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EFFECT OF ADRENALINE ON EXTRADURAL ANAESTHESIA, PLASMA LIGNOCAINE CONCENTRATIONS AND THE FETO-PLACENTAL UNIT DURING ELECTIVE CAESAREAN SECTION
British Journal of Anaesthesia 1991; 67: 683-689
EFFECT OF ADRENALINE ON EXTRADURAL ANAESTHESIA, PLASMA LIGNOCAINE CONCENTRATIONS AND THE FETO-PLACENTAL UNIT DURING ELECTIVE CAESAREAN SECTION A. J. McLINTIC, F. H. DANSKIN, J. A. REID AND J. THORBURN
ing solution, a smaller dose of lignocaine was required to produce an adequate block and the lignocaine concentrations in both mother and neonate were significantly smaller compared with the plain solution. Arterial pressures were less in the adrenaline group, but there was no difference in umbilical flow velocity waveform, fetal heart rate or fetal outcome. Neither fetoplacental circulation nor fetal outcome were affected adversely by episodes of hypotension or the ephedrine used for treatment.
PATIENTS AND METHODS
We studied 20 healthy women undergoing elective Caesarean section. The study was approved by the Ethics Committee of The Queen Mother's Hospital and all patients gave informed consent. The indication for elective Caesarean section was either repeat Caesarean section or breech presentation. There was no evidence of preoperative fetal compromise or maternal disease. Patients were given ranitidine 150 mg by mouth KEY WORDS on the evening before and on the morning of Anaesthesia: obstetric. Anaesthetic techniques: extradural. surgery. Before extradural anaesthesia was inPlacenta, umbilical blood flow. duced, patients were pre-loaded with Hartmann's solution 1 litre. They were then allocated ranAlthough bupivacaine is the agent used most domly to receive either 2 % plain lignocaine (group commonly for Caesarean section under extradural A; n = 10) or 2% lignocaine with adrenaline anaesthesia in the U.K., lignocaine has been 1:200000 (group B; n = 10). Both patient and shown to be an effective alternative and confers investigator were blind to the identity of the certain advantages over bupivacaine in this con- solution used. With the patient in either the text [1]. With a lower p/C., lignocaine has a sitting or lateral position, a 20-gauge extradural shorter latency of effect which facilitates dose catheter was inserted via an 18-gauge Tuohy titration and reduces preoperative preparation needle at L3-4. The extradural space was identtime [1, 2]. In addition, intractable cardiovascular toxicity has not been associated with the use of lignocaine, but is an important toxic effect of This article is accompanied by Editorial I. J. MCLINTIC, M.R.C.P., F.C.ANAES.; JOYCE A . R E I D , bupivacaine [3]. It has been shown, in contexts ALAN F.C.ANAES.; JOHN THORBURN, F.C.ANAES.; Department of other than Caesarean section, that the efficacy of Anaesthesia, Western Infirmary, Dumbarton Road, Glasgow extradural lignocaine may be improved further if G i l 6NT. FIONA H. DANSKIN, D.R.C.O.C, Cruden Medical an adrenaline-containing solution is used [4-6]. Research Fellow in Obstetrics, Department of Midwifery, of Glasgow, The Queen Mother's Hospital, The aim of this study was to determine if a University Yorkhill, Glasgow. Accepted for Publication: June 14, 1991. lignocaine and adrenaline solution has advantages Correspondence to A.J.McL.
Downloaded from http://bja.oxfordjournals.org/ at Florida Atlantic University on July 9, 2015
over a plain lignocaine solution when used to provide extradural anaesthesia for Caesarean Extradural anaesthesia was induced with either section. The comparison between the techniques 2% lignocaine or 2% lignocaine with adrenaline was made in terms of anaesthetic characteristics, 1:200000 in 20 patients undergoing elective plasma concentrations of lignocaine, maternal and Caesarean section. With the adrenaline-contain- fetal haemodynamics and fetal outcome. SUMMARY
BRITISH JOURNAL OF ANAESTHESIA
684
Maximum systolic velocity Minimum diastolic velocity A-B 2. PI = Mean
1. A : B ratio -
A (maximum)
Time FIG. 1. Characteristic umbilical artery flow velocity waveform showing derivation of A:B ratio and pulsatility index (PI). The Dopplcr frequency shift (FD) is directly proportional to flow velocity.
of measurement [7, 8]. As the end-diastolic velocity varies with fetal heart rate (FHR), changes in the A: B ratio may reflect changes in FHR and changes in placental resistance [9]. Therefore, A: B ratios were corrected for FHR using a modal heart rate of 140 beat min"1 and the method described by Mires and colleagues [9]. As the importance of this correction is contentious when the FHR is within normal limits, results are given in both corrected and uncorrected forms [10]. Studies were performed using a Doptek 4-MHz continuous wave Doppler system with on-line spectral analysis. Measurements were made with the patient in the modified supine position. The umbilical artery was located using twodimensional ultrasonography. The Doppler transducer was orientated so that the umbilical arterial signal had maximum amplitude and minimum artefact and could be displayed together with the venous trace. Five consecutive waveforms were recorded at the following times: before insertion of the extradural catheter, immediately before Caesarean section, during episodes of hypotension and after administration of ephedrine. Calculation of the mean A:B ratios, PI and FHR were carried out using on-board custom-written software. Maternal venous blood samples were taken from the non-infusion arm before the test dose, at 10-min intervals from the time at which an adequate block was achieved and immediately after delivery. Umbilical arterial and venous blood samples were taken immediately after delivery for blood-gas and plasma lignocaine analysis. Samples for lignocaine assay were stored at 4 °C after centrifugation and plasma separation. Lignocaine assay was carried out by a solvent extraction method using high pressure liquid chromatography [11]. Neonatal Apgar scores were recorded at 1 min and 5 min. Statistics Statistical evaluation of the data was carried out using the Minitabs Release 7.1 statistical package. Data were analysed by Student's t test, chi-square and Mann—Whitney U test where appropriate. P < 0.05 was considered significant. Values are expressed as mean (SD). RESULTS
One patient in group B required spinal anaesthesia after failure to achieve a level of block above T10. Her results were not included in the analysis.
