Acta Neurochir (Wien)(1995) 135.
179-185
The Haemodynamic Effect of Transcranial Doppler-Guided High-Dose
Nimodipine Treatment in Established Vasospasm after
Subarachnoid Haemorrhage
S. C. Zygmunt and T. J. Delgado-Zygmunt
Department of Neurosurgery, University Hospital of Northern Sweden, Ume~, Sweden
Summary
Eleven patients (7 females) with aneurysmal subarachnoid hae-
morrhage (SAH) and transcranial Doppler (TCD) signs of vaso-
spasm during prophylactic intravenous nimodipine treatment
(2 mg/h) were treated with TCD-guided high-dose (4 mg/h) intra-
venous nimodipine. The patients were followed clinically and with
serial TCD investigations. Increasing nimodipine to high-dose
treatment led to a reduction of the abnormally elevated mean flow
velocities (FV) in all patients. There was also a reversal of clinical
signs of delayed ischaemia. In one patient, repeated computer tomo-
graphic (CT) investigationsrevealed a reversal of ischaemic changes.
Reduction of nimodipine from 4 to 2 mg/hr resulted in a return to
abnormally elevated mean FV as well as a return of clinical signs of
cerebral ischaemia. The outcome was favourable in 82% of the
patients and there was no mortality or vegetative survival. No
patient deteriorated clinically due to vasospasm during treatment
with high-dose nimodipine. The individual effect of nimodipine
treatment can be monitored by the use of serial TCD investigations.
TCD-guided high-dose nimodipine treatment appears to be an
effective treatment in SAH patients developing vasospasm despite
prophylactic standard dose treatment. The data give support for a
direct vascular effect of nimodipine on cerebral vasospasm.
Keywords: Subarachnoid haemorrhage; vasospasm; nimodi-
pine; transcranial Doppler.
Introduction
Since the proposal by Robertson in 1949 that the
delayed ischaemic complications following aneurysm
rupture might be secondary to vasospasm [39], vari-
ous therapeutic protocols have been designed. H o w -
ever, delayed cerebral ischaemia associated with
vasospasm is still an important cause of morbidity
and mortality following aneurysmal subarachnoid
haemorrhage (SAH) [3, 13, 17, 28, 29, 40].
During the last decade, a range of controlled clini-
cal trials as well as open studies have demonstrated
:Acta
N+ochirurgica
9 Springer-Verlag 1995
Printed in Austria
the ability of the calcium channel antagonist nimodi-
pine, to prevent the ischaemic consequences of vaso-
spasm and to improve clinical outcome [4, 7, 26, 32,
34, 36-38, 41]. Nimodipine has also been used for
treatment in patients with established vasospasm [11,
26]. Despite the improvement in clinical outcome
with nimodipine, there are only a few reports demon-
strating a reduction or reversal of angiographic vaso-
spasm with nimodipine treatment [6, 8]. Most studies
have relied on clinical or computer tomographic (CT)
signs of ischaemic brain damage as indicators in the
evaluation of the effectiveness of treatment, perhaps
because of the risk of morbidity and mortality with
angiography [33, 35].
As a result of the transcranial Dopper (TCD) ultra-
sonographic technique, a non-invasive tool for evalu-
ation of vasospasm has become available [1, 2, 18,
19, 22, 31, 42, 45]. TCD studies in patients treated
with intravenous nimodipine have demonstrated an
overall reduction in the severity of TCD vasospasm
and a reduced incidence of delayed cerebral ischae-
mia [15, 16, 23, 43, 44].
In clinical trials using intravenous nimodipine, the
standard dosage has been 2 - 3 mg/h although admin-
istration of dosages up to 4 mg/h has been used in
individual cases [44]. It has been suggested that an
increased nimodipine dosage could reduce the sever-
ity of vasospasm [23].
The aim of this study was to evaluate if TCD could
be used to monitor the individual haemodynamic
effect of standard versus high-dose nimodipine in
patients developing vasospasm in spite of prophylac-
tic standard dose nimodipine treatment.
180 S. C. Zygmunt and T. J. Delgado-Zygmunt: Transcranial Doppler-Guided Nimodipine Treatment in Vasospasm

