Epinephrine Increases the Extracellular Lidocaine Concentration in the Brain: A Possible Mechanism for Increased Central Nervous System Toxicity

Background: Local anesthetics exert central nervous system (CNS) toxicity by inhibiting intracerebral neuronal activity, while epinephrine augments the CNS toxicity of intravenously administered local anesthetics. Viewed together, increases of extracellular concentrations of local anesthetics in the brain may be directly associated with increased CNS toxicity. The authors examined the hypothesis that epinephrine enhances the CNS toxicity of lidocaine by increasing the extracellular concentration in the brain.

Methods: An awake, spontaneously breathing rat model was used. Twenty male Sprague-Dawley rats received an intravenous infusion of lidocaine (3 mg [middle dot] kg-1 [middle dot] min-1; group C) or lidocaine with epinephrine (3 mg [middle dot] kg-1 [middle dot] min-1 and 2 [mu]g [middle dot] kg-1 [middle dot] min-1, respectively; group E) for 10 min (n = 10 in each group). Effects of epinephrine on the convulsive dose and concentrations of total (protein-bound and unbound) and unbound lidocaine in plasma were examined. Concentrations of extracellular lidocaine in the cerebral nucleus accumbens were quantitatively determined by a microdialysis method.

Results: The convulsive dose of lidocaine was significantly lower in group E than in group C (22.4 +/- 5.5 vs. 27.9 +/- 3.1 mg/kg, respectively; P < 0.05). Overall concentrations and area under the plasma concentration-versus-time curve of unbound lidocaine in group E were significantly higher than those in group C. Concentrations of extracellular lidocaine in the nucleus accumbens in group E were comparable to those of unbound fraction in plasma and were also significantly higher than those in group C.     

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis

Purpose  

Nerve growth factor (NGF) has been reported to affect synaptic transmission and cause neuropathic pain. In contrast, lidocaine has been used to reduce neuropathic pain; however, the effect of NGF and lidocaine on spontaneous transmitter release and synapse excitation has not been fully defined. Therefore, the effect of NGF and lidocaine on nerve regeneration, synapse reformation, and subsequent spontaneous transmitter release was investigated. We used Lymnaea stagnalis soma–soma-identified synaptic reconstruction to demonstrate that a transient increase in both frequency and amplitude of spontaneous events of miniature endplate potentials (MEPPs) occurs following NGF treatment and a short burst of action potentials in the presynaptic cell; in addition, the effect of lidocaine on NGF-induced synapse reformation was investigated.     

弱精子症患者精子中电压依赖性钙通道基因表达的变化

目的:探讨弱精子症患者精子中电压依赖性钙通道基因的功能性亚单位α1mRNA表达与弱精子症的关系。方法:首先根据WHO标准用计算机辅助精液分析(CASA)方法对供精者提供的精液进行筛选,然后用Per-coll非连续梯度离心法对精子进行优化,最后应用半定量反转录酶-聚合酶链式反应(RT-PCR)技术分别检测50例正常组成熟运动精子和50例弱精子症患者精子中各类型电压依赖性钙通道的α1mRNA相对表达量。结果:与正常成熟运动精子相比,弱精子症患者精子中电压依赖性钙通道的α1B(39.40±9.47)、α1C(48.30±11.60)、α1E(3.20±0.78)、α1G(8.40±2.03)、α1H(5.70±1.47)mRNA表达的差异具有极显著意义(P<0.01)。结论:L型和/或非L型电压依赖性钙通道的基因表达异常可能是导致人类精子运动能力下降的原因之一,为人类弱精子症病因提供了新的研究方向。     

Lidocaine Suppresses the Anoxic Depolarization and Reduces the Increase in the Intracellular Ca sup 2+ Concentration in Gerbil Hippocampal Neurons

Background: The movement of ions, particularly Ca2+, across the plasma membrane of neurons is regarded as an initial element of the development of ischemic neuronal damage. Because the mechanism by which lidocaine protects neurons against ischemia is unclear, the effects of lidocaine on the ischemia-induced membrane depolarization, histologic outcome, and the change in the intracellular Ca2+ concentration in the gerbil hippocampus were studied.

