# Presentation: 098978

## PHOTOTHERAPY-A REVIEW

**WILLIAM OH, MD**
**BROWN MEDICAL SCHOOL**
**FDA CONFERENCE, JUNE 11,2003**

## OUTLINE

**HISTORICAL NOTES**
**MECHANISM-HOW IT WORKS**** **
**EFFICACY DATA**** **
**SIDE EFFECTS**** **
**LONG TERM OUTCOME**

## HISTORICAL NOTE

**FIRST PAPER ON PHOTOTHERAPY PUBLISHED IN 1958 (CREMER,LANCET) BASED ON THEIR IN VITRO OBSERVATION OF FALLING VALUES OF BILIRUBIN WHEN SERUM SAMPLES WERE EXPOSED TO LIGHT**

## HISTORICAL NOTES-CONT’D

**SEVERAL CLINICAL TRIALS IN THE ’60s CONFIRMED THE EFFICACY OF PHOTOTHERAPY LEADING TO ITS USE AS STANDARD CARE****TRIALS ALSO SHOWED MORE EFFICACY AMONG LOW BIRTH WEIGHT INFANTS**

## MECHANISM

**BILIRUBIN ABSORS PHOTON FROM LIGHT AT 450 nm ( IN VITRO)**** **
**PHOTOCHEMICAL REACTIONS**** **
**FORMATION OF THREE MAJOR PRODUCTS THAT ENHANCES ELIMINATION**

## ABSORPTION SPECTRUM OF BILIRUBIN

## ABSORPTION OF LIGHT BY BILIRUBIN IN VIVO

**BECAUSE BILIRUBIN IN VIVO IS BOUND TO ALBUMIN ,SPECTRUM OF MAXIMUM ABSORPTION IS SHIFTED TO THE RIGHT ( 450 TO 475 nm)**** **
**THIS EXPLAINS THE VARIABLE EFFICACY OF  LIGHT USED IN CLINICAL SETTING**

##        PHOTOCHEMICAL    REACTIONS

**LIGHT********B****ILIRUBIN ABSORBS PHOTON****                             **
** ********‘ ****EXCITED’ BILIRUBIN         ****↓**
**          ↓                  ****↓             ↓ **
**PHOTO-OXIDATION ** **                    ****         ****↓****          **
**STRUCTURAL ISOMEZARATION **  **  ** **              (LUMIRUBIN)****         ↓                    **
**                       ****CONFIGURATIONAL**
**                       ****ISOMERIZATION**
**                         ****( 4E,15Z,4Z,15E AND 4E,15E**
**                           ****PHOTOISOMERES)**

## PHOTO-OXIDATION

**SINCE CREMER’S REPORT(1958), IT HAS BEEN ASSUMED THAT PHOTO-OXIDATION IS THE MECHANISM FOR ******** BILIRUBIN EXCRETION**** **
**1984, ISOMERE FORMATION FOUND TO BE THE MAJOR MECHNISM**

## CONFIGURATIONAL ISOMERIZATION (4Z,15E)

## STRUCTURAL ISOMERIZATION (LUMIRUBIN)

## PHYSICAL PROPERTY OF BILIRUBIN AND ITS PRODUCT

**NATIVE BILIRUBIN ( 4Z,15Z) HYDROPHOBIC AND LIPOPHYLIC**** **
**BILIRUBIN ISOMERES ARE LESS LIPOPHYLIC AND HYDROPHOBIC**** **
**ENHANCE ELIMINATION VIA BILE AND URINE**

## RATE OF FORMATION & ELIMINATION OF BILIRUBIN

**RATE OF FORMATION:4Z,15E ISOMERES ****>**** LUMIRUBIN ****> ****PHOTO-OXIDATION PRODUCTS**** **
**RATE OF EXCRETION:LUMRUBIN ****>****4Z,15E ****>**** PHOTOOXIDATION PRODUCTS**** **
**  ****LUMIRUBIN APPEARS TO BE  **
**    ****THE MAJOR FORM OF ELIMIATION**
**           **

