Plasma Bupivacaine Research Articles

Use of an orbital epidural catheter to control pain after orbital implant surgery.

The surgical placement of orbital implants for eviscerations, enucleations, and secondary implantations can cause severe postoperative pain that may not be relieved with high doses of narcotics. We analyzed the effectiveness of a method for postoperative pain control in orbital implant surgery using an orbital epidural pain catheter connected to a patient-controlled analgesia bupivacaine hydrochloride pump. One hundred nineteen patients undergoing orbital hydroxyapatite implant surgery received placement of an orbital epidural catheter for the infusion of local anesthetics at the conclusion of their surgery. Patients were asked to gauge their level of comfort into the following 3 categories: total, some, or no pain relief in the first week after surgery. A separate numerical grading scale was used to further quantitate pain. Blood samples were collected in 4 patients to assess the systemic levels of bupivacaine. Most patients (88.2%) responded with total or some pain relief, with only 11.8% suffering severe pain. The mean numerical pain score was 2.8, within a range of 0 (no pain) to 10 (severe pain). The average plasma bupivacaine level in the 4 patients in whom this was measured was 0.38 microg/mL, which is well below the toxic level of 4.0 microg/mL. Furthermore, there were only 5 minor complications caused by the catheters, ie, 1 retrobulbar hemorrhage and 4 catheters that did not work. No permanent problems arose from any of the complications. The orbital epidural pain catheter is an effective means to achieve postoperative pain control after orbital implant surgery. The simple technique of insertion and management of the catheters was well tolerated in our patient population.

Simultaneous analysis of ketamine and bupivacaine in plasma by high-performance liquid chromatography

A reversed-phase HPLC technique for the simultaneous measurement of both bupivacaine and ketamine in plasma is described. Plasma samples (0.5 ml) were prepared using a rapid and simple back-extraction technique. Resolution of both analytes and the internal standard, desipramine, from medicines coadministered to surgical paediatric patients was obtained using a 5 μm cyano (CN) (250×4.6 mm) column and a mobile phase comprising methanol–acetonitrile–orthophosphoric acid–0.01 M sodium dihydrogenphosphate (200:80:2:718). Good sensitivity for both analytes was observed using UV detection at a wavelength of 215 nm. The method has been validated according to the criteria established by the Journal of Chromatography B.

The use of interpleural analgesia using bupivacaine for pain relief in advanced cancer.

The use of interpleural analgesia is described in six patients with a variety of advanced malignancies suffering from pain uncontrolled by opioids. The benefits and complications of the technique are discussed including management of the catheters at home and the measurement of plasma bupivacaine concentrations. Interpleural analgesia can provide good analgesia in a small, selected population of patients with otherwise uncontrolled pain of malignant origin.

EPIDURAL EPINEPHRINE INFUSION COMBINED WITH BUPIVACAINE MAY INCREASE BLOOD LOSS DURING LABOR AND DELIVERY

S261 INTRODUCTION: Epidural epinephrine in addition to a local anesthetic can decrease the maternal and fetal peak plasma concentrations of the local anesthetics in obstetrics patients. However, it has been reported that epinephrine containing solution administered into the epidural space decreases uterine activity due to the mimetic agonist effect. Therefore, we examined the effects of epidural epinephrine on the uterine and umbilical blood flow resistance with ultrasonography. We also evaluated the plasma bupivacaine concentrations in mother and fetus, and blood loss during labor and delivery. METHODS: Twenty-eight parturients whose pregnancies were without obstetric problems were enrolled in this study. This study protocol was approved by our hospital's investigation committee on ethics and informed consent was obtained from each patient the day before the study. Labor was induced electively by constant oxytocin infusion under lumber epidural anesthesia. Pregnant women were randomly assigned into two groups after the epidural administration of a bolus of 12ml plus 4ml/hr bupivacaine 0.25% with or without epinephrine (1:200,000). If patients requested additional local anesthetic because of labor pain, we added 6-10 ml of 1% lidocaine. Before induction of epidural analgesia and 20, 60 and 120 min after the first epidural bolus injection, resistance indices of the fetal umbilical artery and the uterine artery were measured with a percutaneous ultrasonography. We also measured the maternal and fetal plasma concentrations of bupivacaine at birth using high performance lipid chromatography, and blood loss during labor and delivery. Data were analyzed using Mann-Whitney U-tests (statistical significance, p<0.05). RESULTS: The resistance index of uterine artery 20 min after bolus injection of bupivacaine was significantly different between the two groups (0.53 +/- 0.08 with epinephrine vs. 0.66 +/- 0.11 without epinephrine, mean +/- SD). However, the resistance indices of fetal umbilical and uterine artery 60 and 120 min after bolus injection of bupivacaine were not significantly different between the two groups. There was also no differences in fetal/maternal bupivacaine concentration ratios between the two groups (0.35 +/- 0.22 with epinephrine vs. 0.41 +/- 0.40 without epinephrine, mean +/- SD). However, the blood loss in the group with epinephrine was significantly more than that without epinephrine (338 +/- 185 g vs. 169 +/- 77 g, mean +/- SD). DISCUSSION: A significant finding of this study was that epidural epinephrine administration combined with bupivacaine increased blood loss during labor and delivery. This may be due to vasodilation caused by the mimetic effects low dose epinephrine (20 [micro sign]g/hr). The utero-placental blood flow resistance was not different between the two groups except for the uterine artery resistance 20 min after bolus injection of bupivacaine. Our results suggest that the low dose epidural epinephrine does not significantly deteriorate uterine activity but may increase blood loss during delivery.