Methods: The changes in the direct-current potential shift in the hippocampal CA1 area produced by transient forebrain ischemia for 4 min were compared in animals given lidocaine (0.8 micro mol administered intracerebroventricularly) 10 min before ischemia and those given saline. The histologic outcome was evaluated 7 days after ischemia by assessing delayed neuronal death in hippocampal CA1 pyramidal cells in these animals. In a second study, hypoxia-induced intracellular Ca2+ increases were evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effects of lidocaine (10, 50, and 100 micro Meter) on the Ca2+ accumulation were examined. In addition, the effect of lidocaine (100 micro Meter) drug perfusion with a Ca2+ -free ischemia-like medium was investigated.

Results: The preischemic administration of lidocaine delayed the onset of the ischemia-induced membrane depolarization (anoxic depolarization) and reduced its maximal amplitude. The histologic outcome was improved by the preischemic treatment with lidocaine. The in vitro hypoxia-induced increase in the intracellular concentration of Ca2+ was suppressed by the perfusion with lidocaine-containing mediums (50 and 100 micro Meter), regarding the initiation and the extent of the increase. The hypoxia-induced intracellular Ca2+ elevation in the Ca2+ -free condition was similar to that in the Ca2+ -containing condition. Perfusion with lidocaine (100 micro Meter) inhibited this elevation in the Ca2+ -free condition.     

Epinephrine Increases the Neurotoxic Potential of Intrathecally Administered Lidocaine in the Rat

Background: Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat.

Methods: Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation.

Results: Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls.     

Lidocaine excites both pre- and postsynaptic neurons of reconstructed respiratory pattern generator in Lymnaea stagnalis

Lidocaine causes both inhibition and excitation in the central nervous system, including the respiratory pattern. The excitation induced by an excessive dose of local anesthetic is thought to be the result of an initial blockade of an inhibitory pathway in the cerebral cortex. To clarify the effect of lidocaine on the pre- and postsynaptic neurons of an inhibitory synapse, a cultured soma-soma respiratory pattern generator model consisting of two neurons from the snail Lymnaea stagnalis were reconstructed in vitro. First we investigated the effects of lidocaine on single presynaptic (RPeD1) or postsynaptic (VD4) neurons. While RPeD1 and VD4 were simultaneously recorded, the number of action potentials, the membrane potential, and the wavelength of the action potential were compared before and after lidocaine (0.01, 0.1, and 1 mM) administration. Lidocaine increased the number of action potentials and the wavelength of a single action potential, and it depolarized the resting membrane potential in both RPeD1 and VD4 neurons in a dose-dependent manner. Furthermore, lidocaine decreased outward potassium currents. In soma-soma pairs, RPeD1 excitation and VD4 suppression occurred in 0.01 mM lidocaine, whereas both RPeD1 and VD4 neurons were excited by 0.1 and 1 mM lidocaine. In conclusion, lidocaine causes a reduction in synaptic transmission and general neuronal excitation in both presynaptic and postsynaptic neurons.     

Lidocaine Concentration in Oral Tissue by the Addition of Epinephrine

The vasoconstrictive effect due to the addition of epinephrine to local anesthetic has been clearly shown by measuring blood-flow volume or blood anesthetic concentration in oral mucosal tissue. However, there are no reports on the measurement of anesthetic concentration using samples directly taken from the jawbone and oral mucosal tissue. Consequently, in this study, the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine was considered by quantitatively measuring lidocaine concentration within the tissue. Japanese white male rabbits (n = 96) were used as test animals. General anesthesia was induced by sevoflurane and oxygen, and then cannulation to the femoral artery was performed while arterial pressure was constantly recorded. Infiltration anesthesia was achieved by 0.5 mL of 2% lidocaine containing 1 : 80,000 epinephrine in the upper jawbone (E⁺) and 0.5 mL of 2% of epinephrine additive–free lidocaine (E⁰) under the periosteum. At specified time increments (10, 20, 30, 40, 50, and 60 minutes), samples from the jawbone, oral mucosa, and blood were collected, and lidocaine concentration was directly measured by high-performance liquid chromatography. No significant differences in the change in blood pressure were observed either in E⁺ or E⁰. In both E⁺ and E⁰ groups, the serum lidocaine concentration peaked 10 minutes after local anesthesia and decreased thereafter. At all time increments, serum lidocaine concentration in E⁺ was significantly lower than that in E⁰. There were no significant differences in measured lidocaine concentration between jawbone and mucosa within either the E⁺ or the E⁰ groups at all time points, although the E⁰ group had significantly lower jawbone and mucosa concentrations than the E⁺ group at all time points when comparing the 2 groups to each other. Addition of epinephrine to the local anesthetic inhibited systemic absorption of local anesthetic into the blood such that a high concentration could be maintained in the tissue. Epinephrine-induced vasoconstrictive effect was observed not only in the oral mucosa but also in the jawbone.Key Words: Lidocaine concentration, Jawbone, Epinephrine, Infiltration anesthesia, RabbitDuring dental and oral surgery, a significant local anesthetic effect is needed, as not only do the soft tissues require surgery, but also the hard tissue such as jawbones because of surgical interventions. In current clinical dentistry practice, vasoconstrictive agents such as epinephrine are commonly added to local anesthetics to inhibit bleeding from the surgical site and to enhance local anesthetic efficacy by delaying absorption of the local anesthetic into the blood and thus prolonging activity.^1–5 Currently, the vasoconstrictor effect due to the addition of epinephrine to local anesthetic has been sufficiently confirmed. In most reports, however, anesthetic concentration in tissue was indirectly considered by measuring blood-flow volume or serum anesthetic concentration.^1,6–11 In regard to the vasoconstrictive effect in bone due to the addition of epinephrine, only a few reports using methods such as electrodialytical hydrogen clearance and radioisotope measurement have been published,^12–14 and no reported studies have directly measured lidocaine concentration using samples directly taken from the jawbone. Consequently, in this study, we studied the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine, by quantitatively determining lidocaine concentration directly in tissue.     

Lidocaine increases intracellular sodium concentration through voltage-dependent sodium channels in an identified lymnaea neuron

BACKGROUND: The local anesthetic lidocaine affects neuronal excitability in the central nervous system; however, the mechanisms of such action remain unclear. The intracellular sodium concentration ([Na]i) and sodium currents (INa) are related to membrane potential and excitability. Using an identifiable respiratory pacemaker neuron from Lymnaea stagnalis, the authors sought to determine whether lidocaine changes [Na]i and membrane potential and whether INa is related to these changes. METHODS: Intracellular recording and sodium imaging were used simultaneously to measure membrane potentials and [Na]i, respectively. Measurements for [Na]i were made in normal, high-Na, and Na-free salines, with membrane hyperpolarization, and with tetrodotoxin pretreatment trials. Furthermore, changes of INa were measured by whole cell patch clamp configuration. RESULTS: Lidocaine increased [Na]i in a dose-dependent manner concurrent with a depolarization of the membrane potential. In the presence of high-Na saline, [Na]i increased and the membrane potential was depolarized; the addition of lidocaine further increased [Na]i, and the membrane potential was further depolarized. In Na-free saline or in the presence of tetrodotoxin, lidocaine did not change [Na]i. Similarly, hyperpolarization of the membrane by current injections also prevented the lidocaine-induced increase of [Na]i. In the patch clamp configuration, membrane depolarization by lidocaine led to an inward sodium influx. A persistent reduction in membrane potential, resulting from lidocaine, brings the cell within the window current of INa where sodium channel activation occurs. CONCLUSION: Lidocaine increases intracellular sodium concentration and promotes excitation through voltage-dependent sodium channels by altering membrane potential in the respiratory pacemaker neuron.     

Ketamine Inhibits Sodium Currents in Identified Cardiac Parasympathetic Neurons in Nucleus Ambiguus

Background: Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated the possibility that ketamine increases heart rate by inhibiting the central cardiac parasympathetic mechanisms.

Methods: We used a novel in vitro approach to study the effect of ketamine on the identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording, and ketamine effects on isolated potassium (K+) and sodium (Na+) currents were studied.

