Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2003
Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures.
Postoperative immunosuppression is partly ascribed to anesthesia and has been suggested to compromise patients' resistance to infection and tumor metastasis. We compared the effects of various anesthetics on natural killer (NK) cell activity and on resistance to experimental metastasis, and studied mediating mechanisms and prophylactic measures. Fischer 344 rats served as controls or were anesthetized for 1 h with ketamine, thiopental, halothane, or propofol. Anesthetized rats were either maintained in normothermia or left to spontaneously reach 33 degrees C-35 degrees C. Rats were then injected IV with MADB106 tumor cells, and 24 h later lung tumor retention was assessed, or 3 wk later, lung metastases were counted. Additionally, the number and activity of circulating NK cells were assessed after anesthesia. All anesthetics, except propofol, significantly reduced NK activity and increased MADB106 lung tumor retention or lung metastases. Hypothermia had no significant effects. Ketamine increased metastasis most potently, and this effect was markedly reduced in rats pretreated with a beta-adrenergic antagonist (nadolol) or with chronic small doses of an immunostimulator (polyriboinosinic:polyribocytidylic acid). Overall, the marked variation in the NK-suppressive effects of anesthetics seems to underlie their differential promotion of MADB106 metastasis. Prophylactic measures may include perioperative immunostimulation and the use of beta-blockers. ⋯ This study in a rat model of pulmonary metastasis demonstrates that some anesthetics, but not others, increase susceptibility to tumor metastasis, apparently by suppressing natural killer cell activity. Ketamine was most deleterious, and its effects were prevented by peripheral blockade of beta-adrenoceptors combined with low levels of immunostimulation.
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Anesthesia and analgesia · Nov 2003
Minimum anesthetic concentration of sevoflurane with different xenon concentrations in swine.
In a previous study, we described a partial antagonism of xenon (Xe) in combination with isoflurane. One hypothetical explanation suggested that Xe and isoflurane probably induced anesthesia via different pathways at the neuronal level. This warranted investigating the combination of Xe with other inhaled anesthetics to examine the relationship between Xe and volatile anesthetics in general. We therefore investigated the influence of Xe on the minimum alveolar concentration (MAC) of sevoflurane. The study was performed in 10 swine (weight 30.8 kg +/- 2.6, mean +/- SD) ventilated with xenon 0%, 15%, 30%, 40%, 50%, and 65% in oxygen. At each Xe concentration, various concentrations of sevoflurane were administered in a stepwise design. For each a supramaximal pain stimulus (claw clamp) was applied. The appearance of a withdrawal reaction was recorded. The sevoflurane MAC was defined as the end-tidal concentration required to produce a 50% response rate. At each Xe concentration, the animals' responses to the pain stimulus were categorized and a logistic regression model was fitted to the results to determine sevoflurane MAC. Sevoflurane MAC was decreased by inhalation of Xe in a linear manner from 2.53 with 0% Xe to 1.54 with 65% Xe. In contrast to Xe and isoflurane, the anesthetic effects of Xe and sevoflurane appear to be simply linear. ⋯ We investigated the influence of the anesthetic gas, xenon, on the minimum alveolar concentration (MAC) for the volatile anesthetic sevoflurane. The study was performed in 10 swine ventilated with fixed xenon and various concentrations of isoflurane. The sevoflurane MAC is decreased by inhalation of xenon in a linear relationship.
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Anesthesia and analgesia · Nov 2003
An animal model for surgical anesthesia and analgesia: characterization with isoflurane anesthesia and remifentanil analgesia.
