Propofol Infusion Rate Research Articles

Remifentanil in combination with propofol for spontaneous ventilation anaesthesia

We have investigated the effect of four doses of remifentanil on the incidence of respiratory depression and somatic response at incision. Remifentanil was administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1, respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in 88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40% in the other groups. Respiratory depression after incision increased from 6% with remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1. Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05 microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

EMERGENCE AND RECOVERY FROM BIS-GUIDED ADMINISTRATION OF ANESTHESIA

S499 INTRODUCTION: Remifentanil, a short-acting opioid has been shown to reduce the amount of co-administered hypnotic required. [1] Bispectral index (BIS), a processed EEG variable, correlates with the level of hypnosis during anesthesia. [2,3] BIS levels under 60 are required to obtain adequate hypnosis during surgical procedures. [4,5] This study compares emergence and recovery from BIS-guided anesthesia with remifentanil with either isoflurane or propofol. METHODS: After HIC approval, 76 consenting patients were randomized to two groups, one receiving remifentanil and isoflurane (ISO), the other remifentanil and propofol (PRO). In both groups, anesthesia was induced with propofol and remifentanil. Hemodynamic responses were used to titrate remifentanil infusion rates, maintaining MAP and heart rate within a 20% range compared with awake baseline. BIS was used to titrate ISO/PRO, maintaining BIS between 45 and 60. Thirty minutes before end of surgery 0.15 mg/kg morphine was administered for postoperative pain control. 15 min. before end of surgery anesthetics were reduced to keep BIS between 60 and 75. At the end of surgery, remifentanil and anesthetic agents were discontinued. Patients were observed for return of spontaneous and adequate respiration, return of consciousness and extubation. Postanesthetic assessment was performed using a modified Aldrete-score (0-10). [6] A score of 9 was needed for discharge. Statistical analysis was performed using Chi square and repeated t-testing (Bonferoni-Holms adjusted). RESULTS: Demographic data showed no significant differences between the groups (Table 1). Surgical duration was significantly shorter with isoflurane (94 +/- 40 min) than with propofol (121 +/- 53 min).Table 1: Demographic dataRecovery data were calculated from end of drugs' administration to return of spontaneous respiration (spont resp), adequate respiration (adeq resp), consciousness (ROC), extubation (EXT) and and full recovery (REC). (Table 2)Table 2: Recovery times (min)Mean remifentanil infusion rate was significantly lower (p<0.001) with ISO (0.18 +/- 0.06 [micro sign]g/kg/min) than with PRO (0.31 +/- 0.20 [micro sign]g/kg/min). Average isoflurane endtidal concentration was 0.66 +/- 0.13 %, propofol infusion rate 123 +/- 48 [micro sign]g/kg/min. CONCLUSIONS: BIS-guided anesthesia with remifentanil in combination with both isoflurane or propofol has comparably short recovery times. At comparable hypnotic levels, controlled by BIS, hemodynamic control requires higher doses of remifentanil with propofol, than with isoflurane.

Postoperative Sedation with Propofol Infusion

This study was designed to investigate the haemodynamic response and pharmacokinetics of a low-dose propofol continuous infusion in providing sedation in patients who required mechanical ventilation after coronary artery bypass grafting surgery. 22 male patients, aged between 45 and 65 years, were evaluated in an open, uncontrolled study. At the end of the surgical procedure, a low-dose (1 mg/kg/h) propofol infusion was started and adjusted to optimise sedation according to the Ramsay scale. The mean propofol infusion rate was 1.42 +/- 0.4 mg/kg/h. Electrocardiogram, systemic and pulmonary arterial pressure, and central venous pressure were monitored continuously. Left ventricular shortening fraction was calculated by transoesophageal echocardiography. Propofol plasma levels were calculated in 10 patients to evaluate the pharmacokinetics. Throughout the duration of the study all patients were haemodynamically stable. Sedation was maintained for 363 +/- 244 minutes and was adequate in all patients. The clinical recovery time (postsedation responsiveness) was 15.7 +/- 6.2 minutes, after infusion suspension. There was no correlation between propofol plasma levels or propofol infusion rate and the depth of sedation (respectively, r = 0.39 and r = 0.23), while there was a good correlation (r = 0.62) between propofol infusion rate and plasma levels. Open two-compartment model pharmacokinetics were demonstrated. Low-dose propofol infusion (1 to 2 mg/kg/h) proved to be well tolerated and effective in maintaining sedation after cardiac surgery. Sedation was quickly obtained without a propofol loading dose; steady-state plasma concentrations of 0.6 to 0.8 mg/L were rapidly achieved. Propofol pharmacokinetics ensure rapid clearance with rapid clinical recovery.

