喉上神经阻滞联合利多卡因雾化吸入在支气管镜诊疗中的应用

摘要 目的：比较喉上神经阻滞联合利多卡因雾化吸入法与利多卡因含漱法用于支气管镜诊疗的治疗效果及安全性。方法：选取新疆医科大学第三临床医学院首次行气管镜诊疗的患者120例，随机分为4组。利多卡因含漱组：2%盐酸利多卡因注射液喉部含漱；利多卡因雾化吸入组：2%利多卡因注射液雾化吸入；喉上神经阻滞组：B超定位下以1%利多卡因阻滞双侧喉上神经内支。联合组：联合使用喉上神经内支阻滞与利多卡因雾化吸入。记录各组在诊疗中咳嗽、憋喘、体动次数及操作期间患者血压、心率、血氧饱和度等情况，以及诊疗后疼痛视觉模拟评分（VAS评分）。结果：利多卡因含漱组呛咳、憋喘发生率最高，显著高于其余各组（P＜0.01）；联合组呛咳、憋喘发生率最低，显著低于其余各组（P＜0.05）。利多卡因含漱组患者血压、心率在支气管镜进入声门时及气管内诊疗时显著高于各组（P＜0.01）；联合组患者的平均动脉压及心率在支气管镜进入声门时低于（P＜0.05）其余两组。各组SpO₂均高于90%，其中利多卡因含漱组患者最低（P＜0.01），联合组最高（P＜0.05）。各组疼痛VAS评分多低于3分，但在各组之间均有差异（P＜0.05），其中联合组最低（P＜0.05）。结论：喉上神经内支阻滞联合利多卡因雾化吸入用于支气管镜诊疗可以有效地抑制气管应激反应，减少疼痛刺激，有利于维持诊疗期间的血流动力学稳定，其安全性和有效性优于利多卡因含漱法及单独采用利多卡因雾化吸入或喉上神经阻滞法。支气管镜诊疗过程中患者多为轻度疼痛，咽喉部不适引起的呛咳、憋喘才是患者难以耐受的原因。     

Local anaesthetic block protects against electrically-induced damage in peripheral nerve

This study is one of a series addressing the mechanisms involved in the production of neural damage caused by continuous, prolonged electrical stimulation of peripheral nerve. It has been previously shown that sustained, high frequency electrical stimulation of the cat's peroneal nerve may cause irreversible neural damage in the form of axonal degeneration of the large myelinated fibres. In this study we demonstrate that blocking the action potentials on most of the nerve fibres with local anaesthetics (10% procaine or 2% lidocaine) almost completely prevents the axonal degeneration. The abolition of axonal injury by local anaesthetic block strongly suggests that the electrically-induced damage is due to prolonged electrical excitation of axons. Furthermore, since less than complete suppression of the induced neural activity by local anaesthetic engenders essentially complete sparing of all axons, our results suggest that the damage to individual axons derives, at least in part, from stimulation-induced global changes in the nerve.     

Cardiac sodium channels (hH1) are intrinsically more sensitive to block by lidocaine than are skeletal muscle (mu 1) channels