Prolonged intercostal nerve blockade in sheep using controlled-release of bupivacaine and dexamethasone from polymer microspheres.

Previous work from the authors' group characterized a prolonged percutaneous blockade of the sciatic nerve in rats using bupivacaine-dexamethasone microspheres. The goals of the current study are to examine the (1) efficacy of bupivacaine microspheres with and without dexamethasone for intercostal blockade in sheep; (2) scaling of dose and duration with a 100-fold increase in body size from rats to sheep; (3) local toxicity and adverse systemic reactions to bupivacaine microspheres with and without dexamethasone. Intercostal blocks were performed percutaneously in sedated sheep. Sensory blockade was measured at repeated time points by absent flinch response to skin pinch. Plasma bupivacaine concentrations were measured using high performance liquid chromatography. Chest wall specimens were examined by light microscopy. The duration of intercostal blockade increased with bupivacaine dose for animals receiving from 8 to 80 mg/kg of microspheres with and without dexamethasone. At each dose, microspheres containing dexamethasone had a longer duration of block than microspheres without dexamethasone. From 8 to 80 mg/kg, the mean duration of block with bupivacaine-dexamethasone microspheres increased from 4 to 13 days. Plasma concentrations of bupivacaine remained 10-fold below the convulsive EC50 concentration for sheep. Chest wall histology showed a significant granulomatous reaction around bupivacaine microspheres but not around bupivacaine-dexamethasone microspheres. A single administration of bupivacaine-dexamethasone microspheres produces an effective chest wall analgesia of several days' duration. This may prove useful clinically for thoracic surgery or trauma.

Maternal, fetal and placental distribution of lidocaineepinephrine and bupivacaine after epidural administration for cesarean section

Bupivacaine and lidocaine are both lipophilic drugs, bupivacaine being more lipophilic and protein-bound. Our earlier studies, using human placenta perfused in vitro, showed that increased placental binding of bupivacaine restricts fetal transfer compared to the higher fetal transfer of lidocaine. However, placental tissue concentrations of local anesthetics have not been determined in the clinical context. Term parturients were randomized to receive either 2% lidocaine-epinephrine (n = 10) or 0.5% bupivacaine (n = 10) through a lumbar epidural catheter for elective cesarean section. Total drug concentrations of lidocaine and bupivacaine in maternal and umbilical plasma and placental tissue were determined. There was a higher incidence of maternal hypotension in the lidocaine-epinephrine group than in the bupivacaine group ( 7 10 vs 1 10 , P < 0.05). At delivery, fetal/maternal ratios for total concentrations of lidocaine and bupivacaine were similar (0.49 vs 0.42). The mean placental tissue/maternal plasma concentration ratio of lidocaine was higher than that of bupivacaine (1.45 vs 1.01, P < 0.05). The mean amount of the drug retained in the placenta per unit of dose (mg/kg) was also higher in the lidocaine-epinephrine group, although this difference did not reach statistical significance (0.46 mg/unit dose vs 0.40 mg/unit dose). Values for area under the concentration-time curves per unit of dose were similar. In conclusion, maternal plasma concentrations, fetal/maternal concentration ratios and placental tissue binding of lidocaine resembled those of bupivacaine after epidural administration. These findings are probably explainable by the effect of maternal hypotension on the distribution of lidocaine.