Material and Methods Transcranial Doppler

The material consists of 11 SAH patients (7 females) develop-
ing TCD signs of vasospasm during prophylactic nimodipine treat-
ment. The patients were admitted to the Department of Neurosur-
gery, University Hospital of Northern Sweden, Ume~ between
November 1991 and June 1993. All patients had subarachnoid hae-
morrhage (SAH) after rupture of an anterior circulation cerebral
aneurysm. The mean age was 46 (24-58) years. Four patients had
hypertension and one borderline hypertension. Seven patients were
admitted within 48 hours of the SAH, the othe~ four were admitted
on day 3, 5, 13 and 14, respectively (day of SAH defined as day 0).
The clinical status on admission was classified according to Hunt
and Hess (H & H) [25]; four patients were in grade II, four were in
grade III and three in grade V (Table 1). Five of the patients were
operated on early (<72 h), one subacutely (day 4) and five were
operated on late (>8 days) (for classification see Ohman and Heis-
kaner [34]). The aneurysms were ligated using standard microsur-
gical technique. None of the patients were treated with antifibrino-
lytic agents or hypertensive/hypervolaemic therapy.
Radiographic Assessment
All patients were investigated using CT scanning and angiogra-
phy. The distribution of blood on the CT scans was graded accord-
ing to the criteria of Fisher et al. [12]. Four patients were in gra-
de II, two in grade III and five in grade IV (Table 1). CT scanning
was repeated if clinical deterioration occurred.
Four vessel angiography was performed in ten patients. One
patient had two vessel angiography performed because of technical
problems during the investigation. Four patients had multiple aneu-
rysms. The location of the ruptured aneurysm was as follows: in
five patients the anterior communicating artery (ACoA), in four the
middle cerebral artery (MCA) and in two the posterior communi-
cating (PCoA). Five of the patients had signs of vasospasm on the
initial angiography (Table 1). Follow-up angiography was per-
formed in three of these patients.
TCD measurements of the systolic, diastolic and the mean flow
velocities (FV) in the supraclinoid portion of the internal carotid
artery (ICA), MCA and the proximal segment of the anterior cere-
bral artery (A1) on both sides were performed using EME TC2-
64B (EME, Oberlingen, Germany). Mean FV values above
80 cm/sec were considered pathological. An elevation of the mean
FV in the MCA and/or ICA above 120 cm/sec was used as a criter-
ion for vasospasm while in the ACA, values above 100 cm/sec
were used [1, 22, 42, 46].
Nimodipine Treatment
All patients were initially treated with a prophylactic standard
dose (2 rag/h) of nimodipine (Nimotop| Bayer AG) intravenous-
ly and followed clinically and with the use of TCD. Upon develop-
ment of TCD signs of vasospasm despite standard dose treatment,
the dosage was increased to 4 mg/h "high dose". Daily bilateral
TCD measurements were performed and the haemodynamic effect
of nimodipine treatment on cerebral vasospasm was studied. The
high-dose treatment was administered for 24 hours in all patients.
After this, the TCD investigation was repeated whereafter the dose
was reduced to 2 mg/h. TCD measurements after another 24 hours
revealed a return to abnormally elevated values in all patients
resulting in re-introduction of high-dose treatment. The nimodipine
dose was subsequently decreased under TCD control. Standard
laboratory tests including electrolyte evaluation, liver tests and
urine analyses were performed before the initiation of treatment, at
least twice a week during treatment and following termination of
the treatment.
Assessment of Outcome
The outcome at six months after the SAH was assessed using
Glasgow Outcome Scale (GOS) [27].

Table 1. Clinical Data

Case Age Sex Clinical ~ CT b Ruptured Multiple Angiographic FVm~c DID d GOS e
no. (yrs) grade aneurysm aneurysm vasospasm (cm]sec)

1 56 M V IV ACoA - + 126 (ACA) - severe disability

2 46 F III IV ACoA - - 160 (MCA) + good recovery
3 58 F V IV ACoA - - 200 (MCA) - severe disability
4 47 F II IV MCA + + 156 (MCA) - good recovery
5 51 M II II MCA - + 128 (MCA) - moderate
disability
6 41 F III IV MCA + + 142 (MCA) good recovery
7 57 F III II ACoA + + 196 (MCA) + good recovery
8 33 M II II ACoA - - 164 (ICA) + good recovery
9 24 F II III PCoA - - 140 (ICA) + good recovery
10 50 M V II MCA + - 138 (ICA) + good recovery
11 46 F III III PCoA - - 172 (ICA) + good recovery

a Admission grade according to Hunt and Hess (1968).

b Grading according to Fisher et al. (1980).
~ Maximal mean flow velocity on TCD.
a Delayed ischaemic deficits prior to high-dose nimodipine treatment.
Glasgow outcome scale [26].