Lidocaine Levels Research Articles

Placental transfer of local anaesthetics in the premature sheep fetus

This study was designed to test whether there is any difference in the placental transfer of bupivacaine or lidocaine in the early compared to the late preterm maternal/fetal sheep preparation; and whether the premature lamb fetus reacts to a steady state local anaesthetic infusion differently from the same lamb near term. Eleven ewes were studied in two groups receiving bupivacaine (group A) or lidocaine (group B). Hysterotomy and insertion of fetal and maternal lines were performed at 110 days gestation, and studies were repeated weekly using the same local anaesthetic until delivery. We found no difference in maternal or fetal cardiovascular responses to bupivacaine or lidocaine in the early (mean 119 days) compared to the late (mean 132 days) preparations. The levels of bupivacaine and lidocaine in the fetal blood were similar in early and late fetuses, as were the fetal/maternal ratios of both drugs.

Local anesthesia in reduction mastoplasty for out-patient surgery.

To perform a breast reduction under local anesthesia we need a large amount of anesthetic with lasting effects. For this I use a solution of 25 cc of lidocaine, 25 cc of bupivacaine, and 1 cc of epinephrine in 350 cc of saline solution. The bupivacaine allows a 4-6-hour operation. Once the breast is infiltrated, a great amount of anesthetic is lost in the incision, in the dissection, and in the resected tissue. Thus, a low dose remains subcutaneously to be metabolized by the liver. The serum lidocaine levels are low during these operations, as demonstrated by fluorescence polarization immunoassay. Under analgesic sedation the submammary sulcus and the retroglandular space are infiltrated, blocking the perforants of the intercostal nerves, under the areola, beneath the skin where the incision is made and where the areola is placed. This procedure has been applied to many techniques of breast reduction by modifying the infiltration under the incision lines. For hypertrophy up to 1000 g, 200-300 cc of anesthetic solution is used for both breasts at one stage, while for gigantomastia, about 400 cc of anesthetic is used, infiltrating and reducing one after the other. As the blood loss is minimal and the recovery very fast, with an appropriate adhesive bandage and a "soutien," the patient could be discharged in the afternoon. Our experience includes 94 reduction mastoplasties with local anesthesia, and also 74 other mastoplasties with equally good results. There were no patient complaints and, in general, they felt very comfortable, awakening without pain or side effects.

Operative laparoscopy and postoperative pain relief

To evaluate the immediate postoperative pain and discomfort in patients who underwent operative laparoscopy under general anesthesia with or without peritoneal lidocaine and incisional bupivacaine instillations.Fifty-four participants were prospectively randomized to three groups: group I, intraperitoneal (IP) lidocaine + intraincisional bupivacaine; group II, intraincisional bupivacaine; and group III, no additional drugs after general anesthesia (controls).University Hospital, Reproductive Endocrinology and Infertility Clinics.Private patients needing operative laparoscopy.One hundred milligrams of lidocaine were instilled with the irrigation device into the peritoneal cavity at the completion of surgery. Twenty-five milligrams of bupivacaine were injected into infraumbilical and suprapubic incisions.The analgesic use and modified McGill Present Pain Intensity scores were used for pain evaluation.McGill Present Pain Intensity scores for pain, and narcotic use in the recovery room were less in IP lidocaine-instilled group of patients (P less than 0.05). The mean maximum plasma lidocaine level achieved was 1.01 +/- 0.25 micrograms/mL.Peritoneal lidocaine and incisional bupivacaine use in operative laparoscopy as described after general anesthesia is safe and effective in reducing postoperative pain in the recovery room.

Systemic lidocaine and human somatosensory-evoked potentials during sufentanil-isoflurane anaesthesia.

The effect of systemically administered lidocaine on somatosensory evoked potentials (SSEPs) during general anaesthesia has not been widely reported. Knowledge of the influence of anaesthetic agents on evoked potentials assists in interpreting evoked potential waveforms. Accordingly, we studied the behaviour of cortical and subcortical (recorded at the second cervical vertebra) SSEPs after administration of intravenous lidocaine (3 mg.kg-1 bolus followed by infusion at 4 mg.kg-1.hr-1) during a sufentanil-based anaesthetic regimen in 16 patients undergoing abdominal or orthopaedic surgery. When compared to awake baseline recordings, the sufentanil-nitrous oxide, low-dose isoflurane anaesthetic depressed N1 amplitude by approximately 40% and prolonged latency by 10%. Fifteen minutes after establishment of this anaesthetic, the amplitude and latency of N1 were 1.13 +/- 0.56 microV and 19.81 +/- 1.63 msec, respectively. Within five minutes of adding lidocaine, amplitude decreased further to 0.84 +/- 0.39 microV (P = 0.001), while latency was extended to 20.44 +/- 1.48 msec (P = 0.01). Lidocaine did not affect cervical amplitude and prolonged latency only minimally. Despite the observed effects on amplitude and latency, SSEP waveforms were preserved and interpretable. Plasma lidocaine levels obtained at 5, 20, and 40 minutes after lidocaine were 5.17 +/- 1.33, 3.76 +/- 1.14, and 3.66 +/- 0.9 micrograms.dl-1, respectively. Our results indicate that systemically administered lidocaine at therapeutic plasma levels acts synergistically with a sufentanil-based anaesthetic to depress the amplitude and prolong the latency of SSEPs.

