Prolonged Block Research Articles

Selective activation of carotid nerve fibers by acetylcholine applied to the cat petrosal ganglion in vitro

The petrosal ganglion innervates carotid body chemoreceptors through the carotid (sinus) nerve. These primary sensory neurons are activated by transmitters released from receptor (glomus) cells, acetylcholine (ACh) having been proposed as one of the transmitters involved in this process. Since the perikarya of primary sensory neurons share several properties with peripheral sensory endings, we studied the electrical responses of the carotid nerve and glossopharyngeal branch to ACh locally applied to the cat petrosal ganglion superfused in vitro. Ganglionar applications of AChCl (1 μg−1 mg) generated bursts of action potentials conducted along the carotid nerve, while only a few spikes were exceptionally recorded from the glossopharyngeal branch in response to the largest doses. Carotid nerve responses to ACh were dose-dependent, the higher doses inducing transient desensitization. Application of nicotine to the petrosal ganglion also evoked dose-dependent excitatory responses in the carotid nerve. Responses to ACh were reversibly antagonized by adding hexamethonium to the superfusate, more intense and prolonged block of ACh responses being produced by mecamylamine. Ganglionar applications of γ-amino butyric acid and serotonin, in doses of up to 5 mg, did not induce firing of action potentials in any of the branches of the glossopharyngeal nerve. Our results indicate that petrosal ganglion neurons projecting through the carotid nerve are selectively activated by ACh acting on nicotinic ACh receptors located in the somata of these neurons. Thus, cholinosensitivity would be shared by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception.

R-156. Treatment of infertile patients with recurrent endometriomas by assisted invasive reproduction after prolonged ovarian block

R-156. Treatment of infertile patients with recurrent endometriomas by assisted invasive reproduction after prolonged ovarian block

Vecuronium Infusion Requirements in Paediatric Patients in Intensive Care Units

Neuromuscular blocking drugs in intensive care units (ICU) may cause complications, including prolonged neuromuscular block as a result of overdosage and post-ventilation muscle weakness. These may be increased by using inappropriately high infusion rates for infants, in whom published studies are scarce, and by failure to monitor neuromuscular block. There is little ICU experience of acceleromyography, which may permit more reliable monitoring. To determine appropriate vecuronium infusion rates, 12 neonates/infants (median age 4 (interquartile range (IQR) 2-5) months) and 18 children (median age 3.07 (2-10 yr) were studied. The vecuronium infusion rate was adjusted to maintain train-of-four (TOF) at 1 response using the TOF guard accelerometer. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 0.7. Neonates and infants required 45% less vecuronium (mean infusion rate 54.7 (SEM 4.23) micrograms kg-1 h-1) than older children (98.7 (7.07) micrograms kg-1 h-1) and had faster recovery to 70% T4/T1 (45 (IQR 20-51) min vs 65 (55-103) min), with no evidence of prolonged weakness. Routine monitoring of neuromuscular block in ICU is essential; acceleromyography is convenient and reliable.

Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres.

Previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here. Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres. Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively. Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.

Genetics and anaesthesia

Genetic diseases are of considerable interest to the anaesthesiologist, particularly those that provoke abnormal responses to medication. Three of the most important disorders: malignant hyperthermia, porphyria and cholinesterase deficiency are reviewed here. Malignant hyperthermia is a hereditary syndrome that affects skeletal muscle. Its presence is indicated by an episode of muscle hypermetabolism after exposure to certain drugs. Generally transmitted as an autosomal dominant trait with variable penetrance, on occasion it appears to be recessive or even multigenic. An acute episode is characterized by hypercapnia, tachycardia, hyperthermia, muscle contracture and tachypnoea. The most reliable diagnostic test is that of contracture. The specific therapy is dantrolene. Different types of acute porphyria share common features; they are transmitted by autosomal dominant inheritance with variable penetrance. The factors that might trigger an attack of porphyria are hormonal changes, dehydration, stress and infection; however, enzyme-inducing drugs are the principal triggering factors. In most cases of porphyria, the patient can be anaesthetized with relative safety since measures can be taken to identify susceptible individuals and potentially porphyrinogenic agents. In the presence of inhibited, diminished or genetically atypical plasma cholinesterase levels, prolonged block can be produced. The presence of an individual with absent or near zero cholinesterase activity in an apparently normal family would alert us to the existence of abnormal genes. Genetic studies are necessary to identify possible atypical variants and thus prevent adverse reactions.

Complications of muscle relaxants

T HIS ARTICLE reviews the complications of muscle relaxants in clinical practice. Their introduction more than 50 years ago revolutionized the practice of anesthesia but was also associated with a new set of anesthetic-induced complications. Much of the development of new compounds has been with the aim of avoiding or reducing these effects, some of which contributed to postoperative morbidity and mortality. This review emphasizes the complications that have attracted recent attention, and is restricted to those agents in current use and to the recently introduced compounds, doxacurium, mivacurium, pipecuronium, and rocuronium. It should be considered an update of the article published in this journal 10 years ago. ~ Complications of muscle relaxants can be unwanted effects of the normal action of the drugs at the neuromuscular junction, actions at other sites, abnormal or idiosyncratic responses, or result from their use in unusual situations. Some of the complications are common to all relaxants (general complications), eg, slow recovery from block or residual blockade, anaphylaxis, etc, others are restricted to a few or single drugs (specific complications), eg, prolonged block after succinylcholine or mivacurium from a decrease in plasma cholinesterase activity. This review has less emphasis on succinylcholine, in part because most of its specific complications are well recognized but also because it is now used much less frequently than the estimate 10 years ago of its use in 75% of all anesthetics.

Effect of NMDA and non-NMDA receptor antagonists on pulsatile luteinizing hormone secretion in the adult male rat.

To determine the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH in the adult male rat, specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors [2-amino-5-phosphono-pentanoic acid (AP-5, 10 micrograms)] and quisqualate/kainate (non-NMDA) receptors [6,7-dinitroquinoxaline-2,3-dione (DNQX; 30 nM)] were administered through intracerebroventricular injection to orchiectomized adult rats. Blood samples were collected from indwelling jugular catheters at 10-min intervals for plasma LH and FSH determinations. The results revealed that administration of a single central injection of AP-5 significantly suppressed LH and FSH mean levels, trough levels and pulse amplitude but not pulse frequency. The non-NMDA receptor antagonist DNQX had no effect on any parameter of LH or FSH secretion after a single central injection. In a second set of experiments, three central injections of the EAA antagonists at 0, 20 and 40 min were utilized in order to give a more prolonged block of the EAA receptors and the effect on pulsatile LH secretion was determined. Regardless of the three injections, AP-5 still did not significantly alter LH pulse frequency. However, the prolonged treatment with DNQX now significantly suppressed mean and trough LH levels as well as LH pulse amplitude with no effect observed on LH pulse frequency. Taken as a whole, the present studies suggest that EAAs are involved in enhancing gonadotropin pulsatility in the male rat and that the effect is exerted primarily on pulse amplitude rather than pulse frequency.

Adverse Effects of Nondepolarising Neuromuscular Blocking Agents

Nondepolarising muscle relaxants block neuromuscular transmission, acting as antagonists of the nicotinic receptors at the neuromuscular junction. Their undesired effects are frequently caused by interaction with acetylcholine receptors outside this junction, and autonomic cardiovascular effects may result. Other adverse effects include anaphylactic or anaphylactoid reactions, and histamine release. Various disease states may present specific considerations in the use of nondepolarising muscle relaxants. Although many complications of these drugs (such as prolonged block or resistance) are easily treated, others may necessitate immediate intervention and vigorous therapy. Careful selection of an appropriate relaxant for a particular patient will usually prevent the occurrence of complications.

Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan

The behavioral effects of 5-methoxy-6-methyl-2-aminoindan (MMAI) were examined using the drug discrimination procedure and direct observation for classification of the characteristic syndrome induced by MMAI. The stimulus effects of MMAI were studied in 5 different groups of rats trained to discriminate MMAI (1.71 mg/kg; 8 μM/kg), MDMA (3,4-methylenedioxymethamphetamine; 1.75 mg/kg; 7.6 μM/kg), (+)-MBDB ((+)- N-methylamino-(1,3-benzodioxo-5-yl)-2-butanamine; 1.75 mg/kg; 7.18 μM/kg), (+)-amphetamine (1 mg/kg; 5.4 μM/kg), or LSD ((+)-lysergic acid diethylamide tartrate; 0.08 mg/kg; 186 nM/kg) from saline. In substitution tests in rats trained to discriminate MMAI from saline, all the compounds which fully mimicked MMAI were serotonin (5-hydroxytryptamine, 5-HT) releasing agents. This substitution is symmetrical for MDMA and (+)-MBDB. Nevertheless, the dose-response curve of MMAI is parallel to those of (+)-fenfluramine ( m-trifluoromethyl- N-ethylamphetamine) and p-chloroamphetamine. The results also show that MMAI lacks amphetamine-like and LSD-like discriminative stimulus effects, suggesting that MMAI is neither a psychostimulant nor a hallucinogen. Tests of the discriminability of MMAI after 5-HT depletion with the selective serotonin synthesis inhibitor p-chlorophenylalanine (2×200 mg/kg i.p., pretreatment 72 h before test), showed only saline appropriate responding. Prolonged block (ca. 1 week) of the MMAI cue by p-chlorophenylalanine further supports the conclusion that endogenous 5-HT is essential for MMAI discrimination. Fluoxetine (10 mg/kg) or paroxetine (2.5 mg/kg), both selective 5-HT uptake inhibitors, reduced the discriminability of MMAI to 40% and 50%, respectively. None of the antagonists (ketanserin, methiothepin, pindolol, yohimbine, haloperidol) used in antagonism tests inhibited the stimulus properties of MMAI. These results and data from radioligand binding studies support the conclusion that direct activation or inhibition of known neurotransmitter receptors did not play a significant role in the discriminative cue of MMAI. The administration of 5, 10, or 20 mg/kg of MMAI to rats induced a behavioral syndrome consisting of hypolocomotion with accompanying catalepsy-like posture, turning, Straub tail, flat body posture, and suppressed sleeping time. In general, this is qualitatively similar to what is seen after administration of 5-HT precursors or 5-HT receptor agonists. In conclusion, the data from the drug discrimination study and the behavioral syndrome induced by MMAI suggest that MMAI is a potential selective releaser of serotonin.

Adverse Effects of Depolarising Neuromuscular Blocking Agents

Muscle relaxants block neuromuscular transmission, acting at nicotinic acetylcholine receptors of the neuromuscular junction. Suxamethonium (succinylcholine) is a depolarising agent, whereas all other relaxants in clinical use are nondepolarising. The desired neuromuscular block results from the structural similarity of muscle relaxants to acetylcholine, enabling the interaction with receptors at the neuromuscular junction. Adverse effects of suxamethonium are generally related to its agonist mode of action. Autonomic cardiovascular effects may result. Other adverse effects include anaphylactic or anaphylactoid reactions, and histamine release. Various disease states may present specific considerations in the use of muscle relaxants. Although many complications of muscle relaxants (such as prolonged block or resistance) are easily treated, others may require immediate intervention and vigorous therapy. Careful selection of appropriate relaxants for particular patients will usually prevent the occurrence of complications.

The use of rocuronium (ORG 9426) in patients with chronic renal failure

The pharmacodynamics of an initial dose of 0.6 mg.kg-1 rocuronium followed by three maintenance doses of 0.15 mg.kg-1 were studied during nitrous oxide/oxygen/isoflurane anaesthesia in patients with normal renal function (n = 12) and chronic renal failure (n = 12). The mean (SD) duration (min) of block after the initial dose was 28.0 (5.5) and 25.6 (11.7) respectively. The mean (SD) duration (min) of the effect of the three maintenance doses was 15.3 (4.0) and 14.2 (7.0); 17.3 (3.2) and 17.4 (8.7); 18.1 (2.8) and 19.1 (10.1) for the normal and renal failure patients respectively. The induced and spontaneous recovery indices were 3.7 (0.7) and 17.1 (6.9) in the normal group compared with 3.9 (0.5) and 19.0 (12.5) in the renal failure group and these values did not differ between the two groups. In this small study rocuronium appears to be suitable for patients with chronic renal failure. There is no evidence of prolonged block even when the drug is given in repeated doses for maintenance.

