Yonago Acta medica 1998;41:73–81

Ameliorated Outcome of Subarachnoid Hemorrhage Patients Treatedwith Reduced Form Glutathione
Hisayo Okamoto, Hirochika Takeuchi, Michiharu Tanabe, Keiichi Akatsuka,
Makoto Nishiyama, Takashi Watanabe and Tomokatsu Hori
Division of Neurosurgery, Institute of Neurological Sciences, Faculty of Medicine, Tottori
University, Yonago 683-0826, Japan
This study was designed to investigate the effects of glutathione (GSH) on delayed
vasospasm and the outcome of subarachnoid hemorrhage (SAH) patients. Seventyseven SAH patients who were admitted to 4 hospitals and operated on within 72 h after
SAH, were injected intravenously with GSH (2.4 g/day) every 6 h for 14 days. Seventy
SAH patients who were not treated with GSH in the same period were selected as thecontrol group. Patient background, the outcome at 3 months after SAH according to
the Glasgow Outcome Scale and the occurrence of symptomatic vasospasm were investigated. There were no statistically significant differences in patient backgrounds
between the 2 groups. Regarding patient outcome, 57 patients (74%) showed good
recovery, 8 (10%) were moderately disabled, 9 (12%) were severely disabled, 2 (3%)
were in vegetative survival and 1 (1%) died in the GSH group, versus 39 (56%), 9(13%), 15 (21%), 3 (4%) and 4 (6%) in the control group, respectively. These overalloutcomes in the GSH group were significantly better than those in the control group (P< 0.05). In the GSH group, 31 patients (40%) showed symptomatic vasospasm, significantly lower than 46 (66%) in the control group (P < 0.01). Administration of GSH
could be a good treatment for SAH patients.
Key words: glutathione; lipid peroxide; patient outcome; subarachnoid hemorrhage; vasospasm

serum after SAH and were thought to play apertinent role in the pathogenesis of delayed
cerebral vasospasm (Asano et al.,1981; Sasaki etal.,1981a, 1981b; Romero et al.,1984; Shimizu etal.,1988; Watanabe et al.,1988a, 1988b, 1992).
Recently in Japan, anti-lipid peroxidative drugs
or radical scavengers such as nizofenone fumarate (Ohta et al., 1986), ozagrel natrium (Suzuki
et al., 1989), AVS [1,2-bis(nicotinamide)propane, (Asano et al., 1984, 1996)], ebselen(Watanabe et al., 1990, 1997; Saito et al., 1998)
and MCI-186 [3-methyl-1-phenyl-pyrazolin-5one (Nakagome et al., 1990; Watanabe et al.,1994)] have been applied to SAH patients toprevent the occurrence of vasospasm and have
had some considerable effects on patient outcomes. These agents are however all artificial
and foreign to the human body. Activation of

Although outcomes of patients who suffer fromsubarachnoid hemorrhage (SAH) have been improving over the last decade because of upgrading in microsurgical techniques and patient management, along with the development of various anti-spasmogenic drugs, these outcomes are
not yet satisfactory to most neurosurgeons especially in elderly patients and patients graded
into the worse group according to their conditions on admission. Disney and colleagues(1988) reported that 6 of 79 SAH patients (7.6%)
aged more than 60 years and 30 of 184 patients(16.3%) classified as Grade III, IV or V on the
Hunt and Hess scale showed good recovery on
the Glasgow Outcome Scale at 3 months after
the onset. Lipid peroxidations based on free
radical reactions were reported to increase in
the cerebrospinal fluid, vascular vessels andAbbreviations: CT, computerized tomography; GOS, Glasgow Outcome Scale; GSH, glutathione; SAH,
subarachnoid hemorrahge; WFNS, World Federation of Neurological Surgeons73