When lidocaine is given systemically, cardiac Na channels are blocked preferentially over those in skeletal muscle and nerve. This apparent increased affinity is commonly assumed to arise solely from the fact that cardiac Na channels spend a large fraction of their time in the inactivated state, which exhibits a high affinity for local anesthetics. The oocyte expression system was used to compare systematically the sensitivities of skeletal (mu 1-beta 1) and cardiac (hH1-beta 1) Na channels to block by lidocaine, under conditions in which the only difference was the choice of alpha subunit. To check for differences in tonic block, Na currents were elicited after 3 min of exposure to various lidocaine concentrations at -100 mV, a potential at which both hH1-beta 1 and mu 1-beta 1 channels were fully reprimed. Surprisingly, hH1-beta 1 Na channels were threefold more sensitive to rested-state block by lidocaine (402 +/- 36 microM, n = 4-22) than were mu 1-beta 1 Na channels (1,168 +/- 34 microM, n = 7-19). In contrast, the inactivated state binding affinities determined at partially depolarized holding potentials (h infinity approximately 0.2) were similar (Kd = 16 +/- 1 microM, n = 3-9 for hH1-beta 1 and 12 +/- 2 microM, n = 4-11 for mu 1-beta 1). Lidocaine produced more use- dependent block of peak hH1-beta 1 Na current elicited by trains of short-(10 ms) or long- (1 s) duration step depolarizations (0.5 Hz, -20 mV) than of mu 1-beta 1 Na current. During exposure to lidocaine, hH1- beta 1 channels recover from inactivation at -100 mV after a prolonged delay (20 ms), while mu 1-beta 1 channels begin repriming immediately. The overall time course of recovery from inactivation in the presence of lidocaine is much slower in hH1-beta 1 than in mu 1-beta 1 channels. These unexpected findings suggest that structural differences in the alpha subunits impart intrinsically different lidocaine sensitivities to the two isoforms. The differences in steady state affinities and in repriming kinetics are both in the correct direction to help explain the increased potency of cardiac Na channel block by local anesthetics.     

L’ischémie du gland: une complication de la circoncision sous bloc pénien

Dorsal penile nerve block is a common procedure and can provide effective analgesia after penile surgery. Ischaemic complications are rare and generally result from trauma or inadvertent administration of vasoconstrictor solutions. We describe a case of glans penis ischaemia in a 15-year-old male after dorsal penile nerve block with lidocaine 2% and bupivacaine 5% for circumcision. The event occurred nearly 12 hours after the procedure. This was successfully treated with intravenous infusion of lloprost (a PGI2 analogue) and oral administration of pentoxifylline. The appearance returned to normal after 72 hours. This rare complication associated with circumcision and dorsal penile nerve block is reviewed and discussed.     

Rhythm transformation in nerve fibers by local anesthetics: From biophysics of sodium channels to physiology of anesthesia

The review considers the basic stages in the study of rhythm transformation in the nerve fibers by local anesthetics and underlying use-dependent block of sodium channels. A potency of use-dependent local anesthetics to produce the rhythm transformation in nociceptive nerve fibers sufficient to attain local anesthesia without complete block of conduction was examined. A hypothesis was tested on attaining the conditions of local anesthesia by a decrease in discharge frequency of C-fiber nociceptors below the critical level separating the firing frequency in these sensors corresponding to their excitation with subnociceptive and nociceptive chemical stimuli. This critical level (about 2 Hz) was determined by comparison of the discharges in feline cutaneous C-fiber nociceptors during injection of chemical nociceptive and non-nociceptive stimuli. The discharge frequency in C-fiber nociceptors can be decreased in a use-dependent manner below the critical level by subcutaneous injection of lidocaine or N-propyl-ajmaline. The importance of use-dependent local anesthesia for preservation of trophic influences of the nervous system in the damaged tissue is discussed.     

Calcium reverses lidocaine-induced conduction block in rat fimbria in vitro

1. We have tested the effect of changed concentrations of Ca2+ upon lidocaine-induced conduction block in rat fimbria. 2. With bath [Ca2+] of 0.25 mM, 0.5 mM lidocaine reduced the amplitude of the compound action potential to 20.2% +/- 2.25% of baseline (n = 5). 3. On changing the bath [Ca2+] to 4.4 mM, with no change in lidocaine concentration, the compound action potential increased by 33.5 +/- 6.5%. 4. In the absence of lidocaine, changing bath [Ca2+] had opposite effects. These results replicate findings by others in peripheral nerve.     

