Better methods for meta-analysis available.
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Analgesia, Epidural↗
Biomedical subjects
Nathan L Pace
Publications and source records attributed to Nathan L Pace.
Opioid-volatile anesthetic synergy: a response surface model with remifentanil and sevoflurane as prototypes.
BACKGROUND: Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane. METHODS: Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were combined with previously reported pharmacokinetic models to identify the combination of remifentanil and sevoflurane that yielded the fastest recovery (Observer's Assessment of Alertness/Sedation score > or = 4) for anesthetics lasting 30-900 min. RESULTS: Remifentanil synergistically decreased the amount of sevoflurane necessary to produce sedation and analgesia. Simulations revealed that as the duration of the procedure increased, faster recovery was produced by concentration target pairs containing higher amounts of remifentanil. This trend plateaued at a combination of 0.75 vol% sevoflurane and 6.2 ng/ml remifentanil. CONCLUSION: Response surface analyses demonstrate a synergistic interaction between remifentanil and sevoflurane for sedation and all analgesic endpoints.
Adult↗
Improved statistical methods for quantal assay.
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Bupivacaine↗
Transient neurologic symptoms after spinal anesthesia with lidocaine versus other local anesthetics: a systematic review of randomized, controlled trials.
Lidocaine has been used for spinal anesthesia since 1948, seemingly without causing concern. However, during the last 10 years, a number of reports have appeared implicating lidocaine as a possible cause of neurologic complications after spinal anesthesia. Follow-up of patients who received uncomplicated spinal anesthesia revealed that some of them developed pain in the lower extremities--transient neurologic symptoms (TNS). In this study, we sought to compare the frequency of 1) TNS and 2) neurologic complications after spinal anesthesia with lidocaine with that after other local anesthetics. Published trials were identified by computerized searches of The Cochrane Library, MEDLINE, LILAC, and EMBASE and by checking the reference lists of trials and review articles. The search identified 14 trials reporting 1347 patients, 117 of whom developed TNS. None of these patients showed signs of neurologic complications. The relative risk for developing TNS after spinal anesthesia with lidocaine was higher than with other local anesthetics (bupivacaine, prilocaine, procaine, and mepivacaine), i.e., 4.35 (95% confidence interval, 1.98-9.54). There was no evidence that this painful condition was associated with any neurologic pathology; in all patients, the symptoms disappeared spontaneously by the 10th postoperative day.
Adult↗
Preoperative "fentanyl challenge" as a tool to estimate postoperative opioid dosing in chronic opioid-consuming patients.
UNLABELLED: When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression. We studied 20 chronically opioid-consuming patients having elective multilevel spine fusion. Preoperatively, each patient received a fentanyl infusion of 2 microg x kg(-1) x min(-1) until the respiratory rate was <5 breaths/min. Pharmacokinetic simulations were used to estimate the effect site concentration at the time of respiratory depression and to predict the patient-controlled analgesia settings that would provide an effect-site fentanyl concentration that was 30% of the concentration associated with respiratory depression. Postoperatively, patient-controlled analgesia settings were adjusted to achieve 2-3 demand doses per hour. At steady-state patient-controlled analgesia settings, arterial blood gases and plasma fentanyl levels were measured. Sixteen patients required no adjustment or one patient-controlled analgesia adjustment. The median arterial Pco(2) level was 41 mm Hg and the interquartile range was 39-46 mm Hg. Plasma fentanyl levels demonstrated a significant correlation to the estimated effect-site concentration associated with respiratory depression determined during the preoperative fentanyl challenge. A preoperative fentanyl challenge used with pharmacokinetic simulations may be a useful tool to individualize the administration of analgesics to chronically opioid-consuming patients. IMPLICATIONS: In chronically opioid-consuming patients, doses causing respiratory depression and analgesia may differ from those in opioid-naive individuals. A preoperative infusion of fentanyl, used in conjunction with pharmacokinetic simulation, may be a valuable tool for identifying clinical end-points, such as respiratory depression and analgesia, and individualizing postoperative treatment of pain in patients who chronically consume opioids.
Analgesics, Opioid↗
Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: a pharmacokinetic and pharmacodynamic analysis.
BACKGROUND: Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol. METHODS: After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 microg x kg(-1) x min(-1)) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. RESULTS: The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale. CONCLUSIONS: Hemorrhagic shock followed by resuscitation with lactated Ringer's solution did not alter the pharmacokinetics but did increase the potency of propofol. These results demonstrate that alterations in propofol pharmacokinetics observed in moderate to severe blood loss can be reversed with resuscitation. These results suggest that a modest reduction in propofol is prudent to achieve a desired drug effect after resuscitation from severe hemorrhagic shock.
