ABSTRACT
BACKGROUND: Intravenous lidocaine is increasingly used in surgical patients. As it has neuromuscular blocking effects, we tested the impact of an intravenous lidocaine infusion on the time course of a rocuronium-induced neuromuscular block. METHODS: Fifty-two adults undergoing surgery were randomly allocated to intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of 2 mg/kg/h or physiological saline (control) throughout surgery. Anaesthesia was induced and maintained with a target-controlled propofol infusion and sufentanil. After loss of consciousness, rocuronium 0.6 mg/kg was given. Neuromuscular transmission was measured using train-of-four (TOF)-watch SX (Organon, Swords Co., Dublin, Ireland) acceleromyography. RESULTS: Onset time (to 95% depression of first twitch) was on average 113.9 s (standard deviation 35.3) with lidocaine and 119.5 s (44.9) with saline (P = 0.618). Total recovery time (TOF ratio 0.9) was on average 58.1 min (15.1) with lidocaine and 54.3 min (16.9) with saline (P = 0.394). Clinical duration (until first twitch has recovered to 25%) was on average 33.3 min (7.2) with lidocaine and 30.6 min (8.1) with saline (P = 0.21). Recovery index (time between 25% and 75% recovery of the first twitch) was on average 11.5 min (5.0) with lidocaine and 10.6 min (4.1) with saline (P = 0.458). Recovery time (between 25% recovery of the first twitch and TOF ratio 0.9) was on average 24.8 min (9.3) with lidocaine and 23.2 min (9.2) with saline (P = 0.541). CONCLUSION: A continuous intravenous infusion of lidocaine has no impact on the time course of the neuromuscular blockade induced by a standard intubation dose of rocuronium.
Subject(s)
Androstanols/pharmacology , Anesthetics, Local/pharmacology , Lidocaine/pharmacology , Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents/pharmacology , Adult , Female , Humans , Injections, Intravenous , Male , Middle Aged , RocuroniumABSTRACT
OBJECTIVE: The primary outcome of this study was to evaluate the effect of adding sufentanil to hyperbaric bupivacaine on duration of sensory blockade of spinal anesthesia in chronic opioid users in comparison with non-addicts. METHODS: Sixty patients scheduled for orthopedic surgery under spinal anesthesia were allocated into four groups: group 1 (no history of opium use who received intrathecal hyperbaric bupivacaine along with 1mL saline as placebo); group 2 (no history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5µg]); group 3 (positive history of opium use who received intrathecal bupivacaine along with 1mL saline as placebo) and group 4 (positive history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5µg]). The onset time and duration of sensory and motor blockade were measured. RESULTS: The duration of sensory blockade in group 3 was 120±23.1min which was significantly less than other groups (G1=148±28.7, G2=144±26.4, G4=139±24.7, p=0.007). The duration of motor blockade in group 3 was 145±30.0min which was significantly less than other groups (G1=164±36.0, G2=174±26.8, G4=174±24.9, p=0.03). CONCLUSIONS: Addition of 5µg intrathecal sufentanil to hyperbaric bupivacaine in chronic opioid users lengthened the sensory and motor duration of blockade to be equivalent to blockade measured in non-addicts.
Subject(s)
Analgesics, Opioid/pharmacology , Anesthesia, Spinal/methods , Bupivacaine/pharmacology , Opium/pharmacology , Substance-Related Disorders/complications , Sufentanil/pharmacology , Adult , Anesthetics, Local/pharmacology , Chronic Disease , Drug Therapy, Combination , Drug Users , Humans , Male , Time FactorsABSTRACT
PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.
