Br.J. Anaesth. (1985), 57, 264-270
CONTINUOUS EXTRADURAL INFUSION OF 0.0625% OR 0.125%
BUPIVACAINE FOR PAIN RELIEF IN PRIMIGRAVID LABOUR
D. F. LI, G. A. D. REES AND M. ROSEN
Continuous extradural analgesia is practised widely
to relieve pain in labour. However, intermittent
"top-ups" of local anaesthetic agents cause "surges"
of calls upon medical and midwifery staff and, occasionally, marked changes in maternal cardiovascular
function. Previous studies have shown the effectiveness of a continuous infusion with either 0.25% or
0.375% bupivacaine although frequent manipulation of the patient's posture was required to optimize
pain relief (Glover, 1977; Evans and Carrie, 1979;
Matouskova, Hanson and Elmen, 1979; Davies and
Fettes, 1981; Taylor, 1983). This approach appears
to offer better haemodynamic stability, and should
avoid delay in topping-up when anaesthetic or midwifery staff are busy. However, the potential risk of
a dural puncture by the catheter during infusion
remains a cause for concern. Hence, a compromise
between efficacy and safety has been sought by using
a "safe" volume of a solution of lower concentration.
It has been shown by Kenepp, Cheek and Jutsche
(1983) that, with the same total dose of infused
bupivacaine, a 0.125% solution blocks more dermatomes than does either a 0.25% or 0.5% solution,
possibly because a larger volume of fluid was
infused. Clinical experience with the 0.125% concentration is inadequate as previous reports involved
either a small number of patients or a short duration
of infusion (less than 2 h) (Glover, 1977; Clark,
1982). The present study was designed to assess the
use of low concentrations of bupivacaine for
extradural infusion in a controlled manner, and to
determine the optimal volume of infusion necessary
to prolong effectively the interval between top-ups
D. F . Li*, M.B., B.S., M.R.C.O.G.; G. A. D. REES, M.B., B.CH.,
F.F.A.R.C.S.; M. ROSEN, M.B..CH.B, F.F.A.R.C.S.; Department of
Anaesthetics, University Hospital of Wales, Cardiff, United
Kingdom.
•Present address: Department of Obstetrics and Gynaecology,
University of Hong Kong, Hong Kong.
Correspondence to M.R.
SUMMARY
The efficacy of an extradural infusion of 0.0625%
or 0.125% bupivacaine was studied in 98 primigravid mothers in active labour. No special
measures were taken to posture the mother (except to avoid aorto-caval compression). The
study regimen included a control group (no infusion) receiving intermittent top-ups (0.25%.
bupivacaine 8-10 ml), two groups receiving
bupivacaine 6.25 mg h~1 infusion in different concentrations (0.0625% and 0.125%), a fourth
group receiving 0.125% bupivacaine 12.5 mg h~1
infusion, and a fifth group receiving 0.125%
bupivacaine 18.75 mg h~1 infusion. The optimum
infusion rate was 0.125% bupivacaine 10 mlh~\
at which 69% of primigravid mothers required
none or only one "top-up" of 0.25% bupivacaine
8-10 ml during a mean duration of 7.1 h labour. In
the group who had no extradural infusion, only
32% of mothers managed with one or no top-up.
The median interval between top-ups was
increased from 145 min in the no infusion group to
245 min in those mothers receiving 0.125%
bupivacaine 10 ml h~r by infusion. Increasing the
rate of infusion to 15 ml h'1 did not improve the
results. Spread of local anaesthetic to higher
levels was limited (<T5) so that testing sensory
loss at the T5-6 level at 2-hourly intervals should
detect accidental spinal blockade resulting from
inadvertent intrathecal infusion.
in patients in active labour.
