Quality of lidocaine analgesia with and without midazolam for intravenous regional anesthesia

Purpose

Midazolam has analgesic effects mediated by gamma aminobutyric acid-A receptors. This study was designed to evaluate the effect of midazolam on anesthesia and analgesia quality when added to lidocaine for intravenous regional anesthesia (IVRA).

Methods

Forty patients undergoing hand surgery were randomly assigned to two groups to receive IVRA. The control group received 3 mg/kg lidocaine 2% w/v diluted with saline to a total volume of 40 ml, and the midazolam group received an additional 50 μg/kg midazolam. Sensory and motor block onset and recovery times, tourniquet pain, intraoperative analgesic requirements, sedation, and anesthesia quality were recorded. Postoperative pain and sedation scores, time to first analgesic requirements, analgesic use in the first 24 h, and side effects were noted.

Results

Sensory and motor block onset and recovery times did not differ significantly between groups. Tourniquet pain scores were lower at 10, 15, 20, and 30 min (P < 0.0001) in the midazolam group. Three (15%) patients in the midazolam group required fentanyl for tourniquet pain compared with thirteen (65%) patients in the control group (P = 0.02). Patients in both groups received fentanyl once. Midazolam group showed that significantly less patients required diclofenac for postoperative analgesia (P < 0.01) and analgesic-free period during first postoperative 24 h was significantly longer (726.8 ± 662.8 min vs. 91.0 ± 35.9 min, P < 0.0001). Postoperative pain scores were lower (P < 0.0001) and sedation scores higher (P < 0.05) for the first 2 h in the midazolam group.

Conclusion

Addition of midazolam to lidocaine for IVRA improves anesthesia quality and enhances intraoperative and postoperative analgesia without causing side effects.     

大鼠静脉输注罗哌卡因与利多卡因混合液的毒性反应

目的 探讨罗哌卡因与利多卡因混合应用对中枢神经系统(CNS)和心血管(CV)毒性反应的影响。方法 Wistar大鼠36只,随机分为3组,每组12只。A组静脉注射(ⅳ)0.5％罗哌卡因2mg·ks~(-1)·min~(-1),B组ⅳ 1.0％利多卡因4mg·ks~(-1)·min~1,C组ⅳ 0.5％罗哌卡因2mg·kg~(-1)·min~(-1) 1.0％利多卡因4mg·kg~(-1)·min~(-1)。麻醉及相关操作后持续监测脑电图、心电图、平均动脉压(MAP)。待呼吸、循环稳定20min后,血气分析值正常,记录此时的MAP、心率(HR)作为基础值,输入相应的局麻药。记录出现CNS毒性(SZ)、心律失常(DYS)和心脏停搏(ASYS)三个中毒点的时间、计算输入局麻药累积剂量。在各点采动脉血,用高效液相色谱仪测血浆中局麻药浓度。结果 A组发生SZ、ASYS时罗哌卡因累积剂量大于C组(P<0.05),但发生DYS时差异无显著性。B组发生SZ、DYS、ASYS时利多卡因累积剂量大于C组(P<0.05)。A组发生SZ、DYS、ASYS时罗哌卡因血药浓度与C组比较差异无显著性;B组发生SZ、DYS、ASYS时利多卡因血药浓度与C组比较差异无显著性。结论 0.5％罗哌卡因与1.0％利多卡因混合应用后增加了CNS和CV系统毒性。     

