operative intervention in ich: results of the international surgical trial in intracerebral...
TRANSCRIPT
Operative intervention in ICH: Results of the International Surgical Trial in Intracerebral Haemorrhage
(STICH)
A David Mendelow,
Department of Neurosurgery,
Newcastle upon Tyne, England
On behalf of the STICH Investigators
(Lancet January 29th 2005)
Question in STICH
• Does a policy of “Early Surgery” improve outcome in patients with spontaneous supratentorial intracerebral haemorrhage compared with a policy of “Initial Conservative Treatment”?
– Randomisation within 72 hours of ictus– Surgery within 24 hours of randomisation
7266-7260-66
54-6048-54
42-4836-42
30-3624-30
18-2412-18
6-12<6
%
20
15
10
5
0
Treatment
early surgery
initial conservative
Time since ictus
hrs
Median 20 hrs
STICH Randomisation by Country
ArgentinaAustralia
AustriaBelgium
ChinaCzech Republic
GermanyGreece
HungaryIndiaItaly
JapanLatvia
LithuaniaMacedonia
MalaysiaNetherlands
PolandRussia
SingaporeSouth Africa
SpainSwedenTurkey
UKUkraine
USA
No. Patients
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Primary Outcome(Prognosis Based)
Early Surgery Initial Conservative treatment
Favourable 122 (26.1%) 118 (23.8%)
Unfavourable 346 (73.9%) 378 (76.2%)
Primary Outcome:Prognosis Based
Mortality
Early Surgery Initial Conservative treatment
Alive 304 (63.7%) 316 (62.6%)
Dead 173 (36.3%) 189 (37.4%)
Mortality
Survival Functions
days
2101801501209060300
Pro
ba
bili
ty o
f su
rviv
al
1.0
.9
.8
.7
.6
Early Surgery
Initial Conservative Treatment
KaplanMeierPlot ofSurvival
Secondary OutcomeRankin (Prognosis Based)
Early Surgery Initial Conservative treatment
Favourable 152 (32.8%) 137 (28.1%)
Unfavourable 312 (67.2%) 351 (71.9%)
Secondary OutcomeRankin (Prognosis Based)
Secondary OutcomeBarthel (Prognosis Based)
Early Surgery Initial Conservative treatment
Favourable 124 (26.7%) 110 (22.6%)
Unfavourable 341 (73.3%) 377 (77.4%)
Secondary OutcomeBarthel (Prognosis Based)
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus
• Crossovers• Meta-analysis
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus
• Crossovers• Meta-analysis
Pre-specifiedsubgroupanalysis
Favours surgery Favours control
Depth
Favours surgery Favours control
GCS
Craniotomy
Lobar
Conclusions
• While there is no evidence to support a policy of “Early Surgery” compared with a policy of “Initial Conservative Treatment” in patients with spontaneous supratentorial intracerebral haemorrhage (Timing), pre-specified subgroup analysis has suggested that Superficial haematomas treated with craniotomy do better with “Early Surgery”.
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus
• Crossovers• Meta-analysis
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus DANGER
• Crossovers• Meta-analysis
Post-hoc analysis of IVH and hydrocephalus (All CT scans read per protocol – Neurosurgery Focus 2003)
Of 902 readable CT scans:
42% (377) had IVH
of whom 55% (208) had hydrocephalus.
(Paramasweram Battathiri et al.Ann Arbour 2005)
Overall favourable outcomes – No IVH - 31.4%
– IVH - 15.1%
(p<0.00001)• IVH alone - 19.5%
• IVH + hydrocephalus - 11.5%
(p=0.031)
Midline shift (cm)
> 1.0< = 1.0.00
% f
avo
ura
ble
ou
tco
me
40
30
20
10
0
no IVH
IVH only
IVH + HCP
Volume of haematoma (ml)
> 8040 - 80< = 40
%fa
vou
rab
le o
utc
om
e40
30
20
10
0
no IVH
IVH only
IVH + HCP
Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)
Total Number of patients in that group
Lobar
109 112 27 31 21 270
10
20
30
40
50
60no ivh ES
no ivh ICT
ivh ES
ivh ICT
ivh+hcp ES
ivh+hcp ICT
% f
avo
ura
ble
ou
tco
me Basal ganglionic
94 125 48 33 59 65
Both
31 32 19 11 16 19
Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)
Total Number of patients in that group
Lobar
109 112 27 31 21 270
10
20
30
40
50
60no ivh ES
no ivh ICT
ivh ES
ivh ICT
ivh+hcp ES
ivh+hcp ICT
% f
avo
ura
ble
ou
tco
me Basal ganglionic
94 125 48 33 59 65
Both
31 32 19 11 16 19
Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis
based outcome)Early surgery
Initial Conservative Treatment
Favourable outcome
53 (49%) 42 (37%) 95
Unfavourable outcome
56 70 126
109 112 221
P=0.095
Lobar haematomas with No IVH and No Hydrocephalus
(prognosis based outcome)
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus
• Crossovers (26% ICT group)• Meta-analysis
Crossovers from intention to treat (ICT = Initial Conservative Treatment)
0
50
100
150
200
250
300
350
400
450
500
Surgery ICT
Non Crossover
Crossover
(M Prasad et al.Ann Arbour 2005)
Crossovers and GCS in ICT group of 140 crossovers to surgery
• Average drop in GCS at crossover was 3 points
GCS
5 7 8
14 15 1317
12
23
1511
0
5
10
15
20
25
5 6 7 8 9 10 11 12 13 14 15
Volume in ICT group of 140 crossovers to surgery (in red)
Volume of haematoma (CT)
> 100 ml80-10060-8040-6020-40<20 ml
%
100
90
80
70
60
50
40
30
20
10
0
had surgery
no
yes
Depth from cortical surface in ICT group of 140 crossovers (in red)
Depth from cortical surface
> 2 cm1- 2 cm< = 1 cm.00
%
100
90
80
70
60
50
40
30
20
10
0
had surgery
no
yes
Factors that drove crossovers to surgery from Initial Conservative
Treatment (ICT)• Deterioration in Glasgow Coma Score (GCS)
• Larger volume
• Bigger midline shift
• Superficial
• Focal deficit
• NOT– IVH– hydrocephalus
Primary and Secondary Outcome
• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE
• Can we now use this information to help with decision making in our patients?
• Subgroups– Pre-specified: published in Lancet paper– Post-hoc: IVH and hydrocephalus
• Crossovers• Meta-analysis
Meta-analysis of 12 trials of surgery for ICH (Mortality only)
Meta-analysis of 12 trials of surgery for ICH (Death or disability)
Conclusions
• While there is no evidence to support a policy of “Early Surgery” compared with a policy of “Initial Conservative Treatment” in patients with spontaneous supratentorial intracerebral haemorrhage (Timing), pre-specified subgroup analysis has suggested that Superficial haematomas treated with craniotomy do better with “Early Surgery”.
• Meta-analysis suggests:– Superficial clots – consider craniotomy– Deep clots – consider aspiration
• New Meta-analysis to evaluate lobar vs. deep with no IVH (12 trials)
• Patients with IVH and/or hydrocephalus have much poorer outcomes and should be considered separately (new trials)
Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)
Total Number of patients in that group
Lobar
109 112 27 31 21 270
10
20
30
40
50
60no ivh ES
no ivh ICT
ivh ES
ivh ICT
ivh+hcp ES
ivh+hcp ICT
% f
avo
ura
ble
ou
tco
me Basal ganglionic
94 125 48 33 59 65
Both
31 32 19 11 16 19
Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis
based outcome)Early surgery
Initial Conservative Treatment
Favourable outcome
53 (49%) 42 (37%) 95
Unfavourable outcome
56 70 126
109 112 221
P=0.095
Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis
based outcome)Early surgery
Initial Conservative Treatment
Favourable outcome
53 (49%) 42 (37%) 95
Unfavourable outcome
56 70 126
109 112 221
P=0.095
Lobar haematomas with No IVH and No Hydrocephalus
(prognosis based outcome)
STICH II
• Supratentorial LOBAR ICH with no IVH or hydrocephalus
• Randomisation within 48 hours of ictus
• Surgery within 12 hours of randomisation
• Outcome as in STICH I
• 600 patients needed
• Funding applied for from UK MRC
How do we manage a patient with Supratentorial ICH?
• Observation clinically or with ICP/CPP monitoring and operate with deterioration
• Craniotomy if there is deterioration from GCS between 9 and 12 and if the clot is superficial
• Aspiration if the clot is deep: another large trial is needed (data from meta-analysis of aspiration methods)
Acknowledgements
• UK Stroke Association
• UK Medical Research Council (MRC)
• NIH, Northern Brainwave Appeal and NNF
• Investigators, patients and relatives from 107 centres in 27 countries
• MRC Steering Committee
• MRC Data Monitoring and Ethics Committee
• All Co-investigators and Fellows