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ified using loss of resistance with local analgesia comprising 0.5 % prilocaine 2 ml. Extradural block was then induced with the patient in the left lateral position. An initial test dose of 3 ml of the allocated solution was followed by a 10-ml dose after 5 min. At 5-min intervals thereafter the level of anaesthesia to pinprick was assessed and further increments given according to the extent of spread. This was continued until an adequate block was achieved (loss of pinprick sensation from S5 to T6 bilaterally). The time taken to achieve an adequate block (measured from the time of test dose), the total dose of lignocaine used to produce the block, and the time at which further analgesia was required were recorded. Arterial pressure and heart rate were measured using a 2200 I Datascope at 1-min intervals from the time of catheter insertion. The incidence of significant hypotension (systolic arterial pressure ^ 90 mm Hg) was noted. Hypotension was treated by increasing the rate of infusion and, if necessary, by a bolus dose of ephedrine 6 mg. The feto-placental circulation was assessed using Doppler velocimetry. When placental vascular resistance increases, the umbilical artery flow decreases [7]. This is reflected in a reduction in diastolic flow velocity and Doppler frequency. The resulting changes in the umbilical arterial flow velocity waveform may be assessed quantitatively by measuring the peak systolic: minimum diastolic velocity ratio (A:B ratio) and the pulsatility index (PI) (fig. 1). An increase in one of these values reflects an increase in flow resistance within the vascular bed distal to the site
LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
685
TABLE I. Patient characteristics (mean (.range or SD)). No significant differences between groups
2% Lignocaine 2% Lignocaine + adrenaline
n
Age (yr)
Gestation (weeks)
10 9
29.0(19-37) 29.3 (17-37)
38.4 (0.88) 38.8(1.32)
Weight (kg) 55.3 (8.44) 62.1(13.95)
Height (m)
1.59(0.05) 1.62(0.09)
TABLE II. Characteristics of extradural anaesthesia. Mean (SD or, median and range)
Dose required (mg) Onset time (min) Time to further analgesia (min)
493 (64.2) 35.8(17.00) 92.9(86; 11-220)
2% Lignocaine + adrenaline (« = 9)
P
400(108) 29.9(9.14) 237(100; 12-694)
<0.05 ns ns
TABLE III. Mean (sn) maternal and umbilical vein plasma concentrations of lignocaine, and plasma lignocaine concentration (mg litre'1): dose (mg) ratio calculated using peak (30 mm) plasma concentration of lignocaine
Lignocaine concn (ug ml"1) Time after onset (min)
2 % Lignocaine (n = 10) 2% Lignocaine + adrenaline (n = 9) P
vein:
Plasma
10
20
30
40
vein
vein ratio
dose ratio
1.309 (0.521) 0.542 (0.349)
1.715 (0.660) 0.854 (0.511)
2.22 (0.556) 1.317 (0.570)
2.03 (0.649) 0.78
1.411 (0.573) 0.804 (0.370)
0.600 (0.17) 0.605 (0.29)
0.0047 (0.0012) 0.0034 (0.0012)
< 0.005
< 0.005
<0.02
There was no significant difference in the mean age, weight, height or gestation of the patients in the two groups (table I). The mean dose of lignocaine required to produce an adequate block in group A was 493 (SD 64.2) mg; this was significantly greater than that required in group B (400 (108) mg) (P < 0.05). The mean time taken to produce an adequate block in each group was 35.8 (17.0) min in group A and 29.9 (9.14) min in group B (ns). The mean time interval between establishing an adequate block and the first analgesia requirements was 92.9 min (median 86 min, range 11-220 min) in group A and 237 min (median 100 min, range 12-694 min) in group B (ns) (table II). Plasma concentrations of lignocaine were significantly greater in group A at each time interval, except at 40 min where there were insufficient numbers in group B to make statistical comparison
—
<0.02
ns
< 0.024
(table III). Umbilical venous plasma concentrations were also significantly greater in group A (1.411 (0.573) ug ml"1 compared with 0.804 (0.370) ug ml"1 (P < 0.02)). There was no difference in the umbilical venous to maternal venous lignocaine concentration ratio between the two groups. The peak plasma lignocaine concentration : dose ratio was significantly greater in group A than in group B (0.0047:1 (0.0012) vs 0.0034:1 (0.0012) (P < 0.024)). Systolic and diastolic arterial pressures in group A were greater than those in group B, although the difference reached significance only at 15 min (fig. 2). There was no significant difference in the incidence or duration of systolic hypotension of 90 mm Hg or less (six patients in group A with a mean duration of 2.2 min and nine in group B with a mean duration of 2.8 min) or in the requirement for ephedrine (four in group A and
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2% Lignocaine (n = 10)
BRITISH JOURNAL OF ANAESTHESIA
686 160
cantly alter the A: B ratio, corrected A: B ratio, PI or FHR (table IV). There was no difference in umbilical arterial pH or Apgar scores between the two groups. A:B ratios, PI and FHR were not altered significantly during episodes of hypotension or after treatment with ephedrine (table V). The umbilical arterial pH and Apgar scores of neonates from mothers who had had hypotensive episodes were not significantly different from those of neonates from mothers who had remained normotensive throughout the procedure (table VI).
Systolic
140 120 jP 100 E
80
£ 60
i r"i
Q.
<
40 20 0
5
10
15
20
25
30
35
40
Complications
140
Transient symptoms suggestive of lignocaine toxicity (nasal paraesthesiae) occurred in one patient in group A at a plasma concentration of lignocaine 2.09 |ig ml"1. One patient in group B experienced pain when the uterus was exteriorized after delivery and required general anaesthesia to complete surgery.
