Blood Concentrations Of Lidocaine Research Articles

Treatment of the cutaneous pain of acute herpes zoster with 9% lidocaine (base) in petrolatum/paraffin ointment

Treatment of the pain of acute herpes zoster by local anesthetic injections has drawbacks. Topical percutaneous local anesthesia (TPLA) may offer another strategy of providing regional analgesia in affected patients. We evaluate the analgesic efficacy and safety of 9% (wt/vol) lidocaine (base) in petrolatum/paraffin ointment in patients with acute herpes zoster. Ointment was applied to the affected skin of 22 patients. Pain, tenderness, sensitivity to pinprick and cold, and blood lidocaine concentration were measured repeatedly during a 20-hour interval and intermittently thereafter. Mean pain, tenderness, and cutaneous sensation scores were reduced at measurements taken from 4 to 20 hours after ointment application (p < 0.05), but not every patient obtained relief. No patient had local skin irritation or systemic toxic effects related to the local anesthetic. TPLA is a promising therapy for control of cutaneous pain of acute herpes zoster. Controlled studies should be performed to prove efficacy, determine optimal TPLA formulation, and define dosage limits.

Effects of Epinephrine on Blood Concentration of Lidocaine and Epidural Block during Cesarean Section

Effects of Epinephrine on Blood Concentration of Lidocaine and Epidural Block during Cesarean Section

Blood Concentration of Lidocaine after Subarachnoid Administration

Blood Concentration of Lidocaine after Subarachnoid Administration

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 (<0.05 μg/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 μg/ml (mean ± SEM); p > 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.

Lidocaine for treatment of severe seizures in newborn infants. II. Blood concentrations of lidocaine and metabolites during intravenous infusion

The blood concentrations of lidocaine and its main active metabolites, methylethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in 24 newborn infants during anticonvulsive treatment with an iv infusion of lidocaine. After a bolus dose of 1.5-2.2 mg/kg and continuous infusion of lidocaine (4.7-6.3 mg/kg/h) there was accumulation of the drug and MEGX within 24 h. After termination of the iv infusion, both lidocaine and the metabolites were eliminated within 24-48 h. The anticonvulsive effectiveness--estimated by clinical observation and continuous amplitude integrated EEG monitoring (cerebral function monitor)--was immediate in 15 infants (nine term and six preterm). There was no correlation between blood concentrations of lidocaine and metabolites, and anticonvulsive effect (i.e. good, intermediate or no response). No differences in blood concentrations were found between full-term and preterm babies, or between infants with or without birth asphyxia. In combination with a fast withdrawal of the drug, few adverse reactions were seen with the dosages used, even though blood concentrations were high. Routine measurements of lidocaine concentrations during anticonvulsive treatment in neonates seem to be of little clinical value. For evaluation of the anticonvulsive effect and for early detection of seizure activity during lidocaine withdrawal, continuous EEG monitoring is preferable.

Venous blood concentration of lidocaine after nasopharyngeal application of 2% lidocaine gel.

In 34 subjects undergoing topical anaesthesia with lidocaine gel (2% xylocaine gel), the concentrations of lidocaine base were measured in repeated venous blood samples. Twenty-three patients (Group I) were given 20 ml of 2% lidocaine gel (400 mg of lidocaine) and six subjects (Group II) 40 ml of 2% lidocaine gel (800 mg of lidocaine) nasopharyngeally, the gel reaching the pharynx being swallowed. Five minutes after administration of the gel, a gastric tube was introduced via the nasal cavity. In six patients (Group III), the bladder was catheterised in addition to insertion of a gastric tube. Before the catheter was introduced, these patients were given lidocaine gel nasopharyngeally (400 mg) and endourethrally (400 mg). After the introduction of the gastric tube, all subjects (except four volunteers in Group II) were given general anaesthesia. Before intubation, the patients in Group III also received lidocaine spray laryngotracheally (50 mg; 10% xylocaine spray). The initial absorption of lidocaine was rapid, although the blood concentrations were low. The mean peak concentrations (Cmax) of lidocaine in the three groups were 0.57, 1.39 and 0.73 micrograms/ml, respectively. The blood concentration in Group II was significantly higher than those in Groups I and III. The mean length of time between the nasopharyngeal application of lidocaine gel and the time when Cmax was reached (tpeak) was the same in all three groups (60-70 min).(ABSTRACT TRUNCATED AT 250 WORDS)

