High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice

BACKGROUND: Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS: Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS: Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. CONCLUSIONS: These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.     

Effect of hypercapnia on arterial hypotension after induction of anaesthesia

We evaluated the effectiveness of intentional hypercapnia against hypotension after induction of anaesthesia with thiopental and isoflurane (TI) or propofol (P). For each group, 24 patients were anaesthetized with thiopental 4 mg kg(-1) (TI) or propofol 2 mg kg(-1) (P) for tracheal intubation and then lightly anaesthetized with isoflurane at 0.6% end-expiratory concentration (TI) or by 6 mg kg(-1) h(-1) infusion of propofol (P). In both anaesthesia groups, patients were randomly assigned to either normocapnia (end-tidal CO(2) = 35 mmHg) or hypercapnia (end-tidal CO(2) = 45 mmHg), which were achieved through adjusting the tidal volume. Systolic arterial pressure (SAP) 15 min after intubation was compared with the preanaesthetic baseline value. Under normocapnia, both TI and P induced a comparable, statistically significant suppression of SAP by approximately 20 mmHg from baseline. Hypercapnia prevented the decrease in SAP in TI but not in P. No patient in the TI-hypercapnia group experienced SAP below 100 mmHg, unlike those in the other groups. In conclusion, mild hypercapnia was effective in the prevention of hypotension in patients receiving thiopental followed by 0.6% end-expiratory isoflurane, but not in patients receiving 6 mg kg(-1) h(-1) propofol.     

Comparison of propofol with thiopental and isoflurane for induction and maintenance of general anesthesia

Propofol, a phenol compound with a short elimination half-life, was compared with thiopental and isoflurane for induction and maintenance of general anesthesia in 60 consenting ASA I, II, and III patients. The study was randomized and open label in design. Hemodynamically, the propofol patients showed a mean +/- SEM decrease in systolic blood pressure in comparison with the thiopental/isoflurane group at 2 (115.1 +/- 4.9 vs. 136.6 +/- 6.0 mmHg), 3 (125.7 +/- 5.1 vs. 149.4 +/- 5.6 mmHg), and 5 min (126.6 +/- 3.8 vs. 144.4 +/- 6.1 mmHg) postinduction and at intubation (135.2 +/- 4.7 vs. 157.8 +/- 6.0 mmHg) (p less than 0.05). The heart rate was lower in the propofol group throughout the induction period (p less than 0.05). Patients who received propofol were ready for discharge from the recovery room sooner (67.9 +/- 4.0 vs. 80.0 +/- 3.6 min) than the thiopental/isoflurane-treated patients (p less than 0.05). Propofol is as safe and effective for induction and maintenance of general anesthesia as thiopental and isoflurane.     

Comparison of propofol and thiopental/halothane for short-duration ENT surgical procedures in children

Experiences with propofol in pediatric anesthesia are limited. We undertook a study to evaluate the quality of induction and recovery from anesthesia with propofol compared to thiopental/halothane. Twenty children received 3 mg.kg-1.min-1 of propofol as a loading dose followed by a maintenance dose of 0.1 mg.kg-1.min-1 (+/- 10%). Twenty children received 5-7 mg/kg of thiopental, and maintenance was provided with halothane (0.5%-1.5%). The interval between the end of the administration of propofol or thiopental/halothane and extubation, as well to discharge to the ward, was significantly shorter with propofol (4.4 versus 13.5 min and 7.22 versus 30.4 min, respectively). Spontaneous movements and pain on injection were seen significantly more frequently with propofol, whereas laryngospasm and hiccup were only observed with thiopental. During the first 6 h after the surgical procedure, analgesics were needed significantly more often in the thiopental group. Nausea and vomiting also were observed more frequently in the thiopental group. In conclusion, propofol used as a single anesthetic is a satisfactory technique for ENT surgery of short duration in children.     

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.     

