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Department of Anesthesiology and Intensive Care Medicine, University of Cologne, Cologne, Germany
To the Editor:
Hallworth et al. (1) demonstrated in vitro that the addition of glucose to intrathecally administered bupivacaine produced solutions of predictable density in a linear manner. For local anesthetic/opioid mixtures, they stated that the final glucose concentration, not the opioid, largely determines a solution’s density and expressed the following formula:
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In our hospital, bupivacaine 0.5%/8% glucose had been switched to bupivacaine 0.5%/5% glucose. In the first two patients who underwent cesarian section under spinal anesthesia with the new drug, we observed an insufficient spread of the block after administration of bupivacaine 0.5%/5% glucose with 20 µg fentanyl. The clinical efficacy of both local anesthetics should have been identical (2). Dextrose concentrations between 1.25% and 8% resulted in equivalent block heights (3). Hare et al. (4) presented a formula for calculating local anesthetic/opioid mixture density based on individual components:
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Hare et al. exemplified the clinical utility of the equation by determining the final density of an anesthetic/opioid mixture containing 15 mg hyperbaric bupivacaine 0.75% (2 mL), 0.4 mg morphine (0.8 mL), and 25 µg fentanyl (0.5 mL). The density changed from 1.0252 g/mL, for the anesthetic alone, to 1.0135 g/mL, for the final mixture, representing a decrease of 0.0117 g/mL. Calculating the density change based on the formula from Hallworth et al. for the same drug combination, the change would be 0.00877 g/mL, a value close to that calculated with Hare’s equation.
In our patients with the insufficient spread, we calculated a density of 1.0094 g/mL, 1.0098 g/mL respectively (using Hare’s formula). Nevertheless, solutions with a density higher than 1.0018 g/mL should behave hyperbarically (2). We could not find a clinical study confirming the theoretical value of Barash et al.
Based on this information we felt that the addition of fentanyl might have produced a critical dilution of the bupivacaine 0.5%/5% glucose leading to the observed insufficient spread of spinal anesthesia in our patients.
References
Dept of Anesthesia, Royal Free Hospital, Hampstead, London
In Response:
Thank you for allowing us to reply to the comments by Dr Kampe and her colleagues:
It is unfortunate that her patients failed to achieve adequate block heights following administration of 0.5% bupivacaine in 5% glucose. Naturally there are many reasons besides from density, which could account for an inadequate block. For example, what was the total dose of bupivacaine used for the spinal anesthetic? This is not indicated in the letter.
Two studies have compared plain (glucose-free) glucose with bupivacaine containing 5% or 8% glucose. Although there were differences in spread between the plain and the glucose containing solutions, there was no difference in spread between the 5% and 8% glucose groups (1,2) .
The mean (SD) density of fentanyl measured as part of our study was 0.99959 (0.00001) g/ml. The density of plain (glucose-free) bupivacaine was 0.99950 to 0.99970 g/ml. As you can see, the densities of the two agents are virtually identical, so when glucose is added to this mixture to produce a 5% solution, the addition of fentanyl will have a negligible effect on the final density of the solution. Based on a bupivacaine density of 0.99950 g/ml, then using the formula, the final density of a 5% glucose-containing solution will be 1.00085 g/ml. Such a solution should behave as a hyperbaric solution indistinguishable to standard 0.5% bupivacaine containing 8% glucose. We appreciate that they have added 0.4 ml fentanyl to the 5% bupivacaine solution and that there will be a small dilution effect but the solution itself will still be significantly hyperbaric.
We believe that the formula used by Hare et al underestimates the effect of glucose and overestimates the effect of opioids in altering the density of bupivacaine. We cannot explain why Dr Kampe’s 5% mixture was inadequate for anesthesia, although acquiring a density measuring machine (accurate to 5 decimal places) to measure the solution itself would be one suggestion. If the density of the plain bupivacaine solution was measured at the same time they should find that the densities correspond to the equation in our study.
References
This article has been cited by other articles:
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  A. Dutta and A. Taneja Minimum Effective Dose of Bupivacaine Required for Transurethral Procedures Remains Uncertain Anesth. Analg., October 1, 2007; 105(4): 1170 - 1170. [Full Text] [PDF]
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