British Journal of Anaesthesia 1997; 79: 301–305
Transient neurological symptoms after spinal anaesthesia with 4%
mepivacaine and 0.5% bupivacaine
A. HILLER AND P. H. ROSENBERG
Summary
Several studies have reported transient neurological symptoms after spinal anaesthesia with 5%
lignocaine. In order to evaluate the role of concentrated solutions of local anaesthetic in the
development of transient neurological symptoms,
200 ASA I or II patients undergoing minor
orthopaedic or rectal surgery under spinal anaesthesia were allocated randomly to receive 4%
mepivacaine 80 mg or hyperbaric 0.5% bupivacaine 10 mg. All patients were interviewed by an
anaesthetist approximately 24 h after spinal
anaesthesia, and after 1 week patients were asked
to return a written questionnaire. The incidence
of transient neurological symptoms consisting of
pain in the buttocks or pain radiating symmetrically to the lower extremities differed (P:0.001)
between patients receiving mepivacaine (30%) and
those receiving bupivacaine (3%). Hyperbaric 0.5%
bupivacaine can be recommended for minor
operations on the lower abdomen or lower
extremities. (Br. J. Anaesth. 1997; 79: 301–305).
Key words
Anaesthetic
techniques,
subarachnoid.
local,
mepivacaine.
Anaesthetics
local,
Complications, neurological.
Anaesthetics
bupivacaine.
The first report of transient neurological symptoms,
termed initially transient neurological impairment or
transient radicular irritation, after spinal anaesthesia
with hyperbaric 5% lignocaine by Schneider and
colleagues in 19931 was confirmed later by several
other studies.2–6 It is thought that a localized local
anaesthetic toxic effect may be an important
contributing factor in the development of transient
neurological symptoms after spinal anaesthesia
with concentrated solutions.7 8 The occurrence of
this complication is rare after the use of 0.5%
bupivacaine for spinal anaesthesia.5 9 10
Mepivacaine has been used for spinal anaesthesia
since the beginning of the 1960s.11 In the first
large-scale report of 20 000 mepivacaine spinal
anaesthetics, outcome was favourable and no neurological complications were noted.12 However, as
with 5% hyperbaric lignocaine, the hyperbaric spinal
anaesthetic solution of mepivacaine is also quite concentrated (4%) and post-spinal sequelae similar to
those after hyperbaric lignocaine spinal anaesthesia
should be expected. In this study, we examined the
occurrence of transient neurological symptoms
after spinal anaesthesia with either 4% hyperbaric
mepivacaine or hyperbaric 0.5% bupivacaine.
Patients and methods
Two hundred ASA I or II patients undergoing minor
orthopaedic, varicose vein, rectal or gynaecological
operations were studied in a randomized, doubleblind manner (table 1). Patients with a pre-existing
neurological disease or diabetes mellitus were
excluded. The study was approved by the Ethics
Committee of the hospital, and informed consent
was obtained from the patients.
All patients were premedicated with diazepam
5–15 mg orally. Patients were allocated randomly by
sealed envelope to receive 4% mepivacaine 80 mg
with glucose 95 mg ml91 (Scandicain 40 mg ml91,
Astra, Wedel, Germany) or 0.5% hyperbaric bupivacaine 10 mg with glucose 80 mg ml91 (Marcain
spinal 5 mg ml91, Tung, Astra, Södertälje, Sweden).
An identical volume of 2 ml was drawn into a syringe
by an independent anaesthesia nurse so that the
anaesthetist (A. H.) performing the block was
unaware of which drug was given. Although the
doses are not equipotent from a theoretical point
of view, similar spread and duration of spinal
anaesthesia have been observed after a dose of 10 mg
of 0.5 % hyperbaric bupivacaine and 80 mg of
hyperbaric mepivacaine.13 14
A peripheral i.v. infusion with acetated Ringer’s
solution was started before operation. Thereafter
spinal anaesthesia was performed at the L3–4 interspace with the patient in the lateral position using a
27-gauge Quincke needle. However, if the puncture
was considered difficult, a higher interspace, larger
needle or the sitting position was chosen to perform
spinal anaesthesia. Free flow of cerebrospinal fluid
was verified before and after injection of the local
anaesthetic. Immediately after spinal puncture, the
patient was turned to the supine position with the
operating table in a slight head-up tilt position.
