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PubMed2005

Impact of the Narcotrend Index on propofol consumption and emergence times during total intravenous anaesthesia with propofol and remifentanil in children: a clinical utility study.

BACKGROUND AND OBJECTIVE: The electroencephalographic Narcotrend Index (NI) is a measure of the hypnotic component of general anaesthesia. The purpose of this study was to evaluate the impact of Narcotrend guidance on propofol consumption and emergence times in children receiving total intravenous anaesthesia with propofol and remifentanil. METHODS: Thirty children, aged 1-11 yr, scheduled for paediatric urological surgery were enrolled. Remifentanil was given to all patients at a constant infusion rate of 0.3 microg kg [-1] min[-1] throughout anaesthesia. Patients were randomly allocated to receive a continuous propofol infusion adjusted either according to a conventional clinical practice (Group C: n=15) or guided by Narcotrend monitoring (Group NI: n=15; target NI 60+/-5). All patients were connected to the Narcotrend Monitor, but in Group C the anaesthetist was blinded to the screen of the monitor. Propofol consumption (mg kg[-1]h[-1]) and emergence times (min) were the primary and secondary outcome measures. RESULTS: Propofol consumption (median [inter-quartile range]) was significantly lower in Group NI compared to Group C (NI: 7.0 [6.4--8.2] vs. C: 9.3 [8.3--11.0] mg kg[-1]h[-1]; P<0.001), whereas Log-Rank-analysis revealed no intergroup difference in emergence times (Group NI: mean [95% confidence interval (CI)] 12.8 [11.2--14.4] min; Group C: 16.4 [12.6--20.2] min; P=0.10). Haemodynamic variables remained stable within age-related limits, and there were no observations of adverse events, especially no clinical signs of intraoperative awareness in any patient. CONCLUSION: Narcotrend monitoring for guidance of propofol/remifentanil anaesthesia in children results in reduced propofol consumption compared to a conventional clinical practice.

Anesthesia Recovery Period↗

PubMed2000

Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.

The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.

Anesthetics, Intravenous↗

PubMed1990

Study of the possible interaction between fentanyl and propofol using a computer-controlled infusion of propofol.

A computer-controlled infusion of propofol designed to achieve a target blood concentration of propofol 3 microgram ml-1 was used to investigate the possibility of an interaction between propofol and fentanyl in 32 patients undergoing body surface surgery. In 16 patients who were not receiving a neuromuscular blocker during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood concentrations of propofol between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. In a further 16 patients who received vecuronium during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood propofol concentrations between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. Fentanyl administered i.v. immediately before a computer-controlled infusion of propofol resulted in more satisfactory anaesthetic conditions than when fentanyl was not used, but did not significantly prolong the recovery time.

Adult↗

PubMed1999

Propofol versus propofol-ketamine sedation for retrobulbar nerve block: comparison of sedation quality, intraocular pressure changes, and recovery profiles.

UNLABELLED: We compared sedation quality, intraocular pressure (IOP) changes, and recovery profiles in patients who received propofol or propofol-ketamine sedation during placement of the retrobulbar nerve block (RBB). Seventy elderly patients undergoing cataract extraction according to a prospective, randomized, double-blinded protocol were preoperatively evaluated with a Mini-Mental State examination and baseline IOP. A hypnotic dose was provided with either propofol (Group P) or a propofol-ketamine (Group PK) combination. The IOP measurement was repeated, and the surgeon initiated the RBB. Supplemental study drug was given if needed. The level of sedation was considered acceptable if the patient exhibited minimal or no movement and grimacing with needle insertion. Patients were evaluated in terms of quality of sedation, cardiopulmonary stability, and recovery profile. Compared with patients in Group P, patients in Group PK had a significantly faster onset of acceptable sedation (Group P 235 +/- 137 s versus Group PK 164 +/- 67 s) and required significantly less supplemental sedation (Group P 1.1 +/- 1.9 mL versus Group PK 0.15 +/- 0.3 mL). Additionally, none of the Group PK patients required ventilatory assistance, but two patients in Group P required assisted mask ventilation. In conclusion, the addition of ketamine (13.2 +/- 3.3 mg) to propofol (44 +/- 11 mg) decreased the hypnotic requirement and improved the quality of sedation without prolonging recovery. IMPLICATIONS: Anesthesiologists frequently perform retrobulbar blocks while simultaneously providing sedation. Using ketamine to supplement propofol sedation provided a faster onset and improved the quality of sedation during the retrobulbar block procedure.