Subject(s)
Bupivacaine/analogs & derivatives , Neuromuscular Blockade , Neuromuscular Junction/drug effects , Pancuronium/pharmacology , Synaptic Transmission/drug effects , Anesthetics, Local/pharmacology , Animals , Bupivacaine/pharmacology , Diaphragm/drug effects , Diaphragm/innervation , Drug Therapy, Combination , Electric Stimulation/methods , Levobupivacaine , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Models, Animal , Neuromuscular Junction/physiology , Neuromuscular Nondepolarizing Agents/pharmacology , Rats, Wistar , Synaptic Transmission/physiologyABSTRACT
Long alkyl chain quaternary ammonium ions (QA), the local anesthetics (LA) tetracaine and lidocaine, imipramine, and pancuronium cause inactivation of the alamethicin-induced conductance in lipid bilayer membranes. The alamethicin-induced conductance undergoes inactivation only when these amphipathic compounds are added to the side containing alamethicin. The concentration of QA required to cause a given amount of inactivation depends on the length of the hydrocarbon chain and follows the sequence C9 greater than C10 greater than C12 greater than C16. LA and imipramine, in contrast to QA or pancuronium, are able to promote appreciable inactivation only if the pH of the alamethicin-free side is equal to or lower than the pK of these compounds. The membrane permeability to QA, LA, or imipramine is directly proportional to the alamethicin-induced conductance and is larger than the one for potassium. The observed steady state and time-course of the inactivation are well described by a model similar to that proposed by Heyer et al. (1976. J. Gen. Physiol. 67:703--729) and extended for any value of the diffuse double layer potential and for LA and imipramine. In this model QA, LA, or imipramine are able to permeate through the membrane only when the alamethicin-induced conductance is turned on. The amphipathic compounds then bind to the other membrane surface, changing the transmembrane potential and turning the conductance off. For a given concentration of QA, LA, or imipramine the extent of inactivation depends on two factors: first, the binding characteristics of these compounds to the membrane surface and second, their ability to permeate through the membrane when the alamethicin-induced conductance is turned on. The several possible mechanisms of permeation of the amphipathic molecules tested are discussed.
Subject(s)
Alamethicin/antagonists & inhibitors , Anesthetics, Local/pharmacology , Anti-Bacterial Agents/antagonists & inhibitors , Cell Membrane Permeability/drug effects , Membranes, Artificial , Quaternary Ammonium Compounds/pharmacology , Imipramine/pharmacology , Lidocaine/pharmacology , Membrane Lipids , Membrane Potentials , Pancuronium/pharmacology , Tetracaine/pharmacologyABSTRACT
OBJECTIVE: To investigate in vitro effects of isoeugenol on neuromuscular transmission in tissues obtained from rats. SAMPLE POPULATION: Tissues (phrenic nerve and diaphragm) obtained from 15 male Sprague-Dawley rats. PROCEDURE: Rats were euthanatized, and tissues (phrenic nerves and diaphragm) were obtained. Phrenic nerve-diaphragm preparations were examined in vitro. The phrenic nerve was stimulated with weak electrical impulses. Muscle-twitch responses were recorded before and after the addition of drugs (pancuronium, neostigmine, isoeugenol, and benzocaine). RESULTS: Pancuronium and isoeugenol in low concentrations (10 to 206 microM) caused a distinct decrease in twitch response, which could be reversed by the addition of neostigmine. The decrease in twitch response caused by benzocaine or high concentrations of isoeugenol could not be reversed by the addition of neostigmine. CONCLUSIONS AND CLINICAL RELEVANCE: Isoeugenol caused a competitive blockade of neuromuscular transmission. Neostigmine restored this transmission by inhibiting acetylcholinesterase, which led to increased concentrations of acetylcholine. Because isoeugenol is used as an anesthetic in fish, further investigations are necessary to determine whether fish exposed to isoeugenol are sedated and unconscious or whether they are only paralyzed but have intact perception in afferent sensory nerves.
Subject(s)
Diaphragm/drug effects , Diaphragm/innervation , Eugenol/analogs & derivatives , Eugenol/pharmacology , Neuromuscular Blockade , Phrenic Nerve/drug effects , Anesthetics, Local/pharmacology , Animals , Benzocaine/pharmacology , Drug Therapy, Combination , In Vitro Techniques , Male , Muscle Contraction/drug effects , Neostigmine/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Abstract Objective: The primary outcome of this study was to evaluate the effect of adding sufentanil to hyperbaric bupivacaine on duration of sensory blockade of spinal anesthesia in chronic opioid users in comparison with non-addicts. Methods: Sixty patients scheduled for orthopedic surgery under spinal anesthesia were allocated into four groups: group 1 (no history of opium use who received intrathecal hyperbaric bupivacaine along with 1 mL saline as placebo); group 2 (no history of opium use who received intrathecal bupivacaine along with 1 mL sufentanil [5 µg]); group 3 (positive history of opium use who received intrathecal bupivacaine along with 1 mL saline as placebo) and group 4 (positive history of opium use who received intrathecal bupivacaine along with 1 mL sufentanil [5 µg]). The onset time and duration of sensory and motor blockade were measured. Results: The duration of sensory blockade in group 3 was 120 ± 23.1 min which was significantly less than other groups (G1 = 148 ± 28.7, G2 = 144 ± 26.4, G4 = 139 ± 24.7, p = 0.007). The duration of motor blockade in group 3 was 145 ± 30.0 min which was significantly less than other groups (G1 = 164 ± 36.0, G2 = 174 ± 26.8, G4 = 174 ± 24.9, p = 0.03). Conclusions: Addition of 5 µg intrathecal sufentanil to hyperbaric bupivacaine in chronic opioid users lengthened the sensory and motor duration of blockade to be equivalent to blockade measured in non-addicts.
