Plasma Lidocaine Concentrations Research Articles

Cutaneous ionto-phoretic application of condensed lidocaine

The purpose of this study was to determine whether iontophoretic application of high concentrations of lidocaine, with the same current, would produce cutaneous local anaesthesia rapidly enough for clinical practice. Twenty healthy volunteers, 17 male and three female, were selected for study. After five-minute or ten-minute iontophoresis using lidocaine 4, 10, 20, 30, 50%, we assessed the response to pin prick with a 27-gauge sterile needle inserted to the depth of 2 mm at five random locations in the iontophoretically-stimulated area. Also, plasma lidocaine concentrations were measured in the venous blood samples which had been taken from three male subjects, at 3, 10, and 30 min after iontophoresis with lidocaine 50%. The pain score after five-minute iontophoresis was higher than that after ten-minute iontophoresis, using each concentration of lidocaine (P < 0.001), whereas the pain scores had no correlation with lidocaine concentration within five-minute and ten-minute iontophoresis groups, respectively (P: NS). On the other hand, plasma lidocaine concentration was < 1.0 micrograms.ml-1 in all samples. No side effects other than erythema were observed after iontophoresis using high concentrations of lidocaine up to 50%. These results showed that by increasing the lidocaine concentration of the applied solution up to 50%, the application time of iontophoresis cannot be reduced from ten to five minutes without losing analgesic effect, although iontophoresis itself can be performed with safety.

Low plasma lidocaine concentration does not affect oxygen uptake at awakening from isoflurane anesthesia.

To clarify the effects of lidocaine in plasma after epidural administration on oxygen uptake (VO2) at awakening from isoflurane anesthesia, we measured VO2 in 45 patients undergoing abdominal hysterectomy under four conditions: control group, intravenous normal saline; epidural group, 3 mg/kg of 1.5% lidocaine epidurally as a bolus; and groups CIV-A and CIV-B, continuous intravenous infusion of 2% lidocaine, 0.5 and 1 mg/kg, respectively, for 5 min followed by 30 micrograms.kg-1 x min-1. VO2 at both periods of steady state during anesthesia before lidocaine administration and awakening from anesthesia were measured using a mass spectrometer system during spontaneous breathing. At awakening, VO2 in the control, CIV-A, and CIV-B groups increased significantly (P < 0.02) from 142 to 262-328 mL.min-1 x m-2 which as more (P < 0.01) than that in the epidural group which increased from 166 to 159 mL.min-1 x m-2. These results indicate that epidural lidocaine prevents the increase in VO2 associated with arousal from isoflurane anesthesia. This effect is not due to the absorbed plasma lidocaine but due to the epidural neural block.

Attenuation of arterial baroreflex control of renal sympathetic nerve activity during lidocaine infusion in alpha–chloralose–anesthetized dogso

The purpose of this study was to identify the relationship between sensitivity of arterial baroreflex and plasma concentrations of lidocaine. Using twelve mongrel dogs anesthetized with alpha-chloralose, the left kidney was exposed retroperitoneally, and renal sympathetic nerve activity was recorded continuously. Lidocaine was infused in four different doses: 2 mg.kg BW-1 bolus + 100 micrograms.BW-1 x min; 3 mg.kg BW-1 bolus + 200 micrograms.kg BW-1 x min; 6 mg.kg BW-1 bolus + 400 micrograms.kg BW-1 x min; and 12 mg.kg BW-1 + 800 micrograms.kg BW-1 x min. Baroreflex depressor and pressor tests using sodium nitroprusside (5-10 micrograms.kg-1) and phenylephrine (2-4 micrograms.kg-1) were performed before and at 10 min after beginning lidocaine infusion. Plasma lidocaine concentrations determined by high performance liquid chromatography revealed that the steady-state levels were maintained during the baroreflex tests. Baroreflex sensitivity was preserved at plasma concentrations of lidocaine below 5 micrograms.ml-1. However, cardiac and sympathetic baroreflex sensitivity were significantly attenuated (P < 0.01) when plasma lidocaine concentrations were well above human convulsion levels (10 micrograms.ml-1). The results indicate that hemodynamic derangement observed in the lidocaine-induced central nervous system toxicity is, at least in part, due to the attenuated arterial baroreflex.

