利多卡因对气管平滑肌舒张作用的研究

利多卡因是临床上常用的局部麻醉药和抗室性心律失常药物;除此之外,利多卡因还具有较强的扩张气道、抑制气道炎症、降低气道高反应性的作用。此方面的研究最早可追溯到上世纪60年代,利多卡因在围术期预防和处理支气管痉挛中所占的地位已得到充分肯定,现将近10余年来利多卡因对气道平滑肌影响的主要研究成果综述如下。     

Effects of the α2-Adrenoceptor Agonist Dexmedetomidine on Bronchoconstriction in Dogs

Background: Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that [alpha]2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective [alpha]2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown.

Methods: After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 [mu]g/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.

Results: At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone).     

Combined Intravenous Lidocaine and Inhaled Salbutamol Protect against Bronchial Hyperreactivity More Effectively than Lidocaine or Salbutamol Alone

Background: Airway instrumentation in persons with asthma is linked to the risk of life-threatening bronchospasm. To attenuate the response to airway irritation, intravenous lidocaine is recommended (based on animal experiments) and mitigates the response to histamine inhalation in asthmatic volunteers. However, the effects of lidocaine have not been compared with standard prophylaxis with [Greek small letter beta]-sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol, combined treatment, and placebo control were tested in awake volunteers with bronchial hyperreactivity.

Methods: After approval from the local ethics committee, 15 persons, who were selected because they showed a decrease in forced expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a placebo-controlled, double-blind, and randomized study. The challenge was repeated on four different days and the volunteers were pretreated with either intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also measured. Statistical analyses included the Friedman test and Wilcoxon's rank sum.

Results: The baseline PC20 was 6.4 +/- 4.3 mg/ml. Intravenous lidocaine and salbutamol aerosol both significantly increased the histamine threshold to 14.2 +/- 9.5 mg/ml and 16.8 +/- 10.9 mg/ml, respectively (mean +/- SD). However, the combination of lidocaine and salbutamol significantly increased the PC20 even further to 30.7 +/- 15.7 mg/ml than did salbutamol or lidocaine alone.     

Effects of the alpha2-adrenoceptor agonist dexmedetomidine on bronchoconstriction in dogs

BACKGROUND: Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown. METHODS: After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated. RESULTS: At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone). CONCLUSION: alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.     

Airway Anesthesia Alone Does Not Explain Attenuation of Histamine-induced Bronchospasm by Local Anesthetics: A Comparison of Lidocaine, Ropivacaine, and Dyclonine

Background: Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity.

Methods: Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD.

Results: The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]).     

Lidocaine exerts its effect on induced bronchospasm by mitigating reflexes, rather than by attenuation of smooth muscle contraction

BACKGROUND: Lidocaine inhalation attenuates histamine-induced bronchoconstriction, as well as bronchoconstriction elicited by mechanical irritation. This effect could be mediated by direct effects on smooth muscle or by reflex attenuation. Therefore, we evaluated whether lidocaine attenuated the bronchial response of direct smooth muscle stimulation with methacholine. METHODS: In 15 volunteers with bronchial hyperreactivity, a methacholine challenge was performed following the inhalation of lidocaine, dyclonine (which does not attenuate bronchial reactivity) or saline on three different days in a randomized, double-blind fashion. Lung function, response to methacholine, and lidocaine and dyclonine plasma concentrations were measured. RESULTS: The inhaled methacholine concentration (PC20) necessary for a 20% decrease in the forced expiratory volume in 1 s (FEV1) was 8.8 +/- 6.1 mg/ml at the screening evaluation. The sensitivity to methacholine challenge (PC20) remained unchanged regardless of which solution was inhaled (9.1 +/- 7.5 mg/ml for lidocaine, 10.2 +/- 9.0 mg/ml for dyclonine and 9.8 +/- 8.3 mg/ml for saline; P = 0.58, means +/- standard deviation). Furthermore, the inhalation of all three solutions caused a significant decrease in FEV1 from baseline (P = 0.0007), with a significantly larger effect for dyclonine than lidocaine (P = 0.0153). CONCLUSIONS: Although both inhaled and intravenous lidocaine attenuates histamine-evoked bronchoconstriction, it does not alter the response to methacholine. Therefore, the attenuation of bronchial reactivity by lidocaine appears to be related solely to neurally mediated reflex attenuation, rather than to the attenuation of direct constriction of airway smooth muscle.     

