Anesthesiology
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Randomized Controlled Trial Clinical Trial
Pharmacokinetics of ropivacaine and bupivacaine for bilateral intercostal blockade in healthy male volunteers.
Intercostal blockade produces the highest serum local anesthetic concentrations of all regional anesthetic techniques. The purpose of this study was to determine the pharmacokinetic properties of ropivacaine and bupivacaine after bilateral intercostal blockade. ⋯ The results of this pharmacokinetic study indicate that 0.25% ropivacaine and 0.25% bupivacaine (56 ml, 140 mg) produce peak plasma levels less than those considered toxic when used in bilateral intercostal blockade. Studies of ropivacaine for intercostal blockade in surgical patients are necessary before the optimum concentration for efficacy and anesthetic/analgesic duration is identified.
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Randomized Controlled Trial Clinical Trial
A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Analgesic, respiratory, and pharmacokinetic effects.
A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. ⋯ Application of TTSF patches 2 h preoperatively is associated with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.
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Randomized Controlled Trial Clinical Trial
Amelioration of lactic acidosis with dichloroacetate during liver transplantation in humans.
Marked lactic acidosis occurs during orthotopic liver transplantation (OLT), especially during the anhepatic phase. Current standard therapy is NaHCO3, although it may exacerbate intracellular acidosis, increase plasma lactate, and contribute to hypernatremia. Alternatively, dichloroacetate (DCA) stimulates pyruvate oxidation in vivo, reduces plasma lactate, and moderates intracellular acidosis. The aims of this study were to test the efficacy of DCA to control lactic acidosis, reduce the NaHCO3 requirement and incidence of hypernatremia, and stabilize perioperative acid-base homeostasis. Others aims were to examine the DCA pharmacokinetic profile during OLT and the role of lactate metabolism in OLT-associated hyperglycemia. ⋯ DCA safely and effectively attenuated lactic acid accumulation and moderated acidosis during OLT. DCA decreased the requirement for NaHCO3 therapy and the incidence of hypernatremia. OLT-associated hyperglycemia did not result from lactate-induced stimulation of hepatic gluconeogenesis. Postoperative metabolic alkalosis was not substantially influenced by lactate metabolism.
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Tachyphylaxis to local anesthetics has been shown to be promoted by longer interanalgesic intervals between injections. We hypothesized that thermal hyperalgesia also would accelerate the development of tachyphylaxis. The n-methyl-D-aspartate antagonist ((+)-5 methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine, or dizocilpine) (MK-801) has been shown to prevent thermal hyperalgesia. We therefore also hypothesized that MK-801 would prevent tachyphylaxis. ⋯ Thermal hyperalgesia accelerates the development of tachyphylaxis to rat sciatic nerve blockade, and MK-801 prevents tachyphylaxis in this model. n-Methyl-D-aspartate receptor antagonists may have future clinical utility in increasing the duration of effectiveness of prolonged local anesthetic administration.
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Injection of formalin in the hindpaw of the rat induces intense C-fiber activity accompanied by brief flinching of the injected paw (phase 1) and gives rise to facilitated spinal processing characterized by renewed flinching beginning 15 min after injury and lasting 40 min or more (phase 2). In previous work, isoflurane, administered during phase 1, slightly reduced phase-2 activity, whereas the addition of intrathecal morphine dramatically inhibited phase 2, even with naloxone reversal 6 min after the formalin injection. We used a similar model to determine whether intrathecal morphine could block spinal sensitization in the absence of inhalation anesthetic. ⋯ Intrathecal morphine, administered before formalin injection but antagonized before the onset of phase 2 of the formalin test, significantly suppresses sensitization of dorsal horn neurons. This suppression is significantly increased by coadministration of halothane anesthesia.