RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
SYNOPSIS
OF
DISSERTATION
“ELECTROLYTE CHANGES IN NEONATES RECEIVING
PHOTOTHERAPY FOR NEONATAL
HYPERBILIRUBINEMIA WITH SPECIAL REFERENCE TO
HYPOCALCEMIA IN A TERTIARY CARE HOSPITAL”
Submitted by
Dr. UDAY SHANKAR SURABHI
M.B.B.S.
POST GRADUATE STUDENT IN
PAEDIATRICS (M.D)
Under the guidance of
Dr. RAMALINGE GOWDA NISARGA
MBBS, DCh, MD
PROFESSOR AND HEAD,
DEPARTMENT OF PAEDIATRICS
DEPARTMENT OF PAEDIATRICS
ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,
B.G.NAGARA-571448
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1
NAME OF THE CANDIDATE
AND ADDRESS
(in block letters)
Dr. UDAY SHANKAR SURABHI
P.G. IN PAEDIATRICS,
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES, B.G. NAGARA,
MANDYA DISTRICT -571448
2.
NAME OF THE INSTITUTION
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES, B.G.NAGARA.
3.
COURSE OF STUDY AND SUBJECT
M.D. IN PAEDIATRICS
4.
DATE OF ADMISSION TO COURSE
31ST MAY 2012
5.
TITLE OF THE TOPIC
6.
BRIEF RESUME OF INTENDED WORK
7
“ELECTROLYTE CHANGES IN
NEONATES RECEIVING
PHOTOTHERAPY FOR NEONATAL
HYPERBILIRUBINEMIA WITH SPECIAL
REFERENCE TO HYPOCALCEMIA IN A
TERTIARY CARE HOSPITAL”
APPENDIX-I
6.1 NEED FOR THE STUDY
APPENDIX-IA
6.2 REVIEW OF LITERATURE
APPENDIX-IB
6.3 OBJECTIVES OF THE STUDY
APPENDIX-IC
MATERIALS AND METHODS
APPENDIX-II
7.1 SOURCE OF DATA
APPENDIX-IIA
7.2 METHOD OF COLLECTION OF
DATA : (INCLUDING SAMPLING
PROCEDURE IF ANY)
APPENDIX-IIB
7.3 DOES THE STUDY REQUIRE ANY
INVESTIGATION OR INTERVENTIONS
TO BE CONDUCTED ON PATIENTS OR
OTHER ANIMALS, IF SO PLEASE
DESCRIBE BRIEFLY.
YES
APPENDIX-IIC
7.4 HAS ETHICAL CLEARENCE BEEN
OBTAINED FROM YOUR INSTITUTION
IN CASE OF 7.3
YES
APPENDIX-IID
8.
LIST OF REFERENCES
APPENDIX – III
9.
SIGNATURE OF THE CANDIDATE
1
10.
REMARKS OF THE GUIDE
11
NAME AND DESIGNATION
(in Block Letters)
The topic chosen by the candidate is relevant
to know the electrolyte abnormalities while
treating the neonate with phototherapy in our
institution.
11.1 GUIDE
Dr. RAMALINGE GOWDA NISARGA
MBBS, DCh, MD
PROFESSOR AND HEAD,
DEPARTMENT OF PAEDIATRICS,
AIMS, B.G. NAGARA-571448
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY)
-
11.4 SIGNATURE
-
11.5 HEAD OF DEPARTMENT
Dr. RAMALINGE GOWDA NISARGA
MBBS, DCh, MD
PROFESSOR AND HEAD,
DEPARTMENT OF PAEDIATRICS,
AIMS, B.G. NAGARA-571448
11.6 SIGNATURE
12
12.1 REMARKS OF THE CHAIRMAN
AND PRINCIPAL
The facilities required for the investigation will
be made available by the college
Dr. M.G SHIVARAMU M.B.B.S., MD
PRINCIPAL,
AIMS, B.G. NAGARA.
