Is nitroglycerin (NTG) safe to use in a patient with an intracranial (IC) bleed?

Nitroglycerin in Intracranial Hemorrhage

Nitroglycerin should be avoided in patients with intracranial hemorrhage due to its propensity to increase intracranial pressure through cerebral vasodilation and its potential to compromise cerebral perfusion pressure through systemic hypotension. 1, 2

Primary Contraindications

The FDA drug label explicitly contraindicates nitroglycerin in patients with increased intracranial pressure 2. This is directly applicable to intracranial hemorrhage, where elevated ICP is a common and life-threatening complication.

Mechanism of Harm in IC Bleed

• Cerebral vasodilation caused by NTG increases cerebral blood volume within the noncompliant cranial vault, directly elevating ICP 1, 3
• Worsening cerebral edema can occur as NTG-induced vasodilation exacerbates mass effect from the hemorrhage 1
• Hypotension from NTG reduces cerebral perfusion pressure (CPP = MAP - ICP), which is critical to maintain in acute intracranial hemorrhage 1
• The combination of increased ICP and decreased MAP creates a dangerous reduction in CPP that can extend secondary brain injury 1

Evidence from Intracranial Pressure Studies

Multiple studies demonstrate NTG's harmful effects on ICP:

• In neurosurgical patients, NTG infusion increased ICP from 14.2 mmHg to 30.8 mmHg while decreasing cerebral perfusion pressure from 90.2 torr to 38.2 torr 3
• Animal studies showed ICP increases from 7 torr to 12 torr with corresponding blood pressure reductions 4
• Dose-dependent ICP elevations occur, with larger blood pressure decreases associated with larger ICP increases 4, 5

Important Caveat from Japanese Study

One study in acute hemorrhagic stroke patients found that NTG caused significant ICP elevation only in patients with normal baseline ICP (<15 mmHg), but not in those with already elevated ICP 6. However, this finding should not change clinical practice because:

• The study was small (31 patients) and from 1992 6
• The FDA contraindication and guideline recommendations take precedence 2, 1
• The risk-benefit ratio remains unfavorable given safer alternatives exist

Guideline-Based Blood Pressure Management in IC Bleed

The American Heart Association specifically cautions against nitrates when systolic blood pressure is <90 mmHg or ≥30 mmHg below baseline 7, 1. For hypertension management in acute stroke (including hemorrhagic stroke):

• Preferred agents include labetalol or nicardipine, which allow precise titration without increasing ICP 1
• Beta-blockers are generally preferred for blood pressure control when treatment is necessary 1
• Controlled blood pressure reduction is critical—excessive reduction can worsen outcomes 1

Absolute Contraindications to NTG Relevant to IC Bleed

• Increased intracranial pressure (FDA contraindication) 2
• Hypotension (SBP <90 mmHg or ≥30 mmHg below baseline) 7, 1, 2
• Recent PDE-5 inhibitor use (within 24 hours for sildenafil/vardenafil, 48 hours for tadalafil) 7, 2
• Extreme bradycardia (<50 bpm) or tachycardia (>100 bpm without heart failure) 1

Clinical Algorithm

For any patient with confirmed or suspected intracranial hemorrhage:

1. Do not administer nitroglycerin regardless of indication 1, 2
2. If hypertension requires treatment, use labetalol or nicardipine with careful titration 1
3. If the patient is already on NTG, discontinue immediately upon diagnosis of IC bleed 1
4. Monitor ICP and CPP if invasive monitoring is in place, as these guide all hemodynamic interventions 1

The only theoretical exception would be life-threatening acute coronary syndrome with pulmonary edema in a patient with IC bleed, but even then, alternative agents (morphine, diuretics, other vasodilators) should be strongly preferred 7.