Results: Cardiac nucleus ambiguus neurons (n = 14) were inherently silent, but depolarization evoked sustained action potential trains with little delay or adaptation. Ketamine (10 [mu]m) reduced this response but had no effect on the voltage threshold for action potentials (n = 14;P > 0.05). The current-voltage relations for the transient K+ current and the delayed rectified K+ current (n = 5) were unaltered by ketamine (10 [mu]m-1 mm). Ketamine depressed the total Na+ current dose-dependently (10 [mu]m-1 mm). In addition, ketamine shifted the Na+ current inactivation curves to more negative potentials, thus suggesting the enhancement of the Na+ channel inactivation (P < 0.05; n = 7). In the presence of Cd2+, ketamine (10 [mu]m) continued to inhibit voltage-gated Na+ currents, which recovered completely within 10 min.     

Lidocaine Concentration in Blood after Topical Anaesthesia of the Upper Respiratory Tract

The venous blood concentration oflidocaine was determined after stepwise application of lidocaine spray (270 mg) to the upper respiratory tract in 10 patients scheduled for bronchography, and after oropharyngeal application (150 mg) to live intubated patients under general anaesthesia. The peak level oflidocaine (about 1 pg/ml) occurred 20–30 min after spraying in the bronchography group, while there was a level plateau at about 0.5 pg/ml after oropharyngeal application of the local anaesthetic. There was great variation in the lidocaine concentration in both groups, but the highest observed concentration, 2.7 μg/ml, was safely below the toxic level. The mean rise in systolic and diastolic blood pressures at the various stages of spraying and on passing the bronchography tube in the local anaesthesia patients was 14.5–17.5/6.5–11 mmHg (1.9–2.3/0.9–1.5 kPa) compared to preanaesthetic values. In a similar group of patients, also scheduled for diagnostic bronchography, thiopentone anaesthesia, succinylcholine relaxation and laryngotracheal lidocaine spray resulted in a peak blood pressure increase of 36.5/27 mmHg (4.9/3.6 kPa) on passing the tube. The mean increases in pulse rate (21–26/min) were similar in both bronchography patient groups. No serious cardiac arrhythmias were observed in any of the patients.     

Chronic Cocaine Administration Reversibly Increases Isoflurane Minimum Alveolar Concentration in Sheep

Background: Significant numbers of patients are seen for surgery and anesthesia with a history of chronic cocaine use. However, little is known about how cocaine use influences anesthetic physiology and pharmacology. The purpose of this study was to investigate the effect of chronic cocaine exposure on the minimum alveolar concentration (MAC) of isoflurane in sheep.

Methods: Isoflurane MAC was determined at baseline in 12 sheep using a standard protocol. The animals were subsequently exposed to cocaine for 18 days. Cocaine exposure consisted of a continuous subcutaneous cocaine infusion at 0.2 mg *symbol* kg sup -1 *symbol* h sup -1, twice daily 4-mg/kg intravenous boluses and repeated hourly 4 mg/kg cocaine boluses for 8 h on day 18. Minimum alveolar concentration determinations were repeated again on days 15, 18, and on day 28 after 10 days of cocaine abstinence.

Results: Compared to baseline MAC (1.53+/-0.12%) cocaine exposure significantly increased isoflurane MAC on days 15 (1.91 +/-0.14%) and 18 (1.78+/-0.13%; P = .005). MAC decreased after discontinuation of cocaine and was not different from baseline on day 28 (1.67+/-0.11).     

可乐定对兔利多卡因硬膜外麻醉效果及药物浓度影响的实验研究

本文评价了兔利多卡因硬膜外麻醉时，可乐定对阻滞效果和利多卡因血药浓度的影响。１８只白兔随机分为利多卡因对照组（１组）、肾上腺素组（２组）和可乐定组（３组）。采用盲法硬膜外分别注射上述三组药物。结果显示，可乐定能延长感觉和运动阻滞时间，降低血清利多卡因水平。其作用类似于肾上腺素，可能是可乐定通过作用于脊髓肾上腺素能受体发挥镇痛效应和／或发挥α２受体介导的缩血管作用。     