Lidocaine inhalation for local anaesthesia and attenuation of bronchial hyper-reactivity with least airway irritation. Effect of three different dose regimens

The inhalation of lidocaine attenuates bronchial hyper-reactivity but also causes airway irritation. However, how lidocaine dose and plasma concentration influence relationships are unknown. Accordingly, we evaluated the effects of three concentrations of lidocaine (1, 4, and 10%, total dose of 0.5, 2.0, and 5.0 mg kg-1, respectively) vs. placebo in 15 mild asthmatic patients, selected by their response to a histamine challenge (decrease in FEV1 > 20% to less than 18 mg mL-1 of histamine [PC20]). Baseline lung function, histamine-induced bronchoconstriction, topical anaesthesia, and lidocaine plasma concentrations were obtained. FEV1 following lidocaine inhalation showed the greatest decrease for the highest dose (from 3.79 +/- 0.15-3.60 +/- 0.15; P = 0.0012). Lidocaine inhalation increased baseline PC20 (6.1 +/- 1.3 mg mL-1) significantly (to 11.8 +/- 3.1, 16.1 +/- 3.3, and 18.3 +/- 4.5 mg mL-1, respectively) with no difference between the two highest doses. The duration of local anaesthesia was not significantly different between lidocaine concentrations of 4% and 10%. Thus, lidocaine inhalation, with increasing concentrations of the aerosolized solution, increases initial bronchoconstriction while significant attenuation of bronchial hyper-reactivity is not further enhanced with increasing concentrations from 4 to 10%. Plasma concentrations of lidocaine were always far below the toxic threshold. In conclusion, when local anaesthesia of the airways is required a lidocaine dose of 2.0 mg kg-1 as a 4% solution can be recommended for local anaesthesia and attenuation of bronchial hyper-reactivity with the least airway irritation.     

Airway anesthesia alone does not explain attenuation of histamine-induced bronchospasm by local anesthetics: a comparison of lidocaine, ropivacaine, and dyclonine

BACKGROUND: Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity. METHODS: Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD. RESULTS: The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]). CONCLUSION: Both lidocaine and the new amide local anesthetic ropivacaine significantly attenuate histamine-induced bronchospasm. In contrast, dyclonine, despite its longer lasting and more intense local anesthesia, does not alter histamine-evoked bronchoconstriction and irritates the airways. Thus, airway anesthesia alone does not necessarily attenuate bronchial hyperreactivity. Other properties of inhaled local anesthetics may be responsible for attenuation of bronchial hyperreactivity.     

Lidocaine Induces a Reversible Decrease in Alveolar Epithelial Fluid Clearance in Rats

Background: Lidocaine is widely used in patients with acute cardiac disorders and has also been recently implicated as a possible cause of pulmonary edema after liposuction. The objective of this study was to assess the effect of lidocaine on alveolar fluid clearance, the primary mechanism responsible for the resolution of alveolar edema.

Methods: Alveolar fluid clearance was measured in 29 ventilated rats using our well-validated method over 1 h using a 5% albumin solution instilled into the distal air spaces of the lung. Lidocaine was added to the instilled albumin solution (10-5 m) or administered intravenously at a dose estimated to achieve a clinically relevant plasma concentration of 10-5 m. Standard agonists and antagonists were used to determine the effect of lidocaine on alveolar fluid clearance. To determine whether lidocaine acted predominantly on the apical or basal surface, we also used QX314, lidocaine n-ethyl bromide quaternary salt, an analog of lidocaine, which is unable to cross the alveolar epithelium. The effect of lidocaine on the apical epithelial sodium channel transfected in Xenopus oocytes was also studied.

