Effect of Postoperative Administration of Saireito for Bilateral Chronic Subdural Hematomas

doi:10.4236/ijcm.2011.23047

Paper Menu >>

Journal Menu >>

International Journal of Clinical Medicine, 2011, 2, 285-288

doi:10.4236/ijcm.2011.23047 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)

285

Effect of Postoperative Administration of Saireito

for Bilateral Chronic Subdural Hematomas

Satoshi Utsuki, Hidehiro Oka, Chihiro Kijima, Madoka Inukai, Katsutoshi Abe, Kimitoshi Sato,

Sachio Suzuki, Kiyotaka Fujii

Department of Neurosurgery, School of Medicine, Kitasato University, Sagamihara, Japan.

Email: [email protected]

Received April 1st, 2011; revised April 29th, 2011; accepted May 26th, 2011.

ABSTRACT

The aim of this retrospective study was to investigate the efficacy of saireito for bilateral chronic subdural hematomas

(B-CSDH). Between April 2006 and March 2010, a total of 18 patients undergoing unilateral burr hole drainage for

B-CSDH took part in a controlled clinical study. Postoperative status of the nonsurgical side was subsequently evalu-

ated, with (n = 10) and without (n = 8) saireito administration. Two in the saireito-treated group patients and four in

the control group patients ultimately required contralateral surgical intervention. The remainder, including eight

saireito-treated hematomas, resolved without further surgery, generally within eight weeks of the surgical side proce-

dure. However, two of the four resolving control lesions took longer to regress. The hydragogue and anti-inflamma-

tory/steroid-evoking properties ascribed to saireito may facilitate hematoma resolution. After unilateral surgery for

B-CSDH, saireito administration may prevent symptomatic deterioration of a contralateral low-density CSDH, pre-

empting subse quent surgery.

Keywords: Bilateral Chronic Subdural Hematomas, Contralatera l Hematoma, Medical Treatment, Saireito,

Steroid-Like Effect

1. Introduction

Patients with chronic subdural hematoma (CSDH) often

present with mental dullness, hemiparesis, and headache,

indicating that surgical intervention is needed. Should a

patient refuse surgery or have few, if any, symptoms,

therapeutic success has been reported with the Japanese

traditional medicine, goreisan [1,2], as an alternative to

steroid [3-5]. Similarly, saireito is an herbal remedy in-

corporating the ingredients and activity of goreisan, but

with added steroid-like effect [6,7]. Since saireito has

therapeutic potential for treatment of CSDH, this study

was conducted to evaluate its administration after uni-

lateral surgical drainage in patients with bilateral CSDH

(B-CSDH). The contralateral lesions were assessed

postoperatively, with and without saireito treatment.

2. Materials and Methods

Between April 2008 and March 2010, 10 patients with

B-CSDH, undergoing unilateral surgical drainage, were

evaluated for postoperative changes in the contralateral

lesions with administration of saireito (saireito group).

All B-CSDH cases of this period were enrolled in con-

trolled clinical study. The medication was given as a

single 3.0 gm dose before mealtime with cold water,

from the day following surgery until the hematoma re-

solved. Dimensions of clot were measured from the in-

ner skull to the brain on axial CT views. Contralateral

lesions were assessed at hematoma maximum dimension

and hematoma density by CT, and change in CT density,

spontaneous resolution and number of required surgeries

were recorded.

Between April 2006 and March 2008, eight control

patients treated with unilateral surgery for B-CSDH

were studied for comparison retrospectively as control

group. None received postoperative saireito.

CT scans of the head were performed on all patients at

four-week intervals or when there were signs of deterio-

ration due to hematoma, for example declining mental

faculties, hemiparesis and headache.

Significant differences were analyzed using Stat View

5.0 software. The p value using a t-test for age, the

maximum dimension of contralateral hematoma and

interval until surgery for contralateral hematoma was

calculated, and a chi-square test (Fisher’s exact test) was

Effect of Postoperative Administration of Saireito for Bilateral Chronic Subdural Hematomas

286

used to determine the significance in the other factors.

