Effect of clonidine on lidocaine clearance in vivo: a microdialysis study in humans.

BACKGROUND: The addition of clonidine to local anesthetics has been shown to prolong both peripheral and central neuraxial local anesthetic blocks. Whether clonidine prolongs local anesthetic block by a pharmacokinetic effect or a pharmacodynamic effect is unclear. By directly measuring lidocaine tissue concentrations at the site of injection in the presence and absence of clonidine, this study was designed to address this question. METHODS: Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of seven volunteers. Plain lidocaine (1%) was injected along one nerve, and lidocaine with clonidine (10 microg/ml) was injected along the other nerve in a double-blind, randomized manner. The extracellular fluid was then sampled for lidocaine concentration at 5-min intervals using microdialysis, cutaneous blood flow was assessed by laser Doppler at 10-min intervals, and sensory block was assessed every 10 min until resolution. RESULTS: Consistent with previous studies, clonidine prolonged lidocaine sensory block. Blood flow increased in both groups but was significantly lower in the clonidine group, especially during the first 60 min. Consistent with the lower blood flow, the area under the lidocaine concentration-versus-time curve was significantly greater in the clonidine group during the first 60 min. CONCLUSION: When added to lidocaine, clonidine prolonged peripheral nerve block. The pharmacokinetic data suggest that the mechanism of prolongation is at least in part pharmacokinetic.

A comparison of epidural levobupivacaine 0.5% with or without epinephrine for lumbar spine surgery.

Levobupivacaine, the S(-) isomer of bupivacaine, is less cardiotoxic than racemic bupivacaine. In this prospective, randomized, double-blinded study of epidural anesthesia, we compared the onset, extent, and duration of sensory and motor blockade produced by plain 0.5% levobupivacaine (15 mL, 75 mg) with that of 0.5% levobupivacaine with the addition of 1:400,000 or 1:200,000 epinephrine in 117 patients undergoing elective spine surgery. The time to onset of adequate sensory block (T10 dermatome) was similar in all groups (12.4 +/- 6.6 min for plain levobupivacaine, 13.9 +/- 7.9 min for levobupivacaine with 1:400,000 epinephrine, and 12.7 +/- 4.9 min for levobupivacaine with 1:200,000 epinephrine), with an average peak block height of T5. Time to complete regression of sensory blockade was also similar between groups (357 +/- 119 min for plain levobupivacaine, 378 +/- 98 min for levobupivacaine with 1:400,000 epinephrine, and 348 +/- 80 min for levobupivacaine with 1:200,000 epinephrine). Peak serum levobupivacaine levels were reduced in each of the epinephrine-containing groups. We conclude that 0.5% levobupivacaine with or without 1:200,000 or 1:400,000 epinephrine produced effective epidural anesthesia in patients having lumbar spine surgery. Epinephrine 1:400,000 is as effective as 1:200,000 in reducing the resultant serum levobupivacaine levels after epidural anesthesia.

Hospital discharge after ambulatory knee arthroscopy: A comparison of epidural 2-chloroprocaine versus lidocaine.

BACKGROUND AND OBJECTIVES: This prospective, randomized, double-blind study compares the efficacy of epidural 2-chloroprocaine and lidocaine for attaining hospital discharge criteria after ambulatory knee arthroscopy. We hypothesized that 2-chloroprocaine would facilitate earlier discharge than lidocaine. METHODS: American Society of Anesthesiologists (ASA) I and II patients were randomized to receive equipotent doses of epidural 3% 2-chloroprocaine or 1.5% lidocaine, both without epinephrine. Time to block resolution and discharge were compared between groups, along with the need for epidural reinjection, surgical times, and postoperative back pain. RESULTS: Twenty-seven patients completed the study, 13 in the 2-chloroprocaine group and 14 in the lidocaine group. The 2-chloroprocaine group was ready for discharge significantly earlier than the lidocaine group (130 +/- 17 min [range, 105 to 160] v 191 +/- 32 min [range 144 to 251]; P <.0001, 90% power). The lidocaine group required more epidural reinjections. Anesthesia-related side effects were similar in both groups. CONCLUSIONS: Epidural 3% 2-chloroprocaine without epinephrine is an advantageous choice for ambulatory knee arthroscopy. It enables readiness for discharge an hour sooner than 1.5% lidocaine, requires fewer reinjection interventions, and may reduce delayed discharge secondary to prolonged time to void. This clinical study shows the superiority of epidural 3% 2-chloroprocaine over 1.5% lidocaine for expediting hospital discharge after ambulatory surgery.

