Rudolf Stienstra

Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: a double-blind comparison.

We compared the effects of continuous epidural infusion of ropivacaine 0.25% with bupivacaine 0.25% on pain relief and motor block during labor, and on the neonate. Seventy-six full-term parturients in active labor requiring epidural analgesia were randomly allocated to receive either bupivacaine 0.25% or ropivacaine 0.25%. Fifteen minutes after a loading dose of 10 mL of the study drug, an epidural infusion with the same drug was started at 6-12 mL/h to maintain an adequate block. Top-up doses of 6-10 mL were given as required. At full cervical dilation, the epidural infusion was discontinued. The onset of pain relief (verbal scale), contraction pain (visual analog scale), intensity of motor block (modified Bromage scale), and duration of motor block were not statistically different between the groups. Apgar scores at 1 and 5 min after delivery were comparable. There was a higher proportion of the neonates in the ropivacaine group (26/31 = 84%) who had a neurologic and adaptive capacity score (NACS) >or=to 35 2 h after delivery than in the bupivacaine group (18/29 = 62%). We conclude that ropivacaine 0.25% and bupivacaine 0.25% are equally effective for epidural pain relief during labor. Ropivacaine may have an advantage over bupivacaine regarding neonatal neurobehavioral performance during the first few hours after delivery, although further studies will be required to substantiate this. (Anesth Analg 1995;80:285-9)

Mechanism of action of an epidural top-up in combined spinal epidural anesthesia.

The purpose of this study was to elucidate the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia. Thirty patients scheduled to undergo lower limb orthopedic surgery were randomly allocated to three groups of 10 patients each. In all patients, a 16-gauge Tuohy needle was introduced into the epidural space. Using the needle through needle technique, each patient received a subarachnoid injection of 10 mg plain bupivacaine 0.5% through a long 27-gauge Whitacre spinal needle introduced into the subarachnoid space through the Tuohy needle. After withdrawal of the spinal needle, an epidural catheter was introduced into the epidural space. After the maximum level of sensory block after the subarachnoid injection had been established, an epidural top-up with 10 mL bupivacaine 0.5% (Group 1) or 10 mL saline (Group 2) was administered; patients in Group 3 received no epidural top-up. The maximum level of sensory block was then assessed for an additional 30 min. After the epidural top-up the maximum level of sensory block increased significantly by 4.8 +/- 1.6 segments in Group 1 and 2.0 +/- 2.0 segments in Group 2. In Group 3 there was a nonsignificant increase of 0.3 +/- 0.5 segments. Intergroup comparisons showed that this increase in Group 1 was significant compared with those in Groups 2 and 3, and that the increase in Group 2 was significant compared with that in Group 3. We conclude that the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia can be explained partly by an epidural volume effect and partly by an effect of the local anesthetic itself. (Anesth Analg 1996;83:382-6)

The Effects of Age on Neural Blockade and Hemodynamic Changes After Epidural Anesthesia with Ropivacaine

We studied the influence of age on the neural blockade and hemodynamic changes after the epidural administration of ropivacaine 1.0% in patients undergoing orthopedic, urological, gynecological, or lower abdominal surgery. Fifty-four patients were enrolled in one of three age groups (Group 1: 18–40 yr; Group 2: 41–60 yr; Group 3: ≥61 yr). After a test dose of 3 mL of prilocaine 1.0% with epinephrine 5 &mgr;g/mL, 15 mL of ropivacaine 1.0% was administered epidurally. The level of analgesia and degree of motor blockade were assessed, and hemodynamic variables were recorded at standardized intervals. The upper level of analgesia differed among all groups (medians: Group 1: T8; Group 2: T6; Group 3: T4). Motor blockade was more intense in the oldest compared with the youngest age group. The incidence of bradycardia and hypotension and the maximal decrease in mean arterial blood pressure during the first hour after the epidural injection (median of Group 1: 11 mm Hg; Group 2: 16 mm Hg; Group 3: 29 mm Hg) were more frequent in the oldest age group. We conclude that age influences the clinical profile of ropivacaine 1.0%. The hemodynamic effects in older patients may be caused by the high thoracic spread of analgesia, although a diminished hemodynamic homeostasis may contribute.

Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation.

Background Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. Methods Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of &agr;1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured. Results Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 ± 0.7 and 2.9 ± 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 ± 0.4 and 0.4 ± 0.2 mg/l (group 1) and 1.2 ± 0.4 and 0.5 ± 0.1 mg/l (group 2) after 72 h infusion. &agr;1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. Conclusions Postoperative increases in plasma &agr;1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.

