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PubMed1999

Propofol anesthesia for invasive procedures in ambulatory and hospitalized children: experience in the pediatric intensive care unit.

OBJECTIVES: To describe our experience with propofol anesthesia to facilitate invasive procedures for ambulatory and hospitalized children in the pediatric intensive care unit (PICU) setting. METHODS: We retrospectively reviewed the hospital records of 115 children who underwent 251 invasive procedures with propofol anesthesia in our multidisciplinary, university-affiliated PICU during a 20-month period. All patients underwent a medical evaluation and were required to fast before anesthesia. Continuous monitoring of the patient's cardiorespiratory and neurologic status was performed by a pediatric intensivist, who also administered propofol in intermittent boluses to obtain the desired level of anesthesia, and by a PICU nurse, who provided written documentation. Data on patient demographics, procedures performed, doses of propofol used, the occurrence of side effects, induction time, recovery time, and length of stay in the PICU were obtained. RESULTS: Propofol anesthesia was performed successfully in all children (mean age, 6.4 years; range, 10 days to 20.8 years) who had a variety of underlying medical conditions, including oncologic, infectious, neurologic, cardiac, and gastrointestinal disorders. Procedures performed included lumbar puncture with intrathecal chemotherapy administration, bone marrow aspiration and biopsy, central venous catheter placement, endoscopy, and transesophageal echocardiogram. The mean dose of propofol used for induction of anesthesia was 1.8 mg/kg, and the total mean dose of propofol used was 8.8 mg/kg. In 13% of cases, midazolam also was administered but did not affect the doses of propofol used. The mean anesthesia induction time was 3.9 minutes, and the mean recovery time from anesthesia was 28.8 minutes for all patients. The mean PICU stay for ambulatory and ward patients was 140 minutes. Hypotension occurred in 50% of cases, with a mean decrease in systolic blood pressure of 25%. The development of hypotension was not associated with propofol doses, the concomitant use of midazolam, or the duration of anesthesia, but was associated with older patient age. Hypotension was transient and not associated with altered perfusion. Intravenous fluid was administered in 61% of the cases in which hypotension was present. Respiratory depression requiring transient bag-valve-mask ventilation occurred in 6% of cases and was not associated with patient age, propofol doses, concomitant use of midazolam, or the duration of anesthesia. Transient myoclonus was observed in 3.6% of cases. Ninety-eight percent of procedures were completed successfully, and no procedure failures were considered secondary to the anesthesia. Patients, parents, and health care providers were satisfied with the results of propofol anesthesia. CONCLUSIONS: Propofol anesthesia can safely facilitate a variety of invasive procedures in ambulatory and hospitalized children when performed in the PICU and is associated with short induction and recovery times and PICU length of stay. Hypotension, although usually transient, is common, and respiratory depression necessitating assisted ventilation may occur. Therefore, appropriate monitoring and cardiorespiratory support capabilities are essential. Propofol anesthesia in the PICU setting is a reasonable therapeutic option available to pediatric intensivists to help facilitate invasive procedures in ambulatory and hospitalized children.

Adult↗
PubMed1996

Propofol. A pharmacoeconomic appraisal of its use in day case surgery.