Resumo Objetivo: Avaliar o efeito da adição de sufentanil à bupivacaína hiperbárica na duração do bloqueio sensorial da raquianestesia em usuários crônicos de opioides em comparação com não adictos. Métodos: Foram distribuídos em quatro grupos 60 pacientes agendados para cirurgia ortopédica sob raquianestesia: Grupo 1 (sem história de uso de ópio, recebeu bupivacaína hiperbárica intratecal juntamente com 1 mL de solução salina como placebo); Grupo 2 (sem história de uso de ópio, recebeu bupivacaína intratecal juntamente com 1 mL de sufentanil [5 µg]); Grupo 3 (com história de uso de ópio, recebeu bupivacaína intratecal juntamente com 1 mL de solução salina como placebo) e Grupo 4 (com história de uso de ópio, recebeu bupivacaína intratecal juntamente com 1 mL de sufentanil [5 µg]). O tempo de início e a duração dos bloqueios sensitivo e motor foram registrados. Resultados: A duração do bloqueio sensorial no Grupo 3 foi de 120 ± 23,1 min, um tempo significativamente menor do que nos outros grupos (G1 = 148 ± 28,7, G2 = 144 ± 26,4, G4 = 139 ± 24,7, p = 0,007). A duração do bloqueio motor no Grupo 3 foi de 145 ± 30,0 min, um tempo significativamente menor do que nos outros grupos (G1 = 164 ± 36.0, G2 = 174 ± 26.8, G4 = 174 ± 24,9; p = 0,03). Conclusões: A adição de 5 µg de sufentanil intratecal à bupivacaína hiperbárica em usuários crônicos de opioides aumenta a duração dos bloqueios sensorial e motor de forma equivalente ao bloqueio avaliado em não adictos.
Subject(s)
Humans , Male , Adult , Opium/pharmacology , Bupivacaine/pharmacology , Sufentanil/pharmacology , Substance-Related Disorders/complications , Analgesics, Opioid/pharmacology , Anesthesia, Spinal/methods , Time Factors , Chronic Disease , Drug Therapy, Combination , Drug Users , Anesthetics, Local/pharmacologyABSTRACT
ABSTRACT PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.
Subject(s)
Animals , Male , Pancuronium/pharmacology , Bupivacaine/analogs & derivatives , Synaptic Transmission/drug effects , Neuromuscular Blockade , Neuromuscular Junction/drug effects , Bupivacaine/pharmacology , Diaphragm/drug effects , Diaphragm/innervation , Rats, Wistar , Neuromuscular Nondepolarizing Agents/pharmacology , Synaptic Transmission/physiology , Models, Animal , Drug Therapy, Combination , Electric Stimulation/methods , Anesthetics, Local/pharmacology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neuromuscular Junction/physiologySubject(s)
Axons/physiology , Ion Channels/physiology , Aconitine/pharmacology , Anesthetics, Local/pharmacology , Animals , Axons/drug effects , Decapodiformes , Ion Channels/drug effects , Membrane Potentials , Neuromuscular Depolarizing Agents/pharmacology , Pancuronium/pharmacology , Strychnine/pharmacology , Synaptic Transmission , Toxins, Biological/pharmacology , Venoms/pharmacologySubject(s)
Nerve Fibers/drug effects , Anesthetics, Local/pharmacology , Animals , Axons/drug effects , Benzocaine/pharmacology , Cell Membrane/drug effects , Ion Channels/drug effects , Membrane Potentials/drug effects , Pancuronium/pharmacology , Quaternary Ammonium Compounds/pharmacology , Saxitoxin/pharmacology , Sodium/metabolism , Strychnine/pharmacology , Terminology as Topic , Tetrodotoxin/pharmacology , Zinc/pharmacologyABSTRACT
The reciprocal activities of the bladder and external urethral sphincter (EUS) are coordinated by descending projections from the pontine micturition center but are subjected to modulation by peripheral afferent inputs. Transection of the somatic pudendal nerve innervating the striated EUS decreases voiding efficiency and increases residual urine in the rat. The reduction in voiding efficiency was attributed to the lack of phasic bursting activity of the EUS following denervation. However, transection of the pudendal nerve also eliminates somatic sensory feedback that may play a role in voiding. We hypothesized that feedback from pudendal afferents is required for efficient voiding and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade revealed that pudendal nerve afferents contributed to efficient voiding. Sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction. These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in regulating bladder function.