Aged↗

PubMed2005

Less postoperative nausea and vomiting after propofol + remifentanil versus propofol + fentanyl anaesthesia during plastic surgery.

BACKGROUND: The effect of different opioids on postoperative nausea and vomiting (PONV) has not been conclusively determined yet, thus the aim of this study was to compare the incidence of PONV in propofol-anaesthetized patients receiving either fentanyl or remifentanil as opioid supplement. METHODS: Sixty ASA physical status I and II patients scheduled for plastic surgery gave their written informed consent for this prospective, randomized, double-blind study. Anaesthesia was induced with propofol, rocuronium and fentanyl (n = 30; 2 microg kg(-1)) or remifentanil (n = 30; 1 microg kg(-1)). After tracheal intubation, anaesthesia was maintained with propofol, oxygen in air and an infusion of the opioid studied, which was modified according to clinical criteria. Baseline postoperative analgesia was achieved with intravenous propacetamol + metamizol. Intravenous morphine was given if visual analogic scale (VAS) for pain was > or = 4 (scale 0-10) and metoclopramide was administered if a patient presented > or = 2 PONV episodes (nausea or vomiting) in less than 30 min. Postoperatively (2, 12 and 24 h), we registered VAS, rescue morphine consumption, number of patients with episodes of PONV and number of patients requiring metoclopramide. P < 0.05 was considered significant. RESULTS: There were no significant differences between groups in the demographic parameters, ASA physical status, propofol dose, VAS, and rescue morphine requirements. Fourteen patients in the fentanyl group and four in the remifentanil group presented PONV episodes 2-12 h postoperative hours' interval; (P < 0.05). Ten patients in the fentanyl group and four in the remifentanil group presented vomiting episodes in the same period (P < 0.05); and eight patients in the fentanyl group and one in the remifentanil group required metoclopramide; (P < 0.05). The number of postoperative PONV episodes were low, both in the 0-2-h period (n = 2 vs. n = 1, fentanyl and remifentanil, respectively) and in the 12-24-h period (n = 3 vs. n = 1). CONCLUSION: Propofol + fentanyl anaesthesia resulted in a higher incidence of PONV and requirements of antiemetic drugs in the period between 2 and 12 postoperative hours compared with propofol + remifentanil, in patients undergoing plastic surgery.

Adolescent↗

PubMed2000

Comparative study of propofol or propofol and ketamine for the induction of anaesthesia in dogs.

The effects of propofol alone or propofol and ketamine for the induction of anaesthesia in dogs were compared. Thirty healthy dogs were premedicated with acepromazine and pethidine, then randomly allocated to either treatment. Anaesthesia was induced with propofol (4 mg/kg bodyweight intravenously) (group 1), or propofol and ketamine (2 mg/kg bodyweight of each intravenously) (group 2). Anaesthesia was maintained with halothane, delivered in a mixture of oxygen and nitrous oxide (1:2) via a non-rebreathing Bain circuit. Various cardiorespiratory parameters were monitored at two, five, 10, 15, 20, 25 and 30 minutes after induction, and the animals were observed during anaesthesia and recovery, and any adverse effects were recorded. During anaesthesia, the heart rate, but not the systolic arterial pressure, was consistently higher in group 2 (range 95 to 102 beats per minute) than in group 1 (range 73 to 90 beats per minute). Post-induction apnoea was more common in group 2 (11 of 15) than in group 1 (six of 15). Muscle twitching was observed in three dogs in each group. Recovery times were similar in both groups. Propofol followed by ketamine was comparable with propofol alone for the induction of anaesthesia in healthy dogs.

Anesthesia, Intravenous↗

PubMed2003

Propofol alone, sevoflurane alone, and combined propofol-sevoflurane anaesthesia in electroconvulsive therapy.

