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Objective We hypothesised that videolaryngoscopy modifies practice of tracheal intubation. Design Randomised single-blinded study (video and no-video groups). Setting Three institutions: one academic, one non-profit and one profit. Participants Patients >18 years, requiring orotracheal intubation, without predicted difficult intubation. Non-inclusion criterion was patients requiring a rapid-sequence intubation. 300 patients were included, 271 randomised, 256 analysed: 123 in the no-video and 133 in the video groups. Intervention Tracheal intubation using a McGrath Mac videolaryngoscope, the sequence being video recorded. Primary and secondary outcome measures The primary outcome was the proportion of intubations where assistance is necessary on request of the operator. Secondary outcomes included intraoperative variables (intubation difficulty scale and its components, percentage of glottic opening score, oesophageal Intubation, duration of intubation, removal of the screen cover in the no-video group, global evaluation of the ease of intubation, bispectral index, heart rate and blood pressure), intraoperative and postoperative complications (hoarseness or sore throat) and cooperation of the anaesthesiology team. Results Requirement for assistance was not decreased in the Video group: 36.1% (95% CI 27.9 to 44.9) vs 45.5% (95% CI 36.5 to 54.7) in the no-video group, p=0.74; OR: 0.7 (95% CI 0.4 to 1.1) and absolute risk: 0.10 (95% CI −0.03 to 0.22). Intubation difficulty scale was similar in both groups (p=0.05). Percentage of glottic opening score was better in the Video group (median of 100 (95% CI (100 to 100) and 80 (95%CI (80 to 90) in the no-video group; p Conclusion In patients without predicted difficult intubation, videolaryngoscopy did not decrease the requirement for assistance to perform intubation. Trial registration number NCT02926144; Results.

This study assessed whether a focal glove hypnotic hand anesthesia induced thermal changes within the area of hypnotic protection. Skin temperature of hands, wrists, and forearms was continuously recorded bilaterally using infrared thermography in 30 volunteers. Thermal recordings were obtained prior to, after glove building, and after its withdrawal, with the contralateral upper limb serving as control side. Analgesic glove induced a statistically significant difference in temperature variation within the hand, wrist, and distal forearm on the glove side, compared with proximal forearm and control side. Hypnotic glove analgesia provides significant changes in skin temperature within protected areas. Further research is required to determine the mechanisms of these objective changes induced by hypnosis.

The purpose of this study was to evaluate the effects of a hypnotically-based intervention for pain and fear in women undergoing labor who are about to receive an epidural catheter. A group of 155 women received interventions that included either (a) patient rocking, gentle touching, and hypnotic communication or (b) patient rocking, gentle touching, and standard communication. The authors found that the hypnotic communication intervention was more effective than the standard communication intervention for reducing both pain intensity and fear. The results support the use of hypnotic communication just before and during epidural placement for women who are in labor and also indicate that additional research to evaluate the benefits and mechanism of this treatment is warranted.

Resume L’objet de cette mise au point pratique consiste a detailler l’organisation d’un circuit court ambulatoire ou « fast-track », en prenant comme exemple le parcours d’un patient opere en ambulatoire d’une chirurgie du pied sous anesthesie locoregionale, en reprenant en detail une communication video diffusee lors du congres VIDEOCAA en 2016.

Resume De nombreuses interventions sont pratiquees sur le genou. Cet article presente l’evolution des techniques d’analgesie postoperatoire adaptees a la prothese totale du genou, en prenant en consideration la necessite de mettre en place une recuperation amelioree apres chirurgie avec comme imperatif une deambulation precoce. La technique analgesique de reference apres prothese totale de genou demeure le bloc femoral, mais son inconvenient majeur est le bloc moteur qui rend le lever precoce difficile. Les techniques analgesiques alternatives comme le bloc au canal des adducteurs ou l’infiltration chirurgicale periarticulaire cherchent a minimiser le bloc moteur. Leurs indications respectives sont debattues, mais elles s’integrent bien dans le cadre d’une prise en charge multimodale.

Resume Cet article retrace l’evolution de la pratique de l’hypnose depuis le XVIII e siecle et la transe hypnotique selon Messmer jusqu’a nos jours avec l’appui des neurosciences faisant suite au renouveau impulse notamment par Milton Erickson.