## PHOTO-CHEMICAL REACTION & ELIMINATION OF BILIRUBIN 

## FACTORS AFFECTING EFFICACY OF PHOTOTHERY 

**DEPENDENT ON**** **
**TYPE OF LIGHT USED**** **
**LIGHT INTENSITY**** **
**SURFACE AREA OF SKIN EXPOSED TO LIGHT**** **
**DISTANCE FROM LIGHT TO BABY**

## TYPES OF PHOTOTHERAPY DEVICE

**FLUORESCENT TUBES**
**DAYLIGHT(WHITE)**
**BLUE**
**GREEN**** **
**HALOGEN LAMPS**** **
** ****FIBEROPTIC SYSTEM **** **
**GALLIUM NITRIDE LIGHT EMITTING DIODES (L.E.D)**

## COMPARISON OF DIFFERENT LIGHTS

-  **% REDUCTION IN SERUM BILIRUBIN**

**TAN KL ET AL: PEDIATRICS,114:132,1989**

- P<0.05

## CONCLUSION (TAN)

**PREFERABLE TO USE EITHER DAYLIGHT( PROVIDES ENHANCED  CLINICAL OBSERVATION AND ADEQUATE EFFICACY) OR ****BLUE LIGHT**** (BETTER EFFICACY) **
**NOT**** GREEN LIGHT**** WHICH PROVIDES NEITHER**

## HALOGEN LAMPS 

**MORE COMPACT THAN FLORESCENT LAMP**** **
**CAN NOT BE BROUGHT TOO CLOSE TO INFANT ( RISK OF BURN)**

## FIBEROPTIC SYSTEM (WALLABY)

**ADVANTAGES**
**NO EYE PATCH NECESSARY**
**MORE PORTABLE**
**CONVENIENT FOR MOTHER AND HOME THERAPY**** **
**DISADVANTAGE**
**  ****LOW SPECTRAL POWER**

## FIBEROPTIC VS. CONVENTIONAL

- FIBER
- CONV.

-   **N.S.                                   P<0.05**

**DECLINE IN SERUM BILIRUBIN**
-              (******M/L/HR)**

## LIGHT EMITTING DIODES

- NARROW BAND OF LIGHT SPECTRUM( BLUE-GREEN)
- POWER EFFICIENT AND LOW HEAT EMISSION
- SOMEWHAT EYE-IRRITATING TO THE STAFF

## LIGHT SPECTRUM OF LED

## RCT FOR LED VS HALOGEN LAMP

**ENTRY**
**DURING**

**SERUM BILIRUBIN (****μ****M/L)**

**SEDMAN, DS ET AL J PEDTRIC136:771,2000**

**(N=34)**                         **(N=35)**

##      DIFFERENT MODES 

-      **DIFFERENT MODES **
**	****	****OF **
**         ****PHOTOTHERAPY**

## CONTINUOUS VS INTERMITTENT  PHOTO-THERAPY

-   **PERCENT REDUCTION IN SERUM BILIRUBIN**

- ------N.S.-------

-  **CALDERA,R ET AL ANN PEDIAT 1984**

**N=69                             N=47**

## CONTINUOUS VS INTERMITTENT  PHOTO-THERAPY-2

-  **RATE OF DECLINE IN SERUM BILIRUBIN**
**              ********M/L/HR**

- RUBALTELI
- LAU

- N=10

- N=13                  N=10   N=12

- -N.S.-

## SINGLE VS. DOUBLE PHOTOTHERAPY

-  **DECLINE IN SERUM BILIRUBIN**
-          (******M/L/HR)**

**SHARMA**

**SINGLE**
**DOUBLE**

**P<0.01                 0<0.05****	****          P<0.01**

## HOME PHOTOTHERAPY-AAP GUIDELINES STATEMENT

**AN ACCEPTABLE ALTERNATIVE**** **
**CRITERIA FOR ELIGIBLE INFANT SET BY INSTITUTION**** **
**APPROPRIATE FOLLOW UP FOR BILIRUBIN LEVELS**** **
**IF BILIRUBIN LEVEL DOES NOT DECLINE APPROPRIATELY, ADMIT FOR MORE INTENSIVE RX**
**GUIDELINE FOR PERINATAL CARE, 5****TH**** ED.**