~ 120 c 100
E
4-* CD
.a oc I
80
40 20 0 0
5
10
15
20
25
30
35
40
DISCUSSION
Time (min)
FIG. 2. Maternal heart rate (HR) and arterial pressure (AP) during extradural anaesthesia (mean, SD). Time 0 min is immediately before first dose of local anaesthetic. = 2% Lignocaine; = 2% lignocaine + adrenaline. *P<0.05.
five in group B). There was no significant difference in the maternal hean rates between the two groups. Feto-placental unit Extradural anaesthesia (with or without the adrenaline-containing solution) did not signifi-
The principal effects of adrenaline in local anaesthetic solutions are to reduce local blood flow, limit systemic absorption of local anaesthetic and enhance neuronal uptake [4, 12], resulting in an increased depth of analgesia for a given dose [2]. We were not surprised to find, therefore, that the mean dose of lignocaine required to produce a satisfactory block for Caesarean section was significantly smaller in those who had received the adrenaline-containing solution. The potential for maternal lignocaine toxicity is high in Caesarean section because large doses are used over a short
TABLE IV. Feto-placental unit. FHR ^fetal heart rate; U = uncorrecud for FHR: C = corrected for FHR. Mean values (.SD). No significant differences between groups A:B ratio
2% Lignocaine U (n = 10) C
2% Lignocaine U + adrenaline (n = 9) c
Pulsatility index
No. of patients with Apgar
FHR (beat min"1)
extradural
surgery
extradural
surgery
extradural
2.15 (0.39) 2.19 (0.27) 2.11 (0.25) 2.12 (0.18)
2.30 (0.50) 2.26 (0.54) 2.20 (0.29) 2.11 (0.16)
0.89 (0.20)
0.89 (0.17)
143.5 (9.23)
0.82 (0.12)
0.82 (0.12)
141.1 (11.39)
pH
1 min
5 min
136.2 (19.39)
7.26 (0.18)
1
0
140.9 (11.96)
7.28 (0.10)
0
0
surgery
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160
LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
687
TABLE V. Effect of hypotension and ephedrine on A:B ratio, pulsatility index and fetal heart rate (FHR) (mean (SD)). U = Uncorrected for FHR; C = corrected for FHR. No significant differences between groups
Before extradural (n = 20)
Hypotension (n = 15)
After ephedrine (n = 9)
2.08 (0.32) 2.09(0.21) 0.91 (0.16)
2.22 (0.24) 2.07 (0.25) 0.94(0.13)
2.15(0.21) 2.00(0.21) 0.89 (0.08)
2.14(0.32) 2.07 (0.22) 0.82(0.14)
141.5(10.44)
132.9(12.80)
129.2 (17.49)
138.1 (14.20)
Before surgery (i =
19)
A:B ratio U
C Pulsatility index FHR
(beat min"1)
No. of patients with Apgar scores < 8 Umbilical arterial pH Normotensive (n = 4) Hypotensive (n=15)
1 min
5 min
7.29 (0.29) 7.24 (0.07)
time interval. Placental transfer of lignocaine also occurs readily and one (unconfirmed) report has described neonatal hypotonicity as a consequence [13]. It was important, therefore, to find that both maternal and neonatal plasma concentrations of lignocaine were reduced significantly when the adrenaline-containing solution was used. The fact that this was caused by reduced systemic absorption rather than merely the smaller doses used in the adrenaline group was reflected in the lower plasma concentration: dose ratios. Lignocaine toxicity in adults may begin to occur at plasma concentrations of 5 ug ml"1 and is manifest usually by central nervous system disturbance [14]. Plasma concentrations in diis study were all considerably smaller than this value, including those in the patient who experienced nasal paraesthesia. The enhanced neuronal uptake afforded by adrenaline might have been expected also to produce the more rapid onset of block which Bromage and colleagues have shown with 2% lignocaine and Murphy and colleagues have shown with etidocaine [4, 5]. However, this effect has not been confirmed by all investigators and
Abboud and colleagues have demonstrated a slowing of the onset of anaesthesia when adrenaline was used with 2% lignocaine [15]. Although the difference did not reach statistical significance in our study, there was a trend towards faster onset of block when the adrenaline solution was used. One concern with the use of 2 % lignocaine for Caesarean section is whether or not the duration of action is long enough to provide consistently complete analgesia throughout the operation. It is our experience that, if the block is adequate before the start of surgery, 2% lignocaine provides anaesthesia for the duration. In this study, the failure of anaesthesia which necessitated intrathecal block was almost certainly caused by incorrect placement of the extradural catheter and that which necessitated general anaesthesia was a result of a combination of prolonged surgery with exteriorization of uterus. The addition of adrenaline to lignocaine for extradural analgesia in labour has been shown to prolong the duration of useful analgesia [6]. To determine if this was true also of the analgesia provided by extradural block in Caesarean section, we documented the time at which further analgesia was required. Again, although it appeared from the mean values that those who received the plain solution required analgesia earlier, the wide range of values within each group suggested that the difference from the adrenaline group was not significant. The trend towards a faster onset and longer duration of block in the adrenaline group was, however, in keeping with the distinct clinical impression that the dose was easier to titrate and the block more reliable when adrenaline was used. Several studies have examined the effect of adrenaline-containing extradural solutions on
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TABLE VI. Comparison of fetal outcome where mothers have been hypotensive with that where mothers have been entirely normotensive (mean (SD)). NO significant differences between groups
688
We conclude that, while 2% lignocaine may provide satisfactory extradural anaesthesia for elective Caesarean section, addition of adrenaline 1:200000 to the solution has several advantages: it reduces dose requirements, plasma concentra-
tions of lignocaine and, probably, the time to onset of satisfactory block, without adverse effects on mother or fetus. ACKNOWLEDGEMENTS This study was supported by a generous grant from the Obstetric Anaesthetist's Association. Thanks are also due to Joseph Smith of the Department of Clinical Biochemistry, Glasgow Royal Infirmary, for the lignocaine assays. REFERENCES 1. Reid JA, Thorbum J. Extradural bupivacaine or lignocaine anaesthesia for elective Caesarean section: the role of maternal posture. British Journal of Anaesthesia 1988;61: 149-153. 2. Covino BG. General considerations, toxicity and complications of local anaesthesia. In: Nimmo WS, Smith G, eds. Anaesthesia. Oxford: Blackwell, 1989; 1011-1033. 3. Marx GF. Cardiotoxicity of local anesthetics—the plot thickens. Anesthesiology 1984; 60: 3-5. 4. Bromage PR, Burfoot MF, Crowell DE, Pettigrcw RT. Quality of epidural blockade. 1: Influence of physical factors. British Journal of Anaesthesia 1964; 36: 342-352. 5. Murphy TM, Mather LE, Stanton-Hicks Md'A, Bonica JJ, Tucker GT. The effects of adding adrenaline to etidocaine and lignocaine in cxtradural anaesthesia. 1: block characteristics and cardiovascular effects. British Journal of Anaesthesia 1976; 48: 893-897. 6. Abboud TK, David S, Nagappala S, Costandi J, Yanagi T, Haroutunian S, Yeh SU. Maternal, fetal, and neonatal effects of lidocaine with and without epinephrine for epidural anesthesia in obstetrics. Anesthesia and Analgesia 1984; 63: 973-979. 7. Trudingcr BJ, Giles WB, Cook CM, Bombardicri J, Collins L. Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. British Journal of Obstetrics and Gynaecology 1985; 92: 23-30. 8. Gosling RG, King DH. Ultrasonic angiology. In: Harcus AW, Adamson L, eds. Arteries and Veins, 1st Edn. Edinburgh: Longman, 1975; 61-98. 9. Mires G, Dempster J, Patel NB, Crawford JW. The effect of fetal heart rate on umbilical artery flow velocity waveforms. British Journal of Obstetrics and Gynaecology 1987; 94: 665-669. 10. Mansouri H, Gagnon R, Hunse C. Relationship between fetal heart rate and umbilical blood flow velocity in term human fetuses during labor. American Journal of Obstetrics and Gynecology 1989; 160: 1007-1012. 11. Howard PJ, Moore J. The estimation of lignocaine concentrations in plasma by HPLC. Chromatography and Analysis 1990; Feb: 9-10. 12. Tucker GT, Mather LE. Clinical pharmacokinetics of local anaesthetics. Clinical Pharmacokinetics 1979; 4: 241-278. 13. Scanlon JW, Brown TO jr, Weiss JB, Alper MH. Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology 1974; 40: 121-128. 14. Foldes FF, Molloy R, McNall PG, Koukal LR. Comparison of toxicity of intravenously given local anesthetic agents in man. Journal of the American Medical Association 1960; 172: 1493-1498.
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maternal cardiovascular variables, but results have differed. Abboud and his co-workers have found that, while the addition of adrenaline to bupivacaine produced less hypotension, the incidence of hypotension was not affected when adrenaline was used with lignocaine solution [6, 15, 16]. Conversely, Bonica and colleagues showed that lignocaine and adrenaline solutions produced more hypotension (and faster heart rates) than plain lignocaine solutions [17]. These investigators believe that the haemodynamic differences may be attributed to the systemic beta-adrenergic effect of absorbed adrenaline. The cardiovascular changes caused by the adrenaline-containing solution in our study were similar to the findings of Bonica with smaller arterial pressures and an early (although not statistically significant) increase in heart rate. Beta-adrenergic stimulation might account fully for these differences as well, but a contributory factor could also have been the trend of the adrenaline group to have a faster onset of block and, therefore, more rapid peripheral vasodilatation. There has been uncertainty regarding the effect of systemically absorbed adrenaline on the fetoplacental circulation [18-21]. In this study the influence of anaesthetic technique on umbilical blood flow was assessed by measuring indices of placental resistance. This has been used successfully to predict acute and chronic fetal compromise [7, 22, 23]. It was important to find, therefore, that not only was the placental flow resistance unaltered by extradural anaesthesia itself, but also it was unaffected by the use of the adrenaline-containing solution. Adequacy of umbilical blood flow was supported by the fact that fetal outcome (in terms of umbilical arterial pH and Apgar scores) was the same whether adrenaline was used or not. In addition, neither the short-lived episodes of hypotension nor the ephedrine used for treatment had an adverse effect on umbilical blood flow or fetal outcome. Although this could have been the result of prompt detection and treatment, there is evidence that an autoregulatory mechanism exists within the umbilical circulation which may compensate for brief changes in maternal pressure [24].
BRITISH JOURNAL OF ANAESTHESIA
LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
Jouppila R, Jouppila P, Kuikka J, Hollmen A. Placental blood flow during Caesarean section under lumbar extradural analgesia. British Journal of Anaesthesia 1978; 50: 275-278. Albright GA, Jouppila R, Hollmen AI, Jouppila P, Vierola H, Koivula A. Epinephrine does not alter human inatervillous blood flow during epidural anesthesia. Anesthesiology 1981; 54: 131-135. Lingman G, Laurin J, Marsal K. Circulatory changes in fetuses with imminent asphyxia. Biology of the Neonate 1986; 49: 66-73. Trudinger BJ, Cook CM, Jones L, Giles WB. A comparison of fetal heart rate monitoring and umbilical artery waveforms in the recognition of fetal compromise. British Journal of Obstetrics and Gynaecology 1986; 93: 171-175. Kingdom JCP, Ryan G, Whittle MJ, Doyle J, Connell JMC. Atrial naturetic peptide: a regulator of the fetoplacental circulation? American Journal of Obstetrics and Gynecology 1991; 164: 242.
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15. Abboud TK, Kim KC, Noueihed R, Kuhnert BR, 20. DerMardirossian N, Moumdjian J, Sarkis F, Nagappala S. Epidural bupivacaine, chloroprocaine or lidocaine for Cesarean section—maternal and neonatal effects. Anesthesia and Analgesia 1983; 62: 914-919. 21. 16. Abboud TK, Shiek-ol-Eslam A, Yanagi T, Murakawa K, Costandi J, Zakarian M, Hoffman D, Haroutunian S. Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics. Anesthesia and 22. Analgesia 1985; 64: 585-591. 17 Bonica JJ, Akamatsu TJ, Berges PU, Morikawa K, Kennedy WF. Circulatory effects of pcridural block. 23. Anesthesiology 1971; 34: 514-522. 18. Rosenfeld CR, Banon MD, Meschia G. Effects of epinephrine on distribution of blood flow in the pregnant ewe. American Journal of Obstetrics and Gynecology 1976; 124: 156-163. 24. 19. deRosayro AM, Nahrwold ML, Hill AB. Cardiovascular effect of epidural epinephrine in the pregnant sheep. Regional Anesthesia 1981; 6: 4—7.