Clonidine does not affect lidocaine seizure threshold in rats.

We investigated the effect of clonidine on intravenous (i.v.) lidocaine-induced haemodynamic changes and convulsions in awake rats. Wistar rats (200-250 g) were divided into three groups of eight and were pretreated with i.v. clonidine or normal saline 15 min before lidocaine infusion. Group 1 received normal saline; Group 2, 1 microgram.kg-1 clonidine; and Group 3, 10 micrograms.kg-1 clonidine. After surgical preparation and recovery from anaesthesia, all groups received a continuous i.v. infusion of lidocaine (15 mg.ml-1) at a rate of 4 mg.kg-1.min-1 until generalized convulsions occurred. Oxygenation was well maintained in all groups. Pretreatment with clonidine changed neither cumulative convulsant doses (Group 1: 41.8 +/- 2.2, Group 2: 43.8 +/- 2.6, Group 3: 42.3 +/- 2.0 mg.kg-1, respectively) nor plasma concentrations of lidocaine at the onset of convulsions (Group 1: 10.5 +/- 0.3, Group 2: 10.8 +/- 0.3, Group 3: 10.6 +/- 0.3 micrograms.ml-1, respectively). The mean arterial blood pressures in Groups 2 and 3 were decreased after clonidine pretreatment (Group 2: 93 +/- 1, P < 0.01, Group 3: 90 +/- 1%, P < 0.01, respectively) and they gradually increased during lidocaine infusion. The heart rates decreased after clonidine pretreatment (Group 2: 94 +/- 2, P < 0.05, Group 3: 86 +/- 2%, P < 0.01, respectively) and the combination of clonidine and lidocaine potentiated the bradycardic effect of lidocaine at a subconvulsant dose. Our results indicate that clonidine has neither anticonvulsant nor proconvulsant effects on lidocaine-induced convulsions. However, the interactions of clonidine and lidocaine on blood pressure and heart rate should be investigated further.

Effect of lidocaine onin Vivo hepatic function

Lidocaine is administered to assess donor or recipient liver function during hepatic transplantation. This study was performed to determine whether lidocaine administered at a constant concentration affected hepatic function or had demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were randomly allocated to receive either a two-stage infusion of lidocaine hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic portal venous and hepatic arterial blood flow readings made on animals anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for histological analysis and determination of adenine nucleotide status prior to and after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine concentration of 5.9 micrograms/ml was achieved during the second hour of infusion. There were no differences between the two groups in a large number of indices of hepatic function and plasma composition prior to and during the second hour of the respective infusions. Hepatic blood flow was also similar at these times. On histological examination there were no electron microscopic changes that could be specifically attributed to the administration of lidocaine. However, there were progressive changes with time. This study suggests that in anesthetized pigs a constant lidocaine concentration of about 6 micrograms/ml has no detrimental effect on hepatic function. Progressive hepatic ultrastructural changes occurred that could not be attributed to the administration of lidocaine. These may be the result of anesthetic administered or the surgery performed.

Tumescent Technique for Local Anesthesia Improves Safety in Large-Volume Liposuction

The tumescent technique for local anesthesia improves the safety of large-volume liposuction ( > or = 1500 ml of fat) by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia. Results of two prospective studies of large-volume liposuction using the tumescent technique are reported. In 112 patients, the mean lidocaine dosage was 33.3 mg/kg, the mean volume of aspirated material was 2657 ml, and the mean volume of supernatant fat was 1945 ml. The mean volume of whole blood aspirated by liposuction was 18.5 ml. For each 1000 ml of fat removed, 9.7 ml of whole blood was suctioned. In 31 large-volume liposuction patients treated in 1991, the mean difference between preoperative and 1-week postoperative hematocrits was -1.9 percent. The last 87 patients received no parenteral sedation. In a second study, a 75-kg woman received 35 mg/kg of lidocaine on two separate occasions, first without liposuction and 25 days later with liposuction; peak plasma lidocaine concentrations occurred at 14 and 11 hours after beginning the infiltration and were 2.37 and 1.86 micrograms/ml, respectively.