H. Okamoto et al.

was obtained. Every 6 h, 0.6 g of GSH which wasdissolved with 100 mL of saline, was administered to the patient intravenously for 1 h. This
treatment was started just after operation andwas continued for 14 days. In this GSH group,
no other drugs which were generally accepted
as therapeutic against delayed vasospasm wereadministered. Temporary administration of calcium antagonists and steroids for the purpose of
decreasing arterial blood pressure and reducing
brain swelling after the surgery were permitted.
As a control group, 70 patients were selected randomly from the remaining 214 candidates, retrospectively. These patients weretreated with at least one of several therapeutics
such as nizofenone fumarate, ozagrel natrium,
AVS, Ebselen and MCI-186.
In both groups, no other aggressive treatments such as cisternal perfusion therapy or
hypervolemic hypertensive therapy were performed.

natural anti-lipid peroxidative systems such as
the glutathione (GSH) cycle which are inherent
in living organisms was considered to lower thelipid peroxide content and to have beneficial
effects on delayed vasospasm (Watanabe et al.,1988b). Reduced form GSH is converted to its
oxidized form by GSH peroxidase, reducing
lipid peroxides in the process and the oxidized
form GSH is converted back to GSH by GSH
reductase. Administration of GSH was expected to reduce lipid peroxide levels, since it wasvery difficult to increase these 2 enzyme activities. We observed that GSH injected intravenously decreased lipid peroxide contents inthe serum and 5-lipoxygenase activity in thebasilar artery compared with the untreatedgroup and simultaneously ameliorated angiographical delayed vasospasm of the basilar
artery in a canine two-hemorrhage model (unpublished data). The present study was designed to investigate the effects of GSH on delayed
cerebral vasospasm and the outcome of SAH
patients. We administered GSH to SAH patients randomly and compared the findings withdata from patients who were not treated with
GSH.

Clinical Assessment
After admission, each patient’s neurologicalcondition was assessed using the Japan Coma
Scale and/or the Glasgow Coma Scale, and thepresence or absence of paresis was assessed
every day and at any time when required. The
patient’s state before the operation was gradedfrom I to V according to the World Federationof Neurological Surgeons (WFNS) SAH scale(Drake, 1988).
A computerized tomography (CT) scan was
taken on admission and classified according to
Fisher’s grouping (Fisher et al.,1980). Whenthe patient’s state deteriorated due to reruptureof the aneurysm before surgery, a further CT
scan was performed and was employed as a preoperative test. Serial CT scans were done todiagnose cerebral infarctions due to the vasospasm. The CT scan taken immediately after
the operation could reveal brain damage due tosurgery.
The site of the ruptured aneurysm was determined from the results of the first cerebral
angiography, the CT scan and the operation. In
most cases, the second angiography was performed between Day 21 and Day 60, not to veri-

Subjects and Methods

Patient GroupThe SAH patients admitted to Tottori University
Hospital, Nojima Hospital, Tokyo Police Hospitaland National Yokohama Hospital between
January 1986 and January 1993 and underwent
clipping surgery within 72 h after SAH were
nominated for this study. No patients wereruled out in terms of sex, age, site of ruptured
aneurysm or clinical state before operation, theonly exception being a patient under 20 years
old. The number of total SAH patients in the 4
hospitals in the above period was 478, of whom
291 were operated on within 72 h after SAH, 75
were operated on after 72 h, and 112 received
no operation.
Of the 291 candidates, 77 patients were selected at random before surgery and treatedwith 2.4 g/day of GSH after informed consent
74

GSH ameliorated outcome of SAH patients

Table 1. Characteristics of patients in the 2 treatment groups
Factor

GSH group

Control group

P value

Number of patients
77
70
Sex
0.20
Male
40
(51.9)
29(41.4)
Female37(48.1)
41(58.6)
Age (year)
55.0 ± 11.6
54.7 ± 11.6
0.89
WFNS grade
0.13
I
29
(37.7)
35(50.0)
II
19(24.7)
15(21.4)
III4( 5.2)
4( 5.7)
IV
20(26.0)
12(17.1)
V5( 6.5)
4( 5.7)
Location of ruptured aneurysm
0.70
Anterior communicating artery
26(33.8)
21(30.0)
Middle cerebral artery25(32.5)
22(31.4)
Internal carotid artery
19(24.7)
21(30.0)
Anterior cerebral artery3( 3.9)
5( 7.1)
Vertebral artery3( 3.9)
1( 1.4)
Basilar artery1( 1.3)
0( 0.0)
Fisher CT group0.59
1
1( 1.3)
0( 0.0)
2
7( 9.1)
14(20.0)
3
49(63.6)
36(51.4)
420(26.0)
20(28.6)
Shown are number and (%), except age expressed as mean ± SD.
There were no statistically significant differences in patients’ backgrounds between the 2 groups.
CT, computerized tomography; GSH, glutathione; WFNS, World Federation of Neurological Surgeons.