689
EFFECT OF ADRENALINE ON EXTRADURAL ANAESTHESIA, PLASMA LIGNOCAINE CONCENTRATIONS AND THE FETO-PLACENTAL UNIT DURING ELECTIVE CAESAREAN SECTION A. J. McLINTIC, F. H. DANSKIN, J. A. REID AND J. THORBURN
ing solution, a smaller dose of lignocaine was required to produce an adequate block and the lignocaine concentrations in both mother and neonate were significantly smaller compared with the plain solution. Arterial pressures were less in the adrenaline group, but there was no difference in umbilical flow velocity waveform, fetal heart rate or fetal outcome. Neither fetoplacental circulation nor fetal outcome were affected adversely by episodes of hypotension or the ephedrine used for treatment.
PATIENTS AND METHODS
We studied 20 healthy women undergoing elective Caesarean section. The study was approved by the Ethics Committee of The Queen Mother's Hospital and all patients gave informed consent. The indication for elective Caesarean section was either repeat Caesarean section or breech presentation. There was no evidence of preoperative fetal compromise or maternal disease. Patients were given ranitidine 150 mg by mouth KEY WORDS on the evening before and on the morning of Anaesthesia: obstetric. Anaesthetic techniques: extradural. surgery. Before extradural anaesthesia was inPlacenta, umbilical blood flow. duced, patients were pre-loaded with Hartmann's solution 1 litre. They were then allocated ranAlthough bupivacaine is the agent used most domly to receive either 2 % plain lignocaine (group commonly for Caesarean section under extradural A; n = 10) or 2% lignocaine with adrenaline anaesthesia in the U.K., lignocaine has been 1:200000 (group B; n = 10). Both patient and shown to be an effective alternative and confers investigator were blind to the identity of the certain advantages over bupivacaine in this con- solution used. With the patient in either the text [1]. With a lower p/C., lignocaine has a sitting or lateral position, a 20-gauge extradural shorter latency of effect which facilitates dose catheter was inserted via an 18-gauge Tuohy titration and reduces preoperative preparation needle at L3-4. The extradural space was identtime [1, 2]. In addition, intractable cardiovascular toxicity has not been associated with the use of lignocaine, but is an important toxic effect of This article is accompanied by Editorial I. J. MCLINTIC, M.R.C.P., F.C.ANAES.; JOYCE A . R E I D , bupivacaine [3]. It has been shown, in contexts ALAN F.C.ANAES.; JOHN THORBURN, F.C.ANAES.; Department of other than Caesarean section, that the efficacy of Anaesthesia, Western Infirmary, Dumbarton Road, Glasgow extradural lignocaine may be improved further if G i l 6NT. FIONA H. DANSKIN, D.R.C.O.C, Cruden Medical an adrenaline-containing solution is used [4-6]. Research Fellow in Obstetrics, Department of Midwifery, of Glasgow, The Queen Mother's Hospital, The aim of this study was to determine if a University Yorkhill, Glasgow. Accepted for Publication: June 14, 1991. lignocaine and adrenaline solution has advantages Correspondence to A.J.McL.
Downloaded from http://bja.oxfordjournals.org/ at Florida Atlantic University on July 9, 2015
over a plain lignocaine solution when used to provide extradural anaesthesia for Caesarean Extradural anaesthesia was induced with either section. The comparison between the techniques 2% lignocaine or 2% lignocaine with adrenaline was made in terms of anaesthetic characteristics, 1:200000 in 20 patients undergoing elective plasma concentrations of lignocaine, maternal and Caesarean section. With the adrenaline-contain- fetal haemodynamics and fetal outcome. SUMMARY
BRITISH JOURNAL OF ANAESTHESIA
684
Maximum systolic velocity Minimum diastolic velocity A-B 2. PI = Mean
1. A : B ratio -
A (maximum)
Time FIG. 1. Characteristic umbilical artery flow velocity waveform showing derivation of A:B ratio and pulsatility index (PI). The Dopplcr frequency shift (FD) is directly proportional to flow velocity.
of measurement [7, 8]. As the end-diastolic velocity varies with fetal heart rate (FHR), changes in the A: B ratio may reflect changes in FHR and changes in placental resistance [9]. Therefore, A: B ratios were corrected for FHR using a modal heart rate of 140 beat min"1 and the method described by Mires and colleagues [9]. As the importance of this correction is contentious when the FHR is within normal limits, results are given in both corrected and uncorrected forms [10]. Studies were performed using a Doptek 4-MHz continuous wave Doppler system with on-line spectral analysis. Measurements were made with the patient in the modified supine position. The umbilical artery was located using twodimensional ultrasonography. The Doppler transducer was orientated so that the umbilical arterial signal had maximum amplitude and minimum artefact and could be displayed together with the venous trace. Five consecutive waveforms were recorded at the following times: before insertion of the extradural catheter, immediately before Caesarean section, during episodes of hypotension and after administration of ephedrine. Calculation of the mean A:B ratios, PI and FHR were carried out using on-board custom-written software. Maternal venous blood samples were taken from the non-infusion arm before the test dose, at 10-min intervals from the time at which an adequate block was achieved and immediately after delivery. Umbilical arterial and venous blood samples were taken immediately after delivery for blood-gas and plasma lignocaine analysis. Samples for lignocaine assay were stored at 4 °C after centrifugation and plasma separation. Lignocaine assay was carried out by a solvent extraction method using high pressure liquid chromatography [11]. Neonatal Apgar scores were recorded at 1 min and 5 min. Statistics Statistical evaluation of the data was carried out using the Minitabs Release 7.1 statistical package. Data were analysed by Student's t test, chi-square and Mann—Whitney U test where appropriate. P < 0.05 was considered significant. Values are expressed as mean (SD). RESULTS
One patient in group B required spinal anaesthesia after failure to achieve a level of block above T10. Her results were not included in the analysis.
