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British
Journal ofAnaesthesia
1995; 74: 517-520
Prophylactic i m ephedrine in bupivacaine spinal anaesthesia
J.-E. STERNLO, A. RETTRUP ANDR. SANDIN
Summary
Inadou ble-bl ind, p lacebo-control led,randomized
study, we have investigatedtheefficacy of i.m.
ephedrine
in 98elderly patients undergoinghip
arthroplasty
under spinal anaesthesia with plain
bupivacaine. Fifty patients received ephedrine
0.6 mg
k g
1
body weight, deepinthe paravertebral
musclesimmediately after injectionofbupivacaine,
an d
48 received an equal volume
ofsaline.
Patients
in both groups were giventhesame volumesof
f luid before anaesthesia. Systolic arterial pressure
during the first 60 min after anaesthesia remained
signif icantly
more stable
in the
ephedrine-treated
group,and therewasalsoasignificantly smaller
numberofpatientsin this group who had decreases
inpressureofmore than 30%ofpre-block levels,
and
fewer required rescue
i.v.
ephedrine.
An
increaseinheart rate or systolic pressureof 20%
from baselinewasfound in twopatients in the
ephedrinegroup andinone patientinthe placebo
group.
Weconclude that ephedrine 0.6 mg kg
1
body
weight administered
in the
paravertebral
musclesimmediately after plain bupivacaine spinal
anaesthesia is a simple andeffective meansof
reducing
the incidence
of
hypotensive episodes
in
th e
elderly patient.
Br. J. Anaesth.
1995;
74:
517 -520 )
Key words
Anaesthetic techniques, subarachnoid. Sympathetic nervous
system, ephedrine. Complications, hypotension.
Ephedrine is analkaloid originally extracted from
the Chinese plant MaHuang, used in traditional
Chinese medicine
for
centuries.
In the
late 1920s,
this sympathomimetic amine wasintroduced as a
vasopressor into anaesthetic practice byOckerblad
and Dillon [1]. Its modern synthetic congener
remains
a
drug
of
choice
for
treating hypotension
found this regimen satisfactory
in
counteracting
hypotension without undue hypertension ortachy-
cardia
[6].
In all previous studies with the i.m. route,
fixed dosesofephedrine have been used.
The aim of our study was to investigate the
efficacy ofephedrineinmaintaining haemodynamic
stability inelderly patients when administered in a
single i.m.dose determined by body weightand
givenatthe same timeasspinal anaesthesia.
Patients and methods
This double-blind, placebo-controlled, randomized
study was approved by the Ethics Committeeat the
University inLinkoping. We studied 100 consecu-
tive patients undergoing total hip replacement under
spinal anaesthesia with plain bupivacaine. One
patient
was
excluded
as it was not
possible
to
perform thespinal block, andanother becauseof
incomplete data, leaving 98 patientsforevaluation.
Premedication
was
given approximately
1h
before
anaesthesia with i.m.ketobemidone 5-10 mgand
i.m. dixyrazine 10-20 mg according to age and body
weight (ketobemidone is notavailable in the UK;
ketobemidone
is an
opioid, 5 mg
is
equipotent
to
morphine 5-8 mg
[7],
dixyrazine
is a
low-dose
phenothiazine with sedative and marked antiemetic
properties[8]).Patients medicated with beta receptor
or calcium channel blockers were given theiror-
dinary morning doses. During the20-min period
before anaesthesia the patients received 3 % dextran
solution (Plasmodex, Pharmacia AB, Sweden) 7 ml
kg
1
body weight. Systolic arterial pressure (SAP)
was measured with
a
calibrated aneroid sphyg-
momanometer and radial pulse palpation. Heart rate
(HR) was obtained from a three-lead ECG. Spinal
anaesthesia with 0.5 % plain bupivacaine 20 mg was
performed
in
the L2-3
or
L3-4 interspaces with the
patient in the sitting position. Morphine 0.3 mg was
added to the bupivacaine solution. Immediately after
completionof thespinal injection, theneedlewas
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British Journal of Anaesthesia
th e3% dextran solution wascontinued at arateof
1mlkg
1
h
1
and a crystalloid solution with 2.5%
glucose (Rehydrex Pharmacia AB, Sweden) was
started and continued at a rate of 4 ml
kg
1
h
1
throughout surgery.