抗不整脈薬リドカインのＢａｙｅｓｉａｎ ｍｅｔｈｏｄによる血中濃度予測法の検討

抗不整脈薬リドカインのＢａｙｅｓｉａｎ ｍｅｔｈｏｄによる血中濃度予測法の検討

The Influence of a Right-to-left Cardiac Shunt on Lidocaine Pharmacokinetics

The pharmacokinetics of lidocaine were studied in 1-2-month-old lambs with surgically created, intracardiac right-to-left shunts (RLS) and in age-matched control lambs. Shunts were prepared by anastomosing the pulmonary artery to the left atrial appendage to achieve arterial oxygen saturation of 65-75%. Catheters were implanted both in the right atrium for drug infusion and in the ascending aorta for blood sampling. Lidocaine, 1 mg/kg, injected as a rapid bolus, or 12 mg/kg, injected as a continuous infusion over 15 min, was delivered into the right atrium. Serial samples of arterial blood were obtained every 2.5 s for 1 min following the bolus injection and up to 4 h following the continuous infusion. Samples were analyzed for lidocaine by gas chromatography. Peak arterial whole blood concentration of lidocaine in the shunted animals was 37.0 +/- 2.1 micrograms/ml compared to 21.1 +/- 0.1 microgram/ml in the control animals; P less than .01. The peak arterial concentrations during the lidocaine infusion were 12.6 +/- 3.5 micrograms/ml in the RLS and 5.8 +/- 1.5 micrograms/ml in the controls. Total body clearance of lidocaine was decreased in the shunted animals to 30.7 +/- 13.2 ml.kg-1.min-1 from 68.1 +/- 12.1 ml.kg-1.min-1 in the control animals; P less than .001. The steady-state volume of distribution was also decreased in the shunted animals, 1.0 +/- 0.2 l/kg versus 2.0 +/- 0.7 l/kg in the controls; P less than .02. To induce convulsions 4.75 +/- 0.46 mg/kg of lidocaine was required in the shunted animals and 7.37 +/- 0.44 mg/kg in the control animals (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Lidocaine on Regional Blood Flows and Cardiac Output in the Non-Stressed and the Stressed Foetal Lamb

Lidocaine has been used in obstetrical anaesthesia for many years but there are still concerns about possible adverse affects of this drug on the foetus in utero. To examine in greater detail the effects of lidocaine in the foetus, the following two-part study was done. In Part A, seven pregnant ewes were surgically prepared with maternal and foetal arterial and venous catheters. After recovery from surgery lidocaine was infused intravenously, initially into the ewe and then into both ewe and foetus. Blood lidocaine concentrations were monitored and foetal regional blood flows were determined by the radioactive microsphere method. In Part B, 14 ewes were prepared as in Part A with the addition of an inflatable loop around the umbilical cord. During each study the loop was inflated to partially compress the cord and produce foetal acidosis. In all animals this cord compression was maintained for 30 minutes. In seven animals a lidocaine infusion was given, to examine the effect of lidocaine in the acidotic foetus. Organ blood flows were measured and cardiac outputs calculated. The normal foetuses in Part A showed no change in organ blood flow or cardiac output with arterial lidocaine concentrations of 1.5-3.4 mgsu-1 1. In the acidotic foetuses, lidocaine concentrations of 1.4-1.5 mg-ml-1 produced a tachycardia and an increase in cerebral blood flow compared to the control acidotic foetuses. There were no other significant changes. We conclude that arterial lidocaine concentrations of less than 3.5mg-m-l do notproduce significant alterations in organ blood flow in normal foetal lambs. A lidocaine concentration of 1.5 mg-ml-1 does not produce significant deterioration in acidotic foetuses.

The effect of lidocaine on regional blood flows and cardiac output in the non-stressed and the stressed foetal lamb.

Lidocaine has been used in obstetrical anaesthesia for many years but there are still concerns about possible adverse affects of this drug on the foetus in utero. To examine in greater detail the effects of lidocaine in the foetus, the following two-part study was done. In Part A, seven pregnant ewes were surgically prepared with maternal and foetal arterial and venous catheters. After recovery from surgery lidocaine was infused intravenously, initially into the ewe and then into both ewe and foetus. Blood lidocaine concentrations were monitored and foetal regional blood flows were determined by the radioactive microsphere method. In Part B, 14 ewes were prepared as in Part A with the addition of an inflatable loop around the umbilical cord. During each study the loop was inflated to partially compress the cord and produce foetal acidosis. In all animals this cord compression was maintained for 30 minutes. In seven animals a lidocaine infusion was given, to examine the effect of lidocaine in the acidotic foetus. Organ blood flows were measured and cardiac outputs calculated. The normal foetuses in Part A showed no change in organ blood flow or cardiac output with arterial lidocaine concentrations of 1.5-3.4 mg X ml-1. In the acidotic foetuses, lidocaine concentrations of 1.4-1.5 mg X ml-1 produced a tachycardia and an increase in cerebral blood flow compared to the control acidotic foetuses. There were no other significant changes. We conclude that arterial lidocaine concentrations of less than 3.5 mg X ml-1 do not produce significant alterations in organ blood flow in normal foetal lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Antifibrillatory effects of lidocaine and bretylium immediately postcardiopulmonary resuscitation