Algorithms↗
The pharmacokinetics and pharmacodynamics of propofol in a modified cyclodextrin formulation (Captisol) versus propofol in a lipid formulation (Diprivan): an electroencephalographic and hemodynamic study in a porcine model.
UNLABELLED: The currently marketed propofol formulation has a number of undesirable properties that are in part a function of the lipid emulsion formulation, including pain on injection, serious allergic reactions, and the support of microbial growth. A modified cyclodextrin-based formulation of propofol (sulfobutyl ether-beta-cyclodextrin) has been developed that may mitigate some of these formulation-dependent problems. However, reformulation may alter propofol's pharmacologic behavior. Our aim in this study was to compare the pharmacokinetics and pharmacodynamics of propofol in the currently marketed lipid-based formulation with those of the novel cyclodextrin formulation. We hypothesized that the pharmacokinetics and pharmacodynamics of the propofol in cyclodextrin would be substantially similar to those of the propofol in lipid. Thirty-two isoflurane-anesthetized animals were instrumented with pulmonary artery, arterial, and IV catheters and were randomly assigned to receive either propofol in lipid or propofol in cyclodextrin by continuous infusion. Arterial blood samples for propofol assay were collected. The processed electroencephalogram, heart rate, mean arterial blood pressure, and cardiac output were measured continuously. The propofol formulations were compared by using model-independent analysis techniques. Combined kinetic/dynamic models were also constructed for simulation purposes. There were no significant differences in the pharmacokinetics or pharmacodynamics of the two propofol formulations. The simulations based on the combined pharmacokinetic/pharmacodynamic models confirmed the substantial similarity of the two formulations. The hypothesis that the propofol-in-cyclodextrin formulation would exhibit pharmacokinetic and pharmacodynamic behavior that was substantially similar to the propofol-in-lipid formulation was confirmed. IMPLICATIONS: A modified cyclodextrin-based formulation of propofol has been developed that may mitigate some of the problems associated with propofol in lipid emulsion. However, reformulation of propofol may change its clinical characteristics. This study in a pig model showed that the novel propofol formulation was substantially similar to the lipid emulsion propofol formulation.
Anesthetics, Intravenous↗
The anatomic relationship of the sciatic nerve to the lesser trochanter: implications for anterior sciatic nerve block.
UNLABELLED: Classic descriptions of the anterior sciatic nerve block suggest needle placement at the level of the lesser trochanter of the femur. Recently, investigators have reported that the sciatic nerve is not accessible at this level. To define more accurately the anatomic relationship of the sciatic nerve to the lesser trochanter, we analyzed magnetic resonance scans performed on 20 patients in the supine position. After IRB approval, magnetic resonance scans of the hip and proximal femur were reviewed in 20 supine patients in the neutral position. Images from five axial levels were studied, specifically, at the level of the lesser trochanter and at 1-cm intervals inferior to the lesser trochanter for 4 cm. In each axial image, the medial or lateral distance was measured from the sciatic nerve to a sagittal plane at the medial border of the femur. If the sciatic nerve was lateral to this sagittal plane (inaccessible), the distance was assigned a negative value, and if the sciatic nerve was medial to the sagittal plane (accessible), the distance was assigned a positive value. The distance between the coronal plane at the anterior border of the femur and the coronal plane through the sciatic nerve was also recorded for each level. At the level of the lesser trochanter, the sciatic nerve was lateral to the femoral border (inaccessible) in 13 of 20 patients with a mean distance of -4.0 +/- 7.7 mm. At 4 cm below the lesser trochanter, the sciatic nerve was medial to the femoral border (accessible) in 19 of 20 patients with a mean distance 7.8 +/- 5.8 mm. The distance from the anterior border of the femur to the sciatic nerve was 42.9 +/- 5.8 mm at the level of the lesser trochanter and 45.7 +/- 9.5 mm at 4 cm below the lesser trochanter. The classic description of the anterior approach to the sciatic nerve suggests that the needle be walked off medially at the level of the lesser trochanter. Our data are consistent with recent reports suggesting that in the majority of subjects, the position of the sciatic nerve relative to lesser trochanter made it inaccessible from an anterior approach at this level. In contrast, at 4 cm below the lesser trochanter, the sciatic nerve was medial to the femur in 19 of 20 subjects. We conclude that needle insertion medial to the proximal femur, 4 cm below the lesser trochanter, is a more direct anatomical approach to the anterior sciatic nerve block. IMPLICATIONS: Magnetic resonance images suggest that in the majority of supine subjects, the sciatic nerve is lateral to the lesser trochanter of the femur and therefore not accessible using the classic anterior approach. By contrast, 4 cm below the lesser trochanter, the sciatic nerve is consistently medial to the femoral shaft and therefore may be more accessible using an anterior approach.
Adult↗