Electroconvulsive therapy is an effective treatment for severe and medication-resistant depression. There have been no reports describing how a volatile anaesthetic affects haemodynamic responses, seizure duration, and recovery characteristics during electroconvulsive therapy. We carried out a repeated-measure crossover study to compare the effects on haemodynamic responses, seizure duration, and recovery characteristics of the following types of anaesthesia in electroconvulsive therapy: propofol alone, sevoflurane alone, and propofol combined with sevoflurane. We recruited 50 patients requiring electroconvulsive therapy for depression. For anaesthesia induction, 1.5 mg/kg propofol (condition P), 5% sevoflurane in oxygen following a vital capacity rapid inhalation induction (condition S), or 1.5 mg/kg propofol followed by 5% sevoflurane in oxygen (condition PS) was administered. Succinylcholine 1.5 mg/kg was then given. Electrical stimulation was administered after fasciculation. Measurements were obtained before anaesthesia induction (baseline), prior to succinylcholine administration, prior to electroconvulsive therapy, and at the peak after electroconvulsive therapy. After electroconvulsive therapy, peak heart rate and peak mean arterial pressure were highest in condition S. Whereas recovery time was longest in condition PS, motor seizure duration was significantly shorter than in either condition P or S. Electroencephalographic seizure duration was significantly shorter in condition PS than in condition P and significantly shorter in condition S than in condition P. Sevoflurane anaesthesia alone is most disadvantageous in terms of haemodynamics. Propofol-sevoflurane anaesthesia is advantageous in terms of haemodynamics, but disadvantageous in terms of seizure duration and recovery time. Propofol alone is most advantageous in terms of seizure duration.

Adult↗

PubMed1992

Comparison of induction, maintenance, and recovery characteristics of sevoflurane-N2O and propofol-sevoflurane-N2O with propofol-isoflurane-N2O anesthesia.

Induction of, maintenance of, and recovery from sevoflurane anesthesia were compared with propofol and isoflurane anesthesia when administered with nitrous oxide to patients undergoing gynecologic surgery. Seventy-five healthy (ASA I or II), consenting patients were randomly assigned to receive either (I) propofol for induction of anesthesia and isoflurane-nitrous oxide for maintenance (control), (II) propofol for induction and sevoflurane-nitrous oxide for maintenance, or (III) sevoflurane-nitrous oxide for induction and maintenance of anesthesia. Inhaled induction of anesthesia with sevoflurane-nitrous oxide was rapid (109 +/- 25 s to loss of consciousness) and without any untoward hemodynamic changes or episodes of coughing and laryngospasm. Mean arterial blood pressure after induction of anesthesia with propofol (71 +/- 11, 73 +/- 12 mm Hg for groups I and II, respectively) was lower than when sevoflurane (80 +/- 14 mm Hg) was used. The emergence time after discontinuation of isoflurane-nitrous oxide (6.7 +/- 2.2 min) was significantly longer than after propofol-sevoflurane-nitrous oxide or sevoflurane-nitrous oxide alone (4.1 +/- 2.2 and 4.0 +/- 2.0 min for groups II and III, respectively). However, later recovery events did not differ between groups. Serum fluoride levels increased after administration of sevoflurane but not isoflurane. The levels of fluoride ions correlated with the degree of exposure to sevoflurane in MAC-hours. In conclusion, induction of anesthesia with either propofol or sevoflurane-nitrous oxide was rapid and without significant side effects. Emergence and early recovery after maintenance of anesthesia with sevoflurane-nitrous oxide was significantly faster than that after an isoflurane-nitrous oxide combination.

Adult↗

PubMed2000

[Effect of pre-mixed lidocaine with propofol on propofol injection pain in elderly patients].

The purpose of this study was to compare the younger and older patients in the incidence and the severity of the pain during injection of propofol. Thirty-four, elderly patients (60-80-yr-old) and 52 patients (20-40-yr-old) scheduled to undergo elective surgery were studied. We conducted a prospective, randomized and double-blinded trial. All patients were randomly allocated to one of two groups according to the agents added to 1% propofol 20 ml; Group S, normal saline 2 ml, and Group L, 2% lidocaine 2 ml. The pain on injection was rated as none, mild, moderate, or severe. Seventy percent of patients in the S group of elderly patients experienced pain, while 22% of patients experienced pain in the L group in elderly patients. The incidence of pain on injection in the S group of older patients was comparable with S group of younger patients. The severity of pain in elderly patients was significantly decreased after premixing with lidocaine. There were no significant differences between older and younger patients in the severity of propofol injection pain in both S group and L group. In conclusion, elderly patients suffered the pain on injection of propofol with the same incidence as the younger patients did. Lidocaine premixed with propofol significantly reduces the incidence and the severity of pain associated with propofol in elderly patients.

Adult↗

PubMed2001

[The effects of the fat component of propofol solution of ketogenesis during propofol anesthesia].