PLASMA BUPIVACAINE LEVELS FOLLOWING CONTINUOUS FEMORAL THREE IN ONE BLOCK

S329 INTRODUCTION: The purpose of this study was to compare levels of bupivacaine and its metabolites following continuous infusion of bupivacaine via femoral 3 in 1 catheter after knee arthroplasty. METHODS: After IRB approval and informed written consent 13 patients scheduled for elective knee arthroplasty had femoral catheters inserted using a peripheral nerve stimulator. They were randomized to receive either 0.1 or 0.2% bupivacaine. After an initial bolus of 30 all patients received an infusion at a rate of 10 ml/h for 48 hours. Venous blood samples were drawn for measurement of bupivacaine and its metabolites, 30 min after the initial bolus, and daily for 3 days. Levels were measured using high performance liquid chromatography with reversed phase column (RPDB 18 Supelco[registered sign]). Gradient elution of acetonitryl acid phosphate buffer (pH 2.4). Wavelength of light used was 205 nm. Liquid extraction of a mixture of cyclohexane and dichloromethane was performed using mepivacaine as an internal standard. RESULTS: (Table 1)Table 1DISCUSSION: Following femoral catheter infusions a dose dependent increase in plasma bupivacaine levels are noted. The levels increase with time but do not exceed toxic levels. The highest level observed was 3.3mcg/ml. The levels of desbutylbupivacaine also increase with continuous infusion. With these levels no clinical evidence of local anesthetic toxicity was observed.

Bupivacaine-induced convulsion is suppressed by MK-801

Background and Objectives. Not only the facilitation of inhibitory synapses but also the suppression of excitatory synapses may be effective in treating convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and hemodynamic changes were studied. Methods. Cortex and hippocampal (A4; L5.5; H8) electroencephalogram (EEG), heart rate, and mean arterial pressure were measured in 21 cats anesthetized with urethane. Blood samples were obtained when cats demonstrated arrhythmias, convulsed, and became hypotensive. In the control group (n = 7), bupivacaine was continuously infused until a hypotensive state of 40 mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously 15 minutes before the bupivacaine injection. In the MK-801 treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the appearance of convulsive EEG after the bupivacaine injection. Results. Bupivacaine produced convulsion in the control group (17.1 ± 2.4 μg/mL), but not in the MK-801 pretreated group. In the treatment group, convulsive EEG was suppressed gradually after injection of MK-801. The mean plasma bupivacaine concentrations (μg/mL) reaching arrhythmia and hypotension were 9.5 ± 2.9 and 23.0 ± 3.0, respectively, in the control group; 10.9 ± 3.5 and 22.5 ± 4.9, respectively, in the MK-801 pretreated group; and 7.5 ± 1.6 and 21.0 ± 3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and heart rate did not differ among the three groups. Conclusions. These results demonstrated that one mechanism of bupivacaine-induced convulsion is the excitatory neurotransmitter system in central nervous system and that MK-801 is effective in suppressing the convulsion without any effects on hemodynamics.

Continuous cervical epidural anesthesia in reconstructive hand surgery

Continuous cervical epidural anesthesia was used for 17 operations in 16 patients undergoing immediate reconstructive surgery after upper-extremity injuries or tumor resection and was continued for postoperative pain management. Routine hemodynamics, arterial blood gases, plasma bupivacaine levels, and skin temperatures were recorded before and after the block. The surgery time ranged from 3 to 18 hours. Postoperative pain management was maintained for up to 6 days. The blocks were adequate for surgery and postoperative pain treatment in all cases. There were no signs or symptoms indicating local anesthetic toxicity. Circulatory and respiratory integrity was well maintained. The patients were all ambulatory the day after surgery and could start physiotherapy immediately. This regional anesthesia technique may have significant advantages over branchial plexus block or general anesthesia for lengthy surgical procedures of the upper extremity.

