Anaesthesia, 1991, Volume 46,pages 1023-1029

The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine

A. P. BARANOWSKI, Y. DEAN,

AND

C. E. PITHER

Summary

Twenty-four patients receiving epidural anaesthesia were studied to test the hypothesis that 1:200 000 adrenaline administered into the epidural space 5 minutes before 20 ml bupivacaine 0.5% would improve nerve block and delay systemic absorption of the local anaesthetic. Group AIB received 20 ml adrenaline 1:200 000 5 minutes before 20 ml bupivacaine O.S%, group SIBA 20 ml saline followed by 20 ml bupivacaine 0.5% with 100 pg adrenaline, and group SJB saline 20 ml followed by 20 ml plain bupivacaine 0.5%. Mean maximum plasma concentrations of bupivacaine tended to be lower in the adrenaline groups. A delay in the time to peak plasma concentration of bupivacaine was noted in the AIB group; this indicated that priming with adrenaline may be effective at delaying early systemic uptake of the local anaesthetic. In both adrenaline groups a more prolonged epidural block and increased eficacy were noted, although this was only significant for the duration of block at T6 (p = 0.023) and duration of motor block at Bromage level I ( p = 0.016) in group AIB. There seems little clinical advantage in administering adrenaline 5 minutes before bupivacaine. Key words

Anaesthetic techniques regionab epidural. Anaesthetics, local; bupivacaine. Adrenaline.

Bupivacaine is an amide local anaesthetic often used to provide epidural analgesia. It is described as a long-acting agent, but the duration of action is affected significantly by the vascularity of the area into which it is injected.’.’ Increased vascularity is associated with an increased systemic absorption rate and a decreased duration of neural blockade. Bupivacaine may enhance its own absorption directly by causing vasodilatation and indirectly by sympathetic blockade.’ Vasoconstrictors are added to injections of local anaesthetic to lower peak plasma concentration and hence reduce the risk of systemic t o x i ~ i t y .They ~.~ may also increase the duration of blockade, the depth of blockade and, in the case of epidural anaesthesia, the extent of the block. The recommended concentration of adrenaline to produce maximum effect with minimum side effects is thought to be l:200000.2,4 In the numerous studies reviewed by Tucker and Mather’ in 1979, and in a recent study,’ vasoconstrictors lowered the peak plasma concentrations of local anaesthetic after epidural injection, but did not always prolong the time to peak concentrations. This suggests that significant absorption of the local anaesthetic

occurs before the full vasoconstricting effect of adrenaline becomes a~parent.’,~Some support for this suggestion comes from a recent study on the effect of 1:200000 adrenaline on the absorption of diamorphine. Priming the epidural space with adrenaline resulted in lower mean plasma diamorphine levels than observed when the adrenaline was given at the same time as the diamorphine.6 It is also known that adrenaline takes approximately 5 minutes to exert its vasonconstrictor effect.’ Therefore, we decided to investigate the effect of priming the epidural space with 1:200 000 adrenaline 5 minutes before the injection of bupivacaine. We compared results in the pretreated group with those in a group in whom the adrenaline was given at the same time as the bupivacaine, and with those in a group that was given plain bupivacaine alone. Methods

Local ethics committee permission was obtained and all patients gave informed written consent. All patients were ASA grades 1 and 2, aged less than 60 years and scheduled

A.P. Baranowski, BSc, MB, BS, FFARCS, Research Fellow, Department of Physiology, and Honorary Registrar, Department of Anaesthetics, Y. Dean, LRCP, MRCS, FCAnaes, Honorary Research Registrar, C.E. Pither, MB, BS, FFARCS, Consultant, Department of Anaesthetics, St. Thomas’ Hospital, Lambeth Palace Rd, London SEl 7EH. Accepted 15 May 1991. 0003-2409/91/121023 +07 $03.00/0

