MATERNAL AND FETAL HAEMODYNAMIC EFFECTS OF SPINAL AND EXTRADURAL ANAESTHESIA FOR ELECTIVE CAESAREAN SECTION

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1 British Journal of Anaesthesia 1992; 68: MATERNAL AND FETAL HAEMODYNAMIC EFFECTS OF SPINAL AND EXTRADURAL ANAESTHESIA FOR ELECTIVE CAESAREAN SECTION S. C. ROBSON, R. J. BOYS, C. RODECK AND B. MORGAN SUMMARY Serial haemodynamic investigations were performed in 32 women who were allocated randomly to receive either spinal or extradural anaesthesia for elective Caesarean section. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. Doppler flow velocity waveforms were recorded also from the umbilical artery. Preloading with Ringer lactate solution 1 litre increased cardiac output in both groups. After injection of bupivacaine, cardiac output remained increased in the extradural group, but decreased in the spinal group. This was associated with an increase in umbilical artery pulsatility index in the spinal group. Umbilical artery ph was less in the spinal group (7.22 vs 7.27), although no neonate was depressed at birth. The maximum percentage change in cardiac output and umbilical artery pulsatility index correlated with umbilical artery ph (r = 0.54, r = 0.72, respectively). There was no significant correlation with change in arterial pressure. KEY WORDS Anaesthesia: obstetric. Anaesthetic techniques: extradural, spinal. Placenta: umbilical artery flow. Measurement techniques Doppler ultrasound, echocardiography. Controversy exists on the optimal regional anaesthetic technique for elective Caesarean section [1]. The haemodynamic changes associated with regional anaesthesia represent the greatest potential hazard of these techniques for mother and fetus [2] and evidence suggests that hypotension and neonatal acidaemia are more common after spinal anaesthesia [3]. However, because of the changes in peripheral resistance, changes in maternal arterial pressure do not necessarily reflect changes in maternal cardiac output [4] and it is changes in the latter which may pose the greatest risk to the fetus. The poor correlation between the degree of hypotension after regional anaesthesia and umbilical acid base status lends support to this suggestion [3, 5]. Relatively little is known about the changes in cardiac output during regional anaesthesia for Caesarean section. Studies during extradural anaesthesia have suggested that cardiac output does not decrease unless hypotension develops [4, 6, 7]. In two of these studies [6,7], cardiac output was measured by impedance cardiography, which has been shown to correlate poorly with stroke volume measured by thermodilution during Caesarean section [8]. Cardiac output may be calculated from Doppler ultrasound measurement of ascending aortic blood velocity combined with cross-sectional echocardiographic measurement of aortic orifice area. The technique has been validated in pregnancy [9] and allows reproducible measurements of cardiac output in pregnant subjects [10]. Doppler velocimetry has been used also to assess the fetal umbilical circulation after extradural anaesthesia [11, 12]. The aim of the present study was to compare maternal and fetal haemodynamic changes following spinal or extradural administration of bupivacaine for Caesarean section. PATIENTS AND METHODS Thirty-two healthy women (table I) with a singleton pregnancy admitted for elective primary or repeat Caesarean section at term were allocated randomly to receive either spinal or extradural anaesthesia. The TABLE I. Patient characteristics {mean {range or SD)) and operation details, t Suspected genital herpes {not confirmed); $High head/unfavourable cervix at 42 weeks gestation {noo); elderly prirmgravida /IVF pregnancy {one) Age (yr) Height (m) Weight (kg) Gestation (weeks) Indication for CS Previous CS Breech/unstable lie Other Birthweight (kg) Extradural group {n = 16) 30.5(21-36) 1.62(0.80) 72.5(12.0) 38.6(1.0) 10 5 It 3.36 (0.48) Spinal group {n = 16) 32.1 (24-^10) 1.59(0.62) 75.3 (7.5) 38.8(1.3) 9 6 3* 3.35 (0.57) S. C. ROBSON*, M.R.C.O.G.; C. RODECK, F.R.c.o.G.; B. MORGAN, F.C.ANAES.; R.P.M.S. Institute of Obstetrics, Queen Charlotte's and Chelsea Hospital, Goldhawk Road, Chiswick, London. R. J. BOYS, PH.D., B.SC., Department of Statistics, University of Newcastle Upon Tyne, Claremont Road, Newcastle Upon Tyne. Accepted for Publication: July 26, Address for correspondence: Department of Obstetrics, University College Hospital, Chenies Mews, London WC1E 6HX.