Pharmacokinetic nature of tachyphylaxis to lidocaine: Peripheral nerve blocks and infiltration anesthesia in rats

Tachyphylaxis to peripheral neural blockade was determined with repeated injections of a constant dose of lidocaine in three experimental models: sciatic nerve block, produced by intraneural or extraneural injections, and infiltration anesthesia. A decrease in the duration of the subsequent blocks was used as the index of tachyphylaxis development The anesthetic content in the nerve or skin was determined using radiolabeled lidocaine. Repeated injections of a constant dose of lidocaine resulted in a marked decrease in the duration of the blocks. Accelerated decline in lidocaine content of nerve or skin was observed with repeated blocks. Our data show that tachyphylaxis rapidly develops with both sciatic nerve blocks and infiltration anesthesia. The data also suggest that the mechanism is largely pharmacokinetic in nature.     

Simultaneous determination of local anesthetics including ester-type anesthetics in human plasma and urine by gas chromatography–mass spectrometry with solid-phase extraction

The present study describes the simultaneous determination of seven different kinds of local anesthetics and one metabolite by GC–MS with solid-state extraction: Mepivacaine, propitocaine, lidocaine, procaine (an ester-type local anesthetics), cocaine, tetracaine (an ester-type local anesthetics), dibucaine (Dib) and monoethylglycinexylidide (a metabolite of lidocaine) were clearly separated from each other and simultaneously determined by GC–MS using a DB-1 open tubular column. Their recoveries ranged from 73–95% at the target concentrations of 1.00, 10.0 and 100 μg/ml in plasma, urine and water. Coefficients of variation of the recoveries ranged from 2.3–13.1% at these concentrations. The quantitation limits of the method were approximately 100 ng/ml for monoethylglycinexylidide, propitocaine, procaine, cocaine, tetracaine and dibucaine, and 50 ng/ml for lidocaine and mepivacaine. This method was applied to specimens of patients who had been treated with drip infusion of lidocaine, and revealed that simultaneous determination of lidocaine and monoethylglycinexylidide in the blood and urine was possible.     

Plasma concentrations of monoethylglycinexylidide during and after breast augmentation

MEGX (monoethylglycinexylidide) is the main metabolite of lidocaine and is 83 percent as potent as an antiarrhythmic drug and with the same toxicity as lidocaine. In this study, plasma levels of MEGX were measured in 10 other wise healthy women during and after breast augmentation. A total dose of 825 to 1,280 mg of lidocaine of 0.2% and 0.5% lidocaine with epinephrine corresponding to 16.3 to 21.8 mg/kg (mean, 18.2 mg/kg) was injected in the spatium between the pectoralis muscle and the mammary gland. The peak plasma concentrations of MEGX varied between 0.40 and 0.99 microg/ml (mean, 0.49 microg/ml) and occurred between 8 and 12 hours (mean, 9.1 hours), postoperatively. In three patients, the concentration of MEGX was still increasing after 12 hours. In comparison, the peak plasma concentrations of lidocaine varied between 0.96 and 3.12 microg/ml (mean, 1.49 microg/ml) and occurred between 4 and 12 hours (mean, 7.3 hours) after the end of the injection. The peak lidocaine + MEGX concentrations varied between 1.45 and 3.58 microg/ml (mean, 2.02 microg/ml) and occurred between 5 and 12 hours (mean, 8.5 hours), postoperatively. These data suggest that MEGX might contribute to lidocaine toxicity when high doses of lidocaine are injected. The substantial interindividual variation strongly indicates that recommendations about maximum safe doses of lidocaine should be made with caution.     

Effect of lidocaine and epinephrine on Staphylococcus aureus in a guinea pig model of surgical wound infection

