Pharmacokinetics and efficacy of 40 ml ropivacaine 7.5 mg/ml (300 mg), for axillary brachial plexus block--an open pilot study.

In this study, the pharmacokinetics, tolerability and efficacy of 40 ml of ropivacaine 7.5 mg/ml (300 mg) for axillary brachial plexus block were investigated. With institutional review board approval, 10 patients presenting for surgery of the upper limb were enrolled in this open study. The axillary plexus was identified with a nerve stimulator and the study drug was injected into the neurovascular sheath. Fifteen venous blood samples were obtained from each patient for pharmacokinetic measurements over a 24-h period. All blocks were sufficient for surgery after 45 min without any need for supplemental analgesia or general anesthesia. The mean (SD) peak plasma concentration was 2.3 (0.8) mg/l at median tmax 54 min (range 16-92 min). The mean (SD) maximum free plasma concentration was calculated to be 0.12 (0.06) mg/l (range 0.07-0.29 mg/l). The t 1/2 was about 6 h. There were no clinical signs or symptoms of central nervous system and/or cardiac toxicity in any patient. Ropivacaine 7.5 mg/ml, used in a dose of 300 mg, was effective and well tolerated for axillary brachial plexus block.

Gene therapy for pediatric AIDS.

Gene therapy is an experimental treatment modality under investigation for applications to HIV-1 infection. We have developed retroviral vectors carrying anti-HIV-1 genes, demonstrated that these genes cause significant suppression of HIV-1 replication in cultures of primary hematopoietic cells, and performed a clinical trial in pediatric AIDS patients. Four HIV-1-infected children and adolescents underwent bone marrow harvest from which CD34+ cells were isolated and transduced by a retroviral vector carrying an RRE decoy gene. The cells were re-infused into the subjects, without complications, showing that gene transfer in pediatric AIDS patients in safe and feasible. However, gene-containing leukocytes in the peripheral blood were seen only at a low level and only in the first months following cell infusion. To attain some degree of efficacy, it will be necessary to achieve a higher level of gene transfer and to obtain sustained gene expression. We are currently developing new gene transfer methods and vectors designed to improve the results in future trials. If it becomes possible to reach the ideal goal of producing high percentages of T lymphocytes and monocytic cells that are resistant to HIV-1 infection, gene therapy could serve as a complement to antiretroviral drug therapy and help to sustain immunologic function.

Axillary brachial plexus block with ropivacaine 7.5 mg/ml. A comparative study with bupivacaine 5 mg/ml.

BACKGROUND: Ropivacaine is less cardiotoxic than bupivacaine and may be used in higher doses in order to increase the quality of a block. The aim of this study was to compare the efficacy and safety of 40 ml ropivacaine 7.5 mg/ml (300 mg) and 40 ml bupivacaine 5 mg/ml (200 mg) for axillary plexus block. METHODS: One hundred and four adult patients were included in a prospective, double-blind study. Sensory and motor block were tested for the five main terminal nerves of the arm at 10-min intervals until start of surgery and every second hour there-after until full resolution of the block. RESULTS: The overall evaluation of the block by the surgeon and the anesthesiologist showed a significantly better quality in the ropivacaine patients, regarding both anesthesia and motor block. There were no differences in the time to onset and duration of the block. Except for one patient, who had seizures after an accidental IV injection of ropivacaine, there were no major side effects. CONCLUSION: Ropivacaine 7.5 mg/ml, 40 ml, produces axillary plexus block of similar onset and duration but better quality than 40 ml of bupivacaine 5.0 mg/ml.

Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and bupivacaine: a prospective meta-analysis.

In this prospective meta-analysis, we have evaluated the effect of epidural analgesia with ropivacaine for pain in labour on neonatal outcome and mode of delivery compared with bupivacaine. In six randomized, double-blind studies, 403 labouring women, primigravidae and multiparae, received epidural analgesia with ropivacaine or bupivacaine 2.5 mg ml-1. The drugs were administered as intermittent boluses in four studies and by continuous infusion in two. Apgar scores, neurological and adaptive capacity scores (NACS), degree of motor block and mode of delivery were recorded. The studies were designed prospectively to fit meta-analysis of the pooled results. Results showed similar pain relief and consumption of the two drugs. In the vaginally delivered neonates, NACS scores were approximately equal for both groups at 2 h, but at 24 h there were fewer infants with NACS less than 35 in the ropivacaine compared with the bupivacaine group (2.8% vs 7.6%; P < 0.05). Spontaneous vaginal deliveries occurred more frequently overall with ropivacaine than with bupivacaine (58% vs 49%; P < 0.05) and instrumental deliveries (forceps and vacuum extraction) less frequently (27% vs 40%; P < 0.01), while the frequency of Caesarean section was similar between groups. The intensity of motor block was lower with ropivacaine. There were no significant differences in adverse events.

