Phototherapy as a Drug – a Pharmacological Perspective
Introduction
Early detection of neonatal jaundice and its effective management have led to the use of non-pharmacological therapies such as phototherapy (PT). PT is commonly used to treat neonatal jaundice but there is substantial variation in its application and the measured irradiance.1 To improve clinical outcomes, Angelo Lamola, Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, introduced a pharmacological perspective on the topic of PT and the use of photons as a drug when prescribing it.2 M. Jeffrey Maisels, MB, BCh, DSc, Division of Newborn Medicine, Department of Pediatrics, William Beaumont School of Medicine, Beaumont Children’s Hospital, further demands that “we should apply the same therapeutic rigor to the use of phototherapy as we do to the use of a pharmacologic agent in the newborn.” 3
A pharmacological example
Imagine a case in which you are caring for your patient Meggie. Meggie is a 35-weeks gestational age (GA) newborn weighing 2,350 g and suffers from a patent ductus arteriosus (PDA).
Due to the symptoms, you strive for a pharmacological closure. Based on clinical evidence, ibuprofen is the drug of your choice and should be administered. Now, a choice needs to be made, whether to administer the 4 ml or 8 ml vial of ibuprofen. However, this depends on the required dosage and not on the volume of the vial. Let’s modify the example so that Meggie is dealing with severe jaundice instead of a PDA, and according to the relevant nomogram, she requires treatment with PT. What kind of PT should be prescribed?
Many factors arise that need to be considered when prescribing PT. Should it be single or double PT therapies? How high should the intensity be: low, middle or high? What about using older bulb versions or new LEDs? How does the angle or distance influence the workplace set up? While it is known that the dosage of pharmacological agents is an important factor, the correct dosage of PT has not yet been routinely evaluated. 4 Should the considerations for PT dosage be different than the same considerations for pharmacological agents?
Guidelines and clinical evidence
The 2022 released American Academy of Pediatrics (AAP) guidelines give further recommendations on how the dosage of PT can be safest and most efficiently determined. “Intensive phototherapy requires a narrow spectrum LED blue light with an irradiance of at least 30 μW/cm2/nm at a wavelength approximately 475 nm. Light outside the 460 to 490 nm range provides unnecessary heat and potentially harmful wavelengths.” 5,6 In general, shorter wavelengths involve the formation of free radical and reactive oxygen species (ROS) causing oxidative damage. 7
To measure the PT dosage accurately, a radiometer is used. It calculates the irradiance in μW/cm2/nm, requiring careful attention to ensure the measurement is correct. But measuring the irradiance with a radiometer over a broader spectrum (e.g. 400-500 nm) can be misleading as the irradiance of >30 μW/cm2/nm might be reached but with light outside of the effective spectrum. Furthermore, “the general approach is to provide intensive phototherapy to as much of the infant’s surface area as possible.”4 But research has shown that 4 out of 6 PT lights tested are not able to cover the surface area of a newborn of 32 weeks and only one can cover the area of a term newborn of 40 weeks of gestational age. 8 To support Meggie and all other babies needing PT, “Healthcare providers should be aware of spectral irradiance levels and footprint differences between LED-based PT devices.
Therefore, we recommend performing spectral irradiance measurements to enable patient-specific PT, considering PT as a “drug” to be dosed cautiously and appropriately, in analogy to Lamola’s pharmacologic view of PT 3 and in accordance with national guidelines.
Your checklist for safe and effective phototherapy
To properly administer and dose PT, consider the followingfactors based on industry guidelines and clinical evidence:
- Light spectrum: Unconjugated bilirubin absorbs light most strongly in the blue region around 460-490 nm. When thinking of PT in the context of pharmacological agent dosage, the light spectrum is akin to the drug concentration.
- Irradiance: Irradiance, or intensity, is inversely proportional to the square of the distance from the source of the light source. When considering irradiance in the terms of drug administration, think of it as the dosage. The smaller the distance, the higher the irradiance, and the greater the distance, the lower the irradiance. The recommended minimal distance is 12in/30cm from baby.
