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
Clinical TrialReduced duration of intrathecal sufentanil analgesia in laboring cocaine users.
On the basis of our previous clinical experience, we hypothesized in this study that the duration and/or quality of labor analgesia produced by intrathecal sufentanil was less in cocaine-abusing parturients compared with nonabusing parturients. Ten micro g of sufentanil was given intrathecally as part of a combined spinal-epidural (CSE) technique to two groups of laboring parturients: 1). those whose urine tested positive for cocaine (cocaine group), and 2). those whose urine tested negative for cocaine (control group). The epidural catheter was not injected with local anesthetic until the patient requested additional pain relief. The time from injection of intrathecal sufentanil until patient request for additional pain relief was defined as duration of analgesia. Baseline visual analog pain score (VAPS) and cervical dilation were measured before the CSE was performed. After injection of intrathecal sufentanil, VAPS was recorded at specific intervals. Cervical dilation was again documented when the patient requested additional analgesia. We found that both groups reported high baseline VAPS and a marked decrease in VAPS after injection of sufentanil that did not differ between groups. Geometric mean duration of pain relief with adjustment for cervical dilation was 87 min in the cocaine group compared with 139 min in the control group (P = 0.019). All patients experienced itching. We conclude that intrathecal sufentanil produces a similar quality but shorter duration of analgesia in cocaine-abusing parturients compared with nonabusing parturients. ⋯ Intrathecal sufentanil administered as part of a combined spinal-epidural technique produces similar quality but reduced duration of labor analgesia in cocaine-abusing parturients compared with nonabusing parturients.
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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.