12.2 SIGNATURE
2
APPENDIX-I
6.BRIEF RESUME OF THE INTENDED WORK:
APPENDIX –I A
6.1 NEED FOR THE STUDY:
Jaundice in newborn is quite common affecting nearly 70% of term and 80% of preterm
neonates during first week of life. Hyperbilirubinemia is one of the most common sign
encountered in newborns. In most cases its a benign problem. Nevertheless untreated, severe
unconjugated hyperbilirubinemia is potentially neurotoxic and conjugated hyperbilirubinemia
is a harbinger of underlying serious illness.1
Neonatal hyperbilirubinemia is a reflection of liver’s immature excretory pathway for
bilirubin at a time of non physiological or pathological hyperbilirubinemia is known to occur in
5-10% of healthy term newborns and is the most common reason for readmission of neonates
in first week of life in current era of postnatal discharge from hospital.2
Premature babies have much higher incidence of neonatal jaundice requiring
therapeutic intervention than term neonates. Hyperbilirubinemia was found to be the most
common morbidity 65% among 137 extremely low birth weight neonates born over a period of
7 years in AIIMS.3
Newborns appear jaundiced when the serum bilirubin level is more than 7 mg/dl. The
term physiologic jaundice generally is applied to newborns whose total serum bilirubin (TSB)
level falls within the normal range, but because of the significant differences in TSB levels in
different populations, it is difficult to define what is normal or abnormal, physiologic or nonphysiologic.
The yellow colour usually results from the accumulation of unconjugated, non polar,
lipid soluble bilirubin pigment in the skin. It may also be due impart to deposition of
3
conjugated, polar, water soluble bilirubin pigment. Conjugated Hyperbilirubinemia indicates
potentially serious hepatic disorders or systemic illnesses. Unconjugated (indirect)
hyperbilirubinemia occurs as a result of excessive bilirubin formation and because the neonatal
liver cannot clear bilirubin rapidly enough from the blood.
Elevated levels of unconjugated bilirubin can lead to bilirubin encephalopathy and
subsequently kernicterus, with devastating, permanent neurodevelopment handicaps.
Although most newborns with jaundice are otherwise healthy, every baby who is
jaundiced necessitates attention at the earliest to look for features of pathological jaundice
because; unconjugated bilirubin is potentially toxic to the central nervous system. And hence
appropriate management of Neonatal Hyperbilirubinemia is of paramount importance.
Hyperbilirubinemia4 can be treated in three ways:
a. Exchange transfusion removes bilirubin mechanically;
b. Phototherapy converts bilirubin to products that can bypass the liver's conjugating
system and be excreted in the bile or in the urine without further metabolism; and
c. Pharmacologic agents that interfere with heme degradation and bilirubin production,
accelerate the normal metabolic pathways for bilirubin clearance, or inhibit the
enterohepatic circulation of bilirubin.
Significant neonatal jaundice is defined as TSB level beyond which baby required
intervention (Phototherapy and/or Exchange Transfusion) for neonatal jaundice.
Premature babies have much higher incidence of neonatal jaundice requiring
therapeutic intervention than term neonates.
4
As any treatment has its side effects, phototherapy also have its adverse effects 5 like
hyperthermia, feed intolerance, vomiting, decreased urine output, bronze baby syndrome,
dehydration, electrolyte changes.
Unlike other side effects a very few studies are currently available that depicts the
adverse effects of phototherapy on serum electrolytes. Neonates requiring phototherapy are at a
higher risk of developing hypocalcemia. Therefore, it is suggested that newborn requiring
phototherapy administration of calcium may be considered in them. Hence emphasis is given in
special reference to hypocalcemia. Very few studies are available regarding the changes in the
other electrolytes (sodium, potassium, chloride).
One of the side effect of phototherapy is diarrhoea. As diarrhoea can lead to electrolyte
changes, I thereby want to study the electrolyte changes due to phototherapy whether any
significant changes in sodium, potassium occurs in addition to hypocalcemia.
APPENDIX –I B
6.2 REVIEW OF LITERATURE
Phototherapy has emerged as the most widely used form of treatment, and is the current
treatment of choice to reduce severity of neonatal unconjugated hyperbilirubinemia, regardless
of its etiology.
Phototherapy is simple and easily available therapeutic intervention for effective
management of hyperbilirubinemia. With timely intervention in both term and preterm, severe
complications of hyperbilirubinemia are prevented.
Hospital based studies in the United States have shown that 5 to 40 infants per 1000
term and late-preterm infants receive phototherapy before discharge from the nursery and that
an equal number are readmitted for phototherapy after discharge.2,6
5
National Neonatal Perinatal Database Network reported an incidence of Neonatal
Hyperbilirubinemia requiring phototherapy 5.7% in Inborn and 32.99% in Out born admitted
babies during the period 2002-2003.7
Data collected at district and sub-district hospitals during same period showed an
incidence of 1.5% and 12.7% for inborn and out born respectively.