Titration of propofol infusion using processed electroencephalogram during combined general and spinal anesthesia.

To determine the necessary mean infusion rate of propofol during combined nitrous oxide (N2O) and propofol spinal anesthesia by using the processed electroencephalogram (pEEG). Twelve elective gynecological patients were monitored by a Dräger pEEG monitor under N2O and propofol spinal anesthesia. To make it easier to detect an inadequate depth of anesthesia, muscle relaxants were not given and the patients breathed spontaneously through a laryngeal mask airway. Manual step-down infusion of propofol was employed to provide intraoperative hypnosis. Propofol infusion was titrated to maintain cardiorespiratory parameters within 20% of baseline and the 90th percentile of the spectral edge frequency (SEF 90) of the pEEG between 10 and 13.5 Hz. The mean (SD) induction dose of propofol was 2.9 (0.4) mg·kg-1. The mean (SD) maintenance infusion rate was 4.2 (0.5) mg·kg-1·h-1. The mean (SD) time from the end of propofol infusion to the opening of the patient's eyes was 5.4 (2.0) min. No gross movements or intraoperative awareness was recognized. The mean (SD) SEF 90 during the maintenance of anesthesia was 12.2 (1.5) Hz, which increased significantly to 16.2 (1.9) Hz at 1 min before the patients opened their eyes in reponse to verbal commands. Titration of propofol infusion using SEF during combined general and spinal anesthesia provided a rapid recovery without any clinical signs of inadequate anesthesia.

The changing role of monitored anesthesia care in the ambulatory setting.

The changing role of monitored anesthesia care in the ambulatory setting.

Use of Alfentanil and Propofol for Outpatient Monitored Anesthesia Care

Propofol and alfentanil are both rapid and short-acting drugs that can be used for sedation and analgesia during monitored anesthesia care (MAC). This study was designed to determine the optimal infusion rates of propofol and alfentanil when administered during local anesthesia. In this randomized, double-blind study, we evaluated the effects of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery. Seventy-two consenting ASA physical status I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups. All patients received midazolam, 2 mg intravenously (IV) for premedication. Propofol was infused at 0, 25, 50, or 75 micro g [center dot] kg-1 [center dot] min-1 during the operation. Sedation was evaluated using the Observer's Assessment of Alertness/Sedation (OAA/S) scale at 5-min intervals by a blinded observer. Two minutes before the infiltration of the local anesthetic solution, a bolus of alfentanil, 2.5 micro g/kg IV, was administered, followed by a maintenance infusion of 0.5 micro g [center dot] kg-1 [center dot] min-1. The alfentanil infusion rate was subsequently varied to maintain patient comfort and stable cardiovascular and respiratory function. Pictures were shown at the start of the propofol infusion, upon initiating the alfentanil infusion, and at 45 min after the skin incision to evaluate recall of intraoperative events. Propofol produced dose-dependent increases in the level of sedation (with median OAA/S scores of 2-4, P < 0.05). Higher infusion rates of propofol (50-75 micro g [center dot] kg-1 [center dot] min-1) produced significant amnesia, opioid-sparing effects (alfentanil 0.3 +/- 0.2 vs 0.6 +/- 0.2 micro g [center dot] kg-1 [center dot] min-1), and less postoperative nausea and vomiting (P < 0.05). However, episodes of transient hemoglobin oxygen desaturation were more common in the deeply sedated patients. Thus, in healthy outpatients premedicated with midazolam, 2 mg IV, a propofol infusion of 25-50 micro g [center dot] kg-1 [center dot] min-1 in combination with an alfentanil infusion of 0.2-0.4 micro g [center dot] kg-1 [center dot] min (-1) is recommended for sedation and analgesia during MAC in the ambulatory setting. Implications: Sedation is often given during local anesthesia. This study demonstrated that administration of an intravenous anesthetic, propofol, in combination with an opioid infusion (i.e., alfentanil) to provide sedation analgesia and amnesia with a low incidence of side effects, such as nausea and vomiting and respiratory depression in outpatients premedicated with midazolam. (Anesth Analg 1997;85:566-72)

Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to various noxious stimuli.

Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation. The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp50loss of consciousness, 4.4 microg/ml (range, 3.8-5.0); Cp50tetanus, 9.3 microg/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 microg/ml (range, 8.9-10.8); Cp50skin incision, 10.0 microg/ml (range, 8.1-12.2); and Cp50intubation, 17.4 microg/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion. The authors successfully defined the propofol concentration required for various stimuli. Tracheal intubation was the strongest stimulus. The absence of somatic reactions for propofol does not guarantee hemodynamic stability without fentanyl. Propofol with fentanyl was able to suppress motor and hemodynamic reactions to various noxious stimuli.

Safe anesthetic management of patients undergoing a novel method of treating human hepatocellular cancer

Study Objective: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. Design: Nonrandomized open study. Setting: University cancer center operating room. Patients: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). Interventions: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 μg/kg) and one of alfentanil (2 μg/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. Measurements and Main Results: End-tidal CO 2 (P ETCO 2), respiratory rate, oxygen saturation (SaO 2), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 μg) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and P ETCO 2 level of 38 ± 4 mmHg and SaO 2 greater than 94 % were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 ± 88 mg and 23.7 ± 3.6 μg/kg/min; alfentanil, 3,350 ± 1,468 μg and 0.32 ± 0.14 μg/kg/min. Conclusions: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.

A pharmacodynamic study of propofol or propofol and ketamine infusions in ponies undergoing surgery

The pharmacodynamics of infusions of propofol alone (group 1) were compared with the pharmacodynamics of infusions of propofol and ketamine together (group 2) in eight ponies undergoing castration. Anaesthesia was induced with detomidine, 20 μg kg −1, followed by ketamine, 2·2 mg kg −1. Subsequently, a bolus dose of propofol, 0·5 mg kg −1, was administered intravenously to both groups, and an infusion of propofol was given for an average of 74 minutes to group l, and an infusion of propofol and ketamine was given for 60 minutes to group 2. The mean ( sd) infusion rates of propofol were 0·330 (0·050) mg kg −1 min −1 in group 1, and 0·124 (0·009) mg kg −1 in group 2, and the ketamine infusion rate was maintained constant at 40 μg kg −1 mint. Arterial hypotension and marked respiratory depression were evident in some of the ponies receiving propofol alone, whereas in the ponies anaesthetised with propofol and ketamine, respiratory and cardiovascular parameters were well maintained. All the ponies in both groups recovered quickly from anaesthesia, with mean times to sternal recumbency and standing of 19·8 (8·0) minutes and 27·2 (7·4) minutes respectively for group 1 and 8·4 (3·2) min and 14·9 (10·1) minutes for group 2.

A comparison of propofol and remifentanil during monitored anesthesia care

To compare remifentanil, an esterase-metabolized opioid, to a standard propofol-based sedation technique for monitored anesthesia care (MAC). Non-randomized, open label. University hospital. 44 healthy female outpatients undergoing breast biopsy procedures under local anesthesia. All patients received intravenous (IV) midazolam 2 mg, followed by a continuous infusion of either propofol 75 micrograms/kg/min, or remifentanil 0.1 microgram/kg/min, which was subsequently titrated to maintain optimal patient comfort without respiratory depression. Surgical-related pain was treated by injecting additional local anesthetic solution and "rescue" boluses of fentanyl 25 micrograms IV. Sedation, pain, and discomfort were monitored using standardized rating scales at 1 to 5 minute intervals. Recovery times were measured from the end of the study drug infusions. Propofol resulted in significantly higher median sedation scores compared with remifentanil, with 73% of patients requiring a decrease in the propofol infusion rate because of "excessive" sedation. Local anesthetic requirements, pain, and discomfort scores during surgery were similar in both groups. Remifentanil resulted in greater respiratory depression compared with propofol, with decreases in the remifentanil infusion rate required by 41% of patients because of a slow respiratory rate (< 8 bpm) and/or oxygen desaturation measured by pulse oximetry (SpO2 < 90%). Median times to ambulation and to being judged "fit for discharge" were significantly shorter following propofol (40 and 47 minutes, respectively) compared with remifentanil (52 and 58 minutes, respectively). Remifentanil provided comparable intraoperative conditions and patient comfort at a lower sedation level compared with propofol. However, remifentanil was associated with greater respiratory depression and a longer time to home readiness.