@ 1991 The Association of Anaesthetists of Gt Britain and Ireland

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for routine extracorporeal shock wave lithotripsy. Routine ECGs were performed on all patients, who were allocated randomly into one of three groups; the study was performed in a double-blind manner. The treatment protocols were assigned by choice of sealed envelopes and both protocol and drug were checked by an independent anaesthetist. No premedication was used. A large bore intravenous cannula was inserted into a vein in each arm. One was used to administer an infusion of compound sodium lactate solution, and the other, which was kept patent with heparinised saline, was used to take blood samples. An epidural catheter was inserted using a 16 G Tuohy needle at the L2-3level by the midline approach and loss of resistance to saline method. The catheter was flushed with saline before insertion and introduced to leave 4 cm in the epidural space. Following fixation of the catheter, the patient was returned to the sitting position at approximately 45". A continuous ECG monitor was attached to the patient and blood pressure was measured at one minute intervals using an automatic noninvasive technique. One litre of compound sodium lactate solution was infused intravenously before the injections into the epidural space. A 3 ml epidural test dose of I % plain lignocaine was given, followed 4 minutes later by the priming drug, 20 ml of either saline or 1:200 000 adrenaline in saline, injected over one minute. After a further 5 minutes, 20 ml of bupivacaine, either with adrenaline 1:200 000 or as plain solution, was given over 2 minutes. The end of this injection was taken as time zero. The three patient groups were designated: S/B = saline prime followed by plain bupivacaine, S/BA = saline prime followed by bupivacaine with 1:200 000 adrenaline, A/B = adrenaline 1 :200 000 prime followed by plain bupivacaine. Over a 2 hour period serial measurements of systolic, diastolic and mean blood pressure, and pulse rate were made. The spread of sensory analgesia, as detected by loss of sensation to the blunt end of a 27 G short dental needle, was recorded at 2, 5, 10, 15, 25, 30 minutes and every 30 minutes thereafter until the block had worn off. Motor blockade (MB) was measured at the same time using a modified Bromage scale. The grades of MB were: 0 = no paralysis, full flexion of knee and feet; 1 = inability to raise extended leg, just able to move knees; 2 = inability to flex knees, can move feet only; 3 = inability to flex ankle joint or any part of leg. The quality of analgesia was scored from 1-3 (I, no pain; 2, mild discomfort; 3, severe pain). Any concomitant medication or complications were also noted.

Table 1. Demographic data

Mean age years; (SD) Mean weight kg: (SD) Mean height cm: (SD)

Statistical analysis For normally distributed data, multiple group comparisons were performed by the analysis of variance (ANOVA) statistical test. This was followed by the two-sided unpaired Student's t-test when indicated. Nonparametric data analysis involved the use of the Kruskal-Wallis test followed by the Mann-Whitney U test when indicated. Statistical comparisons of frequency were made with the Chi-squared test (with Yates' continuity correction). Statistical significance was assumed at the 5% level.

Results The three groups of patients were matched for age, weight and height (Table 1). The S/B and S/BA groups comprised men only, the A/B group included two females. The male bias was due to the nature of the surgery. In each group seven out of the eight patients had satisfactory analgesia, with one patient requiring supplementary analgesia. No patients developed complications. Figure I shows the mean cardiovascular changes associated with the three epidural treatments. Adrenaline caused a mean rise in pulse rate greater than the 95% confidence interval at several time points. However, the highest mean rise in pulse rate at any time within the monitored 2 hour period was not significantly different between groups and the time spent with a relatively raised pulse rate of either 10% or 15% was also not significantly different at the 5 % level (Table 2). Systolic, diastolic and mean blood pressure fell in all three groups. The time spent at a systolic blood pressure of either 90% or 75% of the baseline value was not significantly different between the groups; the maximum fall in systolic blood pressure was also not significantly different (Table 2). One patient in each of the groups required ephedrine and atropine, and one patient in each of the SJBA and A/B groups required ephedrine alone. The amount of intravenous fluid given was similar in all groups. Figure 2 shows the mean extent of sensory block (as measured by loss of touch sensation) as a function of time. From one to three hours the adrenaline groups had a mean

Table 2. Changes in cardiovascular parameters expressed in terms of percentage of preblock values. Preblock values = 100%. Mean (SEM).

