Marc E. Gentili

The effect of local anesthetics and amitriptyline on peroxidation in vivo in an inflammatory rat model: preliminary reports.

We studied the inhibition of peroxidation by local anesthetics in an inflammatory animal model. Inflammatory lipid peroxidation was assessed by the thiobarbituric assay in plasma from rats injected or not injected with carrageenan (Carra) and killed 1, 2, 4, 6, 12, and 24 h thereafter. Thiobarbituric acid reactive substances (TBARS) values in inflammatory animals were maximal 6 h after Carra administration. This result, in accordance with the evolution of paw edema width during time, supports that TBARS reflect the intensity of inflammation. Local anesthetics (bupivacaine, lidocaine, ropivacaine, or bupivacaine-loaded microspheres) or amitriptyline were injected in clinically relevant concentrations as a sciatic nerve block or intraperitoneally in inflamed animals. Ropivacaine did not exhibit any protective effect on Carra-induced lipid peroxidation in rats. With all the other drugs administered as a sciatic nerve block, the maximal TBARS increase was not observed at 6 h. Our conclusion is that bupivacaine (plain or encapsulated), lidocaine, and amitriptyline in clinically relevant concentrations administered via the sciatic nerve showed antioxidant properties toward lipid peroxidation induced by Carra inflammation. Intraperitoneal injection of those drugs gave the same effect as nerve block; this result suggests that their mechanism of action is not strictly limited to the nerve.

Severe respiratory failure after infraclavicular block with 0.75% ropivacaine: a case report.

Upper extremity surgery is usually performed with an axillary block. There is a risk of pneumothorax and phrenic nerve block when interscalene or supraclavicular block are used in day case surgery, or in patients with chronic obstructive pulmonary disease. The infraclavicular block is a simple, reliable, and easy to learn method to block the brachial plexus. No clinically relevant respiratory effects have been reported with infraclavicular block. Nonetheless, we report a case of a chronic obstructive pulmonary disease patient who developed severe respiratory failure requiring tracheal intubation after an infraclavicular block.

Alkalinization of Intracuff Lidocaine: Efficacy and Safety

When alkalinized lidocaine instead of air is used to fill the endotracheal tube (ETT) cuff, coughing, and bucking are decreased during extubation when ventilation is controlled with N2O. However, sodium bicarbonate (NaHCO3) used to transform lidocaine hydrochloride (L-HCl) to lidocaine base induces a pH increase that could be irritating for mucosa in the case of cuff rupture. Therefore, we determined, in a randomized controlled study with controlled patient ventilation without N2O, whether the smallest concentrations of NaHCO3 (1.4% versus 8.4%) reduced diffusion (in vitro evaluation) and other secondary clinical benefits. After pH determination of different solutions (2 mL of 2% L-HCl and 2 to 6 mL of 8.4%, or 1.4% NaHCO3), an in vitro lidocaine diffusion through the ETT cuffs was evaluated (2 mL of 2% L-HCl and 3 mL of 8.4% or 1.4% NaHCO3). Then, adult patients scheduled for total thyroidectomy surgery were consecutively enrolled (n = 20 for each group). The ETT cuff was filled with air (group air) or with alkalinized lidocaine (2 mL of 2% L-HCl) using 8.4% (group large dose) or 1.4% (group small dose) of NaHCO3. After tracheal extubation, sore throat was evaluated by visual analog scale as the main end-point of the study. Hoarseness, bucking, dysphonia, dysphagia, cough, restlessness, and postoperative nausea and vomiting were also evaluated. There was a slight tendency toward a slower release when a small concentration of NaHCO3 was used (i.e., 1.4%). Compared with group air, the alkalinized-lidocaine groups had a significant reduction in sore throat during the 24-h postoperative period (P < 0.0001). The difference was not significant between the two alkalinized lidocaine groups. This increase in ETT tolerance was confirmed by the analysis of secondary end-points. No laryngospasm, rupture of ETT cuff, or depression of the swallowing reflex were recorded. A decrease in sore throat during the postoperative period was recorded when the cuff was inflated with a small dose of alkalinized lidocaine (i.e., 40 mg of L-HCl and 1.4% of NaHCO3) rather than with air when ventilation was controlled without N2O.

Sciatic nerve block with bupivacaine-loaded microspheres prevents hyperalgesia in an inflammatory animal model.