Background Sensory assessment to estimate spread and effectiveness of a peripheral nerve block is difficult because no clinical test is specific for small sensory fibers. Occurrence of a swelling illusion (SI) during a peripheral nerve block corresponds to the impairment of small sensory fibers. The authors investigated the usefulness of SI in predicting successful peripheral nerve block by assessing the temporospatial correlation between progression of sensory impairment in cutaneous distributions anesthetized and localization of SI during peripheral nerve block installation. Methods Interscalene, infracoracoid, or sciatic nerve blocks were performed using a nerve stimulator and 1.5% mepivacaine in 53 patients, with a total of 201 nerves to be anesthetized. Pinprick, cold, warm, touch, and proprioception were assessed every 3 min, while patients were asked to describe their perception of size and shape of their anesthetized limb and localization of these illusions. Data are presented as mean +/- SD and percentage (95% confidence interval). Results Failure occurred in 12 cutaneous distributions out of a total of 201 theoretically blocked nerves. SI appeared earlier than warmth impairment (4.3 +/- 2.7 vs. 6.2 +/- 2.0 min; P < 0.05), always corresponding to successfully anesthetized cutaneous distributions, with the exception of 1 patient, who developed SI in 2 cutaneous distributions while sensory testing indicated failure in 1 distribution. SI successfully predicted the blockade of a cutaneous distribution with a sensitivity of 1.00 (0.98-1.00), a specificity of 0.92 (0.65-0.99), and an accuracy of 0.99 (0.97-1.00). Conclusions Swelling illusion may provide an early assessment of the success of a peripheral nerve block in unsedated patients.

Objective The objective of this article is to describe a late-onset phantom-limb pain during a continuous analgesic popliteal nerve block after foot surgery and its alleviation and recurrence when stopping and resuming the local anesthetic infusion. Case Report A 29-year-old woman undergoing a left hallux valgus repair received a continuous popliteal sciatic nerve block for postoperative analgesia. Postoperatively, 6 hours after the commencement of a ropivacaine 0.2% infusion, she reported feelings of tingling, clenching pain, and missing-limb sensation below the ankle. The surgical site remained painless. Sensation elicited by touch and propioception were normally perceived. Only sensations for pinprick and heat were impaired. The ropivacaine infusion was stopped, followed 2.5 hours later by the complete regression of any abnormal sensation. Meanwhile, pain at the surgical site was scored at 50 mm on a 100-mm visual analogic scale. As the infusion of ropivacaine was resumed, the abnormal sensations reappeared. The catheter was removed, and abnormal sensations again disappeared. The patient was discharged from hospital without further complications. Conclusions This observation suggests that phantom-limb pain can be of late-onset and might occur during a continuous infusion of low-concentration local anesthetic responsible only for an analgesic block, as shown by the fact that only thermal and pinprick sensations, known to depend on Aδ-fibers and C-fibers, were altered. Therefore, this case contradicts the usual belief that a profound block is necessary to elicit phantom-limb pain.

Background Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery. Methods Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval. Results Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min] vs.150 min [range, 105-160 min]; P< 0.05) and motor (357 min [range, 270-475 min] vs. 150 min [range, 90-210 min]; P< 0.05) blockade. Duration of complete sensory block was significantly correlated with age (rho = 0.56; P< 0.05). Conclusions Age is a major determinant of duration of complete motor and sensory blockade with peripheral nerve block, perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the elderly population.

Objectives: To evaluate the accuracy of bispectral index (BIS) monitoring for the diagnosis of brain death in severely comatose patients. Design: A prospective study in an intensive care unit of a university hospital. Population: Fifty-six severely comatose patients (Glasgow Coma Score ≤5) admitted to the ICU mainly because of intracerebral hemorrhage, head injury, or postanoxic coma. Methods: BIS was recorded continuously during the hospitalization in the ICU. Where necessary, clinical brain death was confirmed by EEG or cerebral angiography. Measurements and results: Twelve patients were already clinically brain dead at the time of admission, and their individual BIS values were 0. In each of these 12 patients brain death was thereafter confirmed by EEG or cerebral angiography. Forty-four patients were not clinically brain-dead at the time of admission, and their individual BIS values were between 20 and 79. Twenty-seven of these patients became brain-dead, and their individual BIS values dropped to 0 in a few hours to a few days. In these 27 patients EEG or cerebral angiography was performed after the BIS value decreased to 0 and confirmed brain death in all cases. Seventeen patients who did not become brain dead during their hospitalization in the ICU had persistent electrocerebral activity on EEG, and their average BIS values remained above 35. Conclusion: BIS can be used in severely comatose patients as an assessment of brain death onset, enabling appropriate scheduling of either EEG or cerebral angiography to confirm brain death.

