A double-blind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery.

BACKGROUND AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic agent with similar potency to that of bupivacaine when administered for epidural anesthesia. Ropivacaine, however, may be less cardiotoxic than bupivacaine. Epidural bupivacaine and ropivacaine have been shown to be equally effective in providing sensory block for lower extremity surgery, but they have not been compared for their ability to produce abdominal wall relaxation. METHODS: Sixty-six American Society of Anesthesiologists I-III women, 18-70 years old undergoing elective gynecologic surgery were studied in a randomized, double-blind manner after giving informed consent in an institutionally approved protocol. Thirty-four patients received a single epidural injection of 20 ml 0.75% bupivacaine at the L2-L3-L4 interspace and 32 patients received 20 ml 0.75% ropivacaine in a similar manner. Sensory block was tested with pinprick; motor block with a modified Bromage scale, rectus abdominis muscle (RAM) test and surgeon satisfaction. Statistical analysis was performed using the SigmaStat for Windows computer software. Parametric data were analyzed with Student's t-test, while nonparametric data was analyzed using the Mann-Whitney rank sum test. RESULTS: Results are expressed as mean +/- SD. Times to maximal sensory block and peak sensory level achieved were similar in both groups. However, time to complete sensory regression was significantly longer with bupivacaine than ropivacaine (458 +/- 77 vs. 404 +/- 62 minutes, P < .03). Bupivacaine lower extremity motor block onset was significantly faster than ropivacaine (9 +/- 3 vs. 12 +/- 3 minutes, P < .0013). Time to maximum lower extremity motor block was significantly shorter with bupivacaine than ropivacaine (28 +/- 12 vs. 40 +/- 15 minutes, P < .0234). Duration of lower extremity motor block was significantly longer with bupivacaine than ropivacaine (371 +/- 97 vs. 310 +/- 65 minutes P < .069). There was no significant difference between the two groups for changes in RAM scores or the time to achieve those changes. Maximum motor block scores using the modified Bromage score and surgeon satisfaction with operating conditions also did not demonstrate a significant difference between the two groups. In one instance (with ropivacaine), anesthesia was judged clinically inadequate despite evidence of bilateral epidural anesthesia. CONCLUSIONS: Both 0.75% ropivacaine and 0.75% bupivacaine provide adequate surgical anesthesia for lower abdominal surgery when administered epidurally. However, lower extremity motor block with ropivacaine is significantly shorter and of slower onset and sensory block shorter at these concentrations.

Future of regional anaesthesia and pain management.

Consideration of the future practice of regional anaesthesia and pain management must include more than scientific advances. With advances in technology, the practice of medicine will increasingly become international in scope. Socio-economic issues will also have increasing impact on the practice of regional anaesthesia and pain management. More attention will be given to improved outcome and reduced morbidity as addressed by the "closed claims study" of the American Society of Anesthesiologists. Advances in the practice of spinal and epidural anaesthesia will come through improved understanding of nociceptive conduction and receptor physiology. New drugs will focus on specific neural function so that motor, sensory and autonomic blockade may be invoked and antagonized as clinical circumstances require. Advances in peripheral neural blockade will focus on drugs that can provide markedly prolonged effects in the range of days to weeks. Alternate approaches will be the development of neural specific lytic agents that will not spread to or damage surrounding tissues.

Pharmacokinetics of intravenous and epidural ropivacaine in the rhesus monkey.