Implantable cardioverter-defibrillator placement in patients with mild-to- moderate left ventricular dysfunction: hemodynamics and recovery profile with two different anesthetics used during deep sedation

OBJECTIVE: To compare the effects of thiopental and propofol during defibrillation threshold testing (DFT) on hemodynamics and recovery profile in patients requiring automatic internal cardioverter-defibrilator placement. DESIGN: Prospective clinical investigation. SETTING: University hospital. PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients received thiopental by slow injection and patients in group II (GII) (n = 17) received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p > 0.05). Hemodynamics did not show significant differences between the groups at any recording time. Average time needed to regain the pretest sedation level was 16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3 minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%) and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS: Deepening the sedation level by slow injection of thiopental or propofol before DFT provided satisfactory conditions during brief episodes of VF. Delay in recovery of arterial pressure after DFT with propofol and delay in arousal and discharge of patients with thiopental are major disadvantages of the regimens.     

Comparison of the effects of fentanyl on respiratory mechanics under propofol or thiopental anaesthesia

Twenty patients were randomly anaesthetized with either thiopental 5 mg/kg followed by a 15 mg/kg/h continuous infusion, or propofol 2.5 mg/kg followed by a 9 mg/kg/h continuous infusion, paralysed with vecuronium 0.1 mg/kg, intubated and ventilated with nitrous oxide 50% in oxygen. Fifteen minutes after induction, fentanyl 5 micrograms/kg was injected. Inspiratory tracheal pressure (PT), gas flow (V) and volume (V) were continuously measured while the lungs were inflated with a constant inspiratory flow ventilator. Respiratory compliance (Crs) and resistance (Rrs) were calculated from the regression of PT on V. In both groups Crs decreased following anaesthesia. Fentanyl injection elicited an increase in Rrs (from 1.04 +/- 0.70 to 1.63 +/- 0.92 kPa x l-1 x s) and a further decrease in Crs (from 0.55 +/- 0.30 to 0.42 +/- 0.10 l x kPa-1) in the thiopental group but not in the propofol group (Rrs: 1.26 +/- 0.69 to 1.08 +/- 0.44 kPa x l-1 x s, Crs: 0.49 +/- 0.11 to 0.48 +/- 0.13 l x kPa-1). These results suggest that the dose of propofol administered in this study may prevent fentanyl-induced bronchoconstriction.     

Comparison of the Effects of Etomidate, Propofol, and Thiopental on Respiratory Resistance after Tracheal Intubation

Background: Tracheal intubation frequently results in reversible bronchoconstriction. Propofol has been reported to minimize this response in healthy patients and in asthma patients, but may be unsuitable for hemodynamically unstable patients for whom etomidate may be preferable. The current study examined respiratory resistance after tracheal intubation after induction with either thiopental, etomidate, or propofol. A supratherapeutic dose of etomidate was used to test the hypothesis that the bronchoconstrictive response could be minimized by deep intravenous anesthesia.

Methods: Seventy-seven studies were conducted in 75 patients. Anesthesia was induced with either 2.5 mg/kg propofol, 0.4 mg/kg etomidate, or 5 mg/kg thiopental. Respiratory resistance was measured at 2 min after induction.

Results: Respiratory resistance at 2 min was 8.1+/-3.4 cmH sub 2 O *symbol* l sup -1 *symbol* s (mean+/-SD) for patients receiving propofol versus 11.3+/-5.3 for patients receiving etomidate and 12.3+/-7.9 for patients receiving thiopental (P less than or equal to 0.05 for propofol vs. either etomidate or thiopental).     

Pretreatment with thiopental for prevention of pain associated with propofol injection

Propofol causes pain on IV injection in 28%-90% of patients. A number of techniques have been tried to minimize propofol-induced pain, with variable results. We compared the efficacy of pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg and lidocaine 40 mg after venous occlusion for prevention of propofol-induced pain. One-hundred-twenty-four adult patients, ASA physical status I-II, undergoing elective surgery were randomly assigned into 4 groups of 31 each. Group I received normal saline, group II received lidocaine 2% (40 mg), and groups III and IV received thiopental 0.25 mg/kg and 0.5 mg/kg, respectively. All pretreatment drugs were made in 2 mL and were accompanied by manual venous occlusion for 1 min. Propofol was administered after release of venous occlusion. Pain was assessed with a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain at the time of propofol injection. Twenty-four patients (77%) complained of pain in the group pretreated with normal saline as compared with 12 (39%), 10 (32%), and 1 (3%) in the groups pretreated with lidocaine 40 mg, thiopental 0.25 mg/kg, and thiopental 0.5 mg/kg, respectively (P < 0.05). Thiopental 0.5 mg/kg was the most effective treatment. We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with venous occlusion for 1 min for prevention of pain associated with propofol injection. IMPLICATIONS: Pain associated with IV injection of propofol is seen in 28%-90% patients. Pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg after manual venous occlusion for 1 min effectively attenuated pain associated with propofol injection. Thiopental 0.5 mg/kg was the most effective in prevention of propofol pain and can be used routinely.     