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ified using loss of resistance with local analgesia comprising 0.5 % prilocaine 2 ml. Extradural block was then induced with the patient in the left lateral position. An initial test dose of 3 ml of the allocated solution was followed by a 10-ml dose after 5 min. At 5-min intervals thereafter the level of anaesthesia to pinprick was assessed and further increments given according to the extent of spread. This was continued until an adequate block was achieved (loss of pinprick sensation from S5 to T6 bilaterally). The time taken to achieve an adequate block (measured from the time of test dose), the total dose of lignocaine used to produce the block, and the time at which further analgesia was required were recorded. Arterial pressure and heart rate were measured using a 2200 I Datascope at 1-min intervals from the time of catheter insertion. The incidence of significant hypotension (systolic arterial pressure ^ 90 mm Hg) was noted. Hypotension was treated by increasing the rate of infusion and, if necessary, by a bolus dose of ephedrine 6 mg. The feto-placental circulation was assessed using Doppler velocimetry. When placental vascular resistance increases, the umbilical artery flow decreases [7]. This is reflected in a reduction in diastolic flow velocity and Doppler frequency. The resulting changes in the umbilical arterial flow velocity waveform may be assessed quantitatively by measuring the peak systolic: minimum diastolic velocity ratio (A:B ratio) and the pulsatility index (PI) (fig. 1). An increase in one of these values reflects an increase in flow resistance within the vascular bed distal to the site
LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
685
TABLE I. Patient characteristics (mean (.range or SD)). No significant differences between groups
2% Lignocaine 2% Lignocaine + adrenaline
n
Age (yr)
Gestation (weeks)
10 9
29.0(19-37) 29.3 (17-37)
38.4 (0.88) 38.8(1.32)
Weight (kg) 55.3 (8.44) 62.1(13.95)
Height (m)
1.59(0.05) 1.62(0.09)
TABLE II. Characteristics of extradural anaesthesia. Mean (SD or, median and range)
Dose required (mg) Onset time (min) Time to further analgesia (min)
493 (64.2) 35.8(17.00) 92.9(86; 11-220)
2% Lignocaine + adrenaline (« = 9)
P
400(108) 29.9(9.14) 237(100; 12-694)
<0.05 ns ns
TABLE III. Mean (sn) maternal and umbilical vein plasma concentrations of lignocaine, and plasma lignocaine concentration (mg litre'1): dose (mg) ratio calculated using peak (30 mm) plasma concentration of lignocaine
Lignocaine concn (ug ml"1) Time after onset (min)
2 % Lignocaine (n = 10) 2% Lignocaine + adrenaline (n = 9) P
vein:
Plasma
10
20
30
40
vein
vein ratio
dose ratio
1.309 (0.521) 0.542 (0.349)
1.715 (0.660) 0.854 (0.511)
2.22 (0.556) 1.317 (0.570)
2.03 (0.649) 0.78
1.411 (0.573) 0.804 (0.370)
0.600 (0.17) 0.605 (0.29)
0.0047 (0.0012) 0.0034 (0.0012)
< 0.005
< 0.005
<0.02
There was no significant difference in the mean age, weight, height or gestation of the patients in the two groups (table I). The mean dose of lignocaine required to produce an adequate block in group A was 493 (SD 64.2) mg; this was significantly greater than that required in group B (400 (108) mg) (P < 0.05). The mean time taken to produce an adequate block in each group was 35.8 (17.0) min in group A and 29.9 (9.14) min in group B (ns). The mean time interval between establishing an adequate block and the first analgesia requirements was 92.9 min (median 86 min, range 11-220 min) in group A and 237 min (median 100 min, range 12-694 min) in group B (ns) (table II). Plasma concentrations of lignocaine were significantly greater in group A at each time interval, except at 40 min where there were insufficient numbers in group B to make statistical comparison
—
<0.02
ns
< 0.024
(table III). Umbilical venous plasma concentrations were also significantly greater in group A (1.411 (0.573) ug ml"1 compared with 0.804 (0.370) ug ml"1 (P < 0.02)). There was no difference in the umbilical venous to maternal venous lignocaine concentration ratio between the two groups. The peak plasma lignocaine concentration : dose ratio was significantly greater in group A than in group B (0.0047:1 (0.0012) vs 0.0034:1 (0.0012) (P < 0.024)). Systolic and diastolic arterial pressures in group A were greater than those in group B, although the difference reached significance only at 15 min (fig. 2). There was no significant difference in the incidence or duration of systolic hypotension of 90 mm Hg or less (six patients in group A with a mean duration of 2.2 min and nine in group B with a mean duration of 2.8 min) or in the requirement for ephedrine (four in group A and
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2% Lignocaine (n = 10)
BRITISH JOURNAL OF ANAESTHESIA
686 160
cantly alter the A: B ratio, corrected A: B ratio, PI or FHR (table IV). There was no difference in umbilical arterial pH or Apgar scores between the two groups. A:B ratios, PI and FHR were not altered significantly during episodes of hypotension or after treatment with ephedrine (table V). The umbilical arterial pH and Apgar scores of neonates from mothers who had had hypotensive episodes were not significantly different from those of neonates from mothers who had remained normotensive throughout the procedure (table VI).
Systolic
140 120 jP 100 E
80
£ 60
i r"i
Q.
<
40 20 0
5
10
15
20
25
30
35
40
Complications
140
Transient symptoms suggestive of lignocaine toxicity (nasal paraesthesiae) occurred in one patient in group A at a plasma concentration of lignocaine 2.09 |ig ml"1. One patient in group B experienced pain when the uterus was exteriorized after delivery and required general anaesthesia to complete surgery.
