Infusion Of Levobupivacaine Research Articles

Continuous peripheral nerve blocks: state of the art

This review was performed through a Medline research to evaluate articles published between January 2004 and April 2005. Technical procedures, indications, drugs, infusion regimens, and complications of continuous peripheral nerve blocks were considered. A total of 27 articles were reviewed. With respect to technical procedures, the authors focused on advantages of stimulating catheters or ultrasound guidance. With the help of these techniques, a correct catheter placement as close to the targeted nerve as possible was obtained. The total amount of local anesthetic administered was thereby reduced. Using ultrasound needle guidance, the spread of local anesthetic around the nerve could be visualized. Articles dealing with the choice of local anesthetic showed equianalgesia and equipotency of continuous perineural infusion of levobupivacaine 0.125% and ropivacaine 0.2%. The best infusion regimen for postoperative analgesia appears to be a combination of a preset basal rate administered together with small bolus doses in almost all continuous peripheral nerve blocks. Overall, complications such as infections, local anesthetic toxic plasma levels, hematoma formation, or nerve injury seem to be rare in continuous peripheral nerve blockade. Continuous peripheral nerve blockade is an effective and safe technique for postoperative analgesia, even when administered at home. To optimize this technique, further studies are needed to help minimize the risk of side effects, improve techniques to locate the targeted nerve (stimulating catheters or ultrasound imaging) and choose less toxic drugs (levobupivacaine and ropivacaine) with more effective infusion regimens.

Automated regular boluses for epidural analgesia: a comparison with continuous infusion

Intermittent epidural bolus dosing is a method of drug delivery that can prolong the duration of labour analgesia induced by a combined spinal epidural (CSE). In this randomized, double-blinded study, we compared the analgesic efficacy of two drug delivery systems: regular intermittent epidural boluses and continuous epidural infusion and assessed the incidence of breakthrough pain after CSE. With the approval of the Hospital Ethics Committee, we recruited 60 parturients into this randomized controlled trial. A CSE was performed with intrathecal fentanyl 25 mug in all patients. The parturients were then randomly allocated into two groups. The infusion group received a continuous epidural infusion of levobupivacaine 0.1% with fentanyl 2 microg/mL at a rate of 10 mL/h. The bolus group received 5-mL epidural boluses every half hour. The sample size was computed to detect a 40% reduction in the rate of breakthrough pain. The bolus group had a lower incidence of breakthrough pain than the infusion group (10% vs. 37%, P < 0.05). The bolus group also had significantly higher satisfaction scores for labour analgesia: 97+/-8 (mean+/-SD) vs. 89+/-7 (P < 0.05). Automated regular bolus delivery of epidural analgesia when compared with continuous infusion decreased the incidence of breakthrough pain and increased maternal satisfaction. In a busy obstetric unit, this may also serve to decrease the anesthetists' workload.

Dexmedetomidine Decreases the Convulsive Potency of Bupivacaine and Levobupivacaine in Rats: Involvement of α2-Adrenoceptor for Controlling Convulsions

Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in combination with local anesthetics for sedation and analgesia. We tested the hypothesis that dexmedetomidine used for sedation alters the convulsive potency of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing rats. In the first experiments, male Sprague-Dawley rats were randomly divided into six groups: bupivacaine with no dexmedetomidine (bupivacaine control; BC), bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose dexmedetomidine (BL), levobupivacaine with no dexmedetomidine (levobupivacaine control; LC), levobupivacaine with small-dose dexmedetomidine (LS), and levobupivacaine with large-dose dexmedetomidine (LL) (n = 10 for each group). Continuous infusion of dexmedetomidine (Groups BC and LC, 0 microg x kg(-1) x h(-1); Groups BS and LS, 3.6 microg x kg(-1) x h(-1); and Groups BL and LL, 10.8 microg x kg(-1) x h(-1)) was started after bolus injection (Groups BC and LC, 0 microg/kg; Groups BS and LS, 0.5 microg/kg; and Groups BL and LL, 1.5 microg/kg). Fifteen minutes after the start of the dexmedetomidine infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until tonic/clonic convulsions occurred. Dexmedetomidine achieved significantly different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and LL (P < 0.05). Convulsive doses of bupivacaine and levobupivacaine were significantly larger in Groups BL and LL than in Groups BC and LC, respectively (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma and in brain at the onset of convulsions were also larger in Groups BL and LL than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine (1 mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5 microg/kg, followed by 10.8 microg x kg(-1) x h(-1)). Convulsive doses and plasma and brain concentrations of bupivacaine and levobupivacaine at the onset of convulsions in rats receiving yohimbine and dexmedetomidine were significantly smaller than in those receiving only dexmedetomidine (P < 0.05 for all) and were similar to those without dexmedetomidine or yohimbine. We conclude that dexmedetomidine used for sedation decreases the convulsive potency of both bupivacaine and levobupivacaine in rats. Alpha(2)-adrenoceptor agonism may be involved in this anticonvulsant potency.

Effects of CNS site-directed carotid arterial infusions of bupivacaine, levobupivacaine, and ropivacaine in sheep.

Previous preclinical safety studies in ewes have found intravenous levobupivacaine and ropivacaine to be less potent toward causing central nervous system (CNS) and cardiac toxicity than bupivacaine. Analogous cardiotoxicity has been demonstrated directly in various cardiac preparations ex vivo. Moreover, drug-related arrhythmogenicity has been demonstrated from direct CNS injection of local anesthetic agents in vivo, suggesting CNS-related cardiotoxicity. This study investigated whether CNS site-directed blood-borne drug administration (with minimal systemic recirculation) would demonstrate drug-related cardiotoxicity. Direct CNS effects and indirect cardiotoxic sequelae were determined after bilateral carotid arterial infusions of levobupivacaine, bupivacaine, or ropivacaine in ewes. After pilot studies to validate the procedures, equimolar doses (24-96 micromol, approximately 7.5-30 mg) were infused over 3 min using a crossover design. Behavioral CNS signs, quantitative electroencephalographic (EEG), cardiovascular, and electrocardiographic effects were recorded. Drug blood concentrations in superior sagittal sinus and aorta were measured serially. Blood drug concentrations in the superior sagittal sinus were 5-10 times those concurrently in the aorta, confirming highly selective CNS delivery with minimal systemic recirculation. Dose-dependent CNS excitatory behavior and EEG changes, with increased mean arterial blood pressure, heart rate, cardiac output, and myocardial contractility, were found, consistent with sympathetic nervous system stimulation. The overall rank order of potency for these effects was ropivacaine < levobupivacaine < bupivacaine. Nonfatal cardiac arrhythmias were observed, but the type or frequency did not differ between drugs. Although CNS site-selective drug delivery produced quantitative differences between bupivacaine, levobupivacaine, and ropivacaine in some CNS effects and cardiac sequelae, no differences were found in their arrhythmogenic potential.

The efficacy and safety of epidural infusions of levobupivacaine with and without clonidine for postoperative pain relief in patients undergoing total hip replacement.

We assessed the efficacy and tolerability of epidural infusions of levobupivacaine, levobupivacaine plus clonidine, and clonidine for postoperative analgesia in 86 patients undergoing total hip replacement. For each group, an epidural cannula was inserted before surgery and 15 mL of 0.75% plain levobupivacaine was administered. Three hours later, an epidural infusion (6 mL/h) of levobupivacaine 0.125% (L), levobupivacaine 0.125% plus clonidine 8.3 microg/mL (LC) or clonidine alone (8.3 microg/mL) (C) was initiated. Morphine consumption was recorded for the following 24 h as were visual analog pain scores and the degree of sensory and motor blockade. The mean (median) morphine consumption was lowest in the combination group (LC),14 (7) mg; higher in the clonidine group (C), 23 (21) mg; and highest in the levobupivacaine group (L), 37 (36) mg (P = 0.022). The median times until the first request for analgesia which were 2. 9, 5.9, and 12.5 h for Groups L, C, and LC, respectively (P < or = 0. 01). There were no statistical differences among the groups regarding the maximum degree of postoperative motor blockade. On average, the systolic blood pressure in the two clonidine groups was slightly lower than in those from the levobupivacaine group. We conclude that the epidural administration of a combination of levobupivacaine plus clonidine is well tolerated and gives better analgesia than either drug used alone. In patients undergoing total hip replacement, the addition of the alpha(2)-adrenergic agonist clonidine to epidural infusions of levobupivacaine significantly improved postoperative analgesia.