Propofol is an intravenous anaesthetic agent that has become widely used in day case surgery. It induces anaesthesia rapidly and 'smoothly', is associated with a quick recovery and has a lower incidence of postoperative nausea and vomiting (PONV) than other agents. In studies comparing propofol with other intravenous anaesthetics (most commonly thiopental sodium) in day case surgery, the use of propofol as induction and/or maintenance anaesthesia was associated with a shorter time to intermediate recovery (street fitness or time to discharge), although the mean time difference was generally less than 1 hour. However, when compared with volatile anaesthetics (particularly desflurane), the differences in time to discharge were smaller. Propofol is also associated with less PONV than barbiturates, volatile anaesthetics or barbiturate/volatile anaesthetic combinations in the immediate postoperative period. The faster recovery time and the decreased incidence of PONV have potential pharmacoeconomic implications. Delayed recovery can increase the use of hospital resources and decrease patient throughput and PONV can incur costs due to an increase in adjunctive medications usage (e.g. antiemetics), nursing time or unintended admissions. The pharmacoeconomic significance of these properties of propofol requires formal evaluation. Pharmacoeconomic investigations, such as cost-effectiveness, cost-benefit and cost-minimisation studies, which include clinical outcome parameters are difficult to conduct in anaesthesia since there are no objective measures of equipotency between anaesthetic agents and because there is no specific health outcome associated with the delivery of anaesthesia. At present, cost-utility studies are not possible because there are no validated instruments for measuring utility in the provision of anaesthesia. To date, pharmacoeconomic analyses of propofol (and other anaesthetic agents) in day case surgery have been restricted to partial cost analyses. Only 2 of these have included the cost of drug wastage, an important consideration since propofol contains no preservative. With 1 exception, these studies have only included drug acquisition costs and propofol was reported to be approximately 1- to 3-fold as costly as other intravenous/inhalational agents. However, these limited analyses have little applicability since they do not include all relevant costs. In addition to drug acquisition costs, pharmacoeconomic studies should also include other direct costs such as the cost of adjunctive medications (including treatment necessary for adverse events), equipment and staff time, indirect costs such as loss of productivity and/or wages and intangible costs such as patient satisfaction and quality of life. A few studies have attempted to quantify some of these factors. Based on differences in recovery time, 2 studies have estimated a decreased demand for nursing staff time associated with the use of propofol compared with thiopental sodium/isoflurane. In addition, informal patient satisfaction assessments show propofol to be equal to or better than other anaesthetic agents. With these broader considerations, it thus remains for future studies to quantify the intangible and indirect costs associated with propofol anaesthesia, to determine whether differences in recovery between propofol and other agents (especially the newer inhalational anaesthetics) are of economic importance, and to identify those instances where propofol use provides the greatest value for available funds.

Ambulatory Surgical Procedures↗
PubMed2003

Effect of variable-dose propofol alone and in combination with two fixed doses of ketamine for total intravenous anesthesia in cats.

OBJECTIVE: To determine the minimum infusion rate (MIR50) for propofol alone and in combination with ketamine required to attenuate reflexes commonly used in the assessment of anesthetic depth in cats. ANIMALS: 6 cats. PROCEDURE: Propofol infusion started at 0.05 to 0.1 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine (low-dose ILD] constant rate infusion [CRI] of 23 microg/kg/min or high-dose [HD] CRI of 46 microg/kg/min), and after 15 minutes, responses of different reflexes were tested. Following a response, the propofol dose was increased by 0.05 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine, and after 15 minutes, reflexes were retested. RESULTS: The MIR50 for propofol alone required to attenuate blinking in response to touching the medial canthus or eyelashes; swallowing in response to placement of a finger or laryngoscope in the pharynx; and to toe pinch, tetanus, and tail-clamp stimuli were determined. Addition of LD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, finger, toe pinch, and tetanus stimuli but did not change those for laryngoscope or tail-clamp stimuli. Addition of HD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, toe pinch, tetanus, and tail-clamp stimuli but did not change finger or laryngoscope responses. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol alone or combined with ketamine may be used for total IV anesthesia in healthy cats at the infusion rates determined in this study for attenuation of specific reflex activity.

Anesthesia↗
PubMed1999

Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial.

OBJECT: Sedation regimens for head-injured patients are quite variable. The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used. METHODS: Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95+/-87 hours) and 19 patients in the morphine group (mean time of morphine usage 70+/-54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events. CONCLUSIONS: Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.

Adult↗
PubMed2000

Induction pain perception after premedication with propofol vs lidocaine: a pilot study.

Propofol, an intravenous (i.v.) sedative-hypnotic agent, is commonly used for the induction of general anesthesia. It has, however, a substantial potential for causing burning pain at the i.v. site. Several preinduction pharmacologic agents are used routinely to blunt or diminish this burning sensation. Little is published on the effect of a preinduction dose of propofol for pain reduction. Lidocaine, the most studied agent, is recommended by the manufacturer of propofol as a preinduction agent to minimize this burning sensation. If lidocaine could be eliminated, time and cost savings from decreased use of drug, syringes, needles, and alcohol swabs would be realized. The purpose of this study was to determine the clinical effectiveness of administering preinduction doses of lidocaine vs propofol for decreasing pain experienced during anesthetic induction with propofol. Thirty unmedicated patients, ASA physical status I or II, scheduled to undergo general anesthesia for a surgical procedure were included. Patients were randomly assigned, using a random number chart, to receive 20 mg propofol or 40 mg lidocaine intravenously before entering the operating room suite. A minimum of 30 seconds, but not more than 45 seconds, following the administration of randomized drug with open-flow i.v. fluid, the induction dose of propofol (2.5 mg/kg) was begun through the same i.v. site. When one half of the dose had been administered and cleared the tubing by visualization, the patient was asked whether any discomfort was felt in the hand. If the response was yes, the patient was asked to rate the pain as mild, moderate, or severe. Then, the anesthetic process continued normally. No statistically significant difference occurred in pain prevention between treatment groups. In the lidocaine group, 53% (8/15) of patients were pain-free; in the propofol group, 47% (7/15) were painfree. However, when pain occurred, it was more likely to be classified as severe by the propofol group, 50% (4/8), compared with the lidocaine group, 14% (1/7). No difference existed in the ability of propofol or lidocaine to decrease the incidence of pain during an induction dose of propofol. The incidence of severe pain, however, was more frequent in the propofol group. The small number of patients experiencing severe pain precluded statistical analysis. Blunting pain associated with propofol warrants further study.