Continuous axillary brachial plexus block for postoperative pain relief: Intermittent bolus versus continuous infusion

The aim of this study was to compare the efficacy and safety of continuous axillary brachial plexus block by infusion and by intermittent injection of bupivacaine 0.25% in the management of postoperative pain. Two methods of continuous axillary brachial plexus block for pain management were compared in a prospective randomized trial. Twenty 16- to 62-year-old male patients (ASA I and II), undergoing microsurgery, received 0.25% bupivacaine following surgery, by either continuous infusion (group C, n = 10), or intermittent hourly bolus (group B, n = 10), via an axillary brachial plexus catheter inserted prior to operation. Efficacy assessments and analysis of plasma bupivacaine levels were performed for up to 38 hours postsurgery. There was no difference between groups with respect to pain scores, degree of motor block, or supplemental narcotic requirements. Plasma bupivacaine levels were higher in group C, with the difference reaching significance after 26 hours (means +/- SEM: C = 1.03 +/- 0.10 micrograms/mL, B = 0.73 +/- 0.08 microgram/mL, P < .05). There were no significant differences in cumulative bupivacaine doses or infusion rates between the groups. Complications included one case of axillary artery puncture at insertion, two unplanned premature catheter removals, and a self-limited grand mal convulsion in a known epileptic. Overall, both techniques provided safe and effective postoperative analgesia. As compared with continuous infusion, intermittent bolus administration resulted in lower plasma bupivacaine levels despite similar infusion rates.

Simultaneous determination of lidocaine and bupivacaine in human plasma: application to pharmacokinetics.

High-performance liquid chromatography has been applied to the simultaneous determination of lidocaine and bupivacaine levels in human plasma, using etidocaine as internal standard. The method was found to be linear in the range 10-2,000 micrograms/l for lidocaine and 20-1,000 micrograms/l for bupivacaine. Within-day and day-to-day coefficients of variation were generally lower than 12%. The method was applied to a pharmacokinetic study of lidocaine and bupivacaine during peribulbar anesthesia in ocular surgery. Both compounds displayed a slow apparent elimination rate. The method described here permitted the determination of the complete pharmacokinetic profiles of the two anesthetics, although they were administered at quite different doses.

Modification of bupivacaine toxicity by nonselective versus neuronal nitric oxide synthesis inhibition.

We have previously shown that pretreatment of rats with a nonselective nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), enhances the cardiovascular system (CVS) toxicity and reduces the central nervous system (CNS) toxicity of local anesthetics. This study was performed to differentiate the neuronal from the endothelial effects of L-NAME on the CNS and CVS toxicity of bupivacaine by comparing the effects of L-NAME with a neuronal selective NOS inhibitor, 7-nitroindazole (7-NI). Lightly anesthetized rats were premedicated for 30 min with L-NAME (2 mg kg(-1) x min(-1) intravenously [I.V.]), 7-NI (30 mg/kg intraperitoneally), or saline (control) then bupivacaine (2 mg x kg(-1) x min(-1)) was infused I.V. until asystole occurred. Bupivacaine doses required to produce seizures were the same among groups (saline = 10.1 +/- 2.6 mg/kg; L-NAME = 9.0 +/- 1.2 mg/kg; 7-NI = 10.2 +/- 1.0 mg/kg). However, plasma bupivacaine concentration (microg/mL) at seizure onset was significantly higher in animals pretreated with L-NAME (16.4 +/- 2.1) and, to a lesser degree, 7-NI (11.6 +/- 1.3) than that of control (9.7 +/- 1.6). Seizure duration and the number of epileptiform bursts were significantly reduced in L-NAME versus the other two groups. Doses for arrhythmias and asystole as well as plasma bupivacaine concentrations at arrhythmia onset were dramatically smaller in L-NAME-pretreated rats than in the other two groups. In summary, endothelial NOS inhibition dramatically alters both the CVS and CNS toxicity of bupivacaine with neuronal NOS inhibition playing a minor role.