Postoperative wound infection, most often with, is of ubiquitous concern in surgical practice, occurring in an average of 1.5 to 5 percent of all procedures. The antimicrobial properties of local anesthetics have been documented over the past 25 years by in vitro studies. This study evaluates the effects of lidocaine preparations on in an in vivo setting. In a wound infection model using live albino guinea pigs, inoculum was introduced for the reproducible bacterial colonization of clean surgical wounds. One of two sites on the dorsum of each animal was infiltrated with a commercial lidocaine preparation (with and without epinephrine) prior to inoculation with (10 cfu/ml). The other site, inoculated with without preinfiltration with lidocaine, served as the control. Cultures from the sites treated with lidocaine were then compared with cultures from the control sites. All control sites had a consistent presence >or=10 cfu/ml, the threshold for bacterial inhibition of wound healing. Infiltration of the wound with 2 ml of 2% lidocaine prior to inoculation was associated with an average decrease in bacterial count of >70 percent ( n= 19). On the other hand, the addition of epinephrine (1:100,000) to lidocaine was associated with a 20-fold in bacterial counts compared with control values ( n= 10). This is the first study to demonstrate inhibition of by a local anesthetic agent in an in vivo model of a surgical wound. This information suggests a possible role for local anesthetics in prophylaxis against surgical wound infection.     

Multiple open channel states revealed by lidocaine and QX-314 on rat brain voltage-dependent sodium channels

We have recently reported that brain sodium channels display periods with high (low-Kd) and low (high-Kd) levels of lidocaine-induced open channel block (Salazar, B.C., D.O. Flash, J.L. Walewski, and E. Recio- Pinto. 1995. Brain Res. 699:305-314). In the present study, we further characterize this phenomenon by studying the effects of the permanently charged lidocaine analogue, QX-314. We found that the detection of high- and low-Kd periods does not require the presence of the uncharged form of lidocaine. The level of block, for either period, at various QX-314 concentrations indicated the presence of a single local anesthetic binding site. Increasing the concentration of QX-314 decreased the lifetime of the high-Kd periods while it increased the lifetime of the low-Kd periods. These results could be best fitted to a model with two open channel conformations that display different local anesthetic Kd values (low and high Kd), and in which the channel area defining the local anesthetic Kd consists of multiple interacting regions. Amplitude distribution analysis showed that changes in the Kd values reflected changes in the kon rates, without changes in the koff rates. Both lidocaine and QX-314 were found to be incapable of blocking small- channel subconductance states (5-6 pS). Changes in the local anesthetic kon rates for blocking the fully open state and the lack of local anesthetic block of the small subconductance state are consistent with the presence of channel conformational changes involving the intracellular permeation pathway leading to the local anesthetic binding site.     

Plasma concentrations of lidocaine and alpha1-acid glycoprotein during and after breast augmentation

Plasma levels of lidocaine and the main binding proteins of lidocaine in plasma alpha1-acid glycoprotein (AAG) and albumin were measured in 10 otherwise healthy women during and after breast augmentation. A total dose of 825 to 1280 mg of 0.2% and 0.5% lidocaine with epinephrine corresponding to 16.3 to 21.8 mg/kg (mean 18.2 mg/kg) was injected in the spatium between the pectoralis muscle and the mammary gland. The peak plasma concentrations of lidocaine varied between 0.96 and 3.12 microg/ml (mean 1.49 microg/ml) and occurred between 4 and 12 hours (mean 7.3 hours) postoperatively. The plasma concentration of AAG varied between 0.42 and 1.73 g/liter (mean 0.49 g/liter, normal range 0.54 to 1.17 g/liter). There was a significant correlation between the plasma concentration of AAG and lidocaine. The mean concentration of albumin was 37.2 g/liter, ranging from 33 to 42 g/liter (normal range 35 to 50 g/liter). No patient showed signs of lidocaine toxicity. These data indicate that a dose of 20 mg/kg of lidocaine with epinephrine probably is safe in breast augmentation when the drug is administrated as described in this study. There are significant individual differences in the plasma concentration curves between patients, partly explained by different concentrations of AAG. Further studies with a larger number of patients are needed to establish definitive recommendations of safe maximal doses.     