Pharmacokinetics and Technique of Endotracheal and Deep Endobronchial Lidocaine Administration

To determine absorption characteristics of endotracheal lidocaine, we administered lidocaine to hemodynamically stable patients by different techniques. Blood samples were taken for measurement of lidocaine plasma concentrations (fluorescence polarization immunoassay), and pharmacokinetics were calculated by regression analysis. Plasma concentrations at 1.5 and 2 min after drug administration were higher (P < 0.05) after instillation into the endotracheal tube (1.40 +/- 0.19 and 1.26 +/- 0.14 microgram/mL) than after deep endobronchial administration (1.00 +/- 0.08 and 0.83 +/- 0.05 microgram/mL). A biphasic absorption with a division of the area under the curve (AUCtot) into two parts (AUC1 and AUC2) could be assumed. After tube instillation, the AUC1/AUCtot ratio (2.6%) was higher (P < 0.05) than after deep endobronchial instillation (1.1%). To achieve high plasma concentrations within a short time, AUC1, representing a nearly instantaneous absorption, seems to be more important than AUC2, representing a higher but delayed absorption (depot effect). Because deep endobronchial lidocaine administration accentuated the late absorption, presumably by preventing drug distribution to the whole lung, this technique was detrimental to obtaining high plasma concentrations within a short period of time.

Neuropathic Pain in a Cancer Patient Responding to Subcutaneously Administered Lignocaine

To demonstrate difficulties encountered in alleviating neuropathic pain in a terminally ill cancer patient, with the very tentative diagnosis of postherpetic neuralgia. A multidisciplinary pain department in a university hospital. A patient with Hodgkin's lymphoma and leiomyosarcoma in the liver developed an unusual manifestation of neuropathic pain. Oral drug treatment with morphine associated with amitriptyline, valproic acid, mexilitine, flufenazine, and methylprednisolone failed to suppress pain attacks. Only the subcutaneous instillation of lidocaine (2 mg/kg/h) could partially suppress pain. A dorsal root entry zone lesion intervention could only temporary stop the pain attacks. Infiltration and nervous stimulation techniques were not helpful. In determining pain control, the visual analog scale rating scale and the number of attacks per hour were considered. Only the subcutaneous administration of lignocaine could partially suppress pain. Because of the patient's poor hepatic circulation, variable lidocaine plasma concentrations were responsible for intolerable side effects. Subcutaneous lignocaine administration remains a useful method in treating neuropathic cancer pain. The poor metabolic condition of the patient can lead to deleterious high plasma levels. A dorsal root entry zone lesion could only temporarily stop the pain.

Intravenous Lidocaine as a Suppressant of Coughing During Tracheal Intubation in Elderly Patients

The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 micrograms/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing.

Intravenous Lidocaine as a Suppressant of Coughing During Tracheal Intubation in Elderly Patients

The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 μg/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing. (Anesth Analg 1993;77:309-12)

Stellate Ganglion Blockade

In order to study the effect of epinephrine on the pharmacokinetics of lidocaine injected for stellate ganglion blockade, 6 patients free of hepatic or renal disease received 1.5 mg/kg of 1% lidocaine, with or without 1/200,000 epinephrine, injected via the anterior paratracheal approach. Using a crossover study design, each patient was investigated twice at least 4 days apart in a double-blind randomised manner. Venous blood samples were collected over 8 hours and plasma lidocaine concentrations were measured using gas liquid chromatography. There was no difference in time to block onset nor in quality of pain relief between the two solutions. No adverse events were observed in either group. The maximum concentration was significantly lower and the time to maximum concentration significantly delayed when epinephrine-containing solutions were used. In addition, the mean residence time was significantly longer when epinephrine was used. However, the difference in the elimination half-life was not statistically significant between the two treatment groups. It is concluded that epinephrine decreases the rate of absorption of lidocaine when injected for stellate ganglion blockade.