Highest pulse rate: % Time spent with pulse rate 110%; minutes Time spent with pulse rate > 115%; minutes Lowest systolic BP; % Time spent with systolic BP < 90%; minutes Time spent with systolic BP < 75%; minutes

SJB

SJBA

AJB

1I5 (3.4)

I 24 (4.5)

128 (5.4)

26.6 (10.7)

43.1 (15.6)

58.1 (15.0)

16.6 (7.6) 82.7 (3.4)

30.9 (13.0) 75.6 (5.52)

38.4 (10.2) 77.1 (4.5)

44.3 (17.4)

59.5 (16.4)

47.7 (15.4)

3.1 (1.9)

28.1 (13.9)

11.9 (8.0)

Efect of adrenaline on bupivacaine epidural blockade

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Fig. 2. Mean segmental spread of analgesia as determined by loss of sensation to a 27 G short dental needle. The top chart shows the spread in the upward direction away from the site of the catheter and the lower chart the downward spread. The data are expressed as SJBA; 0,A/B. mean (SEM 1.96) 8 , SIB;

m,

Table 4. Sensory block characteristics. Table 3. Number of patients achieving analgesia to specific levels.

6 2

Time taken to achieve highest sensory level; minutes, mean (SEM) Time spent at highest sensory level; minutes, mean (SEM) Overall duration of sensory block; minutes, mean (SEM)

SIB

S/BA

A/B

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the S/BA and A/B groups just failed to reach significance (Chi-square (Y) = 5.58, p = 0.06). The onset times for the three levels of motor blockade were not significantly different amongst the groups. However, the A/B group had a longer duration of motor block at level 1 compared to the S/B group (t-test, p = 0.016). The S/BA group also had a greater level 1 motor block duration but this just failed to reach significance (r-test, p = 0.051). Mean plasma bupivacaine concentrations in the three groups are shown in Figure 4. Mean values of the maximum concentration (C,& the time taken to achieve maximum concentration (T,,J and the area under the concentration/time curve (AUC) are given in Table 6 . There were no statistical differences between the maximum bupivacaine levels found, or the time to these maximum levels, although the mean level with the S/B group is higher and the time taken to reach the maximum level for the A/B group is longer. There was no statistical difference between the groups with regard to area under the curve.

upward spread greater than the 95% confidence limit for the S/B group. Table 3 shows the number of patients in each group who achieved a particular height of block. The number of patients achieving a clinically useful block of T, or T, was not significantly different between the groups when the Yates' correction to the Chi-squared test was applied. Figure 3 shows the mean time spent at each block height. The time spent at T, (for those patients who achieved this level) was also not significantly different between the groups. However, for T, block the A/B group spent more time blocked at that level than the S/B group (t-test, p = 0.023) but not the S/BA group. The mean time to achieve the highest sensory block, the mean length of time spent at that level and the overall duration of sensory block are shown in Table 4 for all three groups. No significant differences were noted between the groups for these parameters. Data on motor blockade are summarised in Table 5. The number of lower limbs in each group blocked to a grade 2 or higher was increased when adrenaline was used, significantly so in group A/B (Chi-square (Y) = 6.282, p = 0.043). The number of lower limbs blocked to grade 3 in

Discussion The addition of adrenaline to local anaesthetic solutions for epidural analgesia has been common practice for many

Table 5. Motor block (MB) characteristics.