~ 120 c 100
E
4-* CD
.a oc I
80
40 20 0 0
5
10
15
20
25
30
35
40
DISCUSSION
Time (min)
FIG. 2. Maternal heart rate (HR) and arterial pressure (AP) during extradural anaesthesia (mean, SD). Time 0 min is immediately before first dose of local anaesthetic. = 2% Lignocaine; = 2% lignocaine + adrenaline. *P<0.05.
five in group B). There was no significant difference in the maternal hean rates between the two groups. Feto-placental unit Extradural anaesthesia (with or without the adrenaline-containing solution) did not signifi-
The principal effects of adrenaline in local anaesthetic solutions are to reduce local blood flow, limit systemic absorption of local anaesthetic and enhance neuronal uptake [4, 12], resulting in an increased depth of analgesia for a given dose [2]. We were not surprised to find, therefore, that the mean dose of lignocaine required to produce a satisfactory block for Caesarean section was significantly smaller in those who had received the adrenaline-containing solution. The potential for maternal lignocaine toxicity is high in Caesarean section because large doses are used over a short
TABLE IV. Feto-placental unit. FHR ^fetal heart rate; U = uncorrecud for FHR: C = corrected for FHR. Mean values (.SD). No significant differences between groups A:B ratio
2% Lignocaine U (n = 10) C
2% Lignocaine U + adrenaline (n = 9) c
Pulsatility index
No. of patients with Apgar
FHR (beat min"1)
extradural
surgery
extradural
surgery
extradural
2.15 (0.39) 2.19 (0.27) 2.11 (0.25) 2.12 (0.18)
2.30 (0.50) 2.26 (0.54) 2.20 (0.29) 2.11 (0.16)
0.89 (0.20)
0.89 (0.17)
143.5 (9.23)
0.82 (0.12)
0.82 (0.12)
141.1 (11.39)
pH
1 min
5 min
136.2 (19.39)
7.26 (0.18)
1
0
140.9 (11.96)
7.28 (0.10)
0
0
surgery
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160
LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
687
TABLE V. Effect of hypotension and ephedrine on A:B ratio, pulsatility index and fetal heart rate (FHR) (mean (SD)). U = Uncorrected for FHR; C = corrected for FHR. No significant differences between groups
Before extradural (n = 20)
Hypotension (n = 15)
After ephedrine (n = 9)
2.08 (0.32) 2.09(0.21) 0.91 (0.16)
2.22 (0.24) 2.07 (0.25) 0.94(0.13)
2.15(0.21) 2.00(0.21) 0.89 (0.08)
2.14(0.32) 2.07 (0.22) 0.82(0.14)
141.5(10.44)
132.9(12.80)
129.2 (17.49)
138.1 (14.20)
Before surgery (i =
19)
A:B ratio U
C Pulsatility index FHR
(beat min"1)
No. of patients with Apgar scores < 8 Umbilical arterial pH Normotensive (n = 4) Hypotensive (n=15)
1 min
5 min
7.29 (0.29) 7.24 (0.07)
time interval. Placental transfer of lignocaine also occurs readily and one (unconfirmed) report has described neonatal hypotonicity as a consequence [13]. It was important, therefore, to find that both maternal and neonatal plasma concentrations of lignocaine were reduced significantly when the adrenaline-containing solution was used. The fact that this was caused by reduced systemic absorption rather than merely the smaller doses used in the adrenaline group was reflected in the lower plasma concentration: dose ratios. Lignocaine toxicity in adults may begin to occur at plasma concentrations of 5 ug ml"1 and is manifest usually by central nervous system disturbance [14]. Plasma concentrations in diis study were all considerably smaller than this value, including those in the patient who experienced nasal paraesthesia. The enhanced neuronal uptake afforded by adrenaline might have been expected also to produce the more rapid onset of block which Bromage and colleagues have shown with 2% lignocaine and Murphy and colleagues have shown with etidocaine [4, 5]. However, this effect has not been confirmed by all investigators and
Abboud and colleagues have demonstrated a slowing of the onset of anaesthesia when adrenaline was used with 2% lignocaine [15]. Although the difference did not reach statistical significance in our study, there was a trend towards faster onset of block when the adrenaline solution was used. One concern with the use of 2 % lignocaine for Caesarean section is whether or not the duration of action is long enough to provide consistently complete analgesia throughout the operation. It is our experience that, if the block is adequate before the start of surgery, 2% lignocaine provides anaesthesia for the duration. In this study, the failure of anaesthesia which necessitated intrathecal block was almost certainly caused by incorrect placement of the extradural catheter and that which necessitated general anaesthesia was a result of a combination of prolonged surgery with exteriorization of uterus. The addition of adrenaline to lignocaine for extradural analgesia in labour has been shown to prolong the duration of useful analgesia [6]. To determine if this was true also of the analgesia provided by extradural block in Caesarean section, we documented the time at which further analgesia was required. Again, although it appeared from the mean values that those who received the plain solution required analgesia earlier, the wide range of values within each group suggested that the difference from the adrenaline group was not significant. The trend towards a faster onset and longer duration of block in the adrenaline group was, however, in keeping with the distinct clinical impression that the dose was easier to titrate and the block more reliable when adrenaline was used. Several studies have examined the effect of adrenaline-containing extradural solutions on
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TABLE VI. Comparison of fetal outcome where mothers have been hypotensive with that where mothers have been entirely normotensive (mean (SD)). NO significant differences between groups
688
We conclude that, while 2% lignocaine may provide satisfactory extradural anaesthesia for elective Caesarean section, addition of adrenaline 1:200000 to the solution has several advantages: it reduces dose requirements, plasma concentra-