Results: Alveolar or intravenous lidocaine decreased alveolar fluid clearance by 50%, an effect that was reversible with the [beta]2 agonist, terbutaline. Lidocaine acted predominantly on the basal surface of the epithelium because n-ethyl bromide quaternary salt decreased alveolar fluid clearance only when it was given intravenously and because lidocaine did not inhibit the apical epithelial sodium channel when expressed in oocytes.     

静脉注射利多卡因对哮喘患者气道张力和肺功能的影响

背景为防止哮喘患者发生反射性支气管痉挛，通常以局部麻醉药喷雾或静脉注射作为辅助用药。利多卡因可减轻气道对可增加气道张力的神经性刺激的反应性，但仍缺乏有关利多卡因对气道基础张力影响的相关报道。因此，本研究检验了静脉注射利多卡因对哮喘患者气道基础张力的影响。方法用计算机X线断层扫描技术对15例哮喘志愿者基础状态下和输注利多卡因时的小气道（2～5mm）、中气道（5—8mm）和大气道（〉8mm）进行扫描，以分析在基础状态和输注利多卡因时气道管腔直径和气道壁厚度的变化，以及利多卡因引起的肺功能的改变。结果利多卡因显著降低1秒钟用力呼气量（forced expiratory volume in 1s，FEV1）（7±2％，P=0．006）。与基础状态相比，输注利多卡因期间气道管腔直径缩小并具有统计学意义（-3±0．5％，P〈0．001）。而且，FEV1的变化与气道管腔直径变化之间呈明显相关（r^2=0．47，P=0．01）。结论尽管利多卡因能减低气道对刺激感觉神经致气道痉挛药物的反应性，却并不降低基础气道张力。相反，即便是静注利多卡因亦会导致气道张力增高和气道狭窄。因此，当使用利多卡因预防气管插管所致支气管痉挛时，应用听诊法保持对气道的监测，即使是静注利多卡因期间亦应如此。     

Lidocaine and increased respiratory resistance produced by ultrasonic aerosols.

Respiratory resistance significantly increased from 5.0 to 8.0 cm H2O/1/sec in anesthetized patients who were given ultrasonically nebulized water for 20 minutes via an endotracheal tube. Intravenous administration of lidocaine failed to reverse the provoked increase in resistance. In another group, respiratory resistance significantly increased from 5.8 to 7.5 cm H2O/1/sec in response to nebulized water despite prior and con-current intravenous administration of lidocaine. In a third group, initial respiratory resistance was 5.6 cm H2O/1/sec and did not increase during a 20-minute challenge with intratracheally administrered ultrasonically nebulized 2 per cent lidocaine. In a final group, resistance was increased from 5.0 to 6.9 cm H2O/1/sec with nebulized water. When challenge was continued with nebulized 2 per cent lidocaine, resistance remained elevated for about 10-12 minutes. It then decreased and returned to its initial control value at about 17 minutes, despite continuing lidocaine aerosol administration. Lidocaine, when administered intratracheally as an aerosol, both prevented and reversed provoked increases in respiratory resistance. Intravenously administered lidocaine was ineffective. Intratracheal administration of ultrasonically nebulized lidocaine might be another useful technique for management of bronchoconstriction in anesthetized patients.     

Lidocaine blood levels following aerosolization and intravenous administration.

STUDY OBJECTIVE: To determine whether, following aerosolization of lidocaine for topical airway anesthesia, intravenous (IV) lidocaine produces toxic lidocaine blood concentrations. DESIGN: Randomized, double-blind study. SETTING: University-affiliated hospital. PATIENTS: Forty healthy patients scheduled for outpatient surgery. INTERVENTIONS: The patients received in a randomized, double-blind manner aerosolized lidocaine or placebo followed 10 minutes later by IV lidocaine or placebo. MEASUREMENTS AND MAIN RESULTS: After completion of lidocaine or placebo aerosolization and 2 minutes following IV administration of either lidocaine or the placebo, venous blood samples were obtained. Lidocaine concentration was measured using a homogenous enzyme assay. The group receiving both aerosolized and IV placebo and the group receiving aerosolized lidocaine and an IV placebo had undetectable (less than 0.05 micrograms/ml) serum lidocaine levels. The groups that received either an aerosolized placebo or aerosolized lidocaine and IV lidocaine had similar serum lidocaine concentrations [3.34 +/- 0.46 vs. 3.24 +/- 0.55 micrograms/ml (mean +/- SEM); p greater than 0.05 by Mann-Whitney U test]. CONCLUSION: IV lidocaine can be safely administered following aerosolization of lidocaine in spontaneously breathing patients without producing toxic blood lidocaine concentrations.     