Hakanson Do et al (1981) reported that when young rats were exposed to white
fluorescent light, the serum concentration of calcium did decrease. He showed that this calcium
drop was accompanied by a decrease in serum melatonin concentration. This effect can be
prevented by shielding the occiput, by inhibiting corticosterone synthesis, and by
administration of exogenous melatonin. They also reported that propranolol could reduce
serum calcium by inhibiting synthesis of melatonin. Light-induced hypocalcemia may result
from increased calcium uptake by bone when the blocking effect of melatonin decreases after
pineal inhibition by transcranial illumination.8
Zecca et al (1983) reported that administration of 25-hydroxy vitamin D3 was not able
to lower the incidence of the phototherapy-induced hypocalcemia in preterm infants. He
concluded that vitamin D was unlikely to play an important role in the pathogenesis of
phototherapy-induced hypocalcemia.9
Curtis et al (1989) studied diarrhoea in jaundiced neonates treated with phototherapy.
Study showed that absorption of sodium, chloride and potassium was significantly impaired in
the patients receiving phototherapy.10
Sethi et al (1990) has studied the effects of phototherapy in 20 term & 20 preterm
hyperblirubinemic neonates. They observed that 75% of term & 90% of preterm neonates
developed hypocalcaemia after phototherapy.11
6
In a study done by Jain et al (1998), the prevalence of phototherapy induced
hypocalcemia was 55% in preterm infants and 30% in full-term neonates. Among the affected
preterm babies with hypocalcemia 63.6% had jitteriness and 27.3% had irritability. In the
hypocalcemic full-term neonates 50% had jitteriness and 16.7% were irritable. To prevent
hypocalcemia, they recommended administration of supplemental calcium in the neonates
treated by phototherapy.12
Karamifar et al(2002) study was performed on 153 jaundiced neonates (62 premature,
91 full-term) that were managed with phototherapy. These neonates were completely normal
on physical examination. Serum calcium was checked on arrival, 48 hours after starting
phototherapy. The first samples were considered as controls. Twenty- two neonates (14.4%)
developed hypocalcemia. There were significant differences between the prevalence of
hypocalcemia in premature (22.6%) and full-term neonates (8.7%) (p=0.018). This study
showed that neonates under phototherapy are at high risk of hypocalcemia. This risk is greater
in premature neonates.13
Hunter et al (2004) hypothesized that phototherapy inhibits pineal secretion of
melatonin which blocks the effect of cortisol on bone calcium. Cortisol exerts a direct
hypocalcemic effect and increases bone uptake of calcium as well.14
Medhat et al (2006) of Cairo University observed that 75% of term & 90% of preterm
developed hypocalcaemia after phototherapy.15
Rajesh KY etal(2011) has studied the effects of phototherapy in 20 term & 20 preterm
hyperblirubinemic neonates. After 48 hours of phototherapy , a significant fall in calcium level
in 66.6% of term & 80% of preterm neonates was observed. It is suggested that calcium level
be assessed in neonates treated with phototherapy for more then 48 hours and managed
accordingly.16
7
Tan KL et al study was performed on 3 groups of healthy full term infants with
hyperbilirubinemia exposed to continous phototherapy. This study showed raised potassium
levels at 72 hrs in 2 of 3 phototherapy groups, but reverted to normal with cessation of
phototherapy.17
Dee Beresford and Glenys Conolly in the book Neonatal Intensive Care Nursing states
that babies under phototherapy can have sodium imbalances due to insufficient fluid
replacements.18
APPENDIX –IC
6.3 AIMS AND OBJECTIVES OF STUDY
To evaluate the electrolyte changes in neonates receiving phototherapy for neonatal
jaundice with a special reference to hypocalcemia at Adichunchanagiri Institute of Medical
Sciences, a tertiary care hospital at Bellur, B.G.Nagara, Nagamangala Taluk, Karnataka.
8
APPENDIX-II
7.0 MATERIALS AND METHODS
APPENDIX-II A
7.1 SOURCE OF DATA
Study will be a prospective hospital based comparative study conducted on neonates
admitted in the Neonatal Intensive Care Unit receiving phototherapy who are delivered at
Adichunchanagiri Institute of Medical Sciences and research hospital, a tertiary care hospital at
Bellur, B.G.Nagara, Nagamangala Taluk, Karnataka.
Our study will be conducted over a period of 18 months (December 2012 - May 2014).
Hyperbilirubinemia is defined as the value of bilirubin according to AAP Guidelines above
which Phototherapy or exchange transfusion or both are required.19
Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation. TSB = total
serum bilirubin. (Management of hyperbilirubinemia in the newborn infant 35 or more weeks
of gestation. Pediatrics 2004; 114:297-316.)
Risk Factors = Isoimmune hemolytic disease, G6PD deficiency, asphyxia, significant lethargy,
temperature instability, sepsis, acidosis, or albumin <3mg/dl.
