I recently received a question on the optimal dosing and administration of nitroglycerin in the NICU when vasodilation is required due to limb ischemia.

As mentioned here, these cases are rare, therefore, experience is limited. Nevertheless, we can use available data and pharmacological reasoning to suggest optimal care.

While 2% nitroglycerin ointment is perceived as preferable for neonates, mainly due to better control of dosing and extent of exposure, sometimes nitroglycerin patches may be the only available option.

Properties of nitroglycerin transdermal patches:

Most nitroglycerin transdermal systems contain 25 or 50 mg of nitroglycerin dispersed over an area of 10 or 20 cm², delivering 5 or 10 mg of nitroglycerin over 24 hours, respectively. According to manufacturers, the nominal release rate of the patched in vivo is 20-25 mcg/cm²/hour.

The best described dosing recommendations for topical nitroglycerin in neonates are 0.1-2.5 mg/kg/day, according to the 2021 systematic review by Mosalli et al.

Thus, to calculate the maximal and minimal duration of exposure (T) to nitroglycerin ("patch-on"), we simply need to divide the maximum dose by the hourly delivery rate and multiply by the infant's weight (W), that is:

Maximum Delivery Rate (0.25 mg/hr):
T = (2.5 mg/kg × W kg) / 0.25 mg/hr = 10 × W hours

Minimum Delivery Rate (0.20 mg/hr):
T = (2.5 mg/kg × W kg) / 0.20 mg/hr = 12.5 × W hours

From this we can conclude that to find the maximum duration that will administer the maximum dose of 2.5 mg/kg/day, all we need to do is multiply the infant's weight by 10 ('Rule of 10'). That is, for a 1.7 kg infant, patch-on duration of 17 hours would mean up to 2.5 mg/kg (assuming maximum delivery rate of 0.25 mg/hour from the patch), while leaving 7 hours of patch-off period. One could also convert this into a more convenient dosing schedule of 16 hours on/8 hours off, which would deliver a slightly lower dose of up to 2.35 mg/kg/day. Furthermore, depending on clinical monitoring and response, two 8 hours on/4 hours off 'rounds' may be considered within any 24 hour period.

Weight "limitation"

Do note that this 'shortcut' has a limitation of weight, since infants beyond 2.4 kg would require more than 24 hours of uninterrupted nitroglycerin exposure (assuming the maximum delivery rate of 0.25 mg/hour), and when the lower delivery rate is assumed, the weight limit is even lower.

Therefore, for larger infants, the patch-off time (P_off) has to be factored into the calculation:

Generalized Equation:
Total Dose (mg/kg/day) = [Rate (mg/hr) × (24 - P_off hours)] / W kg

Maximum Delivery Rate (0.25 mg/hr):
Dose (mg/kg/day) = [0.25 × (24 - P_off)] / W

Minimum Delivery Rate (0.20 mg/hr):
Dose (mg/kg/day) = [0.20 × (24 - P_off)] / W

Thus, for a 2-kg infant, P_off would have to be 4 hours to deliver 2.5 mg/kg under the assumption of 0.25 mg/hour delivery rate. For a 3-kg infant, 2.5 mg/kg/day would not longer be feasible at all since even when setting P_off to 0 (which is not recommended, to avoid nitrate intolerance), the maximum feasible dose is 2 mg/kg/day. However, dosing within the suggested range mentioned above can still be achieved.

Summary:

Using transdermal patches in neonates is not optimal, but may sometimes be unavoidable. When that day comes, clinicians should be aware of the design and pharmacokinetics of such systems to accommodate all variables for avoiding toxicity or subtherapeutic dosing.

Disclaimer: The concepts, equations, and calculations provided here are intended strictly for educational purposes and theoretical discussion. Any clinical application or treatment decision based on this material must be made solely at the discretion and professional judgment of the treating clinician.

References:

1. New Zealand SmPC (NITRODERM® TTS), last update: 2023

2. Canadian product monograph (TRANSDERM-NITRO®), last update: 2015

3. NITRO-BID- nitroglycerin ointment, Dailymed, last update: 2026

4. Mosalli, R., Khayyat, W., Al Qarni, S., Al Matrafi, A., El Baz, M., & Paes, B. (2021). Topical nitroglycerin in newborns with ischemic injuries: A systematic review. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 29(7), 764–774. https://doi.org/10.1016/j.jsps.2021.05.008

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