What is the recommended dosing for Nitroglycerin (NTG) in Subarachnoid Hemorrhage (SCAPE)?

Nitroglycerin Dosing in Sympathetic Crashing Acute Pulmonary Edema (SCAPE)

For SCAPE, intravenous nitroglycerin should be initiated at 10 mcg/min and rapidly titrated upward by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response, with doses potentially reaching 200-400 mcg/min for optimal afterload reduction. 1

Initial Dosing and Titration Protocol

• Begin IV nitroglycerin at 10 mcg/min via continuous infusion through non-absorbing tubing 1
• Increase by 10 mcg/min every 3-5 minutes until symptom relief or blood pressure response 1
• If no response at 20 mcg/min, continue with 10 mcg/min increments, then increase to 20 mcg/min increments for more aggressive titration 1
• Once partial blood pressure response is observed, reduce dosage increments and lengthen intervals between increases 1
• For SCAPE specifically, higher doses (>100 mcg/min) are often required to achieve the necessary afterload reduction 2, 3

Maximum Dosing Considerations

• Although no official maximum dose is established in guidelines, a ceiling of 200 mcg/min is commonly used 1
• Recent research in SCAPE has demonstrated safety with doses up to 400 mcg/min 4
• Even prolonged (2-4 weeks) infusion at 300-400 mcg/min does not increase methemoglobin levels 1
• High-dose nitroglycerin boluses (median 872 μg) followed by infusions (cumulative dose ~35 mg) have been safely used in SCAPE patients 3

Blood Pressure Management

• Systolic blood pressure should generally not be titrated below 110 mmHg in previously normotensive patients 1
• In hypertensive patients, do not reduce mean arterial pressure by more than 25% below baseline 1
• Avoid nitroglycerin if initial systolic blood pressure is <90 mmHg or >30 mmHg below baseline 1
• Also avoid with marked bradycardia or tachycardia 1

Duration and Transition

• Tolerance to hemodynamic effects typically develops after 24 hours of continuous therapy 1
• For patients requiring NTG beyond 24 hours, periodic dose increases may be needed to maintain efficacy 1
• When patients are symptom-free for 12-24 hours, attempt to reduce IV NTG dose and transition to oral/topical nitrates 1
• Use non-tolerance-producing regimens (lower doses and intermittent dosing) when possible 1

Special Considerations for SCAPE

• SCAPE represents the severe end of acute heart failure with pulmonary edema in all lung zones 2
• The pathophysiology involves excessive afterload due to systemic vasoconstriction and hypertension 2
• Higher NTG doses (>100 μg/min) are specifically needed for arterial dilation and afterload reduction 2, 4
• Combined with non-invasive positive pressure ventilation, high-dose NTG has shown excellent outcomes in preventing intubation 2, 3

Contraindications and Precautions

• NTG is contraindicated after sildenafil use within 24 hours, tadalafil within 48 hours, or with hypotension 1
• Phosphodiesterase inhibitors can cause profound hypotension, MI, and even death when combined with nitrates 1
• For patients with subarachnoid hemorrhage specifically, careful monitoring is required as transient ICP increases may occur, though research suggests these are minimal when combined with dopamine 5

Administration Preparation

• Dilute NTG in dextrose 5% or sodium chloride 0.9% prior to infusion 6
• Standard concentration: 50 mg NTG in 500 mL yields 100 mcg/mL 6
• Alternative concentration: 5 mg NTG in 100 mL yields 50 mcg/mL 6
• For prolonged therapy, concentration may be increased up to 400 mcg/mL to limit fluid administration 6
• When changing concentration, flush or replace the infusion set before using the new concentration 6