Anesthesiology
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Randomized Controlled Trial Comparative Study Clinical Trial
Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period.
In an attempt to maintain stable levels of an alpha 2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery. We determined the clinical efficacy of a high- and a low-dose clonidine regimen on sedation, hemodynamic parameters, anesthesia, and analgesia. The low-dose clonidine group of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS #2), which was supplemented with oral doses of clonidine approximately 3 micrograms.kg-1 on the evening prior to surgery and on the morning of surgery. ⋯ Isoflurane was added when the blood pressure exceeded 110% of the patient's prestudy value. For pain relief postoperatively, the patients received morphine, 1-2-mg iv boluses, via a patient-controlled analgesia pump. The low-dose clonidine patient group had mean plasma clonidine concentrations that varied from 1.47 ng.ml-1 (preoperative) to 1.32 ng.ml-1 (postoperative day 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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In seeking a means to reverse local anesthetic block of peripheral nerve, we examined the actions of veratridine (VTD), an agent known to antagonize competitively the binding of local anesthetics to Na channels. The actions of VTD, a steroidal alkaloid "activator" of voltage-gated Na channels, were studied in the rabbit vagus nerve by two methods. In one, the effects of VTD on compound action potentials (APc) propagating through a "veratrinized" segment (11-mm) of nerve were measured by extracellular recording. ⋯ Repetitive stimulation, particularly of C-fibers, produced a cumulative VTD-induced depolarization (VID) that was sustained over several seconds and during which the C-fiber APc was selectively reduced. We propose that this local, use-dependent VID provides the means to inhibit impulses propagating through the veratrinized region. The preferential effect of VTD on C-fibers suggests its possibilities as a relatively selective agent for block of impulse trains in nociceptive afferents.
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Central body temperature, which usually is well controlled, typically decreases more than 1 degree C during the 1st h of general anesthesia. This hypothermia has been attributed partially to an anesthetic-induced peripheral vasodilation, which increases cutaneous heat loss to the environment. Based on the specific heat of humans, heat loss would have to increase more than 70 W for 1 h (in a 70-kg person) to explain hypothermia after induction of general anesthesia. ⋯ Isoflurane anesthesia decreased mean arterial blood pressure approximately 20%. Average skin-surface temperature increased over 15 min to 0.5 degree C above control. Heat loss from the trunk, head, arms, and legs decreased slightly, whereas loss from the hands and feet (10.5% of the body surface area) doubled (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Seven dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic, portal, and renal blood flows. Each animal was studied on two separate occasions, awake and during 1.2, 1.4, 1.75, and 2.0 MAC isoflurane and enflurane. Both anesthetics induced tachycardia; to a greater degree than isoflurane, enflurane lowered mean aortic blood pressure in a dose-dependent manner (-37, -45, -48, and -62% vs. -19, -25, -41, and -44%, respectively) and cardiac output (-20, -26, -41, and -48% vs. -3, -5, -11, and -15%, respectively). ⋯ Likewise, neither anesthetic significantly changed renal blood flow, except for enflurane at 2.0 MAC, which was associated with a 35% reduction. Both anesthetics led to similar systemic, hepatic, and renal vasodilations. Our data suggest that high concentrations of enflurane are associated with decreases in portal, total hepatic, and renal blood flows, most likely as a result of an anesthetic-induced cardiac depression.
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Comparative Study
Pharmacokinetics, pharmacodynamics, and rational opioid selection.
Fentanyl, alfentanil, and sufentanil have important pharmacokinetic and pharmacodynamic differences. Selecting one of these opioid analgesics as an adjunct to general anesthesia requires appreciation of the relationship between the pharmacokinetic and pharmacodynamic characteristics of these drugs and the onset of and recovery from drug effect. Using a pharmacokinetic-pharmacodynamic model, the authors simulated the decrease in plasma fentanyl, alfentanil, and sufentanil concentration after intravenous administration by either bolus injection, brief infusion, or prolonged infusion. ⋯ Alfentanil may also be the most appropriate drug to provide a transient peak effect after a single bolus. Although sufentanil has longer distribution and elimination half-lives than alfentanil, recovery from sufentanil infusions may be more rapid than recovery from alfentanil infusions for operations shorter than 6-8 h. These computer simulations demonstrate that simply comparing pharmacokinetic parameters (e.g., half-lives) of different drugs will not predict the relative rates of decrease in effect site concentrations after either an intravenous bolus or a continuous infusion.