Pharmacokinetics of ropivacaine and bupivacaine during 21 hours of continuous epidural infusion in healthy male volunteers.

The aim of the present study was to evaluate the pharmacokinetics of ropivacaine and to compare the results with those of bupivacaine during prolonged epidural infusion. Ropivacaine 1, 2, or 3 mg/mL (0.1%, 0.2%, or 0.3%), bupivacaine 2.5 mg/mL (0.25%), or placebo (sodium chloride 0.9%) was given randomly and in a double-blind manner to five parallel treatment groups (37 healthy volunteers) as a continuous epidural infusion for 21 h. A 10-mL epidural bolus dose was first given, and the epidural infusion was started immediately afterward. The subjects received 10 mL/h corresponding to infusion rates of 10, 20, or 30 mg/h ropivacaine and 25 mg/h bupivacaine, respectively. Peripheral blood samples for measurements of ropivacaine or bupivacaine were taken during a 25-h period. The total plasma concentration increased continuously but seemed to reach a plateau (C5-10h) after approximately 5 h infusion, remaining fairly constant up to approximately 10 h after the start of administration. The C5-10h values were proportional to the dose of ropivacaine and were estimated as 0.3, 0.6, and 0.9 mg/L, and for bupivacaine as 0.7 mg/L. During the subsequent infusion the plasma concentration increased, with maximum plasma levels at the end of the infusion and with corresponding values of 0.4, 0.9, 1.2, and 0.9 mg/L. The highest individual plasma concentration was 1.7 mg/L (20 mg/h), and no patient showed signs of toxic systemic plasma levels. The free concentrations also increased continuously during the infusion. The free fraction was independent of the dose (6.1% for ropivacaine and 4.8% for bupivacaine).(ABSTRACT TRUNCATED AT 250 WORDS)

An open study comparison of 0.5%, 0.75% and 1.0% ropivacaine, with epinephrine, in epidural anesthesia in patients undergoing urologic surgery.

Ropivacaine 0.5%, 0.75% and 1.0% with epinephrine 5 micrograms/ml was investigated in an open, multi-center study for lumbar epidural anesthesia in 46 patients undergoing urologic surgery. The onset time for analgesia to T12 was 5-7 minutes after the end of the ropivacaine injection. Maximum segmental levels of analgesia (T4-6) were not different between the groups. Complete motor blockade was obtained in 3/15, 7/15 and 10/15 patients in the 0.5%, 0.75% and 1.0% groups, respectively. Duration of analgesia at the T10 level was 2.5 hours in the 0.5% group, and increased to 4 hours in the 1.0% group. Analgesia was satisfactory for surgery in all patients except for 2/15 in each of the 0.5% and 0.75% groups and 1/15 in the 1.0% group. Hypotension was experienced by three, six and three patients in the 0.5%, 0.75% and 1.0% groups, respectively. Bradycardia was seen in two patients in the 0.5% group and one patient in the 1.0% group. Backache was experienced by seven patients (four in the 0.5%, two in the 0.75% and one in the 1.0% group). No late-occurring adverse experiences were observed. In conclusion, 0.5%, 0.75% and 1.0% ropivacaine with epinephrine provide adequate analgesia and motor blockade for urologic surgery.

Venous blood concentrations after subarachnoid administration of bupivacaine.

Peripheral venous blood concentrations of bupivacaine were measured in 51 patients given 0.5% (4 ml, 20 mg) or 0.75% (3 ml, 22.5 mg) bupivacaine, both solutions with or without glucose, for spinal anesthesia. The initial absorption of bupivacaine, as measured in peripheral venous blood, was rapid, although the blood concentrations were low. The mean peak concentration (Cmax) did not differ when glucose was added to 0.5 or 0.75% bupivacaine. When glucose-free and glucose-containing bupivacaine groups were combined, 22.5 mg bupivacaine give a significantly higher venous blood concentration than 20 mg of the solution. The mean time between subarachnoid injection and the time when Cmax was reached (tpeak) was influenced by the density of bupivacaine, i.e., the tpeak of bupivacaine with glucose was significantly shorter than with glucose-free solution (35 min; P less than 0.05). No correlation was found between Cmax and the age, height, or weight of the patients, or between Cmax and the maximum cephalad level of analgesia in the different groups. In addition, there was no correlation between tpeak and the age, height, or weight of the patients. The maximal cephalad level of analgesia did not influence tpeak in the different groups (the correlation coefficients less than 0.3).

A double-blind study of motor blockade in the lower limbs. Studies during spinal anaesthesia with hyperbaric and glucose-free 0.5% bupivacaine.

Sensory and motor blockade were studied double-blind during spinal anaesthesia in 20 urology patients who received 0.5% bupivacaine solution 4 ml with or without glucose. Using a new method for determining muscle strength, motor blockade during anaesthesia was recorded quantitatively for flexion of the hip, extension of the knee and plantar flexion of the big toe. Movements of the lower part of the thoracic cage were recorded at the same time. Complete motor blockade of longer duration was observed for all three movements following the administration of the glucose-free solution compared with the solution containing glucose. During the regression phase, the muscle strength returned significantly later (knee extension and hip flexion) when glucose-free bupivacaine solution was given. There was no significant difference between the two anaesthetic solutions regarding plantar flexion of the big toe during this phase. For hip flexion (L1-L3) there was no noteworthy difference between the levels of analgesia and the motor blockade, whereas for plantar flexion of the big toe (L5-S2) the level of analgesia was 2-3 segments higher than the level of motor blockade. Thoracic movements (maximal inspiration to normal expiration) did not appear to be notably influenced by the level of analgesia. Complete regression of motor blockade was not observed for any of the movements at grade O of a modified Bromage scale. Not until 1.5-2 h after the attainment of this grade was the muscle strength of all movements restored (90% of control value).

Spinal anaesthesia with glucose-free 0.5% bupivacaine: effects of different volumes.

The effects of different volumes (1.5, 2, 3, and 4 ml) of glucose-free 0.5% bupivacaine used for spinal anaesthesia were compared in 40 patients scheduled for urological surgery. The blocks were performed with the patients in the sitting position. The time to maximum cephalad spread of analgesia varied between 13 and 18.5 min. A significant difference was found in cephalad spread between the 1.5-and 2-ml groups and the 3-and 4-ml groups. The duration of analgesia increased, the time to complete motor blockade of the lower limbs decreased and the frequency of complete motor blockade increased with increasing volume. Spinal anaesthesia with 3-4 ml of glucose-free 0.5% bupivacaine proved satisfactory for transurethral resection of the prostate.

Spinal anaesthesia with hyperbaric 0.5% bupivacaine: effects of volume.

Different volumes (1.5, 2, 3 and 4 ml) of hyperbaric 0.5% bupivacaine (8% glucose) were compared in spinal anaesthesia for urological surgery in 40 patients. The blockade was given with the patient in the sitting position. Two minutes after the injection the patient was placed in the lithotomy position. The time required for maximum cephalad spread of analgesia was about 20 min for all volumes. The maximum cephalad spread was directly related to log volume of the local anaesthetic solution. The onset time for motor blockade of the lower limbs decreased and the frequency increased with increasing volume. Four ml produced complete blockade in all patients. The duration of analgesia increased with increasing volume: 3-4 ml produced analgesia at T8 for 1.5-2.5 h and at L1 for 2-3 h. With this volume, complete motor blockade was obtained for 1.5-2.5 h. Satisfactory surgical anaesthesia for transurethral resection was obtained with 3-4 ml of the local anaesthetic solution.