Ropivacaine is a new long-acting amide local anesthetic which is possibly less cardiotoxic than bupivacaine. The absorption and disposition of ropivacaine were characterized in six rhesus monkeys in an open two-way crossover study following intravenous and epidural administration. For these studies, animals were anesthetized for placement of intravenous and intraarterial catheters. For the epidural studies, a PE-10 catheter was also inserted 3 cm into the lumbar epidural space. After recovery from anesthesia, animals received ropivacaine 1 mg kg-1 intravenously over 1 min or 10 mg of ropivacaine epidurally (two 1 ml doses of 0.5%, 5 min apart), and arterial blood samples were obtained over 5 h. Serum ropivacaine concentrations were determined by gas chromatography with NP detection. Concentration-time data following i.v. and epidural administration were fitted simultaneously. Initial parameter estimates were obtained by analyzing each route separately. Input rates and their corresponding extent of absorption were estimated using deconvolution. Mean (+/- SD) disposition parameters included: Vss = 1.11 +/- 0.198 l kg-1; CL = 0.711 +/- 0.158 l h-1 kg-1; t1/2,z = 2.07 +/- 0.438 h. Mean (+/- SD) absorption parameters included: F1 = 0.506 +/- 0.221; t1/2,kal = 0.060 +/- 0.078 h; F2 = 0.444 +/- 0.182; t1/2,ka2 = 6.45 +/- 11.09 h. Ropivacaine's biphasic absorption and bioavailability are similar to those of other amide local anesthetics. The biphasic absorption may be related to partitioning into fat or regional changes in blood flow induced by the drug.

Tourniquet pain: the response to the maintenance of tourniquet inflation on the upper extremity of volunteers.

This investigation examined the effect of three factors--tourniquet width, tourniquet inflation pressure, and application of the tourniquet to the left or right extremity--on the intensity of tourniquet pain and duration of tourniquet inflation, as well as the circulatory effects associated with maintenance of inflation of a pneumatic tourniquet on an upper extremity of 12 healthy, unmedicated volunteers. All subjects manifested a time-dependent circulatory response to maintenance of tourniquet inflation, characterized by increases in heart rate and systolic and diastolic blood pressure. The mean duration of tourniquet inflation was 34 +/- 13 minutes (mean +/- SD). No difference was demonstrated with respect to the width of the tourniquet, the tourniquet inflation pressure, or the application of the tourniquet to the left or right extremity on the intensity of pain or the duration of tourniquet inflation.

A double-blind comparison of 0.5% bupivacaine and 0.75% ropivacaine administered epidurally in humans.

In an attempt to compare equipotent doses of epidurally administered bupivacaine and ropivacaine, 44 healthy patients, aged 18-70 years, undergoing lower extremity orthopedic procedures were studied in a randomized, double-blind manner. Twenty-one patients received a single epidural injection of 20 ml 0.5% bupivacaine at the L23 or L34 interspace and 23 patients received 20 ml 0.75% ropivacaine in a similar manner. Onset of and recovery from sensory anesthesia and motor block were recorded. No significant differences were found between the two anesthetic groups except for time to two-segment regression. Maximum block height (median (range] was T4 (T2-T8) and T5 (T2-L1) for bupivacaine and ropivacaine, respectively, and maximum motor block scores were 4 (2-6) and 4 (0-6) using the modified Bromage scale. Times to maximum height of sensory block for bupivacaine and ropivacaine, respectively, were 28 +/- 12 and 28 +/- 13 minutes; times to onset of block to T12 were 6 +/- 4 and 9 +/- 10 minutes; times to onset of maximum motor block were 32 +/- 17 and 47 +/- 29 minutes; times to two-segment regression were 2.7 +/- 0.8 and 3.4 +/- 1.0 hours (p less than 0.05); times to regression to T12 level were 4.8 +/- 0.9 and 4.7 +/- 0.95 hours; times to total recovery of sensation were 6.5 +/- 0.9 and 6.6 +/- 1.0 hours, and times to recovery of motor function were 4.4 +/- 0.9 and 4.1 +/- 0.9 hours. In two instances (both with bupivacaine), anesthesia was judged clinically inadequate.

Pharmacodynamics and pharmacokinetics of epidural ropivacaine in humans.