双氯芬酸钠盐酸利多卡因注射液超前镇痛在腹腔镜手术中的应用

目的探讨双氯芬酸钠盐酸利多卡因注射液超前镇痛用于腹腔镜手术患者的安全性和有效性。方法 2011年12月～2012年3月,选择ASAⅠ～Ⅱ级,择期行腹腔镜手术的患者50例,按手术通知单顺序编号,依次交替分为实验组和对照组,每组25例,均采用全凭静脉麻醉,诱导前10 min实验组臀部肌肉注射双氯芬酸钠盐酸利多卡因注射液2 ml,对照组不做处理,术后2 h（T2）、6 h（T6）、12 h（T12）、24 h（T24）用视觉模拟评分法（VAS）进行疼痛评分和布氏评分法（BCS）进行舒适评分,并记录术后不良反应发生情况。结果 2组麻醉苏醒时间差异无显著性（P〉0.05）。实验组术后24 h内各时点VAS评分及BCS评分显著优于对照组（P〈0.05）。与对照组相比,实验组苏醒期躁动发生例数少（2例vs.9例,χ2=5.711,P=0.017）,追加镇痛的例数少（3例vs.10例,χ2=5.094,P=0.024）。2组术后恶心呕吐差异无显著性（P〉0.05）。结论双氯芬酸钠盐酸利多卡因注射液超前镇痛用于腹腔镜手术患者,可明显减轻术后疼痛,减少镇痛药的使用及苏醒期烦躁,且给药方便,不良反应少,可以安全用于临床。     

Propofol Fails to Attenuate the Cardiovascular Response to Rapid Increases in Desflurane Concentration

Background: A rapid increase in desflurane concentration to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating catecholamine concentration. Because propofol decreases sympathetic outflow, it was hypothesized that propofol would blunt these responses.

Methods: To test this hypothesis, five healthy male volunteers were studied three times. After induction of anesthesia with 2 mg *symbol* kg sup -1 propofol, anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. On separate occasions, in random order, either no propofol or 2 mg *symbol* kg sup -1 propofol was administered either 2 or 5 min before increasing end-tidal desflurane concentration from 4% to 8%.

Results: Without propofol pretreatment, the increase to 8% desflurane transiently increased heart rate (from 63+/-3 beats/min to 108 +/-5 beats/min, mean+/-SEM; P < 0.01), mean arterial pressure (from 73+/-1 mmHg to 118+/-6 mmHg; P < 0.01), and epinephrine concentration (from 14+/-1 pg *symbol* ml sup -1 to 279+/-51 pg *symbol* ml sup -1; P < 0.05). There was no significant change in norepinephrine concentration (from 198+/-37 pg *symbol* ml sup -1 to 277+/-46 pg *symbol* ml sup -1). The peak plasma epinephrine concentration was attenuated by each propofol pretreatment (158+/-35 pg *symbol* ml sup -1, propofol given 2 min before, and 146 + 41 pg *symbol* ml sup -1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment modified the cardiovascular or norepinephrine responses.     

Succinylcholine Metabolite Succinic Acid Alters Steady State Activation in Muscle Sodium Channels

Background: Animal experiments revealed that succinylcholine produced masseter muscle rigidity and activated myotonic discharges despite neuromuscular blockade with a nondepolarizing blocker. These results suggest that either succinylcholine or its metabolites might interfere directly with voltage-operated ion channels of the sarcolemma. The aim of this study was to examine effects of one product of succinylcholine hydrolysis, succinic acid, on voltage-gated muscle sodium (Na+) channels.

Methods: Alpha subunits of human muscle sodium channels were heterologously expressed in HEK293 cells. Activation of Na+ currents was examined applying standard whole-cell voltage-clamp protocols in the absence (control and washout) and presence of succinic acid in different concentrations (0.05-10 mm).

Results: Succinic acid shifted the midpoints of steady state activation plots in the direction of more negative test potentials, indicating that channels open during smaller depolarizations in the presence of the drug. The maximum amount of the negative shift in 10 mm succinic acid was -6.3 +/- 1.7 mV; the EC50 for this effect was 0.39 mm. In addition, succinic acid (10 mm) significantly enhanced maximum currents after depolarizations with respect to a series of control experiments.     

Local Anesthetics Inhibit Substance P Binding and Evoked Increases in Intracellular Calcium sup 2+

Background: During spinal and epidural anesthesia, local anesthetics reach concentrations in cerebrospinal fluid and spinal cord tissues at which their actions may extend beyond the classic blockade of sodium channels. This study examines the effects of several clinical and experimental local anesthetics on the binding and actions of a peptide neurotransmitter, substance P, known to be important in nociceptive transmission in the dorsal horn.

Methods: The binding of radiolabeled (Bolton-Hunter modified) substance P was studied in chick brain membranes in the presence of local anesthetics. The increase in intracellular calcium [Ca2+]in evoked by substance P was measured by the fluorescent indicator fura-2 loaded in a murine cell line expressing substance P (NK1) receptors. Cells were preincubated with bupivacaine before and during the transient addition of substance P.

Results: Both substance P binding and Calcium2+ increase were inhibited half-maximally by approximately 1 mM bupivacaine at pH 7.5, whereas tetracaine, lidocaine, and benzocaine were slightly less potent at inhibiting binding. Concentration-dependent substance P-binding studies showed that bupivacaine's inhibition was not competitive. Inhibition of substance P binding by bupivacaine increased with increasing pH, but the protonated species appears to have some inhibitory activity, and quaternary lidocaine also inhibited binding. There was no stereoselectivity to the binding inhibition.     

蛙皮素对PC-3细胞骨架及细胞内游离Ca~(2+)的影响

目的:观察蛙皮素(BBS)对前列腺癌PC-3细胞骨架形态及细胞内游离Ca2+([Ca2+]i)浓度的影响。方法:①利用免疫荧光法(IH),结合激光扫描共聚焦显微镜(LSCM)检测10-5mol/L浓度BBS处理的PC-3细胞角蛋白(CK)的表达,以反映其对细胞骨架形态的影响;②应用Fluo-3/AM荧光标记技术和LSCM检测不同浓度BBS(10-9、10-7、10-5mol/L)处理的PC-3细胞[Ca2+]i浓度。结果:①10-5mol/L浓度的BBS可促进PC-3细胞CK表达及伪足形成;②BBS可提高PC-3细胞[Ca2+]i浓度,并具有浓度依赖性。结论:实验证明一定浓度的BBS可明显提高PC-3细胞[Ca2+]i浓度及CK表达,进而影响PC-3细胞骨架形态。本研究为探索BBS应用于肿瘤研究以及BBS作用后细胞内信息传递途径提供了基础。     

Addition of Sodium Bicarbonate to Lidocaine Decreases the Duration of Peripheral Nerve Block in the Rat

Background: Adding sodium bicarbonate to lidocaine to enhance its efficacy during peripheral nerve block is controversial. The authors studied the effect of adding sodium bicarbonate to lidocaine with and without epinephrine versus equivalent alkalinization by sodium hydroxide (NaOH) on onset, degree, and duration of peripheral nerve block.

Methods: Part I examined alkalinization by sodium bicarbonate versus NaOH to pH 7.8 on 0.5% lidocaine, with and without epinephrine (1:100,000), prepared from crystalline salt. Part II examined 0.5% and 1.0% commercial lidocaine solutions, with and without epinephrine, either unalkalinized or alkalinized with sodium bicarbonate or NaOH. With NaOH, pH was adjusted to 7.8, but with sodium bicarbonate, no pH adjustments were made to simulate clinical conditions.

Results: In part I, addition of either NaOH or sodium bicarbonate to 0.5% lidocaine without epinephrine produced a faster onset than did unalkalinized lidocaine, without effecting degree or duration of block. In solutions with epinephrine there were no differences in onset, degree, or duration between lidocaine alkalinized with sodium bicarbonate versus NaOH. In part II, addition of sodium bicarbonate or NaOH to 1.0% commercial lidocaine without epinephrine did not accelerate onset compared with the unalkalinized solution. However, adding sodium bicarbonate decreased the degree and duration of block by 25% and more than 50%, respectively, compared with lidocaine unalkalinized and alkalinized with NaOH. With epinephrine, sodium bicarbonate hastened onset without effecting degree and duration compared with the unalkalinized solution.