Computer Control of Propofol Infusion using Quantitative and Qualitative Approaches

A two-level hierarchical structure using quantitative and qualitative approaches for controlling propofol infusion rate is proposed in this paper. The first level merges online measurements (i.e. systolic arterial pressure and heart rate) to interpret the primary depth of anaesthesia. The second level uses an average three-comparanent pharmacokinetic model to predict the propofol concentration in the blood of the patient Then, using fuzzy set theory to combine these two levels, a lookup table to administer the propafol infusion rate is obtained. This lookup table has given confidence of anaesthetists to perform automatic. control of propofol in clinical trials at the next stage.

A pharmacokinetically based propofol dosing strategy for sedation of the critically ill, mechanically ventilated pediatric patient.

To assess the pharmacokinetics and pharmacodynamics of propofol sedation of critically ill, mechanically ventilated infants and children. A prospective clinical study. A pediatric intensive care unit (ICU) in a university hospital. Clinically stable, mechanically ventilated pediatric patients were enrolled into our study after residual sedative effects from previous sedative therapy dissipated and the need for continued sedation therapy was defined. Patients were generally enrolled just before extubation. A stepwise propofol dose escalation scheme was used to determine the steady-state propofol dose necessary to achieve optimal sedation, as defined by the COMFORT scale, a validated scoring system which reliably and reproducibly quantifies a pediatric patient's level of distress. When in need of continued sedation, study patients received an initial propofol loading dose of 2.5 mg/kg and were immediately started on a continuous propofol infusion of 2.5 mg/kg/hr. The propofol infusion rate was adjusted and repeat loading doses were administered, if needed, using a coordinated dosing scheme to maintain optimal sedation for a 4-hr steady-state period. After 4 hrs of optimal sedation, the propofol infusion was discontinued and simultaneous blood sampling and COMFORT scores were obtained until the patient recovered. Additional blood samples were obtained up to 24 hrs after stopping the infusion and analyzed for propofol concentration by high-performance liquid chromatography. Twenty-nine patients were enrolled into this study. One patient was withdrawn from this study because of an acute decrease in blood pressure occurring with the first propofol loading dose; 28 patients completed the study. All patients were sedated immediately after the first 2.5-mg/kg propofol loading dose. Eight patients were adequately sedated with the starting propofol dose regimen, whereas five patients required downward dose adjustment and 11 patients required dosage increases to achieve optimal sedation. Four patients failed to achieve adequate sedation after five dose escalations and the drug was stopped. Recovery from sedation (COMFORT score of > or = 27) after stopping the propofol infusion was rapid, averaging 15.5 mins in 23 of 24 evaluable patients. In 13 patients who were extubated after stopping the propofol infusion, the time to extubation was also rapid, averaging 44.5 mins. Determination of the blood propofol concentration at the time of recovery from propofol sedation was possible in 15 patients. The blood propofol concentration was variable, ranging between 0.262 to 2.638 mg/L but < or = 1 mg/L in 13 of 15 patients. Similarly, tremendous variation was observed in propofol pharmacokinetics. Propofol disposition was best characterized by a three-compartment model with initial rapid distribution into a small central compartment, V1, and two larger compartments, V2 and V3, which are two-and 20-fold greater in volume, respectively, than V1. Redistribution from V2 and V3 into V1 was much slower than ingress, underscoring the importance of the propofol concentration in V1 as reflective of the drug's sedative effect. Propofol was well tolerated. Two patients experienced an acute decrease in blood pressure which resolved without treatment. We conclude that a descending propofol dosing strategy, which maintains the propofol concentration constant in the central compartment (V1) while drug accumulates in V2 and V3 to intercompartmental steady-state, is necessary for effective propofol sedation in the pediatric ICU. Our proposed dosing scheme to achieve and maintain the blood propofol concentration of 1 mg/L would appear effective for sedation of most clinically stable, mechanically ventilated pediatric patients.