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.

Experimental Studies of Transient Mass Transfer and Reaction in the Liver: Interpretation with a Heterogeneous Compartment Model

The uptake and metabolism of lipophilic compounds by the liver were studied by administering a model compound, lidocaine, to the isolated rat liver. Lidocaine was continuously infused into the liver until steady state was reached. Subsequent step changes in the inlet concentration were used to obtain information on rates of cellular uptake and release and to assess the extent of mixing within the organ. A simple heterogeneous model combining mass transfer and enzyme reactions was required to simulate the effluent levels of lidocaine and two primary metabolites, monoethylglycinexylidide and 3-hydroxylidocaine. The rate constants for uptake and release of lidocaine were 1200 and 46min1, respectively. The rate-limiting step was intracellular reaction, with a rate constant of 0.49min−1. Although the rate of lidocaine uptake was fast, it was 50 times slower than the rate of facilitated uptake of galactose, a fact suggesting passive transport of lidocaine between the tissue and the vasculature. The rates of mass transfer of lidocaine and its metabolites differed, but the ratios of the rate of uptake to the rate of release were the same. The results suggested that all three species had an affinity for the cellular region of the liver; concentrations in tissue were approximately five times greater than concentrations in effluent. Because of the large capacity of the organ for uptake of lidocaine and its metabolites, concentrations from washout experiments were controlled by linear mass transfer from the tissue. The transit time for flow across the sinusoids was very short relative to the time scales for elimination and interphase mass transfer; therefore, effluent concentrations were insensitive to mixing phenomena occurring in the liver vasculature. This model gives a mechanistic interpretation for the success of the well-mixed model for hepatic elimination.

Operative laparoscopy and postoperative pain relief

To evaluate the immediate postoperative pain and discomfort in patients who underwent operative laparoscopy under general anesthesia with or without peritoneal lidocaine and incisional bupivacaine instillations. Fifty-four participants were prospectively randomized to three groups: group I, intraperitoneal (IP) lidocaine + intraincisional bupivacaine; group II, intraincisional bupivacaine; and group III, no additional drugs after general anesthesia (controls). University Hospital, Reproductive Endocrinology and Infertility Clinics. Private patients needing operative laparoscopy. One hundred milligrams of lidocaine were instilled with the irrigation device into the peritoneal cavity at the completion of surgery. Twenty-five milligrams of bupivacaine were injected into infraumbilical and suprapubic incisions. The analgesic use and modified McGill Present Pain Intensity scores were used for pain evaluation. McGill Present Pain Intensity scores for pain, and narcotic use in the recovery room were less in IP lidocaine-instilled group of patients ( P < 0.05). The mean maximum plasma lidocaine level achieved was 1.01 ± 0.25 μ g/mL. Peritoneal lidocaine and incisional bupivacaine use in operative laparoscopy as described after general anesthesia is safe and effective in reducing postoperative pain in the recovery room.

Venous levels of lidocaine and bupivacaine after midtarsal ankle block.

No data are available on blood levels of local anesthetics after ankle block. Eighteen patients received 13 ml 2% lidocaine and ten received 30 ml 0.75% bupivacaine for unilateral or bilateral midtarsal ankle blocks, respectively. Blood levels were drawn at 15, 30, 45, 60, 90, 120, and 180 minutes after injections. All patients had forefoot surgery with elastic bandages (Esmarch) applied as a tourniquet immediately above the ankle intraoperatively. The mean peak level of lidocaine was 1.1 micrograms/ml, and of bupivacaine, 0.5 micrograms/ml. The mean duration of analgesia was 17 hours with 0.75% bupivacaine. Duration could not be assessed in the lidocaine group because these were ambulatory patients. The low peak level of local anesthesia and the prolonged analgesia confirmed the safety and efficacy of midtarsal ankle block for forefoot surgery and suggest that bupivacaine may be the local anesthetic agent of choice.