3. Results

Mean age of patients given saireito was 70 ± 9.3 years

(range, 61 - 86 years). Seven were males and three were

females. Mean age for the control group was 66 ± 13.1

years (range, 45 - 85 years), with four males and four

females. The mean maximum dimension of contralateral

CSDH was 14.0 ± 5.3 mm (range 6.0 - 21.0 mm) in

saireito recipients and 11.0 ± 4.5 mm (range 6.0 - 16.0

mm) in the control group. Contralateral lesions were

initially mixed or isodense on CT scan in seven patients

of the saireito treatment group and in three members of

the control group, but showed a low density in three

saireito-treated patients and five control patients. There

were no significant differences between groups relative

to these features (Table 1). Overall, two patients on

saireito and four control subjects needed surgical drain-

age of enlarging contralateral hematomas. The period

before the onset of symptoms was one to two weeks for

those receiving saireito, but up to eight weeks (mean,

five weeks) for the control patients. Contralateral hema-

tomas resolved without further surgery in eight

saireito-treated patients and in four controls. While all

eight hematomas of saireito group resolved in less than

eight weeks (Figure 1), two of the four resolving lesions

in the control group took longer (12 - 16 weeks) to re-

gress.

Of the contralateral hematomas eventually needing

surgical drainage, three were mixed or isodense (two in

saireito group, Figure 2), and three were low-density at

presentation. Three hematomas requiring surgical inter-

vention at later time points (Figure 3) were all in control

patients, and all were low-density lesions.

Maximum dimension of contralateral hematomas at

presentation did not differ by patient group (Figure 4).

Table 1. Summary of patient characteristics.

Saireito Control

group (n = 10) group (n = 8)

Age (mean) 61 - 86 (70) 45 - 85 (66)

Male:Femal 7:3 4:4

Use of the anticoagulant 210 18

Contralateral hematoma

Maximum dimension (mm) 6 - 21 6 - 16

Mean (mm) 14 11

Density of hematoma

Mixed or iso 7 3

Low 3 5

Surgery required 210 48

Interval until surgery 1 - 2 w 1 - 8 w, mean 5 w

Regression without surgery 810 48

Regression time

<8 weeks 8 2

>8 weeks < 0 2

(a) (b)

Figure 1. Cranial CT of 76-year-old female hospitalized

with left hemiplegia (a). Evacuated mixed-density B-CSDH

on right; left lesion asymptomatic and unchanged in post-

operative CT (b). Single-dose saireito (3.0 gm) given before

meal with cold water, initiated on day following surgery.

Four weeks after right-sided CSDH surgery, mixed-density

left CSDH appears low-density and diminished in size (c).

Both hematomas resolved eight weeks postoperatively (d).

(a) (b) (c)

Figure 2. Cranial CT of 83-year-old female hospitalized

with left hemiplegia (a). Mixed density B-CSDH with sur-

gery on right; left asymptomatic and unchanged in postop-

erative CT (b). Single-dose saireito (3.0 gm) given before

meal with cold water, initiated on day following surgery.

Right hemiplegia one week later, cranial CT with expanded

CSDH on left (c).

(a) (b) (c)

Figure 3. Cranial CT of 71-year-old female hospitalized

with left hemiplegia (a). Right-sided mixed (slightly low)

density CSDH with the midline shift to left; surgery per-

formed on right. Improved midline shift on postoperative

CT and left CSDH unchanged (b). Right hemiplegia eight

weeks postoperatively ; cranial CT with expanded CSDH on

left (c). No saireito given.

Effect of Postoperative Administration of Saireito for Bilateral Chronic Subdural Hematomas 287

Figure 4. Contralateral hematoma: Maximum size and

status comparison in saireito-treated and control groups. In

mixed or isodense hematomas > 16.0 mm, surgical treat-

ment was uniformly needed. However, only three patients

in the control group required surgery for low-density he-

matomas < 8.0 mm.

More sizeable lesions (≥16.0 mm) subjected to surgery

were mixed or isodense. In contrast, small lesions (≤8.0

mm) subjected to surgery were low-density, and all were

confined to the control group.

In the three instances of mixed or isodense presenta-

tion, the interval from initial surgical side to contralat-

eral surgery was less than two weeks. However, when

hematoma density was low (three cases), the time for the

onset of new neurologic symptoms (four to eight weeks)

was longer (Figure 5).