Subject(s)
Lumbosacral Plexus/physiology , Neurons, Afferent/physiology , Urethra/innervation , Urinary Bladder/innervation , Urination/physiology , Acetic Acid/pharmacology , Anesthetics, Intravenous , Anesthetics, Local/pharmacology , Animals , Bungarotoxins/pharmacology , Electromyography , Female , Irritants/pharmacology , Lidocaine/pharmacology , Lumbosacral Plexus/cytology , Neuromuscular Nondepolarizing Agents/pharmacology , Neurons, Afferent/drug effects , Pancuronium/pharmacology , Rats , Rats, Sprague-Dawley , Urethane , Urethra/physiology , Urinary Bladder/physiologySubject(s)
Analgesics/pharmacology , Anesthesia, Obstetrical , Fetus/drug effects , Analgesics/administration & dosage , Anesthetics, Local/pharmacology , Barbiturates/pharmacology , Chloral Hydrate/pharmacology , Diazepam/pharmacology , Female , Heroin/pharmacology , Humans , Injections, Intramuscular , Injections, Intravenous , Levallorphan/pharmacology , Maternal-Fetal Exchange , Meperidine/pharmacology , Morphine/pharmacology , Nalorphine/pharmacology , Opium/pharmacology , Pentazocine/pharmacology , Phenoperidine/pharmacology , Phenothiazines/pharmacology , Pregnancy , Scopolamine/pharmacologyABSTRACT
Se comparará la cardiotoxicidad de tres anestésicos locales: dos altamente difundidos, Bupivacaína y Lidocaína, y un nuevo anestésico local por aparecer en el mercado argentino: Ropivacaína. Esta es una aminoamida cuyo perfil anestésico es similar a la Bupivacaína, en su pKa, unión a proteínas, pero con una liposubilidad intermedia entre Bupivacaína y Lidocaína (es 2 a 3 veces menos liposoluble que la Bupivacaína). Para su uso correcto es necesario conocer la influencia de las variables Farmacocinéticas y Farmacodinámicas en el desarrollo de toxicidad.
Subject(s)
Humans , Male , Female , Pregnancy , Infant, Newborn , Adult , Aged , Anesthetics, Local/pharmacokinetics , Anesthetics, Local/pharmacology , Anesthetics, Local/toxicity , Bupivacaine/administration & dosage , Bupivacaine/toxicity , Heart Conduction System/drug effects , Lidocaine/administration & dosage , Lidocaine/toxicity , Clonidine/therapeutic use , Hypotension , Phenylephrine/therapeutic use , Homeopathic Dosage , Risk FactorsABSTRACT
La investigación de nuevos anestésicos locales con un aumento de la liposolubilidad de sus moléculas ha permitido hallar drogas con mayor potencia y duración del efecto. Sin embargo, los mismos cambios moleculares que incrementan la duración de acción y la potencia también pueden aumentar la toxicidad local y sistémica. En el caso de una excesiva dosis utilizada, ya sea por una rápida absorción o por una inyección intravascular inadvertida, durante el procedimiento para el bloqueo se pueden producir efectos sistémicos de importancia. El primer sistema afectado es el nervioso central, donde produce una excitación, llegando luego a deprimir el sistema cardiovascular. Los estudios comparativos para numerosas indicaciones no han podido demostrar fehacientemente diferencias en cuanto a la toxicidad de la levobupivacaína, la ropivacaína y la bupivacaína.