Anesthesia and analgesia
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Anesthesia and analgesia · Jul 2003
Case ReportsLocal anesthetic switching for intrathecal tachyphylaxis in cancer patients with pain.
Switching from bupivacaine to lidocaine may improve intrathecal morphine analgesia in advanced cancer patients, possibly because of different spinal mechanisms limiting the hyperalgesic processes.
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Anesthesia and analgesia · Jul 2003
Clinical TrialA model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans: bupivacaine-loaded microcapsules.
Biodegradable microcapsules produce an ultra-long duration of local anesthesia. We hypothesized that this duration is caused by the sustained-release of bupivacaine from the microcapsules into the surrounding tissue. Previous studies investigated the pharmacokinetics (PKs) of bupivacaine after release from microcapsules and absorption into the systemic circulation. Microdialysis sampling can determine the PKs of any drug at its site of injection. This study was performed to characterize the PKs of bupivacaine and dexamethasone released from microcapsules at a subcutaneous injection site over a 96-h period in volunteers. Bupivacaine concentrations were compared with clinical variables of local anesthetic blockade. This study demonstrates that bupivacaine is released in a sustained manner from microcapsules, that bupivacaine concentrations increase for 24-34 h after microcapsule injection, and that analgesia parallels the tissue bupivacaine concentration obtained by microdialysis. Analgesia was equally rapid in onset with aqueous and microcapsule bupivacaine (P = 0.23). Analgesia was still present at 78% of microcapsule-injected sites after 96 h, significantly longer than for aqueous bupivacaine (P < 0.001). Mild pruritus was the most common side effect, occurring with 56% of the microcapsule injections. Dexamethasone-containing bupivacaine microcapsules are well tolerated and produce a prolonged duration of skin analgesia. Systemic absorption of bupivacaine produces higher peak plasma levels after aqueous injection than after microcapsule injection, despite the injection of a threefold larger load of bupivacaine in the latter. ⋯ Microcapsules loaded with bupivacaine and dexamethasone and administered by subcutaneous injection produce prolonged cutaneous anesthesia and analgesia. Determination of local tissue pharmacokinetic variables of bupivacaine by microdialysis confirms that the prolonged duration of anesthesia is caused by the extended release characteristics of the microcapsules.
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Anesthesia and analgesia · Jul 2003
Clinical TrialImplicit memory varies as a function of hypnotic electroencephalogram stage in surgical patients.
Previous studies have observed a correlation of implicit memory with certain electroencephalogram (EEG) measures during anesthesia. Here, we tested the relationship between hypnotic depth determined by computer system (Narcotrend(TM)) and implicit memory in anesthetized patients, assessed by a postoperative reading speed test. Thirty-two patients undergoing laparoscopic herniotomy and 30 age-matched volunteer controls were included the study. All patients received IV midazolam 2-3 mg followed by an induction dose of propofol and remifentanil. The anesthesia was maintained with propofol and remifentanil infusions and cisatracurium. Each patient was exposed to 2 of 4 stories, repeated 6 times. The first story was presented during light to moderate hypnotic EEG stages, and the second story was presented during deep hypnosis. Presentation of stories was balanced between patients and hypnotic stages. The controls listened to the two stories without receiving anesthesia. The reading speed for the previously presented stories and two new stories was measured approximately 7 h later with a computer program. No signs of inadequate anesthesia were observed, and no explicit memories of intraoperative events were revealed by a structured interview. No change of reading speed was observed for words presented during deep hypnotic stages. In contrast, an increased reading speed of 20 ms per word was found for content words (i.e., nouns, verbs, and adjectives), but not for function words (conjunctions, prepositions, and so on), presented during light to moderate hypnotic stages. Increased reading speed for semantically rich content words indicates that anesthetized patients are able to process acoustic information during light and moderate, but not deep, hypnosis. ⋯ In this study, implicit memory was observed during general anesthesia at light to moderate, but not deep, hypnotic stages. Hypnotic stages were determined by a commercial electroencephalogram device, and implicit memory was measured by using a postoperative reading speed task. During lighter phases of anesthesia, patients should be protected against acoustic information that could negatively influence their postoperative outcome.
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Anesthesia and analgesia · Jul 2003
The effects of fresh frozen plasma on neutrophil-endothelial interactions.
Leukocyte adhesion to endothelial cells contributes to microcirculatory disturbances during severe shock syndromes. Whereas certain plasma expanders inhibit leukocyte adhesion, contaminants of plasma protein solutions upregulate endothelial cell adhesion molecules in certain cases. We performed this study to determine whether fresh frozen plasma (FFP) affects neutrophil-endothelial interactions in cocultures of neutrophils and human umbilical vein endothelial cells (HUVEC) in vitro. HUVEC (n = 9) were incubated with either 20% FFP or 20% serum in medium for 6 h. Expression of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule-1 was induced by tumor necrosis factor alpha (0.5 ng/mL for 4 h) and measured by flow cytometry. Neutrophil adhesion was examined in a parallel plate flow chamber in which isolated neutrophils were perfused over pretreated HUVEC under postcapillary flow conditions. Incubation with FFP decreased E-selectin and intercellular adhesion molecule 1 on activated HUVEC by 28% and 22%, respectively (P < or = 0.01; analysis of covariance). Consequently, neutrophil adhesion decreased by 20%-41% in FFP-treated cocultures (n = 4; P < or = 0.01; paired Student's t-test). We conclude that FFP attenuates the inflammatory response of endothelial cells with regard to neutrophil-endothelial interactions. Because the composition of patients' plasma is affected not only by transfusion, but more frequently by shock treatment with IV fluids, plasma dilution in critically ill patients could be important. ⋯ During shock, fluid administration leads to a massive dilution of plasma. Apart from maintaining hemodynamics, this might affect tissue damage by influencing leukocyte accumulation in the microvasculature. Using endothelial cells, isolated neutrophils, and a parallel plate flow chamber, we studied the effects of fresh frozen plasma on neutrophil-endothelial interactions.
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Anesthesia and analgesia · Jul 2003
Comparative StudyThe 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.
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. ⋯ 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.