Inhibition of fast axonal transport in vitro by the local anesthetics prilocaine, mepivacaine, and bupivacaine

The aim of the present study was to establish the concentrations of prilocaine, mepivacaine, and bupivacaine which are effective at blocking fast axonal transport, to determine whether prilocaine and mepivacaine offer a better prospect of dissociating conduction block and transport block in vivo than does lidocaine and whether bupivacaine offers a better prospect than etidocaine in the same context. Fast axonal transport of [3H]leucine-labeled proteins was studied in vitro in bullfrog spinal nerves and quantitated by liquid scintillation counting. Exposure of spinal nerves to 14 mM prilocaine reduced the quantity of 3H-labeled proteins which accumulated at a ligature by 86%, and exposure to 14 mM mepivacaine reduced it by 70%; 10 mM prilocaine reduced this same parameter by 54%, a degree of inhibition close to the 44% reduction caused by 14 mM lidocaine. The D(-) and L(+) stereoisomers of mepivacaine each reduced transport to the ligature by approximately 50% at a concentration of 14 mM. Bupivacaine reduced the accumulation of 3H-labeled proteins at the ligature by 49% at a 10 mM concentration (pH 6.2); its potency is close to that found for etidocaine in a previous study. Since prilocaine and mepivacaine are at least as potent as lidocaine as transport inhibitors and at blocking impulse conduction, these two anesthetics offer no advantage over lidocaine to achieve dissociation of conduction block from transport block in vivo. Bupivacaine appears to offer no advantage over etidocaine in the same context, as the two agents have a similar potency as local anesthetics and a similar potency as inhibitors of fast axonal transport.     

Kinetics of local anesthetic inhibition of neuronal sodium currents. pH and hydrophobicity dependence.

This study assesses the importance of local anesthetic charge and hydrophobicity in determining the rates of binding to and dissociation from neuronal Na channels. Five amide-linked local anesthetics, paired either by similar pKa or hydrophobicity, were chosen for study: lidocaine, two tertiary amine lidocaine homologs, a neutral lidocaine homolog, and bupivacaine. Voltage-clamped nodes of Ranvier from the sciatic nerve of Bufo marinus were exposed to anesthetic externally, and use-dependent ("phasic") block of Na current was observed. Kinetic analysis of binding (blocking) rates was performed using a three parameter, piecewise-exponential binding model. Changes in extracellular pH (pHo) were used to assess the role of drug protonation in determining the rate of onset of, and recovery from, phasic block. For those drugs with pKa's in the range of pHo tested (6.2-10.4), the forward binding rate during a depolarizing pulse increased at higher pH, consistent with an increase in either intracellular or intramembrane concentration of drug. The rate for unbinding during depolarization was independent of pHo. The dissociation rate between pulses also increased at higher pHo. The pHo dependence of the dissociation rate was not consistent with a model in which the cation is trapped relentlessly within a closed channel. Quantitative estimates of dissociation rates show that the cationic form of lidocaine dissociates at a rate of 0.1 s-1 (at 13 degrees C); for neutral lidocaine, the dissociation rate is 7.0 s-1. Furthermore, the apparent pKa of bound local anesthetic was found to be close to the pKa in aqueous solution, but different than the pKa for "free" local anesthetic accessible to the depolarized channel.     

Neurotoxic action of some antiarrhythmic agents: comparative effects of propafenone,lidocaine and amiodarone on leech Retzius nerve cell

A series of antiarrhythmic drugs was studied on spontaneous spike activity and depolarizing outward potassium current in leech Retzius nerve cells. Propafenone (0.7 μM/ml) produced a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated after 250 msec by a rapid repolarization. The effect of lidocaine (0.7 μM/ml) on spontaneous spike activity was less pronounced, and early afterdepolarization has been recorded. Amiodarone at the same and much higher concentrations (3 μM/ml) did not generate either a cardiac-like action potential or an early afterdepolarization. In the voltage clamp experiments, fast and slow calcium-activated outward potassium currents were suppressed with propafenone and lidocaine but not with amiodarone. These results suggest that the antiarrhythmic drugs, propafenone and lidocaine modulate calcium-activated potassium channels in leech Retzius nerve cells.     