Adolescent↗
PubMed2006

[The injection pain of propofol with different emulsion].

BACKGROUND: Incidence and intensity of pain on intravenous injection of propofol were assessed with emulsion of long-chain/medium-chain triglycerides (LCT/MCT, 50: 50) and only long-chain triglycerides (LCT, 100) in patients undergoing different elective surgical interventions in this prospective, randomized, cross over and double-blinded study. METHODS: 1) Forty six patients were assigned to two groups. One group received 0.2 mg x kg(-1) LCT/ MCT propofol prior to LCT propofol administration. The other group received 0.2 mg x kg(-1) LCT propofol prior to LCT/MCT propofol administration. Pain elicited upon questioning was assessed with each injection in the two groups. Patients were asked to grade the pain as VAS of 0 to 100 mm. 2) Fifty one patients were randomly assigned to two groups. One group received 0.4 mg x kg(-1) LCT propofol. The other group received 0.4 mg x kg(-1) LCT/MCT propofol. Patients were asked to grade the pain as VAS of 0 to 100 mm. RESULTS: Pain of LCT propofol injection was stronger than LCT/MCT propofol. As incidence of 0.4 mg x kg(-1) propofol injection, VAS on LCT/MCT propofol and LCT propofol gave score as 0 and 23.5 (P=0.0019). CONCLUSIONS: Propofol with emulsion of long- and medium-chain triglycerides appears to reduce the injection pain than with emulsion of only long-chain triglycerides.

Anesthesia, Intravenous↗
PubMed2006

[Bispectral index, cerebral state index and the predicted effect-site concentration at different clinical end-points during target-controlled infusion of propofol].

OBJECTIVE: To examine the predicted effect-site concentration of propofol at two clinical end-points: loss of verbal contact (LVC) and loss of consciousness (LOC), and to explore the relationship between bispectral index (BIS) values, cerebral state index (CSI) values and the predicted effect-site concentration during the target-controlled infusion of propofol. METHODS: In 20 patients during the target-controlled infusion of propofol, the propofol infusion was set at an initial effect-site concentration of 0.5 mg/L, and increased by 0.5 mg/L every 5 min until 5 min after the modified observer's assessment of alertness/sedation scale (OAA/S) values reached zero. The predicted effect-site concentration of propofol, the values of CSI and BIS were recorded, and the sedation level was examined by the modified OAA/S every 20s. The predicted effect-site concentrations of propofol in target-controlled infusion (TCI) system were recorded when they increased by more than 0.1 mg/L. The predicted effect-site concentrations of propofol and the values of BIS and CSI at LVC and LOC in 5%, 50% and 95% of the patients were calculated. RESULTS: There was good linearity between BIS and the predicted effect-site concentration of propofol (R(2)=0.787), as well as between CSI and the predicted effect-site concentration of propofol (R(2)=0.792). The predicted effect-site concentrations of propofol at LVC in 5%, 50% and 95% of the patients were 1.1,1.8 and 2.4 mg/L, respectively. The values of BIS and CSI at LVC in 5%, 50% and 95% of the patients were 79.2, 69.2 and 59.2; 74.9, 65.9 and 56.8, respectively. The predicted effect-site concentrations of propofol at LOC in 5%, 50% and 95% of the patients were 1.5, 2.5 and 3.4 mg/L, respectively. At LOC, the values of BIS and CSI in 5%, 50% and 95% of the patient were 73.6, 57.1 and 40.6; 65.2, 54.8 and 44.3, respectively. CONCLUSION: During target-controlled infusion of propofol, LVC and LOC occur within a definite range of predicted effect-site concentrations. There is the good linearity between BIS, CSI and the predicted effect-site concentrations of propofol. CSI may be more useful than BIS in predicting LVC and LOC.