PATIENTS AND METHODS
Primigravid mothers in active labour who requested
extradural analgesia were included. The plan of
investigation was approved by the ethics committee,
and consent obtained from each patient. All mothers
CONTINUOUS EXTRADURAL INFUSION IN LABOUR
received Hartmann's solution 500-1000 ml before
the local anaesthetic was injected. Lumbar
extradural blockade was performed via the L2-3 or
L3-4 intervertebral space with a 16-gauge Tuohy
needle. A catheter (Portex) was inserted leaving
about 3-4 cm inside the extradural space. Ten
millilitre of 0.5% bupivacaine was given initially and
the effects assessed after 10-15 min. Solutions
of 0.125% and 0.0625% bupivacaine were prepared
by dilution of 0.5% bupivacaine 62.5 ml in physiological saline 187.5 ml and 0.5% bupivacaine 31.25
ml in physiological saline 218.75 ml, respectively.
The patients were then randomly allocated to the
following groups:
Group I: control group with no infusion.
Group II: 0.0625% bupivacaine infusion at
10 ml 1 ^ ( 6 . 2 5 nigh" 1 )
Group III: 0.125% bupivacaine infusion at 5 ml h ~ '
(6.25 m g h " 1 )
Group IV: 0.125% bupivacaine infusion at
10 ml I T 1 (12.5 mg h" 1 )
An additional group (group V) was added to determine whether a more rapid flow improved results:
Group V: 0.125% bupivacaine infusion at 15 ml h ~ '
(18.75 m g h " "
The infusion was given by an IMED volumetric
pump through a bacterial filter. At first, mothers
were assessed every 60 min for the extent of sensory
and motor blockade, but it became obvious that this
265
was unnecessary, and assessment was carried out
every 2 h. The sensory level was determined by pinprick and lower limb weakness graded on a scale
from 0 to 3 (Bromage, 1978). Arterial pressure was
measured every 30 min and at 5-min intervals for
30 min following each top-up. The fetal heart was
monitored continuously. If analgesia was considered
inadequate by the mother, a top-up was given
(0.25% bupivacaine 8-10 ml) and the time
recorded. No special attempt was made to position
the mother except to avoid aorto-caval compression.
At delivery, a top-up was administered if perineal
analgesia was inadequate. The mode of delivery,
duration of labour and condition of the baby were
recorded. Venous blood samples were taken from
the mother and from the umbilical cord for analysis
of bupivacaine concentration. The samples were
stored at - 2 0 °C until analysed. Each mother was
interviewed the day after delivery. The overall
assessment of pain relief, degree of drowsiness and
sickness experienced in labour were determined by
10-cm linear analogue scales. The durations of sensory and motor loss after delivery were noted. The
condition of the baby was assessed by the mother
and by the observer.
The results were analysed by t test, chi-square test
with Yates' correction and one-way variance
analysis. The intervals between top-ups were
analysed by the log-rank test (see below).
TABLE I. Patient data (mean (SD)). There were no statistical differences between the five groups.
Group I
Bupivacaine
Concentration
Infusion dose
(mgh-1)
No. of patients
Age(yr)
Height (cm)
Length of
gestation (weeks)
Duration of
labour (h)
1st stage
2nd stage
Birth weight (kg)
Group II
0.0625%
Group III
0.125%
Group IV
0.125%
Group V
0.125%
6.25
6.25
12.5
18.75
19
20
20
19
20
24.1
(4.1)
158.8
(5.1)
24.1
(4.4)
160.6
(6.4)
23.8
(4.7)
160.1
(4.9)
24.8
(5.0)
158.8
(6.1)
25.5
(6.2)
161.9
(7.5)
40.5
(1.4)
40.0
(1.6)
40.5
(1.2)
39.8
(1.2)
40.5
(1.1)
11.5
(4.9)
2.0
(1.1)
3.4
(0.4)
11.3
(3.6)
1.7
(0.9)
3.3
(0.4)
11.0
(4.8)
1.9
(1.3)
3.3
(0.4)
10.5
(5.3)
1.8
(1.0)
3.3
(0.6)
12.9
(5.1)
1.7
(1.0)
3.4
(0.5)
0
BRITISH JOURNAL OF ANAESTHESIA
266
RESULTS
Ninety-eight primigravid mothers were included.