A. HILLER, MD, PHD, Department of Anaesthesia, Kuusankoski
District Hospital, FIN-45750 Sairaalamäki, Finland. P. H.
ROSENBERG, MD, PHD, Department of Anaesthesiology, Helsinki
University Central Hospital, FIN-00290 Helsinki, Finland.
Accepted for publication: April 10, 1997.
Correspondence to A. H.
302
British Journal of Anaesthesia
Patients were monitored with electrocardiography,
automated arterial pressure and pulse oximetry.
Hypotension (systolic arterial pressure :90 mm Hg
or 930% decrease from baseline) was treated with
5-mg increments of ephedrine or 200-␮g increments
of phenylephrine. Bradycardia (heart rate :50
beat min91 was treated with atropine 0.5 mg or
glycopyrronium 0.2 mg.
Testing of pinprick analgesia and motor block was
performed at 5, 10, 15, 60 min, and thereafter at
30-min intervals. A modified Bromage scale was
used for testing motor block: 0:no paralysis (full
flexion of the knees and feet), 1:inability to flex
the extended leg (just able to move the knees), 2:
inability to flex the knee (able to move the feet only),
3:inability to flex the ankle joint (unable to move
the feet or knees). Patients were discharged from the
recovery room when recovery of motor block was
complete. Nurses on the ward recorded the time
when patients reported that they had normal
sensation in the buttocks and feet.
All patients were interviewed by the investigator
on the first postoperative morning. They were asked
if they had experienced any of the symptoms on the
following standardized symptom checklist: headache, backache, pain not associated with surgery,
sensory disturbances, change in muscle strength, or
difficulties in voiding or in hearing. Special attention
was paid to lower extremity symptoms, type of pain
and radiation of pain.3
One week after spinal anaesthesia, patients were
asked to return a mailed questionnaire. They were
asked to mention symptoms which they particularly
associated with spinal anaesthesia. Enquiries concerning symptoms and their duration included
headache, backache, pain in the operation area and
pain in the thighs, buttocks, calves or elsewhere.
Patients were also asked to assess the degree of
satisfaction with their spinal anaesthesia.
Transient neurological symptoms were defined as
symmetrical bilateral pain in the back or buttocks or
pain radiating to the lower extremities after recovery
from spinal anaesthesia.
Student’s t test and Fisher’s exact test were used
to compare differences. P:0.05 was considered
significant.
Results
The characteristics of the patients and details of the
operations and spinal anaesthetic procedures are
summarized in tables 1 and 2. Motor block was
complete in 96% of patients in the mepivacaine
group and in 81% of patients in the bupivacaine
group (P:0.001). Details of motor block are presented in table 3. In one case, bupivacaine provided
inadequate surgical anaesthesia although free flow of
cerebrospinal fluid was verified before and after
injection of the drug.
Eighty-nine of 99 (90%) patients in the
mepivacaine group and 88 of 99 (89%) patients in
the bupivacaine group returned the questionnaire.
Twelve patients in the mepivacaine group and two
patients in the bupivacaine group were not satisfied
with their spinal anaesthesia (P:0.05). Two patients
who had received mepivacaine spinal anaesthesia
had headache at home, one for 3 days and the other
for 1 week. Neither needed an extradural blood
patch. Two patients who had received bupivacaine
spinal anaesthesia reported transient deterioration in
hearing.