Midazolam and awareness with recall during total intravenous anaesthesia

A double-blind study was undertaken to evaluate the influence of graded doses of midazolam on propofol infusion requirements, recovery characteristics and the quality of recovery, associated with propofol/alfentanil/O2 total intravenous anaesthesia (TIVA). Ninety ASA Class I and II subjects scheduled for arthroscopic knee surgery were randomly allocated to receive either placebo (Group PLAC), or midazolam doses of 15, 30 or 45 micrograms.kg-1 (Groups M-15, M-30 and M-45, respectively). Anaesthesia was induced and maintained with propofol (infused initially at 100 micrograms.kg-1.min-1, and adjusted there after according to anaesthetic depth) and alfentanil (loading dose of 20 micrograms.kg-1, followed by infusion at 0.5 microgram.kg-1. min-1). Postoperatively, times to awakening, recovery, and discharge were evaluated, in addition to psychometric evaluations using the Trieger Dot Test (TDT). The study was discontinued prematurely, as six patients unexpectedly experienced intraoperative awareness with recall (4/21 = 19.1% of patients with PLAC vs 2/69 = 2.9% of patients in the midazolam groups, P < 0.04). Induction requirements of propofol were found to be lower in the M-30 and M-45 groups when compared with PLAC (P < 0.05), whereas propofol infusion requirements were similar among groups. Times to awakening and discharge from the Recovery Room and Day Care Unit, as well as TDT scores, were no greater in any midazolam group than in PLAC. Midazolam 30-45 micrograms.kg-1 decreases the amount of propofol required for anaesthetic induction, without influencing recovery profiles or patient discharge times from the Day Care Unit. Despite careful modulation of the propofol infusion rate, six patients unexpectedly experienced intraoperative awareness with recall, with the lowest incidence occurring in those groups where patients had received midazolam.

Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg −1 intravenously (group 1) or with a mixture of propofol at 3 mg kg −1 and ketamine at 1 mg kg −1 intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean ( SD) duration of anaesthesia was 64·8 (3·1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56·6 (13·1) minutes in group 1 and 50·3 (21·4) minutes in group 2; the mean volume of distribution at steady state was 1037 (0480) litre kg −1 in group 1 and 1·515 (0939) litre kg −1 in group 2; the mean body clearance was 85·4 (28·0) ml kg −1 min −1 in group 1 and 1280 (35·0) ml kg −1 min −1 in group 2; the mean residence time corrected for a bolus injection was 12·1 (4·2) minutes in group 1 and 11·9 (6·6) minutes in group 2; for the infusion, the mean residence time was 72·1 (4·2) minutes in group 1 and 69·9 (7·9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2·8 (0·4) 6·3 (1·2) and 10·9 (1·6) minutes from the end of the infusion, and the times for group 2 were 5·3 (0·9), 11·2 (1·7) and 15·1 (2·2) minutes.

Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study

The pharmacokinetics of propofol and ketamine administered together by infusion were investigated in four ponies. Blood propofol and plasma ketamine and norketamine concentrations were measured by high performance liquid chromatography. After premedication with detomidine (20 μg kg −1) anaesthesia was induced with ketamine (2·2 mg kg −1 intravenously). The trachea was intubated and the ponies were allowed to breathe 100 per cent oxygen. A bolus dose of propofol (0·5 mg kg −1) was then administered intravenously and propofol and ketamine were infused for 60 and 45 minutes, respectively. The average mean infusion rate of propofol was 0·136 mg kg −1 min −1, and the ketamine infusion rate was maintained at 50 μg kg −1 min −1. The mean ( SD) elimination half-lives of propofol and ketamine were 69·0 (8·0) and 89·8 (26·7) minutes, the mean volumes of distribution at steady state were 0·894 (0·161) litre kg −1 and 1·432 (0·324) litre kg −1 the mean body clearances were 33·1 (4·5) and 23·9 (3·8) ml kg −1 min −1 and the mean residence times for the infusion were 87·1 (4·1) and 110·7 (8·2) minutes, respectively. Norketamine, the main metabolite of ketamine, was detected throughout the sampling period. The mean residence time for norketamine was 144 (16) minutes. All the ponies recovered quickly from the anaesthesia; the mean times to sternal recumbency and standing were 11·1 (5·3) and 30·0 (20·8) minutes, respectively, from the end of the infusion.