Mothers with extradural blockade-delivery intervals of less than 3 h were excluded from the statistical analysis. There were no significant differences
between any group of patients (including group V)
in age, height, gestational period or birth weight
(table I). The duration of the first stage of labour
varied between a mean of 10.5 h and 12.9 h, and the
mean durations of the second stage from 1.7 to 2.0 h
(ns).
The mean interval between the induction of the
extradural blockade and delivery ranged from 7.1 h
to 8.6 h (ns), and the mean total dose used from
135.2 mg to 197.9 mg (P < 0.05) (table II). In only
three patients did the total dose required exceed
300 mg: a mother in group II received 330 mg over
12 h; another in group III received 337 mg over
15 h; and a third in group V required 350 mg over
14 h. The mean dose per hour for each group
showed a progressive increase in the amount of
bupivacaine with increasing infusion dose
(P < 0.005) (table II). There were, however, no significant differences between the results in groups II
and III, that is mothers who received the same total
dose given in different concentrations.
Fifty-two per cent of primigravid mothers
required three or more top-ups when no infusion
was given, compared with 5% and 0% who had
0.125% bupivacaine 10 or l S m l r T 1 (table III).
Sixty-nine percent of mothers required none or only
one top-up with an infusion of 0.125% bupivacaine
10 ml h . This compares favourably with 32% in
the control group and 35% and 45% of the mothers
receiving 6.25 mg h" 1 infusion (groups II and III,
respectively). When the infusion rate was increased
to 0.125% bupivacaine 15 ml h" 1 , the number who
required one or less top-up increased to 70%. Only
one mother who received an infusion at 12.5 mg h~'
required more than two top-ups.
The time of each top-up was recorded and each
interval representing the duration of adequate
analgesia calculated. For most mothers in the period
from the final dose to delivery, adequate analgesia
was maintained right up to the time of delivery (and
could have extended beyond this time). Some
mothers had a top-up immediately before operative
delivery. In those patients the last duration was discarded.
Cumulative percentage graphs were drawn for the
durations of adequate analgesia for each infusion
regimen (fig. 1). This included all periods for each
group, that is, several per subject. Groups were
compared by the log-rank test (Peto et al., 1976,
1977) which was also used to examine variations
between subjects within groups. In the control
group the interval between top-ups varied between
25 min and 270 min with a median interval of
145 min. In the group receiving 0.0625%
bupivacaine lOmlh" 1 , intervals varied between
90 min and 430 min (median duration of 190 min).
In the group receiving 0.125% bupivacaine
5 ml h~', the interval between top-ups varied
between 40 min and 462 min with a median interval
of 195 min; these are similar means.
At an infusion rate of 0.125% bupivacaine
TABLE II. Duration of extradural infusion and total dose of bupivacaine (mean (SD)). fNo
statistical differences between the five groups; *?<O.0S (between each group); **?<0.005 (between
each group)
Group I
Bupivacaine
Concentration
Infusion dose
(mgh-1)
Extradural — delivery
interval (h)f
Total dose used
in labour (mg)
(loading + infusion
+ 1st stage
top-ups)*
Mean dose per
hour (mgh"1)**
_
Group II
Group III
Group IV
0.125%
Group V
0.0625%
0.125%
0.125%
0
6.25
6.25
12.5
18.75
7.7
(3.1)
8.6
(2.6)
8.4
(3.0)
7.1
(2.3)
8.1
(2.6)
135.2
(52.2)
165.2
(67.2)
170.8
(64.9)
161.0
(52.0)
197.9
(63.6)
18.9
(6.4)
19.2
(5.0)
20.9
(4.8)
23.6
(7.9)
24.7
(3.0)
CONTINUOUS EXTRADURAL INFUSION IN LABOUR
267
TABLE III. Percentage of patients requiring top-ups in labour. V<O.OdS: no significant differences
between groups II and III, and IV and V
Group II
Group I
Bupivacaine
Concentration
_
Infusion dose
(ragh- 1 )
0
No. top-ups
0
1
2
3+
0
32
16
52
10 ml h ', the intervals varied between 38 min and
438 min with a median interval of 245 min. Variations between the first four groups were highly
significant (chi-square = 22.65, d.f. = 3,
P < 0.001). Variation between subjects was no
greater than would be expected had each duration
come from
a different
individual
(chisquare = 71.02, d.f. = 74, ns). When the infusion
rate of 0.125% bupivacaine was set at 15 ml h"1,
the median interval of 265 min was not significantly
different from that noted in those mothers receiving
0.125% bupivacaine 10 ml rT 1 .
IUU
J
ff
CO
inti
r
70
a>
0.125%
6.25
6.25
12.5
18.75
10
25
35
30
5
40
25
30
21
48
26
5
35
35
30
0
0.125%
0.125%
Only one mother had a sensory block which
extended up to T4 during infusion (table IV). The
degree of lower limb paralysis did not vary greatly
between groups. The mode of delivery was not
related to the infusion regimen.
The overall pain, drowsiness and nausea scores at
the postnatal interview (table V) showed no important differences. Babies were active and alert when
examined on the second day. Only eight had any
complication during delivery—all unrelated to
extradural analgesia.
Excluding those from mothers who had the last
a.
40
urn ulati
30
O
20
i
i
j
|
i
i
j
;
\'J r
.
i
J
_.
.1
1' ''
i
i
j ,—'
J r"
H—J
50
,
a>
J
i
;JJ
o
CO
0.0625%
'
J
f r
60
CD
O)
S
'c
Group V
I
80
"o
Group IV
1
90
fl)
Group III
I
i
J
—
—
—
3
Jprf
—
10
100
200
Control : no infusion
1
0.0625 f. Bupivacaine 1 0 m l h '
0.125 X Bupivacaine 5 ml h~1
0.125 7. Bupivacaine 10mlh" 1
0.125 7. Bupivacaine 15 ml h'1
300
400
, 500
Duration of interval (min)
600
700
FIG. 1. Cumulative percentage of intervals between top-ups for each bupivacaine infusion regimen.
BRITISH JOURNAL OF ANAESTHESIA
268
TABLE IV. Degree of sensory and motor blockade. Grade 0 = flexion of hip, knee and ankle; grade
I = flexion of knee and ankle only; grade II = flexion of ankle only, grade III = unable to move
legorfoot. *No statistical differences between the five groups
Group I
Bupivacaine
Concentration
_
Infusion dose
(nigh" 1 )
0
Highest level of
analgesia
T6
Degree of motor
block*
Grade 0
Group II
Group III
0.0625%
0.125%
6.25
6.25
T8
Group IV
0.125%
Group V
0.125%
12.50
18.75
T6
T4
T5
0%
5.3%
5%
5%
Grade I
10.5%
25%
10%
21%
30%
Grade II
47.4%
50%
50%
73.7%
55%
Grade III
36.8%
20%
35%
5.3%
15%
top-up given for operative delivery (forceps and
Caesarean section), 44 paired blood samples were
available for bupivacaine analysis (table VI). At
delivery, venous bupivacaine concentrations were
greater in those mothers who had an extradural infusion than in control subjects, and ranged from
0.325 \igm\~1 to 0.543 \igml~1. This difference
was not statistically significant (P = 0.175). The
bupivacaine concentration in the umbilical cord
remained low both in controls and in mothers receiving the extradural infusion (P = 0.38).
