Why should Nitroglycerin (NTG) not be used in ischemic or hemorrhagic stroke?

Why Nitroglycerin Should Not Be Used in Ischemic or Hemorrhagic Stroke

Nitroglycerin (NTG) should be avoided in patients with ischemic or hemorrhagic stroke due to its potential to worsen outcomes through cerebral vasodilation, increased intracranial pressure, and harmful hemodynamic effects that can compromise cerebral perfusion.

Contraindications in Stroke Patients

Increased Intracranial Pressure

• NTG is explicitly contraindicated in patients with increased intracranial pressure according to FDA drug labeling 1
• Cerebral vasodilation caused by NTG can potentially worsen cerebral edema and increase intracranial pressure in stroke patients 2, 3

Worsened Outcomes in Hemorrhagic Stroke

• Prehospital treatment with transdermal glyceryl trinitrate (nitroglycerin) was associated with worse outcomes in patients with intracerebral hemorrhage 4
• NTG administration in hemorrhagic stroke was linked to larger hematoma size, increased hematoma growth, greater mass effect, and more midline shift on neuroimaging 4

Potential Harm in Ischemic Stroke

• The vasodilatory effects of NTG can cause a "steal phenomenon" where blood flow is diverted away from ischemic areas to normal brain tissue, potentially worsening the ischemic injury 2
• Hypotension induced by NTG can reduce cerebral perfusion pressure in areas already compromised by ischemia 2

Hemodynamic Concerns

Blood Pressure Reduction

• Excessive blood pressure reduction in acute stroke can be detrimental to cerebral perfusion 2
• NTG can cause a >15% reduction in blood pressure over the first 24 hours in 60% of cases, which exceeds the recommended safe reduction for ischemic stroke patients 5
• Maintaining adequate cerebral perfusion pressure is critical in the acute phase of stroke 2

Risk of Hypotension

• NTG causes venodilation and arterial dilation that can lead to significant hypotension 2
• Hypotension in the setting of acute stroke can extend the area of ischemia by reducing perfusion to the penumbra (the salvageable tissue surrounding the core infarct) 2

Specific Contraindications in Guidelines

American Heart Association Guidelines

• Guidelines specifically caution against the use of nitrates in patients with:
  • Hypotension (SBP < 90 mm Hg or 30 mm Hg below baseline) 2
  • Extreme bradycardia (< 50 bpm) or tachycardia (> 100 bpm) in the absence of heart failure 2
  • Right ventricular infarction 2

Clinical Trial Evidence

• The RIGHT-2 trial showed that prehospital treatment with GTN (nitroglycerin) worsened outcomes in patients with intracerebral hemorrhage 4
• The global analysis of five clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN in hemorrhagic stroke patients 4

Practical Considerations

Monitoring Challenges

• Inadequate blood pressure monitoring after NTG administration is common in stroke settings, with mean time to first BP measurement following initiation of antihypertensive therapy being 117 ± 43 minutes in ischemic stroke and 88 ± 89 minutes in hemorrhagic strokes 5
• This delayed monitoring can lead to undetected prolonged hypotension, which is particularly dangerous in stroke patients 5

Alternative Approaches

• For hypertension management in acute stroke, guidelines recommend more controlled approaches using medications like labetalol or nicardipine that allow for more precise titration 2
• Beta-blockers are generally preferred for blood pressure control in acute stroke settings when treatment is necessary 2

Common Pitfalls

• Using NTG for blood pressure control in stroke patients without adequate monitoring can lead to excessive blood pressure reduction 5
• Failure to recognize that the cerebral autoregulation is impaired in acute stroke, making patients more vulnerable to hypotension 2
• Inappropriate use of sublingual nifedipine or transdermal nitroglycerin paste despite guideline recommendations against these agents in acute stroke 5