V. Collet

Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages.

Background and objective Cellular immunity varies in the perioperative period. We evaluated the effects of fentanyl, clonidine and ketamine at different time points after surgery and in animals in different conditions (young vs. old). Materials and methods Rats undergoing laparotomy under sevoflurane anaesthesia were assigned to receive saline, fentanyl (40 μg kg−1), clonidine (10 μg kg−1) or ketamine (10 mg kg−1) 1 h before surgery. Natural killer (NK) activity was quantified at different time points (immediately or after 18, 24, 48, 72 h and 8 days) in vitro by the lysis of YAC-1 cells. In-vivo assessment included counting the number of lung metastases induced by the MADB-106 cells. Results During the first 24 h after surgery, a rapid increase in NK activity was noted, followed by a significant depression returning to baseline at 8 days. Analgesics show specific effects: fentanyl depressed NK activity with or without surgery. Clonidine depressed NK activity in nonoperated animals and during the first 24 h after surgery. Ketamine depressed NK activity in nonoperated animals but, after surgery, this activity varied with the same time course as saline. Ketamine and clonidine significantly reduced the number of lung metastases in operated animals. Ketamine significantly reduced the number of metastases in old nonoperated animals. Finally, ageing has a significant negative influence. Conclusion Surgery, analgesics and co-existing conditions significantly influence cellular immunity. The importance of these changes varies with time. Fentanyl had a worse influence than clonidine and ketamine, but seemed equally protective against the development of metastases.

An evaluation of the postoperative antihyperalgesic and analgesic effects of intrathecal clonidine administered during elective cesarean delivery.

BACKGROUND:Intrathecal clonidine improves intraoperative anesthesia and postoperative analgesia after cesarean delivery. Clonidine also possesses antihyperalgesic properties. Hyperalgesia contributes to postoperative pain and may be associated with increased risk of chronic pain after surgery. In this study, we evaluated the postoperative antihyperalgesic effect of intrathecal clonidine after caesarean delivery. METHODS:Ninety-six parturients undergoing elective cesarean delivery were randomly assigned to receive intrathecal bupivacaine-sufentanil (BS group), bupivacaine-sufentanil-clonidine 75 &mgr;g (BSC group), or bupivacaine-clonidine 150 &mgr;g (BC group). The primary outcome was the extent and the incidence of periincisional punctate mechanical hyperalgesia as assessed by response to application of a von Frey filament at 24 and 48 h after cesarean delivery. Postoperative morphine requirements and pain scores, as well as residual pain at 1, 3, and 6 mo, were also assessed. RESULTS:The BC group had a significantly reduced area of periincisional hyperalgesia at 48 h (median, 25th–75th percentiles): 1.0 (1.0 – 3.3) cm2 vs 9.5 (5.0–14.0) cm2 in the BS group vs 5.0 (2.5–12.3) cm2 in the BSC group (P = 0.02 with the BS group). The incidence of hyperalgesia at 48 h was also lower in the BC group: 16% vs 41% in the BS group vs 34% in the BSC group (P = 0.03 with BS group). Postoperative morphine consumption, pain scores, and incidence and intensity of residual pain did not differ among groups. CONCLUSIONS:Intrathecal clonidine 150 &mgr;g combined with bupivacaine had a postoperative antihyperalgesic effect expressed as a significant reduction in the extent and incidence of periincisional punctate mechanical hyperalgesia at 48 h after elective cesarean delivery compared with intrathecal bupivacaine-sufentanil and intrathecal clonidine 75 &mgr;g-bupivacaine-sufentanil.

Can determining the minimum alveolar anesthetic concentration of volatile anesthetic be used as an objective tool to assess antinociception in animals

We intended to evaluate the reliability of the minimum anesthetic alveolar concentration (MAC)-sparing effect as an objective measure of the antinociceptive properties of a drug. For this purpose, we tested different variables and analyzed the significance of the results obtained. In a first set of experiments, we studied rats under mechanical ventilation and sevoflurane anesthesia. Outcome variables such as gross purposeful movements consecutive to tail clamping, paw withdrawal consecutive to increasing pressure, and cardio-circulatory reactivity (MACBAR) after these stimuli were recorded. In a second set of experiment, sevoflurane-anesthetized rats under spontaneous breathing conditions were used. Thermal stimuli were compared with pressure. The MAC-sparing effect of several doses of sufentanil and clonidine was evaluated in both anesthetized and awake rodents. When considering the stimulus applied, larger concentrations of sevoflurane were required to suppress reactivity after tail clamp than after paw pressure or radiant heat (1.81 ± 0.28 versus 1.45 ± 0.22 and 1.53 ± 0.26; P < 0.05). For the two first stimuli, no significant differences were noted between the concentrations that suppress motor or cardio-circulatory reactions. All doses of sufentanil tested significantly reduced (P < 0.05) the different MAC values except the smallest one (0.005 &mgr;g · kg−1 · min−1) that significantly increased MACBAR in ventilated animals and both MAC and MACBAR in spontaneously breathing rodents (P < 0.05). Clonidine, at its optimal dose (10 &mgr;g/kg), significantly reduced both MAC and MACBAR to the same degree. In awake animals submitted to radiant heat or pressure challenge, none of the clonidine doses nor sufentanil doses (0.005 and 0.07) were active. In conclusion, the MAC-sparing effect provides several reliable and quantifiable variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of antinociceptive effects of the tested drugs but rather that of complex interactions between these drugs and a halogenated vapor.