DISCUSSION
In this study mothers with an extradural blockadedelivery interval of less than 3 h were excluded. This
decision was taken since the initial loading dose
could be effective within this period and would bias
the results from the infusion; this was confirmed by
the findings in the control group: 50% of mothers
0%
had adequate analgesia for over 2 h after a single
extradural dose of bupivacaine. Therefore, previous
studies in which an infusion was given for less than
2 h may not be valid (Evans and Carrie, 1979; Clark,
1982).
No special manipulation of the mother's posture
was attempted. The physical behaviour of the infusion of bupivacaine in the extradural space is still far
from clear (Bromage, 1978). Frequent manipulation
of labouring mothers causes excessive stress on the
midwifery staff and inconvenience to the mothers.
Time spent on frequent postural changes allowing
infusions to "catch-up" could then be greater than
giving top-ups in the usual way.
A continuous infusion of 0.125% bupivacaine
10 ml h" 1 resulted in 69% of these primigravid
mothers requiring no or only one top-up. This is
in agreement with the findings of Matouskova, Hanson and Elmen (1979) with 0.25% bupivacaine
TABLE V. Results of postnatal interview (mean (SD)). There were no statistical differences between
the five groups for each of the three scores
Group I
Bupivacaine
Concentration
Infusion dose
(mgh- 1 )
_
Group II
0.0625%
0
Group III
0.125%
Group IV
0.125%
Group V
0.125%
6.25
6.25
12.50
18.75
Pain score
30.2
(23.2)
34.5
(25.2)
41.0
(26.4)
45.3
(28.2)
41.9
(18.0)
Drowsiness score
32.8
(28.6)
24.2
(28.6)
30.9
(36.0)
25.8
(29.0)
31.3
(28.5)
Nausea score
22.6
(27.5)
20.4
(23.9)
9.2
(17.5)
17.0
(21.9)
24.1
(29.6)
CONTINUOUS EXTRADURAL INFUSION IN LABOUR
269
TABLE VI. Maternal and cord blood concentrations of bupivacaine (mean (SD)). * P <0.02; ** P
= 0.175; fP = 0.38; fP = 0.06
Group I
Infusion dose
(High"1)
0.0625%
0.125%
6.25
Group IV
0.125%
Group V
0.125%
12.5
18.75
11
8
0
6.25
No. of paired
samples
10
9
Last bolus dosedelivery interval*
(h)
1.68
(1.36)
1.87
(1.11)
3.70
(2.63)
3.31
(1.52)
3.75
(1.50)
Maternal concn
MV**(ugml-')
0.240
(0.088)
0.328
(0.095)
0.543
(0.606)
0.438
(0.194)
0.325
(0.146)
Umbilical cord
concn UVf
(ugrnl"1)
0.164
(0.083)
0.152
(0.118)
0.122
(0.034)
0.159
(0.051)
0.103
(0.038)
0.67
(0.28)
0.44
(0.26)
0.45
(0.31)
0.41
(0.16)
0.37
(0.17)
UV/MVJ
infused at 5 ml h ! . When the infusion rate was
increased by 50% to 15 ml h" 1 , the percentage of
success did not increase. This plateau of effect was
also evident in the median intervals between topups.
In each test group the median duration between
250
200
I
|
c
c
TO
1
100.
0
Group III
Group II
Bupivacaine
Concentration
6.25
12.5
18.75
1
Bupivacaine infusion dose (mg h" )
FIG. 2. Regression of the median intervals between top-ups for
each bupivacaine infusion dose.
6
top-ups was 145,190,195,245 and 265 min, respectively. A regression of the median interval between
top-ups follows a straight line with increasing dose
of infusion until a plateau is reached at the higher
doses (fig. 2). Therefore 0.125% bupivacaine
10 ml h" 1 appears optimal.