咪唑安定预先给药对罗哌卡因致大鼠中枢神经系统毒性反应的影响

目的 探讨咪唑安定预先给药对罗哌卡因致大鼠中枢神经系统毒性反应的影响及其机制。方法SD大鼠30只，4-6月龄，体重250-300g，随机分为3组（n=10）：空白对照组（C组）、罗哌卡因组（R组）和咪唑安定＋罗哌卡因组（MR组）。R组以0．5ml／min速率静脉输注0．75％罗哌卡因，至大鼠出现惊厥时停药；MR组于输注罗哌卡因前5min静脉注射咪唑安定0．8mg／kg；C组以0．5ml／min速率输注生理盐水2ml。停止输注罗哌卡因后即刻处死大鼠，取静脉血1ml，测定pH值，并用紫外比色法测定乳酸浓度；用高效液相色谱技术测定脑组织谷氨酸（Glu）、天冬氨酸（Asp）、甘氨酸（Gly）和γ-氨基丁酸（GABA）的含量。结果与C组比较，R组静脉血乳酸浓度增加，pH值降低，MR、R组大鼠惊厥时脑组织各种氨基酸含量均升高（P〈0．05）；与R组比较，MR组大鼠惊厥时罗哌卡因剂量增加，静脉血乳酸浓度降低，脑组织Asp、Gly和GABA含量降低（P〈0．05）。结论咪唑安定预先给药可预防罗哌卡因对大鼠中枢神经系统的毒性，并通过降低脑组织兴奋性氨基酸的水平，降低罗哌卡因致中枢神经系统毒性反应的程度。     

Plasma lidocaine concentrations during continuous epidural infusion of lidocaine with and without epinephrine

Plasma lidocaine concentrations were measured over a five-hour period in 20 patients following continuous epidural infusion of lidocaine for surgical anaesthesia. Patients were divided into two groups: Group I received plain lidocaine; Group II received lidocaine with epinephrine. Patients initially received 10 ml followed by a constant infusion of 10 ml.hr-1 of two per cent lidocaine. The mean plasma concentrations of lidocaine were significantly higher for the first 40 min in Group I than in Group II. However, from one to five hours, there was no significant difference between the groups. These results demonstrate that the addition of epinephrine to lidocaine does not decrease the plasma concentration of lidocaine during continuous epidural infusion for long operations.     

Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery.

Lidocaine with epinephrine is currently the most common local anesthetic agent used for impacted third molar surgery. The purpose of the present study was to define the adverse hemodynamic effects and plasma concentrations of lidocaine and epinephrine on 17 healthy patients during the impacted teeth operations. Arterial blood pressure (systolic blood pressure, diastolic blood pressure), heart rate, peripheral oxygen saturation range, and electrocardiography were measured by an automatic noninvasive pressure device and monitor. High-performance liquid chromatography was used to measure the changes of plasma concentrations of epinephrine and lidocaine from blood samples taken 5 different times during the operation. We concluded that lidocaine-epinephrine is effective local anesthetic and had no important adverse events in healthy patients during the third molar surgery.     

Comparison of the clinical effectiveness of lidocaine hydrocarbonate and lidocaine hydrochloride with and without epinephrine in epidural anaesthesia

Epidural analgesia was administered to one hundred patients undergoing various types of surgical procedures. They were divided at random into four equal groups who received lidocaine hydrocarbonate or lidocaine hydrochloride, both with or without epinephrine. A double blind method was used. The study was designed first to test the validity of claims that lidocaine hydrocarbonate produces a shorter period of onset for effective analgesia, a more profound sensory and motor block, and a higher spread of analgesia than the hydrochloride salt and secondly, to identify the respective roles of carbon dioxide and epinephrine in obtaining this alleged superior effectiveness. The results of the study showed that carbon dioxide improved the quality of sensory block, but we could not find any significant difference between lidocaine hydrocarbonate and lidocaine hydrochloride salt, with and without epinephrine, with regard to rapidity of onset, upward spread of analgesia and quality of motor block. As was already known, duration of analgesia was prolonged by the addition of epinephrine but not by the addition of carbon dioxide. The study also showed that the compliance of the epidural space was decreased in the lidocaine hydrocarbonate groups compared to those with lidocaine hydrochloride. There is a positive correlation between the duration of sensory block or the upper level of analgesia and compliance in the hundred patients studied. It is concluded that the hydrocarbonate base, because of its more profound sensory block in the L₅-S₁ segment, can be useful for operations on the lower extremities, especially in the L₅-S₁ segmental distribution. However, knowing that the hydrocarbonate base is more expensive, one must use his own judgment in appraising the cost-benefit of its use.     

