Jean-Pierre Estebe

Infraclavicular plexus block: Multiple injection versus single injection

Background and Objectives This prospective, randomized, and multicentered study was undertaken to evaluate the success rate of coracoid infraclavicular nerve block performed with a nerve stimulator when either 1 or 3 motor responses were sought. Methods Eighty patients who presented for elbow, forearm, or wrist surgery were randomly allocated to one of the following groups: in group 1 (single stimulation), 30 mL local anesthetic (LA) was injected after locating only 1 of the median, ulnar, or radial motor responses. In group 2 (multistimulation), 3 responses were located: musculocutaneous, median or ulnar, and radial response, corresponding, respectively, to the lateral, medial, and posterior cords. A total of 10 mL LA was injected on each response. Bupivacaine 0.5% and lidocaine 2% with epinephrine 1:200,000 (1:1 vol) were used as the LA mixture. Sensory and motor blocks were tested by a blinded observer. Results Block duration was slightly increased in the multistimulation group (P = .004). The onset time of sensory and motor block was faster in each nerve distribution, particularly in the radial, musculocutaneous, and antebrachial nerves. The success of anesthesia increased in the multistimulation group. The success rate of the block, without any additional block, sedation, or general anesthesia, increased from 40% in the single stimulation group to 72.5% in the multistimulation group (P < .0001). If the brachial and antebrachial cutaneous nerves were not included in the evaluation, success rate reached 87.5%. Conclusions We conclude that by performing an infraclavicular block with stimulation of all 3 cords of the brachial plexus, the success rate is higher than when only a single stimulation is used.

Amitriptyline neurotoxicity: dose-related pathology after topical application to rat sciatic nerve.

Background: Amitriptyline is a tricyclic antidepressant drug used systemically for the management of neuropathic pain. Antidepressants, as a class of drugs with direct neurologic actions, are becoming widely used for the management of chronic pain, although their mechanisms are not entirely understood. Amitriptyline exerts potent effects on reuptake of norepinephrine and serotonin and blocks &agr;2A adrenoreceptors and N-methyl-d-aspartate receptors. Because amitriptyline is also a particularly potent blocker of sodium channels and voltage-gated potassium and calcium channels, it has been recommended as a long-acting local anesthetic agent. Unfortunately, amitripty-line has significant toxic side effects in the central nervous system and cardiovascular system that are dose-related to its systemic administration. Therefore, before amitriptyline can be used clinically as a local anesthetic agent, it should be thoroughly explored with respect to its direct neurotoxic effect in the peripheral nervous system. Methods: The left sciatic nerve of Sprague-Dawley rats (12/ group) received a single topical amitriptyline dose of 0.625, 1.25, 2.5, or 5 mg; a saline group (n = 2) was used as control. Neuropathologic evaluations were conducted in separate animals (n = 4) 1, 3, and 7 days later. Results: Amitriptyline topically applied in vivo to rat sciatic nerve causes a dose-related neurotoxic effect. Drug doses of 0.625–5 mg all caused Wallerian degeneration of peripheral nerve fibers, with the number of affected fibers and the severity of the injury directly related to the dose. Conclusion: Because the effective local anesthetic dose is within this dose range, the authors strongly recommend that amitriptyline not be used as a local anesthetic agent.

Alkalinization of intracuff lidocaine improves endotracheal tube-induced emergence phenomena.