The incidence of transient neurological symptoms
differed (P:0.001) between patients who received
Table 1 Characteristics of patients and variables of spinal
anaesthesia (median (range) or number)
Characteristic/variable
4% Mepivacaine 0.5% Bupivacaine
n
100
Sex (M/F)
45/55
Age (yr)
41 (21–68)
Height (cm)
170 (148–191)
Weight (kg)
76 (49–115)
Needle size
25-gauge
16
27-gauge
84
Patient position during injection
Sitting
4
Lateral
96
Duration of operation
(min)
32 (9–115)
Patient position during operation
Supine
95
Lithotomy
2
Prone
3
100
47/53
44 (20–70)
171 (150–193)
75 (50–116)
17
83
3
97
32 (7–87)
94
4
2
Table 2 Details of the spinal anaesthetic procedures. ***P<0.001
n
Sex (M/F)
Surgery
Arthroscopy of knee
Other orthopaedic
Varicose veins
Rectal or gynaecological
Attempts at dural puncture
1
2–3
>3
Paraesthesia during dural puncture
Median maximum height of block
(range)
All patients
Patients with transient neurological
symptoms
4% Mepivacaine 0.5% Bupivacaine
4% Mepivacaine 0.5% Bupivacaine
100
45/55
30***
14/16
3
1/2
100
47/53
67
17
13
3
58
21
15
6
22
3
3
2
2
1
0
0
88
5
7
6
86
8
6
5
25
4
1
2
2
1
0
0
T6 (T3–12)
T8 (T8–12)
T6 (T3–12)
T7 (T3–L4)
Neurological symptoms after hyperbaric spinal anaesthesia
303
Table 3 Characteristics of the motor block (median (range)). Motor block 3:unable to move the feet or knees,
2:able to move the feet only, 1:just able to move the knees. ***P<0.001
All patients
Patients with transient neurological
symptoms
4% Mepivacaine 0.5% Bupivacaine
4% Mepivacaine
n
100
Motor block
3
96***
2
3
1
0
No paralysis
1
Time to maximum motor block (min) 8 (5–60)***
Time to total recovery of motor block
(min)
135 (90–210)
Table 4 Nature of pain and analgesic requirement in patients
with transient neurological symptoms (NSAID:non-steroidal
anti-inflammatory drug). ***P:0.001
4% Mepivacaine 0.5% Bupivacaine
n
30***
Location of pain
Buttocks
13
Buttocks and thighs
13
Thighs
0
Buttocks, thighs and legs 4
Severity of pain
Mild or moderate
20
Severe
10
Onset of pain after recovery of block (h)
1–6
16
6–12
8
12–24
2
24–48
4
Duration of pain (h)
<12
11
12–24
9
24–72
9
120
1
Needed analgesia
Yes
23
NSAID
14
Opioids
1
Both NSAID and opioids 8
No
7
3
0
1
1
1
3
0
1
1
1
0
3
0
0
0
2
1
0
1
1
mepivacaine (30%) and those who had received
bupivacaine (3%). The mean age of patients with
transient neurological symptoms in the mepivacaine
group was 44 (range 21–68) yr and in the bupivacaine group 51 (47–54) yr. Mean weight was 77
(56–105) kg in the mepivacaine group and 77
(75–80) kg in the bupivacaine group. There was no
association between the incidence of transient
neurological symptoms and patient sex, weight or
age. All patients who experienced transient neurological symptoms had been in the supine position
during operation, except for one who was in the
lithotomy position. Furthermore, in all patients with
transient neurological symptoms the spinal puncture
had been performed in the lateral position. There
was no association between transient neurological
symptoms and difficulty of block placement or
paraesthesia. In all three patients in the bupivacaine
group and in 26 of 30 patients with symptoms in the
mepivacaine group, pain occurred within the first
24 h. In one patient who had both pain and dysaesthesia in the buttocks, symptoms lasted for 5 days. In
100
30***
81
14
1
4
17 (5–60)
127 (60–240)
29
1
0
0
8 (5–60)
130 (90–210)
0.5% Bupivacaine
3
3
0
0
0
13 (5–60)
100 (60–120)
14 patients in the mepivacaine group and in one
patient in the bupivacaine group, pain was relieved
by non-steroidal anti-inflammatory drugs; nine
patients also needed opioids. Five patients reported
that the pain was worse in the supine position and it
was relieved when they stood up and started to walk
(table 4).
