Anesthesia and analgesia
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Anesthesia and analgesia · Sep 1997
The effect of GP683, an adenosine kinase inhibitor, on the desflurane anesthetic requirement in dogs.
The availability of an analgesic compound devoid of the side effects associated with the commonly used opioid and nonsteroidal antiinflammatory drugs would be useful during the perioperative period. Although adenosine has analgesic and anesthetic-sparing properties, it also produces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardiovascular or respiratory depression. This preliminary study investigated the effects of a novel adenosine kinase-inhibiting drug, GP683, on the minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GP683 dose regimens (or the solvent) by intravenous infusion on separate occasions according to a cross-over study design. After determining the baseline desflurane MAC value, GP683 was infused at 75, 150, or 300 microg x kg(-1) x min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 microg x kg(-1) x min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-180 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals before, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, respectively. In addition, there was good correlation between the decrease in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by the highest infusion rate of GP683, adjustments in the desflurane concentration to an equi-MAC value resulted in normalization of the MAP values. Furthermore, GP683 produced no changes in heart rate. In conclusion, the adenosine kinase-inhibiting drug, GP683, produced dose-dependent decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. ⋯ An investigational drug (GP683) that can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular system.
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Anesthesia and analgesia · Sep 1997
Comparative StudyA comparative study of the vasodilator effects of prostaglandin E1 in patients with pulmonary hypertension after mitral valve replacement and with adult respiratory distress syndrome.
To determine whether the vasodilator effects of prostaglandin E1 (PGE1) differ according to the etiology and pathophysiology of pulmonary hypertension, we studied 30 patients with pulmonary hypertension after mitral valve replacement (MVR) (n = 16) or with the adult respiratory distress syndrome (ARDS) (n = 14). PGE1 was administered to decrease the mean pulmonary artery pressure to below 30 mm Hg in both groups. Cardiac index and oxygen delivery tended to increase, whereas mean systemic artery pressure, mean pulmonary artery pressure, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) significantly decreased in both groups. A vasodilatory index was defined in this study to allow evaluation of vasodilation relative to PGE1 dose: systemic vasodilatory index (VIs) = SVRI change/PGE1 dose; and pulmonary vasodilatory index (VIp) = PVRI change/PGE1 dose. The VIp was similar in both groups, but the VIs was significantly greater in the ARDS group compared with the MVR group (13.3 +/- 7.8 vs 4.8 +/- 5.1, P < 0.01). A good correlation was found between the pretreatment intrapulmonary shunt fraction (Qs/Qt [%]) value and PGE1 extraction rate in the lung (r = 0.60), and between the pretreatment Qs/Qt value and PGE1 concentration in the radial artery (r = 0.65) in an additional 15 patients. We conclude that the vasodilator effects of PGE1 on the pulmonary circulation are similar in the two groups, whereas the vasodilator effects on the systemic circulation are significantly greater in the ARDS group and that significant reduction in VIs in the ARDS group was associated with decreased PGE1 extraction in the lung. ⋯ Pulmonary hypertension after mitral valve replacement, or with adult respiratory distress syndrome, is a major medical problem. The authors found that administration of prostaglandin E1 significantly dilated the pulmonary circulation with a concomitant decrease in pulmonary artery pressure. Because the systemic vasodilatory effect was greater in the adult respiratory distress syndrome group, the authors concluded that prostaglandin E1 concentrations in the systemic circulation depend on the severity of lung injury.
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Anesthesia and analgesia · Sep 1997
Comparative StudyThe effects of sevoflurane on recovery of brain energy metabolism after cerebral ischemia in the rat: a comparison with isoflurane and halothane.
Isoflurane is an appropriate anesthetic for neuroanesthesia. We evaluated whether the effect of sevoflurane is similar to that of isoflurane or halothane on brain energy metabolism after cerebral ischemia followed by reperfusion using 31P-magnetic resonance spectroscopy. Wistar rats (n = 21) were divided into three groups: isoflurane-, sevoflurane-, or halothane-treated. After anesthesia induction and surgical preparation, each anesthetic concentration was adjusted to 1 minimum alveolar anesthetic concentration. Cerebral ischemia was induced with bilateral carotid occlusion and reduction of mean arterial blood pressure to 30-40 mm Hg by blood withdrawal. Magnetic resonance measurements were performed during ischemia and for 120 min of reperfusion. Intracellular pH in the isoflurane-treated, sevoflurane-treated, and halothane-treated groups decreased to 6.180 +/- 0.149, 6.125 +/- 0.134, and 6.027 +/- 0.157, respectively, at the end of ischemia. There were no differences in the change of phosphorous compounds and intracellular pH between the isoflurane-treated and the sevoflurane-treated groups during ischemia and reperfusion. However, in the halothane-treated group, we observed a significant delay in the recovery of adenosine triphosphate and intracellular pH (0.038 +/- 0.013 pH unit/min compared with 0.064 +/- 0.011 in the isoflurane-treated group and 0.058 +/- 0.008 in the sevoflurane-treated group) until 24 min of reperfusion (P < 0.05). We conclude that sevoflurane has effects similar to isoflurane on brain energy metabolism during and after cerebral ischemia. ⋯ It is important to know whether anesthetics adversely effect brain metabolism during ischemia and reperfusion. A new anesthetic, sevoflurane, affected the brain in a manner similar to isoflurane, which has been used for many years as an anesthetic.
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Anesthesia and analgesia · Sep 1997
Comparative StudyThe impact of choice of muscle relaxant on postoperative recovery time: a retrospective study.
To test the hypothesis that the use of long-acting muscle relaxants is associated with prolonged postoperative recovery when compared with the use of shorter-acting relaxants, we undertook a retrospective study of 270 patients with induced paralysis recovering from general anesthesia. We calculated the mean recovery time associated with each muscle relaxant used. Regression analyses were performed to control for potential confounding of the results by length and type of surgery, as well as age and sex. Taking these into account, the adjusted difference in mean recovery time between patients receiving short- and intermediate-acting relaxants (mivacurium, atracurium, and vecuronium) versus those receiving long-acting relaxants (d-tubocurarine, pancuronium, and pancuronium and d-tubocurarine combination) was 30 min (95% confidence interval [CI] 8-53). The adjusted difference in mean recovery time between patients receiving vecuronium and those receiving pancuronium (i.e., the single most frequently used drug in each category) was 33 min (95% CI 1-66). Shortened recovery time accounted for an estimated average $37.95 decrease in recovery room charge per patient when vecuronium was used instead of pancuronium, versus a $22.84 increase in drug cost. Our data and analyses support the hypothesis that the use of long-acting muscle relaxants is associated with prolonged recovery after surgery and provide preliminary evidence that restricting the use of the more expensive, shorter-acting muscle relaxants may represent a false economy. ⋯ In this retrospective study, the use of old-fashioned, inexpensive, long-acting paralyzing drugs was found to be associated with prolonged postoperative recovery. This has implications when deciding whether, as an economic measure, to restrict the use of the more expensive, shorter-acting paralyzing drugs, because prolonged recovery also has a price.