The effect of lidocaine dose and pretreated diazepam on cardiovascular system and plasma concentration of lidocaine in dogs ansthetized with halothane-nitrous oxide

Lidocaline if frequently administered as a component of an anesthetic : for local or regional nerve blocks, to mitigate the autonomic response to laryngoscopy and tracheal intubation, to suppress the cough reflex, and for antiarrythmic therapy. Diazepam dectease the potential central nervous system (CNS) toxicity of local anesthetic agents but may modify the sitmulant action of lidocaine in addition to their own cardiovascular depressant. The potential cardiovascular toxicity of local anesthetics may be enhanced by the concomitant administration of diazepam. This study was designed to investigate the effects of lidocaine dose and pretreated diazepam to cardiovascular system and plasma concentration of lidocaine. Lidocaine in 100 mcg/kg/min, 200 mcg/kg/min, and 300 mcg/kg/min was given by sequential infusion to dogs anesthetized with halothane-nitrous oxide (Group I). And in group II, after diazepam pretreatment, lidocaine was infused by same way when lidocaine was administered in 100 mcg/kg/min, the low plasma levels ( mcg/ml) caused a little reduction in cardiovascular hemodynamics. As administered in 200 mcg/kg/min, 300 mcg/kg/min, the higher plasma levels ( mcg/ml) reduced mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), left ventricular stroke work index (LVSWI), and right ventricular stroke work index (PVSWI) and increased pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), systemic vascular resistance index (SVRI), but was associated with little changes of heart rate (HR), mean pulmonary artery pressure (MPAP), and pulmonary vascular resistance index (PVRI). When lidocaine with pretreated diazepam was administered in 100 mcg/kg/min, the low plasma level, the lower level than when only lidocaine administered, reduced MAP, but was not changed other cardiovascular hemodynamics. While lidocaine was infused in 200 mcg/kg/min, 300 mcg/kg/min in dogs pretreated diazepam, the higher plasma level ( mcg/ml) was maintained and was associated with reduced CI, SI, LVSWI and incresed PAWP, CVP, SVRI but was a little changes of HR, MPAP, PVRI. After administeration, CI, SI, SVRI, LVSWI was recovered but PAWP, CVP was rather increased than recovered. The foregoing results demonstrate that pretreated diazepam imposes no additional burden on cardiovascular system when a infusion of large dose of lidocaine is given to dogs anesthetized with halothanenitrous oxide. But caution may be advised if the addition of lidocaine is indicated in subjects who have impared autonomic nervous system and who are in hypercarbic, hypoxic, or acidotic states.

Plasma Concentrations of Lidocaine Associated with Axillary Brachial Plexus Block

Brachial plexus block, axillary approach appears to be a safe and reliable technique for upper extremity surgery from shoulder to hand. However, the maximum dose of lidocaine that is recommended by the manufactured is 4 mg per kg (approximately 300 mg) regardless of the injection site. The maximum recommended dose for lidocaine with epinephrine is 7 mg per kg (approximately 500 mg). These maximum recommended amounts are insufficient for brachial plexus block. We question the logic behind these recommended dosages and may exceed them. The aim of this study was to determine whether commonly acceptable dosages used in brachial plexus block within a safe range. The time courses of the plasma concentration were observed in 20 healthy patients to whom were axillary injected with 1.5% lidocaine mixed 1: 200,000 epinephrine. The plasma concentrations were measured by immunofluororesence assay at the intervals of 5, 10, 20, 30 and 60 minutes. The values of plasma concentration were 2.65±75, 4.29±2.75, 5.95 ±2.02, 4.76±1.91 and 4.48±1.90 pg/ml in group 1, and 3.71±1.68, 4.76±1.91, 6.68±3.43, 5.57±3.08 and 5.56±2.86 ug/ml in group 2, and 2.86±1.82, 5.08±3.74, 5.92±3.84, 6.82±3.84 and 5.49±3.29 ug/ml in group 3 (Mean+SD). The peak plasma concentration was 5.95±2.02 and 6.68±3.43 ug/ml at 20 minutes in group 1 and 2 respectively and 6.82±3.84 ug/ml at 30 minutes in group 3. These results indicated that the lidocaine 750 mg with epinephrine (5 ug/ml) in brachial plexus block is considered to be safe because plasma concentration dose not exceed the toxic level.

Effects of flumazenil on intravenous lidocaine-induced convulsions and anticonvulsant property of diazepam in rats.

We investigated the effect of flumazenil on intravenous (IV) lidocaine-induced convulsions with and without diazepam pretreatment in rats. Wistar rats (200-250 g) were divided into four groups of seven each and were pretreated with IV diazepam or normal saline solution at 6 min and flumazenil or normal saline solution at 3 min before lidocaine infusion. The control group received normal saline solution; the diazepam group received 0.2 mg/kg of diazepam and normal saline solution; the diazepam+flumazenil group received 0.2 mg/kg of diazepam and 0.1 mg/kg of flumazenil; and the flumazenil group received normal saline solution and 0.1 mg/kg of flumazenil. After surgical preparation and recovery from anesthesia, all groups received a continuous IV infusion of lidocaine (15 mg/mL) at a rate of 4 mg.kg-1.min-1 until tonic/clonic convulsions occurred. The values of pH and blood gases were maintained within physiologic ranges. Heart rate was significantly decreased after 5 min of lidocaine infusion, but arterial blood pressure did not change until convulsions occurred in all groups. Pretreatment with diazepam alone increased both cumulative convulsant doses and plasma concentrations of lidocaine at the onset of convulsions. Flumazenil reversed these effects of diazepam. Pretreatment with flumazenil alone changed neither cumulative convulsant doses nor plasma concentrations of lidocaine at the onset of convulsions. Our data show that IV flumazenil reverses the anticonvulsant property of IV diazepam against lidocaine-induced convulsions and that flumazenil itself has no effect on lidocaine-induced convulsions in rats.

Therapeutic lidocaine concentrations have no effect on blood platelet function and plasma catecholamine levels.

The effects of therapeutic plasma concentrations of lidocaine on blood platelet function and plasma catecholamine levels were assessed in 9 healthy subjects. There were no significant effects on plasma levels of beta-thromboglobulin, collagen and adenosine diphosphate-stimulated platelet aggregation, thromboxane-B2-concentration in plasma after collagen and ADP stimulated platelet aggregation, or on plasma nor-adrenaline and adrenaline. No significant correlation could be demonstrated between any of the variables tested. Thus, it appeared that lidocaine had no effect on platelets that could be of benefit in acute myocardial infarction. It should be possible to use lidocaine, in combination with thrombolytic therapies without increasing the risk of bleeding complications.

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 Added Epinephrine on Plasma Concentration of Lidocaine Following Epidural Anesthesia

Effects of Added Epinephrine on Plasma Concentration of Lidocaine Following Epidural Anesthesia

Pregnancy Does Not Alter the Threshold for Lidocaine-Induced Seizures in the Rat

Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy-induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg.kg-1.min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 +/- 5.5, nonpregnant female = 12.1 +/- 4.9, pregnant female = 10.8 +/- 4.1 micrograms/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 +/- 6.3, nonpregnant female = 16.8 +/- 4.5, pregnant female = 16.7 +/- 4.2 micrograms/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats.

Changes of Plasma Concentration of Lidocaine Associated with Pediatric Caudal Anesthesia

Changes of Plasma Concentration of Lidocaine Associated with Pediatric Caudal Anesthesia

Endotracheal and endobronchial lidocaine administration

To compare four different methods of endotracheal lidocaine administration with respect to the site of administration. Randomized controlled trial. University hospital. Thirty-two female patients (43.6 +/- 11.5 years old) undergoing elective gynecologic operations with an anesthesiologic risk classification not higher than ASA II. All patients gave their written informed consent to participate in the study. Lidocaine at a dose of 2 mg/kg, diluted with normal saline to a total volume of 10 mL, was administered to eight patients by instilling the drug solution from a 10-mL syringe directly into the outer aperture of the endotracheal tube. All other study patients received lidocaine under bronchoscopic control through the work channel of the bronchoscope either a) deep endotracheally, b) into the right main bronchus, or c) into the right lower lobe bronchus. At 10 points in time after drug administration, blood samples were taken for measurement of lidocaine plasma concentration (using high-pressure liquid chromatography) and blood gas analysis. Therapeutic blood concentrations (greater than or equal to 1.4 micrograms/mL) could be achieved and toxic blood concentrations (greater than or equal to 6 micrograms/mL) could be avoided with all methods of administration. No significant difference was found between the different methods with regard to peak concentration, time to peak, onset and duration of therapeutic levels, or relative bioavailability. A significant (p less than .05) decrease in PaO2 to 75% of the baseline was seen with all methods used. Because no route of lidocaine administration was superior to the others, the simplest method (instillation into the endotracheal tube) should be used.