實證暨流病中心評核結果：
日期： 2011/02/28
 ■ Satisfactory: (■ 第一次通過)
 Very good
 Search Strategy只限於systematic, 過於
簡略會擔心有遺漏最新研究證據的可能
(2007年之後的研究不包括在內）
 若有修訂或進一步更新，歡迎將新檔案
email到本中心。
1
神經科
實證期刊閱讀報告
EBM-style Journal Reading
報告人：張凱茗
Email: 146903@cch.org.tw
指導臨床教師：莊介森
日期：2011-01-10
地點：神經科醫研室
Clinical Scenario （臨床情境）
 53y/o male admitted due to frequent
posture change related dizziness.
 Loss of consciousness and left
hemiparesis on 2010/12/8
 Brain CT: Subarachnoid hemorrhage over
right frontotemopral regions
 Transfer to NCU on the same day
3
Background knowledge
 Oral nimodipine reduce poor outcome
(death or dependency) related to
aneurysmal SAH (Class I, Level of
Evidence A).
 The number needed to treat (NNT) with
nimodipine to prevent one poor outcome
was 13 (95% CI 8-30).
 60 mg orally Q4H started within 4 days *
3 weeks
Pract Neurol 2009; 9: 195–209
Stroke. 2009;40:994-1025
4
Background knowlege
 Nimodipine is effective in the prevention of
ischaemic complications after haemorrhage
 Possible mechanisms include
(1)Neuroprotection via reduction of calciumdependent excitotoxicity,
(2)Diminished platelet aggregation,
(3)Dilation of small arteries not visible on
angiograms,
(4)Inhibition of ischemia triggered by red blood
cell products.
5
Clinical Uncertainty → PICO 問題
Can Nimodipine reduce poor
outcome in tramatic subarachnoid
hemorrahge patient?
6
臨床個案的PICO
Patient / Problem
Adult patient with tramatic
subarachnoid hemorrahge
Intervention
Nimodipine
Comparison
Placebo
Outcome
Death/severe disability
Type of Question: therapy
7
Search Terms & Strategy:
（搜尋關鍵字與策略）
 資料庫： PubMed
 搜尋日期：2011/01/05
 搜尋關鍵字與策略：

systematic[sb] AND (traumatic subarachnoid
hemorrhage and nimodipine)
8
Best available evidence:
（挑選可獲得之最佳研究證據）
 Citation/s:
Effect of nimodipine on outcome in
patients with traumatic subarachnoid
haemorrhage: a systematic review
Lancet Neurol 2006; 5: 1029–32
 Lead author's name :
Mervyn D I Vergouwen
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Evidence about this problem
 1990- HIT 1no reduction in poor
outcome
 1990- HIT-2 trend of beneficial effect
 1996 HIT-3 RR reduction 55%
 Cochrane review 2003pooled odds ratio
for death was 0.59 (95%CI 0.37-0.94); 0.67 for
OR of poor outcome
 未發表 HIT-4  significant increase in
poor outcome in nimodipine-treated
patients.
10
The Study: （研究效度）- 1
 Search strategy and selection criteria of
studies
 Systematically searched the electronic
PubMed and EMBASE databases up to
2006
 Randomised controlled studies
investigating the effect of the calcium
antagonist nimodipine in patients with head
injury were included, irrespective of dose, route
of administration, and duration of treatment.
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The Study: （研究效度）- 2
 Glasgow outcome scale was measured 6
months after head injury
 Outcome definition:
Poor=death, vegetative state, or severe disability
Favourable=moderate disability and good recovery
Secondary outcome=mortality
 Jadad scale as predictor for quality of trails:
All trials scoring 1 or 2 points for randomisation were
included
12
The Study: （研究效度）- 3
 Statistical analysis:
 Intention-to-treat principle and processed in
Review Manager 4.2
 Odds ratios for poor outcome were
calculated with a random-effects model
because of possible heterogeneity
 Level of Evidence: Ia
13
The Study: （研究效度）- 3
本篇文獻的PICO (T)
Patient /
Problem
Patient with traumatic subarachnoid
hemorrhage
Intervention Nimodipine
Comparison Placebo
Outcome
Death, vegetative state, or severe
disability
Time
All trails until 2006
14
The Evidence: （研究重要結果）- 1
 Four trials was found in EMBASE and
Pubmed
 Investigators of HIT 1 and 2 and study by
Pillai were contacted for additional data; HIT3,
only published data were available
 Principal investigator of HIT 4 granted us
permission to analyse and publish the results
of HIT 4, which were described in a table of
the pooled outcome scores of all patients of
all four HITs.
15
HIT-1
HIT-2
852
Total 病 352
人數
(257有CT)
驗證CT
方式
4 observes
check CT
(Review
committee)
tSAH病 71
人數(實 35/36
驗/對照)
HIT-3
HIT-4
Palli
123
592 (15?)
97
(577 for ITT)
原研究主持
人＋review
committee
Committee
cannot
confirm 26 CT,
still evaluate
for ITT
268
119/149
121
60/61
Review
committee
577
290/287
Review
committee
37
18/19
＝1074
525確定有SAH
Dose
1-2mg/h * 7
days
1-2mg/h * 7
days
2mg/h*7-10
day +360mg
PO ~21 days
?
Loss of
f/u
0
0
2
15？
2
16
The Evidence: （研究重要結果）- 2
Quality of methodology
The median score was 3 (range 2–5). As all trials scored
1 or 2 points for randomisation, no studies were excluded.
Randomization 1= 內文有描述，但不夠適當
Randomization 2= 內文有描述，且夠適當
17
The Evidence: （研究重要結果）- 3
Odds ratio 0·88 [95% CI 0·51–1·54]
18
The Evidence: （研究重要結果）- 4
Odds ratio 0·95 [95% CI 0·71–1·26]
19
Comment & Discussion: -1
 The occurrence of poor outcome and
mortality rates did not differ between
patients treated with nimodipine and
those treated with placebo.
 Contrast with those of the Cochrane
review published in 2003.
20
Comment & Discussion: -2
 本文與2003 Cochrane相異之處有三
 Restudied the original data of HIT 1 so
that mortality rates of HIT 1 could be
included
 Obtain additional data from the HIT 4
study and included these data in the
analysis of all patients with tSAH. (In 2003
Cochrane review HIT 4 data were only included in
the overall analysis…)
 Included the results of Palli study.
21
Comment & Discussion: -3
 為何traumatic和aneurysm對nimodipine 反應
不同？
 Nimodipine is probably only effective for
secondary cerebral ischaemia
In aSAH, secondary cerebral ischaemia can occur in the
weeks after hemorrhage (decrease flow 75/65% blood
flow in acute and subacute stage), but much less in
tSAH(85/increase)
 Nimodipine exerts a fibrinolytic effect
(decrease secondary vasospasm in aSAH, but increase
bleeding in tSAH)
22
Comment & Discussion: -4
 此Paper 之缺點：
 The Jadad score of HIT 4 was based on a
limited number of data. With the available
data of HIT 4, the Jadad score was 2.
 The largest study in this systematic review
probably had the lowest quality score.
23
回到臨床個案情境
Clinical bottom line 臨床決策底線
 In patient with traumatic subarachnoid
haemorrhage, nimodipine did not reduce the
poor outcome and mortality.
證據等級1a, 建議等級A
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References:




Langham J, Goldfrad C, Teasdale G, Shaw D, Rowan K.
Calcium channel blockers for acute traumatic brain
injury. Cochrane Database Syst Rev 2003; 4: CD000565.
Fukuda T, Hasue M, Ito H. Does traumatic subarachnoid
hemorrhage caused by diff use brain injury cause
delayed ischemic brain damage? Comparison with
subarachnoid hemorrhage caused by ruptured
intracranial aneurysms. Neurosurgery 1998; 43: 1040–
49.
Gabriel J E Rinkel, Catharine J M Klijn. Prevention and
treatment of medical and neurological complications in
patients with aneurysmal subarachnoid haemorrhage
Pract Neurol 2009; 9: 195–209
Joshua B. Bederson, Guidelines for the Management of
Aneurysmal Subarachnoid Hemorrhage, Stroke
2009;40;994-1025
25
結 論 （標題 Title）
Nimodipine didn’t improve the
outcome and mortality in
patient with traumatic
subarachnoid hemorrhage.
Kill or Update By（下次更新日期）:
Jan. 05, 2012
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