Adult↗
PubMedDate not supplied

In vivo and in vitro effect of cimetidine, inflammation, and hypoxia on propofol kinetics.

Propofol is rapidly cleared from the body by biotransformation; however, the repercussions of changes in cytochrome P-450 activity on propofol rate of elimination are unknown. To assess how changes in cytochrome P-450 activity affect propofol kinetics, one group of rabbits (N = 6) was pretreated with cimetidine, another (N = 6) had an inflammatory reaction produced by the subcutaneous injection of turpentine, and a third one (N = 6) was subjected to mild hypoxia. Propofol was infused (0.3 mg/min/kg) for 40 min; multiple blood samples were withdrawn before and once the infusion was stopped to assess propofol blood kinetics. Cimetidine did not modify propofol kinetics. An inflammatory reaction prolonged propofol half-life without changing significantly its clearance or volume of distribution. Hypoxia decreased propofol clearance and as a consequence, its half-life increased. Parallel studies were conducted in vitro, where propofol metabolism was documented in liver and lung homogenates prepared from controls (N = 6), and from rabbits that were pretreated with cimetidine (N = 3), had an inflammatory reaction (N = 5), or were hypoxic (N = 6). In controls, the lung biotransformed propofol as rapidly as the liver, and both organs generated an unidentified polar metabolite. Cimetidine did not affect the in vitro metabolism of propofol. The inflammatory reaction reduced the in vitro rate of elimination of propofol and, as a consequence, the production rate of the metabolite was also decreased in liver and lung homogenates. Hypoxia diminished hepatic metabolism of propofol but did not influence that in lung homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

ICP is lower during propofol anaesthesia compared to isoflurane and sevoflurane.

OBJECTIVES: Propofol is a cerebral vasoconstrictor while inhalation anaesthetics like isoflurane and sevoflurane act as cerebral vasodilators in both animal and human studies. This difference of action upon cerebral vessels might implicate a lower ICP during propofol anaesthesia. Cerebral metabolism is decreased by all three anaesthetics. In a prospective, randomised multicenter study ICP was compared during anaesthesia with propofol, isoflurane and sevoflurane. METHODS: 117 patients subjected to elective craniotomy for supratentorial tumour. Propofol: N = 41; isoflurane: N = 38; sevoflurane: N = 38. Nitrous oxide was omitted and all anaesthetics were supplemented with a continuous infusion of fentanyl. ICP was measured subdurally after removal of the bone flap. MABP, CPP, PCO2, AVDO2, rectal temperature, tumour size and midline shift were registered too. STATISTICS: Kruskal-Wallis Variance on Ranks. All values in medians with range. P < 0.05 was considered significant. RESULTS: ICP (mmHg): propofol 7 (-1-20), isoflurane 12 (1-29), sevoflurane 11 (2-32). ICP was significantly lower in the propofol group compared to the isofluane and sevoflurane groups. CPP (mmHg): propofol 80 (45-104), isoflurane 60 (32-84), sevoflurane 63 (44-77). CPP was significantly higher in the propofol group compared to the isoflurane and sevoflurane groups. AVDO2 (mmol/l): propofol 3.1 (0.9-5.1), isoflurane 2.5 (1.1-4.5), sevoflurane 2.6 (0.8-4.1). AVDO2 was significantly higher in the propofol group compared to the isoflurane and sevoflurane groups. No significant differences in PCO2, rectal temperature, tumour size and midline shift were found. CONCLUSIONS: Subdural ICP is significantly lower during propofol anaesthesia compared to isoflurane and sevoflurane anaesthesia. CPP and AVDO2 are significantly higher during propofol anaesthesia compared to isoflurane and sevoflurane anaesthesia.

Adult↗
PubMed1991

Disposition of propofol infusions for caesarean section.

The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.

Adult↗
PubMed2006

Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department.