Considering results from mothers having the
same dose but at different concentrations and
volumes (group II and group III), the cumulative
percentages (fig. 1) of the two groups were very close
and median durations of analgesia were 190 and
195 min, respectively. This indicates that more
fluid in the extradural space did not provide longer
analgesia and that the total dose of local anaesthetic
was the decisive factor. This is in disagreement with
the findings of Kenepp, Cheek and Gutsche (1983)
that low concentrations of bupivacaine are more
effective than higher concentrations in extradural
infusion. This finding is in fact in agreement with
Bromage's findings with the use of intermittent topups for continuous extradural analgesia (Bromage,
1978).
The safety of continuous extradural infusion with
local anaesthetics remains a matter of concern to
anaesthetists. Inadvertent puncture of the dura during infusion has been recorded (Matouskova, Hanson and Elmen, 1979). However, results from
studies on bupivacaine used for subarachnoid
analgesia give some indication of possible effects.
After a bolus injection of 0.5% bupivacaine 1520 mg, blockade usually does not extend above T4
(Chambers, Edstrom and Scott, 1981; Kalso,
BRITISH JOURNAL OF ANAESTHESIA
270
Tuominen and Rosenberg, 1982; Tuominen, Kalso
and Rosenberg, 1982; Russell, i983; Ryan, Pridie
and Copeland, 1983; Sheskey et al., 1983; Tattersall, 1983). The block then regresses at about two
segments per hour. Therefore, by infusing a dose of
bupivacaine 12.5 mg h" 1 steadily, it is unlikely that
total spinal blockade with respiratory paralysis
would occur quickly (or even at all) if dural puncture
occurred. There should be at least 2 h of warning
before the blockade extended higher than T9-10
during obstetric analgesia. Sensory testing at T5-6
at 2-hourly intervals would detect advancing spinal
blockade arising from inadvertent intrathecal infusion. In our series, admittedly small, only one
patient had a block reaching T4, so that with this
regimen there would have been only one false alarm
with the proposed procedure. Therefore, it is advocated that testing the level at T5-6 (marked clearly)
every 2 h during an infusion should be easily
accepted by mid wives.
The bupivacaine concentrations in both mother
and baby at delivery were well within the safety
range of 1.5-2.3 \ig ml"' (Widman, 1966; Jorfeldt,
et al., 1968; Hollmen, Kerhonen and Ojala, 1969;
Reynolds and Taylor, 1971). The higher maternal
bupivacaine concentraton in the groups receiving an
infusion probably related to the higher total dose
used in these mothers. However, the umbilical cord
bupivacaine concentration remained constantly low.
This may be related to the higher protein-binding
capacity of bupivacaine and the steady input of a
small bupivacaine dose to the mother during infusion, compared with the high fluctuating concentration of intermittent top-ups. The results obtained
agree with previous reports that the continuous
extradural infusion of bupivacaine is safe for both
mother and fetus (Glover, 1977; Evans and Carrie,
1979; Matouskova and Hanson, 1979; Clark, 1982).
ACKNOWLEDGEMENTS
We are grateful to the obstetricians of University Hospital of
Wales, Cardiff and St David Hospital, Cardiff for their collaboration. We thank Dr R. G. Newcombe, Medical Statistics Department, Welsh National School of Medicine for statistical advice,
Duncan Flockhart & Company for undertaking the bupivacaine
assays, the Medical Illustration Department of University Hospital of Wales for preparing the illustrations and Mrs H. O'Donnell
for secretarial assistance.
REFERENCES
Bromage, P. R. (1978a). Epidural Analgesia, 1st edn, pp.144,
136, 553. Philadelphia: Saunders.
Chambers, W. A., Edstrom, H. H., and Scott, D. B. (1981).
Effect of baricity on spinal anaesthesia with bupivacaine. Br.J.
Anaesih., 53, 279.
Clark, M. J. (1982). Continuous mini-infusion of 0.125 per cent
bupivacaine into the epidural space during labour.J. A.O.A.,
81,484.
Davies, A. O., and Fettes, I. W. (1981). A simple safe method for
continuous infusion epidural analgesia in obstetrics. Can.
