Phototherapy a review
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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.

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Phototherapy a review

PHOTOTHERAPY-A REVIEW

WILLIAM OH, MD

BROWN MEDICAL SCHOOL

FDA CONFERENCE, JUNE 11,2003


Outline

OUTLINE

  • HISTORICAL NOTES

  • MECHANISM-HOW IT WORKS

  • EFFICACY DATA

  • SIDE EFFECTS

  • LONG TERM OUTCOME


Historical note

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

HISTORICAL NOTES-CONT’D

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


Mechanism

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 SPECTRUM OF BILIRUBIN


Absorption of light by bilirubin in vivo

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

PHOTOCHEMICAL REACTIONS

LIGHTBILIRUBIN ABSORBS PHOTON

‘ EXCITED’ BILIRUBIN ↓

↓ ↓ ↓

PHOTO-OXIDATION ↓

STRUCTURAL ISOMEZARATION (LUMIRUBIN) ↓

CONFIGURATIONAL

ISOMERIZATION

( 4E,15Z,4Z,15E AND 4E,15E

PHOTOISOMERES)


Photo oxidation

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

CONFIGURATIONAL ISOMERIZATION (4Z,15E)


Structural isomerization lumirubin

STRUCTURAL ISOMERIZATION (LUMIRUBIN)


Physical property of bilirubin and its product

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 & 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

PHOTO-CHEMICAL REACTION & ELIMINATION OF BILIRUBIN


Factors affecting efficacy of photothery

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

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

COMPARISON OF DIFFERENT LIGHTS

% REDUCTION IN SERUM BILIRUBIN

P<0.05

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


Conclusion tan

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

HALOGEN LAMPS

  • MORE COMPACT THAN FLORESCENT LAMP

  • CAN NOT BE BROUGHT TOO CLOSE TO INFANT ( RISK OF BURN)


Fiberoptic system wallaby

FIBEROPTIC SYSTEM (WALLABY)

  • ADVANTAGES

    • NO EYE PATCH NECESSARY

    • MORE PORTABLE

    • CONVENIENT FOR MOTHER AND HOME THERAPY

  • DISADVANTAGE

    • LOW SPECTRAL POWER


Fiberoptic vs conventional

FIBEROPTIC VS. CONVENTIONAL

DECLINE IN SERUM BILIRUBIN

(M/L/HR)

N.S. P<0.05

FIBER

CONV.


Light emitting diodes

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

LIGHT SPECTRUM OF LED


Rct for led vs halogen lamp

RCT FOR LED VS HALOGEN LAMP

SERUM BILIRUBIN (µM/L)

ENTRY

DURING

(N=34)(N=35)

SEDMAN, DS ET AL J PEDTRIC136:771,2000


Phototherapy a review

DIFFERENT MODES

OF

PHOTOTHERAPY


Continuous vs intermittent photo therapy

CONTINUOUS VS INTERMITTENT PHOTO-THERAPY

PERCENT REDUCTION IN SERUM BILIRUBIN

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

N=69 N=47

CALDERA,R ET AL ANN PEDIAT 1984


Continuous vs intermittent photo therapy 2

CONTINUOUS VS INTERMITTENT PHOTO-THERAPY-2

RATE OF DECLINE IN SERUM BILIRUBIN

M/L/HR

N=10

N=13 N=10 N=12

-N.S.-

RUBALTELI

LAU


Single vs double phototherapy

SINGLE VS. DOUBLE PHOTOTHERAPY

DECLINE IN SERUM BILIRUBIN

(M/L/HR)

P<0.01 0<0.05 P<0.01

SINGLE

DOUBLE

SHARMA


Home phototherapy aap guidelines statement

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, 5TH ED.


Acute side effects of phototherapy

ACUTE SIDE EFFECTS OF PHOTOTHERAPY

  •  INSENSIBLE WATER LOSS

  • LOOSE OR WATERY STOOL

  •  RESPIRATORY RATE

  •  BODY TEMPERATURE


Potential complication

POTENTIAL COMPLICATION

  • TOXIC EFFECT ON THE OPTIC NERVE

  • DEMONSTRATED IN ANIMAL STUDY

  • EYE PATCH USED FOR PRECAUTION


Low birth weight infants

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

PHOTOTHERAPY AND PATENT DUCTUS ARTERIOSUS

%

N=36N=38

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


Multivariate analysis for psb phototherapy

MULTIVARIATE ANALYSIS FOR PSB &PHOTOTHERAPY

YEO KL ET ALPEDIATRICS 102:1426,1998


Limitation of yeo s data

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

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

ONE-YEAR OLD OUTCOME (FULL TERM)

SCORE

N.S. N.S.

PHOTO

CONTROL

N=105 99

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


Six year old outcome pre full term infants

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

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

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


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