Results
fy the angiographical vasospasm but to confirm
the proper clipping of the aneurysmal neck.
Deterioration in the neurological conditionsof patients which occurred between Day 4 andDay 16 was judged to be due to symptomatic
vasospasm when other possible causes such as
brain damage due to surgery, hydrocephalus,
serum electrolytes disorder, meningitis and epilepsy were excluded.
Patient outcome was assessed 3 months
after SAH and was graded as good recovery,
moderately disabled, severely disabled, vegetative survival and dead by the Glasgow Outcome
Scale (GOS).

Comparability of treatment groups
Distribution of sex, age in years, site of ruptured
aneurysm, preoperative WFNS grade andFisher’s preoperative grouping by CT scan inboth the GSH and the control groups are indicated in Table 1. As far as these factors wereconcerned, there were no statistically significant differences between the 2 groups (P >0.1). P values were obtained by the use of thechi-squared test for sex and site of ruptured
aneurysm, Student’s t-test for age, and theMann-Whitney U test for the WFNS grade andFisher grouping by CT, respectively (Table 1).

Statistical Analysis
Symptomatic vasospasm and infarction
due to vasospasm

The data based on the clinical variables fromthe 2 groups were examined by Student’s t-test,or the chi-squared test, or the Mann-Whitney U
test with the level of significance set at 0.05.

Table 2 shows the incidence of symptomatic
vasospasm and infarction due to vasospasm in75

H. Okamoto et al.

Table 2. Incidence of symptomatic vasospasm
and infarction due to vasospasm in the 2 treatment groupsmonths in the GOS versus 39 of 70 patients(56%) in the control group. Regarding theother outcomes, moderately disabled, severely disabled, vegetative survival andFactorGroupdead in the GSH group consisted of 8 paGSH
Controltients (10%), 9 (12%), 2 (3%) and 1 (1%),
Symptomatic vasospasm
31* (40.3) 46*(65.7)
respectively, while these outcomes were
Infarction due to vasospasm 22 (28.6) 25 (35.7)
observed in 9 patients (13%), 15 (21%), 3
Shown are number and (%).
(4%) and 4 (6%) in the control group. The*P < 0.01 by chi-squared test.
outcomes in WFNS grades II and IV andalso in all patients of the GSH group, wereboth groups. The incidence of symptomatic significantly better than those of the control
vasospasm in the GSH group was 31/77 (40%), group as shown in Table 3 (P < 0.05, Mannwhich was significantly lower than the value of Whitney U test). Figure 1 which shows patient
46/70 (66%) in the control group (P < 0.01, chi- outcomes according to the GOS at 3 months issquared test). Infarction due to vasospasm was divided into 2 classes, namely good recovery
revealed on the CT scan in 22 cases (29%) in and others (moderately disabled, severely disthe GSH group and 25 cases (36%) in the con- abled, vegetative survival and dead) in eachtrol group. The difference between these fig- preoperative WFNS grade. The number of paures was not statistically significant, although tients whose preoperative WFNS grade was I
the incidence of infarction due to vasospasm in and represented a good recovery outcome was
the GSH group was lower than that in the con- 26 of 29 (90%) in the GSH group and 30 of 35(86%) in the control group; and in the cases oftrol group.
WFNS grades II, III, IV and V, 18 of 19 (95%),
2 of 4 (50%), 10 of 20 (50%) and 1 of 5 (20%)
Patient outcome
showed good recovery at 3 months in the GSH
Table 3 shows the patient outcome of both group versus 6 of 15 (40%), 2 of 4 (50%), 1 ofgroups in each preoperative WFNS grade. In 12 (8%) and 0 of 4 (0%) in the control group,
all grades, 57 of the 77 patients (74%) in the respectively.
GSH group demonstrated good recovery at 3
Table 3. Outcome of all patients in the 2 treatment groups by WFNS grade
WFNS
grade