Prediction of Movement during Propofol/Nitrous Oxide Anesthesia

Movement in response to painful stimulation is the end point classically used to assess the potency of anesthetic agents. In this study, the ability of modeled propofol effect-site concentration to predict movement in volunteers during propofol/nitrous oxide anesthesia was tested, then it was compared with the predictive abilities of the Bispectral Index and 95% spectral edge frequency of the electroencephalogram, pupillary reflex amplitude, and systolic arterial blood pressure. In addition, the relationships between simple end points of loss and recovery of consciousness, and pupillary, hemodynamic, and propofol concentration indicators were studied. Ten healthy volunteers were anesthetized with an infusion of propofol, which was increased in three equal steps to 21 mg.kg lean body mass-1.h-1. After loss of the ability to hold a syringe and of the eyelash reflex, 60% nitrous oxide was introduced and the trachea was intubated without the use of muscle relaxants. The propofol infusion rate then was decreased to 15.4 mg.kg lean body mass-1.h-1. Ten minutes later, tetanic electrical stimulation was administered to the thigh via needle electrodes: if movement was observed within 1 min, the propofol infusion rate was increased by 1.75 mg.kg lean body mass-1.h-1 5 min after the stimulus; if not, it was similarly decreased. This 15-min sequence was repeated until volunteers "crossed over" from movement to no movement (or vice versa) four times. The propofol infusion rate then was increased to 21 mg.kg lean body mass-1.h-1, nitrous oxide was discontinued, the trachea was extubated, and the infusion rate was decreased in five equal steps over 50 min. The times at which the eyelash reflex returned and the birth date was recalled were recorded. The electroencephalogram was monitored continuously (FP1, FP2, ref: nasion, ground: mastoid). Measurements of the pupillary response, arterial blood pressure, and heart rate were recorded during induction and awakening, just before and for 5 min after each stimulation. Arterial blood samples were obtained for propofol assay, and propofol effect-site concentrations were calculated at each time. The predictive value of indicators was compared using a new static, the prediction probability (PK). Loss and return of the eyelash reflex occurred at greater propofol effect-site concentrations than either dropping the syringe or recall of the birthday. The propofol effect-site concentration (in the presence of 60% nitrous oxide) predicted to prevent movement after a supramaximal stimulus in 50% of volunteers was 1.80 micrograms/ml (95% confidence limits: 1.40-2.34 micrograms/ml). The Bispectral Index (PK = 0.86), 95% spectral edge frequency (PK = 0.81), pupillary reflex amplitude (PK = 0.74), and systolic arterial blood pressure (PK = 0.78) did not differ significantly from modeled propofol effect-site concentration (PK = 0.76) in their ability to predict movement. Indicators of pharmacodynamic effect, such as the electroencephalogram, pupillary light reflex, and systolic arterial blood pressure, predict movement as well as effect-site concentration during propofol/nitrous oxide anesthesia. Loss and return of the eyelash reflex correspond to a deeper level of anesthesia than syringe-dropping or recall of the birth date.

Effects of graded infusion rates of propofol on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in dogs

We have studied the effects of a 30-min infusion of propofol 6, 9, 12, 15, 18 and 21 mg kg-1 h-1 on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in 12 mongrel dogs. Mean plasma concentrations of propofol after infusion of 6 and 21 mg kg-1 h-1 increased from 2.9 (SEM 0.3) to 11.5 (0.1) micrograms ml-1. Propofol produced a progressive decrease in arterial pressure. Heart rate tended to decrease at 15, 18 and 21 mg kg-1 h-1 and cardiac index decreased significantly at infusion rates > or = 9 mg kg-1 h-1. Systemic vascular resistance tended to increase except at 21 mg kg-1 h-1 and left ventricular systolic and diastolic function were depressed. Both coronary sinus blood flow and myocardial oxygen consumption decreased in parallel with a decrease in left ventricular minute work index without producing lactate. Propofol produced progressive decreases in coronary blood flow and myocardial oxygen consumption but did not exert adverse effects on the coronary circulation.