2 HAEMODYNAMICS DURING REGIONAL ANAESTHESIA FOR CAESAREAN SECTION 55 procedure was explained to each subject and written consent was obtained for the study, which was approved by the local Ethics Committee. Each subject received oral ranitidine 150 mg the night before operation and another 150 mg, together with metoclopramide 10 mg, on the morning of operation. Sodium citrate 0.3 mol litre" 1 (30 ml) was given in the operating theatre. Randomization was carried out in the operating theatre by drawing consecutive sealed envelopes. There was 1:1 randomization within balanced blocks of eight. After the insertion of an i.v. cannula, Ringer lactate solution 1 litre was infused over approximately 15 min immediately before anaesthesia. An infusion of Ringer lactate solution 1 litre with ephedrine 60 mg was commenced after the initial preload. Extradural group. With the subject in the left lateral position, an extradural catheter was introduced through a 16-gauge Tuohy needle at the L2-3 or L3-4 intervertebral space. A test dose of 3 ml of 0.5% bupivacaine with adrenaline 1: was given. After 5 min, another ml of 0.5% bupivacaine with adrenaline 1: was given by slow bolus injection. After this injection the subject was turned to the right semi-lateral (45 ) position. Five minutes later the subject was turned to the left semi-lateral (45 ) position. Sensory block was assessed every 5 10 min using the absence of perception of cold sensation to an ethyl chloride spray. Additional 0.5 % bupivacaine with adrenaline 1: (5-7 ml) was given if the sensory block was below T6 at min (n = 2). The rate of the ephedrine infusion was left to the discretion of the anaesthetist. Spinal group. With the subject in the left lateral position, a 26-gauge long spinal needle was introduced into the subarachnoid space through an extradural needle at the L2-3 or L3-^l intervertebral space and 0.5 % bupivacaine heavy ml injected intrathecally. The subject was then turned to the left semi-lateral position and sensory block was assessed every 5 min again using the absence of perception of cold sensation to an ethyl chloride spray. The infusion of Ringer lactate and ephedrine was commenced immediately after injection of bupivacaine. Thereafter the rate was determined by the anaesthetist according to arterial pressure measurements. Arterial pressure was measured by an automatic non-invasive monitor (Marquette). Measurements of systolic, mean and diastolic pressure were obtained every 2 min. Hypotension was denned as a decrease in systolic pressure of > 20 % of the baseline, pre-anaesthetic value. This was treated by increasing the rate of the ephedrine infusion and, if necessary, additional bolus doses of ephedrine 5-10 mg. Cross-sectional and Doppler echocardiographic measurements were performed with the subject in the left semi-lateral (45 ) position. The principles and techniques of aortic flow measurement using Doppler and cross-sectional echocardiography have been described previously [4, 10]. Briefly, ascending aortic blood velocities were recorded with continuous wave Doppler ultrasound using a 2-MHz transducer (Vingmed) placed in the suprastemal notch. A spectrum analyser (Doptek) performed fast Fourier transform analysis of the Doppler signal and the output was converted to velocity of flow according to the Doppler equation. The angulation of the ultrasound beam was adjusted until the highest velocities with the least spectral dispersions were obtained; these were then stored in the computer memory and it was assumed that the measured velocities were those at the aortic orifice and that the beam was parallel to flow. Heart rate and systolic velocity integral (area under the velocity curve) were calculated automatically by the computer. All calculations of velocity integral were made using 15/16 of the maximum frequency in order to exclude high frequency artefacts. The average of 8-10 consecutive beats was used for each determination. Systolic aortic orifice diameters were measured using a 5-MHz cross-sectional transducer (Ausonics). The aorta was imaged in the parasternal long axis plane and measurements were made from the leading edge of the anterior wall to the leading edge of the posterior wall. The diameters from five consecutive beats were averaged and the cross-sectional area was calculated from n (D/2) 2, where D = mean aortic orifice diameter. Cardiac output was calculated from the formula: cardiac output (litre min" 1 ) = stroke volume (ml) x heart rate (beat min" 1 ), where stroke volume = velocity integral (cm) x cross-sectional area (cm*). Arterial pressure measurements were continued every 2 min during the echocardiographic measurements and the mean of two consecutive measurements was used for analysis. Flow velocity waveforms from the umbilical artery were recorded using a 4-MHz continuous wave transducer linked to the same spectral analyser (Doptek). Measurements were made of the pulsatdlity index using 15/16 of the maximum recorded frequency, taking a mean of three consecutive cycles. All investigations were performed with the subject in the left semi-lateral position. Doppler recordings were completed in 2-3 min and cross-sectional echocardiographic recordings in 1-2 min. Measurements were performed in the operating theatre: before any intervention; after preloading with Ringer lactate solution 1 litre; at 10, 20 and 30 min after injection of bupivacaine in the extradural group; and at 5, 10 and 15 min after injection of bupivacaine in the spinal group. The times from the injection of the local anaesthetic to the start of the operation and delivery of the baby were recorded. At the time of delivery the umbilical cord was immediately doubly clamped. Samples of blood were collected from the umbilical artery and vein and blood-gas analysis was performed within 10 min of delivery. One- and 5-min Apgar scores were assigned by a paediatrician. All subjects had an uncomplicated Caesarean section with a mean blood loss of 575 ml (range ml). Statistical analysis. Within the spinal and extradural groups, a repeated measures analysis of variance was performed for each variable using the

3 56 BRITISH JOURNAL OF ANAESTHESIA TABLE II. Operative and neonatal details {mean (SD) or median (range)), f Volume infused at start of operation. * <0.05; ** P < 0.01; *** P < (.Student t test, median test) I.v. fluidf (ml) Ephedrine (mg) Injection-skin incision interval (min) Skin incision-delivery interval (min) Umbilical artery ph Pco, (kpa) Po, (kpa) Base excess (mmol litre" 1 ) Umbilical vein PH Pco, (kpa) Po, (kpa) Base excess (mmol litre" 1 ) Apgar score < 7 1 min 5 min Extradural group Spinal group (n = 16) (n = 16) 1190(241) 6(1-50) 41.4(34-54) 5.1 (3-9) 7.27 (0.02) 6.85 (0.62) 1.74(0.52) -3.56(1.75) 7.34 (0.03) 5.40 (0.57) 5.39 (0.57) -3.53(1.51) 1393(176)*** 30 (6-15)*** 25.0 (18-17)** 6.0 (4-8) 7.22 (0.08)* 7.32(1.55) 1.69(0.43) -6.20(3.61)** 7.31 (0.05) 5.52 (0.41) 3.23 (0.79)*** (2.38) statistical package BMDP. Because of the problem of multiple significance testing, the differences between time points were compared using the studentized range at the 1 % level: where q {v) = critical value for comparing two time points; s i = residual mean square with v degrees of freedom; n = number of subjects. Differences between the spinal and extradural groups were compared using Student's t test for normally distributed data and the median test for non-normally distributed data. The association between the change in various haemodynamic variables and umbilical artery ph was assessed by calculation of Pearson's correlation coefficient. RESULTS The mean dose of 0.5 % bupivacaine administered in the extradural group was 21.0 (sdl.6)ml. Two women were given another 0.5 % bupivacaine 5 ml between 20 and 25 min because of inadequate block. The upper levels of sensory block achieved at 30 min were as follows: T2 (n = 3), T3 (n = 4), T4 (n = 6), T5 (n = 2), and T6 (n = 1). All blocks extended to S5. The mean dose of 0.5% bupivacaine administered in the spinal group was 2.2 (SD 0.2) ml. Upper levels of sensory block achieved at 15 min were as follows: Tl (n = 2), T2 (n = 8), T3 (n = 2) and T4 (n = 4). The operative and neonatal details in the two groups are shown in table II. The volume of fluid infused and the amount of ephedrine given was greater in the spinal group. The interval between injection of bupivacaine and skin incision was shorter in the spinal group, but the skin incision to delivery interval was comparable in the two groups. Umbilical artery ph was less and base excess greater in the spinal group, although no infant in each group had a low Apgar score. Satisfactory cross-sectional and Doppler echocardiographic recordings were obtained in all subjects. In the extradural group, systolic arterial pressure decreased in 12/16 subjects, but in only one did values decrease to less than 80 mm Hg. Decreases in stroke volume, heart rate and cardiac output were recorded in six, five and three women, respectively. Relative to basal values, no subject had a decrease in cardiac output of more dian 1 litre. Diastolic and mean arterial pressure decreased, relative to basal values, at 10 and 20 min after bupivacaine (table III). Stroke volume and cardiac output increased after preloading. Cardiac output remained increased at 10, 20 and 30 min after bupivacaine because of increases in both stroke volume (at 10 and 20 min) and heart rate (at 20 and 30 min). Total peripheral resistance was decreased, relative to basal values, at 10, 20 and 30 min after bupivacaine. No statistically significant changes were found in fetal heart rate and umbilical artery Doppler pulsatility index. In the spinal group, systolic arterial pressure decreased in 15/16 subjects. Infivesubjects, systolic pressure decreased to less than 80 mm Hg and an ephedrine bolus (5-15 mg) was given. In two of these patients, hypotension lasted for more than 5 min. Decreases in stroke volume, heart rate and cardiac output were observed in 16, nine and 12 women, TABLE III. Haemodynamic results in extradural group (n = 16). SR = Studentized range; PI = pulsatility index. Differences between time points greater than SR significant at P < 0.01 Basal Post preload Time after bupivacaine (min) SEM SR Arterial pressure (mm Hg) Systolic Diastolic Mean Aortic area (cm 1 ) Velocity integral (cm) Stroke volume (ml) Heart rate (beat min' 1 ) Cardiac output (litre min ) Total peripheral resistance (dyn s" 1 cm"') Fetal heart rate (beat min ') Umbilical artery PI