Group

Good
recovery

Moderately
disabledI

Severely
disabled

GSH
26(89.7)
2 ( 6.9)
1 ( 3.4)
Control
30(85.7)
2 ( 5.7)
2 ( 5.7)
II
GSH*
18(94.7)
0 ( 0.0)
1 ( 5.3)
Control*6(40.0)
2 (13.3)
7 (46.7)
IIIGSH
2(50.0)
1 (25.0)
1 (25.0)
Control2(50.0)
1 (25.0)
1 (25.0)
IVGSH*
10(50.0)
5 (25.0)
4 (20.0)
Control*
1( 8.3)
4 (33.3)
4 (33.3)
V
GSH
1(20.0)
0 ( 0.0)
2 (40.0)
Control0( 0.0)
0 ( 0.0)
1 (25.0)
Total
GSH*
57
(74.0)
8 (10.4)
9 (11.7)
Control*
39(55.7)
9 (12.9)15 (21.4)
Shown are number and (%).
GSH, glutathione; WFNS, World Federation of Neurological Surgeons.
Outcome was evaluated according to the Glasgow Outcome Scale.
* P < 0.05 by Mann-Whitney U test.

76

Vegetative
survival
0
1
0
0
0
0
0
0
2
2
2
3

( 0.0)( 2.9)( 0.0)( 0.0)( 0.0)( 0.0)( 0.0)( 0.0)(40.0)(50.0)( 2.6)( 4.3)

Dead
0
0
0
0
0
0
1
3
0
1
1
4

( 0.0)( 0.0)( 0.0)( 0.0)( 0.0)( 0.0)( 5.0)(25.0)( 0.0)(25.0)( 1.3)( 5.7)

GSH ameliorated outcome of SAH patients

Vasospasm and outcome in elderly
patients

Grade GSH [29]I
Control [35]
GSH

II

[19]

In elderly patients 60 years or older, theControl [15]incidence of symptomatic vasospasm in[ 4]
the GSH group was 12/29 (41%) which
III GSH[was significantly lower than 25/27
Control 4](93%) in the control group (P < 0.001,
chi-squared test). Infarctions due to
GSH [20]
IV
Control [12]delayed vasospasms as shown on the CT
scan occurred in 9 cases (31%) in the
GSH [ 5]
GSH group and 14 cases (52%) in theV
Control [ 4]control group. This difference was notstatistically significant. Table 4 shows
the outcome of elderly patients in each Total GSH [77]Control [70]preoperative WFNS grade. Concerning
0
50
100
all patients, 17 of 29 cases (59%) in the
Incidence (%)
GSH group and 7 of 27 cases (26%) in
Good
GR recovery
Othersthe control group demonstrated good recovery at 3 months. Regarding the other Fig. 1. Bar graph showing outcomes of all patients in theclasses of outcomes, moderately dis- reduced form glutathione (GSH) and the control groups ineach preoperative World Federation of Neurological Surgabled, severely disabled, vegetative sur- eons (WFNS) grade. Dark bars and light bars indicate goodvival and dead in the GSH group were recovery and the other outcomes based on the Glasgow Outobserved in 3 (10%), 6 (21%), 2 (7%) come Scale, respectively. The number of patients is indicatedand 1 case(s) (3%), respectively, while in brackets.
these were observed in 4 (15%), 11(41%), 3 (11%) and 2 cases (7%) in the control significantly better than those in the control
group. These outcomes in the GSH group were group (P < 0.05, Mann-Whitney U test). In
Table 4. Outcome of elderly patients in the 2 treatment groups by WFNS grade
WFNS
grade