Effect of Local Anesthetic Volume (15 vs 40 mL) on the Duration of Ultrasound-Guided Single Shot Axillary Brachial Plexus Block A Prospective Randomized, Observer-Blinded Trial

Background and Objectives One of the advantages of ultrasound-guided peripheral nerve block is that visualization of local anesthetic spread allows for a reduction in dose. However, little is known about the effect of dose reduction on sensory and motor block duration. The purpose of the present study was to compare the duration of sensory and motor axillary brachial plexus block (ABPB) with 15 or 40 mL mepivacaine 1.5%. Methods Thirty patients were randomly allocated to receive ultrasound-guided ABPB with either 15 (group 15 mL, n = 15) or 40 mL (group 40 mL, n = 15) mepivacaine 1.5%. Onset, efficacy, and duration of sensory and motor block were compared. Results Two patients in group 15 mL needed an additional rescue block before surgery and were excluded from subsequent analysis. The overall median duration of sensory and motor block was significantly shorter in group 15 mL (225 [148–265] mins vs 271 [210–401] mins and 217 [144–250] mins vs 269 [210–401] mins, respectively; P < 0.01). Duration of sensory and motor block of individual nerves was significantly shorter in group 15 mL (20%–40% reduction for sensory and 18%–37% for motor block). Time to first request of postoperative analgesia was also significantly reduced in group 15 mL (163 [SD, 39] vs 235 [SD, 59] mins, respectively, P < 0.05). There were no differences in the other block characteristics. Conclusions In ABPB with mepivacaine 1.5%, reducing the dose from 40 mL to 15 mL (62.5%) shortens the overall duration of sensory and motor block by approximately 17% to 19%, reduces sensory and motor block duration of individual nerves by 18% to 40%, and decreases the time to first request of postoperative analgesia by approximately 30%.

Lumbar epidural catheter insertion: the midline vs. the paramedian approach

Background and objective: The purpose of this study was to compare the characteristics of epidural catheter insertion via the midline or the paramedian approach with regard to ease of catheter insertion, incidence of paraesthesias and efficacy of epidural block. In addition to the type of approach, the prognostic value of Patients characteristics variables with regard to the incidence of paraesthesias was assessed. Methods: Thirty patients scheduled for surgery under epidural anaesthesia were randomly assigned to one of two groups of 15 patients each. Epidural anaesthesia was performed via a midline or paramedian approach using loss of resistance to saline. Variables measured were: time needed to identify the epidural space, time needed for and ease of epidural catheter insertion and the incidence of paraesthesias. After completion of these observations, epidural anaesthesia was established with 150 mg ropivacaine 1%. Efficacy of the epidural block was assessed by the need for intraoperative analgesics and by the patient on a three‐point scale (good/fair/poor). Results: Quality of sensory blockade was adequate in both groups. Catheter insertion was significantly faster using the paramedian approach. The difference between the two approaches with regard to the incidence of paraesthesias was not significant, however, there was a trend towards more paraesthesias in the midline group. In the multivariate analysis, type of approach was an independent significant predictor of paraesthesias and we found a trend towards a higher incidence of paraesthesias in female patients. Conclusions: Catheter insertion was faster in the paramedian group and we found a trend towards a higher incidence of paraesthesias with the midline approach.

The effect of age on the systemic absorption and systemic disposition of ropivacaine after epidural administration.

Knowledge about the systemic absorption and disposition of ropivacaine after epidural administration is important in regard to its clinical profile and the risk of systemic toxicity. We investigated the influence of age on the pharmacokinetics of ropivacaine 1.0% after epidural administration, using a stable-isotope method. Twenty-four patients were enrolled in 1 of 3 groups according to age (group 1: 18–40 yr; group 2: 41–60 yr; group 3: ≥61 yr). Patients received 150 mg ropivacaine hydrochloride epidurally. After 25 min, patients received 50 mL 0.44 mg/mL deuterium-labeled ropivacaine (D3-ropivacaine) IV. Arterial blood samples were collected up to 24 h after epidural administration. Total plasma concentrations of ropivacaine and D3-ropivacaine were determined using liquid chromatography mass spectrometry. In the oldest patients, elimination half-life was significantly longer (ratio of the geometric means 0.60; 95% confidence interval, 0.37–0.99) and clearance was significantly decreased (mean difference, 194 mL/min; 95% confidence interval, 18-370 mL/min) compared with the youngest patients. The systemic absorption was biphasic. Absorption kinetics for ropivacaine (fractions absorbed: (F1, F2) and half-lives: (t½,a1, t½,a2) during the fast and slow absorption process: 0.27 ± 0.08 and 0.77 ± 0.12, respectively; 10.7 ± 5.2 min and 248 ± 64 min, respectively) were in the same range as for other long-acting local anesthetics. F1 was on average 0.11 (95% confidence interval, 0.002-0.22) higher in the youngest compared with the middle age group. Observed age-dependent pharmacokinetic differences do not likely influence the risk of systemic toxicity in the elderly after a single epidural dose of ropivacaine.