No patient had sensory disturbances, change in
muscle strength or difficulties in voiding on the first
postoperative morning.
Three patients who had transient neurological
symptoms after mepivacaine spinal anaesthesia had
experienced similar symptoms before, one after 5%
hyperbaric lignocaine spinal anaesthesia and two
after 4% hyperbaric mepivacaine anaesthesia. All
three patients who had transient neurological
symptoms in the bupivacaine group returned the
questionnaire and were satisfied with the spinal
anaesthesia. In the mepivacaine group, 27 of 30
patients returned the questionnaire and 20% were
not satisfied with spinal anaesthesia; four because
of transient neurological symptoms, one because
of painful puncture and one patient complained of
difficulty in breathing because of the maximum
height of block (T4) during operation.
All complaints were transient and had disappeared
by the time the patients mailed the questionnaire.
Discussion
In this study, transient neurological symptoms
occurred in 30% of patients who received spinal
anaesthesia with mepivacaine but also in 3% of
patients who received spinal anaesthesia with hyperbaric bupivacaine. However, duration of symptoms
after bupivacaine spinal anaesthesia was less than
12 h compared with 12–120 h after mepivacaine
spinal anaesthesia.
In 1993, Schneider and colleagues published the
first case reports of transient neurological symptoms
after spinal anaesthesia with 5% hyperbaric
lignocaine.1 Other later studies have shown similar
symptoms, termed transient radicular irritation
(TRI) after 5% hyperbaric lignocaine spinal anaesthesia in 10–37% of patients.2–5 Thus the incidence
of transient neurological symptoms or TRI after
concentrated solutions of 4% mepivacaine and 5%
lignocaine is similar. In the study of Pollock and
colleagues the incidence of TRI was 16% after both
304
5% hyperbaric lignocaine and 2% lignocaine without
glucose, but 0% after 0.75% hyperbaric bupivacaine.5 In the study by Tarkkila, Huhtala and
Tuominen, only one of 110 patients had TRI after
0.5% hyperbaric bupivacaine.10 The neurotoxic
potential of 5% hyperbaric lignocaine and 0.75%
bupivacaine has been evaluated.7 Exposure of
amphibian nerves to 0.75% isobaric bupivacaine
produced partially reversible conduction block,
whereas 5% lignocaine with or without glucose
caused irreversible block of impulses.7 Furthermore,
it has been shown in an in vitro study that lignocaine
80 mmol, which is equivalent to a concentration of
2% lignocaine, caused complete ablation of impulse
activity.8 In clinical studies, decreasing the concentration of lignocaine from 5% to 2% did not prevent
the development of TRI.5 15
The doses of mepivacaine and bupivacaine in our
study were based on the clinical study of Pitkänen,
Kalso and Rosenberg, where 80 mg (2 ml) of 4%
hyperbaric mepivacaine resulted in spinal anaesthesia similar to that after a dose of 0.5% hyperbaric
bupivacaine 10 mg (2 ml) or 0.5% hyperbaric lignocaine 100 mg (2 ml).14 Also, spinal anaesthesia with
mepivacaine 60 mg produced analgesia and motor
block of good quality but of short duration compared with spinal anaesthesia with 0.5% hyperbaric
bupivacaine 15 mg.16 Decreasing the dose of mepivacaine from 80 to 60 mg may diminish the development of transient neurological symptoms and still
provide adequate anaesthesia for operations on the
lower extremities.