STUDY OBJECTIVE: We compare the efficacy, adverse events, and recovery duration of etomidate and propofol for use in procedural sedation in the emergency department (ED). METHODS: This was a randomized nonblinded prospective trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients received either propofol or etomidate. Doses, vital signs, nasal end-tidal CO2 (ETCO2), pulse oximetry, and bispectral electroencephalogram analysis scores were recorded. Subclinical respiratory depression was defined as a change in ETCO2 greater than 10 mm Hg, an oxygen saturation of less than 92% at any time, or an absent ETCO2 waveform at any time. Clinical events related to respiratory depression, including an increase in supplemental oxygen, the use of a bag-valve-mask apparatus, airway repositioning, or stimulation to induce breathing, were noted during the procedure. After the procedure, patients completed visual analog scales about perceived pain during the procedure and recall of the procedure. RESULTS: Two hundred twenty patients were enrolled; 214 underwent sedation and were analyzed. One hundred five patients received etomidate and 109 received propofol. No clinically significant complications were noted. Subclinical respiratory depression was observed in 36 of 105 (34.3%) patients in the etomidate group and 46 of 109 (42.2%) in the propofol group (difference -7.9%; 95% confidence interval [CI] -20.9% to 5.1%). Myoclonus was noted in 21 of 105 (20.0%) patients in the etomidate group and 2 of 109 (1.8%) in the propofol group (difference 18.2%; 95% CI 10.1% to 26.2%). The mean difference between baseline systolic blood pressure and the nadir was 3.8% (95% CI 2.3% to 5.3%) for etomidate and 7.9% (95% CI 6.1% to 9.7%) for propofol. Clinical events related to respiratory depression included an increase in supplemental oxygen in 6.7% of etomidate patients and 5.5% of propofol patients (difference 1.2%; 95% CI -5.2% to 7.6%), the use of bag-valve-mask apparatus in 3.8% of patients in the etomidate groups and 4.6% in the propofol group (difference -0.8%; 95% CI -6.1% to 4.6%), airway repositioning in 13.3% of etomidate patients and 11.0% of propofol patients (effect size 2.3%; 95% CI -6.4% to 11.1%), and stimulation to induce breathing in 11.4% of etomidate patients and 11.9% of propofol patients (difference -0.5%; 95% CI -9.1% to 8.1%). The procedures were successful in 93 of 105 (88.6%) for etomidate and 106 of 109 (97.2%) for propofol (difference -7.4%; 95% CI -14.3% to -1.1%). CONCLUSION: Etomidate and propofol appear equally safe for ED procedural sedation; however, etomidate had a lower rate of procedural success and induced myoclonus in 20% of patients.

Adolescent↗
PubMed2001

Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index.

STUDY OBJECTIVE: To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for "adequate depth" of anesthesia. DESIGN: Prospective, open-label study. SETTING: Department of orthopedics of a university hospital. PATIENTS: 20 patients undergoing orthopedic surgery. INTERVENTIONS: Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5-8 microg/mL) and remifentanil (2-15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations. MAIN RESULTS: The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5-8 microg/mL and remifentanil 1-30 ng/mL) is a concave up hyperbola ((0.15. C(prop))(3.13). C(rem) = 1) with C(prop) = propofol plasma concentration [microg/mL] and C(rem) = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole. CONCLUSIONS: The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.

Adult↗
PubMed1999

Use of propofol for office-based anesthesia: effect of nitrous oxide on recovery profile.

STUDY OBJECTIVE: To evaluate the effect of nitrous oxide (N2O) on the recovery profile and the incidence of postoperative nausea and vomiting (PONV) after office-based surgery performed under propofol anesthesia. DESIGN: Prospective, randomized, single-blind study. SETTING: Office-based surgical center. PATIENTS: 69 ASA physical status I, II, and III healthy, consenting outpatients undergoing superficial surgical procedures lasting 15 to 45 minutes. INTERVENTIONS: After a standard propofol induction (1.5 mg.kg-1 i.v.), anesthesia was initially maintained with propofol, 100 micrograms.kg-1.min-1 i.v., in combination with either air or N2O 65% in oxygen. The propofol infusion rate was subsequently varied to maintain an adequate depth of anesthesia. All patients received local anesthetic infiltration prior to the surgical incision, as well as during the operation. No prophylactic antiemetics were administered. MEASUREMENTS AND MAIN RESULTS: Recovery times and the incidences of PONV were recorded during the first 24 hours after surgery. Early and late recovery variables were similar in the two treatment groups; however, 65% N2O produced a 19% decrease in the propofol maintenance dosage requirement. One patient (3%) experienced nausea prior to discharge in the propofol-N2O group, and two patients (6%) experienced nausea at home in the propofol alone group. None of the patients vomited or received antiemetic medication during the 24 hours postdischarge period. Ninety-seven percent of patients receiving propofol alone and all of the patients in the propofol-N2O group were "very satisfied" with their anesthetic experience. CONCLUSIONS: In outpatients undergoing office-based surgical procedures with propofol anesthesia, administration of 65% N2O decreased the anesthetic requirement without increasing PONV. Therefore, use of a propofol-N2O combination may be a cost-effective alternative to propofol alone for office-based anesthesia.