To examine the effects of the fat component in propofol solution on the fat metabolism during propofol anesthesia, we measured the urine ketone body (UKB) and blood concentrations of 3-hydroxybutyrate (3-OHBA) and glucose. The anesthesia was maintained with propofol, fentanyl, and vecuronium. Infusion fluid without glucose was used while we measured the concentration of 3-OHBA. UKB was detected only when the concentration of 3-OHBA was more than 400 mumol.ml-1. The blood concentration of 3-OHBA increased in proportion to the total amount of propofol solution, while UKB did not show any such relationship. Furthermore, the rate of increase of 3-OHBA was larger in the group whose concentration of 3-OHBA was higher than the normal range. The blood concentration of glucose ranged within the normal fasting level. There were no cases who needed special treatment for hyperketonemia in this study. We concluded that 3-OHBA was a more sensitive indicator of ketogenesis than UKB, and that ketogenesis was accelerated both by propofol anesthesia with the lipidemic solution of propofol and by fasting before surgery. The acceleration of ketogenesis was especially marked in the patients with hyperketonemia.

3-Hydroxybutyric Acid↗

PubMed2003

Remifentanil-propofol versus sufentanil-propofol anaesthesia for supratentorial craniotomy: a randomized trial.

BACKGROUND AND OBJECTIVE: Remifentanil has unique pharmacokinetics that might allow faster recovery after neurosurgery. We investigated the effects of a propofol/sufentanil versus a remifentanil/propofol regimen on the primary end-point tracheal extubation time. METHODS: In the Neurosurgery Department of a University Hospital, 36 patients awaiting craniotomy for supratentorial tumour resection were randomly assigned to one of two study groups. In the sufentanil/propofol group, anaesthesia was induced with 0.5 microg kg(-1) sufentanil and 1-2 mg kg(-1) propofol. Propofol infusion and boluses of sufentanil were administered for maintenance. In the remifentanil/propofol group, anaesthesia was started with an infusion of remifentanil (0.2-0.35 microg kg(-1) min(-1)) and a bolus of propofol (1.5-2 mg kg(-1)). Patients received a propofol infusion and a remifentanil infusion for maintenance of anaesthesia. Recovery times were taken from cessation of the propofol infusion. In addition, data about self-reported nausea and vomiting, pain and analgesic requirements were collected. RESULTS: Patients in the remifentanil/propofol group were extubated earlier (mean times 6.4 (+/- SD 4.7) versus 14.3 (+/- 9.2) min; P = 0.003). The two groups were similar with respect to postoperative nausea and vomiting, and patient-reported pain scores. Fifty per cent of the remifentanil/propofol patients and 88% of the sufentanil/propofol patients required no analgesics within 1 h after operation (P = 0.03). CONCLUSIONS: The remifentanil/propofol regimen provided quicker recovery. The two regimens were similar in terms of postoperative nausea and vomiting and patient-reported pain scores, but patients in the remifentanil/ propofol group required more analgesics within 1 h postoperatively.

Aged↗

PubMed1990

[Propofol-ketamine vs propofol-fentanyl in short gynecologic surgery].

The study was performed to investigate efficacy and tolerability of the association propofol-ketamine as alternative to propofol-fentanyl. Forty female, classified ASA I-II, aged 18-50 years and scheduled for short gynecologic procedures under general anesthesia were included in a comparative, randomized, single blind study. Patients were divided in two groups; in group K anesthesia was induced with propofol 1.5 mg/kg and ketamine 1 mg/kg i.v. In group F anesthesia was induced with propofol 2.5 mg/kg and fentanyl 1.5 micrograms/kg. Arterial blood pressure (BP), heart rate (HR), respiratory rate (RR) and arterial O2 saturation (SATO2) were measured. Though preliminary, our data suggest that the association propofol-ketamine reach an adequate level of anesthesia with few and negligible effects on cardiorespiratory system, thus allowing a better operability and safety. The incidence of post operative psychotic disturbances seems to be low and moderate. We can't draw any definitive conclusion, but we think that other studies should be performed to clarify the possible role of ketamine in propofol anesthesia.

Adolescent↗

PubMed1998

[The switching time of propofol syringes for the propofol specific pump is dependent on the familiarity of pumps].

The switching time of syringes during propofol anesthesia was investigated among various anesthesiologists. One hundred and thirty times of exchanges were observed in the early 82 propofol anesthesia cases using a propofol specific syringe pump STC-525 X (Terumo, Japan) since the introduction of propofol in our hospital. The anesthesiologists were divided into three groups: group A; the board certified anesthesiologists with more than one month experience of propofol anesthesia, group B; the board certificed anesthesiologists with less than one month experience, group C: the trainee. There were no cases of intraoperative recall case. The median times of switching syringes were 14 seconds, 26 seconds, 56 seconds in the group A, group B, group C, respectively. Group A is significantly quicker than the other groups. This indicates that switching time is dependent on the experience with propofol and syringe pumps. We conclude that not only trainees but also expert anesthesiologists should be accustomed to switching syringes in order to avoid intraoperative awareness.

