The effect of hematocrit on the efficacy of phototherapy for neonatal jaundice

Abstract

Background:The therapeutic phototherapy action spectrum ranges from 420 to 500 nm. However, a recent report of improved efficacy of fluorescent "turquoise" light (~490 nm) as compared with blue light (~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges. Methods: We used a current semi-empirical model of the optical properties of skin for robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin (Hb), melanin, and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra" were assembled from the calculated values. results: All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Of note, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit (Hct). conclusion: We speculate that a narrow range of light at 476 nm would be 60% more effective than blue (broadband) fluorescent lamps. Because Hb serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the Hct. A high Hct could reduce therapeutic efficiency. a n in vivo model to better define the optimal wavelength range for precision-targeted phototherapy has been elusive. Advances in understanding of skin optical properties have provided an optical model of neonatal skin in the therapeutic range (400-520 nm) that allows facile calculation of the influences of skin structure, melanin pigmentation, and cutaneous hemoglobin (Hb) on the action spectrum for phototherapy. Of these, Hb absorbs most of the visible light in the skin (1,2). As a result, competition from Hb with bilirubin for light should strongly affect the wavelength region of light that is most effective for phototherapy of neonatal jaundice. Although Hb competition has been recognized and used, in part, to predict the action spectrum for phototherapy (3,4), explicit reference to Hb competition appears to be absent from the recent literature. The reports of clinical studies showing that blue-green or green light may be more effective than blue light (5,6) generally rationalize these observations on the general notion that the longer wavelengths "penetrate deeper into the skin" without specific reference to Hb absorbance.Furthermore, significant competition for light by skin Hb also implies that the hematocrit (Hct) may in turn affect the efficacy of phototherapy. This possibility was recognized in 1974 by Lucey and Hewitt (7), who conjectured that the Hct "may be a contributing factor to the differences in response of serum bilirubin to light that one observes in different infants. " They observed in in vitro irradiation studies that changes in the Hct affect diazo-reactive bilirubin disappearance in blood. Almost a decade elapsed before a clinical st...

The effect of hematocrit on in vitro bilirubin photoalteration

“…These findings confirm our semi-empirical model, which predicted an effect of Hct on the efficacy of phototherapy based on the conclusion that Hb competes with bilirubin for light (4). As reported by others, there also appears to be significant effects of Hct (6) and Hb (10) on in vivo bilirubin photoalteration as well.…”

“…Assuming that the loss of diazo-reactive bilirubin after 60 min of exposure accurately reflected the initial rates of loss, we compared the degree of in vitro bilirubin photoalteration for different Hcts with that predicted by our semi-empirical model (4). To this end, we first calculated the relative rates of bilirubin photoalteration in the supernatant fraction of the bilirubin/RBC suspensions after exposure to light at 450 nm over the range of Hcts from 0 to 80% (Figure 1).…”

“…They concluded that this phenomenon was due to a competition between hemoglobin (Hb) and bilirubin for the absorption of light. In a recent report, Lamola et al (4) described a semi-empirical model that enables quantitative calculation of the effect of Hb in neonatal skin on the efficacy of phototherapy. For blue light, this model predicts a significant reduction-by as much as one-third-in efficacy as Hct increases from 40 to 60%.…”

Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes

“…Hemoglobin absorbs visible light in the skin, and is the major competitor with bilirubin for light absorbtion. Therefore, it was recently suggested that a high hematocrit/hemoglobin level could reduce the therapeutic efficacy of phototherapy (26). In a post hoc analysis of hemoglobin data from our patients, we found a significant negative correlation between Hb and photoisomer formation during the early phase of phototerapy (15,30, and 60 min), which disappeared at the later time points.…”

“…The inclusion of patients was completed before the publication by Lamola et al (26), proposing that the level of hemoglobin at the time of phototherapy may impact on the formation of photoisomers. Therefore, we retrospectively abstracted from the charts the hemoglobin values of our patients at the time of phototherapy.…”