Anaesih. Soc.,J.,2S, 484.
Evans, K. R. L., and Carrie, L. E. S. (1979). Continuous
epidural infusion of bupivacaine in labour—a simple method.
Anaesthesia, 34, 310.
Glover, D. J. (1977). Continuous epidural analgesia in the obstetric patient: a feasibility study using a mechanical infusion
pump. Anaesthesia, 32, 499.
Hollmen, A., Kerhonen, M., and Ojala, A. (1969). Bupivacaine
in paracervical block. Plasma levels and changes in maternal
and foetal acid-base balance. Br. J. Anaesih., 41, 603.
Jorfeldt, L., Lofstrom, B., Pernow, B., Persson, B., Wahren, J.,
and Widman, B. (1968). The effect of local anaesthetics on the
central circulation and respiration in man and dog. ActaAnaesthesiol. Scand., 12, 153.
Kalso, E., Tuominen, M., and Rosenberg, P. H. (1982). Effect
of posture and some CSF characteristics on spinal anaesthesia
with isobaric 0.5% bupivacaine. Br. J. Anaesih., 54, 1179.
Kenepp, N. B., Cheek, T. G., and Gutsche, B. B. (1983).
Bupivacaine—continuous infusion epidural analgesia for
labour. Anesthesiology, 59, A407.
Matouskova, A., and Hanson, B. (1979). Continuous mini-infusion of bupivacaine into the epidural space during labour. Part
II—Blood concentration of bupivacaine. Ada Obstet. Gynecol.
Scand. (Suppl.), 83, 31.
Elmen, H. (1979). Continuous mini-infusion of
bupivacaine into the epidural space during labour. Part III—A
clinical study of 225 parturients. Ada Obstet. Gynecol. Scand.
(Suppl), 83, 43.
Peto, R., Pike,M. C , Armitage, P., Breslow, N. E., Cox, D. R.,
Howard, S. V., Mantel, N., McPherson, K., Peto, J., and
Smith, P. G. (1976). Design and analysis of randomized clinical trials requiring prolonged observation of each patient—I.
Introduction and design. Br.J. Ca., 34, 585.
(1977).
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples.
Br.J. Ca.,35, 1.
Reynolds, F. L.,and Taylor, G. (1971). Plasma concentration of
bupivacaine during continuous analgesia in labour. The effect
of adrenaline. Br.J. Anaesih., 43, 436.
Russell, I. F. (1983). Spinal anaesthesia for Caesarean section.
The use of 0.5% bupivacaine. Br.J. Anaesih., 55, 309.
Ryan, D. W., Pridie, A. K., and Copeland, P. F. (1983). Plain
bupivacaine 0.5%: a preliminary evaluation as a spinal
anaesthetic agent. Ann. R. Coll. Surg. Engl., 65, 40.
Sheskey, M. C , Rocco, A. G., Bizzani-Schmid, M., Francis, D.
M., Edstrom, H., and Covino, B. G. (1983). A dose-response
study of bupivacaine for spinal anesthesia. Anesth. Analg., 62,
931.
Tattersall, M. P. (1983). Isobaric bupivacaine and hyperbaric
amethocaine for spinal analgesia. A clinical comparison. Anaesthesia, 38, 115.
Taylor, J. H. C. (1983). Clinical experience with continuous
epidural infusion of bupivacaine at 6ml per hour in obstetrics.
Can. Anaesih. Soc.J., 30, 277.
Tuominen, M., Kalso, E., and Rosenberg, P. H. (1982). Effects
of posture on the spread of spinal anaesthesia with isobaric
0.75% or 0.5% bupivacaine. Br.J. Anaesih., 54, 313.
Widman, B. (1966). LAC-43 (Marcaine)—a new local anaesthetic. Ada Anaeslhesiol. Scand. (Suppl.), 25, 59.