The site of the neuromuscular block produced by polymyxin B and rolitetracycline.

The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve-muscle preparations. Polymyxin B (1.8 X 10(-4) M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 X 10(-3)M) had no local anaesthetic effect. Polymyxin B (6 X 10(-5) M) and rolitetracycline (7 X 10(-4) M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1-1.5 X 10(-4) M) but not rolitetracycline (1 X 10(-3) M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominatly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarine.     

损毁或阻滞面神经核腹内侧区对呼吸节律的影响

实验用兔,在乌拉坦静脉麻醉,自然呼吸或三碘季铵酚麻痹,人工通气条件下进行。观察了损毁或阻滞面神经核腹内侧区(VMNF)对呼吸节律的影响。结果如下:1.单侧损毁或利多卡因局部阻滞 VMNF 区可引起双侧膈神经放电时间延长,此效应在切断双侧颈迷走神经后尤为明显;2.膈神经吸气性放电的递增速度无明显改变。上述结果提示:VMNF 区在中枢呼吸节律调制中具有重要作用,可能是吸气切断机制负反馈神经元回路中的一个重要结构。     

An endogenous pentapeptide acting as a sodium channel blocker in inflammatory autoimmune disorders of the central nervous system

Reversible blockade of sodium channels by endogenous substances has been claimed to account for the fast exacerbations and relapses commonly seen in demyelinating autoimmune diseases. Evidence has been provided that in the cerebrospinal fluid of patients with multiple sclerosis or Guillain-Barré syndrome, a sodium-channel-blocking factor exists that has properties of local anesthetic agents. This factor could contribute to the nerve conduction block and paresis seen in these disorders. We describe here a previously unknown endogenous substance in human cerebrospinal fluid with distinct channel-blocking properties even at very low (0.00001 M) concentrations. The pentapeptide with the sequence Gln-Tyr-Asn-Ala-Asp exerted its blocking action by shifting the steady-state inactivation curve of the sodium channels to more-negative potentials, as most local anesthetics do. In the cerebrospinal fluid of healthy individuals, its concentration was about 3 microM, whereas in patients with multiple sclerosis and Guillain-Barré syndrome, it increased 300-1,400%. At these concentrations, the peptide's blocking efficacy was higher than that of 50 microM lidocaine. At a concentration of 10 microM, lidocaine is able to 'unmask' subclinical lesions in multiple sclerosis; thus, the endogenous pentapeptide may well contribute to the fast changes of symptoms. Furthermore, it may become valuable as a marker of disease activity.     

Plasma thromboxane B2 levels and thromboxane B2 production by platelets are increased in patients during spinal and epidural anesthesia

Concentrations of thromboxane (Tx) B2 in plasma and its production by platelets were measured in 20 spinal and 10 epidural anesthesia patients scheduled for small operations in the lower extremities. The main metabolite of prostacyclin, 6-keto-PGF1 alpha and prostaglandin (PG) E2 in plasma were also determined. Plasma TxB2 and TxB2 production by platelets increased during both spinal and epidural anesthesia. Plasma TxB2 levels also remained elevated 1 h after anesthesia. The plasma concentrations of 6-keto-PGF1 alpha and PGE2 did not change during spinal or epidural anesthesia. In in vitro studies, only low concentrations of lidocaine (0.5-1.0 micrograms/ml) and bupivacaine (0.5-3.0 micrograms/ml) increased platelet TxB2 production. In platelet rich plasma, neither lidocaine nor bupivacaine in concentrations of 0.5-3.0 micrograms/ml caused constant changes in ADP-induced platelet aggregation, but they inhibited it in toxic concentrations (12 micrograms/ml). The results suggest that the increased TxB2 plasma levels and platelet TxB2 production during regional anesthesia are not caused by local anesthetics itself but by other factors, e.g. tissue trauma. In clinically found concentrations, local anesthetics do not cause any constant changes in platelet aggregation.