A comparison of epidural levobupivacaine 0.75% with racemic bupivacaine for lower abdominal surgery.

UNLABELLED: Levobupivacaine, the S(-) isomer of bupivacaine, is less cardiotoxic than racemic bupivacaine. In this prospective, randomized, double-blinded study of epidural anesthesia, the onset, extent, and duration of sensory and motor block produced by 0.75% levobupivacaine (20 mL, 150 mg) was compared with that of 0.75% racemic bupivacaine in 56 patients undergoing elective lower abdominal surgery. The time to onset of adequate sensory block (T10 dermatome) was similar in both treatment groups (13.6 +/- 5.6 min for levobupivacaine and 14.0 +/- 9.9 min for bupivacaine), with an average peak block height of T5 reached at 24.3 +/- 9.4 and 26.5 +/- 13.2 min, respectively. Time to complete regression of sensory block was significantly longer with levobupivacaine (550.6 +/- 87.6 min) than bupivacaine (505.9 +/- 71.1 min) (P = 0.016). Abdominal muscle relaxation was adequate for the scheduled procedure in all patients, and there were no significant differences between the groups in rectus abdominis muscle scores (P = 0.386) and quality of muscle relaxation as determined by the surgeon and anesthesiologist (P = 0. 505 and 0.074, respectively). In conclusion, both 0.75% levobupivacaine and 0.75% bupivacaine produced effective epidural anesthesia and their effects were clinically indistinguishable. IMPLICATIONS: The results of this study indicate that the sensory and motor block produced by 0.75% levobupivacaine is equivalent to that of 0.75% racemic bupivacaine. Both local anesthetics are well tolerated and effective in producing epidural anesthesia for patients undergoing lower abdominal surgery.

A comparison of levobupivacaine 0.125%, fentanyl 4 microg/mL, or their combination for patient-controlled epidural analgesia after major orthopedic surgery.

UNLABELLED: Levobupivacaine, the isolated S(-) isomer of bupivacaine, is less cardiotoxic than racemic bupivacaine in animal studies. We studied the effectiveness of patient-controlled epidural analgesia (PCEA) with either levobupivacaine 0.125% or fentanyl 4 microg/mL alone, or a combination of levobupivacaine and fentanyl in 65 patients after total joint arthroplasty in a prospective, random, double-blinded fashion. Intraoperatively, all patients received 20 mL of 0.75% levobupivacaine. Study medication was infused at an initial rate of 4 mL/h, with additional medication available on patient demand (2 mL/10 min). The combination of levobupivacaine and fentanyl produced better analgesia (longer time to first PCEA request; P = 0.007 combination versus fentanyl and P = 0.006 combination versus levobupivacaine) than either drug alone. Patients in the levobupivacaine groups had appreciable sensory blockade to pinprick with minimal motor impairment. Resting and dynamic visual analog scale pain scores were lower in the combination group than in the plain fentanyl group at 6 (P = 0.022 and 0.036) and 12 h (P = 0.002 and 0.001). The 24-h overall patient- and investigator-rated visual analog scale pain scores were also lower in the combination group (resting P = 0.007, dynamic P = 0.005). There was no significant difference among the groups in the incidence of postoperative nausea (26.2%), pruritus (9.2%), hypotension (23.1%), or sedation (0%). We conclude that the analgesic effects of levobupivacaine 0.125% and fentanyl (4 microg/mL) are additive and beneficial for the management of orthopedic surgical pain by the PCEA method. Patients in this study began demand-dosing later, reported lower pain scores, and had no greater risk of adverse events than those who were given either levobupivacaine or fentanyl alone. IMPLICATIONS: We demonstrated a significant additive effect of the combination of levobupivacaine (0.125%) and fentanyl (4 microg/mL), compared with either drug alone, when using patient-controlled epidural analgesia in patients after total joint arthroplasty.

Effect of epinephrine on lidocaine clearance in vivo: a microdialysis study in humans.