Preparation and evaluation of eudragit gels. V. Rectal gel preparations for sustained release and avoidance of first-pass metabolism of lidocaine.

The release of lidocaine from hydrogel and xerogel preparations was remarkably suppressed compared with polyethylene glycol (PEG) 2000 suppository. The release rate of lidocaine from hydrogel and xerogel increased with the increase in the amount of sodium hydroxide incorporated within the range of 3 to 7 milliequivalent (meq). After an oral administration of lidocaine HCl solution, the plasma concentration of lidocaine was considerably lower than that after intravenous administration for all time periods. The absolute bioavailability (F(oral)) was 5.63%. For the Witepsol S-55 and PEG 2000 suppositories, the plasma levels of lidocaine were higher than those for the oral preparation, and Cmax and area under the concentration-time curve (AUC) values significantly improved (p < 0.01). The absolute bioavailabilities were 21.3 and 29.6%, respectively. On the other hand, Eudispert hv-hydrogel and xerogel preparations showed the characteristics of a sustained-release preparation, especially the xerogel preparation with 5 meq NaOH. Absolute bioavailability for hydrogel and xerogel preparations increased significantly (p < 0.05) by approximately 1.7-3.4 folds compared with those of Witepsol S-55 and PEG 2000 suppositories.

Effects of lidocaine and verapamil on defibrillation in humans

Patients with automatic defibrillators frequently require chronic antiarrhythmic drug therapy or receive acute therapy with the onset of symptoms. The effects on energy requirements for defibrillation of lidocaine hydrochloride and verapamil hydrochloride, two commonly used antiarrhythmic agents, were examined in 20 successive patients undergoing corrective arrhythmia surgery. The minimum energy requirement for ventricular defibrillation before and 5 minutes after the administration of 150 mg of lidocaine intravenously (n = 8), or 10 minutes after 10 mg of verapamil intravenously (n = 12), were determined. Each patient was assigned to receive either verapamil or lidocaine. Three mesh coil defibrillating electrodes (Medtronic 6891, 6892) were sutured to the epicardium of the right and left ventricles. Ventricular fibrillation was induced using alternating current. After a minimum of 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. The preselected drug was then infused and the ventricular defibrillation energy was again determined after 5 or 10 minutes circulation time. Lidocaine did not alter the minimum energy for defibrillation (3.0 +/- 1.4 J vs. 3.0 +/- 1.8 J, mean +/- SD), despite plasma levels of lidocaine that averaged 13.2 +/- 1.9 mumol/l. In contrast, verapamil significantly increased (3.9 +/- 2.2 J vs. 6.5 +/- 2.9 J) the minimum energy necessary for defibrillation. The difference in defibrillation energy was significantly correlated to the fall in systolic blood pressure induced by verapamil administration (r = 0.72). These data reinforce the necessity for determining efficacy of defibrillation when medication changes are instituted. Verapamil should be used with caution in patients with automatic defibrillators and marginal defibrillation threshold.

Serum lidocaine and bupivacaine levels in local technique knee arthroscopy

We investigated serum levels of lidocaine and bupivacaine following their intraarticular and subcutaneous injection for anesthetic effect in local technique knee arthroscopy. Fifteen patients scheduled for knee arthroscopy, but who were otherwise healthy, were studied. Following preparation of the knee, 25 cc of 1% lidocaine with epinephrine (1:100,000) and 25 cc of 0.25% bupivacaine were instilled into the knee joint. An additional 40 cc of the combined solution was used to anesthetize four arthroscopic portal sites from the skin into the joint capsule. The arthroscopic procedure was then performed. We took blood samples 5, 15, 30, 60, and 120 minutes after intraarticular injection. High-performance liquid chromatography was used to determine serum values of the agents. Levels of the anesthetic agents in all of the patients at all time intervals were well within the ranges considered safe. Patient surveys of these and 49 other patients indicated a high degree of satisfaction with the technique. No complications from the anesthetic agents were noted at our hospital in over 500 similar cases. We conclude that local anesthesia as described here is a safe and effective alternative to conventional anesthetic techniques. Additionally, it can save time in the operating room and reduce patient costs.

