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
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.