial BP increases (lower plateau) was shown. This set of data indicated a vagal depression. The sympathetic component of the baroreflex was equally affected, since the maximal tachycardia resulting from artificial BP decreases (higher plateau) was shifted toward lower values. A marked diminution of the baroreflex gain resulted from the reduced activity of both vagal and sympathetic components. The mechanism for this decrease in the baroreflex-dependent total autonomic effector output (HR range) probably reflects the interaction of propofol with the baroreceptor pathways.
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PMID:Attenuation of the baroreceptor reflex by propofol anesthesia in the rat. 247 77

The clinical effects of a propofol-alfentanil association were studied in fifteen patients ASA II (mean age 50.1 +/- 14.1) anaesthetized for E.N.T. endoscopy after informed consent. All the patients received an intramuscular premedication with 0.10 to 0.15 mg.kg-1 midazolam. Propofol 2.5 mg.kg-1 was injected in a peripheral venous line with alfentanil 10 micrograms.kg-1, followed by continuous automatic injection of propofol at a dose of 5 to 10 mg.kg.h-1 and alfentanil 5 micrograms.kg-1 given just before suspension. After induction and during maintenance of anaesthesia, the patients were allowed to breathe oxygen spontaneously O2 assisted when apneic. The following variables were studied before induction (to), after induction (t1), during suspension (t2) and when stopping the infusion (t3): haemodynamic parameters using an invasive method and blood gases. Statistical analysis was performed using the Student's test for paired samples. Surgical conditions and anaesthetic quality were good with early recovery of consciousness and return of all reflexes. After an initial period of cardio vascular depression, the haemodynamic parameters did not vary much during the anaesthesia and propofol-alfentanil appeared to limit considerably the hypertension due to laryngoscopy. However, there was a moderate degree of hypercapnia (p less than 0.001) in most patients, giving evidence of some respiratory depression and possibly a greater depth of anaesthesia than desirable. Indeed, the doses of alfentanil required seemed to be more important with propofol because of a probably interference between the two drugs; the doses of these drugs should therefore be modified according to the length of surgery.
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PMID:[Circulatory and respiratory repercussions to direct suspension laryngoscopy in the adult: value of a propofol-alfentanil combination]. 249 72

Thirty-two patients (14 women and 18 men) whose age ranged between 15 and 76 were admitted on an emergency and anesthetized with propofol in view of various surgical interventions (9 appendectomies, 9 fractures, 5 wound healing, 6 abscess incisions, 2 corneal grafts and one complex trauma surgery) undergone 24 hours after their admission. Premedication included hydroxyzine 1.5 mg.kg-1, atropine sulfate 0.5 to 0.75 mg and pethidine 1 mg.kg-1 according to pain intensity and initial pathology. Narcosis was induced by 2.5 mg.kg-1 propofol injected intravenously. Propofol was then administered continuously at a dose of 9 mg.kg-1 in the first hour and of 4.5 mg.kg-1.h-1 in the following hours for 28 of the patients. Four patients undergoing short operations were given additional injections of one third of the initial dose. Analgesia and myorelaxation were obtained with fentanyl (0.16 +/- 0.06 mg) and vecuronium (9.3 +/- 4 mg). Narcosis proved to be very efficient. The side effects observed (13% myoclonia, 6% rash, 6% bradycardia, 0.3% pains at the time of injection) were similar to those quoted in the literature. Blood pressure stabilized after a short slight depression (13% to 18% of the standard values). Pulse remained regular. We can thus say that propofol is a good hypnotic drug for emergency anesthesia provided that its contra-indications especially shocks of cardiac or septic origin and hypovolemia, are carefully respected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Propofol in emergency anesthesia]. 278 40

An infusion of propofol was compared with intravenous boluses of diazepam as sedation for minor oral surgery under local anaesthesia in 12 healthy patients who had elective bilateral surgical extraction of lower third molars; the patients served as their own controls. Plasma catecholamine, vasopressin and cortisol concentrations were determined from repeated blood samples. The total administered dose of propofol was 3.93 (SD 1.34) mg/kg and of diazepam 0.28 (SD 0.07) mg/kg. No cardiovascular depression or airway problems occurred. Other side effects were also rare but some discomfort on injection was frequent with propofol. Recovery times were faster after propofol than after diazepam as assessed by the Maddox wing and visual analogue scales. Propofol also provided better amnesia compared to diazepam at the time of the extraction of the teeth. Eight of the 12 patients subjectively preferred propofol sedation. There was no hormonal stress response in either group.
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PMID:Propofol infusion for sedation in outpatient oral surgery. A comparison with diazepam. 280 18