Number of lower limbs achieving MB level 1 MB level 2 MB level 3 in minutes, mean (SEM) Onset time for MB level 1 MB level 2 MB level 3 in minutes, mean (SEM) Duration of MB level 1 MB level 2 MB level 3 in minutes, mean (SEM)

15 3 0

12 7 6

16 11 6

17.8 (2.5) 25.0 (5.0) N/A

15.8 (1.9) 52.9 (34) 75.8 (52)

18.8 (2.3) 39.0 (8.2) 56.7 (32)

(26.9) (23.5) (23.3)

205 (46) 113 (36.7) 100 (20.4)

81 70

(17.7) (0.0) N/A

148 92 74

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A.P Baranowski, Y. Dean and C.E. Pither

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Fig. 4. Mean plasma bupivacaine concentrations (SEM 1.96). A, A/B; 0,S/BA; x , S/B.

years and is widely recommended in standard It has been shown that adrenaline-bupivacaine mixtures tend to produce a denser and more reliable block than when a plain solution is used.’-” The addition of adrenaline lowers the peak plasma concentration of local anaesthetic but does not necessarily alter the time to attain that peak.12 This may reflect a slow onset of action; adrenaline-induced vasoconstriction is not attained until a proportion of the dose of bupivacaine has been ab~orbed.~,’ The extent and intensity of the block, both motor and sensory, will depend upon the amount of local anaesthetic available to penetrate the neural tissue. If less local anaesthetic is eliminated as a result of a decreased blood flow in the epidural space, more drug should be available to enter neural tissues with an improved degree of b10ckade.I~Thus the effect of adrenaline may not be optimal when given simultaneously with bupivacaine. We postulated that by administering the adrenaline 5 minutes before the local anaesthetic, vasoconstriction might be maximal at a time when the bupivacaine was injected. This would be expected to enhance the blockade, providing better quality sensory analgesia with lower plasma bupivacaine concentrations. The results of this study, however, demonstrate that whilst priming of the epidural space with adrenaline tends to improve both the extent and duration of sensory analgesia, priming has no clear advantage over injecting adrenaline and bupivacaine simultaneously. Priming with adrenaline improves motor block by reducing onset time and increasing duration of block, but it is again questionable whether these minimal differences are likely to confer significant benefit in the clinical situation. Bupivacaine Table 6. Parameters describing the plasma bupivacaine time

course. S/B

S/BA

AIB

0.69 (0.11) 20 190 (100)

0.49 (0.11) 20 120 (19.5)

0.49 (0.10) 20 149 (40.8)

~

C,,,; pg/ml, mean (SD)

T,,,; minutes, median value AUC; pg/ml/minute, mean (SD)

concentrations are seen to be reduced in the adrenaline groups; this is in agreement with the work of others.’2J4 The plasma bupivacaine levels in the two adrenaline groups do not differ significantly from each other. Pretreatment with adrenaline delays the peak absorption when compared to the bupivacaine combined with adrenaline group. The power of this study could have been increased by use of larger patient groups. However, eight patients in each group would have given us a 90% power at the 0.05% significance for a 25% difference in maximum plasma bupivacaine concentrations. There is some indication that adrenaline 1:200 000 may be beneficial in epidural anaesthesia. However, it seems that priming the epidural space with adrenaline confers little advantage in the clinical situation when compared to injections of bupivacaine mixed with adrenaline. Acknowledgments We thank Professor G.T. Tucker, Department of Medicine and Pharmacology, University of Sheffield, and his laboratory for the analysis of plasma bupivacaine concentrations and in particular for his help with this manuscript. We thank Mr N. Taub, Lecturer in Medical Statistics, St Thomas’ Hospital, for his advice on the statistical analysis of the results. References 1. COUSINS, MJ, PO BRIDENBAUGH. Neural blockade In: Clinical anaesthesia and management of pain, 2nd edn. Philadelphia: J.P. Lippincott Co., 1988; 65. 2. TUCKERGT, MATHERLE. Clinical pharmacokinetics of local anaesthetics. Clinical Pharmacokinetics 1979; 4 241-78. 3. TUCKERGT. Pharmacokinetics of local anaesthetics. British Journal of Anaesthesia 1986; 58: I 1 7-3 1. 4. BURFOOT MF, BROMAGE PR. The effects of epinephrine on mepivacaine absorption from the spinal epidural space. Anesthesiology 1971; 3 5 488-92. 5. BURMAGL, VAN KLEEFJW, GLADINES MPRR, OLTHOFG, SPIERDIJKJ. Epidural anesthesia with lidocaine and bupivacaine: effects of epinephrine on the plasma concentration profiles. Anesthesia and Analgesia 1986; 6 5 1281-4. 6. JAMOUS MA, HANDCW, MOORERA, TEDDYPJ, MCQUAY HJ.