Intravenous Lidocaine and Bupivacaine Dose-dependently Attenuate Bronchial Hyperreactivity in Awake Volunteers

Background: In standard textbooks, intravenous lidocaine is recommended for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bronchial hyperreactivity in humans is unknown. Accordingly, nine awake volunteers with known bronchial hyperreactivity were subjected to an inhalational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double-blinded fashion.

Methods: Baseline acetylcholine threshold concentrations were determined 3-5 days before initiation of the investigation. The response to the acetylcholine challenge was defined as hyperreactive, if forced expiratory volume in 1 s decreased by at least 20%. In addition, the acetylcholine threshold for a 100% increase in airway resistance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30-min intravenous infusion period of three doses of lidocaine (1, 3, and 6 mg *symbol* min sup -1) or bupivacaine (0.25, 0.75, and 1.5 mg *symbol* min sup -1), during saline placebo infusion, respectively. Acetylcholine-threshold concentrations were presented with the respective plasma concentrations of the local anesthetic.

Results: The infusion of lidocaine and bupivacaine resulted in plasma concentrations (means+/-SD) of 0.29+/-0.11, 1.14 +/-0.39, and 2.02+/-0.5 micro gram *symbol* ml sup -1 for lidocaine and 0.11+/-0.04, 0.31+/-0.09, and 0.80 +/-0.18 micro gram *symbol* ml sup -1 for bupivacaine, respectively. Compared to baseline, the acetylcholine threshold for a 20% decrease of forced expiratory volume in 1 s as well as the threshold for a 100% increase in total airway resistance increased significantly with increasing plasma concentrations of both local anesthetics. Compared to placebo, acetylcholine threshold was almost quadrupled for lidocaine and tripled for bupivacaine with the highest plasma concentration of each local anesthetic.     

Lidocaine and Mexiletine Inhibit Mitochondrial Oxidation in Rat Ventricular Myocytes

Background: Accumulating evidence suggests that mitochondrial rather than sarcolemmal adenosine triphosphate-sensitive K+ (KATP) channels may have an important role in the protection of myocardium during ischemia. Because both lidocaine and mexiletine are frequently used antiarrhythmic drugs during myocardial ischemia, it is important to investigate whether they affect mitochondrial KATP channel activities.

Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. The authors measured flavoprotein fluorescence to evaluate mitochondrial redox state. Lidocaine or mexiletine was applied after administration of diazoxide (25 [mu]m), a selective mitochondrial KATP channel opener. The redox signal was normalized to the baseline flavoprotein fluorescence obtained during exposure to 2,4-dinitrophenol, a protonophore that uncouples respiration from ATP synthesis and collapses the mitochondrial potential.

Results: Diazoxide-induced oxidation of flavoproteins and the redox changes were inhibited by 5-hydroxydecanoic acid, a selective mitochondrial KATP channel blocker, suggesting that flavoprotein fluorescence can be used as an index of mitochondrial oxidation mediated by mitochondrial KATP channels. Lidocaine (10-3 to 10 mm) and mexiletine (10-3 to 10 mm) reduced oxidation of the mitochondrial matrix in a dose-dependent manner with an EC50 of 98 +/- 63 [mu]m for lidocaine and 107 +/- 89 [mu]m for mexiletine.     