Oral mucosal blood flow, plasma epinephrine and haemodynamic responses after injection of lidocaine with epinephrine during midazolam sedation and isoflurane anaesthesia

We have investigated the relationship between oral mucosal blood flow and plasma epinephrine concentration, and the effects of conscious sedation vs general anaesthesia on haemodynamic responses after submucosal epinephrine injection in 14 subjects. The same seven patients were studied both as controls and after sedation. For sedation, midazolam i.v. was used. Another seven patients underwent orthognathic surgery with isoflurane anaesthesia. All subjects received a submucosal injection of epinephrine 0.8 microgram kg-1, given as 2% lidocaine hydrochloride with epinephrine 12.5 micrograms ml-1. Baseline mucosal blood flow and peak increase in plasma epinephrine concentration in the general anaesthesia and sedation groups were approximately 2.0 and 1.5 times, respectively, higher than those in the control group. Mean plasma epinephrine concentration reached a maximum 3 min after administration of epinephrine in all groups. Overall, there was a significant correlation (r = 0.65) between baseline mucosal blood flow and the maximum increase in plasma epinephrine concentration. There were no differences in haemodynamic changes except for heart rate, between the three groups. These results suggest that plasma epinephrine concentration after submucosal injection depends on the initial mucosal blood flow in the injected area. Haemodynamic changes, except heart rate, in the sedation and general anaesthesia groups were similar despite different changes in maximum plasma epinephrine concentration.      

利多卡因预先给药对大鼠肾脏缺血再灌注时肾组织HMGB1表达的影响

目的 探讨利多卡因预先给药对大鼠肾脏缺血再灌注时肾组织高迁移率族蛋白-1(HMGB1)表达的影响.方法 健康成年雄性Wistar大鼠36只,体重300 ～ 350 g,采用随机数字表法,将其随机分为3组(n=12):假手术组(S组)、肾脏缺血再灌注组(I/R组)和利多卡因组(L组).I/R组和L组采用夹闭双侧肾动脉60 min恢复灌注的方法建立肾脏缺血再灌注损伤模型.L组于缺血前60min静脉注射利多卡因5mg/kg,随后以2mg·kg-1·h-1速率静脉输注60 min; I/R组给予等容量生理盐水.3组分别于再灌注4、24h时取6只大鼠,取肾组织,采用PCR技术检测HMGB1 mRNA表达,采用Western blot法测定HMGB1表达,分别采用黄嘌呤氧化酶法和硫代巴比妥法测定超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,光镜下观察肾组织病理学结果.结果 与S组比较,I/R组和L组肾组织HMGB1 mRNA及其蛋白表达和MDA含量升高,肾组织SOD活性降低(P＜0.05);与I/R组比较,L组肾组织HMGB1 mRNA及其蛋白表达和MDA含量降低,肾组织SOD活性升高(P＜0.05).L组肾组织病理学损伤轻于I/R组.结论 利多卡因可减轻大鼠肾脏缺血再灌注损伤,其机制与下调肾组织HMGB1表达有关.     

Plasma concentrations of lidocaine and its principal metabolites during continuous epidural infusion of lidocaine with or without epinephrine

