What are the indications and contraindications for using injection Nitroglycerin (NTG) in a patient with acute stroke?

Nitroglycerin in Acute Stroke: Not Indicated and Potentially Harmful

Intravenous nitroglycerin has no established indication in acute stroke management and carries significant contraindications, particularly in hemorrhagic stroke where it can dangerously elevate intracranial pressure. The evidence provided addresses nitroglycerin use in acute myocardial infarction and unstable angina, not stroke—these are fundamentally different clinical scenarios with opposing hemodynamic goals.

Critical Contraindications in Stroke

Absolute Contraindications

Nitroglycerin is absolutely contraindicated in patients with increased intracranial pressure, which occurs in both hemorrhagic stroke and large ischemic strokes with edema 1. The mechanism of harm is direct:

• Cerebral vasodilation increases cerebral blood volume within the rigid cranial vault, directly elevating intracranial pressure 1
• Worsening cerebral edema occurs as vasodilation exacerbates mass effect from hemorrhage 1
• Hypotension reduces cerebral perfusion pressure, which is critical to maintain in acute stroke 1
• The combination of increased ICP and decreased MAP creates dangerous reductions in cerebral perfusion pressure that extend secondary brain injury 1

Hemodynamic Contraindications

• Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline is an absolute contraindication 1, 2
• Marked bradycardia or tachycardia, especially with relative hypotension, contraindicates nitroglycerin use 3
• Recent PDE-5 inhibitor use (within 24 hours for sildenafil/vardenafil, 48 hours for tadalafil) 1

Why Cardiac Indications Don't Apply to Stroke

The FDA-approved indications for IV nitroglycerin are perioperative hypertension, congestive heart failure in acute MI, refractory angina, and induction of intraoperative hypotension 4—none of which are stroke. The provided guidelines are from the American College of Cardiology/American Heart Association for acute myocardial infarction 3 and unstable angina 3, not stroke management.

Key Physiologic Differences

• In acute MI, reducing preload and afterload decreases myocardial oxygen demand 3
• In acute stroke, maintaining cerebral perfusion pressure is paramount—blood pressure lowering can worsen ischemic injury 1
• Preferred agents for hypertension in acute stroke are labetalol or nicardipine, which allow precise titration without increasing intracranial pressure 1

Research Evidence: Disappointing Results

Recent large-scale trials have failed to demonstrate benefit:

RIGHT-2 Trial (2019)

• Prehospital transdermal GTN (n=1,149) showed no improvement in functional outcome at 90 days (mRS 3 in both groups, adjusted OR 1.04,95% CI 0.84-1.29, p=0.69) 5
• Treatment-related deaths were numerically higher in the GTN group (36 vs 23, p=0.091) 5
• Median time to treatment was 71 minutes, representing ultra-acute intervention 5

Perfusion Study (2021)

• NTG was not associated with improved cerebral perfusion in acute ischemic stroke patients using serial PWI-MRI measurements 6
• Mean absolute CBF in hypoperfused regions at 72 hours was similar between NTG (29.9 ± 12 ml/100g/min) and untreated groups (24.1 ± 10 ml/100g/min, p=0.8) 6

Limited Positive Data

• One small experimental study (n not specified for humans) suggested potential benefit when given intra-arterially post-recanalization 7, but this is not clinically applicable or validated
• Early pilot data (n=312) suggested benefit when given within 6 hours 8, but this was not confirmed in the larger RIGHT-2 trial 5

Clinical Algorithm: When Nitroglycerin Should Never Be Used

In Hemorrhagic Stroke

Absolute contraindication—never use 1:

• Any intracranial hemorrhage (intracerebral, subarachnoid, subdural, epidural)
• Mechanism: increases ICP and worsens cerebral edema 1

In Ischemic Stroke

Not indicated—use alternative agents 1:

• No proven benefit on functional outcomes 5
• Risk of hypotension outweighs theoretical benefits 1
• If blood pressure management needed, use labetalol or nicardipine instead 1

Common Pitfalls to Avoid

• Do not extrapolate cardiac indications to stroke patients—the hemodynamic goals are fundamentally different
• Do not assume "blood pressure lowering" is universally beneficial—in stroke, excessive reduction worsens outcomes 1
• Do not use nitroglycerin for "chest pain" in a stroke patient without first ruling out increased ICP and ensuring adequate blood pressure 1, 2

Summary of Evidence Quality

The highest quality, most recent evidence (RIGHT-2 trial, 2019, n=1,149) published in Lancet shows no benefit and potential harm 5. This directly contradicts earlier, smaller studies suggesting benefit 8. The FDA label does not include stroke as an indication 4, and current stroke guidelines recommend labetalol or nicardipine for blood pressure management 1.