The field of newborn phototherapy (PT) has clearly arrived at a strategic
period of transition from the use of traditional light sources, such as
fluorescent, halogen and halogen/fiberoptic, towards the use of presently
fast developing, versatile solid state light emitting diode (LED)
technology. The time also appears to be ripe for the replacement of
ineffective, defective, and worn-out devices that deliver inadequate
therapy, as has been demonstrated through recent surveys in India,
Nigeria, and Brazil [1-3]. Because of a rapidly expanding global market
for PT devices, the medical device industry, particularly in India,
appears to be actively engaged in the production of newer and,
undoubtedly, more effective and affordable LED-based devices.
In order to assist physicians, hospitals, and clinic
administrators with the selection of the most appropriate device for their
clinical needs, it is important that uniform and comprehensive device
characterizations and criteria be established and made available. Thus, it
is becoming increasingly important that devices be evaluated for their
physical and spectrophotometric characteristics as well as their clinical
efficacy to affect the photochemical alteration of bilirubin (BR) in the
newborn skin and circulation. The study reported by Subramanian, et al.
[4] in this issue of Indian Pediatrics significantly adds to the
efforts that have already been made towards this goal [5-7], while it also
demonstrates the diversity of traditional and new technologies.
The primary parameters that determine the efficacy of a
PT device are: the spectral quality of the light (optimal within the blue
to green range of 400-520 nm) that is delivered, the irradiance (light
intensity), and the treatable body surface area (BSA) of a patient (the
light foot print). In addition to these device characteristics, patient
and caregiver-related parameters also contribute significantly to the
efficacy of treatment. These include, the initial plasma BR level and BR
production rate of an infant and treatment initiation, duration of PT, and
irradiance level chosen by the caregiver. Basic physical and
spectrophotometric data are usually provided by device manufacturers.
Frequently, some time after devices have been made commercially available,
clinical studies may be performed by clinical researchers with a variety
of more or less appropriate methods and measurement techniques that make
meaningful comparisons difficult. For instance, measurements of irradiance
using an inappropriate light meter can be a serious source of error [8].
Obviously, the most appropriate evaluation of device
efficacy is through measurements of the decline of plasma BR levels or PT
duration through clinical studies with jaundiced newborns under carefully
defined conditions. However, besides the fact that it is morally
indefensible to treat newborns with potentially inferior devices, when
proven devices are available, it is also a strategic and practical problem
to evaluate a new device or series of devices, on a sufficient number of
jaundiced newborns over a reasonable time period to achieve statistical
significance.
Thus, efforts are being made to comprehensively
evaluate PT devices in the laboratory as a surrogate for in vivo
clinical studies. Besides measuring the (spectro-) physical
characteristics of devices, typical methods include estimations of BR
photodegradation through use of various concentrations of BR with or
without human serum albumin in varying solvent systems, which are exposed
to PT light with a carefully selected level of irradiance. The %BR
remaining is then determined using various methods, ranging from direct
spectrophotometry, diazo method, to HPLC with spectrophotometric or mass
spectrometry detection.
Specifically, Subramanian, et al. exposed very
low concentrations (1 ug/mL or 0.1 mg/dL) of BR, dissolved in methanol to
the maximum (rather than the mean) irradiance of PT devices and measured
the %BR left through measurements of lumirubin, a reaction product which
represents one of the three recognized BR photoalteration mechanisms. The
use of the latter strategy or endpoint may explain the observed leveling
off for the observed %BR degraded. The authors also raised an interesting
and important testing topic, stating that the devices were tested with
"regulated" power. Obviously, it is appropriate to test devices with
regulated voltage. However, it may also be valuable to test devices under
conditions of voltage fluctuations and outages, which often occur under
actual field and hospital conditions, especially in India and elsewhere.
Information about electrical ruggedness could be of critical importance in
the selection of the appropriate device for a particular clinical setting.
However, it needs to be kept in mind that the validity
and value of bench-testing towards estimating in vivo device
efficacy has its limitations, because it employs static (test tube)
methodology to model the efficacy of a complex dynamic system.
Furthermore, the method also ignores the aforementioned effects that
patient and caregiver parameters contribute towards PT efficacy.
Obviously, more effort needs to be made to refine the methodology used to
date, particularly those aspects that relate to determining the relative
BR photodegradation rate as a functional efficacy estimate. Interestingly,
after half a century of PT research, many aspects, such as the optimum PT
wavelength (range), the minimal effective, optimum, and maximum safe
irradiance levels for both term and preterm infants are still being
debated. Clearly these issues are very relevant to the design of safe and
effective PT devices.
Hopefully, further research in this interesting field
of endeavor will be carried out with the assistance and leadership of a
new generation of young and enlightened researchers.
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