- Measurement: To accurately measure the irradiance or “dosage” of PT, utilize a radiometer calibrated to the same spectrum of light (460-490 nm).
- Distribution: Illuminating as much skin surface area as possible has been shown to increase the speed of bilirubin clearance in relation to the rate at which bilirubin is produced by the infant so broad distribution is critical.
- Protection: Eye protection is needed when administering PT, but rest of the baby’s clothing or positioning aids should be minimal or transparent so as not to inhibit surface area coverage.
One baby, one light
Dräger’s BiliLux LED phototherapy light system is designed to check the boxes in delivering safe and effective PT, fulfilling the requirements of the AAP guidelines. BiliLux is one of the very few phototherapy lights available to deliver light specifically in the 460 to 490 nm spectrum (think concentration). Unlike other PT lights with only low and high settings, the BiliLux phototherapy light features five levels of irradiance so clinicians can fine tune the treatment to the individual baby, whether they are in an open or closed care space. For example, if the light must be positioned farther away from the baby, as in closed care, the caregiver can increase the irradiance level to maintain adequate intensity (think dosage).
The BiliLux Radiometer instantly measures the irradiance and helps ensure the correct positioning of the baby under the phototherapy light and the adequate irradiance that the baby receives (30 to 50 μW/cm2/nm). With regards to PT distribution, the BiliLux phototherapy light features a large surface area to cover full term and premature babies. The irradiance is evenly distributed over the entire mattress to help ensure effective phototherapy.
Conclusion
The application of phototherapy (PT) for the treatment of neonatal jaundice requires a level of precision and consistency comparable to pharmacological interventions. By adhering to industry guidelines and clinical evidence—and employing technology aligned with them—clinicians can optimize PT administration through careful consideration of factors such as light spectrum, irradiance, measurement, distribution, and protection.
References
- Maisels, M J, J F Watchko, V K Bhutani, and D K Stevenson. “An Approach to the Management of Hyperbilirubinemia in the Preterm Infant Less than 35 Weeks of Gestation.” Journal Of Perinatology 32 (June 7, 2012): 660
- Lamola, Angelo A. “A Pharmacologic View of Phototherapy.” Clinics in Perinatology 43, no. 2 (June 2016): 259–76. doi: 10.1016/j.clp.2016.01.004
- Maisels, M J, J F Watchko, V K Bhutani, and D K Stevenson. “An Approach to the Management of Hyperbilirubinemia in the Preterm Infant Less than 35 Weeks of Gestation.” Journal Of Perinatology 32 (June 7, 2012): 660
- Dam-Vervloet, Alida J., Nienke Bosschaart, Henrica L. M. van Straaten, Lieke Poot, and Christian V. Hulzebos. “Irradiance Footprint of Phototherapy Devices: A Comparative Study.” Pediatric Research, November 2, 2021. https://doi.org/10.1038/ s41390-021-01795-x.
- Lamola, Angelo A. “A Pharmacologic View of Phototherapy.” Clinics in Perinatology 43, no. 2 (June 2016): 259–76. doi:10.1016/j.clp.2016.01.004.
- Kemper, Alex R, Thomas B Newman, Jonathan L Slaughter, M Jeffrey Maisels, Jon F Watchko, Stephen M Downs, Randall W Grout, et al. “Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation” 150, no. 3 2022). https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/ Clinical-Practice-Guideline-Revision-Management-of.
- Lamola, Angelo A. “A Pharmacologic View of Phototherapy.”Clinics in Perinatology 43, no. 2 (June 2016): 259–76. doi:10.1016/j.clp.2016.01.004.
- Dam-Vervloet, Alida J., Nienke Bosschaart, Henrica L. M. van Straaten, Lieke Poot, and Christian V. Hulzebos. “Irradiance Footprint of Phototherapy Devices: A Comparative Study.” Pediatric Research, November 2, 2021. https://doi.org/10.1038/s41390-021-01795-x.
This article was originally published by Dräger Inc. in Neonatal Intensive Care, Vol. 37, No. 4 (Fall 2024), pp. 13–14, and is adapted here with permission.
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