Ambulatory Surgical Procedures↗
PubMed1998

Influence of different fat emulsion-based intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol.

PURPOSE: The influence of different intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol was investigated using the effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. METHODS: Propofol was administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats. Propofol was formulated as a 1% emulsion in an Intralipid 10%-like fat emulsion (Diprivan-10, D) or as a 1%- or 6% emulsion in Lipofundin MCT/LCT-10% (P1% and P6%, respectively). EEG was recorded continuously and arterial blood samples were collected serially for the determination of propofol concentrations using HPLC. RESULTS: Following bolus infusion, the pharmacokinetics of the various propofol emulsions could adequately be described by a two-compartmental pharmacokinetic model. The average values for clearance (Cl), volume of distribution at steady-state (Vd,ss) and terminal half-life (t1/2, lambda 2) were 107 +/- 4 ml/min/kg, 1.38 +/- 0.06 l/kg and 16 +/- 1 min, respectively (mean +/- S.E. n = 22). No significant differences were observed between the three propofol formulations. After continuous infusion these values were 112 +/- 11 ml/min/kg, 5.19 +/- 0.41 l/kg and 45 +/- 3 min, respectively (mean +/- S.E., n = 20) with again no statistically significant differences between the three propofol formulations. Comparison between the bolus- and the continuous infusion revealed a statistically significant difference for both Vd,ss and t1/2, lambda 2 (p < 0.05), whereas Cl remained unchanged. In all treatment groups infusion of propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop was observed between blood concentrations and EEG effect for all formulations. The hysteresis was minimized by a semi-parametric method and resulted in a biphasic concentration-effect relationship of propofol that was described non-parametrically. For P6% a larger rate constant onset of drug effect (t1/2,keo) was observed compared to the other propofol formulations (p < 0.05). CONCLUSIONS: The pharmacokinetics and pharmacodynamics of propofol are not affected by to a large extent the type of emulsion nor by the concentration of propofol in the intravenous formulation.

Anesthetics, Intravenous↗
PubMed1995

Stability of propofol with parenteral nutrient solutions during simulated Y-site injection.

The stability of propofol in three parenteral nutrient (PN) solutions was studied. Nine combinations of three PN solutions (with amino acid concentrations of 1.5, 2.5, and 5.0%) and three propofol concentrations (0.5, 2.0, and 3.0 mg/mL) were prepared in triplicate and stored at 22 degrees C under fluorescent light. Duplicate samples were visually inspected for color changes, precipitation, or gas formation, and the pH of the samples was determined. These samples were evaluated for propofol content by high-performance liquid chromatography at zero, one, three, and five hours. The stability of the vehicle for propofol injection (similar in composition to fat emulsion) was evaluated by visual inspection, pH determination, and particle-size measurements at zero, one, three, and five hours. The concentration of propofol in all of the propofol-PN combinations remained greater than 90% of the initial concentration except for the combination of propofol 0.5 mg/mL and the 1.5% amino acid PN solution, which contained only 72% of the initial propofol concentration five hours after the start of the study. Visual examination revealed no evidence of color change, precipitation, gas formation, creaming, or streaking in any of the propofol-PN solution combinations. No substantial changes in pH occurred. The particle size of the vehicle for propofol remained relatively constant throughout the study period. Propofol 2 and 3 mg/mL was stable for five hours during simulated Y-site injection with PN solutions containing 1.5, 2.5, and 5% amino acids. Propofol 0.5 mg/mL was stable during simulated Y-site injection with the same PN nutrition solutions for five hours, except for the solution containing 1.5% amino acid.

Chemistry, Pharmaceutical↗
PubMed2003

Target-controlled infusion of propofol and remifentanil in cardiac anaesthesia: influence of age on predicted effect-site concentrations.