Metoclopramide and prochlorperazine do not decrease propofol hypnotic requirements

One hundred patients scheduled for minor surgery were given either saline, metoclopramide 0.1 mg.kg-1 or 0.2 mg.kg-1, or prochlorperazine 0.1 mg.kg-1 or 0.2 mg.kg-1 before induction of anaesthesia with a fixed rate infusion of propofol. Neither metoclopramide nor prochlorperazine reduced the induction dose of propofol. The possibility that these agents increased the induction dose could not be excluded.

Use of analgesics during propofol sedation: A comparison of ketorolac, dezocine, and fentanyl

Study Objective: To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 μg when used as analgesic supplements to a propofol infusion during monitored anesthesia care (MAC). Design: Randomized, double-blind, placebo-controlled study. Setting: Ambulatory surgery facility at a university medical center. Patients: 80 outpatients undergoing breast biopsy or inguinal herniorraphy procedures under MAC. Interventions: All patients received midazolam 2 mg intravenously (IV) followed by 1 ml of the study medication containing either dezocine 3 mg IV, ketorolac 30 mg IV, fentanyl 50 μg IV, or normal saline. A propofol infusion was initiated at 75 μg/kg/min and then varied to maintain a stable level of sedation ( i.e., Observer Assessment of Alertness/Sedation scale score of 3). An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution. During the operation, supplemental (rescue) medication consisted of fentanyl 25 μgIV, bolus injections in all four treatment groups. Measurements and Main Results: Propofol infusion and supplemental fentanyl dosage requirements, oxygen saturation values, respiratory rates, recovery times, and postoperative side effects were recorded. Visual analog scales were used to assess sedation, anxiety, pain, and nausea preoperatively (baseline), upon entry into the postanesthesia care unit, and at 30-minute intervals until discharge. The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control (saline) group. The saline and ketorolac groups required rescue analgesic medication more frequently and/or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups. Compared with the three analgesic treatment groups, postoperative pain scores were only marginally higher in the control group. Ketorolac-treated patients had consistently (but not significantly) shorter recovery times to oral intake, ambulation, and discharge than those in the dezocine or fentanyl groups. No postoperative nausea, vomiting, or pruritis was reported in the ketorolac group. Conclusion: Compared with ketorolac 60 mg, fentanyl 100 μg and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC. However, the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile.

The influence of nitrous oxide on propofol dosage and recovery after total intravenous anaesthesia for day‐case surgery

We studied the influence of nitrous oxide on the maintenance dose of propofol and recovery characteristics in 42 patients, aged 18-62 years, ASA 1 or 2, scheduled for day case inguinal herniotomy. Using a double-blind, randomised design, patients received anaesthesia with propofol-alfentanil-vecuronium-oxygen and either nitrous oxide or room air (FIO2 = 0.30). The rate of propofol infusion was adjusted depending on anaesthetic depth as judged using standard clinical criteria; alfentanil was administered on a weight basis. Patients' lungs were manually ventilated after tracheal intubation and muscle relaxation was reversed at the end of surgery with neostigmine and atropine. A series of psychomotor tests was performed pre-operatively and 30 and 120 min postoperatively. The mean maintenance doses of propofol were 0.084 mg.kg-1.min-1 in the N2O group and 0.088 mg.kg-1.min-1 in the air group (p = 0.97). In the nitrous oxide group the mean (SD) interval to spontaneous eye opening was 13.1 (7.3) min compared to 8.1 (4.9) min in the air group (p = 0.01). Similarly, the interval until obtaining a standardised response was 13.5 (5.3) min and 9.8 min (5.4) in the nitrous oxide and air groups, respectively (p = 0.04). The addition of nitrous oxide to propofol-alfentanil-vecuronium anaesthesia does not reduce propofol requirements and prolongs early recovery compared to air.