ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect.MethodsThe authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 [micro sign]g [middle dot] kg-1[middle dot] min-1) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion.ResultsTwenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min-1. The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50values for loss of consciousness of 2.35, 1.8, and 1.25 [micro sign]g/ml in volunteers who were 25, 50, and 75 yr old, respectively.ConclusionsSemilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundDrug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients.MethodsA target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 [micro sign]g/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (keO) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile.ResultsThe half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients.ConclusionsThe effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundGuidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy.MethodsAfter institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4.ResultsThe groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not.ConclusionsLow-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundIntrathecal neostigmine produces analgesia in volunteers and patients. However, the use of epidural neostigmine has not been investigated. The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures.MethodsAfter Institutional Review Board approval and informed consent, 48 patients (n = 12) undergoing knee surgery were randomly allocated to one of four groups and studied in a prospective way. After 0.05-0.1 mg/kg intravenous midazolam premedication, patients were randomized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine (85 mg) with saline (control group); 1 [micro sign]g/kg epidural neostigmine (1 [micro sign]g group); 2 [micro sign]g kg epidural neostigmine (2 [micro sign]g group); or 4 [micro sign]g/kg epidural neostigmine (4 [micro sign]g group). The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Post-operatively, pain was assessed using the visual analog scale, and intramuscular 75 mg diclofenac was available at patient request.ResultsGroups were demographically the same and did not differ in intraoperative characteristics (blood pressure, heart rate, ephedrine consumption, oxyhemoglobin saturation, sensory loss before start of surgery, or duration of sensory motor block). The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). The time (min +/- SD) to first rescue analgesic was as follows: control group: 205 +/- 48; 1-[micro sign]g group: 529 +/- 314; 2-[micro sign]g group: 504 +/- 284; 4-[micro sign]g group: 547 +/- 263 (P < 0.05). The analgesic consumption (number of intramuscular diclofenac injections [mean, 25th-75th percentile]) in 24 h was as follows: control group: 3 [3 or 4]; 1-[micro sign]g group: 1[1 or 2]; 2-[micro sign]g group: 2[1 or 2]; 4-[micro sign]g group: 2[1-3](P < 0.05). The 24-h-pain visual analog scale score (cm +/- SD) that represents the overall impression for the last 24 h was as follows: control group: 5 +/- 1.6; 1-[micro sign]g group: 1.6 +/- 1.8; 2-[micro sign]g group: 1.4 +/- 1.6; 4-[micro sign]g group: 2.2 +/- 1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05).ConclusionEpidural neostigmine (1, 2, or 4 [micro sign]g/kg) in lidocaine produced a dose-independent analgesic effect ([approximate] 8 h) compared to the control group ([approximate] 3.5 h), and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe (NMDA) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia. Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans. Although it is disputed, the actions of ketamine have been ascribed not only to NMDA receptor antagonism, but also to opioid receptor agonism. A study therefore was designed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone.MethodsTwenty-five volunteers were subjected to three treatment regimens. A standardized first-degree burn injury was induced. On appearance of primary and secondary hyperalgesia, one of the following infusion schemes was applied in a randomized, double-blind, cross-over fashion: (1) infusion of naloxone (0.8 mg/15 min followed by 0.4 mg/h), succeeded by infusion of ketamine (0.3 mg [middle dot] kg-1[middle dot] 15 min-1followed by 0.3 mg [middle dot] kg-1[middle dot] h-1); (2) infusion of placebo, succeeded by infusion of ketamine (0.3 mg [middle dot] kg-1[middle dot] 15 min-1followed by 0.3 mg [middle dot] kg-1[middle dot] h-1); and (3) infusion of placebo, succeeded by infusion of placebo. Heat-pain detection thresholds, magnitude of secondary hyperalgesia around the burn injury, and side effects were determined.ResultsKetamine reduced secondary hyperalgesia. Naloxone did not affect the action of ketamine. The magnitudes of side effects were equal if the subjects received ketamine, regardless of preceding infusion of naloxone.ConclusionsIn this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundCerebrospinal fluid (CSF) outflow to intra- and extracranial subarachnoid spaces caused by arterial inflow to the brain predominantly compensates systolic increases in cerebral blood volume. Phase-contrast magnetic resonance imaging is a new tool for noninvasive assessment of CSF displacement by measuring CSF peak velocity (CSFVPeak). The authors tested this new tool in an experimental human model of increased intracranial pressure and reduced cerebral capacity by means of continuous positive airway pressure (CPAP) breathing.MethodsThe authors investigated systolic CSFVPeakin the aqueduct of Sylvius in 11 awake, normocapnic (end-tidal carbon dioxide [ETCO(2)] = 40 mmHg) volunteers without CPAP and at two different CPAP levels (6 and 12 cm H2O) by means of electroencephalography-gated phase-contrast magnetic resonance imaging.ResultsAdministration of 6 cm H2O CPAP did not change systolic CSFVPeak(-4.9 +/- 2.8 cm/s vs. control: -5.1 +/- 2.7 cm/s), whereas 12 cm H2O CPAP significantly reduced systolic CSFVPeak(-4.0 +/- 1.8 cm/s vs. control: -5.1 +/- 2.7 cm/s; P < 0.05).ConclusionsThese findings in awake volunteers show that monitoring CSFVPeakin the aqueduct of Sylvius is a sensitive method for detecting even minor impairment of cerebral capacity caused by experimentally induced increases in intracranial pressure.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated.MethodsTwenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied:15 received phenytoin during operation (10 mg/kg), and the others served as controls.Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl, 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins.ResultsThe first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change.ConclusionPhenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundRemifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil.MethodsThirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined.ResultsOnly 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50values. The EC50(mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC (50) for alfentanil was 49.4 (32.4-66.5) ng/ml.ConclusionBased on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID