Nitro and Morphine Dosing Interval - Cardiac Ischemia

Following the third dose of nitro, the ALS PCS permits paramedics to consider morphine for management of suspected ischemic chest pain.

Nitro can reduce myocardial oxygen demand and ultimately ischemic chest pain by dilating peripheral vasculature, thus lowering cardiac preload/afterload as well as dilating coronary arteries. Morphine is administered primarily for its analgesic effect but also possesses vasodilatory properties.

Why does morphine cause hypotension?

• Morphine creates a histamine release resulting in vasodilation and ultimately decrease in systemic vascular resistance (SVR). Consequently, the vasodilation from morphine can reduce preload and cardiac output which can ultimately result in clinical decompensation.
  • Histamine release → vasodilation → ↓ SVR.
  • CNS depression → ↓ sympathetic tone.
  • Venodilation → ↓ preload and cardiac output.

Why does nitroglycerin cause hypotension?

• Nitroglycerin converts to nitric oxide which increases cGMP leading to smooth muscle relaxation. On the venous side, this reduces preload whereas on the arterial side it reduces afterload. This combined effect effectively reduces blood pressure and can result in hypotension.
  • Converts to nitric oxide (NO) → ↑ cGMP → smooth muscle relaxation.
  • Venodilation (low doses) → ↓ preload.
  • Arterial dilation (high doses) → ↓ afterload.
  • Combined effect lowers blood pressure.

As both of these medications act on smooth muscle to cause vasodilation, they carry the risk of hypotension which is compounded if they are co-administered (administered in the same 5-minute dosing interval). It is also worth noting that the risk from hypotension in the setting of cardiac ischemia is exacerbated because perfusion is reduced to an already stressed organ posing further risk to the heart and other organs. The heart perfuses during diastole further emphasizing the importance of maintenance of blood pressure during an ischemic event.

To safely manage these patients, we offer the following suggestions;

• Following the 5-minute dosing interval (after the third nitro), paramedics may choose to administer additional nitro (for non-STE chest pain) OR morphine based on clinical judgment (risks vs benefits).
• After each subsequent 5-minute dosing interval elapses, paramedics may again choose to administer nitro OR morphine (should conditions be met, and no contraindications exist).
• Paramedics may continue this regimen until a cumulative total has been reached (6 sprays of nitro for non-STE related chest pain, 3 sprays for STE related chest pain) or 10mg morphine).

Considerations:

• Generally, analgesia aims to target the treatment of cardiac chest pain through vasodilation and acting on smooth muscle (I.e. nitroglycerin).
• A key determinant when considering morphine is how the patient has responded (or not responded) to previous doses of nitro. If nitro is working, it may be best to continue nitrating. If the pain is refractory, considering switching to morphine if not contraindicated.
• AHA guidelines suggest primarily starting with nitroglycerin then transition to using alternative means of pain management (i.e. morphine) once the patient is maximally tolerated anti-ischemic medications.