Group

Good
recovery

Moderately
disabledI

Severely
disabled

Vegetative
survival

Dead

GSH
8
(80.0)
1 (10.0)
1 (10.0)0 ( 0.0)0 ( 0.0)
Control4(50.0)
1 (12.5)
2 (25.0)
1 (12.5)0 ( 0.0)
IIGSH
5(83.3)
0 ( 0.0)
1 (16.7)0 ( 0.0)0 ( 0.0)
Control3(30.0)
2 (20.0)
5 (50.0)0 ( 0.0)0 ( 0.0)
IIIGSH
1(50.0)
1 (50.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)
Control0( 0.0)
1 (50.0)
1 (50.0)0 ( 0.0)0 ( 0.0)
IV
GSH
2(33.3)
1 (16.7)
2 (33.3)0 ( 0.0)
1 (16.7)
Control0( 0.0)
0 ( 0.0)
3 (60.0)0 ( 0.0)
2 (40.0)
V
GSH
1(20.0)
0 ( 0.0)
2 (40.0)
2 (40.0)0 ( 0.0)
Control0( 0.0)
0 ( 0.0)0 ( 0.0)
2 (100.0)
0 ( 0.0)
Total
GSH*
17
(58.6)
3 (10.3)
6 (20.7)
2 ( 6.9)
1 ( 3.4)
Control*
7(25.9)
4 (14.8)
11 (40.7)
3 (11.1)
2 ( 7.4)
Shown are number and (%).
GSH, glutathione; WFNS, World Federation of Neurological Surgeons.
Outcome was evaluated according to the Glasgow Outcome Scale. “ Elderly patients “ is defined as patients
aged 60 years or older.
* P < 0.05 by Mann-Whitney U test.

77

H. Okamoto et al.

operative condition, amount and location of subarachnoid clot, and patient’s
age were suggested to be crucial for
eventual outcome (Fisher et al., 1980;
[ 6]
GSH
II
Disney et al., 1988). The mean age inControl [10]both groups was about 55 and almost
equal to each other. The ratio of the[ 2]
III GSH
number of patients classified into
Control [ 2]WFNS grades IV and V to all patients in
the GSH group was 33%, which was
[ 6]
GSH
IV
higher than the 23% value in the control
Control [ 5]group, although the P value in compar[
5]
ing the 2 groups by the Mann-Whitney
GSH
V
Control [ 2]U test was 0.13, which was rather low.
The incidence of Fisher’s groups 3 and 4[29]
GSH
in the GSH group was 90% which was
Total
Control [27]higher than the 80% value in the control
050100
group. Thus, if the patient outcomes in
Incidence (%)
the GSH group would be better thanGood
GR recovery
Othersthose in the control group, as indeed
they were, these results would be reliFig. 2. Bar graph showing outcomes of elderly patients
aged over 60 in the reduced form glutathione (GSH) and theable, since the GSH group was at a discontrol groups in each preoperative World Federation ofadvantage compared to the control
Neurological Surgeons (WFNS) grade. Dark bars and lightgroup in terms of the latter 2 factors.
bars indicate good recovery and the other outcomes based
Moreover, only GSH was administeredon the Glasgow Outcome Scale, respectively. The number
as an agent against delayed vasospasmof patients is indicated in brackets.
in the GSH group, while one or morekinds of drugs were used in the control
each preoperative WFNS grade, the outcome in group as mentioned above.
the GSH group showed a tendency to be better
GSH has been applied to other kinds ofthan that in the control group, although the diseases such as hepatitis, toxicosis, toxemia ofdifferences were not statistically significant. pregnancy, exanthema, dermatitis, cataracts,
As shown in Fig. 2, the ratio of the patients etc., but the cost for the administration of GSH
whose outcomes were good recovery to the pa- to SAH patients is not covered by health insurtients of the GSH group in each preoperative ance in Japan. Therefore, it was impossible for
WFNS grade seemed to be higher than that in us to use GSH for all SAH patients. This fortuthe control group.
nately enabled us to compare the outcome of the
GSH group with that of the control group. GSH
is a drug which we can safely use for patients,
Discussion
because it shows almost no side-effects such asallergy, hypotension of arterial blood pressure
Although this was a retrospective study, the as- or platelet dysfunction. Administration of GSH
sumption was that it was worthwhile to com- for 14 days also costs far less than any otherpare the clinical outcomes of these 2 groups, treatment against vasospasm currently in use insince there were no statistically significant Japan. This is and will be a very important matdifferences in the backgrounds among patients, ter regardless of whether the health insurance
such as sex, age, preoperative WFNS grade, site system covers its use or not.
of ruptured aneurysm or Fisher’s grouping by
As shown in Tables 2 and 3, the administraCT scan. Of these factors, the patient’s pre- tion of GSH for 2 weeks not only reduced theGrade GSH [10]I
Control [ 8]78GSH ameliorated outcome of SAH patients

