Combining intra-dialytic exercise and nutritional supplementation in malnourished older haemodialysis patients: Towards better quality of life and autonomy.

Protein-energy wasting (PEW), defined as a loss of body protein mass and fuel reserves, is a powerful predictor of adverse outcomes in haemodialysis (HD) patients. Robust arguments suggest that intra-dialytic exercise, combined with oral/parenteral nutrition, enhances the effect of nutritional interventions in HD patients. This pilot randomized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW, physical functioning (gait, balance, muscle strength) and quality of life (QoL) in older HD patients (mean age 69.7 ± 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were randomly assigned to Nutrition-Exercise group (GN-Ex , n = 10) or Nutrition group (GN , n = 11). Both groups received nutritional supplements in order to reach recommended protein and energy intake goals. In addition GN-Ex completed a cycling program. No significant difference between groups was found in the number of patients having reached remission of PEW. Likewise, no change was observed in serum-albumin, -prealbumin, C-reactive protein, body mass index, lean- and fat-tissue index, or quadriceps force. Interestingly, we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidenced by a significant improvement in the 6-min walk test (+22%), the absence of decline in balance (unlike the GN ), and a noteworthy increase in QoL (+53%). Combining intra-dialytic exercise and nutrition in HD patients is feasible, and well accepted, improves physical function and QoL but it appears not to have the potential to reverse PEW.

Electrical vagus nerve stimulation and nicotine effects in peritonitis-induced acute lung injury in rats.

The cholinergic anti-inflammatory pathway has been identified as playing a key role in the communication between the central nervous system and the immune system during inflammation. The potential beneficial role of vagus nerve stimulation (VNS) remains to be clarified in established sepsis. We hypothesized that VNS or nicotine administration would reduce lung injury and mortality in established sepsis. We conducted a prospective, randomized experimental study. Four hours after peritonitis induction by cecal ligation and puncture (CLP), rats were randomized into three groups of seven animals according to the intervention: control group, VNS group (15 V, 2 ms, 5 Hz during 20 min), and nicotine group (400 µg/kg intraperitoneal). Survival was determined as lung injury score 4 and 8 h after CLP. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, cytokine-induced neutrophil chemoattractant (CINC)-3 and thrombin-antithrombin complexes (TATc) were measured at baseline and at 4 and 8 h after CLP. Survival at 8 h was 71.4%, 100%, and 23.8% in the control, VNS, and nicotine groups, respectively (p < 0.05). All animals had lung damage but without significant difference between groups even if nicotine-treated animals tended to have a higher score than the controls (p = 0.09). Neutrophil polymorphonuclear (PMN) infiltration was more pronounced in the nicotine group compared with the VNS group (p = 0.015) but not with the controls. TNF-α, IL-6, IL-10, CINC-3, and TATc were elevated in all groups (NS). In this model of established sepsis, posttreatment by VNS was associated with increased survival, while nicotine administration increased lung PMN infiltration and mortality. Nicotine-induced bacterial clearance impairment and nicotine systemic effects may explain these observations.

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 microg kg(-1)), clonidine (10 microg 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 microg (BSC group), or bupivacaine-clonidine 150 microg (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) cm(2) vs 9.5 (5.0-14.0) cm(2) in the BS group vs 5.0 (2.5-12.3) cm(2) 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 mug 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 mug-bupivacaine-sufentanil.

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

UNLABELLED: 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 micro g x kg(-1) x 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 micro 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. IMPLICATIONS: The MAC-sparing effect provides several variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of the antinociceptive effects of the tested drugs but rather the result 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.