4. Discussion

CSDH may be asymptomatic and may dissipate sponta-

Figure 5. Distribution of contr alateral hematoma density by

maximum size and time between surgeries. In the saireito

group, two patients required additional surgery within two

weeks of initial intervention due to symptomatic enlarge-

ment of contralateral hematomas. In contrast, three pa-

tients in the control group experienced contralateral hema-

toma enlargement, with symptoms, at four to eight weeks

postoperatively. These three lesions were of low density.

neously, or symptoms may develop with a gradually

enlarging CSDH [8]. Even with B-CSDH, symptoms are

often attributable to a unilateral hematoma [9]. Although

surgery is standard therapy for symptomatic CSDH, it is

difficult to judge by images at a single point in time

whether or not a silent contralateral hematoma will be-

come symptomatic or regress spontaneously.

CSDH typically evolves from subdural hygroma or

acute subdural hematoma (ASDH). Repeated micro-

hemorrhages occur in the subdural space [8], provoked

by local inflammation [10]. Any CSDH that enlarges

with rebleeding, thus exceeding the capacity for absorp-

tion, may become symptomatic.

High or isodense CSDH on CT equates with propor-

tionately higher red blood cell, hemoglobin, and protein

concentrations, compared with those of low-density le-

sions [11]. Also, the time required for an acute hema-

toma to become chronic is often shorter than if subdural

effusion or hygroma is involved [12,13]. In this study,

mixed or isodense hematomas requiring contralateral

surgery were 16.0 mm or larger at presentation, and the

time prior to symptoms was relatively short (1 - 2

weeks). Understandably, they were unresponsive to

saireito, just as with ASDH. In contrast, low-density

hematomas where contralateral surgery was needed were

typically 8.0 mm or smaller at presentation and re-

mained asymptomatic longer (4 - 8 weeks). While con-

tralateral lesions of some saireito-treated patients were

small and showed a low density, none were symptomatic,

and all eventually resolved without further surgery.

Conversion of a contralateral subdural effusion or hy-

groma to CSDH is therefore seemingly prevented by

saireito, suggesting that small, low-density CSDH is an

indication for treatment.

In instances where asymptomatic hematomas re-

gressed, the time required for resolution was also shorter

with saireito, compared with that in controls. Use of

goreisan1, [2] and steroid [3-7] in tandem for CSDH

may reduce capsular inflammation, in addition to aug-

menting (via goreisan) resorption of clot. Saireito is ac-

tually a combination of goreisan and shosaikoto, another

herbal anti-inflammatory; and it is believed that en-

dogenous steroid production is boosted by saireito

through enhanced expression of subthalamic corticotro-

pin releasing factor [6,7]. Mechanistically, it is likely

that saireito controls local inflammation to reduce con-

tinued CSDH bleeding and that absorption of accumu-

lated blood is facilitated through its fluidic effects [14].

5. Conclusions

The therapeutic efficacy of sairei-to with CSDH reflects

its hydragogue properties and its capacity to raise en-

dogenous steroid levels. After unilateral surgery for

Effect of Postoperative Administration of Saireito for Bilateral Chronic Subdural Hematomas

288

B-CSDH, saireito administration may prevent sympto-

matic deterioration of a contralateral low-density CSDH,

preempting subsequent surgery.

REFERENCES

[1] M. Miyagami and Y. Kagawa, “Effectiveness of Kampo

Medicine Gorei-San for Chronic Subdural Hematoma,”

No Shinkei Geka, Vol. 37, No. 8, 2009, pp. 765-770.

(Japanese, with English abstract)

[2] M. Muramatsu, T. Yoshikawa and K. Hanabusa, “Effec-

tiveness of Kampo Medicine Gorei-San-Ryo for Chronic

Subdural Hematoma in very Elderly Patients,” No Shinkei

Geka, Vol. 33, No. 10, 2005, pp. 965-969. (Japanese,

with English abstract)

[3] T. F. Sun, R. Boet and W. S. Poon, “Non-surgical Pri-

mary Treatment of Chronic Subdural Haematoma: Pre-

liminary Results of Using Dexamethasone,” British

Journal of Neurosurgery, Vol. 19, No. 4, 2005, pp. 327-

333. doi:10.1080/02688690500305332

[4] J. L. Voelker, “Nonoperative Treatment of Chronic Sub-

dural Hematoma,” Neurosurgery Clinics of North Amer-

ica, Vol. 11, No. 3, 2000, pp. 507-513.

[5] S. Zarkou, M. I. Aguilar, N. P. Patel, K. E. Wellik, D. M.

Wingerchuk and B. M. Demaerschalk, “The Role of Cor-

ticosteroids in the Management of Chronic Subdural He-

matomas: A Critically Appraised Topic,” Neurologist,

Vol. 15, No. 5, 2009, pp. 299-302.

doi:10.1097/NRL.0b013e3181b65558

[6] I. Iwai, T. Suda, F. Tozawa, Y. Nakano, Y. Sato, N. Oh-

mori, T. Sumitomo, M. Yamada and H. Demura, “Stimu-

latory Effect of Saireito on Proopiomelanocortin Gene

Expression in the Rat Anterior Pituitary Gland,” Neuro-

science Letters, Vol. 157, No. 1, 1993, pp. 37-40.

doi:10.1016/0304-3940(93)90637-Z

[7] Y. Nakano, T. Suda, F. Tozawa, I. Dobashi, Y. Sato, N.

Ohmori, T. Sumitomo and H. Demura, “Saireito (A Chi-

nese Herbal Drug)-Stimulated Secretion and Synthesis of

Pituitary ACTH Are Mediated by Hypothalamic Cortico-

tropin-Releasing Factor,” Neuroscience Letters, Vol. 160,

No. 1, 1993, pp. 93-95.

doi:10.1016/0304-3940(93)90921-7

[8] K. S. Lee, “Natural History of Chronic Subdural Haema-

toma,” Brain Injury, Vol. 18, No. 4, 2004, pp. 351-358.

doi:10.1080/02699050310001645801

[9] T. H. Tsai, A. S. Lieu, S. L. Hwang, T. Y. Huang and Y.

F. Hwang, “A Comparative Study of the Patients with

Bilateral or Unilateral Chronic Subdural Hematoma: Pre-

cipitating Factors and Postoperative Outcomes,” Journal

of Trauma. Vol. 68, No. 3, 2010, pp. 571-575.

doi:10.1097/TA.0b013e3181a5f31c

[10] H. J. Hong, Y. J. Kim, H. J. Yi, Y. Ko, S. J. Oh and J. M.

Kim, “Role of Angiogenic Growth Factors and Inflam-

matory Cytokine on Recurrence of Chronic Subdural

Hematoma,” Surgical Neurology, Vol. 71, No. 2, 2009,

pp. 161-166. doi:10.1016/j.surneu.2008.01.023

[11] H. Fujisawa, S. Nomura, E. Tsuchida and H. Ito, “Serum

Protein Exudation in Chronic Subdural Haematomas: A

Mechanism for Haematoma Enlargement?” Acta Neuro-

chirungica Supplements (Wien), Vol. 140, No. 2, 1998,

pp. 161-166. doi:10.1007/s007010050077

[12] C. K. Park, K. H. Choi, M. C. Kim, J. K. Kang and C. R.

Choi, “Spontaneous Evolution of Posttraumatic Subdural

Hygroma into Chronic Subdural Haematoma,” Acta

Neurochirungica Supplements (Wien), Vol. 127, No. 1-2,

1994, pp. 41-47. doi:10.1007/BF01808545

[13] S. H. Park, S. H. Lee, J. Park, J. H. Hwang, S. K. Hwang

and I. S. Hamm, “Chronic Subdural Hematoma Preceded

by Traumatic Subdural Hygroma,” Journal of Clinical

Neuroscience, Vol. 15, No. 8, 2008, pp. 868-872.

doi:10.1016/j.jocn.2007.08.003

[14] T. Ono, N. Liu, T. Makino, F. Nogaki, E. Muso, G.

Honda and T. Kita, “Suppressive Mechanisms of Sairei-to

on Mesangial Matrix Expansion in Rat Mesangioprolif-

erative Glomerulonephritis,” Nephron Experimental Ne-

phrology, Vol. 100, No. 3, 2005, pp. e132-e142.

doi:10.1159/000085059