Intravenous Lidocaine Attenuates Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits

Background: Neutrophils play a crucial role in the pathogenesis of acid-induced acute lung injury. Lidocaine inhibits the function of neutrophils. This study aimed to determine whether lidocaine attenuates acute lung injury induced by hydrochloric acid (HCl) instillation.

Methods: In study 1, rabbits were divided into four groups (n = 7 each). Lung injury was induced by intratracheal HCl (0.1 N, 3 ml/kg) in two groups. The other two groups received saline intratracheally. Lidocaine given intravenously (2 mg/kg bolus + 2 mg [center dot] kg-1 [center dot] h-1 infusion) was started 10 min before intratracheal instillation in one HCl and one saline group, and saline was given intravenously in the other two groups. In study 2, rabbits (four groups of seven animals each) received HCl (0.1 N, 3 ml/kg) intratracheally. Treatment with intravenous lidocaine was started 10 min before, 10 min after, or 30 min after acid instillation, or saline was given intravenously 10 min before instillation.

Results: In study 1, HCl caused deterioration of the partial pressure of oxygen (PaO2), lung leukosequestration, decreased lung compliance, and increased the lung wet-to-dry weight ratio and albumin, interleukin-6 (IL-6), and IL-8 levels in bronchoalveolar lavage fluid. Lidocaine pretreatment attenuated these changes. Hydrochloric acid increased superoxide anion production by neutrophils and caused morphologic lung damage, both of which were lessened by lidocaine. In study 2, lidocaine given 10 min after acid instillation was as effective as pretreatment in PaO2, lung mechanics, and histologic examination. However, PaO2 changes in lidocaine 30 min after injury were similar to those in saline given intravenously.     

Inhaled Albuterol, but Not Intravenous Lidocaine, Protects Against Intubation-induced Bronchoconstriction in Asthma

Background: The ability of intravenous lidocaine to prevent intubation-induced bronchospasm is unclear. The authors performed a prospective, randomized, double-blind, placebo-controlled trial to test the ability of intravenous lidocaine and inhaled albuterol to attenuate airway reactivity after tracheal intubation in asthmatic patients undergoing general anesthesia.

Methods: Sixty patients were randomized to receive either 1.5 mg/kg intravenous lidocaine or saline, 3 min before tracheal intubation. An additional 50 patients were randomized to receive 4 puffs of inhaled albuterol or placebo 15-20 min before tracheal intubation. Anesthesia was induced with propofol. Immediately after intubation and at 5-min intervals, transpulmonary pressure and airflow were recorded, and lower pulmonary resistance (RL) was calculated. Isoflurane was administered after the initial two measurements to assess reversibility of bronchoconstriction. A bronchoconstrictor response to intubation was defined as RL greater than or equal to 5 cm H2O [middle dot] l-1 [middle dot] s-1 in the first two measurements after intubation and RL subsequently decreasing by 50% or more after isoflurane.

Results: The lidocaine and placebo groups were not different in the peak RL before administration of isoflurane (8.2 cm H2O [middle dot] l-1 [middle dot] s-1vs. 7.6 cm H2O [middle dot] l-1 [middle dot] s-1) or frequency of airway response to intubation (lidocaine 6 of 30 vs. placebo 5 of 27). In contrast, the albuterol group had lower peak RL (5.3 cm H2O [middle dot] l-1 [middle dot] s-1vs. 8.9 cm H2O [middle dot] l-1 [middle dot] s-1;P < 0.05) and a lower frequency of airway response (1 of 25 vs. 8 of 23;P < 0.05) than the placebo group.     

Lack of Impact of Intravenous Lidocaine on Analgesia, Functional Recovery, and Nociceptive Pain Threshold after Total Hip Arthroplasty

Background: The analgesic effect of perioperative low doses of intravenous lidocaine has been demonstrated after abdominal surgery. This study aimed to evaluate whether a continuous intravenous low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty.