Wound infiltration with liposomal bupivacaine prolongs analgesia in rats

Wound infiltration with local anesthetics does not reliably produce satisfactory postoperative analgesia, and the dose of local anesthetic which may be safely administered is limited by the potential for systemic toxicity. This study evaluated the efficacy of a slow-release liposomal bupivacaine formulation on duration of wound analgesia. Multilammelar liposomes containing bupivacaine were assessed using a rat paw wound model. Twenty-four hours after surgical incision, paw wounds determined to be hyperalgesic to graded force testing with von Frey hairs were infiltrated with 0.3 ml of 2% liposomal bupivacaine, 0.5% plain bupivacaine, saline, or "empty' (normal saline) liposomes (n = 6/group). The duration of analgesia was measured. The 0.5% plain concentration was chosen because, in preliminary experiments, larger doses were often fatal. Analgesia duration was compared using Mann-Whitney U test at P < 0.05. In other rats, plasma bupivacaine levels after wound infiltration with either 2% liposomal formulation or 0.5% plain formulation were assessed (n = 8/group). The mean duration of analgesia was 23 +/- 3 (SD) min for plain bupivacaine and 180 +/- 30 min for liposomal bupivacaine. No wound analgesia was detected in animals given normal saline or "empty' liposomes. Plasma bupivacaine levels tended to be lower after liposomal than plain bupivacaine. The 8-fold increase in duration of wound analgesia and the lower plasma levels seen with the liposomal formulation are explained by gradual drug release from the liposomal depot. These results may have important implications for achieving safe and effective analgesia with wound infiltration techniques in humans.

Plasma bupivacaine concentrations associated with continuous extradural infusions in babies

The maximum recommended dose for extradural infusions of bupivacaine in children older than 1 month is 0.5 mg kg-1 h-1 but there are few specific reports of the associated blood concentrations during infusions in babies. Toxic symptoms can occur in children at plasma concentrations of bupivacaine as low as 2 micrograms ml-1. We attempted to measure venous plasma concentrations of total and free bupivacaine in babies aged 3-12 months during extradural infusions given at a rate commonly used in our hospital. We studied eight babies (mean age 33 weeks; mean weight 7.8 kg). After a mean initial dose of 1.2 mg kg-1 (range 1.1-1.3 mg kg-1), bupivacaine was infused at a mean rate of 0.38 (0.36-0.39) mg kg-1 h-1 for a mean of 31 (4-44) h. Blood was obtained at 4, 8, 16, 24, 32 and 40 h after starting the infusion and plasma separated by centrifugation. Total plasma bupivacaine concentration was measured using high pressure liquid chromatography (HPLC). Plasma concentrations of total bupivacaine were mostly less than 2 micrograms ml-1. One baby had a concentration of 2.02 micrograms ml-1 at 32 h and showed clear evidence of accumulation of bupivacaine. Babies can accumulate bupivacaine and achieve plasma concentrations above the threshold for toxic side effects, despite infusion rates below the currently accepted maximum. The samples size in our study was small but we believe an extradural infusion rate of 0.375 mg kg-1 h-1 is probably an absolute maximum for babies younger than 12 months.

Comparative study of the determination of bupivacaine in human plasma by gas chromatography-mass spectrometry and high-performance liquid chromatography

A comparison was made between high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) as methods for determining bupivacaine in human plasma. Both methods utilized pentycaine as an internal standard, were found to be linear in the range 5–320 ng and had acceptable precision and accuracy. The precision for the HPLC method was better than that for the GC-MS method. The limits of detection of the HPLC and GC-MS methods were ca. 1.0 and 0.1 ng, respectively. Good agreement between the HPLC and GC-MS methods was obtained for the analysis of samples taken from a patient receiving bupivacaine topically. For most purposes the HPLC method would be slightly better. However, for samples containing interfering peaks GC-MS provides a higher degree of resolution from such interferants.

Myocardial extraction of bupivacaine in anaesthetized sheep and by hearts of sheep and rats in vitro

We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system, particularly in the pulmonary artery, the upper part of the descending aorta and the coronary sinus of anaesthetized sheep, each of which received a high dose infusion into the central vein. In some experiments dilution curves were monitored for the non-extracted dye, indocyanine green. Concentrations of bupivacaine were approximately 20% lower in the aorta than in the pulmonary artery. This gradient of bupivacaine was present across the lung for 5-10 min. Concentrations of bupivacaine in the coronary venous plasma were also markedly lower than at the arterial site. Initially more than 50% of the amount of bupivacaine at the arterial site was removed by the heart. Later, the myocardial extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time, concentrations of bupivacaine in the pulmonary artery were approximately 12 micrograms ml-1. Therefore, approximately 0.3-0.6 mg of bupivacaine were extracted per minute by the sheep heart in vivo. On the other hand, isolated perfused rat hearts did not substantially remove bupivacaine (2 micrograms ml-1) from the medium. Approximately one-third of 14C-bupivacaine was retained in slices of rat and sheep myocardial tissue. However, there was no evidence that metabolism played a substantial role in the cardiac kinetics of bupivacaine.