Response of human growth hormone to anesthesia induction with propofol

Although there are distinct differences in both pharmacokinetics and chemical structure, propofol has sedative effects similar to those of benzodiazepines. Both diazepam and thiopental, commonly used agents for inducing anaesthesia, show some typical neuroendocrine effects such as liberation of human growth hormone (hGH) in addition to their well-known influences on the cardiovascular system. It was our aim to examine the endocrine response of hGH after induction of anaesthesia with propofol and to compare any possible effects with those of diazepam and thiopental. The study was performed on 30 non-premedicated patients, who underwent plastic-surgery (mean age: x = 35 +/- 8.3 years, mean body weight: x = 68.9 +/- 23.2 kg). No signs of endocrine disturbances were found in the patients prior to the study. Patients were divided in a random fashion into 3 groups of 10 persons each: In group 1 propofol was given in a bolus injection (2 mg/kg) and then by infusion for a period of 10 min (0.2 mg/kg/min). In group 2 diazepam (0.3 mg/kg) and in group 3 thiopental (5 mg/kg) were administered as a bolus to induce anesthesia. All patients were intubated immediately after induction of anesthesia and then relaxed using vecuronium (1 mg/kg). Ventilation was performed mechanically during the entire operative period (N2O/O2 - FiO2:0.33, tidal volume 10 ml/kg, respiratory rate: 14/min). To maintain anesthesia halothane (0.5-1.0 vol.-%) and meperidine (0.75 mg/kg) were added 15 min after induction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 in rats

BACKGROUND AND OBJECTIVE: We studied the pharmacokinetics and pharmacodynamics of GPI 15715 (Aquavan injection), a new water-soluble prodrug metabolized to propofol by hydrolysis. METHODS: Nine adult male Sprague-Dawley rats (398 +/- 31 g) received a bolus dose of 40 mg GPI 15715. The plasma concentrations of GPI 15715 and propofol were determined from arterial blood samples, and the pharmacokinetics of both compounds were investigated using compartment models whereby the elimination from the central compartment of GPI 15715 was used as drug input for the central compartment of propofol. Pharmacodynamics were assessed using the median frequency of the EEG power spectrum. RESULTS: A maximum propofol concentration of 7.1 +/- 1.7 microg mL(-1) was reached 3.7 +/- 0.2 min after bolus administration. Pharmacokinetics were best described by two-compartment models. GPI 15715 showed a short half-life (2.9 +/- 0.2 and 23.9 +/- 9.9 min), an elimination rate constant of 0.18 +/- 0.01 min(-1) and a central volume of distribution of 0.25 +/- 0.02 L kg(-1). For propofol, the half-life was 1.9 +/- 0.1 and 45 +/- 7 min, the elimination rate constant was 0.15 +/- 0.02 min(-1) and the central volume of distribution was 2.3 +/- 0.6 L kg(-1). The maximum effect on the electroencephalogram (EEG)--EEG suppression for >4 s--occurred 6.5 +/- 1.2 min after bolus administration and baseline values of the EEG median frequency were regained 30 min later. The EEG effect could be described by a sigmoid Emax model including an effect compartment (E0 = 16.9 +/- 7.9 Hz, EC50 = 2.6 +/- 0.8 microg mL(-1), ke0 = 0.35 +/- 0.04 min(-1)). CONCLUSIONS: Compared with known propofol formulations, propofol from GPI 15715 showed a longer half-life, an increased volume of distribution, a delayed onset, a sustained duration of action and a greater potency with respect to concentration.     