Background — In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. Methods and Results — Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2–related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482±14 versus 420±14 ms in the saline-treated group, P P Conclusions — Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.

Background Indirect evidence supports a role of spinal cholinergic neurons in tonically reducing response to noxious mechanical stimulation and in effecting analgesia from alpha2-adrenergic agonists. This study directly assessed the role of cholinergic neurons in regulating the level of mechanical allodynia and in participating in the antiallodynic effect of the clinically used alpha2-adrenergic agonist, clonidine, in an animal model of neuropathic pain. Methods Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Rats received a single intrathecal injection of saline or one of three different doses of the cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64-A; 2, 5, and 15 nmol). Seven days later, allodynia was assessed before and after intrathecal injection of 15 microg clonidine. The spinal cord was removed, and spinal cord acetylcholine content, cholinergic neuron number and distribution, and alpha2-adrenergic receptor expression were determined. Results AF64-A administration reduced both the number of cholinergic cells and the acetylcholine content of the lumbar dorsal spinal cord by 20-50% but did not affect level of mechanical allodynia. AF64-A did, however, completely block the anti-allodynic effect of clonidine. AF64-A did not reduce alpha2-adrenergic ligand binding in dorsal lumbar cord. Conclusions These data suggest that spinal cholinergic tone does not affect the level of mechanical allodynia after peripheral nerve injury. There is a quantitative reliance on spinal cholinergic neurons in the allodynia relieving properties of intrathecal clonidine, and this reliance does not depend on alpha2-adrenergic receptors colocalized on spinal cholinergic interneurons.

Background Clonidine produces analgesia after spinal injection by activating alpha2-adrenergic receptors. Recently, clonidine has been demonstrated to increase spinal release of norepinephrine (NE) in vivo, in contrast to that anticipated by classic presynaptic autoinhibition. The purpose of the current study was to determine if clonidine could inhibit release of NE in a preparation of spinal cord tissue lacking synaptic circuits. Methods Crude synaptosomes were prepared from male Sprague-Dawley rat spinal cord, loaded with [3H]NE, and stimulated by potassium chloride to release [3H]NE. Samples were incubated with clonidine in the absence or presence of various inhibitors. To study the effect of alpha2a-adrenergic receptor subtypes, some animals were pretreated with an oligodeoxynucleotide (ODN) composed of a sense or antisense sequence to a portion of this receptor. Results Potassium chloride produced a concentration-dependent increase in [3H]NE release, and this release was inhibited by clonidine with a concentration producing 50% maximal inhibition (IC50) of 1.3 microm. The effect of clonidine was inhibited by the alpha2-adrenergic antagonists, yohimbine and idazoxan, but not by alpha1-adrenergic, muscarinic, or opioid antagonists. Intrathecal pretreatment with antisense ODN to alpha2A-adrenergic receptors reduced alpha2A-adrenergic receptor protein expression compared with sense ODN control and also reduced clonidine-induced inhibition of [3H]NE release. Conclusions These data demonstrate the existence of classic autoinhibitory alpha2-adrenergic receptors in the spinal cord, probably of the alpha2Asubtype. They further suggest that clonidine-induced stimulation of spinal NE release must occur from indirect actions, presumably due to activation of a spinal circuit.

Multiple nerve blocks may be painful and a source of discomfort. We assessed the efficacy of sufentanil 5 microg combined with midazolam 1 mg in decreasing pain in outpatients after a midhumeral multiple nerve stimulation technique. Visual analog scores for pain were significantly lower in those patients who received sedation before the block, both at the time of block performance (14 +/- 1 vs 27 +/- 2 mm, P < 0.0001) and at discharge (11 +/- 1 vs 24 +/- 2 mm, P < 0. 0001). We conclude that the association of sufentanil and midazolam produced minimal sedation while significantly reducing pain experienced by patients undergoing multiple nerve stimulation.