9
PHOTOTHERAPY IN PRETERM NEONATES AS PER WEIGHT AND SERUM
BILIRUBIN LEVEL
PHOTOTHERAPY
(SERUM BILIRUBIN LEVEL)
WEIGHT
< 1000 gm
Started with in 24 hrs
1000-1500 gm
7-9 mg/dl
1500-2000 gm
10-12 mg/dl
2000-2500 gm
13-15 mg/dl
APPENDIX-II B
7.2 METHOD OF COLLECTION OF DATA
INCLUSION CRITERIA
1. Neonates receiving phototherapy for unconjugated hyperbilirubenemia without any comorbidities like birth asphyxia, septicaemia, renal failure.
EXCLUSION CRITERIA
1. Neonates with Conjugated Hyperbilirubinemia.
2. Neonates with co-morbidities like
 Birth asphyxia,
 Septicaemia
 Renal failure.
Blood from the neonates included in the study is collected and sent for Total bilirubin,
Direct bilirubin, Electrolytes (Sodium, Potassium, Chloride, Calcium).
 Total and direct bilirubin is measured by Diazo method.
 Electrolytes (Sodium, Potassium, Chloride) measured by Easylyte plus Na/K/Cl
analyzer.
 Calcium is measured by Arsenazo III method.
10
DATA ANALYSIS
Electrolytes were checked at 0 hours and at 48 hours of phototherapy or at
discontinuation of phototherapy whichever is earlier. The first sample were considered as
controls. Comparative study was made between these groups to determine the changes in
electrolytes.
All data of various groups will be tabulated and statistically analysed using suitable
statistical tests (Student's t test).
Consent :
Details of study will be explained to mother and informed consent will be taken before
recruitment.
APPENDIX-II C
7.3 Does the study require any investigation or intervention to be conducted on the
patients or animals, if so please describe briefly
YES
The following investigations are required:
 Total bilirubin.
 Direct Bilirubin.
 Electrolytes (Sodium, Potassium, Chloride, Calcium).
11
APPENDIX-IID
PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL
SECTION A
Title of the study
“ELECTROLYTE CHANGES IN NEONATES
RECEIVING PHOTOTHERAPY FOR
NEONATAL HYPERBILIRUBINEMIA WITH
SPECIAL REFERENCE TO HYPOCALCEMIA
IN A TERTIARY CARE HOSPITAL”
b
Principle investigator
(Name and Designation)
Dr. UDAY SHANKAR SURABHI
P.G. IN PAEDIATRICS,
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES, B.G. NAGARA,
MANDYA DISTRICT -571448
c
Co-investigator
(Name and Designation)
d
Name of the Collaborating
Department/Institutions
NIL
e
Whether permission has been obtained from
the heads of the collaborating departments &
Institution
NA
a
Dr. RAMALINGE GOWDA NISARGA
MBBS, DCh, MD
PROFESSOR AND HEAD,
DEPARTMENT OF PAEDIATRICS,
AIMS, B.G. NAGARA-571448
Section – B
Summary of the Project
Section – C
Objectives of the study
Section – D
Methodology
APPENDIX – II
APPENDIX – IC
APPENDIX - IIB
S.A.H. & R.C., B.G.NAGARA
A Where the proposed study will be undertaken
B Duration of the Project
18 MONTHS
C Nature of the subjects:
Does the study involve adult patients?
YES
Does the study involve Children?
YES [NEONATES]
Does the study involve normal volunteers?
NO
Does the study involve Psychiatric patients?
NO
Does the study involve pregnant women?
NO
12
D If the study involves health volunteers
I. Will they be institute students?
NO
II. Will they be institute employees?
NO
III. Will they be Paid?
NA
IV. If they are to be paid, how much per
NA
session?
E Is the study a part of multi central trial?
NO
F If yes, who is the coordinator?
(Name and Designation)
NA
Has the trail been approved by the ethics
Committee of the other centers?
NA
If the study involves the use of drugs please
indicate whether.
NA
I. The drug is marketed in India for the
indication in which it will be used in the study.
NA
II. The drug is marketed in India but not for
the indication in which it will be used in the
study
NA
III. The drug is only used for experimental use
in humans.
NA
IV. Clearance of the drugs controller of India
has been obtained for:
NA
 Use of the drug in healthy volunteers
 Use of the drug in-patients for a new
indication.
NA
 Phase one and two clinical trials
 Experimental use in-patients and healthy
volunteers.
13
G How do you propose to obtain the drug to be
used in the study?