Comparison of the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol,thiopental or etomidate

BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate. METHODS: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 microg kg(-1), whereas the others received a remifentanil infusion at 0.5 microg kg(-1) min(-1). Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand. RESULTS: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 +/- 13.6s (mean +/- SD) versus 74.9 +/- 27.0s (P < 0.01), with thiopental 42.9 +/- 16.8s versus 77.2 +/- 27.8s (P < 0.01) and with etomidate 54.7 +/- 17.6s versus 72.3 +/- 24.0s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (-29%, P < 0.05), thiopental (-25%, P < 0.05) or etomidate (-32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: -26% with propofol, -181% with thiopental and -14% with etomidate (all P < 0.01). CONCLUSIONS: During anaesthetic induction, a remifentanil infusion of 0.5 microg kg(-1) min(-1) over 5 min is a suitable alternative to a 1.5 microg kg(-1) bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.     

Effect of intravenous clonidine on the dose of thiopental required to induce anesthesia.

A randomized, double-blind, controlled trial was conducted to investigate the influence of intravenous clonidine on thiopental dose requirements when used for induction of anesthesia and associated hemodynamic effects. Sixty ASA physical status I or II patients were randomly allocated to one of three treatment groups: normal saline solution (control, n = 20); clonidine (2.5 micrograms/kg, n = 20); or clonidine (5 micrograms/kg, n = 20). The test drug was administered 15 min before induction of anesthesia with intravenous thiopental. The dose of thiopental to produce loss of lash reflex was recorded as well as mean arterial blood pressure and heart rate at 3-min intervals up to induction of anesthesia and then at 1-min intervals for 5 min. Significant decreases in thiopental dose were observed in both groups receiving clonidine compared with the control group, but there was no significant difference between clonidine groups. With dosage calculated according to total body mass, the control group required 5.50 +/- 1.15 mg/kg (mean +/- SD) of thiopental, whereas those who received 2.5 micrograms/kg of clonidine required 4.15 +/- 1.46 mg/kg of thiopental (a reduction of 25%), and those who received 5.0 micrograms/kg of clonidine required 3.48 +/- 1.06 mg/kg of thiopental (a reduction of 37%). When thiopental dose was adjusted for lean body mass, similar reductions were obtained. Clonidine, in both doses, produced more sedation than control, and the 2.5-mg/kg dose produced less sedation than the larger dose. Mean arterial blood pressure was lower in the groups receiving clonidine. There were no significant differences in heart rate among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral vascular effects of thiopental and propofol in humans with artificial hearts

The peripheral vascular effects of thiopental 5 mg/kg and propofol 2.5 mg/kg were compared in five patients whose lungs were being ventilated and in whom a Jarvik-7 artificial heart had been implanted. The patients were monitored, using catheters that had been surgically inserted into the radial artery, the right and left atria, and the pulmonary artery. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient received both drugs, with the interval between each drug ranging from 16 to 28 h. Hemodynamic parameters and catecholamine and atrial natriuretic peptide plasma concentrations were measured before drug administration and 5, 10, 15, 30, and 45 min later. Both drugs significantly decreased arterial pressure, systemic vascular resistance index, pulmonary arterial pressure (PAP), and right and left atrial pressures (RAP and LAP, respectively). However, propofol 2.5 mg/kg induced a significantly greater and more prolonged decrease in arterial pressure, systemic vascular resistance index, and RAP than that after administration of thiopental 5 mg/kg (P less than 0.05). Five minutes after drug injection, mean arterial pressure decreased by 21% after thiopental and by 39% after propofol (P less than 0.01); systemic vascular resistance index decreased by 21% after thiopental and by 44% after propofol (P less than 0.05); RAP decreased by 20% after thiopental and by 50% after propofol (P less than 0.05); mean PAP decreased by 18% after thiopental and by 32% after propofol (P less than 0.09); and LAP decreased by 40% after thiopental and by 46% after propofol (P less than 0.2). With both drugs, atrial natriuretic peptide, norepinephrine, and epinephrine plasma concentrations remained stable throughout the study period. Because cardiac output was maintained constant throughout the study, these results suggest that propofol 2.5 mg/kg is a more potent vasodilator of venous and arterial beds than is thiopental 5 mg/kg.     

