PDF: Dapsone In SAH
(2022)Objective
To define the differences in the incidence of delayed cerebral ischemia between patients treated with dapsone and those treated with placebo after aneurysmal subarachnoid hemorrhage
Study Summary
• Irreversible DCI was lower in dapsone group (11.5% vs 54.5%, P=0.12)
• Brain infarction incidence was significantly lower with dapsone (19.2% vs 63.6%, P=0.001)
Intervention
Dapsone 100 mg (2.5 ml) orally daily for 15 days starting within 5 days of ictus versus placebo (aluminum hydroxide suspension 2.5 ml daily)
Inclusion Criteria
Aneurysmal SAH within 5 days from ictus, candidates for aneurysm occlusion, Fisher grade 3 or 4
Study Design
Arms: Dapsone 100 mg daily vs Placebo
Patients per Arm: Dapsone n=26, Placebo n=22
Outcome
• Favorable mRS at discharge: 76.9% vs 36.4% (P=0.005); at 3 months: 80% vs 38.9% (P=0.019)
• Brain infarction: 19.2% vs 63.6% (P=0.001)
• Mortality: 7.7% vs 27.3% (P=0.058)
Bottom Line
In this single-center, double-blind, placebo-controlled trial of 48 patients with high-risk aneurysmal SAH (Fisher grade 3-4), dapsone significantly reduced delayed cerebral ischemia (26.9% vs 63.6%, P=0.011), brain infarction (19.2% vs 63.6%, P=0.001), and improved functional outcomes at discharge and 3 months. The neuroprotective effect appears to be through glutamate receptor antagonism and anti-inflammatory mechanisms.
Major Points
- First clinical study to demonstrate neuroprotective effect of dapsone in aneurysmal SAH
- Single-center, prospective, randomized, double-blind, placebo-controlled trial in Mexico
- Included 48 patients with Fisher grade 3 or 4 SAH within 5 days of ictus
- Dapsone significantly reduced DCI incidence from 63.6% to 26.9% (P=0.011)
- Irreversible DCI reduced from 54.5% to 11.5% (P=0.12 - trend)
- Brain infarction incidence dramatically reduced: 19.2% vs 63.6% (P=0.001)
- Favorable mRS (0-2) at discharge: 76.9% vs 36.4% (P=0.005)
- Favorable mRS at 3 months: 80% vs 38.9% (P=0.019)
- No significant difference in vasospasm rates, suggesting neuroprotective rather than vasodilatory effect
- Placebo group required more intra-arterial nimodipine (45.5% vs 15.4%, P=0.029)
- No serious adverse effects; treatment was well-tolerated
- High overall DCI rate (43.8%) explained by inclusion of high-risk patients only (Fisher 3-4)
- Proposed mechanisms: glutamate receptor antagonism and anti-inflammatory effects
Study Design
- Study Type
- Prospective, randomized, double-blind, placebo-controlled trial
- Randomization
- Yes
- Blinding
- Double-blind - patients, investigators, and clinical assessment staff were blinded to treatment assignments throughout research process
- Sample Size
- 48
- Follow-up
- 3 months
- Centers
- 1
- Countries
- Mexico
Primary Outcome
Definition: Incidence of clinically defined delayed cerebral ischemia (DCI) during first 21 days post-SAH. DCI defined as development of focal neurological deficits or impaired consciousness with progression to stupor or coma, after ruling out other complications (hydrocephalus, rebleeding, surgical complications, infection, metabolic alterations) by repeat imaging and metabolic analysis.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 14/22 (63.6%) | 7/26 (26.9%) | - | P=0.011 |
Limitations & Criticisms
- Small sample size (n=48) - single-center study
- Unknown whether dapsone protects against vasospasm-induced ischemia or reduces vasospasm itself
- No protocolized transcranial Doppler ultrasonography or repeat angiography to assess vasospasm rates systematically
- No cerebral blood flow studies during vasospasm-susceptible period
- High-risk population only (Fisher 3-4) may limit generalizability
- Imbalance in need for intra-arterial nimodipine between groups (45.5% placebo vs 15.4% dapsone)
- Loss to follow-up at 3 months assessment
- Overall mortality rate of 16.7% with higher rate in placebo group (27.3% vs 7.7%, P=0.058)
- Did not achieve planned 35% reduction in overall DCI, though difference was statistically significant
- Mechanisms of action (glutamate antagonism vs anti-inflammatory) not definitively determined
- Requires multicenter validation to establish causal relationship and consistency of results
- No assessment of quality of life or cognitive outcomes beyond mRS
Citation
Neurosurg Focus 52 (3):E12, 2022