The purpose of this study was to characterize the pharmacodynamics and pharmacokinetics of three concentrations of the new long-acting amide local anesthetic, ropivacaine, given epidurally in 15 physical status ASA I or II patients for elective lower-extremity orthopedic procedures using a nonrandomized open-label design. Three groups of five patients each received either 0.5%, 0.75%, or 1.0% ropivacaine. Upper and lower levels of analgesia to pinprick were determined at frequent intervals until normal sensation had completely returned. Motor blockade was assessed by use of a modified Bromage scale after each determination of level of analgesia. Fifteen venous blood samples were collected over 12 h after ropivacaine injection. Pharmacokinetic parameters were derived using serum concentration-time data. No significant differences were found between the three groups in terms of onset or recovery of motor and sensory blockade. Median maximum thoracic levels of analgesia achieved were 8, 6, and 5 for the 0.5%, 0.75%, and 1.0% groups, respectively, and occurred at 29 +/- 11, 37 +/- 21, and 30 +/- 9 min. Respective times to two-segment regression were 2.8 +/- 1.0, 3.0 +/- 0.5, and 2.9 +/- 0.6 h. Total durations of sensory blockade were 5.4 +/- 0.7, 6.5 +/- 0.4, and 6.8 +/- 0.8 h, respectively. No statistically significant differences were noted between the three groups in terms of clearance (CL). The mean residence time (MRT) was significantly longer for the 0.5% group when compared with the 1% group. The peak concentration (Cmax) for the 0.5% group was found to be significantly lower than for either the 0.75% or 1% groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative analgesia.

In recent years hospitals have begun to institute special postoperative pain services staffed by anesthesia department personnel. The charter for such services is to provide the best and most appropriate postoperative analgesia for surgical patients, in particular for the increasing numbers of patients who, released from hospital soon after surgery, still require pain relief on an outpatient basis. This review focuses on the relative benefits and risks of the currently available options for postoperative pain relief: intramuscular (i.m.) and intravenous (i.v.) administration of narcotics; epidural or subarachnoid administration of narcotics and/or local anesthetics; and peripheral nerve blocks with local anesthetics. In terms of efficacy, cost, risk, and personnel requirements, the particular advantages of continuous analgesia techniques--including patient-controlled analgesia--are discussed.

Hypotension in spinal anesthesia: a comparison of isobaric tetracaine with epinephrine and isobaric bupivacaine without epinephrine.

Two isobaric spinal anesthetic solutions (bupivacaine 0.5%/20 mg without epinephrine and tetracaine 0.5%/15 mg with 0.2 mg epinephrine) were compared in a double-blind study of 60 patients. Patients were injected while in the lateral recumbent position and were immediately turned supine and horizontal. Up to 30 min after injection, no differences were found between the groups regarding segmental level of analgesia, changes in heart rate, and onset to or maximum decrease in mean arterial pressure (MAP). No correlation was found between maximum decrease in MAP and level of analgesia. At time of maximum decrease in MAP (tetracaine group - 16.7 +/- 12.8% (mean + SEM), bupivacaine group -19.4 + 14.8%) the level of analgesia was significantly higher in the tetracaine group (T5-6) than in the bupivacaine group (T7-8). Hypotension occurred in five patients in the bupivacaine group and in six in the tetracaine group. Two patients in the tetracaine group (but none in the bupivacaine group) had bradycardia. Hypotension together with bradycardia was observed in one patient in the tetracaine group but in no patient in the bupivacaine group. Two patients in each group developed postlumbar puncture headache. The authors conclude that the choice of local anesthetic agent, by itself, is not the sole cause of hypotension seen with spinal anesthesia.

Tourniquet pain: a volunteer study.