Lambert, Lambert and Strichartz demonstrated
synergistic neurotoxic effects of lignocaine and
glucose in vitro, in frog sciatic nerve.7 The loss of
neural activity was not found to correlate with the
glucose concentration and inhibition could not be
induced without local anaesthetic. The hyperbaric
mepivacaine solution has a higher concentration of
glucose (95 mg ml91) compared with hyperbaric
lignocaine (62.5 mg ml91) or hyperbaric bupivacaine
(80 mg ml91). The greater the baricity of the
solution the greater the chance of gravitydetermined spread restriction. This, together with
the use of small gauge pencil-point needles with one
side hole near the tip, could result in pooling of the
concentrated local anaesthetic solution. Repeated
injections through thin intrathecal catheters may,
therefore, result in cauda equina syndrome.17
Beardsley and colleagues showed that sacral direction of the needle orifice and a slow injection rate
with a Whitacre needle may be predisposing factors
to transient neurological complications with 5%
hyperbaric lignocaine.18 However, other studies have
failed to confirm this.3 10 In contrast, in this study we
injected via Quincke-type needles (orifice at the
bevelled tip) and initial directional pooling of the
local anaesthetic in the sacral region was unlikely.
In addition to a toxic effect of the local anaesthetic, the lithotomy position during surgery has
been thought to be a possible cause of transient
neurological symptoms.1 4 10 The lithotomy position
may contribute to transient neurological symptoms
by stretching the cauda equina and sciatic nerves,
thus decreasing the vascular supply and increasing
British Journal of Anaesthesia
vulnerability to injury. In our study, four patients in
the bupivacaine group and two in the mepivacaine
group were in the lithotomy position during surgery.
Only one patient in the mepivacaine group had
transient neurological symptoms starting 24–48 h
after anaesthesia. However, transient neurological
symptoms occurred in 22 patients undergoing
arthroscopy of the knee. In our hospital, arthroscopy
patients have both legs straight at the hip, and flexed
90⬚ at the knee. The operative leg position is varied
throughout surgery. The position and manipulation
may contribute to neural stretching and thus to the
development of transient neurological symptoms.
Also, Pollock and colleagues found a higher
incidence of transient neurological symptoms in
patients undergoing arthroscopy than in those
having inguinal hernia repair.5
Individual physical characteristics of patients may
predispose to the development of transient neurological symptoms after spinal anaesthesia.
Interestingly, in this study three patients who had
transient neurological symptoms after mepivacaine
spinal anaesthesia had experienced similar
symptoms before, one after 5% hyperbaric lignocaine and two after 4% hyperbaric mepivacaine
spinal anaesthesia. It has been shown that the
anatomical configuration of the spinal column
affects the spread of subarachnoid anaesthetic
solutions that move under the influence of
gravity.19 20 Both lumbar lordosis and thoracic
kyphosis differ between individuals, particularly with
respect to the lowest point of the thoracic spinal
canal.21 Musculoskeletal disturbances in the back
and leg symptoms cannot be totally excluded.
We speculate that profound relaxation of the
supportive muscles of the lumbar spine may result
in straightening of the lordotic curve, and even
transient spondylolisthesis, when the patient is lying
on the operating table. This may be responsible in
part for the radiating back symptoms which occurred
after the intense motor block, observed during
mepivacaine spinal block in particular.
In summary, the incidence of transient neurological symptoms was greater after spinal anaesthesia
with 4% hyperbaric mepivacaine than after 0.5%
hyperbaric bupivacaine. Patients were more satisfied
with bupivacaine spinal anaesthesia. Except for a
greater number of complete motor blocks after
mepivacaine, spinal anaesthesia and recovery were
similar after both agents. Therefore, hyperbaric
0.5% bupivacaine 10 mg can be recommended for
minor operations on the lower extremities or lower
abdomen lasting less than 90 min.
References
1. Schneider M, Ettlin T, Kaufmann M, Schumacher P,
Urwyler A, Hampl K, von Hochstetter A. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with
5% lidocaine. Anesthesia and Analgesia 1993; 76: 1154–1157.
2. Hampl KF, Schneider M, Drasner K, Stotz G, Drewe J. 5%
hyperbaric lidocaine: A risk factor for transient radicular irritation? Anesthesiology 1993; 79: 3A, A875.