BACKGROUND: Local anesthetic nerve block prolonged by epinephrine is thought to result from local vasoconstriction and consequent decreased local anesthetic clearance from the injection site. However, no study has yet confirmed this directly in humans by measuring tissue concentrations of local anesthetic over time. In addition, recent studies have shown that the alpha2-adrenergic receptor agonist, clonidine, also prolongs nerve block without altering local anesthetic clearance. Because epinephrine is also an alpha2-adrenergic receptor agonist, it is possible that epinephrine prolongs local anesthetic block by a pharmacodynamic mechanism and not a pharmacokinetic one. This study was designed to address this issue. METHODS: Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of eight volunteers. Plain lidocaine (1%) was injected along one peroneal nerve and lidocaine with epinephrine (2.5 microg/ml) was injected along the other nerve in a double-blinded, randomized manner. The concentration of lidocaine in tissue was measured at 5-min intervals, and sensory block and cutaneous blood flow were assessed by laser Doppler at 10-min intervals for 5 h. The resulting data for lidocaine concentration versus time were fit to a two-compartment model using modeling software. RESULTS: Epinephrine prolonged sensory block by decreasing local blood flow and slowing clearance. There was no evidence of a pharmacodynamic effect of epinephrine. CONCLUSION: Although epinephrine activates alpha2-adrenergic receptors, its mechanism for prolonging the duration of local anesthetic block rests on its ability to decrease local anesthetic clearance and not on a pharmacodynamically mediated potentiation of local anesthetic effect.

Hyperbaric spinal ropivacaine: a comparison to bupivacaine in volunteers.

BACKGROUND: Ropivacaine is a newly introduced local anesthetic that may be a useful alternative to low-dose bupivacaine for outpatient spinal anesthesia. However, its relative potency to bupivacaine and its dose-response characteristics are unknown. This double-blind, randomized, crossover study was designed to determine relative potencies of low-dose hyperbaric spinal ropivacaine and bupivacaine and to assess the suitability of spinal ropivacaine for outpatient anesthesia. METHODS: Eighteen healthy volunteers were randomized into three equal groups to receive one spinal administration with bupivacaine and a second with ropivacaine, of equal-milligram doses (4, 8, or 12 mg) of 0.25% drug with 5% dextrose. The duration of blockade was assessed with (1) pinprick, (2) transcutaneous electrical stimulation, (3) tolerance to high tourniquet, (4) electromyography and isometric force dynamometry, and (5) achievement of discharge criteria. Differences between ropivacaine and bupivacaine were assessed with linear and multiple regression. P < 0.05 was considered significant. RESULTS: Ropivacaine and bupivacaine provided dose-dependent prolongation of sensory and motor block and time until achievement of discharge criteria (R2 ranges from 0.33-0.99; P values from < 0.001 through 0.01). Spinal anesthesia with ropivacaine was significantly different from bupivacaine and was approximately half as potent for all criteria studied. A high incidence of back pain (28%; P = 0.098) was noted after intrathecal ropivacaine was given. CONCLUSION: Ropivacaine is half as potent and in equipotent doses has a similar profile to bupivacaine with a higher incidence of side effects. Low-dose hyperbaric spinal ropivacaine does not appear to offer an advantage over bupivacaine for use in outpatient anesthesia.

Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block.

UNLABELLED: The incidence and clinical significance of hemidiaphragmatic paresis after supraclavicular block of the brachial plexus is unknown. Eight healthy volunteers received a supraclavicular block with a standard technique using 30 mL of 1.5% lidocaine. Respiratory function was assessed with ultrasound of the diaphragm, respiratory inductive plethysmography (RIP), and pulmonary function tests (PFT) every 20 min. Sensory block was assessed with pinprick and motor block with isometric force dynamometry every 20 min. Four of eight subjects demonstrated hemidiaphragmatic paresis on both ultrasound and RIP. No subject experienced changes in PFT values or subjective symptoms of respiratory difficulty. Motor and sensory blockade outlasted hemidiaphragmatic paresis. These results are contrasted to the often symptomatic, 100% incidence of hemidiaphragmatic paresis seen after interscalene block. In this study of healthy volunteers, supraclavicular block was associated with a 50% incidence (95% confidence interval 14-86) of hemidiaphragmatic paresis that was not accompanied by clinical evidence of respiratory compromise. IMPLICATIONS: Interscalene block is always associated with diaphragmatic paralysis and respiratory compromise. The significance of these side effects after supraclavicular block is unknown. Using sensitive measures of respiratory function, we determined that diaphragmatic paralysis occurs less often with the supraclavicular approach and is not associated with respiratory difficulties in healthy subjects.

Comparison of lidocaine and saline for epidural top-up during combined spinal-epidural anesthesia in volunteers.