4 HAEMODYNAMICS DURING REGIONAL ANAESTHESIA FOR CAESAREAN SECTION 57 TABLE IV. Haemodynamic results in spinal group (n = 16). SR = Sludenlized range; PI = puhatilily index. Differences between time points greater than SR significant at P < 0.01 Arterial pressure (mm Hg) Systolic Diastolic Mean Aortic area (cm 1 ) Velocity integral (cm) Stroke volume (ml) Heart rate (beat min" 1 ) Cardiac output (litre min" 1 ) Total peripheral resistance (dyn s" 1 cm"') Fetal heart rate (beat min" 1 ) Umbilical artery PI Basal Post preload Time after bupivacaine (min) SR respectively. Cardiac output decreased by > 1 litre, relative to basal values, in nine subjects. Systolic, diastolic and mean arterial pressures were less than basal values at 5 min after bupivacaine (table IV). Diastolic pressure was also decreased at 10 min. Cardiac output increased after preloading then decreased, together with stroke volume, 5 min after bupivacaine. No significant changes were found in heart rate and peripheral resistance during the period of study. Although there was no change in fetal heart rate, umbilical artery Doppler pulsatility index increased 15 min after bupivacaine. Hypotension (decrease in systolic pressure > 20%) occurred in five subjects in the extradural group and 11 in the spinal group (x = 4.5, P < 0.05). No cases of hypotension were recorded between the time of the last haemodynamic measurement and delivery of the infant. The maximum recorded changes in systolic and mean arterial pressure, stroke volume, heart rate, cardiac output and umbilical artery pulsatility index after administration of bupivacaine are shown in figure 1. The maximum decrease in systolic and mean arterial pressure, stroke volume and cardiac output were significantly greater in the spinal group. The correlations between the maximum recorded change in haemodynamic variables and umbilical artery ph for the whole group are shown in table V. A significant correlation was observed with stroke volume, cardiac output and umbilical artery pulsatility index, but not with arterial pressure or heart rate. DISCUSSION Both groups received the same volume of preload and both were given prophylactic i.v. ephednne in an attempt to reduce the incidence and severity of hypotension. Mean cardiac output increased after crystalloid preloading and then decreased in the spinal group, while values were maintained in the extradural group. The maximal reduction in cardiac output and arterial pressure was correspondingly greater in the spinal group, suggesting that spinal anaesthesia was associated with more profound haemodynamic changes. Several previous studies have reported cardiac output measurements during regional anaesthesia for Caesarean section. Ramanathan and Grant [6] measured cardiac output after induction of extradural anaesthesia with 1.5 % lignocaine with 1: adrenaline. Cardiac output did not change in those subjects who remained normotensive (45 %), but decreased substantially in those who developed hypotension. Grant, Ramanathan and Turndorf [7] reported no change in cardiac output during extradural anaesthesia with either 0.5 % bupivacaine plain or with 1: adrenaline. Hypotension developed in three subjects (9 %), who were excluded from the analysis. In both studies, stroke volume was measured by impedance cardiography. In a previous study using the Doppler technique, Robson and colleagues [4] reported an increase in cardiac output after preloading and then a return to baseline values 30 min after administration of 0.5 % bupivacaine. A variable reduction in cardiac output was found in five subjects who developed hypotension. The difference between these results and those of the present study probably reflect the prophylactic administration of ephedrine, which is known to increase cardiac output [4,6], rather than the use of bupivacaine with adrenaline [7]. The incidence of hypotension during extradural anaesthesia was comparable to that reported previously [4, 13, 14]. The incidence of hypotension in the spinal group (69 %) was greater than expected. Previous studies have shown that preloading the circulation reduces the incidence of hypotension during spinal anaesthesia to 50-65% [15, 16] and