Changes in the auditory evoked potentials index by induction doses of four different intravenous anesthetics

BACKGROUND: Many studies have investigated the electroencephalographic changes during the induction and maintenance of anesthesia. However, no comparative studies have been performed on the effects of intravenous anesthetics on the auditory evoked potentials index (AAI). The present study was performed to compare the changes in AAI caused by induction doses of thiopental, propofol, midazolam and ketamine. METHODS: Eighty females, aged 30-70 years, referred for mastectomy, had anesthesia induced with thiopental 4 mg/kg, propofol 2 mg/kg, midazolam 0.1 mg/kg or ketamine 1 mg/kg (each 20 patients). The response to verbal command and the AAI were measured every minute for 5 min. RESULTS: The AAI decreased to less than 40 within 1 min with thiopental and propofol. The AAI increased after 3 min with thiopental, but remained low with propofol. The AAI gradually decreased to less than 40 within 4 min with midazolam, but was higher than the AAI with propofol or thiopental. The AAI increased significantly with ketamine. The AAIs at the loss of verbal command were 19 +/- 7 with thiopental, 21 +/- 8 with propofol, 31 +/- 10 with midazolam and 92 +/- 2 with ketamine. CONCLUSION: The AAI correlated with changes in hypnotic level, as measured by the response to verbal command, with induction doses of thiopental, propofol and midazolam, but not with ketamine. The AAI decreased to lower levels with propofol and thiopental than with midazolam at the induction of anesthesia.     

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.     

Propofol ensures a more stable A-line ARX index than thiopental during intubation

BACKGROUND: The A-line autoregressive modelling with exogenous input index (AAI) is a new method of assessing depth of anesthesia. We examined the effects of tracheal intubation on the AAI and hemodynamics during induction of anesthesia with propofol compared with thiopental in patients aged over 50 yr. METHODS: 40 patients scheduled for a laminectomy, posterior spinal fusion, vertebroplasty, or total hip replacement, ASA physical status I or II and aged over 50 yr, were randomly divided into two groups. Thiopental 5 mg.kg(-1) iv, fentanyl 2.5 microg.kg(-1) iv, and rocuronium 0.7 mg.kg(-1) iv were used in the thiopental group (n = 20) for anesthetic induction; the same protocol was used in the propofol group (n = 20) except that 2 mg.kg(-1) propofol iv was given instead of thiopental. The AAI, non-invasive blood pressure, and heart rate were measured every minute before induction for three minutes, at 1.5 min post-induction, and then each minute post-intubation for eight minutes. RESULTS: The AAI increased significantly at one and two minutes after intubation in the thiopental group (to 56.5 +/- 18.6 at 1 min and 44.7 +/- 18.7 at 2 min after intubation vs 19.9 +/- 7.5 at 1.5 min after induction; P < 0.05). Thereafter, AAI values gradually decreased three minutes after intubation. The AAI was inhibited continuously after intubation in the propofol group, and no significant elevation was seen. CONCLUSION: Our results, using the AAI to monitor anesthetic depth during induction and tracheal intubation, suggest that at equipotent doses propofol provided a more stable level of anesthesia than did thiopental.     

Comparative study of the efficacy and tolerance of propofol and thiopental in induction and in continuous perfusion with neuroleptanesthesia

We have studied 40 ASA I/II patients aged from 18 to 65 years undergoing otorhinolaryngologic surgery of 40-100 minutes of duration. Patients were randomly assigned to two groups. Anesthesia in group I was induced with thiopental, 4 mg/kg and maintained with N2O at 66% and a variable perfusion of fentanyl. In group II, anesthesia was induced with propofol, 2.5 mg/kg and maintained with a perfusion of 6-12 mg/kg/hour and an initial perfusion of fentanyl, 4 micrograms/kg/hour. Loss of consciousness occurred in 37.49 +/- 9.78 seconds in group I and in 46.25 +/- 12.62 seconds in group II, with no significant differences. Two minutes after induction, propofol group presented a significant decrease in systolic blood pressure of - 12 mm Hg and both groups presented comparable increases in systolic blood pressure and heart rate during intubation. Five minutes later, systolic blood pressure regained normal values. Maintenance in group II was achieved in a proper fashion with a mean propofol consumption of 9.5 +/- 2.6 mg/kg/hour and fentanyl consumption of 4.94 +/- 2.22 micrograms/kg/hour whereas in group II, with N2O at 66%, the amount of fentanyl required was 6.85 +/- 2.95 micrograms/kg/hour, which was significantly higher. Eye opening from the time of interruption of anesthetics was achieved at 6.6 +/- 3.2 minutes in group I and 12.44 +/- 6.34 in group II. Consciousness was regained at 11.25 +/- 3.96 and 16.87 +/- 6.95 minutes, respectively. Pain on injection occurred in 15% with propofol and in 10% with thiopental. No patient presented major complications nor phlebitis after administration of the anesthetic.     

