Density determination of local anaesthetic opioid mixtures for spinal anaesthesia

Abstract

Purpose: To measure the density of hyperbaric and isobaric local anaesthetics before and after addition of neuroaxial opioids to define a method for calculating any local anaesthetic/opioid mixture density based on individual component densities. Methods: Density was determined using a volumetric pycnometer (25.0281 _ 0.0013 ml). The density of local anaesthetics (bupivacaine, lidocaine), opioids (fentanyl, morphine) and multiple anaesthetic/opioid mixtures were measured in quadruplicate and expressed in g'ml -~, at 37~ (mean ___ SD). Regression analysis was used to derive a formula for calculating the density of any anaesthetic/opioid mixture. Results: Individual components had the following densities (g.ml-I): bupivacalne 0.75%; 1.0252 +_ 0.0001, lidocaine 5%; 1.0249 _ 0.0001, bupivacaine 0.5%; 0.9994 -+ 0.0001, lidocaine 2%; 1.0000 -+ 0.0001,50pg'ml -~ fentanyl; 0.9936 + 0.0001, and 0.5 mg'ml -I morphine; 1.0001 _ 0.0001. Using regression analysis, linear relationships were demonstrated between density (D) of anaesthetic/opioid mixture and the proportion of anaesthetic in the mixture (fractional volume of anaesthetic) (r = 0.9999, P < 0.001 ). The following formula was derived; DensityMix~ure = (DLc~al anaesthetic-Dopioid) X Fractional Volume Anaesthetic + Dopioid Comparison of calculated and measured densities for multiple clinically relevant anaesthetic/opioid mixtures showed a significant degree of correlation (r = 0.9996, P < 0.001 ). Conclusion: Density of spinal anaesthetic/opioid mixtures can be calculated from the component densities and the proportion of anaesthetic in the mixture.Objectif : Mesurer la densitE de solutions d'anesth&iques Iocaux isobares et hyperbares avant et aprEs addition d'opiacEs neuraxiaux pour determiner une m&hode de calcul de la densitE de tout melange d'anesthEsique Iocal/opiacE bas& sur les densit& des composantes individuelles. M~thodes : La densitE a EtE dEterminEe au moyen d'un pycnomEtre volumEtrique (25,0281 _ 0,0013 ml). La densitE des anesthEsiques Iocaux (bupivacalhe, lidoca/ne), des opiacEs (fentanyl, morphine) et de multiples melanges d'anesthEsiques Iocaux/opiac& a EtE mesurEe en quadruple et exprimEe en g-ml -I & 37~ (moyenne _ Ecart type). Une analyse de regression a EtE utilisEe pour produire une forrnule permettant le calcul de la densitE de tout melange anesth&ique Iocal/opiacE. REsultats : Les diff&entes composantes avalent les densitEs suivantes (g.ml-I): bupivacai'ne 0,75%: 1,0252 _ 0,0001 ; lidocafne 5%: 1,0249 _+ 0,0001 ; bupivacaine 0,5%: 0,9994 _ 0,0001 ; lidoca~'ne 2%: 1,0000 -0,0001 ; fentany150 pg'ml-a: 0,9936 --+ 0,0001; morphine 0,5 ml-~: 1,0001 ___ 0,0001. En utilisant une analyse de regression, des relations linEaires ont ErE dEmontrEes entre la densitE (D) du melange anesth&ique Iocal/opiacE et la proportion de I'anesthEsique local darts le melange (volume fractionnel de I'anesthEsique local) (r >0,9999, P<0,001

The addition of fentanyl does not alter the extent of spread of intrathecal isobaric bupivacaine in clinical practice

“…In conclusion, unlike the results found in the laboratory setting 5 and artificial spine model, 7 the addition of fentanyl to isobaric 0.5% bupivacaine with morphine does not result in a predictable difference in the height of anesthetic block in patients undergoing lower limb procedures. This may be due to wide variability in block level, related to patient or operator characteristics, dynamics of CSF flow, or the relative densities of solutions used.…”

“…These manoeuvres were used to enhance cephalad spread of the local anesthetic and emphasize any difference in baricity between groups, hypothesizing that fentanyl reduces the baricity of the local anesthetic solution. 5 However even with this approach, no difference in height of block was found between the two groups. Some anatomical factors related to positioning may exist which are not possible to control, such as the degree of thoracic kyphosis.…”

“…13 Morphine, in the dose used in the current study, does not substantially alter the density of a solution with bupivacaine 0.5%, or affect its characteristics in a CSF model. 5,7 Thus the findings of this study would not likely be different had fentanyl been mixed with bupivacaine 0.5% alone. Finally, temperature of the injectate affects its spread, with solutions warmed to 37° showing different characteristics in CSF than room temperature solutions.…”

“…Intrathecal morphine provides prolonged, good quality postoperative analgesia, while fentanyl has the advantage of decreasing visceral sensation and may prolong the duration of anesthesia. 3,4 In vitro studies examining the effect of adding opioids to local anesthetics have shown morphine to cause minimal change in baricity of the final solution, whereas fentanyl decreases the density of 0.5% bupivacaine by up to 0.0011 g·mL -1 , 5,6 where a difference of as little as 0.0006 g·mL -1 in density alters the movement of local anesthetics in a spinal model. 2 In a more recent study, our group found that the addition of fentanyl to 0.5% bupivacaine made the resultant solution hypobaric within simulated CSF in a spinal model, leading to increased upward spread.…”

“…The change in density due to fentanyl may thus be calculated to be as low as 0.00040 or as high as 0.00067 g·mL -1 , depending on the reference values used. 5,9 Since a difference of 0.0006 g·mL -1 has been shown to influence the spread of local anesthetic in CSF, 2 it is possible that the dose of fentanyl used in this study did not affect the density sufficiently to consistently alter the movement of the solution in CSF. In addition, CSF density may vary, leading to variability in baricity of the injected solution among individuals.…”