The effect of inflation pressure (300 and 400 mm Hg) and method of exsanguination (gravity and Esmarch bandage) on the time of onset and the severity of tourniquet-induced pain in the lower extremity was investigated in 11 unmedicated adult volunteers. Each volunteer underwent eight experiments in a random order. A visual analog scale was used to assess pain and discomfort. Blood pressure and pulse rate were measured continuously. Experiments were concluded when the pain rose to a prefixed level. All experiments were performed using a standard orthopedic tourniquet (7 cm wide). Ten additional experiments were carried out using a Bier blockade tourniquet (5 cm wide). There were no differences in duration of tourniquet inflation between inflation pressures nor between methods of exsanguination. There was a small and transient but nevertheless statistically significant increase in blood pressure caused by inflation and a significantly larger increase just before deflation. The 5-cm tourniquet experiments, otherwise identical to the 7-cm tourniquet experiments, were tolerated significantly longer due to a longer time of onset and less severe pain. The 5-cm tourniquet also needed significantly higher inflation pressures to fully occlude the arterial supply (240-450 mm Hg). In all instances, 260 mm Hg was adequate to fully occlude the arterial supply when a 7-cm tourniquet was used. Only half of the experiments were concluded due to intolerable pain at the site of the tourniquet. Most of the others were concluded due to pain mainly in the calf or pain throughout the leg.(ABSTRACT TRUNCATED AT 250 WORDS)

Addition of glucose to bupivacaine in spinal anesthesia increases incidence of tourniquet pain.

The effect of baricity of 0.5% bupivacaine on the incidence of tourniquet pain when used for spinal anesthesia was evaluated in 60 patients undergoing orthopedic surgery. Three ml of either hyperbaric (8% glucose) or isobaric (glucose-free) solution was used. A standard 7-cm orthopedic tourniquet was applied at the thigh and was inflated to 300 mm Hg for 2 hr or until the patient experienced pain from the tourniquet. During application time, the levels of sensory block to pin prick were similar in the groups. The incidence of tourniquet pain in the glucose-free group (4/30) was significantly lower than in the hyperbaric group (11/30).

The influence of diazepam on the pharmacokinetics of intravenous and epidural bupivacaine in the rhesus monkey.

Pretreatment of patients with diazepam has been reported to reduce the plasma half-life of epidurally administered bupivacaine. The concentrations of bupivacaine used to estimate its plasma half-life may be influenced by input into the vascular system (rate and extent of absorption from the epidural space) and disposition (distribution and elimination). We conducted a study in Rhesus monkeys in which the input function was known and the influence of intravenous diazepam on the disposition of intravenous bupivacaine could be delineated. Results indicated no differences in the primary pharmacokinetic parameters (i.e., total clearance and volume of distribution) for the disposition of bupivacaine. To determine whether the apparent disparity between these results and a previous study might be due to a diazepam-induced alteration in the input function, the influence of intravenous diazepam or saline on the mean absorption time of epidurally administered bupivacaine was also studied in monkeys. Epidural bupivacaine was completely absorbed whether the animals received intravenous saline or intravenous diazepam. No significant differences in pharmacokinetic parameters were found between animals pretreated with intravenous saline or intravenous diazepam and receiving an epidural injection of bupivacaine. The mean residence time of bupivacaine in the body (P less than 0.01) and plasma elimination half-life (P less than 0.005) were significantly longer after epidural administration than after intravenous administration. Intravenous diazepam does not alter the pharmacokinetics of intravenously or epidurally administered bupivacaine.

The influence of lactic acid on the serum protein binding of bupivacaine: species differences.