UNLABELLED We sought to evaluate the effect of filling an endotracheal tube cuff with 40 mg lidocaine alone (Group L) or alkalinized lidocaine (Group LB) in comparison to an Air Control group (Group C) on adverse emergence phenomena in a randomized controlled study (n = 25 in each group). The incidence of sore throat was decreased for Group LB in comparison to Group L during the 24 postextubation hours. The difference between Group L and Group C remained significant in the two postextubation hours only. Plasma lidocaine levels increased when lidocaine was alkalinized (C(max) were 62.5 +/- 34.0 ng/mL and 3.2 +/- 1.0 ng/mL for Groups LB and L, respectively). Cough and restlessness before tracheal extubation were decreased in Group LB compared with Group L and in Group L compared with Group C. Nausea, postoperative vomiting, dysphonia, and hoarseness were increased after extubation in Group C compared with the liquid groups, and a better tolerance was recorded with Group LB compared with Group L. The increase of arterial blood pressure and cardiac frequencies during the extubation period was less in the liquid groups than in the control group and less in Group LB compared with Group L. We concluded that use of intracuff alkalinized lidocaine is an effective adjunct to endotracheal intubation. IMPLICATIONS Use of 40 mg of alkalinized lidocaine, rather than lidocaine or air, to fill the endotracheal tube cuff reduces the incidence of sore throat in the postoperative period. This approach also decreases hemodynamic effects, restlessness, dysphonia, and hoarseness.

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.

The pharmacokinetics and pharmacodynamics of bupivacaine-loaded microspheres on a brachial plexus block model in sheep.

UNLABELLED: We evaluated bupivacaine-loaded microspheres (B-Ms) using a brachial plexus block model in sheep. In the first step, pharmacokinetic characterization of 75 mg bupivacaine hydrochloride (B-HCl) (IV infusion and brachial plexus block) was performed (n = 12). In the second step, a brachial plexus block dose response study of B-HCl was performed with 37.5 mg, 75 mg, 150 mg, 300 mg, and 750 mg. As a comparison, evaluations were performed using a 750-mg bupivacaine base (B). In the third step, evaluations of brachial plexus block were performed with B-Ms (750 mg of B as B-Ms) using two formulations, 60/40 and 50/50 (w/w %); drug-free microspheres were also evaluated. Toxicity evaluations were also performed after IV administration of B-HCl (750 mg and 300 mg), B-Ms (750 mg), and drug-free microspheres (30 mL over 1 min). As the B-HCl dose increased, the time of onset of block decreased and the duration of complete motor blockade increased at the expense of an increase in bupivacaine plasma concentrations. The time of maximum concentration appeared to be independent of the B-HCl dose. In brachial plexus block, a 37.5-mg dose of B-HCl did not induce motor blockade whereas a dose of 750 mg of B-HCl was clinically toxic. In the case of IV administration, doses of 300 mg of B-HCl were as toxic as 750 mg of B-HCl. Compared with the 75 mg of B-HCl administration for brachial plexus block, administration of 750 mg of B as B-Ms increased the duration of complete motor blockade without significant difference in maximum concentration. No significant clinical difference between the two formulations of B-Ms was demonstrated. The IV administration of B-Ms was safe. We conclude that the controlled release of bupivacaine from microspheres prolonged the brachial plexus block without obvious toxicity. IMPLICATIONS: Administration of 750 mg of bupivacaine as loaded-microspheres resulted in prolongation of brachial plexus block in sheep. The peak plasma concentration was not significantly larger than that obtained with 75 mg of plain bupivacaine. The motor blockade was increased more than six times compared with 75 mg plain bupivacaine.

Prolongation of spinal anesthesia with bupivacaine-loaded (DL-lactide) microspheres.

There is considerable interest in developing a sustained-release local anesthetic formulation to provide long-lasting anesthesia and to decrease systemic toxicity. Bupivacaine (B), 10 mg, loaded in two different types of polylactide microspheres (PLA1 and PLA2) was evaluated after spinal injection and compared with plain bupivacaine (pB), 2 mg. Experiments were performed in six New Zealand rabbits. Duration of motor block was significantly prolonged for PLA1 compared to pB (177.5 +/- 79.5 min vs 44.6 +/- 18.0 min; P < 0.05), as well as for the recovery time (545.0 +/- 299.6 min vs 44.2 +/- 21.5 min; P < 0.05). The duration and recovery were not prolonged for PLA2. Systemic release of B after intrathecal injection was measured from blood samples by using high-performance liquid chromatography. There was no significant difference in maximum B plasma concentration between pB and PLA1 (326 +/- 81 mg/mL vs 321 +/- 57 ng/mL). The time taken to reach the maximum plasma concentration (6.6 +/- 2.6 min vs 41.7 +/- 20.4 min; P < 0.05) was significantly different. This study demonstrated that the use of bupivacaine-loaded (DL-lactide) microspheres can prolong spinal motor block. (Anesth Analg 1995;81:99-103)

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.