Hyperthermic potentiation of BCNU toxicity in BCNU-resistant human glioma cells

Experimental evidence indicating potentiation of the cytotoxic effect of drugs at high temperatures suggests that the utilization of drug-heat combinations for gliomas of the brain might be therapeutically useful. Hyperthermia may increase the cytotoxicity of a particular drug in areas of low drug concentration/time and in cell populations resistant to the drug. We report in vitro experiments with a BCNU resistant, U-373MG, and a BCNU sensitive, U-87MG, human derived glioma cell lines under hyperthermic conditions. Temperatures equal or above 42 degrees C potentiate BCNU cell kill in both lines. The thermo-sensitizer lidocaine increases thermal cell kill but only minimally with concentrations corresponding to therapeutic plasma lidocaine levels. Within our experimental conditions, the best strategy to overcome BCNU resistance involved a combination of heat, BCNU and cis-DDP. BCNU resistant cells have no cross resistance to cis-DDP and the combination of BCNU and cis-DDP is synergistic. At modest hyperthermic conditions (42 degrees C) 99.4% BCNU resistant cells are killed by a combination of BCNU and cis-DDP at drug concentrations identical to plasma concentrations after standard IV doses. Clinical protocols using heat and drug may need to incorporate two or more drugs for optimal effects.

Absorption of lidocaine following topical application in microvascular procedures on rabbits

Fifty rabbits were used to investigate the absorption of lidocaine following its topical application to blood vessels. The lidocaine level in the blood was determined by gas chromatography and the enzyme immunoassay. Animals were divided into five groups according to anatomic site (femoral vs iliac) and according to whether vessels were intact or anastomosed. In the last group (E), a water-tight sleeve was placed on the anastomosed femoral artery so that the lidocaine contacted only a small segment of the artery. In each group, 0.4 and 1 ml of 10% lidocaine were used. Our results revealed that absorption of lidocaine from topical usage was rapid. The absorption peak occurred within 5-15 min. The serum concentration of lidocaine was significantly higher in groups with intact vessels than in those with anastomosed ones. The peak level of lidocaine in the serum occurred sooner in the iliac area than in the femoral area. Absorption in group E was very low due to only a small segment of the artery being immersed with lidocaine. The main absorption site of lidocaine was not through the vessel but through the perivascular area. Toxicity may develop clinically if a high concentration of lidocaine is applied on a vessel during microsurgery.

Prevention of succinylcholine-induced myalgia with lidocaine pretreatment.

We studied the effects of 3 mg.kg(-1) lidocaine iv on the succinylcholine (SCh)-induced myalgia in 94 unpremedicated ambulant patients undergoing dilatation and curettage of the uterus. The post-SCh myalgia was confirmed through interview by telephone. The data were correlated with the degree of fasciculation and changes in the serum electrolytes and creatine kinase (CK) levels following SCh administration. Pretreatment with lidocaine, 3 mg.kg(-1) iv, significantly reduced the incidence of myalgia from 40.4% of control group to 12.8% lidocaine-treated group, but not the CK levels. The severity of myalgia was not related to the intensity of fasciculation assessed by visual observation. The pretreatment with lidocaine had no untoward effect on the circulation, although the peak arterial and peak venous lidocaine levels achieved were 29.6 +/- 23 micro g.ml(-1) and 10.1 +/- 3.3 micro g.ml(-1) respectively. These finding indicated that the pretreatment with lidocaine, 3 mg.kg(-1) iv, was effective in prevention of SCh-induced myalgia.

An improved lidocaine infusion protocol for cardiac surgical patients

A new protocol for lidocaine administration was tested to determine whether it would provide higher free and total serum lidocaine concentrations during and after weaning from cardiopulmonary bypass (CPB), without leading to accumulation toxicity, than those resulting from a conventional protocol (1.5 mg/kg loading dose bolus + 2 mg/min infusion rate). Ten elective adult cardiac surgical patients were studied. Ten seconds prior to aortic cross-clamp release (0 min), each patient received a lidocaine bolus (1.5 mg/kg) and simultaneous lidocaine infusion (5 mg/min for 1 hour, followed by 2 mg/min for 23 hours). Weaning occurred 20 to 30 minutes after cross-clamp release. Lidocaine levels were determined from arterial blood samples at 0, 10, 20, 30, and 60 minutes, and at 2, 4, and 24 hours postcross-clamp release. Compared with the conventional protocol, the new protocol showed a significant increase in mean total lidocaine concentration ( P ⪯ 0.02) at 30 and 60 minutes, and a significant increase in mean free lidocaine concentration ( P ⪯ 0.005) at 20, 30, and 60 minutes. No patient had toxic levels at 24 hours. Results of this study suggest that in patients undergoing cardiac surgery, a “5 + 2” mg/min infusion protocol is safe and superior to a conventional protocol in achieving therapeutic serum levels of free and total lidocaine.