With a traditional clamp test alone, quantitative evaluation of the level of surgical anesthesia/analgesia is not easy. We have developed a rabbit model that allows for repeated quantification of the varying level of surgical anesthesia/analgesia using both mechanical and electrical stimulation as simulated surgical stimuli. After tracheostomy and intravascular cannulations under isoflurane anesthesia, eight rabbits were placed on a sling that allowed for free movement of the head and extremities. The inspired isoflurane concentration was reduced from 3% to 1.5% and then to 0%. Remifentanil was then infused at 4 graded infusion rates (0.1-0.8 microg. kg(-1) x min(-1)). At each drug dose, analgesic variables were determined including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and threshold voltage of subcutaneous electrical stimulation (2 Hz, 5 Hz, and 50 Hz) required to evoke the head lift (HLT, pain detection/arousal threshold) and escape movement responses (EMT, pain tolerance threshold). With increasing drug doses, HLTs and EMTs at 5 Hz increased dose-dependently and most proportionately to increases in the number of nonresponders, a standard indicator of the anesthetic/analgesic level. Therefore, using the HLT and EMT at 5 Hz combined with a clamp test, this rabbit model allows for quantitative evaluation of the varying level of surgical anesthesia/analgesia. ⋯ We have developed a rabbit model of surgical anesthesia and analgesia using both mechanical and electrical stimulation as simulated surgical stimuli, which allows for repeated, quantitative, and qualitative evaluation of the varying level of surgical anesthesia and analgesia, differentiation between sedative/hypnotic and analgesic components of drug actions, and simultaneous monitoring of all the clinically relevant physiological variables including cardiovascular and respiratory variables.
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Anesthesia and analgesia · Nov 2003
Detection of acute tolerance to the analgesic and nonanalgesic effects of remifentanil infusion in a rabbit model.
Although acute tolerance to analgesia develops rapidly with remifentanil, it is unknown whether acute tolerance also develops to its nonanalgesic effects. We investigated the analgesic and cardiorespiratory effects of remifentanil during a continuous infusion in a rabbit model. Ten tracheotomized New Zealand White rabbits with arterial and venous accesses were placed on a sling that allowed for reasonably free movement. In spontaneously breathing conscious animals, remifentanil was infused IV at a constant-rate of 0.3 microg kg(-1)x min(-1) for 360 min. Sedative/analgesic and cardiorespiratory variables were assessed repeatedly during remifentanil infusion, including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and subcutaneous electrical stimulation thresholds required to elicit head lift (HLT: pain detection/arousal threshold) and escape movement responses (EMT: pain tolerance threshold). Within 60-120 min of starting the infusion, the number of nonresponders, HLT, EMT, and PaCO(2) increased significantly, whereas blood pressure, heart rate, and respiratory rate decreased. Thereafter, all variables returned towards preinfusion levels despite continuing infusion. These results indicate that during a remifentanil infusion acute tolerance develops for both its analgesic and cardiorespiratory effects. ⋯ Using a new rabbit model, we found that during continuous, constant-rate remifentanil infusion acute tolerance developed within the first few hours, not only to its analgesic but also to its cardiovascular and respiratory effects, albeit in slightly different time courses.
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Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. To investigate the vasoconstrictive activity of this derivative, we performed functional examinations with dopamine treated with ONOO(-1) or 3-morpholinosydonimine-N-ethyl-carbamine (SIN-1; an ONOO(-1) producer) on isolated strips of rat thoracic aorta. To exclude the direct effect of ONOO(-1), the strips were pretreated with methylene blue, a guanylyl cyclase inhibitor. Dopamine induced concentration-dependent contraction, but dopamine pretreated with ONOO(-1) decreased the contraction in an ONOO(-1)-concentration-dependent manner. Both maximum contractions and 50% effective concentration values for dopamine-induced vasocontraction were significantly decreased by pretreatment with ONOO(-1). Dopamine incubated with SIN-1 also decreased the contraction, the decrease being dependent on the incubation time. ONOO(-1) formation is a favored reaction and occurs easily when cellular production of both nitric oxide and superoxide increases, as in septic shock. These results may, at least in part, account for dopamine's limitation as a vasoconstrictor in septic shock. ⋯ Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. We investigated the vasoconstrictive activity of this derivative with functional examinations using rat thoracic aorta and found the activity decreased. As ONOO(-1) formation increases in septic shock, our results may account for dopamine's limitation as a vasoconstrictor in septic shock.