PurposeThe aim of this study was to evaluate the effect of different durations of local anesthetic neural blockade on hyperalgesia after carrageenan infiltration in a rat model.MethodsInflammation was obtained by injection of carrageenan in the righ hind paw. Hyperalgesia was determined by measuring the threshold of response to increasing mechanical stimuli on the contralateral and on the ipsilateral paw. The development of edema was measured. After identification of the sciatic nerve by nerve stimulation, blockade was performed either one hour before or after carrageenan infiltration. Animals were randomly assigned into three groups: without sciatic nerve block (control group;n = 20), block with bupivacaine (B) and block with bupivacaine-loaded microspheres (B-Ms) injection before or after carrageenan infiltration (n = 10 for each group).ResultsCarrageenan infiltration in the control group induced a severe ipsilateral and contralateral hyperalgesia. After blockade with B (duration = 2 ± 0.5 hr) hyperalgesia was present and delayed only by the duration of the local anesthetic effect. A longer duration of block achieved with B-Ms (duration greater than five hours), was associated with the absence of development of both ipsilateral and contralateral hyperalgesia. No preemptive effect was recorded.ConclusionB-Ms as a drug delivery system prolongs the duration of neural blockade and avoids hyperalgesia phenomena in this rat model of inflammation.RésuméObjectifLe but de cette étude a été d’évaluer, sur un modèle d’inflammation de la patte de rat, l’effet de la durée du bloc sur les phénomènes d’hyperalgésie homo et controlatérale.MéthodeL’inflammation a été obtenue par une infiltration de carragénine. L’hyperalgésie des deux pattes à été évaluée par le test de retrait de la patte à une pression mécanique croissante. L’œdème a été mesuré. Le nerf sciatique a été repéré par neurostimulation, soit une heure avant, soit une heure après l’infiltration de carragénine. Les animaux ont été randomisés en trois groupes: sans bloc sciatique (groupe témoin; n = 20), avec bloc sciatique à la bupivacaïne (B) ou à la bupivacaïne encapsulée dans des microsphères (B-Ms). Les blocs ont été réalisés soit avant soit après l’inflammation (n = 10 par groupe).RésultatsDans le groupe témoin, l’hyperalgésie homolatérale et controlatérale ont été significatives. Après l’injection, de bupivacaïne, et malgré la durée du bloc de deux heures, la bupivacaïne n’a pas empêché l’apparition ou la réapparition des phénomènes d’hyperalgésie homo et controlatérale. Avec la B-Ms la durée de bloc d’environ cinq heures a permis de supprimer ces phénomènes. II n’a pas été retrouvé d’effet préventif.ConclusionLa B-Ms permet non seulement de prolonger la durée du bloc mais aussi de prévenir la survenue des phénomènes d’hyperalgésie.

Lidocaine priming reduces tourniquet pain during intravenous regional anesthesia: A preliminary study.

Background and Objectives Tourniquet pain often limits the use of intravenous regional anesthesia (IVRA). Intravenous (IV) lidocaine has been shown to be effective in the management of acute and neuropathic pains. We tested the hypothesis that a priming IV injection of lidocaine might have an analgesic effect on tourniquet pain during IVRA. Methods A prospective, randomized, double- blind study was conducted on 40 patients scheduled for carpal tunnel decompression. No sedation was given. Each patient received either 1 mg/kg of IV lidocaine (group L) or 0.1 mL/kg of IV isotonic saline (group control = C) 5 minutes before IVRA. Thereafter, they received 3 mg/kg of plain 0.5 % lidocaine into the isolated and exsanguinated arm. A double-cuffed tourniquet was used. Pain at the tourniquet and the surgical sites was assessed every 5 minutes using a linear visual analog scale (VAS) and a verbal rating scale (VRS) during the surgical procedure and the immediate postoperative period (60 minutes). Results Demographic data and duration of proximal and distal tourniquet were similar in each group. Significant differences in the pain scales were observed for the distal tourniquet at tourniquet inflation time and 15 minutes after (P = .03 and .005, respectively) in the group L. For the proximal tourniquet, only the VRS was significantly improved (P = .03). No analgesic benefit was observed in the immediate postoperative period. Conclusions Priming IV lidocaine when compared with isotonic saline is effective in reducing tourniquet pain in IVRA.

The addition of tramadol to lidocaine does not reduce tourniquet and postoperative pain duringiv regional anesthesia

PurposeWe conducted a prospective, randomized, double-blind study to determine whether the combination of tramadol with lidocaine 0.5% had an analgesic effect on tourniquet pain duringiv regional anesthesia and also on postoperative pain.MethodsThirty patients scheduled for carpal tunnel decompression were included in the study. Each patient received 3 mg·kg−1 of plain lidocaine 0.5% with 100 mg of tramadol (Group T) or 2 ml_ of isotonic saline (Group C). The mixture was injected into the isolated and exsanguinated arm. Pain was assessed using a linear visual analog scale and a verbal rate scale during the surgical procedure and the postoperative period (240 min) and subsequently at interview at 24 hr. Analgesic consumption was recorded.ResultThere was no difference in the pain scales and analgesic request at any of the time periods studied.ConclusionWe conclude, therefore, that for carpal tunnel operation underiv regional anesthesia, the combination of tramadol and lidocaine is not more effective than lidocaine alone.RésuméObjectifDéterminer, par une étude prospective, randomisée et à doubie insu, si ia combinaison de tramadoi et de iidocaïne à 0,5 % produit un effet anaigésique sur ia douleur du garrot pendant l’anesthésie iv régionale et sur ia douleur postopératoire.MéthodeTrente patients devant subir ia décompression du canai carpien ont participé à l’etude. Chacun a reçu 3 mg·kg−1 de lidocaïne simple à 0,5 % combinée à 100 mg de tramadol (Groupe T) ou à 2 mL de solution saline isotonique (Groupe C). Le méiange a été injecté dans le bras isoié et exsanguine. La douleur a été évaiuée à l’aide d’une échelle visuelle analogique linéaire et d’une échelle verbaie pendant l’opération et 4 h et 24 h après l’opération, cette dernière évaluation faisant l’objet d’une entrevue. La consommation d’analgésique a été notée.RésultatsTous les scores de douleur et les besoins d’analgésiques ont été semblables d’un groupe à l’autre, et ce, pour tous les temps de mesures.ConclusionLa combinaison de tramadol et de lidocaïne, utilisée pour I’anesthésie iv régionale pendant la compression du canal carpien, n’est pas plus efficace que la lidocaïne employée seule.