The antifibrillatory effects of lidocaine and bretylium in the postcardiopulmonary resuscitation (CPR) setting were examined using ventricular fibrillation threshold (VFT) determinations in anesthetized dogs. The dogs were fibrillated and CPR was carried out with a pneumatic device. Lidocaine and bretylium were administered intravenously at the onset of CPR, and VFT was serially determined after defibrillation following three consecutive 3-minute CPR periods. A dose of 2 mg/kg of lidocaine caused a significant increase in VFT determinations after the first but not subsequent 3-minute CPR periods; a dose of 1 mg/kg of lidocaine was ineffective at any time point. A dose of 5 mg/kg of bretylium elevated the VFT after the second and third but not the first 3-minute period. In dogs who received lidocaine, a significant elevation of VFT determinations were found to be associated with a high blood lidocaine concentration (mean 13.8 ± 8.3 μg/ml). The present study demonstrates that a 2 mg/kg dose of lidocaine administered during CPR rapidly increases VFT determinations after CPR (within 5 minutes), whereas, a 5 mg/kg dose of bretylium significantly elevates VFT determinations but at a later time (within 10 minutes). The observed significant effect of lidocaine appears to be associated with high lidocaine blood concentrations (>6 μg/ml).

Motor paralysis increases brain uptake of lidocaine during status epilepticus.

The effect of pH on brain uptake of lidocaine during status epilepticus was studied by comparing blood and brain lidocaine concentrations and pH in paralyzed and nonparalyzed rats during pentylenetetrazol-induced status. Status produced both brain and blood acidosis; paralysis prevented the blood acidosis. Both brain and blood lidocaine concentrations were increased in the status animals. The increase in brain lidocaine was greatest (10-fold over control) in animals paralyzed during status. These findings probably reflect the fall in brain and blood pH during status affecting the partitioning of the weak base lidocaine (pKa 7.86). Paralysis prevents blood, but not brain, acidosis, thereby maximizing the pH gradient and partitioning of lidocaine into the brain.

Pharmacokinetics of lidocaine and its deethylated metabolite: dose and time dependency studies in man.

The concentrations of lidocaine and of its deethylated metabolite, MEGX, were measured in blood following the intravenous administration of 50 and 100 mg lidocaine hydrochloride, the oral administration of 100, 300, and 500 mg lidocaine hydrochloride monohydrate, and the oral administration of 300 mg lidocaine hydrochloride monohydrate every 8 h for seven doses, to three healthy volunteers. The range of values for the parameters defining the disposition kinetics of lidocaine were: terminal half-life, 50-231 min; total clearance, 13-17 ml/min/kg; initial dilution space, 0.13-2.5 liters/kg; and volume of distribution at steady state, 0.6-4.5 liters/kg. Lidocaine absorption from solution was rapid, but due to presystemic hepatic metabolism, the availability was low, the range of average values lying between 0.19 and 0.38. No dose or time dependency in lidocaine and monoethylglycinexylidide pharmacokinetics following the single dose studies of lidocaine were noted. Effective hepatic blood flow, based on total clearance and availability measurements, was estimated to be 18-27 ml/min/kg. The concentrations of MEGX were approximately one-third of those of lidocaine following intravenous lidocaine and were comparable following oral lidocaine, but as predicted, the dose normalized area under the MEGX concentration-time curve was constant and independent of the route of administration of lidocaine. In two subjects, the blood concentrations of lidocaine and MEGX following multiple doses of oral lidocaine were those predicted from the single dose studies. In the third subject, the degree of accumulation of lidocaine was greater than predicted. The reasons and mechanism for this difference between subjects on multiple dosing remains unclear.

Blood Concentration of Lidocaine After Spinal Anaesthesia Using Lidocaine and Lidocaine with Adrenaline

Blood Concentration of Lidocaine After Spinal Anaesthesia Using Lidocaine and Lidocaine with Adrenaline

The effects of lidocaine on the whole body distribution of radioactively labeled microspheres in the conscious rat.

Radioactively labeled 15-micrometer microspheres were used to evaluate the effects of intravenous lidocaine on cardiac output and distribution of tissue blood flow in awake rats. After a one-hour control period, all animals (n = 22) received 85Sr-labeled microspheres for a control measurement. The animals were then divided into three groups. The control group (n = 6) received a bolus of saline and then an infusion of saline. After 40 minutes, a second microsphere (141Ce) was injected, the animals killed, and tissue blood flow determined. A second group of rats (n = 8) were similarly treated except that they received a bolus and infusion of lidocaine resulting in a plasma concentration of 1.98 +/- 0.3 microgram of lidocaine/ml. A third group of rats (n = 8) received a higher dose of lidocaine which resulted in a plasma concentration of 6.37 +/- 0.3 microgram of lidocaine/ml. In the control and low-dose lidocaine group, there were no changes in blood pressure, heart rate, cardiac output or tissue blood flow. At the higher lidocaine concentration, blood pressure remained the same but cardiac output and heart rate were decreased. Tissue blood flow to brain, heart and muscle was responsible for the increased peripheral resistance. These results suggest that high blood concentrations of lidocaine alter flow to vital organs in the rat.