Time course of ventilatory depression following induction doses of propofol and thiopental.

To improve our understanding of the respiratory pharmacology of intravenous induction agents, the authors compared the acute effects of intravenous (iv) propofol 2.5 mg.kg-1 and iv thiopental 4.0 mg.kg-1 on the ventilatory response to CO2 (VeRCO2) of eight healthy volunteers. The slope of VeRCO2 decreased from 1.75 +/- 0.23 to a minimum of 0.77 +/- 0.14 1.min-1.mmHg-1 (mean +/- standard error) 90 s after propofol; similarly, the slope of VeRCO2 decreased from 1.79 +/- 0.22 to a minimum of 0.78 +/- 0.23 l.min-1.mmHg-1 30 s after thiopental. For both drugs, the slope was less than control in the 0.5-5-min period after injection (P less than 0.05). The slope returned to baseline within 6 min after thiopental; in contrast, after propofol, the slope remained less than control for the entire 20-min follow-up period (P less than 0.05 at 6-10, 11-15, and 16-20 min after injection). Also, from 6-10, 11-15, and 16-20 min after injection, the slope was less after propofol than at corresponding times after thiopental (P less than 0.05). Recovery of consciousness was approximately 4 min slower after propofol than after thiopental; nonetheless, awareness scores returned to baseline within 14 min after both drugs. The authors conclude that propofol 2.5 mg.kg-1 iv produces longer-lasting depression of VeRCO2 than a 4.0 mg.kg-1 iv dose of thiopental; after propofol, ventilatory depression may persist despite apparently complete recovery of consciousness.     

A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia.

STUDY OBJECTIVE: To evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil. DESIGN: Double-blinded, prospective, randomized study. SETTING: Operating room of a medical college hospital. PATIENTS: 30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia. INTERVENTIONS: Patients were randomly allocated to one of three groups: the placebo-propofol-placebo (PP) group, the midazolam-propofol-placebo (MP) group, or the midazolam-propofol-flumazenil (MF) group. After administering placebo or midazolam (10 microg kg(-1)), propofol 250 microg kg(-1) min(-1) was infused. Immediately after confirming that the patient was hypnotized, we terminated the propofol infusion and administered placebo or flumazenil (5 microg kg(-1)). MEASUREMENTS: The dose and the times required to achieve hypnosis (the first endpoint) and to emerge from anesthesia (the second endpoint). The plasma concentration at each endpoint was determined. MAIN RESULTS: Midazolam significantly decreased the dose and time needed to achieve hypnosis [PP vs. MP, 66 +/- 14 vs. 48 +/- 15 mg, 260 +/- 55 vs. 179 +/- 44 sec, respectively (mean +/- SD)]. Thus, the plasma concentration of propofol at hypnosis was significantly lower (PP vs. MP, 3.31 +/- 0.78 vs. 2.41 +/- 0.57 microg mL(-1)). The time to emerge from anesthesia was not prolonged by midazolam, and was further shortened by administration of flumazenil (PP, MP vs. MF, 237 +/- 77, 207 +/- 71 s vs. 126 +/- 56 sec, respectively). Flumazenil also reversed the reduction in propofol concentration induced by midazolam at emergence (PP, MP, and MF, 0.54 +/- 0.17, 0.37 +/- 0.15, and 0.59 +/- 0.22 microg mL(-1), respectively). CONCLUSIONS: Coadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia. Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.