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the effect of epinephrine on the absorption of lidocaine and the accumulation of active metabolites of lidocaine during continuous epidural anesthesia. METHODS: Lidocaine was administered as an initial bolus of 5 mg/kg of 2% lidocaine solution followed by continuous infusion at 2.5 mg/kg/h. Patients in group I (n = 10) received lidocaine alone and patients in group II (n = 10) received lidocaine + epinephrine (5 pg/mL). Concentrations of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in plasma samples obtained after 15 minutes, 30 minutes, and 1, 2, and 3 hours of infusion using high-performance liquid chromatography with ultraviolet detection. RESULTS: Plasma lidocaine concentrations were higher in group I for the first 30 minutes; however, after 1 hour the levels were the same. Plasma MEGX and GX increased continuously in both groups. MEGX levels the were significantly higher in group I, but there was no significant difference in the sum of lidocaine + MEGX after 2 hours. There was no significant difference in GX levels between the two groups. CONCLUSIONS: With respect to continuous epidural administration, addition of epinephrine to lidocaine solutions is ineffective after 2 hours for reducing the potential for systemic toxicity, because the sum of the plasma concentrations of lidocaine and its principal active metabolite, MEGX, are unaffected.     

Effects of local anesthesia on nerve blood flow: studies using lidocaine with and without epinephrine

Peripheral nerves have a dual blood supply of intrinsic exchange vessels in the endoneurium and an extrinsic plexus of supply vessels in the epineurial space that cross the perineurium to anastomose with the intrinsic circulation. The extrinsic supply is responsive to adrenergic stimuli. In this study we measured nerve blood flow in rat sciatic nerves with a laser Doppler flow probe. Normal saline, solutions of 1% or 2% lidocaine HCl with and without 1:200,000 epinephrine, or 1:200,000 epinephrine in normal saline were topically applied to the nerves to determine their effect on nerve blood flow. At the end of the subsequent 10-min recording period, blood flow was significantly depressed for all of the solutions tested except saline. Reductions of blood flow ranged from 19.3% for 1% lidocaine HCl to 77.8% for 2% lidocaine HCl with epinephrine. Epinephrine by itself significantly reduced nerve blood flow; when added to local anesthetic solutions, it reduced nerve blood flow to a greater extent than the reduction caused by anesthetics alone. There was an additional significant reduction in nerve blood flow when the epinephrine groups were compared with the pure local anesthetic groups.     

静脉注射利多卡因对七氟醚复合瑞芬太尼无肌松药条件下气管插管效果的影响

目的 探讨静脉注射利多卡因对七氟醚复合瑞芬太尼无肌松药条件下气管插管效果的影响.方法气管插管全麻病人75例,年龄18～64岁,ASA分级Ⅰ或Ⅱ级.采用随机数字表法,将病人随机分为3组(n=25),A组:七氟醚+瑞芬太尼1 μg/kg;B组:七氟醚+瑞芬太尼1 μg/kg+利多卡因1 mg/kg;C组:七氟醚+瑞芬太尼2 μg/kg.吸入8%七氟醚2 min时,A组静脉注射瑞芬太尼1μg/kg,B组静脉注射瑞芬太尼1 μg/kg和利多卡因1 mg/kg,C组静脉注射瑞芬太尼2 μg/kg.瑞芬太尼注射完毕后行气管插管.从置入喉镜、声带位置、声带活动、咳嗽反射和体动反应5个方面评价气管插管条件,分为满意、良好和欠佳3个级别,记录各项满意的发生情况.于麻醉诱导前、气管插管前即刻和气管插管后即刻记录MAP和HR.结果 病人均完成气管插管.与A组相比,B组和C组咳嗽反射的满意率升高,C组气管插管前即刻和气管插管后即刻MAP、HR降低(P＜0.05),B组气管插管前即刻和气管插管后即刻MAP和HR差异无统计学意义(P＞0.05);B组咳嗽反射的满意率较C组升高(P＜0.05).气管插管期间,C组有3例发生低血压,1例心动过缓,A组和B组均未见低血压或心动过缓发生.结论 七氟醚复合瑞芬太尼用于无肌松药条件下气管插管时,静脉注射利多卡因1mg/kg不仅可优化气管插管条件,还可降低瑞芬太尼用量.