Various animal models have been used for studies of bupivacaine cardiovascular toxicity. These studies are difficult to relate to the clinical situation, since the disposition of bupivacaine in the various species is unknown. The serum protein binding of bupivacaine, therefore, was determined in human, sheep, monkey, dog, and rat at physiologic pH using ultrafiltration. Since a mixed acidosis results during a systemic toxicity reaction to bupivacaine, the influences of an acidic pH, resulting from the addition of lactic acid, also was examined. All sera exhibited two classes of binding sites, a high-affinity, low-capacity class (class 1) and a low-affinity, high-capacity class (class 2). When compared to human serum at physiologic pH, a significantly higher (P less than 0.05) affinity constant for the class 1 sites was observed for all species studied, with the exception of the rat. All species studied exhibited a significantly lower (P less than 0.05) capacity for the class 1 sites. The binding parameters of the class 2 sites displayed no significant difference. An acid pH resulted in a decrease in bupivacaine protein binding over the entire concentration range studied for all species, with the exception of the monkey. Monkey serum exhibited no change in bupivacaine binding with a decrease in pH. Since protein binding explains only a portion of the total disposition of bupivacaine, further delineation of each animal model under both acidotic and physiologic conditions needs to be accomplished before the animal studies currently under investigation can be extrapolated to the clinical situation.

Pharmacokinetics and neural blockade after subarachnoid lidocaine in the rhesus monkey. III. Effects of phenylephrine.

Using a rhesus monkey model, lidocaine (30 mg) in 7.5% dextrose was compared with lidocaine (30 mg) in 7.5% dextrose containing 1.5 mg of phenylephrine (Neosynephrine). Phenylephrine increased both duration of maximum motor block and time for complete motor recovery. A significantly higher sensory dermatome level and significantly longer time for complete sensory recovery was found when the lidocaine solution contained phenylephrine. Time for two-segment regression of sensory blockade was unaffected by phenylephrine. The slope of the regression phase for motor block was parallel for both treatments, suggesting differences in neural blockade were caused by a more profound initial block when phenylephrine was added. Pharmacokinetic analysis revealed identical absorption and elimination constants. Maximum plasma concentrations of lidocaine and time to reach maximum plasma concentrations were identical with and without phenylephrine. The systemic absorption (fraction of drug absorbed from the subarachnoid space) was complete with and without phenylephrine. No lag times for systemic absorption were found for either treatment. Our data demonstrate that there are no clinically significant differences between phenylephrine and epinephrine when added to lidocaine solutions for spinal anesthesia.

Comparison of neural blockade and pharmacokinetics after subarachnoid lidocaine in the rhesus monkey. II: Effects of volume, osmolality, and baricity.

The effects of volume, osmolality, and baricity on lidocaine spinal anesthesia in the rhesus monkey were studied. Changes in neural blockade, physical properties of cerebrospinal fluid, and arterial pharmacokinetics associated with variations in injectate composition were assessed. Wide ranges of volume, baricity, and osmolality were studied using 1, 2, and 5% lidocaine prepared in either sterile water or 7.5% dextrose. Minimal changes in neural blockade were found in the ranges of osmolality and baricity studied, although 5% lidocaine in sterile water resulted in significantly shorter complete recovery times for both sensory and motor block when compared to other solutions. Samples of cerebrospinal fluid obtained after injection of lidocaine showed increases or decreases in specific gravity and osmolality depending on the physical properties of the solution injected. No differences in elimination phase pharmacokinetics were found with any of the lidocaine solutions. Rates of systemic absorption increased with decreasing osmolality. Osmotic potentiation of lidocaine spinal anesthesia could not be demonstrated.

Neural blockade and pharmacokinetics following subarachnoid lidocaine in the rhesus monkey. I. Effects of epinephrine.

A sensitive and reliable animal model for the objective physiologic and pharmacokinetic evaluation of spinal anesthesia has been developed. Using this model, spinal anesthesia using lidocaine (30 mg) in 7.5% dextrose with and without epinephrine was compared. Epinephrine did not alter the degree or duration of time to achieve maximum motor block. However, epinephrine did significantly increase the time for complete motor recovery. A significantly higher dermatome level of sensory block was achieved in the epinephrine-containing solutions, as well as a significantly longer time for complete recovery. This reflects a latent effect of epinephrine, as the time for two-segment regression was independent of epinephrine. Pharmacokinetic analysis showed no effect of epinephrine on absorption and elimination constants. The maximum plasma concentration and time to reach maximum plasma concentration were equal with and without epinephrine.