It has not been proven whether one or multiple nerve stimulations and injections provide a higher rate of complete sensory block in both major sciatic nerve sensory distributions below the knee when a popliteal sciatic nerve block is performed using the lateral approach. This prospective, randomized, single-blinded study compared the success rate of the sciatic nerve block using this approach when one or both major components of this nerve (i.e., tibial nerve and common peroneal nerves) are stimulated in 50 patients undergoing foot or ankle surgery. In Group 1 STIM, 24 patients received a single injection of 20 mL of a mixture of 2% lidocaine and 0.5% bupivacaine with 1:200,000 epinephrine after foot inversion had been elicited. In Group 2 STIM (n = 26), 10 mL of the same solution was injected after stimulation of each sciatic nerve component. For patients with complete sensory motor block, there was no difference in onset between groups. However, Group 2 STIM showed a greater success rate compared with the Group 1 STIM (2 STIM: 88% vs 1 STIM :54%; P = 0.007). When two stimulations were used, the onset time of anesthesia in the cutaneous distribution of the common peroneal nerves was shorter than in the tibial nerve (17.5 vs 30 min; P0.0001). We conclude that a two-stimulation technique provides a better success rate than a single-injection technique when a popliteal sciatic nerve block is performed using the lateral approach with 20 mL of local anesthetic.A better success rate is achieved with a double stimulation technique than with a single injection for the sciatic nerve block via the lateral approach at the popliteal fossa when 20 mL of local anesthetics is used.

Stimulating perineural catheters are developed to overcome technical problems of nonstimulating catheters, but their efficacy remains controversial. However, no volume-response study has compared success rates between stimulating and nonstimulating catheters. This study of stimulating versus nonstimulating catheters compares the minimal effective volume required to successfully block the sciatic nerve in 50% of patients scheduled for unilateral hallux valgus repair.Patients underwent unilateral sciatic nerve block in the popliteal fossa with mepivacaine 1.5%, using either a stimulating (STIM group) or a nonstimulating (NONSTIM group) popliteal catheter. The volume of mepivacaine started at 20 mL and was increased or decreased by increments of 2 mL in subsequent patients, depending on the efficacy of the block in the previous patient, using the technique of up-down sequential allocation described by Dixon (Neurosci Biobehav Rev. 1991;15:47-50). Minimum effective volumes of local anesthetic were calculated using the formula of Dixon. Efficacy of block was defined by a complete sensory-motor block in the cutaneous distributions of the sciatic nerve associated with a pain-free surgery.Twenty-four patients were included in each group. Median effective volume blocking the sciatic nerve was significantly lower (P0.05) in the STIM group (2.7 mL; 95% confidence interval, 0.5-4.9 mL) compared with the NONSTIM group (16.6 mL; 95% confidence interval, 15.2-18.0 mL).Stimulating popliteal catheters dramatically decrease the volume required to block the sciatic nerve in 50% of patients, compared with nonstimulating catheters.

Sensory assessment to estimate spread and effectiveness of a peripheral nerve block is difficult because no clinical test is specific for small sensory fibers. Occurrence of a swelling illusion (SI) during a peripheral nerve block corresponds to the impairment of small sensory fibers. The authors investigated the usefulness of SI in predicting successful peripheral nerve block by assessing the temporospatial correlation between progression of sensory impairment in cutaneous distributions anesthetized and localization of SI during peripheral nerve block installation.Interscalene, infracoracoid, or sciatic nerve blocks were performed using a nerve stimulator and 1.5% mepivacaine in 53 patients, with a total of 201 nerves to be anesthetized. Pinprick, cold, warm, touch, and proprioception were assessed every 3 min, while patients were asked to describe their perception of size and shape of their anesthetized limb and localization of these illusions. Data are presented as mean +/- SD and percentage (95% confidence interval).Failure occurred in 12 cutaneous distributions out of a total of 201 theoretically blocked nerves. SI appeared earlier than warmth impairment (4.3 +/- 2.7 vs. 6.2 +/- 2.0 min; P0.05), always corresponding to successfully anesthetized cutaneous distributions, with the exception of 1 patient, who developed SI in 2 cutaneous distributions while sensory testing indicated failure in 1 distribution. SI successfully predicted the blockade of a cutaneous distribution with a sensitivity of 1.00 (0.98-1.00), a specificity of 0.92 (0.65-0.99), and an accuracy of 0.99 (0.97-1.00).Swelling illusion may provide an early assessment of the success of a peripheral nerve block in unsedated patients.

