GTN Should Not Be Used in Patients with Intracerebral Hemorrhage
Glyceryl trinitrate (GTN) is contraindicated in patients with intracerebral hemorrhage (ICH), particularly in the ultra-acute phase, as it worsens hematoma growth and clinical outcomes.
Evidence Against GTN Use in ICH
Guideline Recommendations
The most recent and authoritative evidence demonstrates clear harm from GTN in ICH patients:
The 2022 Stroke guidelines explicitly warn against GTN use in ICH, noting that in the RIGHT-2 trial, 145 ICH patients who received GTN patches showed greater hematoma growth and poorer outcomes compared to sham controls 1.
GTN may promote vasodilation or disrupt hemostatic mechanisms in ICH, which is particularly problematic in the ultra-acute period when hematoma expansion is most likely to occur 1.
The American Heart Association and American College of Cardiology recommend against using GTN patches for managing hypertensive crisis in ICH patients due to unpredictable blood pressure responses and potential for harm 2.
Clinical Trial Evidence
The strongest research evidence comes from multiple randomized controlled trials:
RIGHT-2 trial (2019): In 145 ICH patients treated with prehospital GTN (median 74 minutes from onset), outcomes were significantly worse with an adjusted common odds ratio for poor outcome of 1.87 (95% CI, 0.98-3.57) 3. GTN was associated with larger hematoma volumes, more hematoma growth, increased mass effect and midline shift, and increased in-hospital death 3.
Long-term follow-up at 1 year confirmed persistent harm, with GTN showing a trend toward worse outcomes in ICH patients (acOR 1.65,95% CI 0.84-3.25) 4.
ENOS trial subgroup analysis (2016): While GTN appeared beneficial when given within 6 hours in a small subgroup (n=61), the overall ICH cohort (n=629) showed no benefit, and the ultra-early benefit finding requires cautious interpretation given the small sample size 5.
Meta-analysis (2022): Pooled data from 5,363 patients across seven trials confirmed that GTN reduces blood pressure but does not improve clinical outcomes in acute stroke, including ICH 6.
Recommended Alternatives for Blood Pressure Management in ICH
Preferred Agents
Use intravenous agents with rapid onset and short duration that allow precise titration 1:
- Nicardipine IV: Used in the ATACH-2 trial, allows smooth BP control with easy titration 1.
- Labetalol IV: First-line agent for hypertensive emergencies in ICH 2.
- Urapidil: Alternative agent for ICH-related hypertensive crisis 2.
Blood Pressure Targets
Target systolic BP <140 mm Hg within 6 hours of symptom onset to reduce hematoma expansion, with intensive lowering to 110-139 mm Hg considered safe in selected patients 1.
Avoid acute lowering of systolic BP to <130 mm Hg in patients with ICH of moderate severity, as this is potentially harmful 1.
Minimize BP variability during the first 24 hours, as increased variability is associated with worse outcomes 1.
Critical Timing Considerations
Why GTN Is Particularly Harmful Early
Hematoma expansion occurs primarily within the first 2-4 hours after ICH onset, and GTN's vasodilatory effects may exacerbate bleeding during this critical window 1.
The RIGHT-2 trial included patients treated at a median of 74 minutes from onset, precisely when hematoma expansion risk is highest 3.
GTN patches have unpredictable BP responses and prolonged duration of action, making them unsuitable for acute ICH management where precise control is essential 2.
Key Clinical Pitfalls to Avoid
Never use GTN patches for prehospital or ultra-acute ICH management (within 2 hours of onset), as this is when harm is most pronounced 1, 3.
Do not assume all BP-lowering agents are equivalent in ICH—the mechanism matters, and venous vasodilators like GTN may worsen outcomes through effects on hemostasis and intracranial pressure 1.
Avoid confusing evidence from ischemic stroke with ICH—while some data suggest potential benefit of ultra-early GTN in ischemic stroke, this does not apply to hemorrhagic stroke 5, 7.
Do not use GTN for its ease of administration as a justification—the convenience of transdermal delivery is outweighed by the risk of harm in ICH 2, 3.
Monitoring Requirements for Alternative Agents
When using recommended IV agents for BP control in ICH 1:
- Continuous BP monitoring in an intensive care setting
- Target smooth, sustained BP reduction to minimize variability
- Measure BP every 15 minutes during active titration
- Avoid bolus dosing that causes rapid BP fluctuations
The evidence is unequivocal: GTN should be avoided in ICH patients, particularly in the ultra-acute phase, and replaced with titratable IV agents that allow precise BP control without promoting hematoma expansion 1, 2, 3.