## ACUTE SIDE EFFECTS OF PHOTOTHERAPY

****** ****INSENSIBLE WATER LOSS**** **
**LOOSE OR WATERY STOOL**** **
****** ****RESPIRATORY RATE**** **
****** ****BODY TEMPERATURE**

## POTENTIAL COMPLICATION

**TOXIC EFFECT ON THE OPTIC NERVE**** **
**DEMONSTRATED IN ANIMAL STUDY**** **
**EYE PATCH USED FOR PRECAUTION**

##  LOW BIRTH WEIGHT INFANTS

**NICHD STUDY ( ’80s) SUGGEST HIGHER MORTALITY RATE AMONG PHOTOTHERAPY GROUP **** **
**EFFECTS ON PATENT DUCTUS ARTERITUS**** **
**ASSOCIATION WITH INCREASE INCIDENCE OF BLINDNESS DUE TO RETINOPATHY OF PREMATURITY (ROP)**

## PHOTOTHERAPY AND PATENT DUCTUS ARTERIOSUS

-   %

-   N=36			N=38

-    ROSENFELD,W ET AL PEDIATRICS,78:10,1086

## MULTIVARIATE ANALYSIS FOR PSB &PHOTOTHERAPY 

|  VARIABLES | OR WITH BLINDNESS
DUE TO ROP |     P VALUE |
| --- | --- | --- |
| PEAK SERUM
BILIRUBIN
< 160 M/L |  4.48 ( CI 1.15-17.1) |       0.03 |
| DURATION OF PHOTO THERAPY | 1.17 ( CI 1.02-1.33) |       0.02 |

**YEO KL ET AL** **PEDIATRICS 102:1426,1998**

## LIMITATION OF YEO’S DATA

**RETROSPECTIVE ANALYSIS**** **
**SMALL SAMPLE SIZE (N=145)**** **
**EYE EXAMS NOT DONE UNIFORMLY**** **
**RESULTS HAVE NOT BEEN CONFIRMED **

## NEURO-DEVELOPMENTAL OUTCOME 

**NICHD TRIALS IN THE EARLY 80’S PROVIDED AN OPPORTUNITY TO EXAMINE THE NEURO-DEVELOPMENTAL  OUTCOME OF PHOTOTHERAPY ****SCHEIDT,PC ET AL PEDIATRICS,85:455,1990**

## ONE-YEAR OLD OUTCOME (FULL TERM)

-   **SCORE**
**              ****N.S.                             N.S.**

**PHOTO**
**CONTROL**

**SCHEIDT,PC ET AL PEDIATRICS,85:455,1990**

-   N=105                 99

## SIX-YEAR OLD OUTCOME (PRE &FULL TERM INFANTS)

**IQ**
**                    ****N.S.                    N.S.**

**PHOTO**
**CONTROL**

- N=328                 325

-  **SCHEIDT,PC ET AL PEDIATRICS,85:455,1990**

## LOW BIRTH WEIGHT INFANTS (<2 KG)

**NO DIFFERENCES WERE OBSERVED BETWEEN PHOTOTHERAPY AND CONTROL IN BOTH 0NE AND SIX YEARS:**** **
**NEUROLOGICAL FINDINGS(CP)**** **
**DEVELOPMENTAL PERFORMANCES**

## SUMMARY

**PHOTOTHERAPY- EFFECTIVE TREATMENT FOR NEONATAL JAUNDICE**** **
**MECHNISM-IS WELL DEFINED**** **
**ACUTE EFFECTS ARE KNOWN AND MANAGEBLE**** **
**NO SIGNIFICANT ADVERSE OUTCOMES IN TERM INFANTS**** **
**SOME LINGERING CONCERNS IN LBW INFANTS-NEED FURTHER INVESTIGATION**