Abstract：

Objective To investigate the effect of intravenous lidocaine on the efficacy of sevoflurane combined with remifentanil for tracheal intubation without neuromuscular relaxants. Methods Seventy-five ASA Ⅰor Ⅱ patients, aged 18-64 yr, scheduled for elective surgery, needing tracheal intubation under general anesthesia, were randomly divided into 3 groups ( n = 25 each) : sevoflurane + remifentanil 1 μg/kg group (group A) ;sevoflurane + remifentanil 1 μg/kg + lidocaine 1 mg/kg group (group B); sevoflurane + remifentanil 2 μg/kg group (group C) . Two minutes after inhalation of 8% sevoflurane for anesthesia induction, remifentanil 1 μg/kg, remifentanil 1 μg/kg + lidocaine 1 mg/kg, and remifentanil 2 μg/kg were injected intravenously in groups A, B and C respectively. Tracheal intubation was performed after completion of remifentanil injection. Intubating conditions were assessed based on ease of laryngoscopy, position of vocal cords, activity of vocal cords, degree of coughing and limb movement. MAP and HR were also recorded before induction and immediately before and after intubation. Results Tracheal intubations were successful in all patients. The satisfactory rates of coughing were significantly higher in groups B and C, and MAP and HR were significantly lower immediately before and after intubation in group C than in group A ( P ＜ 0.05) . The satisfactory rate of coughing was significantly higher in group B than in group C ( P ＜ 0.05) . During intubation, 3 cases developed hypotension and 1 case bradycardia in group C. Conclusion When sevoflurane combined with remifentanil is used for tracheal intubation without neuromuscular relaxants, intravenous lidocaine 1 mg/kg can not only improve intubating conditions, but also decrease the consumption of remifentanil.     

Effect of ciprofloxin on the pharmacokinetics of intravenous lidocaine

BACKGROUND AND OBJECTIVE: Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. We have studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. METHODS: In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg kg[-1] lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 h after the start of the lidocaine infusion. RESULTS: Ciprofloxacin increased the mean peak concentration and area under plasma concentration-time curve of lidocaine by 12% (range [-6] to+46%; P<0.05) and 26% (8--59%; P 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7--38%; P<0.01). Ciprofloxacin decreased the area under the plasma concentration-time curve of monoethylglycinexylidide by 21% (P<0.01) and that of 3-hydroxylidocaine by 14% (P< 0.01). CONCLUSION: The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.     

Modification of intravenous lidocaine-induced convulsions by epinephrine in rats

We studied intravenous lidocaine-induced convulsions in rats to determine whether added epinephrine influences the provocation of lidocaine toxicity. Wistar rats (200–250 g) were divided into three groups of ten, depending on the concentration of epinephrine added to lidocaine. Group 1: plain 1.5% lidocaine; Group 2: 1.5% lidocaine with 1∶200,000 epinephrine; Group 3: 1.5% lidocaine with 1∶100,000 epinephrine. After surgical preparation and recovery from anaesthesia, all rats received a continuous iv infusion of lidocaine (15 mg·ml^?1) at a rate of 4.0 mg·kg^?1·min^?1 until generalized convulsions occurred. The epinephrine-treated animals developed acute hypertension after one minute of lidocaine infusion (105±2 to 141±2 mmHg in Group 2 and 103±2 to 151±2 mmHg in Group 3). The PaO₂ values in the epinephrine groups at the onset of convulsions were decreased significantly (88.3±1.0 to 84.0 ±1.5 mmHg in Group 2 P < 0.05 and 86.9±1.2 to 78.1±2.4 mmHg in Group 3 P<0.01). However, these values were still within physiological ranges. Serum potassium concentrations in all groups were decreased P<0.05, (4.24±0.09 to 3.52±0.12 mEq·L^?1 in Group 1, 4.02±0.09 to 3.63±0.17 mEq·L^?1 in Group 2, and 4.15±0.10 to 3.69 ±0.17 mEq·L^?1 in Group 3). Blood sugar concentrations in all groups were increased at the onset of convulsions, and the levels in the epinephrine groups were higher than in Group 1 P<0.01 (119±4 to 149±7 mg·dl^?1 in Group 1: 120±4 to 195±10 mg·dl^?1 in Group 2, and 127±3 to 190±6 mg·dl^?1 in Group 3). There were differences in the cumulative convulsant doses of lidocaine among the groups, as follows: Group 1=41.9±1.3 > Group 2=30.0±0.7 > Group 3=24.2±0.9 mg·kg^?1; P<0.01. At the onset of convulsions, not only the plasma lidocaine concentrations (Group 1=10.7±0.3 > Group 2=8.3±0.2 (P<0.01) > Group 3=7.5±0.2 μg·ml^?1 (P<0.01 vs Group 1, P < 0.05 vs Group 2), but also the brain lidocaine concentrations which were extracted from the whole brain homogenates: Group 1=48.7±1.9 > Group 2=38.2±1.1 (P<0.01) > Group 3=33.0±1.3 μg·g^?1 (P <0.01 vs Group 1, P<0.05 vs Group 2) showed differences. The brain/plasma lidocaine concentration ratios were, however, similar in the three groups (Group 1=4.5±0.1; Group 2=4.6±0.1; Group 3=4.4±0.2). Our data show that added epinephrine decreases the threshold of lidocaine-induced convulsions dose-dependently; however, the added ephinephrine does not cause a greater proportion of the infused lidocaine to enter the CNS.     