Background The relation between impairment of sensorimotor function and occurrence of phantom limb syndrome (PLS) during regional anesthesia has not been described. This study assessed the temporal relation between PLS and the progression of sensorimotor impairment during placement of a brachial plexus nerve block. Methods Fifty-two patients had their arm randomly placed either alongside their body (group A) or in 90 degrees abduction (group B) immediately after brachial plexus nerve block placement. Responses to pin prick, cold, heat, touch, proprioception, and voluntary movement were assessed every 5 min for 60 min. Meanwhile, patients described their perceptions of the size, shape, and position of their anesthetized limb. Results Phantom limb syndrome occurred 19 +/- 9 min after nerve block placement. Proprioception was impaired and abolished after 22 +/- 9 and 43 +/- 17 min, respectively (P < 0.05 vs. PLS onset). When PLS occurred, responses to pin prick, cold, heat, and proprioception were abolished in 96, 94, 87, and 4% of patients, respectively. Patients were more likely to feel their anesthetized limb in adduction and in abduction in groups A and B (P < 0.05 vs. group A), respectively. After PLS had become motionless, two stereotyped positions were identified: arm adduction, elbow flexion, hand over the abdomen (68% of group A patients) and arm abduction, elbow flexion, hand held close to the homolateral ear (48% of group B patients). Conclusions This study provides a better understanding of the determinants of PLS by showing that the final position of PLS is related both to the abolition of proprioception and the initial position of the anesthetized limb.

Background Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine. However, the role of tonic spinal cholinergic activity and its interaction with alpha2-adrenergic systems in normal and neuropathic conditions and to different sensory methods has not been systematically examined. The authors examined cholinergic receptor involvement in thermal and mechanical sensitivity in normal and neuropathic animals and its interaction with intrathecal clonidine. Methods Normal rats and rats that received L5/L6 spinal nerve ligation were tested with acute radiant heat, paw pressure, and punctate mechanical stimulation before and after the intrathecal administration of saline, the muscarinic receptor antagonist, atropine, or a toxin to destroy cholinergic neurons, and then after intrathecal clonidine. Results Atropine, the cholinergic neuronal toxin, and saline did not alter baseline withdrawal thresholds. In nerve-injured rats, neither saline nor atropine altered antinociception from clonidine to a thermal stimulus, but atropine reduced the effect of clonidine to von Frey filament withdrawal threshold (34 +/- 5.6 vs. 14 +/- 5.8 g [mean +/- SEM], saline vs. atropine; P < 0.05) and to withdrawal threshold to paw pressure after clonidine (174 +/- 18 g vs. 137 +/- 16 g, saline vs. atropine; P < 0.05). Conclusions These data suggest that after nerve injury, mechanical but not thermal antinociception from intrathecal clonidine relies on a muscarinic interaction, because only mechanical antinociception was antagonized by atropine. These results do not favor a regulation of nociceptive transmission by a tonic release of acetylcholine in nerve-injured rats.

UNLABELLED Postoperative pain after laparoscopic surgery is less than after laparotomy, and patients may benefit from an intraperitoneal injection of local anesthetic. Thirty-seven ASA physical status I or II patients received in double-blinded fashion 20 mL of 0.9% saline solution (placebo), ropivacaine 0.25% (Rop 0.25%), or ropivacaine 0.75% (Rop 0.75%) immediately after trocar placement and at the end of surgery. We measured pain and morphine consumption until 20 h after surgery. Plasma ropivacaine concentrations were measured. The three groups were comparable for shoulder pain, parietal pain, and incidence of side effects. Visceral pain at rest, during cough, and on movement and total consumption of morphine were significantly smaller in Groups Rop 0.25% and Rop 0.75% when compared with Placebo. Although no adverse effect occurred in any patient, the largest dose led to large plasma concentrations of ropivacaine (2.93 +/- 2.46 microg/mL and 3.76 +/- 3.01 microg/mL after the first and second injection, respectively). We conclude that intraperitoneal administration of ropivacaine before and after surgery significantly decreases postoperative pain. Because the smaller dosage (2 x 50 mg) provided similar analgesia and was associated with significantly smaller plasma concentrations than the larger dosage (2 x 150 mg), this smaller dosage seems more appropriate. IMPLICATIONS Intraperitoneal ropivacaine 100 mg injected during laparoscopic cholecystectomy significantly decreased postoperative pain when compared with injection of intraperitoneal placebo. At this dose, plasma concentrations remained in the nontoxic range