Spinal alpha(2)-adrenoceptors are involved in the MACbar-sparing effect of systemic clonidine in rats.

UNLABELLED We evaluated the central or spinal mechanism involved in the MACbar-sparing effect of systemic clonidine by using intrathecal alpha-adrenergic antagonist administration. The minimum alveolar concentration of sevoflurane that blocks cardiovascular response to a noxious stimulus (MACbar(sevo)) was determined in rats after treatment with IV saline, IV clonidine 10 micro g/kg, intrathecal (IT) or IV phentolamine 50 micro g, IT or IV yohimbine 200 micro g, IT or IV prazosin 30 micro g, or the combination of IV clonidine and the different IT or IV alpha-adrenergic antagonists. In the studied model, the MACbar(sevo) of saline-treated controls was 2.10 +/- 0.8. After clonidine administration, it decreased to 1.07 +/- 0.4. The IT administration of phentolamine and yohimbine did not modify the MACbar(sevo) of naïve rats, whereas in IV clonidine-treated animals, it totally suppressed the MAC-sparing effect of this drug (phentolamine) or even significantly increased (yohimbine) the MACbar(sevo) (2.78 +/- 1) when compared with controls (P < 0.05). IT prazosin alone significantly reduced the MACbar(sevo) (0.35 +/- 0.3; P< 0.05) and suppressed any hemodynamic reaction when combined with IV clonidine. The IV administration of the different alpha-adrenergic antagonists had no significant effect on the MACbar(sevo) of controls or IV clonidine-treated animals. These results argue for a spinal mechanism of action involved in the MACbar-sparing effect of systemic clonidine. Moreover, the spinally administered alpha-antagonists displayed different effects in rats under sevoflurane anesthesia than those reported in awake animals. IMPLICATIONS Using intrathecal alpha-adrenergic antagonist administration, we demonstrated that a spinal mechanism is involved in the MACbar-sparing effect of systemic clonidine in rats.

Analgesic and hyperalgesic effect of single intrathecal dose of morphine under normal and neuropathic conditions: 14AP2-10

plasma O2 . production was the highest at the just reperfusion and lasted at least 1 week. Mechanical and cold allodynia were present in both hindpaws as early as 4 hr after reperfusion, and lasted at least 4 weeks. Pain behavior was significantly attenuated in G1, G2 and G3 compared with control. In G3, pain behavior was less attenuated than G1 and G2. Microscopic findings showed less inflammatory reaction in the G1 and G2. Conclusion(s): This study suggests that the O2 . is partly responsible for development of the CRPS-I. Even though O2 . inhibition is less effective after CRPS-I has been already developed, O2 . inhibition is still effective for reduce CRPS-I pain. References: 1 White FA, Bhangoo SK, Miller RJ. Nat Rev Drug Discov 2005; 4: 834–44. 2 Kim HK, Park SK, Zhou JL, et al. Pain 2004; 111: 116–24. 3 Coderre TJ, Xanthos DN, Francis L, et al. Pain 2004; 112: 94–105.

Local effect of bupivacaine and amitriptyline infiltration on wound NGF expression after plantar incision in rats: A-739

life in the spinal fluid phase2. We have collected respiratory depression data from 661 patients receiving intrathecal diamorphine up to 1mg for nonobstetric surgery. Materials and Methods: Over a one-year period, details of naloxone administration were collected from 1732 patients undergoing major non-obstetric surgery, of which 77% was major orthopaedic surgery. Patients received either intraoperative intrathecal diamorphine plus postoperative intravenous patient-controlled morphine analgesia (ITD PCA) or PCA alone (PCA group). Intrathecal diamorphine dosage varied from 0.1 mg to 1 mg, although the majority of patients received either 0.5 mg (ITD 0.5 PCA) or 1 mg (ITD1.0 PCA). The relative risk (RR) for receiving naloxone was calculated for each group, using the PCA group as a control. Where available, relative risk stratified by age above and below 80 years was calculated. Results and Discussions: Data are shown in the table.

Effect of abdominal surgery with or without vagotomy on tumor cells proliferation in rat: A-480

dependently from all 2-AR subtypes. At a concentration of 13 mM this displacement was almost complete. In 2A-AR-KO-mice a reduced signal intensity of specifically bound [125J]-PIC – according to the dominant role of this 2-AR subtype – was seen but the displacement by remifentanil was comparable to 2Band 2C-KO mice. Conclusion: Our findings suggest that remifentanil but not sufentanil interact with all subtypes of 2-AR in the central nervous system. This may indicate that clinical effects of remifentanil could be partially mediated by 2-AR. References: 1 Krause T, Tonner PH, Scholz J, et al. Anesthesiology 1999; V91, A388. 2 Takada K, et al. Anesthesiology 2002; 96: 1420–1426.