Epinephrine reduces systemic absorption of extradural diacetylmorphine. Anesthesia and Analgesia 1986; 6 5 12904.

Efect of adrenaline on bupivacaine epidural blockade 7. The Pharmaceutical Codex 11th edn. London: The Pharmaceutical Press, 1979. 8. MOORED. Regional block, 4th edn. Springfield: Charles C. Thomas. 1965. 9. SINCLAIR CJ, SCOTTDB. Comparison of bupivacaine and etidocaine in extradural blockade. British Journal of Anaesthesia 1984; 5 6 147-53. 10. LAISHLEY RS, MORGANBM. A single dose epidural technique for caesarean section-a comparison between 0.5% bupivacaine plain and 0.5% bupivacaine with adrenaline. Anaesthesia 1988; 4 3 100-3. 1 1. CRAWFORDOB. Comparative evaluation in peridural anesthesia of lidocaine, mepivacaine, and L-67, a new local anesthetic agent. Anesthesiology 1964; 2 5 321-9. 12. BURMAGL, VANKLEEFJW, GLADINESMPRR, OLOTHOFG, SPIERDIIK J. Epidural anesthesia with lidocaine and bupivacaine: effects of epinephrine on the plasma concentration profiles. Anesthesia and Analgesia 1986; 65: 128 1-4. 13. COVINOBG, SCOTTDB. Handbook of epidural anaesthesia and analgesia. Copenhagen: Schultz, 1985. 14. ABDEL-SALAM AR, VONWILLER JB, SCOTTDB., Evaluation of etidocaine in extradural block. British Journal of Anaesthesia 1975; 47: 1081-6.

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15. SMITHSL, ALBINMS, WATSONWA, PANTOJA G , BUNEGINL. Spinal cord and cerebral blood flow responses to intrathecal local anesthetics with and without epinephrine. Anesthesiology 1983; 5 9 A312 6. KOZODYR, PALAHNIUK RJ, WADEJG, CUMMINC MO, Puccr WR. The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow. Canadian Anaesthetists’ Society Journal 1984; 31: 503-8. 7. MITCHELL P, GOADR, ERWINCW, CAMPORESIEM, MOON RE, WATKINS WD, BENNETT PB. Effect of epidural lidocaine on spinal cord blood flow. Anesthesia and Analgesia 1989; 68: 312-7. 18. PORTER SS, ALBINMS, WATSONWA, BUNEGIN L, PANTOJA G. Spinal cord and cerebral blood flow responses to subarachnoid injection of local anesthetics with and without epinephrine. Acta Anaesthesiologica Scandinavica 1985; 2 9 330-8. 19. DOHI S, TAKESHIMA R, NAITOH. Spinal cord blood flow during spinal anesthesia in dogs: the effects of tetracaine, epinephrine, acute blood loss, and hypercapnia. Anesthesia and Analgesia 1987; 66: 599-606. JS, HIBRINS. Epidurography using epinephrine 20. EASTERBROOK and tomography. Radiology 1981; 1 4 0 709-1 1. 21. KANERE. Neurologic deficits following epidural or spinal anesthesia. Anesthesia and Analgesia 1981; 60: 150-61.

The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine.

Twenty-four patients receiving epidural anaesthesia were studied to test the hypothesis that 1:200,000 adrenaline administered into the epidural space...
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