Epidural, intrathecal and plasma pharmacokinetic study of epidural ropivacaine in PLGA-microspheres in sheep model.

BACKGROUND Microparticulate local anesthetics-loaded delivery systems are known to provide a controlled release of drug and to reduce systemic toxicity resulting from transient high plasma concentrations. The aim of this study was to evaluate epidural, intrathecal and plasma pharmacokinetics of ropivacaine following epidural administrations of repeated boluses or infusions and to compare them with the epidural administration of polylactide-co-glycolide ropivacaine-loaded microspheres. METHODS In the first step, the epidural and intrathecal pharmacokinetics was evaluated in 3 Lacaunes ewes, receiving epidural continuous infusion of ropivacaine with increasing doses (20, 50 and 100mg/h). Then, six animals received an epidural administration of ropivacaine-loaded microspheres (500 mg), three others received ropivacaine in epidural bolus (30 mg) followed by infusion (2mg/ml during 6h), and the last three animals received three successive epidural boluses of ropivacaine (50mg) at 2h interval. A simultaneous microdialysis technique was used to measure epidural and intrathecal concentrations of ropivacaine. RESULTS After epidural administration of ropivacaine-loaded microspheres, Cmax in plasma was around 100 ng/ml while epidural and intrathecal Cmax of ropivacaine were close to 600 and 150 microg/ml, respectively. The ratios of intrathecal to epidural AUC (AUCit/AUCepi) for bolus administration, bolus+infusion administration, and for microspheres were 13.4+/-2.4; 14.1+/-6.1 and 33.9+/-22.6%, respectively. This suggested that administration of ropivacaine as microspheres increased the transmeningeal passage of ropivacaine in comparison to other administration regimens. CONCLUSIONS Epidural administration of ropivacaine-loaded microspheres led to the sustained levels of ropivacaine in the intrathecal space compared to the boluses of ropivacaine solution. Moreover, epidural administration of microspheres resulted in the highest efficiency in intrathecal uptake of ropivacaine compared to administration in solution.

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.

Endotracheal tube cuffs filled with lidocaine as a drug delivery system: in vitro and in vivo investigations

The purpose of this study was to examine if lidocaine diffusion across an endotracheal tube cuff could improve post-operative tolerance, especially sore throat. The in vitro release of lidocaine from tube cuffs filled with different lidocaine formulations (base form, hydrochloride form or alkalinized lidocaine hydrochloride) was investigated. A preliminary pilot clinical study in anaesthesia for spine surgery in smoker patients was carried out to examine the pharmacokinetic (i.e. systemic uptake) and pharmacodynamic effects (i.e. incidence of sore throat) obtained with the endotracheal tube cuff filled with lidocaine solution, compared to cuffs inflated only with air. From our in vitro experiment, only the hydrophobic neutral base form of lidocaine was able to diffuse (65.1+/-1.1% released after 6 h), while for the charged hydrochloride form, only a permeation phenomenon occurred concerning only 1% of the total drug. Alkalinization of lidocaine hydrochloride (the only form available as a drug) allows smaller amounts to be used compared to previous published studies (20-40 mg vs. 200-500 mg) and no lag time for diffusion. Such a system could provide a controlled release reservoir for lidocaine to adjacent tracheal tissue. This was shown in our pilot study with sustained plasmatic profiles and improved tolerance (decreased pain scores) in the rank order: air group<<lidocaine hydrochloride group