Propofol 2.5 mg/kg was compared with thiopentone 5 mg/kg as an induction agent for elective Caesarean section. Thirty-two healthy women with cephalopelvic disproportion were included in an open randomised study. The placental transfer of propofol was also studied in 10 other mothers given a single dose of 2.5 mg/kg. The induction characteristics and haemodynamic response to propofol and thiopentone were similar. Side effects were rare with both agents, but propofol caused more discomfort on injection compared to thiopentone. Recovery times were shorter after propofol as evaluated by time to orientation, recovery scoring after anaesthesia and measurements with the Maddox wing. Rapid placental transfer and significant fetal uptake were detected for propofol. There was no significant neonatal depression as assessed by Apgar scores and blood gas analyses. Propofol appears to be a suitable alternative to thiopentone as an induction agent for anaesthesia in elective Caesarean section.
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PMID:Comparison of propofol and thiopentone for induction of anaesthesia for elective caesarean section. 280 24

Propofol is a rapidly acting intravenous anesthetic agent which has many advantageous kinetic properties explaining its usefulness by bolus dose for induction of anesthesia or for administration by continuous intravenous infusion. It is rapidly distributed in the body with a half-life of only around 2 min and has an efficient hepatic and extrahepatic clearance (total body clearance may exceed liver blood flow). Premedication has little effect on the already good induction characteristics of propofol. The incidence of cardiorespiratory depression appears to be higher than that of other induction agents, but, on the other hand, the absence of tachycardiac response prevents the increase in cardiac oxygen demands. In patients with cardiac disease, especially after high or repeated doses, propofol may be more depressant to the cardiovascular system than thiopentone resulting in imbalance of regional myocardial oxygen demand and supply. Recovery from propofol is rapid and clear-headed with almost no hangover effect. This makes it very suitable for out-patient anesthesia and for cardioversion. However, even with the new emulsion formulation of the drug, pain on injection is still a problem. With regard to a longer lasting combination anesthesia propofol remains an alternative to older induction agents. When given as a continuous intravenous infusion for total intravenous anesthesia or for sedation in intensive care unit propofol has shown little accumulation. Its clinical effects are predictable, consistent and recovery is rapid, independent of the dose given. Propofol has proved to be a useful induction agent regardless of the age of patients, but in the elderly there appears to exist a marked sensitivity to it. Up to now there is no evidence that propofol in emulsion drug form can produce allergic or anaphylactoid reaction more often than other induction agents in use and no severe hematological nor visceral toxicity have been reported. In the present situation, when althesin is not marketed any more due to a high frequency of anaphylactoid reactions and etomidate will have a limited use in clinical practice because of its blocking effect on adrenocortical function, propofol offers an important alternative anesthetic agent to thiopentone.
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PMID:Propofol, the newest induction agent of anesthesia. 304 41

In 42 patients undergoing major surgery, anaesthesia was induced by intravenous alfentanil 10 micrograms/kg together with methohexitone 1.5 mg/kg or propofol 2 mg/kg. An infusion of six times these doses per hour was then started; the rate was varied subsequently as indicated by the monitoring of arterial blood pressure, heart rate, EEG and frontalis electromyogram. The mean duration of infusion was 76.7 minutes for propofol and 74.5 minutes for methohexitone and the infusion was stopped about 10 minutes before the end of surgery in each group. The induction dose differed, but the total dose requirement for the two drugs was similar. In every case, anaesthesia was satisfactory. Methohexitone caused a significant rise in mean pulse rate throughout anaesthesia (p less than 0.05, paired t-test). There was no change in mean pulse rate during propofol infusion. The dose of alfentanil used provided excellent control of autonomic reflexes, with negligible respiratory depression. Naloxone was not required. Propofol provided better anaesthesia than methohexitone, with fewer side effects (p less than 0.05, Chi squared test), easier control of the level of narcosis and faster recovery (p less than 0.001, t-test after log transformation).
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PMID:Propofol and alfentanil infusion. A comparison with methohexitone and alfentanil for major surgery. 308 51


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