Prolonged Regional Nerve Blockade

Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats. Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions. Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro. Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.

The Role of Hyaluronidase on Lidocaine and Bupivacaine Pharmacokinetics After Peribulbar Blockade

Orbital regional anesthesia is the only circumstance where hyaluronidase is routinely added to local anesthetics to accelerate the onset of the block. The aim of this study was to compare the pharmacokinetics of lidocaine and bupivacaine with or without hyaluronidase for peribulbar blockade. Twenty-one patients scheduled for cataract surgery with lens implantation were included in this prospective randomized study. Peribulbar blocks were achieved with plain bupivacaine 0.5% (5.5 mL), lidocaine 2% (5.5 mL), and hyaluronidase (100 IU = 2 mL) (n = 10) ir sterile water (2 mL) (n = 11). Plasma bupivacaine and lidocaine concentrations were measured by high-performance liquid chromatography at regular intervals from the end of the local anesthetic injection until the 360th minute. Maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained for all the patients except one who needed a supplementary injection and was excluded from the study. The time to onset and duration of the analgesia and akinesia were monitored at the times of sampling. Motor blockade was incomplete in two patients in each group without affecting surgery. The Tmax and absorption half-life (t1/2a) of lidocaine and bupivacaine were not different within each group (P > 0.05). The Tmax of lidocaine was shorter in the presence of hyaluronidase (17.1 +/- 2.6 min vs 32.7 +/- 6.0 min) as well as the Tmax of bupivacaine (16.8 +/- 3.0 min vs 26.5 +/- 4.4 min). The Cmax of lidocaine and bupivacaine were not modified by the addition of hyaluronidase. The clearance, terminal half-life, and volume of distribution were not different between groups. The absorption of lidocaine and bupivacaine from the peribulbar space are hastened by the addition of hyaluronidase. The Tmax of lidocaine is not different from that of bupivacaine within each group suggesting that the absorption of local anesthetics is minimally influenced by the liposolubility of the drugs. Moreover, hyaluronidase influences the absorption kinetics of both lidocaine and bupivacaine in the same manner.

The Role of Hyaluronidase on Lidocaine and Bupivacaine Pharmacokinetics After Peribulbar Blockade

Orbital regional anesthesia is the only circumstance where hyaluronidase is routinely added to local anesthetics to accelerate the onset of the block.The aim of this study was to compare the pharmacokinetics of lidocaine and bupivacaine with or without hyaluronidase for peribulbar blockade. Twenty-one patients scheduled for cataract surgery with lens implantation were included in this prospective randomized study. Peribulbar blocks were achieved with plain bupivacaine 0.5% (5.5 mL), lidocaine 2% (5.5 mL), and hyaluronidase (100 IU = 2 mL) (n = 10) or sterile water (2 mL) (n = 11). Plasma bupivacaine and lidocaine concentrations were measured by high-performance liquid chromatography at regular intervals from the end of the local anesthetic injection until the 360th minute. Maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained for all the patients except one who needed a supplementary injection and was excluded from the study. The time to onset and duration of the analgesia and akinesia were monitored at the times of sampling. Motor blockade was incomplete in two patients in each group without affecting surgery. The Tmax and absorption half-life (t1/2a) of lidocaine and bupivacaine were not different within each group (P > 0.05). The Tmax of lidocaine was shorter in the presence of hyaluronidase (17.1 +/- 2.6 min vs 32.7 +/- 6.0 min) as well as the Tmax of bupivacaine (16.8 +/- 3.9 min vs 26.5 +/- 4.4 min). The Cmax of lidocaine and bupivacaine were not modified by the addition of hyaluronidase. The clearance, terminal half-life, and volume of distribution were not different between groups. The absorption of lidocaine and bupivacaine from the peribulbar space are hastened by the addition of hyaluronidase. The Tmax of lidocaine is not different from that of bupivacaine within each group suggesting that the absorption of local anesthetics is minimally influenced by the liposolubility of the drugs. Moreover, hyaluronidase influences the absorption kinetics of both lidocaine and bupivacaine in the same manner. (Anesth Analg 1996;82:1060-4)

Con: Unreliable benefit after thoracotomy—epidural is a better choice

Con: Unreliable benefit after thoracotomy—epidural is a better choice