Anesthesiology↗

PubMed2005

A comparison of fentanyl-propofol with a ketamine-propofol combination for sedation during endometrial biopsy.

STUDY OBJECTIVE: The purpose of this study was to compare the clinical activities of ketamine and fentanyl when used in combination with propofol for outpatients undergoing endometrial biopsy. The investigated parameters were respiration, sedation, recovery rate, side effects, time to discharge, and patient satisfaction. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PATIENTS: Forty American Society of Anesthesiologists physical status I and II patients (age range 38-61 years) scheduled for elective endometrial biopsy. INTERVENTIONS: Patients received intravenous bolus doses of either fentanyl 1 microg/kg and propofol 1 mg/kg in (group 1 n = 20) or ketamine 0.5 mg/kg and propofol 1 mg/kg in (group 2 n = 20). MEASUREMENTS: Heart rate, systolic and diastolic blood pressure, respiratory rate, and peripheral O(2) saturation were monitored in all patients. Depth of sedation was assessed by the Ramsay sedation score. The Aldrete score was used for postoperative recovery evaluation. The time to Aldrete score >/=8, side effects, and time to discharge were recorded. MAIN RESULTS: Respiratory depression was observed in 5 patients from group 1 and 1 patient from group 2, but the difference was not significant (P > .05). Nausea, vertigo, and visual disturbances were more frequent in group 2 (P < .05). The time to Aldrete score >/=8 was similar in the 2 groups (6.2 +/- 3.5 minutes in group 1 and 7.0 +/- 3.1 minutes in group 2); the time to discharge was significantly longer in group 2 (71.2 +/- 9.7 minutes in group 1 and 115.2 +/- 25.6 minutes in group 2). Frequency of patient satisfaction was 95% in group 1 and 60% in group 2. CONCLUSIONS: Hemodynamic change and degrees of sedation showed that fentanyl-propofol and ketamine-fentanyl combinations can be used safely in patients undergoing endometrial biopsy. However, with regard to side effects and patient satisfaction, the fentanyl-propofol was superior.

Adult↗

PubMed2000

Clonidine premedication decreases propofol consumption during bispectral index (BIS) monitored propofol-ketamine technique for office-based surgery.

BACKGROUND: Propofol-ketamine anesthesia is a room air, spontaneous ventilation (RASV), dissociative intravenous (IV) sedation technique reported to have a near-zero postoperative nausea and vomiting (PONV) rate. Clonidine premedication has been reported to control blood pressure intra- and postoperatively, as well as to reduce the requirements for hypnotic agents. The bispectral index (BIS) monitor is a reproducible, objective, observer independent, quantitative measurement of the hypnotic state. OBJECTIVE: This study was designed to compare the propofol consumption rate during BIS monitored propofol-ketamine anesthesia for office-based, elective female facial rhytidectomy in patients with and without clonidine premedication. METHODS: Six patients receiving clonidine (200 microg oral premedication administered 30-60 minutes prior to induction of anesthesia were compared with a recent, historical control group of six patients who received no premedication. A BIS of 60-70 was chosen as the standard of comparison for light hypnotic state. A dilute propofol solution was used to gradually titrate anesthesia to a BIS of 60-70 prior to the administration of ketamine. RESULTS: A statistically significant reduction in propofol consumption was observed in the clonidine premedicated female elective rhytidectomy patients compared with those not receiving the clonidine. Other than modestly increased requirements for IV fluids, there were no adverse effects observed with clonidine premedication.

Administration, Oral↗

PubMed2003

Conscious analgesia/sedation with remifentanil and propofol versus total intravenous anesthesia with fentanyl, midazolam, and propofol for outpatient colonoscopy.