The Efficacy and Safety of Epidural Infusions of Levobupivacaine With and Without Clonidine for Postoperative Pain Relief in Patients Undergoing Total Hip Replacement

We assessed the efficacy and tolerability of epidural infusions of levobupivacaine, levobupivacaine plus clonidine, and clonidine for postoperative analgesia in 86 patients undergoing total hip replacement. For each group, an epidural cannula was inserted before surgery and 15 mL of 0.75% plain levobupivacaine was administered. Three hours later, an epidural infusion (6 mL/h) of levobupivacaine 0.125% (L), levobupivacaine 0.125% plus clonidine 8.3 μg/mL (LC) or clonidine alone (8.3 μg/mL) (C) was initiated. Morphine consumption was recorded for the following 24 h as were visual analog pain scores and the degree of sensory and motor blockade. The mean (median) morphine consumption was lowest in the combination group (LC),14 (7) mg; higher in the clonidine group (C), 23 (21) mg; and highest in the levobupivacaine group (L), 37 (36) mg (P = 0.022). The median times until the first request for analgesia which were 2.9, 5.9, and 12.5 h for Groups L, C, and LC, respectively (P ≤ 0.01). There were no statistical differences among the groups regarding the maximum degree of postoperative motor blockade. On average, the systolic blood pressure in the two clonidine groups was slightly lower than in those from the levobupivacaine group. We conclude that the epidural administration of a combination of levobupivacaine plus clonidine is well tolerated and gives better analgesia than either drug used alone. Implications In patients undergoing total hip replacement, the addition of the α2-adrenergic agonist clonidine to epidural infusions of levobupivacaine significantly improved postoperative analgesia.

Accidental Intravenous Levobupivacaine

Accidental Intravenous Levobupivacaine

The placental transfer and fetal effects of levobupivacaine, racemic bupivacaine, and ropivacaine.

The purposes of this study were to assess the effects of levobupivacaine on uterine blood flow and fetal well-being and to compare its placental transfer with that of bupivacaine and ropivacaine. After a control period, pregnant ewes that were fitted with instruments for long-term monitoring were randomized to receive a two-step intravenous infusion of levobupivacaine, bupivacaine, or ropivacaine, in a blinded manner, for 1 h. Maternal and fetal hemodynamics were monitored during the study. Arterial blood samples were drawn at 30 and 60 min of infusion from the mother and fetus to determine the acid-base status (60 min only) and serum drug concentrations. The fetal brain, heart, liver, lungs, adrenal glands, and kidneys were obtained to measure tissue drug levels. Maternal blood pressure, central venous and intraamniotic pressures, acid-base status and uterine blood flow were unaffected by any drug infusion. In contrast to the other two local anesthetics, the infusion of bupivacaine was associated with a small but significant decrease in the ewe's heart rate. At the end of the study, the heart rate in the bupivacaine-treated animals was significantly less than in the animals treated with the other two drugs. All fetuses were in good condition at the start of study, and none of the local anesthetics affected fetal well-being. No significant differences were found among the three drugs in the maternal serum, fetal serum, fetal tissue concentrations, and tissue:serum concentration ratios. Levobupivacaine was similar to bupivacaine and ropivacaine in causing no important hemodynamic changes in the pregnant ewe and fetus. There were no significant differences in the fetal serum and tissue levels of the drugs.