Spinal Anesthesia with Plain Bupivacaine 0.5%: Regression of Sensory and Motor Blockade with Different Temperatures of the Anesthetic Solution

Onset (defined as the time between injection and achievement of the highest level of sensory blockade), duration, and regression of sensory and motor blockade after the intra-thecal administration of 3 mL plain bupivacaine 0.5%, previously equilibrated to either 37°C or 20°C, were studied in two groups of 20 patients. In patients receiving the solution equilibrated to 37°C, the maximum level of sensory blockade was significantly higher (T4.6 vs T 7.5), variability was smaller (SEM 0.33 us 0.58), and duration of the sensory level of blockade at or above T 6, T 8, and T 10 was significantly longer (56 min vs 20 min, 101 rnin vs 59 rnin, and 131 min vs 77 min, respectively). There were no significant differences with regard to onset of sensory and motor blockade or either the time needed both for the sensory level of blockade to regress two segments from its highest level and to the first lumbar segment, or the duration of complete motor blockade of the lower limbs. It is concluded that the intrathecal administration of a bupivacaine solution previously equilibrated to 37°C as compared with a solution injected at room temperature results in a higher, more predictable maximum sensory level of blockade with longer duration at or above T 6, T 8. and T 10.

The effect of stimulating versus nonstimulating catheter techniques for continuous regional anesthesia: a semiquantitative systematic review.

Background and Objectives: Stimulating catheters provide feedback regarding the location of the catheter tip in relation to the target nerve or plexus. There is debate concerning whether stimulating catheters may reduce the failure rate of postoperative analgesia or whether they may enhance functional recovery by providing superior and more reliable postoperative analgesia. Methods: Studies comparing the effect of stimulating versus nonstimulating catheters for postoperative analgesia were systematically and independently searched by 2 authors. Results: Eleven randomized controlled studies could be included in this review. One trial was performed in volunteers; the others were clinical trials in patients. Five trials were performed in patients scheduled for a femoral nerve catheter, 4 for a distal sciatic nerve catheter, 1 in patients receiving an interscalene nerve catheter, and 1 in patients with an infraclavicular brachial plexus block. A standard quantitative analysis was deemed inappropriate because of considerable heterogeneity regarding the investigated outcome parameters. A semiquantitative review revealed that efficacy (judged by reduction in the need for rescue analgesics, complete surgery block, or median effective local anesthetic volume blocking the nerve) suggests improvement in stimulating catheters compared with nonstimulating catheters. Patient satisfaction as well as functional recovery was poorly investigated, so no conclusions could be drawn. Conclusions: Published reports of randomized controlled trials provide evidence for a better analgesic effect from stimulating catheters. Future trials should be conducted in a standardized manner with uniform reporting of outcomes, which may facilitate future quantitative analysis.

Pharmacokinetics of the Enantiomers of Bupivacaine and Mepivacaine After Epidural Administration of the Racemates

We investigated the pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural injection of the racemate of each drug into six surgical patients.After epidural administration of either bupivacaine/HCl (115 mg) or mepivacaine/HCl (460 mg), blood samples were collected for 24 h. Unbound fractions were determined by using ultrafiltration for bupivacaine and equilibrium dialysis for mepivacaine. Concentrations in plasma, ultrafiltrate, and dialysate were determined by using stereoselective high-performance liquid chromatography. Peak plasma concentrations of R(+)-bupivacaine (389 +/- 93 ng/mL) and R(-)-mepivacaine (1350 +/- 430 ng/mL) were smaller than those of S(-)-bupivacaine (449 +/- 109 ng/mL, P < 0.0001) and S(+)-mepivacaine (1740 +/- 490 ng/mL, P < 0.002), respectively. However, the unbound peak concentrations of R(+)-bupivacaine (20 +/- 11 ng/mL) were larger than those of S(-)-bupivacaine (15 +/- 9 ng/mL, P < 0.005); unbound peak concentrations of R(-)-mepivacaine (485 +/- 158 ng/mL) and S(+)-mepivacaine (460 +/- 139 ng/mL) did not differ. These observations reflect differences in the systemic disposition (distribution and elimination) of the enantiomers, because the systemic absorption was not enantioselective with either drug. This study supports the opinion that the use of single enantiomers, rather than racemates, is preferable, particularly for bupivacaine. Implications: Measurements of the plasma concentrations of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates demonstrated that the systemic disposition, but not the systemic absorption, of these drugs is enantioselective and supports the opinion that the use of single enantiomers, rather than racemates, is preferable. (Anesth Analg 1998;86:361-6)