BACKGROUND: This study tested the hypothesis that, for colonoscopy, analgesia/sedation with remifentanil and propofol might be more effective compared with anesthesia by intravenous administration of midazolam, fentanyl, and propofol. METHODS: In a prospective, randomized trial, 100 adult patients received either conscious analgesia/sedation (Sedation group) or total intravenous anesthesia (TIVA group). Analgesia/sedation was achieved by infusion of remifentanil (0.20 to 0.25 microg/kg/min) and propofol in titrated doses. TIVA was induced by intravenous administration of fentanyl (2 microg/kg), midazolam (0.05 mg/kg) and propofol (dosage titrated). Cardiorespiratory parameters and bispectral index were monitored and recorded. The quality of the analgesia was assessed with a Numerical Pain Rating Scale (NRS); recovery level and return of psychomotor efficiency were evaluated with, respectively, the Aldrete scale and a Modified Post Anesthesia Discharge Scoring (MPADS) system. RESULTS: Both groups of 50 patients were comparable with respect to demographic data, initial parameters, and duration of colonoscopy. All patients in the TIVA group found the colonoscopy painless (NRS score 0). In the Sedation group, the average pain intensity score was 0.4 (0.8). There was a marked difference between the Sedation and TIVA groups with respect to the time from the end of the procedure until the maximum MPADS score was reached: respectively, -6.9 (4.0) versus 25.7 (8.4) minutes (p < 0.001). In the TIVA group, changes in mean arterial pressure and heart rate and signs of respiratory depression were significant (p < 0.05). CONCLUSIONS: Combined administration of remifentanil and propofol for colonoscopy provides sufficient analgesia, satisfactory hemodynamic stability, minor respiratory depression, and rapid recovery, and allows patients to be discharged approximately 15 minutes after the procedure.

Adolescent↗

PubMed2004

Toward the development of an injectable dosage form of propofol: preparation and evaluation of propofol-sulfobutyl ether 7-beta-cyclodextrin complex.

The objectives of the present study were to undertake activities toward the development of an aqueous-based formulation of propofol (2,6-diisopropyl phenol), using sulfobutylether 7-beta-cyclodextrin (SBECD). Preformulation studies, including high performance liquid chromatography (HPLC) method development and phase-solubility evaluation in the presence of SBECD were conducted. It was determined that equilibrium solubility has been reached by 4-day and 7-day phase-solubility analysis at 30 degrees C and 37 degrees C. The apparent binding constants and various thermodynamic parameters were calculated from this data. These results suggest that "nonclassical hydrophobic effects" are the driving forces for inclusion complex formation. Compounding and lyophilization of the formulation with 20% SBECD yielded a product with propofol concentration of 10 mg/mL. The formulation properties were probed by using techniques that included modulated differential scanning calorimetry (MDSC) and Karl Fischer analysis. MDSC showed that propofol, SBECD, and the Propofol-SBECD complex displayed thermal properties at widely varying temperatures, suggesting the formation of a new solid form. The active pharmaceutical ingredient in the liquid formulation and lyophilized product was determined by the newly developed and qualified HPLC method. Short-term stability studies of the liquid formulation showed that they were stable for a month at 4 degrees C. Short-term stability studies of the freeze-dried cakes showed that the product was stable for over a month at 4 degrees C, 37 degrees C, and 50 degrees C. Based on these preliminary results, we believe that an aqueous based injectable formulation of propofol with sulfobutylether 7-beta-cyclodextrin can be successfully developed.

Algorithms↗

PubMed1990

Total i.v. anaesthesia with propofol and alfentanil: dose requirements for propofol and the effect of premedication with clonidine.

We determined in 51 healthy patients undergoing body surface surgery the dose requirements for propofol, as part of a total i.v. anaesthesia technique with an alfentanil infusion. After premedication with temazepam, patients received alfentanil 50 micrograms kg-1 followed by an infusion of 50 micrograms kg-1 h-1. Patients were anaesthetized with a loading dose of propofol followed by a three-stage infusion designed to reach one of five preselected blood concentrations of propofol. The motor response to the initial surgical incision was noted and probit analysis was used to derive the ED50 (2.94 mg kg-1 h-1; 95% confidence limits: 2.35-3.37 mg kg-1 h-1) and ED95 (4.98 mg kg-1 h-1; 95% limits: 4.13-8.8 mg kg-1 h-1) for the final propotol infusion rate under these conditions. Whole blood concentration!of propofol at the time of the incision was related linearly to the inf!sion rate and the EC50 and EC95 (probit analysis) were derived as !.44 (95% confidence limits 0.62-1.87) and 4.05 (95% confidence lim!ts 2.78-30.5) micrograms ml-1, respectively. Post-operative recovery was!rapid, uncomplicated and uneventful. In a subgroup of eight patients,!the addition of clonidine 0.6 mg to the premedication significantly decreased the requirement for propofol (P less than 0.05) during surgery, but resulted in prolonged recovery times.

Administration, Oral↗