Background Intrathecal neostigmine induces analgesia but also several side effects. Recently, 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects. The authors' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia. In addition, they wanted to determine the incidence of side effects in patients undergoing hand surgery. Methods Sixty-nine outpatients scheduled for carpal tunnel syndrome repair with axillary plexus block were randomly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously (group 1), 500 microg neostigmine in the axillary plexus and saline solution subcutaneously (group 2), or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously (group 3). Sensory and motor block in the four hand nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation. Side effects were also recorded. Results Neostigmine had no effect on sensory and motor block in any of the four nerve distributions, nor did it increase the median duration of sensory block (215 min; range, 120-330 min) compared with group 1 (247 min; range, 190-287 min) or group 3 (236 min; range, 160-280 min). Motor block was slightly shorter (P = 0.045) in group 3 (190 min; range, 135-285 min) compared with group 1 (218 min; range, 145257 min) and group 2 (215 min; range, 105-343 min). Gastrointestinal side effects occurred in 30% of patients in both neostigmine groups but not in group 1 (P < 0.05). Conclusions This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block, but it does cause a relatively high incidence of side effects. These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block.

We report that in vivo injection of endotoxin (EDTX, 6 mg. kg(-)(1)) induces cardiovascular alterations in rats that closely mimic the clinical situation, as assessed by in vivo hemodynamic measurements in anesthetized and conscious, chronically instrumented animals. The patch-clamp technique was used to characterize the L-type calcium current (I(Ca)) and its autonomic regulation in isolated cardiac myocytes. The density of I(Ca) progressively decreased at 12 and 36 h after EDTX injection. However, the dihydropyridine (+/-)Bay K 8644 (100 nM) enhanced I(Ca) to levels similar to those in control and EDTX-treated myocytes. In addition, the net stimulatory effect of a beta-adrenergic agonist (isoproterenol) on I(Ca) was increased 12 h after EDTX injection. This change in the beta-adrenergic effect declined 24 h later. The potentiation in the beta-adrenergic stimulation of I(Ca) was mimicked by L858051 (10 microM), a direct activator of adenylyl cyclase, but not by IBMX (200 microM), a phosphodiesterase inhibitor. Besides, the antiadrenergic effect of acetylcholine on I(Ca) was unchanged 12 h after EDTX injection, but increased 36 h after EDTX injection. These results support the hypothesis that time-dependent changes in the adenylyl cyclase pathway in cardiac myocytes may contribute, via the autonomic regulation of I(Ca), to the severity of myocardial dysfunction during sepsis.

Norepinephrine release from spinal synaptosomes. (Wake Forest University School of Medicine, Winston-Salem, NC) Anesthesiology 2000;93:164–172. The purpose of this study was to determine if clonidine could inhibit release of NE in a preparation of spinal cord tissue lacking synaptic circuits. Crude synaptosomes were prepared from male Sprague-Dawley rat spinal cord, loaded with [3H]NE, and stimulated by potassium chloride to release [3H]NE. Samples were incubated with clonidine in the absence or presence of various inhibitors. To study the effect of α2A-adrenergic receptor subtypes, some animals were pretreated with an oligodeoxynucleotide (ODN) composed of a sense or antisense sequence to a portion of this receptor. Potassium chloride produced a concentration-dependent increase in [3H]NE release, and this release was inhibited by clonidine with a concentration producing 50% maximal inhibition (IC50) of 1.3 μm. The effect of clonidine was inhibited by the α2A-adrenergic antagonists, yohimbine, and idazoxan, but not by α1A-adrenergic, muscarinic, or opioid antagonists. Intrathecal pretreatment with antisense ODN to α2A-adrenergic receptors reduced α2A-adrenergic receptor protein expression compared with sense ODN control and also reduced clonidine-induced inhibition of [3H]NE release. Conclude that these data demonstrate the existence of classic autoinhibitory α2A-adrenergic receptors in the spinal cord, probably of the α2A subtype. They further suggest that clonidine-induced stimulation of spinal NE release must occur from indirect actions, presumably due to activation of a spinal circuit.