An evaluation of a polyamine-deficient diet for the treatment of inflammatory pain

Polyamines are thought to be involved in the regulation of numerous metabolic and electrophysiological processes in the nervous system. In this study we evaluated the effect of a synthetic polyamine-deficient diet on pain in a carrageenan (Car)-induced inflammatory rat model. Inflammation was induced with a unilateral subcutaneous injection of Car in a plantar hindpaw in rats fed without (control group) or with (deficiency group) a polyamine-deficient diet. Ipsilateral and contralateral hyperalgesia was evaluated using the Randall-Sellito pressure test. Heart rate changes were also recorded under general anesthesia. Then, the effects of a bupivacaine sciatic nerve block and subcutaneous injection of naloxone or ketamine were evaluated for Car-induced hyperalgesia. Data were analyzed using analysis of variance followed by unpaired Students t-test (significance P < 0.05). Before Car injection, no significant difference was observed in response to mechanical stimuli between the control and the deficiency groups (n = 114 in pooled data). Car injection induced significant ipsilateral and contralateral hyperalgesia in the control groups, whereas a significant analgesic effect appeared in the deficient groups on both the ipsilateral and contralateral hindpaws. This analgesic effect was confirmed by the electrocardiogram recording that showed a significant increase in heart rate in the control group after Car injection compared with the deficiency group that showed a decrease in heart rate under general anesthesia. Bupivacaine sciatic nerve block had no significant effect on hypoalgesia phenomena induced by polyamine deficiency. Naloxone administration had no effect in the control group but reversed the analgesic effect in the deficiency group. Ketamine administration induced a significant analgesic effect in the control group and partly reversed the analgesic effect in the deficiency group. In conclusion, a synthetic polyamine-deficient diet had a significant general analgesic effect on Car-induced mechanical hyperalgesia. The mechanism of analgesic action remains to be elucidated.

Opioid-Induced Sedation in the Postanesthesia Care Unit Does Not Insure Adequate Pain Relief: A Case-Control Study

BACKGROUND:Sedation can occur during intravenous titration of morphine for acute pain control in the postanesthesia care unit (PACU). We designed this case-control study to evaluate the relationship between opioid-induced sedation in the PACU and adequacy of early postoperative analgesia. METHODS:Intravenous morphine was titrated in 2 mg (body weight ≤60 kg) or 3 mg (body weight >60 kg) boluses every 5 min to treat moderate-to-severe pain in the PACU. Pain was assessed using a 11-point verbal rating scale (VRS) with scores ≥3 representing moderate-to-severe pain. The 6-point Ramsay score was used to assess the level of sedation with scores >3 representing clinically significant sedation. Twenty-six patients, with a Ramsay sedation score >3 and a pain VRS ≥3 at discharge from the PACU, were evaluated 24 h after surgery to assess (a) the recall of early postoperative pain in the PACU, (b) quality of sleep on the first night after surgery, (c) pain on the 24th postoperative hour, and (d) satisfaction with pain management at 24 h after surgery. Two patients discharged from the PACU with VRS pain scores <3 were matched to each of the patients with pain scores ≥3 and Ramsay score >3, as part of a 52 patient control group. RESULTS:Patients with Ramsay scores >3 and pain scores ≥3 more frequently reported moderate-to-severe pain in the PACU (severe/moderate/no pain: 18%/25%/57% vs 58%/16%/26%, P = 0006, for the control and the sedated group, respectively), poorer quality of sleep the night after surgery (well/moderate/bad: 48%/42%/10% vs 23%/23%/54%, P = 0.001, for the control and the sedated group, respectively), and higher pain scores at the 24th hour after surgery (severe/moderate/no pain: 6%/44%/50% vs 50%/42%/8%, P < 0.0001, for the control and the sedated group, respectively). In addition, their overall satisfaction with pain control during the first 24 postoperative hours was lower (satisfied/moderately satisfied/not satisfied: 96%/2%/2% vs 50%/30%/20%, P < 0.0001, for the control and the sedated group, respectively). CONCLUSION:Clinically significant opioid-induced sedation in the PACU does not insure adequate self-reported pain relief.