Methods: Sixty patients participated in this randomized double-blinded study. Patients received lidocaine 1% (lidocaine group) with a 1.5 mg/kg-1 intravenous bolus in 10 min followed by a 1.5 mg [middle dot] kg-1 [middle dot] h-1 intravenous infusion or saline (control group). These regimens were started 30 min before surgical incision and stopped 1h after skin closure. Lidocaine blood concentrations were measured at the end of administration. In both groups, postoperative analgesia was provided exclusively by patient-controlled intravenous morphine. Pain scores, morphine consumption, and operative hip flexion were recorded over 48 h. In addition, pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematically measured at 24 and 48 h.

Results: In comparison with the placebo, lidocaine did not induce any opioid-sparing effect during the first 24 h (median [25-75% interquartile range]; 17 mg [9-28] vs. 15 mg [8-23]; P = 0.54). There was no significant difference regarding the effects of lidocaine and placebo on pain score, pressure pain thresholds, extent in the area of hyperalgesia, and maximal degree of active hip flexion tolerated. Mean plasma lidocaine concentration was 2.1 +/- 0.4 [mu]g/ml.     

Intravenous Lidocaine Inhibits Visceral Nociceptive Reflexes and Spinal Neurons in the Rat

Background: Systemically administered local anesthetics and other sodium channel blockers produce analgesia in patients with hypersensitivity disorders. To assess whether these agents have a role in the treatment of visceral pain, the present study examined the effects of intravenous lidocaine on neuronal and reflex responses to colorectal distension.

Methods: In decerebrate, cervical spinal cord-transected male rats, the lumbosacral spinal cord was exposed by a laminectomy. Dorsal horn neurons demonstrating excitatory responses to colorectal distension were identified using microelectrodes. Sequential doses of lidocaine were administered intravenously. In chronically instrumented, unanesthetized rats, visceromotor responses, pressor responses, and increases in heart rate were elicited by colorectal distension and sequential doses of lidocaine.

Results: Intravenous lidocaine dose-dependently inhibited visceromotor and cardiovascular reflexes and the evoked and spontaneous activity of neurons excited by colorectal distension. There were statistically greater effects on one of the neuronal subgroups (sustained neurons) than on another subgroup (abrupt neurons.)     

Lidocaine sprayed down the endotracheal tube attenuates the airway-circulatory reflexes by local anesthesia during emergence and extubation

To determine whether lidocaine sprayed down the endotracheal tube (ETT) would attenuate airway-circulatory reflexes during emergence, we compared the reflex responses after endotracheal or IV lidocaine (IVL) in 75 patients receiving a standardized anesthetic protocol. At the end of surgery, the patients were divided into 3 groups (n = 25 for each group) and given no drug (Group 1), given 1 mg/kg of 2% lidocaine sprayed down the ETT 5 min before (Group 2), or given the same dose of IVL 3 min before extubation (Group 3). Blood pressure and heart rate were recorded at predetermined time points from 5 min (baseline) before until 5 min after extubation. The number of coughs per patient was continuously monitored during this period. The number (mean +/- SD) of coughs was decreased in Group 2 (4.5 +/- 3.7) compared with the control (10.2 +/- 6.0) (P < 0.01) with no difference for the control versus Group 3 (7.8 +/- 4.6). The increase in blood pressure was only attenuated immediately before extubation (P < 0.05), whereas the increase in heart rate was attenuated (P < 0.05) at all (except baseline) time points (P < 0.05) in Group 2 compared with the control with no difference for the control versus Group 3. The results indicate that lidocaine sprayed down the ETT suppresses the reflexes whereas using the same dose IVL does not, which is probably attributable to the mucosa-anesthetizing effect of lidocaine. IMPLICATIONS: Lidocaine sprayed down the endotracheal tube suppresses the airway-circulatory reflex responses whereas using the same dose IV lidocaine does not. This effect seems to be from the direct local anesthesia rather than from systemic absorption from the airway.     

Low-dose Lidocaine Suppresses Experimentally Induced Hyperalgesia in Humans

Background: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain.

Methods: In a first experimental trial, participants (n = 12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg [middle dot]-1 [middle dot] h-1 for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception.

Results: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments.