STICH2

Early surgery versus initial conservative treatment inpatients with spontaneous supratentorial lobar intracerebralhaematomas (STICH II): a randomised trial

A David Mendelow, Barbara A Gregson, Elise N Rowan, Gordon D Murray, Anil Gholkar, Patrick M Mitchell, for the STICH II Investigators

www.thelancet.com

Published online May 29, 2013 http://dx.doi.org/10.1016/S0140-6736(13)60986-1

Background• Stroke – 3rd highest cause of death (heart disease and

cancer 1 and 2)• Spont ICH – 8-14% strokes• Mortality up to 50%• Independence 20% at 6/12• Large/ expanding Haematoma, hyperglycaemia,

seizures and BP elevation related to outcome

STICH 1• Failed to show a benefit from early surgey

(haematoma evacuation) v conservative Mx - (worse outcomes with surgery especially if large/ intraventricular haemorrhage)• Of the prespecified subgroups that were examined,

patients with an ICH within 1cm of the cortical surface showed a benefit for early surgery • Statistical testing of this subgroup was not adjusted

for the multiple subgroup comparisons

STICH II • Performed to confirm a benefit of surgery in the latter

group• 601 patients who had a spontaneous lobar ICH on

computed tomography (1 cm or less from the cortical surface of the brain)• Volume 10 to 100 mL• <48 hours of ictus• Best motor score on the GCS of 5 or 6• Best eye score of 2 or more. • Randomly assigned to early surgery or conservative

treatment.

• Primary outcome was a prognosis-based favorable or unfavorable outcome as defined by the score on the Extended Glasgow Outcome Scale at 6 months. • This was calculated by answers to 14 questions sent

by mail to patients or their relatives• Large crossover in the conservative group, with 21%

of these patients ending up having surgery, mostly because of deterioration. • The authors noting that: "these are the ones with the

worst prognosis when surgeons are compelled to operate."

Primary analysis (intention to treat) showed a small but nonsignificant increase in the number of patients having a favorable outcome at 6 months in the early surgery group. “Suggestion” of a reduction in mortality – (nonsignificant)

Outcome Early Surgery (%) Conservative Treatment (%)

Odds Ratio (95% Confidence Interval) P Value

Favorable outcome 41 38 0.86 (0.62 - 1.20) .367

Death 18 24 0.71 (0.48 - 1.06) .095

Table. STICH-II: 6-Month Results  

Conclusion..• A benefit of 4% is not really enough to change practice• Deaths were significantly lower in the surgery group at 30 and 90

days but not at 6 months — the time of the primary endpoint.• Underpowered, even with the similar patients from STICH I it

does not quite reach statistical significance• Does provide the best evidence available however still no

evience of benefit• 2 trials using minimally invasive procedures — CLEAR III (Clot

Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III) and MISTIE III (Minimally Invasive Surgery plus rt-PA for ICH Evacuation III) — are continuing

What else..?• BP lowering ineffective – moderate loweringstill

recommended in AHA guidelines (level C evidence)• rF5VIIIa reduces haematoma expansion but did not

impact outcomes• Tight glucose control – nil benefit from glucose

infusions v sliding scales. One study showed significantly worse outcomes

New Avenues or therapy:

• Apoptosis of neurons within the haematoma and surrounding issue occurs with TNF receptor subtypes implicated as a critical component. Attempts to modulate this pathophysiological process has become one of the primary foci of research...

Management• Excellent supportive care• Sensitive discussion with family• Referral to stroke unit• Anticoagulation reversal when applicable

• FFP use to reverse warfarin (contains factors II, VII, IX and X required) - can require 10u (2000ml) to reverse INR - can be a problem in patients with background of cardiac disease .Time to reversal varies in studies: 7-32 hours due to practical considerations.

• PCC (prothrombin complex concentrate) has rapid action (about 20 minutes) with minimum volume required - expensive, risk of thrombotic complications, DIC.

• Vitamin K - has an effect as early as 4 hours and can reverse the INR as early as 8 hours. Risks - anaphylaxis (rare).

• Factor VIIa also reverses the INR within minutes - risk of increased thrombotic complication. $$ expensive