This study was designed to determine the efficacy of saline as an epidural top-up to prolong spinal anesthesia during combined spinal-epidural anesthesia (CSEA). Eight volunteers received three separate CSEAs with intrathecal lidocaine (50 mg). After two-segment regression, each subject received either a saline (10 mL), lidocaine 1.5% (10 mL), or control sham (0.5 mL saline) epidural injection in a randomized, double-blind, triple cross-over fashion. Sensory block was assessed by pinprick and tolerance to transcutaneous electrical stimulation (TES) equivalent to surgical stimulation at the knee and ankle. Motor strength was assessed with iso-metric force dynamometry. Data were analyzed with a repeated measures analysis of variance and a paired t-test. Sensory block to pinprick was prolonged in the thoracolumbar dermatomes only by lidocaine (P < 0.05). Neither lidocaine nor saline prolonged the duration of tolerance to TES at the tested sites. Instead, saline decreased the duration of tolerance to TES by 20 and 24 min at the knee and ankle (P < 0.05). Recovery from motor block at the quadriceps was prolonged by an epidural injection of lidocaine (P < 0.05). We conclude that when 10 mL of epidural saline is administered after two-segment regression, it is an ineffective top-up and may decrease the duration of spinal anesthesia during CSEA.

The regional anesthesia "learning curve". What is the minimum number of epidural and spinal blocks to reach consistency?

BACKGROUND AND OBJECTIVES: Wide variability exists in the amount of regional anesthesia practice to which residents are exposed during training. The number of attempts at various blocks before a trainee becomes proficient at performing these regional anesthetic techniques is not known. This study addresses the question: What is the minimum number of blocks a resident must perform to reach consistency during training in these techniques? METHODS: Every regional anesthetic technique attempted by all beginning CA-1 anesthesiology residents (n = 7) during their first 6 months of training (July 1993 to December 1993) were recorded on a daily basis. Nonregional anesthetic techniques attempted were recorded for comparison. The objective measures used to define the degree of success were obtaining cerebrospinal fluid during attempted spinal anesthesia, subsequent anesthetic block during epidural placement, and detection of end-tidal carbon dioxide for endotracheal intubation. RESULTS: An average of 77 +/- 9 epidural anesthetics, 44 +/- 6 spinal anesthetics, and 86 +/- 13 endotracheal intubations were attempted during the 6 months of training. The learning curves for each technique are of similar shape. Residents show significant (P < .05) improvement over baseline after 20 spinal and 25 epidural anesthetics, but a 90% success rate is not reached and maintained until 45 spinal and 60 epidural anesthetics are performed. CONCLUSIONS: Approximately 20-25 procedures each are necessary before improvement in the techniques of spinal and epidural anesthesia is demonstrated by residents in training. If a 90% success rate is desired, 45 and 60 attempts at spinal and epidural anesthesia, respectively, may be necessary.

The effects of electrical stimulation at different frequencies on perception and pain in human volunteers: epidural versus intravenous administration of fentanyl.

The study was performed to determine whether epidural fentanyl produced segmental sensory changes to electrical stimulation at different frequencies. Eight healthy volunteers received fentanyl 1 microgram/kg both intravenously and epidurally in a randomized, double-blind, cross-over fashion. Perception thresholds and amount of current required to elicit a predetermined level of moderate pain (Cmp) at 5,250, and 2000 Hz stimulation were measured at ipsilateral dermatomes C2 and L2 at 0, 5, 15, 30, 45, and 60 min after injection. Perceptions to 5,250, and 2000 Hz stimulation were unaffected by either intravenous or epidural fentanyl (P > 0.08). Intravenous fentanyl increased Cmp at both 5 and 250 Hz at both dermatomes (P < 0.004) and thus did not produce segmental analgesia. In contrast, epidural fentanyl increased Cmp only at the L2 dermatome and only at 5 Hz (P = 0.005). We conclude that an epidural bolus of fentanyl results in segmental spinal analgesia to transcutaneous electrical stimulation only at specific frequencies. Furthermore, pain produced by stimulation at 5 Hz may have a different pharmacology than pain produced by 250 Hz stimulation.

Comparison of needle deviation during regional anesthetic techniques in a laboratory model.