Taxol as a Radiation Sensitizer: A Flow Cytometric Study

Taxol is an exciting antineoplastic agent with a novel mechanism of action. Taxol has been shown to prolong the G2/M phase of the cell cycle. This cell cycle perturbation has been the explanation given for the radiation-sensitizing effects seen with taxol in vitro. The aim of this study is to evaluate the cell kinetics of the BG-1 human ovarian cancer cell line after treatment with nontoxic doses of taxol and radiation (RT). This cell line was treated in the proliferative state for 90 min with 5 n M taxol and then irradiated 48 hr later with 2 Gy of Cobalt60. Flow cytometric evaluations of cell cycle perturbations were performed at 24-hr intervals from 0 through 216 hr. ATP cell viability assay was performed in parallel to obtain survival data. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. At this nontoxic dose of taxol no cell cycle perturbations as compared to control were seen. Radiation sensitization was still found. Sensitizer enhancement ratio was 2.3 at 10% survival. The RT-related G2/M block peaked at 24 h after RT and then resolved. The combination of taxol and radiation resulted in a large prolonged block in G2/M that did not resolve through the duration of the experiment. In summary, taxol sensitized cells to radiation at a dose that was not cytotoxic and that did not cause cell cycle perturbations.

Prolonged Neuromuscular Block Following Mivacurium

Prolonged Neuromuscular Block Following Mivacurium

Physiology and pharmacology of neuromuscular transmission, with special reference to the possible consequences of prolonged blockade.

There is a deliberate element of flight of fancy in the foregoing discussion, which is intended to illustrate that prolonged and continuous use of neuromuscular blocking drugs may produce pre- or postjunctional changes, or both that would not be predicted from a knowledge of their acute pharmacology. Such effects could result in a gradual development of either decreased or increased effectiveness, depending upon the nature of the long term changes. In addition, accumulating metabolites of the parent drug, especially in those critically ill patients who undergo intensive care, might give rise to untoward effects. Indeed, Segredo et al. [30] attribute prolonged block by vecuronium in intensive care patients, not to vecuronium itself, but to its first metabolite, the 3-desacetyl derivative, which accumulates because of renal failure. This is obviously an important contributing factor, although there is no reason to suppose that it is the only mechanism involved in all cases. In the past, neuromuscular-blocking drugs have not been tested during preclinical development for their potential long term use in intensive care. Consequently, if and when it is necessary to use them clinically in this way, eachoccasion should be regarded as a new experiment, to be accompanied by careful monitoring of their effects. In this way, any changes in sensitivity to the drugs in either direction, or other unusual effect, can be detected as early as possible and appropriate adjustments made. In the meantime, new drugs should be designed and developed in the laboratory, with intensive care especially in mind.

Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro.

1. The effects of bradykinin on nociceptors have been characterized on a preparation of the neonatal rat spinal cord with functionally connected tail maintained in vitro. Administration of bradykinin to the tail activated capsaicin-sensitive peripheral fibres and evoked a concentration-dependent (EC50 = 130 nM) depolarization recorded from a spinal ventral root (L3-L5). 2. The response to bradykinin was unaffected by the peptidase inhibitors, bestatin (0.4 mM), thiorphan (1 microM), phosphoramidon (1 microM) and MERGETPA (10 microM) or by the presence of calcium blocking agents, cadmium (200 microM) and nifedipine (10 microM). 3. Inhibition of cyclo-oxygenase with indomethacin (1-5 microM), aspirin (1-10 microM) and paracetamol (10-50 microM) consistently attenuated responses to bradykinin. 4. The effect of bradykinin was mimicked by the phorbol ester PDBu, an activator of protein kinase C. The response to bradykinin was attenuated following desensitization to PDBu but desensitization to bradykinin did not induce a cross-desensitization to PDBu. The protein kinase C inhibitor staurosporine (10-500 nM) consistently attenuated the effects of PDBu and bradykinin. 5. Bradykinin responses were reversibly enhanced by dibutyryl cyclic AMP (100 microM). However dibutyryl cyclic GMP (0.5 mM) and nitroprusside (10 microM) produced prolonged block of responsiveness to bradykinin. Prolonged superfusion with pertussis toxin did not affect responses to bradykinin. 6. The B1-receptor agonist des Arg9-bradykinin (10-100 microM) was ineffective alone or after prolonged exposure of the tail to lipopolysaccharide (100 ng ml-1) or epidermal growth factor (100 ng ml-1) to induce B1 receptors. The BI-receptor antagonist, des Arg9 Leu8-bradykinin (10 JM) did not attenuate the response to bradykinin. A number of bradykinin B2 antagonists selectively and reversibly attenuated the response to bradykinin. The rank order potency was Hoe 140> LysLys [Hyp3,Thi5 8,D-Phe7]-bradykinin> D-Arg[Hyp3, Thi5'8, D-Phe7]-bradykinin = D-Arg[Hyp2,Thi5'8, D-Phe7]-bradykinin.7. These data show that bradykinin produces concentration-dependent activation of peripheral nociceptors in the neonatal rat tail. The responses were unaffected by calcium channel block and were partially dependent on the production of prostanoids. Bradykinin-evoked responses were consistent with the activation of protein kinase C-dependent mechanisms. Cyclic GMP-dependent mechanisms may be involved in bradykinin-receptor desensitization whereas cyclic-AMP dependent mechanisms increase fibre excitability and facilitate bradykinin-induced responses. The effects of bradykinin were mediated by a B2 receptor.