Lidocaine as a Topical Anesthetic for Bladder Biopsies

The views of the authors do not purport to reflect the position of the Army or the Department of Defense.The use of lidocaine as a topical anesthetic in bladder biopsies is described. Lidocaine was used in 7 patients undergoing random bladder biopsies and serum lidocaine levels were measured 7 to 10 minutes after instillation. Adequate pain control was noted in each patient with negligible serum lidocaine levels even in the face of denuded bladder mucosa.

Subcutaneous lidocaine for treatment of neuropathic cancer pain

Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 μg/ml for each patient.

Circulatory stability and plasma lidocaine levels during continuous and intermittent thoracic epidural analgesia.

Circulatory stability and plasma levels of lidocaine were investigated in 20 patients who received thoracic epidural analgesia with plain lidocaine during elective abdominal surgery under general anesthesia. In one group, bolus injection of 8 ml of 2% lidocaine was followed by volumetric continuous pump-driven infusion (CPI) of 8 ml of 1.5% lidocaine per hour. In the other group, the same initial bolus injection was followed by repetitive intermittent bolus infusions (RII) of 6 ml of 1.5% lidocaine at a 45 min-interval. Circulatory stability was evaluated by a discriminant function. The results showed that epidural analgesia produced smaller circulatory fluctuations with CPI than with RII. Venous plasma lidocaine levels were consistently higher with CPI than with RII. Plasma levels increased stepwise with RII and kept constant with CPI. Differences in plasma levels were significant from 20 min after the initial injection to 135 min. We therefore conclude that epidural analgesia with CPI is superior to that with RII. However, it must be remembered that higher plasma levels may occur with CPI than with RII.

Lidocaine toxicity after subcutaneous infiltration in children undergoing cardiac catheterization

The administration of subcutaneous lidocaine as a local anesthetic is readily observed in dental, orthopedic, and minor surgical procedures as well as for the insertion of monitoring catheters. The use of any local anesthetic presents significant risk to the patient, and extreme caution should be exercised in its administration 1. Significant complications resulting from lidocaine toxicity have been reported. 2–5 However, it is not well recognized that an elevated serum lidocaine level may result from the subcutaneous infiltration of lidocaine. Although the guidelines for the subcutaneous infiltration of lidocaine are established for children, these recommendations are often exceeded. In our study of 10 sequential patients, we describe 2 cases of lidocaine toxicity that occurred in children undergoing cardiac catheterization. This study was designed to determine if elevated serum lidocaine levels could occur after subcutaneous infiltration in children.

Effets de la lidocaïne sur la circulation artérielle et veineuse des membres chez l'homme

The effects of intravenous lidocaine on limb arteries and veins were investigated in a placebo-controlled study. Seven young healthy volunteers, 23 to 28 — years — old, were included. Electrocardiogram, arterial pressure and arm and leg blood flows were recorded continuously. Systolic and diastolic blood pressures were measured in the left arm by finger photoplethysmography. Limb blood flow and the limb venous system were studied by venous occlusive plethysmography. The venous parameters studied were venous tone, lowest closing pressure, venous volume at 30 mmHg, and venous distensibility. After an initial bolus of 1.5 mg · kg −1 lidocaine had been given, 30, and then 60, μg · kg −1 · min −1 were given for one hour each. Plasma noradrenaline and serum lidocaine titres were measured before giving the lidocaine, and at the end of each one hour period. Placebo consisted in a two hour infusion of 0.25 ml · min −1 normal saline. Lidocaine titres were 1.64 ± 0.40 μg · ml −1 after one hour, and 2.55 ± 0.69 μg · ml −1 after two hours. Lidocaine increased vascular resistances in both the forearm (+ 81 % to + 93 %) and the calf (+ 38 % to + 57 %). There was a concomitant increase in mean arterial blood pressure (+ 21 % to + 28 %) without any change in heart rate. There was a significant dose-dependent increase in plasma noradrenaline levels during the second period of the lidocaine infusion with respect to the preinfusion period and the same period during the placebo infusion. Venous capacitance measured before any infusion had been started was greater in the leg than in the arm. Lidocaine induced a progressive increase in forearm venous tone, which became significant during the period of higher infusion rate. There wasn't any change in calf venous tone. It would therefore seem that the arterial and venous effects of lidocaine which have been reported may be due to an increase in adrenergic tone. The vascular effects of therapeutic serum levels of lidocaine may contribute to the good cardiovascular tolerance of this drug, both as local anaesthetic agent, and as antiarrhythmic drug.