Anesthesia and analgesia
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Anesthesia and analgesia · Aug 1998
A molecular description of how noble gases and nitrogen bind to a model site of anesthetic action.
How some noble and diatomic gases produce anesthesia remains unknown. Although these gases have apparently minimal capacities to interact with a putative anesthetic site, xenon is a clinical anesthetic, and argon, krypton, and nitrogen produce anesthesia at hyperbaric pressures. In contrast, neon, helium, and hydrogen do not cause anesthesia at partial pressures up to their convulsant thresholds. We propose that anesthetic sites influenced by noble or diatomic gases produce binding energies composed of London dispersion and charge-induced dipole energies that are sufficient to overcome the concurrent unfavorable decrease in entropy that occurs when a gas molecule occupies the site. To test this hypothesis, we used the x-ray diffraction model of the binding site for Xe in metmyoglobin. This site offers a positively charged moiety of histidine 93 that is 3.8 A from Xe. We simulated placement of He, Ne, Ar, Kr, Xe, H2, and N2 sequentially at this binding site and calculated the binding energies, as well as the repulsive entropy contribution. We used free energies obtained from tonometry experiments to validate the calculated binding energies. We used partial pressures of gases that prevent response to a noxious stimulus (minimum alveolar anesthetic concentration [MAC]) as the anesthetic endpoint. The calculated binding energies correlated with binding energies derived from the in vivo (ln) data (RTln[MAC], where R is the gas constant and T is absolute temperature) with a slope near 1.0, indicating a parallel between the Xe binding site in metmyoglobin and the anesthetic site of action of noble and diatomic gases. Nonimmobilizing gases (Ne, He, and H2) could be distinguished by an unfavorable balance between binding energies and the repulsive entropy contribution. These gases also differed in their inability to displace water from the cavity. ⋯ The Xe binding site in metmyoglobin is a good model for the anesthetic sites of action of noble and diatomic gases. The additional binding energy provided by induction of a dipole in the gas by a charge at the binding site enhanced binding.
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Anesthesia and analgesia · Aug 1998
Minimum alveolar concentrations of noble gases, nitrogen, and sulfur hexafluoride in rats: helium and neon as nonimmobilizers (nonanesthetics)
We assessed the anesthetic properties of helium and neon at hyperbaric pressures by testing their capacity to decrease anesthetic requirement for desflurane using electrical stimulation of the tail as the anesthetic endpoint (i.e., the minimum alveolar anesthetic concentration [MAC]) in rats. Partial pressures of helium or neon near those predicted to produce anesthesia by the Meyer-Overton hypothesis (approximately 80-90 atm), tended to increase desflurane MAC, and these partial pressures of helium and neon produced convulsions when administered alone. In contrast, the noble gases argon, krypton, and xenon were anesthetic with mean MAC values of (+/- SD) of 27.0 +/- 2.6, 7.31 +/- 0.54, and 1.61 +/- 0.17 atm, respectively. Because the lethal partial pressures of nitrogen and sulfur hexafluoride overlapped their anesthetic partial pressures, MAC values were determined for these gases by additivity studies with desflurane. Nitrogen and sulfur hexafluoride MAC values were estimated to be 110 and 14.6 atm, respectively. Of the gases with anesthetic properties, nitrogen deviated the most from the Meyer-Overton hypothesis. ⋯ It has been thought that the high pressures of helium and neon that might be needed to produce anesthesia antagonize their anesthetic properties (pressure reversal of anesthesia). We propose an alternative explanation: like other compounds with a low affinity to water, helium and neon are intrinsically without anesthetic effect.
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Anesthesia and analgesia · Aug 1998
Valuing the work performed by anesthesiology residents and the financial impact on teaching hospitals in the United States of a reduced anesthesia residency program size.