A decrease
in SAP of >
30 % from
the
baseline
recording to less than 100mm Hg was treated
immediately withi.v.ephedrinein 5-mgincrements
until a stable SAP above this threshold levelwas
established. Plasma volume maintenance with 3%
dextran (in additionto the continuous infusion rate
of1mlkg
1
h
1
) andpackedredcell transfusions to
compensateforintraop erative blood loss were based
on acomputer-generated schemeforeach individual
patient, taking into account
age, sex,
body weight
and height, preoperative haemoglobin (Hb) con-
centration and predetermined lowest acceptable
postoperativeHb. Inordertoprovidea comfortable
state during surgery, midazolam was administeredas
requiredindosesof 1.25m g.In a fewpatients small
doses of i.v. fentanyl were given to alleviate pain
from unanaesth etized areas causedbythe uncom fort-
able lateral position. Dixyrazine was given in i.v.
dosesof5mg to treat nausea.
SA P
and HR
were recorded before anaesthesia,
2
an d 5 min after anaesthesia,and every 5min there-
after.AllSAP measurements were obtained fromthe
upper arm. A reduction in SAP >30 from the
baseline levelwasconsidered anegative outcomein
termsof efficacy, whereas increasesin SAP 20 %
toalevel ^1 60 mmH g,and in HR 20 toa level
^ 90beat min
1
were considered adverse reactions.
The groups were comparedbyMann-WhitneyU
test
and
regression analysis,
as
appropriate.
P
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Prophylactic ephedrine 51 9
80
60
-^ 20
< 30 min 30-60 min > 60 min i Total
Figure2 Percentage of patients given i.v. rescue ephedrine
according to study criteria with regard to time after
anaesthesia
in the ephedrine ( ) and placebo ( ) groups. T he difference
obtained within 30 min was significant at P
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British Journal of Anaesthesia
tachycardia, or both, which may be detrimental [2,
3] .In dee d, use of the i.m. route in obstetric spinal or
extradural anaesthesia has been condemned. In a
study by Rolbin and colleagues in which ephedrine
was given i.m. 15-30 m in b efore extradural an-
aesthesia for elective Caesarean section, ephedrine
25 mg was ineffective in redu cing th e incidence
of matern al hyp otensio n, while a dose of 50 mg
produced unacceptable hypertension which was
associated w ith derangem ent in fetal acid-base status
[4].
Rout and co-workers also recommended that
prophylactic i.m. ephedrine not be used before
obstetric spinal or extradural anaesthesia in case the
block should fail and it became necessary to resort to
general anaesthesia [5].
However, in non-obstetric cases, Hemmingsen,
Poulsen and Risbo administered i.m. ephedrine
37.5 mg after an initial i.v. b olus of 12.5 mg . T hi s
was compared with placebo in 48 patients under-
going surgery of the lower abdomen or lower
extremities during bupivacaine spinal anaesthesia.
Greater stability of arterial pressure occurred in
ephedrine-treated patients, especially in a subgroup
of ASA III patients, where all eight patients in the
placebo group had a decrease in mean arterial
pressure exceeding
33
compared with none in the
ephedrine-treated group. Tachycardia or hyperten-
sion was not observed [6].
It seems that the problem associated with i.m.
ephedrine is that of a reliable regimen which is both
effective and also avoids overdosage. Surprisingly,
matching the dose to body mass has not been
undertaken in the earlier studies. From our previous
clinical experience it seemed that an i.m. dose of
0.6 mg kg
1
was appropriate and that reliable ab-
sorption could be expected if ephedrine was injected
deep into the paravertebral muscles. In our study we
found that this regimen provided a significant
stabilizing effect on SAP throughout the study
period of
1
h and that this effect was evident both in
the presence and absence of beta adrenergic or
calcium channel blockers, or both.
The detailed part of this study was terminated
60 m in after anaesth esia, as we expected that the
effects of i.m. ephedrine would have terminated
within this period and also we expected that any
difference in haemodynamic state would be in-
fluenced or obscured by surgical blood loss and
cementing. Nevertheless, the percentage of patients
treated with i.v. ephedrine after the first 60 min was
also significantly hig her (70 %
v s
31%
; P
