Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2001
Luciferase as a model for the site of inhaled anesthetic action.
The in vivo potencies of anesthetics correlate with their capacity to suppress the reaction of luciferin with luciferase. In addition, luciferin has structural resemblances to etomidate. These observations raise the issues of whether luciferin, itself, might affect anesthetic requirement, and whether luciferase resembles the site of anesthetic action. Because the polar luciferin is unlikely to cross the blood-brain barrier (we found that the olive oil/water partition coefficient was 100 +/- 36 x 10(-7)), we studied these issues in rats by measuring the effect of infusion of luciferin in artificial cerebrospinal fluid into the lumbar subarachnoidal space and into the cerebral intraventricular space on the MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to a noxious stimulus in 50% of tested subjects) of isoflurane. MAC in rats given lumbar intrathecal doses of luciferin estimated to greatly exceed anesthetizing doses of etomidate, did not differ significantly from MAC in rats receiving only artificial cerebrospinal fluid into the lumbar intrathecal space. MAC slightly decreased when doses of luciferin estimated to greatly exceed anesthetizing doses of etomidate were infused intraventricularly (P < 0.05). In contrast to the absent or minimal effects of luciferin, intrathecal or intraventricular infusion of etomidate at similar or smaller doses significantly decreased isoflurane MAC. Luciferin did not affect +-aminobutyric acid type A or acetylcholine receptors expressed in Xenopus oocytes. These results suggest that luciferin has minimal or no anesthetic effects. It also suggests that luciferin/luciferase may not provide a good surrogate for the site at which anesthetics act, if this site is on the surface of neuronal cells. ⋯ In proportion to their potencies, anesthetics inhibit luciferin's action on luciferase, and luciferin structurally resembles the anesthetic etomidate. However, in contrast to etomidate, luciferin given intrathecally or into the third cerebral ventricle does not have anesthetic actions, and it does not affect +-aminobutyric acid or acetylcholine receptors in vitro. Luciferase may not provide a good surrogate for the site at which anesthetics act.
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Anesthesia and analgesia · Nov 2001
A simple apparatus for accelerating recovery from inhaled volatile anesthetics.
Hyperpnea increases anesthetic elimination but is difficult to implement with current anesthetic circuits without decreasing arterial PCO2. To circumvent this, we modified a standard resuscitation bag to maintain isocapnia during hyperpnea without rebreathing by passively matching inspired PCO2 to minute ventilation. We evaluated the feasibility of using this apparatus to accelerate recovery from anesthesia in a pilot study in four isoflurane-anesthetized dogs. The apparatus was easy to use, and all dogs tolerated being ventilated with it. Under our experimental conditions, isocapnic hyperpnea reduced the time to extubation by 62%, from an average of 17.5 to 6.6 min (P = 0.012), but not time from extubation to standing unaided. This apparatus may provide a practical means of applying isocapnic hyperpnea to shorten recovery time from volatile anesthetics. ⋯ A simple modification to a standard resuscitation bag allows one to increase ventilation without decreasing blood carbon dioxide levels. In dogs, we confirmed that this circuit can be used to accelerate the elimination of and recovery from volatile anesthetics.
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Anesthesia and analgesia · Nov 2001
The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs.
Diaphragmatic fatigue may contribute to the development of respiratory failure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug; Group 2 was infused with small-dose propofol (0.1 mg/kg initial dose plus 1.5 mg x kg(-1) x h(-1) maintenance dose); Group 3 was infused with large-dose propofol (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of propofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). Compared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05) during propofol administration in Groups 2 and 3. The decrease in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that propofol decreases the contractility of fatigued canine diaphragm in a dose-related fashion. ⋯ Propofol is a widely used IV anesthetic for the induction and maintenance of general anesthesia and sedation. It decreases, in a dose-related fashion, the contractility of fatigued diaphragm in dogs.
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Anesthesia and analgesia · Nov 2001
Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by halothane and isoflurane.
Both in vitro and in vivo evidence supports the reduction of early ischemic, both global and focal, brain injury by volatile anesthetics. However, the protection afforded by volatile anesthetics in later neuronal death, i.e., apoptosis, caused by global ischemia has not been investigated. We induced oxygen and glucose deprivation in neuronal cortical cell cultures prepared from newborn rats on in vitro Days 10-14. This hypoxic (PO2 <50 mm Hg) condition was maintained continuously (30, 60, and 90 min). In a separate experiment, the neuronal cell cultures were exposed to isoflurane (1.13%, 2.3%, or 3.3%) or halothane (1.7%, 3.4%, or 5.1%) before oxygen and glucose deprivation, with continued exposure to isoflurane or halothane during oxygen and glucose deprivation. After 48 h, neuronal apoptosis was assessed with terminal deoxynucleotidyl transferase-mediated in situ nick-end labeling and DNA gel electrophoresis. Oxygen and glucose deprivation (30, 60, and 90 min) caused significant apoptosis of cerebral cortical cultured neurons. However, pretreatment and continued treatment during the period of oxygen and glucose deprivation with halothane or isoflurane resulted in a concentration-dependent attenuation of oxygen and glucose deprivation-induced neuronal apoptosis. ⋯ This is the first investigation to evaluate the effect of volatile anesthetics on oxygen and glucose deprivation-induced neuronal apoptosis. Oxygen and glucose deprivation-induced neuronal apoptosis can be decreased by prior and continued administration of halothane or isoflurane.
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Anesthesia and analgesia · Nov 2001
Resuscitation with Hextend decreases endogenous circulating heparin activity and accelerates clot initiation after hemorrhage in the rabbit.
Hemorrhagic shock can result in a hypercoagulable state and has been associated with both hemorrhagic and thrombotic complications in the perioperative period. The author hypothesized that hemorrhage and resuscitation could result in a hypercoagulable state via changes in the heparin-antithrombin III anticoagulant mechanism in rabbits. Rabbits sedated with ketamine underwent sham operation (n = 8) or hemorrhage (25 mL/kg blood shed) for 60 min, followed by resuscitation with an equal volume of 5% human albumin (n = 8) or Hextend (n = 8). Coagulation analysis with the Thrombelastograph analyzer and determination of endogenous heparin and antithrombin III activity were performed on arterial blood samples obtained before hemorrhage and 30 min after resuscitation. The reaction time significantly decreased by 34% after hemorrhage and resuscitation with Hextend, whereas no other significant changes in Thrombelastograph variables were noted. Antithrombin III activity was significantly less in the Albumin (83% +/- 8% of control, mean +/- SD) and Hextend (88% +/- 8%) Resuscitated groups compared with the Sham-Operated animals. Of interest, only the Hextend-Resuscitated animals demonstrated a significant decrease in heparin activity (53.4 +/- 13.6 mU/mL before hemorrhage, 42.3 +/- 5.6 mU/mL after resuscitation). A Hextend)-mediated decrease of both heparin and antithrombin III activity may explain the acceleration of clot initiation compared with albumin administration after hemorrhage in the rabbit. ⋯ Hemorrhage may result in a hypercoagulable state after resuscitation. Decreases in both endogenous heparin and antithrombin III activity after hemorrhage and Hextend resuscitation in rabbits resulted in a significantly decreased time to clot coagulation analysis initiation without a significant change in the rate of clot formation or final clot strength.