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

The venous blood concentration of lidocaine 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 five intubated patients under general anaesthesia. The peak level of lidocaine (about 1 microgram)ml/occurred 20--30 min after spraying in the bronchography group, while there was a level plateau at about 0.5 microgram/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 micrograms/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.

Toxicity and distribution of lidocaine in nonasphyxiated and asphyxiated baboon fetuses.

The dosage and blood concentration of lidocaine required to produce central nervous and cardiovascular system toxicity in both nonasphyxiated and asphyxiated fetuses were determined in ten pregnant baboons with fetuses of average gestation of 158 days (term, 185 days). Lidocaine was infused into the fetal jugular vein until cardiac arrest occurred, following which fetal brain, heart, lungs liver and kidneys were obtained. Mean dosage and blood concentration of lidocaine associated with seizures were 9.4 mg/kg and 15.2 micrograms/ml, respectively, in the nonasphyxiated fetuses, and 3.9 mg/kg and 5.6 micrograms/ml, respectively, in the asphyxiated ones. The dosage and blood concentration of the drug required to produce cardiac arrest were significantly higher in the nonasphyxiated group (35 mg/kg and 269 micrograms/ml, respectively) compared to the sphyxiated group (9 mg/kg and 40 micrograms/ml, respectively). Tissue-plasma ratios of lidocaine were significantly higher (P less than 0.05) in the brain, heart, and liver of the asphyxiated fetuses as compared with the nonasphyxiated ones. The relative proportion of the injected dose found in the organs was also higher (P less than 0.05) in the asphyxiated group. These results indicate that the increased sensitivity of the asphyxiated fetus to lidocaine may be related in part to a greater uptake of local anesthetics by the fetal organs.

Rectal bioavailability of lidocaine in rats: Absence of significant first-pass elimination

Drugs administered rectally generally are considered to enter the systemic circulation without passing first through the liver since the lower hemorrhoidal veins do not drain into the portal system. To test this hypothesis, the systemic availability of the high clearance drug lidocaine was investigated in rats following oral (20mg) and rectal (20mg) administration to six rats and intraarterial (5mg) administration to another six rats. Whole blood concentrations of lidocaine were determined by capillary GLC with nitrogen detection. Systemic availability was evaluated by two methods. For the rectal route, the results were 105.6 ± 43.3 and 83.1 ± 22.3% compared to those for intraarterial administration; for the oral route, these values were 7.7 ± 2.3 and 7.1 ± 2.3%. These results clearly indicate a significant bypass of the liver following rectal administration of lidocaine. Mean elimination half-lives following oral (54 ± 9 min) and rectal (79 ± 36 min) administration were not significantly different; however, rectal elimination half-lives sometimes were slightly prolonged. The mean peak concentration times of 11.5 ± 7.5 (oral) and 15.6 ± 10.6 (rectal) min were not significantly different whereas the mean peak concentrations were significantly different (p < 0.01) [0.92 ± 0.49 (oral) and 8.71 ± 3.30 (rectal) μg/ml]. The mean elimination half-life following intraarterial administration (33 ± 3 min) was significantly shorter than both the mean oral and rectal half-lives, and the calculated total blood clearance of lidocaine had an average value of 36 ± 9ml/min. The results show that it is possible to bypass the liver, at least partially, when giving a high clearance drug rectally to rats. For lidocaine, this bypass is almost complete.

Lidocaine concentration in blood after topical anaesthesia of the upper respiratory tract.

The venous blood concentration of lidocaine 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 five intubated patients under general anaesthesia. The peak level of lidocaine (about 1 microgram)ml/occurred 20--30 min after spraying in the bronchography group, while there was a level plateau at about 0.5 microgram/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 micrograms/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.

Therapeutic blood lidocaine concentrations after local anesthesia for cardiac electrophysiologic studies.

CLINICAL cardiac electrophysiologic studies are performed to evaluate mechanisms of arrhythmias and their response to therapy.1 2 3 4 5 6 7 8 9 10 Lidocaine, injected to provide local anesthesia before insertion of the electrode catheter, can affect the results of such studies if substantial blood concentrations are achieved. This study was designed to measure lidocaine concentrations in patients undergoing cardiac electrophysiologic studies.Materials and MethodsSeventeen patients were studied after written informed consent was obtained. Lidocaine solution (1 per cent, without epinephrine) was injected subcutaneously into one or both groins before insertion of two to four transvenous electrode catheters. Intravascular injection was avoided by aspiration before each . . .