The effects of tumescent solutions containing lidocaine and epinephrine on skin flap survival in rats

The effects of tumescent solutions consisting of lidocaine and epinephrine on skin flap survival in rats were studied. Dorsal skin flaps of rats were infiltrated using lidocaine (1%) with epinephrine in concentrations of 1:100,000, 1:200,000, 1:400,000, and 1:800,000 prior to elevating flaps of the different experimental groups. The solutions were applied intradermally or subcutaneously, and the flaps were raised "immediately" or "delayed" after injection in the different groups. Control flaps were infiltrated by lidocaine (1%) only. The survival of the flaps was assessed on the seventh day after the operation. As a result, the flaps showed higher necrosis rates in the groups injected by lidocaine with epinephrine in concentration of 1:100,000 and 1:200,000 than of the other experimental or all control groups (P < 0.01). In conclusion, lidocaine with epinephrine in concentrations of 1:400,000 and 1:800,000 was found safe on skin flap survival for tumescent technique in rats.     

Cardiovascular responses to scalp infiltration with different concentrations of epinephrine with or without lidocaine during craniotomy

Intraoperative blood pressure changes alter cerebral blood flow in neurosurgical patients with impaired autoregulation. Infiltration of the scalp before craniotomy may cause hemodynamic changes that depend on the composition of the solution used. We investigated cardiovascular responses to infiltration of the scalp with five different combinations of epinephrine and lidocaine in 112 patients: Group A, lidocaine 0.5%; Group B, lidocaine 0.5% with epinephrine 1:200,000; Group C, lidocaine 0.5% with epinephrine 1:100,000; Group D, normal saline with epinephrine 1:200,000; and Group E, normal saline with epinephrine 1:100,000. Episodes of tachycardia occurred more frequently in group E (P = 0.03). Plain lidocaine did not cause any significant change in blood pressure. The incidence of systolic, diastolic, and mean arterial hypertension was significantly increased in group E (P < 0.01). Episodes of diastolic hypertension occurred more frequently in Group D (P < 0.01). A biphasic diastolic and mean arterial hypotension (around Minute 2 and Minutes 9-15) occurred in Groups C and B (P < 0.001). In conclusion, epinephrine 1:100,000 causes significant tachycardia. Epinephrine in concentrations of 1:100,000 and 1:200,000 causes significant hypertension. The combination of lidocaine and epinephrine attenuates the hypertension but results in a biphasic hypotensive response.