incidence of symptomatic vasospasm but alsoameliorated the outcome in SAH patients, although it did not significantly reduce the incidence of infarction caused by delayed vasospasm.
Regarding each preoperative WFNS grade, patient outcomes in the GSH group in grades II
and IV were significantly better than those in
the control group as clearly shown in Fig. 1,
while there were no statistically significant differences between the outcomes of the 2 groups
in grades I, III and V. The numbers of patientsof both groups in grades III and V were 8 and 9,
respectively, which were too small to compare
statistically. In grade I, 90% of patients in the
GSH group and 86% in the control group recovered to the level of good recovery according to
the GOS at 3 months. This suggests that patients
who suffered from mild SAH would recoverwell irrespective of which drug is administered.
Also, in the elderly patients 60 years orolder, the administration of GSH significantly
reduced the incidence of symptomatic vasospasm and ameliorated the clinical outcome,but did not significantly reduce the incidence of
infarction due to vasospasm. As shown in Fig.
2, GSH treatment tended to improve patient
outcome in each preoperative WFNS grade,
although there were no statistically significant
differences probably because of the small
number of cases.
In the younger patients under 60 and classified into preoperative WFNS grades I to III,
32 of 34 patients (94%) in the GSH group and
31 of 34 patients (91%) in the control group
showed an outcome at 3 months of good recovery. In the case of younger patients who were ingood condition after SAH, clinical outcomes
were already too good to be improved. It may
be almost impossible for an agent against delayed vasospasm to significantly ameliorate an
outcome of just 9% of patients, since these patients would suffer from surgical brain damage
and various kinds of complications at a certain
rate. In WFNS grade IV, 8 of 14 younger patients (57%) in the GSH group and 1 of 7 patients (14%) in the control group showed good
recovery in the GOS. In the younger and severe
SAH patients, GSH treatment tended to show
beneficial effects in patient outcome.

Good effects from GSH in outcomes wereobserved in patients who were older than 60 or
suffered from severe SAH. This has to be
stressed when we investigate effects of antispasmogenic drugs on SAH patient outcomes.
Actually, Petruk and colleagues (1988) reported
that nimodipine treatment increased the rate ofgood outcomes in poor-grade SAH patients in a
double-blind study, although Öhman and colleagues (1991) and Mercier and colleagues (1994)
reported that nimodipine treatment had noeffect on overall outcome in either good-grade
patients or all patients. The mean ages in years
of SAH patients in recent studies were from 44
to 55 (Öhman et al., 1991; Haley et al., 1992,
1993, 1994; Shibuya et al., 1992), which wereequal to or lower than those in our study. If themean age in our study would have been 45,
there might have been no statistically significant difference in overall outcomes between the
GSH group and the control group. The age of
SAH patients is becoming higher with the increasing span of life; actually, the mean age of
SAH patients in Tottori University Hospital
was 64 in the past year. We should thus make agreat effort to treat these elderly SAH patientsand should learn how to manage them effectively.
Above all, the administration of GSH had
beneficial effects on not only the occurrence ofsymptomatic vasospasm but also on the outcome of the SAH patient, although the incidence of infarction due to delayed vasospasm
was not significantly reduced by GSH treatment. In recent reports dealing with antispasmogenic agents, nimodipine (Petruk et al.,
1988; Öhman et al., 1991; Mercier et al., 1994),
nicardipine (Haley et al., 1993), AT877 (Shibuya
et al., 1992), AVS (Asano et al., 1996) andebselen (Saito et al., 1998) could not alter theoverall outcome of SAH patients, althoughthese drugs had beneficial effects on some parameters such as symptomatic vasospasm, infarction shown on CT scan, etc. These findings
revealed that these drugs could not only havebeneficial effects on delayed vasospasm but
also detrimental effects on patients, even if theoccurrence of delayed vasospasm could affectonly a small part of the outcome of SAH pa79