Kang, Abouleish and Caritis [5] suggested this could be reduced to 10% with prophylactic i.v. ephedrine commenced immediately after spinal injection. We did not confirm this finding, despite giving the same total dose of ephedrine. One possible explanation for this difference is the initial rate of ephedrine infusion; Kang's group [5] administered ephedrine 5 mg min" 1 for 2 min then adjusted the rate of infusion to maintain systolic pressure. The initial dose of ephedrine was smaller in the present study (median dose at 5 min after injection of bupivacaine was 5.5 mg (range 2-12 mg)), suggesting that a greater initial infusion rate is required to reduce the incidence of hypotension. Changes in umbilical artery Doppler velocity waveforms are thought to reflect changes in down-

5 BRITISH JOURNAL OF ANAESTHESIA i HR MAP SAP 20 - CD en 0 O P<0.00 P<0.001 P<0.0V FIG. I. Maximum percentage change in haemodynamic measurements during spinal (" = 16) and extxadural O (n = 16) anaesthesia for elective Caesarean section. Median* or mean and 95% confidence intervals. Comparison between groups using median test* or Student t test. For each variable except UAPI, values were calculated from the maximum decrease, expressed as a percentage of the baseline value, after injection of bupivacaine. Where there was no decrease, the minimum increase was used in the analysis. For UAPI, values are calculated from the maximum percentage increase. SAP = Systolic arterial pressure; MAP = mean arterial pressure; HR = heart rate; SV = stroke volume; CO = cardiac output; UAPI = umbilical artery pulsatility index. P<0.05* TABLE V. Correlations between maximum change m haemodynamic measurements and umbilical artery ph (n = 32). Correlation coefficients were calculated using the maximum decrease, expressed as a percentage of baseline values, except umbilical artery pulsatility index (PI), for which maximum percentage increase was used. In subjects in whom the haemodynamic measurement did not decrease to less than baseline, the minimum percentage increase mas used Haemodynamic measurement Systolic arterial pressure Mean arterial pressure Heart rate Stroke volume Cardiac output Umbilical artery PI Correlation coefficient P ns ns ns <0.05 < < stream resistance in the fetal umbilical placental vascular bed. We found no change in the umbilical artery pulsatility index (PI) during extxadural anaesthesia, confirming previous findings [12, 17]. However, PI increased after spinal injection of bupivacaine. This conflicts with the recent findings of Fairlie and colleagues [18], who found no change in PI within 15 min of spinal anaesthesia. Although hypotension occurred in 73 % of their subjects, this was corrected within 5 min. Two particular subjects in our study had marked increases in PI (2.1 and 1.7) associated with hypotension ( 39%), fetal heart rate abnormalities and subsequent umbilical artery acidaemia (7.02 and 7.13, respectively). In both cases cardiac output was reduced ( 50% and 28%, respectively) for more than 5 min. These findings suggest that umbilical placental vascular resistance may be increased during spinal anaesthesia. As there is no evidence from animal or human studies that ephedrine reduces uterine blood flow [19, 20], the most likely explanation for these findings is a reduction in uteroplacental blood flow secondary to a reduction in maternal cardiac output. Uterine blood flow has been shown to decrease during spinal anaesthesia in animals [21]. Only one group have reported studies of intervillous blood flow during spinal anaesthesia in humans [22]. Although they found no difference in mean values, individual changes were extremely large. Several studies have reported a lower mean umbilical artery ph after regional anaesthesia complicated by hypotension [23-25]. Ebner, Barcohana and Bartoshuk [26] suggested that the duration of hypotension was of particular importance, fetal bradycardia only occurring when hypotension had been sustained for over 4 min. However, Corke and colleagues [24] showed that even short-lived hypotension (<2min) reduced umbilical arterial ph. While these results would suggest an association between hypotension and neonatal acid-base status, we found no statistically significant correlation between the maximal decrease in arterial pressure and ph at delivery. Previous studies that have examined the relationship between the degree of hypotension and ph have also shown no correlation [3, 5]. In contrast, we found a significant correlation between the maximum change in maternal cardiac output and umbilical artery PI and the umbilical arterial ph at delivery, suggesting that changes in these variables are better predictors of reduced uteroplacental perfusion than changes in arterial pressure. Evidence in support of this has recently been presented by Skjoldebrand and colleagues [27].

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