Continuous axillary brachial plexus block for postoperative pain relief. Intermittent bolus versus continuous infusion.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the efficacy and safety of continuous axillary brachial plexus block by infusion and by intermittent injection of bupivacaine 0.25% in the management of postoperative pain. METHODS: Two methods of continuous axillary brachial plexus block for pain management were compared in a prospective randomized trial. Twenty 16- to 62-year-old male patients (ASA I and II), undergoing microsurgery, received 0.25% bupivacaine following surgery, by either continuous infusion (group C, n = 10), or intermittent hourly bolus (group B, n = 10), via an axillary brachial plexus catheter inserted prior to operation. Efficacy assessments and analysis of plasma bupivacaine levels were performed for up to 38 hours postsurgery. RESULTS: There was no difference between groups with respect to pain scores, degree of motor block, or supplemental narcotic requirements. Plasma bupivacaine levels were higher in group C, with the difference reaching significance after 26 hours (means +/- SEM: C = 1.03 +/- 0.10 micrograms/mL, B = 0.73 +/- 0.08 microgram/mL, P < .05). There were no significant differences in cumulative bupivacaine doses or infusion rates between the groups. Complications included one case of axillary artery puncture at insertion, two unplanned premature catheter removals, and a self-limited grand mal convulsion in a known epileptic. CONCLUSIONS: Overall, both techniques provided safe and effective postoperative analgesia. As compared with continuous infusion, intermittent bolus administration resulted in lower plasma bupivacaine levels despite similar infusion rates.

Neurotoxicity of local anesthetics: animal data.

OBJECTIVE: To extract experimental data of importance for the understanding of neurotoxicity of local anesthetics, with special reference to continuous spinal anesthesia. METHODS: Literature on clinical experience of and experimental studies on neurotoxic complications of local anesthetics, especially concerning spinal and continuous spinal anesthesia and long-term peripheral nerve block, was reviewed. The overall incidence of neural complications of central and peripheral nerve blocks was extracted, and the results of animal experimental studies on neurotoxicity of local anesthetics were used to characterize the possible mechanisms behind such complications. RESULTS: Persistent neurologic complications of regional anesthesia varied from 0 to 0.09% for central blockades and from 0 to more than 5% for brachial plexus blocks, depending on the technique used. All local anesthetics seem to be involved in clinical reports of neural complications. Experimental studies indicate that all local anesthetics are potentially neurotoxic and that the neurotoxicity parallels their anesthetic potency. In fact, the nerve conduction block may be an expression of a reversible toxic effect of the local anesthetic (LA). The mechanism is not completely understood, but factors of importance are the concentration of the LA and time of exposure of the neural tissue to the LA. Contributing factors are neural trauma and ischemia, both of which may be deleterious by themselves. CONCLUSIONS: Correctly administered LAs of clinical concentration are safe, but animal data indicate that all LAs are potentially neurotoxic. The neurotoxicity seems to be a function of the concentration of the LA and the time of exposure of the nervous tissue to the LA. Concomitant neural trauma, ischemia, or both, may potentiate the neurotoxic effect of the LA.

Baricity and the distribution of lidocaine in a spinal canal model.

The role of the baricity of local anaesthetic solutions in determining the distribution of local anaesthetics injected into the subarachnoid space (and hence the level of anaesthesia) has been challenged. A recent study found no difference in the extent of cephalad spread of hyperbaric and isobaric solutions and concluded that density had no effect on the spread of local anesthetics. The present study, to determine the validity of this conclusion, utilized a spinal model filled with a "cerebrospinal fluid equivalent." Following the injection of hyperbaric lidocaine, the local anaesthetic was most concentrated at the lower end of the column, whereas following the injection of isobaric solution the local anaesthetic was most concentrated around the site of injection. Therefore, baricity is an important determinant of local anaesthetic distribution in the subarachnoid space.

Adrenergic vasoconstriction in peripheral nerves of the rabbit.

The blood flow in the sciatic nerve of the rabbit was estimated from the wash out of intraneurally injected 133Xe. To avoid diffusion of the tracer into the surrounding muscular tissue, the nerve was covered by a gas-tight plastic film. Using this technique, the basal blood flow in the sciatic nerve was estimated to 35 ml X min-1 X 100 g-1. It was found that intraarterial norepinephrine and electrical stimulation of the lumbar sympathetic chain strongly reduced the wash out of 133Xe, which only can be explained by a pronounced reduction of the blood flow in the nerve itself. The blood flow again increased within 4 min of stopping the infusion of norepinephrine or the sympathetic stimulation. The prolonged effect and higher neurotoxicity of local anesthetics containing adrenaline may be explained by an alpha receptor-mediated vasoconstriction of the microvessels of peripheral nerves.

Intratumor distribution of capillary permeability surface area product (PS) correlated to tumor vascular space and blood flow.

The intratumor distribution of the capillary permeability surface area product (PS) correlated to the intratumor distribution of vascular space and of blood flow was studied by labeled albumin in a transplantable rat fibrosarcoma. A wide heterogeneity in intratumor distribution of PS was found. The tumor PS values were not significantly correlated to tumor vascular space or to blood flow values. This might suggest that intravascularly administered drugs could reach a comparative high intratissue concentration also in less vascularized tumor areas.

Local discomfort and thrombophlebitis following intravenous injection of diazepam. A comparison between a glycoferol-water solution and a lipid emulsion.

Diazepam is frequently used for pre- and peroperative sedation. However, at i.v. injection local pain and thrombophlebitis are not uncommon, probably due to tissue irritancy of the various organic solvents necessary to keep diazepam in aqueous solution. In this study the incidence of local adverse effects following i.v. injection of Diazemuls, a new lipid emulsion formulation, was compared with that of Apozepam, a glycoferol-water solution. We found that the latter preparation caused local pain and thrombophlebitis as often as reported with propyleneglycol-phenylcarbinol-ethanol preparations (Stesolid, Valium) and in a statistically higher incidence that the lipid emulsion form, which therefore seems more suitable for intravenous use.