The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine

Twenty-four patients receiving epidural anaesthesia were studied to test the hypothesis that 1:200,000 adrenaline administered into the epidural space 5 minutes before 20 ml bupivacaine 0.5% would improve nerve block and delay systemic absorption of the local anaesthetic. Group A/B received 20 ml adrenaline 1:200,000 5 minutes before 20 ml bupivacaine 0.5%, group S/BA 20 ml saline followed by 20 ml bupivacaine 0.5% with 100 micrograms adrenaline, and group S/B saline 20 ml followed by 20 ml plain bupivacaine 0.5%. Mean maximum plasma concentrations of bupivacaine tended to be lower in the adrenaline groups. A delay in the time to peak plasma concentration of bupivacaine was noted in the A/B group; this indicated that priming with adrenaline may be effective at delaying early systemic uptake of the local anaesthetic. In both adrenaline groups a more prolonged epidural block and increased efficacy were noted, although this was only significant for the duration of block at T6 (p = 0.023) and duration of motor block at Bromage level 1 (p = 0.016) in group A/B. There seems little clinical advantage in administering adrenaline 5 minutes before bupivacaine.

Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene

The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.

Effects of 4-nitroquinoline-1-oxide on population growth, cell-cycle compartmentalization and viability in human lymphoblastoid cells

The mechanism by which the carcinogen 4-nitroquinoline-1-oxide (4-NQO) kills mammalian cells is unclear; however, damage to DNA is presumed to be involved. We examined the relationship between the kinetics of cell death and alteration of cell-cycle compartmentalization after exposure of T5-1 human lymphoblastoid cells to 4-NQO (50 to 500 ng/ml) to establish whether cytotoxicity was related to the perturbation of DNA replication. Dose-dependent reductions in cell proliferation and cell viability were present from 1 day after treatment. Maximal reductions in viability were observed 2 days after exposure. Concentrations of 4-NQO of up to 175 ng/ml did not affect cell-cycle compartmentalization, but 250 ng 4-NQO/ml caused a transient accumulation of cells in S phase after 1 day. Only after 500 ng 4-NQO/ml was a marked and prolonged S-phase block observed from 1 day onwards. The lack of a strong correlation between S-phase block and cell death after exposure to 4-NQO suggests that responses to DNA damage in addition to perturbation of DNA replication entrain 4-NQO-induced cell lethality.

Capsaicin causes prolonged inhibition of voltage-activated calcium currents in adult rat dorsal root ganglion neurons in culture

The effect of capsaicin on voltage-activated calcium currents was investigated in voltageclamped somata of cultured adult rat dorsal root ganglion neurons. About half the neurons studied were sensitive to capsaicin, which induced an inward current at negative membrane potentials accompanied by an increase in membrane conductance. In the sensitive neurons capsaicin inhibited voltage-activated calcium current to an extent that depended on the size and duration of the capsaicin-induced inward current. Calcium channels were protected from the long-lasting inhibitory action of capsaicin by substituting extracellular Ca with Mg or Ba when capsaicin was applied, which suggests that the inhibition was dependent on the presence of extracellular Ca. Substituting Ca with Co did not prevent the prolonged block of calcium channels. It is concluded that the inhibition of voltage-activated calcium currents by capsaicin is secondary to increased intracellular Ca levels due to calcium entry through capsaicin-activated cation-specific ion channels in the plasma membrane. Long-lasting inhibition of voltage-activated calcium channels may contribute to the mechanism of the analgesic and anti-inflammatory effects of capsaicin through inhibition of neurotransmitter release from central and peripheral terminals of primary afferent nociceptive neurons.

Unilateral spinal anaesthesia and prolonged femoral nerve block

Unilateral spinal anaesthesia and prolonged femoral nerve block