BACKGROUND: Propofol-anaesthesia administrated via target-controlled infusion (TCI) has been proposed for cardiac surgery. Age-related changes in pharmacology explain why propofol dose requirement is reduced in elderly patients. However, the Marsh pharmacokinetic model incorporated in the Diprifusor propofol device does not take age into account as a covariable. In the absence of depth of anaesthesia monitoring, this limitation could cause adverse cardiovascular effects resulting from propofol overdose in older patients. We assessed the influence of age on effect-site propofol concentrations predicted by the Diprifusor and titrated to the bispectral index score (BIS) during cardiac anaesthesia. METHODS: Forty-five patients received propofol by Diprifusor and remifentanil by software including Minto model. Propofol and remifentanil effect-site concentrations were adapted to BIS (40-60) and haemodynamic profile, respectively. The influence of age on effect-site concentrations was assessed by dividing patients into two groups: young (<65 yr) and elderly (> or =65 yr). RESULTS: For a similar depth of anaesthesia, effect-site propofol concentrations were significantly lower in elderly patients at the different stages of cardiac surgery. The mean dose of propofol required to perform tracheal intubation was significantly lower in elderly patients. However, the overall doses of propofol were comparable in both groups. Neither effect-site remifentanil concentrations nor overall doses of remifentanil were significantly different between the two groups. CONCLUSIONS: In cardiac anaesthesia, target concentrations of propofol must be reduced in elderly patients. Although this probably contributes to improving intraoperative haemodynamic stability, the absence of decrease in overall dose requirement of propofol suggests that this adjustment is relatively moderate.

Adolescent↗
PubMed2005

Why do women wake up faster than men from propofol anaesthesia?

BACKGROUND: It has repeatedly been shown that female patients wake up faster from propofol anaesthesia than male patients. The reason for this is not clear. It is possible that female patients have a more rapid decline in plasma propofol concentration after termination of an infusion, or there could be gender differences in the sensitivity to propofol, making women wake up at higher concentrations. We tested the hypothesis that women wake up faster because of a more rapid decline in plasma propofol. METHODS: Sixty adult patients (30 female and 30 male; ASA I or II) undergoing lower limb surgery under regional anaesthesia, were enrolled in an open study. Propofol was given as the only hypnotic drug, administered by the plasma target control system (TCI) Diprifusor, titrated to bispectral index (BIS) values of 40-60. Blood samples for propofol measurements were taken just before the propofol infusion was stopped and when the patients woke up. RESULTS: The female patients woke up faster than the male patients (5.6 vs 8.2 min, P=0.003). The plasma propofol concentration declined more rapidly in the women (P=0.02). An additional significant finding was that the TCI algorithm had a better fit for the women than for the men, with a median prediction error (MDPE) of 2% in the female patients compared with 40% in the male patients (P<0.001). At emergence the men had a significantly higher measured propofol concentration than the women (P=0.05). CONCLUSION: The female patients had a more rapid decline in plasma propofol at the end of infusion. Gender differences in pharmacokinetics could explain the faster emergence for female patients after propofol anaesthesia, and gender differences in propofol sensitivity may also be present.

Adult↗
PubMed1998

Propofol clearance and distribution volume increase in patients with hyperthyroidism.

UNLABELLED: We investigated propofol pharmacokinetics in seven hyperthyroid (Group H) and eight euthyroid (Group E) patients undergoing elective subtotal thyroidectomy. Anesthesia was induced with an i.v. injection of 2 mg/kg propofol and maintained with a continuous propofol infusion while ventilation was controlled with 60% nitrous oxide in oxygen. The propofol infusion rate was adjusted in the range of 4-10 mg.kg-1.h-1 based on physiological signs such as heart rate and blood pressure. Arterial blood was sampled to measure the propofol concentration. The mean propofol infusion rates were higher in hyperthyroid than in patients with euthyroidism (median values Group H 10.0 mg.kg-1.h-1, Group E 6.5 mg.kg-1.h-1; P < 0.05), although the reverse was true for average propofol concentrations (Group H 1.8 micrograms/mL, Group E 3.3 micrograms/mL; P < 0.05). Group H also had higher values for propofol clearance (5.1 L/min versus 2.5 L/min; P < 0.05) and distribution volume at steady state (10.0 L/kg versus 2.8 L/kg; P < 0.05). Because distribution volume and clearance in patients with hyperthyroidism were increased, propofol concentrations could not reach anesthetic levels. IMPLICATIONS: Propofol decreases heart rate and blood pressure, which are desirable properties for anesthesia in patients with hyperthyroidism. However, because clearance and distribution volume of propofol are increased, propofol infusion rates had to be increased to reach anesthetic blood concentrations.

Adult↗