tions of lignocaine and, probably, the time to onset of satisfactory block, without adverse effects on mother or fetus. ACKNOWLEDGEMENTS This study was supported by a generous grant from the Obstetric Anaesthetist's Association. Thanks are also due to Joseph Smith of the Department of Clinical Biochemistry, Glasgow Royal Infirmary, for the lignocaine assays. REFERENCES 1. Reid JA, Thorbum J. Extradural bupivacaine or lignocaine anaesthesia for elective Caesarean section: the role of maternal posture. British Journal of Anaesthesia 1988;61: 149-153. 2. Covino BG. General considerations, toxicity and complications of local anaesthesia. In: Nimmo WS, Smith G, eds. Anaesthesia. Oxford: Blackwell, 1989; 1011-1033. 3. Marx GF. Cardiotoxicity of local anesthetics—the plot thickens. Anesthesiology 1984; 60: 3-5. 4. Bromage PR, Burfoot MF, Crowell DE, Pettigrcw RT. Quality of epidural blockade. 1: Influence of physical factors. British Journal of Anaesthesia 1964; 36: 342-352. 5. Murphy TM, Mather LE, Stanton-Hicks Md'A, Bonica JJ, Tucker GT. The effects of adding adrenaline to etidocaine and lignocaine in cxtradural anaesthesia. 1: block characteristics and cardiovascular effects. British Journal of Anaesthesia 1976; 48: 893-897. 6. Abboud TK, David S, Nagappala S, Costandi J, Yanagi T, Haroutunian S, Yeh SU. Maternal, fetal, and neonatal effects of lidocaine with and without epinephrine for epidural anesthesia in obstetrics. Anesthesia and Analgesia 1984; 63: 973-979. 7. Trudingcr BJ, Giles WB, Cook CM, Bombardicri J, Collins L. Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. British Journal of Obstetrics and Gynaecology 1985; 92: 23-30. 8. Gosling RG, King DH. Ultrasonic angiology. In: Harcus AW, Adamson L, eds. Arteries and Veins, 1st Edn. Edinburgh: Longman, 1975; 61-98. 9. Mires G, Dempster J, Patel NB, Crawford JW. The effect of fetal heart rate on umbilical artery flow velocity waveforms. British Journal of Obstetrics and Gynaecology 1987; 94: 665-669. 10. Mansouri H, Gagnon R, Hunse C. Relationship between fetal heart rate and umbilical blood flow velocity in term human fetuses during labor. American Journal of Obstetrics and Gynecology 1989; 160: 1007-1012. 11. Howard PJ, Moore J. The estimation of lignocaine concentrations in plasma by HPLC. Chromatography and Analysis 1990; Feb: 9-10. 12. Tucker GT, Mather LE. Clinical pharmacokinetics of local anaesthetics. Clinical Pharmacokinetics 1979; 4: 241-278. 13. Scanlon JW, Brown TO jr, Weiss JB, Alper MH. Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology 1974; 40: 121-128. 14. Foldes FF, Molloy R, McNall PG, Koukal LR. Comparison of toxicity of intravenously given local anesthetic agents in man. Journal of the American Medical Association 1960; 172: 1493-1498.
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maternal cardiovascular variables, but results have differed. Abboud and his co-workers have found that, while the addition of adrenaline to bupivacaine produced less hypotension, the incidence of hypotension was not affected when adrenaline was used with lignocaine solution [6, 15, 16]. Conversely, Bonica and colleagues showed that lignocaine and adrenaline solutions produced more hypotension (and faster heart rates) than plain lignocaine solutions [17]. These investigators believe that the haemodynamic differences may be attributed to the systemic beta-adrenergic effect of absorbed adrenaline. The cardiovascular changes caused by the adrenaline-containing solution in our study were similar to the findings of Bonica with smaller arterial pressures and an early (although not statistically significant) increase in heart rate. Beta-adrenergic stimulation might account fully for these differences as well, but a contributory factor could also have been the trend of the adrenaline group to have a faster onset of block and, therefore, more rapid peripheral vasodilatation. There has been uncertainty regarding the effect of systemically absorbed adrenaline on the fetoplacental circulation [18-21]. In this study the influence of anaesthetic technique on umbilical blood flow was assessed by measuring indices of placental resistance. This has been used successfully to predict acute and chronic fetal compromise [7, 22, 23]. It was important to find, therefore, that not only was the placental flow resistance unaltered by extradural anaesthesia itself, but also it was unaffected by the use of the adrenaline-containing solution. Adequacy of umbilical blood flow was supported by the fact that fetal outcome (in terms of umbilical arterial pH and Apgar scores) was the same whether adrenaline was used or not. In addition, neither the short-lived episodes of hypotension nor the ephedrine used for treatment had an adverse effect on umbilical blood flow or fetal outcome. Although this could have been the result of prompt detection and treatment, there is evidence that an autoregulatory mechanism exists within the umbilical circulation which may compensate for brief changes in maternal pressure [24].
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LIGNOCAINE AND ADRENALINE IN CAESAREAN SECTION
Jouppila R, Jouppila P, Kuikka J, Hollmen A. Placental blood flow during Caesarean section under lumbar extradural analgesia. British Journal of Anaesthesia 1978; 50: 275-278. Albright GA, Jouppila R, Hollmen AI, Jouppila P, Vierola H, Koivula A. Epinephrine does not alter human inatervillous blood flow during epidural anesthesia. Anesthesiology 1981; 54: 131-135. Lingman G, Laurin J, Marsal K. Circulatory changes in fetuses with imminent asphyxia. Biology of the Neonate 1986; 49: 66-73. Trudinger BJ, Cook CM, Jones L, Giles WB. A comparison of fetal heart rate monitoring and umbilical artery waveforms in the recognition of fetal compromise. British Journal of Obstetrics and Gynaecology 1986; 93: 171-175. Kingdom JCP, Ryan G, Whittle MJ, Doyle J, Connell JMC. Atrial naturetic peptide: a regulator of the fetoplacental circulation? American Journal of Obstetrics and Gynecology 1991; 164: 242.
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15. Abboud TK, Kim KC, Noueihed R, Kuhnert BR, 20. DerMardirossian N, Moumdjian J, Sarkis F, Nagappala S. Epidural bupivacaine, chloroprocaine or lidocaine for Cesarean section—maternal and neonatal effects. Anesthesia and Analgesia 1983; 62: 914-919. 21. 16. Abboud TK, Shiek-ol-Eslam A, Yanagi T, Murakawa K, Costandi J, Zakarian M, Hoffman D, Haroutunian S. Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics. Anesthesia and 22. Analgesia 1985; 64: 585-591. 17 Bonica JJ, Akamatsu TJ, Berges PU, Morikawa K, Kennedy WF. Circulatory effects of pcridural block. 23. Anesthesiology 1971; 34: 514-522. 18. Rosenfeld CR, Banon MD, Meschia G. Effects of epinephrine on distribution of blood flow in the pregnant ewe. American Journal of Obstetrics and Gynecology 1976; 124: 156-163. 24. 19. deRosayro AM, Nahrwold ML, Hill AB. Cardiovascular effect of epidural epinephrine in the pregnant sheep. Regional Anesthesia 1981; 6: 4—7.
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