Is nitroglycerin (glyceryl trinitrate) contraindicated in hemorrhagic stroke?

Nitroglycerin in Hemorrhagic Stroke

Nitroglycerin (glyceryl trinitrate) should be avoided in patients with hemorrhagic stroke as it may worsen outcomes and is considered contraindicated in this population. 1

Evidence and Rationale

Hemorrhagic Stroke Considerations

• The RIGHT-2 trial demonstrated that prehospital treatment with transdermal glyceryl trinitrate (nitroglycerin) worsened outcomes in patients with intracerebral hemorrhage 1:

  • Larger hematoma size and growth
  • Increased mass effect and midline shift on neuroimaging
  • Worse global clinical outcomes (dependency, disability, cognition, quality of life, and mood)
  • Higher in-hospital mortality

• The MR ASAP trial was prematurely terminated due to safety concerns in patients with intracerebral hemorrhage, with a signal of potential early harm in this subgroup 2

• In acute intracerebral hemorrhage, rapid blood pressure reduction is recommended, but nitroglycerin is not the agent of choice 3:

  • Labetalol is the preferred medication
  • Nicardipine and sodium nitroprusside are useful alternatives

Blood Pressure Management in Hemorrhagic Stroke

• For patients with intracerebral hemorrhage, acute BP-lowering treatment to systolic BP <140 mmHg is recommended to reduce intracranial hematoma volume 3

• The European Society of Cardiology position document specifically recommends labetalol as the drug of choice for blood pressure management in hemorrhagic stroke, with nicardipine and sodium nitroprusside as alternatives 3

• Prehospital intervention for blood pressure is not recommended unless the patient is hypotensive (systolic blood pressure <90 mm Hg) 3

Appropriate Uses of Nitroglycerin

Nitroglycerin is indicated for:

1. Acute coronary syndromes 3, 4:

   • Reduces cardiac preload and afterload
   • Dilates coronary arteries and increases collateral flow
   • May inhibit platelet aggregation

2. Acute cardiogenic pulmonary edema 3:

   • Optimizes preload and decreases afterload
   • Nitroprusside is preferred but nitroglycerin is a good alternative

Contraindications and Precautions for Nitroglycerin

• Recent use of phosphodiesterase-5 inhibitors 4
• Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline 4
• Severe bradycardia or tachycardia 4
• Right ventricular infarction 4

Clinical Decision Algorithm

1. For suspected stroke:

   • Determine stroke type (ischemic vs. hemorrhagic) before administering vasodilators
   • Avoid nitroglycerin if hemorrhagic stroke is confirmed or suspected

2. For blood pressure management in hemorrhagic stroke:

   • First-line: Labetalol (0.25–0.5 mg/kg IV bolus; 2–4 mg/min continuous infusion) 3
   • Alternatives: Nicardipine or sodium nitroprusside 3

3. For patients with both acute coronary syndrome and hemorrhagic stroke:

   • Prioritize hemorrhagic stroke management
   • Consider alternative agents for coronary symptoms that won't exacerbate bleeding risk
   • Consult cardiology and neurology for specialized management

Key Pitfalls to Avoid

1. Administering nitroglycerin before confirming stroke type
2. Using nitroglycerin for blood pressure management in hemorrhagic stroke
3. Overlooking the potential for nitroglycerin to worsen outcomes in hemorrhagic stroke patients
4. Failing to recognize that different antihypertensive agents have different safety profiles in hemorrhagic stroke

In summary, while nitroglycerin has established benefits in cardiac conditions, the evidence clearly indicates it should be avoided in hemorrhagic stroke due to potential harm and the availability of safer, more effective alternatives for blood pressure management in this population.