We performed a financial analysis at a large university tertiary care hospital to determine the incremental cost of replacing its anesthesiology residents with alternative dependent providers (i.e., certified registered nurse anesthetists in the operating room, advanced practice nurses and physician assistants outside the operating room). The annual average net cost of an anesthesiology resident during a 3-yr residency is approximately $38,000, and residents performed an average of $89,000 of essential clinical work annually based on replacement costs. The incremental cost (replacement labor cost minus net resident cost) to replace all essential clinical duties performed by an anesthesiology resident at Duke University Medical Center and affiliated hospitals is approximately $153,000 throughout 3 yr of clinical anesthesiology training. If this approach were applied nationwide, incremental costs of substitution would range from $36,000,000 to $93,000,000 per year. We conclude that maintaining clinical service in the face of anesthesiology residency reductions can have a marked impact on the overall cost of providing anesthesiology services in teaching hospitals. Simply replacing residents with alternate nonphysician providers is a very expensive option. ⋯ We sought to calculate the financial burden resulting from a decreased number of anesthesiology residents. Replacing each resident's essential clinical work with similarly skilled healthcare providers would cost hospitals approximately $153,000 over the course of a 3-yr residency. Varying projections yield future nationwide costs of $36,000,000 to $93,000,000 per year. Simply replacing residents with alternate nonphysician providers is a very expensive option.
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Anesthesia and analgesia · Aug 1998
Modifications of the inotropic responses to alpha- and beta-adrenoceptor stimulation by propofol in rat myocardium.
Propofol induces cardiovascular depression but without significant effect on intrinsic myocardial contractility in many species. However, its interactions with adrenoceptor stimulation are unknown. We studied the effects of propofol (1 and 10 microg/mL) and its solvent on the inotropic response induced by phenylephrine (10(-8)-10(-4) M) or isoproterenol (10(-8)-10(-4) M) in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, calcium 0.5 mM, stimulation frequency 12 pulses/min). We also studied the lusitropic effects in isotonic and isometric conditions. In control groups, phenylephrine (127% +/- 3% of baseline; P < 0.05) and isoproterenol (169% +/- 11% of baseline; P < 0.05) induced a positive inotropic effect. Propofol (10 microg/mL) completely abolished the positive inotropic effect of phenylephrine (100% +/- 3% of baseline; P = not significant). In contrast, at the lowest concentration (1 microg/mL), propofol did not modify the positive inotropic effect of phenylephrine. Propofol did not modify the inotropic effect of isoproterenol. Propofol (10 microg/mL) enhanced the positive lusitropic effect of isoproterenol under low-load (P < 0.05) but not under high-load conditions. ⋯ A high concentration of propofol abolished the positive inotropic effect of alpha- but not beta-adrenoceptor stimulation and enhanced the positive lusitropic effect of beta-adrenoceptor stimulation.
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Anesthesia and analgesia · Aug 1998
The effect of thoracic paravertebral blockade on intercostal somatosensory evoked potentials.
The paravertebral nerve blocks used in upper abdominal or thoracic surgery provide excellent pain relief and can inhibit some aspects of the neuroendocrine stress response to surgical trauma, which suggests that a very high-quality afferent block can be effected. To confirm this, we evaluated intercostal somatosensory evoked potentials (SSEPs) in 10 patients undergoing paravertebral nerve blocks as a treatment for chronic pain. SSEPs were recorded before and after ipsilateral thoracic paravertebral deposition of 1.5 mg/kg bupivacaine 0.5%. Sensory loss to temperature was demonstrated in all patients at the level of injection and had a mean superior spread of 1.4 (range 0-4) dermatomes and a mean inferior spread of 2.8 (range 0-7) dermatomes. SSEPs were abolished (the normal waveform was rendered unrecognizable with unmeasurable latencies and a mean amplitude of zero) in all patients at the level of injection. In addition, a two-dermatome SSEP abolition was found in four patients and a three-dermatome abolition was found in two patients. SSEPs were modified, but not significantly, at all other test points. We conclude that cortical responses to thoracic dermatomal stimulation can be abolished at the block level and adjacent dermatomes by thoracic paravertebral nerve blockade. Equivalent results have not been demonstrated with more central forms of afferent blockade, which suggests that thoracic paravertebral nerve blocks may be uniquely effective. ⋯ To improve outcomes after major surgery, as much nociceptive information as possible should be prevented from entering the central nervous and neuroendocrine systems. We have shown that local anesthetics alongside the vertebral column can abolish the usual brain recordings that follow intercostal nerve stimulation, which suggests that paravertebral nerve blocks may be uniquely effective.