3. Tarkkila P, Huhtala J, Tuominen M. Transient radicular
irritation after spinal anaesthesia with hyperbaric 5%
lignocaine. British Journal of Anaesthesia 1995; 74: 328–329.
Neurological symptoms after hyperbaric spinal anaesthesia
4. Salmela L, Aromaa U, Cozanitis DA. Leg and back pain after
spinal anaesthesia involving hyperbaric 5% lignocaine.
Anaesthesia 1996; 51: 391–393.
5. Pollock JE, Neal JM, Stephenson CA, Wiley CE. Prospective
study of the incidence of transient radicular irritation in
patients undergoing spinal anesthesia. Anesthesiology 1966;
84: 1361–1367.
6. Rodríquez-Chinchilla R, Rodríquez-Pont A, Pintanel T,
Vidal-López F. Bilateral severe pain at L3–4 after spinal
anaesthesia with hyperbaric 5% lignocaine. British Journal of
Anaesthesia 1996; 76: 328–329.
7. Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high concentrations of
local anesthetics. Anesthesiology 1994; 80: 1082–1093.
8. Bainton C, Strichartz G. Concentration dependence of
lidocaine-induced irreversible conduction loss in frog nerve.
Anesthesiology 1994; 81: 657–667.
9. Hampl K, Schneider M, Ummenhofer W, Drewe J.
Transient neurologic symptoms after spinal anesthesia.
Anesthesia and Analgesia 1993; 81: 1148–1149.
10. Tarkkila P, Huhtala J, Tuominen M. Transient radicular
irritation after bupivacaine spinal anesthesia. Regional
Anesthesia 1996; 21: 26–29.
11. Knox PR, North WC, Stepher CS. Pharmacologic and
clinical observations with mepivacaine. Anesthesiology 1961;
22: 987–994.
12. El-Shirbing AM, Rasheed MH, Elmaghraby A, Motahew M.
Experiences with carbocaine in spinal anaesthesia. Report of
20000 cases. Acta Anaesthesiologica Scandinavica 1966; 10
(Suppl. 23): 442–448.
305
13. Covino BG, Vassallo HG. Local Anesthetics: Mechanisms of
Action and Clinical Use. New York: Grune and Stratton,
1976; 49, 105.
14. Pitkänen MT, Kalso EA, Rosenberg PH. Comparison of
hyperbaric bupivacaine, lidocaine and mepivacaine in spinal
anesthesia. Regional Anesthesia 1984; 9: 175–182.
15. Hampl KF, Schneider MC, Pargger H, Gut I, Drewe J,
Drasner K. A similar incidence of transient neurologic
symptoms after spinal anesthesia with 2% and 5% lidocaine.
Anesthesia and Analgesia 1996; 83: 1051–1054.
16. Bengtsson M, Edström HH, Löfström JB. Spinal analgesia
with bupivacaine, mepivacaine and tetracaine. Acta
Anaesthesiologica Scandinavica 1983; 27: 278–283.
17. Rigler ML, Drasner K, Krejcic TC, Yelich SJ, Schelnick FT,
DeFontes J, Bohner D. Cauda equina syndrome after
continuous spinal anesthesia. Anesthesia and Analgesia 1991;
72: 275–281.
18. Beardsley D, Holman S, Gantt R, Robinson RA, Lindsey J,
Bazaral M, Stewart SFC. Transient neurologic deficit after
spinal anesthesia: local anesthetic maldistribution with pencil
point needles? Anesthesia and Analgesia 1995; 81: 314–320.
19. Greene N. Distribution of local anesthetic solutions within
the subarachnoid space. Anesthesia and Analgesia 1985; 64:
715–730.
20. Wildsmith J. Baricity and spinal anesthesia: What solution
when? Anesthesiology Clinics of North America 1992; 10: 31–43.
21. Hirabayashi Y, Shimizu R, Saitoh K, Fukuda H, Furuse M.
Anatomical configuration of the spinal column in the supine
position. I. A study using magnetic resonance imaging. British
Journal of Anaesthesia 1995; 75: 3–5.