H. Okamoto et al.

84:792–803.
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after subarachnoid hemorrhage. In: Wilkins RH, ed.
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4 Disney L, Weir B, Grace M. Factors influencing
the outcome of aneurysm rupture in poor grade
patients: a prospective series. Neurosurgery
1988;23:1–9.
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subarachnoid hemorrhage grading scale. J
Neurosurg 1988;68:985–986.
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cerebral vasospasm to subarachnoid hemorrhage
visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9.
7 Haley EC Jr, Kassell NF, Torner JC. The International Cooperative Study on the timing ofaneurysm surgery: the North American experience. Stroke 1992;23:205–214.
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nicardipine in aneurysmal subarachnoid hemorrhage: a report of the Cooperative Aneurysm
Study. J Neurosurg 1993;78:537–547.
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LL, Germanson TP. A randomized trial of two
doses of nicardipine in aneurysmal subarachnoid
hemorrhage: a report of the Cooperative Aneurysm Study. J Neurosurg 1994;80:788–796.
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P, Guy G. Are the calcium antagonists really
useful in cerebral aneurysmal surgery? A retrospective study. Neurosurgery 1994;34:30–37.
11 Nakagome T, Yamakawa K, Tsubaki S, Sasaki T,
Saito I, Takakura K. Effect of a new free radical
scavenger, MCI-186, on experimental cerebral
vasospasm. In: Sano K, Takakura K, Kassell NF,
Sasaki T, eds. Cerebral vasospasm. Tokyo:
University of Tokyo Press; 1990. p. 141–142.
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subarachnoid hemorrhage. J Neurosurg 1986;
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14 Petruk KC, West M, Mohr G, Weir BKA, Benoit
BG, Gentili F, et al. Nimodipine treatment inpoor-grade aneurysm patients, results of a multicenter double-blind placebo-controlled trial. J
Neurosurg 1988;68:505–517.
15 Romero SD, Chyatte D, Byer DE, Romero JC,
Yaksh TL. Measurement of prostaglandins in thetients. Öhman and colleagues (1991) reported
results contrary to ours, namely that the administration of nimodipine reduced the incidence of
infarction due to delayed vasospasm but did notameliorate patient outcome. These conflicting
results suggest that the occurrence of infarction
shown on CT scan could have a rather less effect on patient outcome according to the GOS.
Regarding the amount of GSH for SAH patients, we began with 2.4 g/patient/day, that is
1/5 of the dose (per body weight) with which
the experimental SAH dogs were treated, andcontinued to use this dose for all patients.
Therefore we have no information concerning
the effects of other doses. Lesser doses of GSH
may exert the same effects on vasospasm as observed in this study, or higher doses may havemore effects than that in the case of 2.4 g/day.
In conclusion, intravenous administration of
2.4 g/day of GSH for 14 days ameliorated theoverall outcome of SAH patients, concomitantly decreasing the incidence of symptomatic
vasospasm. GSH can be used rather easily because of its rare detrimental effects and its low
cost, and GSH administration does not inhibit
any other treatments for SAH patients. Therefore, GSH treatment should be a good choice
for management of SAH patients, or at least thisshould be added to treatments which have been
already available for such patients.
Acknowledgments: We greatly appreciate that Drs.
Hisashi Shishido and Takeo Nojima in Nojima
Hospital (Kurayoshi, Japan), Drs. Eiju Watanabe
and Yoshiaki Mayanagi in Tokyo Police Hospital(Tokyo, Japan) and Dr. Masaharu Oda in National
Yokohama Hospital (Yokohama, Japan) gave us
valuable data.
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(Received April 20, Accepted May 18, 1998)

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