Although many characteristics of needles used for spinal and epidural anesthesia have been studied extensively, the amount that a needle deviates from a straight path while passing through tissue has been relatively ignored. A laboratory model was used to determine the amount of needle deviation produced when different types of new spinal needles and epidural needles were passed through porcine tissue. Both needle point design and, to a lesser extent, needle gauge were found to influence the amount and direction of needle deviation. Deviation was found to be the least for the pencil-point spinal needles (Whitacre, Sprotte, Safetap, range 0.60-1.00 mm/50 mm tissue, analysis of variance (ANOVA) P < 0.001). Needles commonly used for epidural anesthesia (Tuohy, Hustead, Crawford) exhibited increased deviation (range 1.73-3.54 mm/50 mm tissue), although the largest amount was seen with beveled spinal needles (Quincke, Atraucan) (range 4.42-5.90 mm/50 mm tissue). The possible clinical significance of needle deviation during the performance of a regional anesthetic is discussed.

Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia.

BACKGROUND: Recent technology allows for quantitative and selective measurement of A beta, A delta, and C fiber nerve transmission. To gain further insight into the physiology of differential block after lidocaine spinal anesthesia, the function of these different fibers was quantitatively measured over time, and these measurements were correlated with regression of anesthesia to pinprick, touch, cold, and tolerance of tetanic electrical current (equivalent to surgical incision). METHODS: Six volunteers received lidocaine spinal anesthesia with 50 mg lidocaine (5% in dextrose). Cutaneous current perception thresholds at 2,000, 250, and 5 Hz, which stimulate A beta, A delta, and C fibers, respectively, were determined at L2-L3 (medial aspect above knee) before and every 10 min after spinal anesthesia. Dermatomal levels to pinprick, touch, and cold were assessed every 5 min after spinal anesthesia. Tolerance to tetanic electrical stimulus was assessed at L2-L3 every 10 min after spinal anesthesia. RESULTS: Differential block was demonstrated by the sequential return of sensation to touch, pinprick, and cold at L2-L3. Recovery of function of A beta, A delta, and C fibers correlated with return of sensation to touch (R2 = 0.7, p = 0.03), pinprick (R2 = 0.75, p = 0.02), and cold (R2 = 0.67, p = 0.04) respectively. Loss of tolerance of surgical anesthesia corresponded to return of A beta current perception thresholds to baseline, whereas current perception thresholds for A delta and C fibers were still increased to greater than baseline (p = 0.025). CONCLUSIONS: Differential sensory block during spinal anesthesia is due to different recovery profiles of A beta, A delta, and C fibers. Return of A beta current perception thresholds to baseline correlated with duration of surgical anesthesia as assessed with an electrical stimulation model.

Pharmacokinetics of ropivacaine and bupivacaine for bilateral intercostal blockade in healthy male volunteers.

BACKGROUND: Intercostal blockade produces the highest serum local anesthetic concentrations of all regional anesthetic techniques. The purpose of this study was to determine the pharmacokinetic properties of ropivacaine and bupivacaine after bilateral intercostal blockade. METHODS: The pharmacokinetics of ropivacaine (n = 7) and bupivacaine (n = 7) were determined in adult human volunteers from venous samples drawn over 24 h after bilateral intercostal blockade of T5-T11 with 140 mg of either drug (0.25% plain solutions, 56 ml). Sensory (pinprick, temperature, and touch) and motor blockade (RAM-test and integrated electromyography) were assessed every 2 h. RESULTS: There was no significant difference between the maximum plasma concentrations (Cmax) obtained for either drug (ropivacaine 1.1 +/- 0.4 microgram/ml, bupivacaine 0.9 +/- 0.2 microgram/ml, P = 0.39), and there were no toxic signs observed in the obtained plasma concentration ranges. Plasma concentrations tended to peak (tmax) earlier with ropivacaine (21 +/- 9 versus 30 +/- 8 min, P = 0.09). The terminal half-life (t1/2 beta) of ropivacaine (2.3 +/- 0.8 h) was significantly less than that for bupivacaine (4.6 +/- 2.6 h, P = 0.04). Sensory blockade measured by pinprick was of shorter duration with ropivacaine (6.0 +/- 2.5 h versus bupivacaine 10.0 +/- 3.0 h; P < 0.001). Likewise, motor blockade was less intense and of shorter duration for ropivacaine by RAM-test (P = 0.02). CONCLUSIONS: The results of this pharmacokinetic study indicate that 0.25% ropivacaine and 0.25% bupivacaine (56 ml, 140 mg) produce peak plasma levels less than those considered toxic when used in bilateral intercostal blockade. Studies of ropivacaine for intercostal blockade in surgical patients are necessary before the optimum concentration for efficacy and anesthetic/analgesic duration is identified.