-
Gift from a drug company
-
Hospital supplies
-
Patients will be asked to purchase
-
Other sources (Explain)
NA
H Funding (If any) for the project please state
-
None
-
Amount
-
Source
-
To whom payable
NONE
Does any agency have a vested interest in the
I
NO
out come of the Project?
Will data relating to subjects /controls be stored
J
YES
in a computer?
Will the data analysis be done by
K
-
The researcher
YES
-
The funding agent
NO
L Will technical / nursing help be required form
NO
the staff of hospital.
If yes, will it interfere with their duties?
NO
Will you recruit other staff for the duration of
NO
the study?
If Yes give details of
I.
Designation
II.
Qualification
III.
Number
IV.
Duration of Employment
NA
14
M Will informed consent be taken? If yes
YES
Will it be written informed consent:
YES
Will it be oral consent?
NO
Will it be taken from the subject themselves?
NO
Will it be from the legal guardian?
YES
If no, give reason:
NA
N Describe design, Methodology and techniques
APPENDIX II
Ethical clearance has been accorded.
Chairman,
P.G Training Cum-Research Institute,
A.I.M.S., B.G.Nagara.
Date :
PS : NA – Not Applicable
15
APPENDIX-III
8. LIST OF REFERENCES
1. M J Maisels, Jaundice in Neonatology, Pathophysiology and Management of Newborn,
4th edition, Avery G.B; Pg:765-820
2. M J Maisels, Length of Stay, Jaundice & Hospital Readmission, Pediatrics, 1998,
Pg:995-998.
3. Narayana S, Aggarwal, Upadhyay A, Deorari AK, Sindh M, Paul VK. Survival &
Morbidity in Extremely Low Birth Weight (ELBW) Infants. Indian Pediatrics, 2003;
40(2) : 130 – 5.
4. Meharban S: Jaundice. In: Care of newborns. 7th Edn.; Sagar Publication, New Delhi.
2010; pp. 254-273.
5. Tao Xiong, Yi Qu, Stephanie C, Dezhi Mu. The side effects of phototherapy for
neonatal jaundice. Eur J Pediatr (2011) 170:1247-1255.
6. Eggert LD, Wiedmeier SE, Wilson J, Christensen RD. The effect of instituting a
prehospital discharge newborn bilirubin screening program in an 18-hospital health
system. Pediatrics 2006;117(5):e855-e862.
7. Report 2002 – 03, National Neonatal Perinatal Database Network New Delhi : National
Neonatology Forum of India, 2006.
8. Hakanson DO, Bergstrom WH. Phototherapy induced hypocalcemia in newborn rats,
prevention by melatonin. Science 1981; 214(4522):807-9.
9. Zecca E, Romagnoli C, Tortorol G. Ineffectiveness of vitamin 25 (OH) D3 in the
prevention of hypocalcemia induced by phototherapy. Pediatr Med Chir.1983; 5(5):
317-319.
10. Curtis M D, Guandalini S, Fasano A, Ciccimarra F. Diarrhoea in jaundiced neonates
treated with phototherapy: role of intestinal secretion. Arch Dis Child 1989;64:11611164.
16
11. Sethi H, Saili A, Dutta AK. Phototherapy induced hypocalcemia. Indian Pediatr
993;30:1403-1406.
12. Jain BK, Singh H, Singh D, Toor NS. Phototherapy induced hypocalcemia. Indian
Pediatr 1998; 35(6):566-7.
13. Karamifar H, Pishva N, Amirhakimi GH. Prevalence of Phototherapy Induced
Hypocalcemia. Iran J Med Sci 2002; 27(4):166-168.
14. Hunter KM: Hypocalcemia. In: Manual of Neonatal care. JP Cloherty, EC Eichenwald,
AR Stark(Eds.);5th Edn.; Lippincott Williams & Wilkins, Philadelphia. 2004;pp.579588.
15. Medhat FB; Assessment of phototherapy induced hypocalcemia. Thesis submitted for
M.Sc.Pediatrics in Cairo University. Classification no. 8461;2006.
16. Rajesh KY, Sethi RS, Anuj SS, Lalit K, Chaurasia OS. The Evaluation of Effect of
Phototherapy on Serum Calcium Level.People’s J of Scientific Research, July 2012:
Vol. 5(2).
17. Tan KL, Jacob E. Effect of phototherapy on neonatal fluid and electrolyte status
(PMID: 7304158). Acta Paediatrica Academiae Scientiarum Hungaricae 1981, 22(3):
187-194.
18. Dee Beresford and Glenys conolly. Fluid and electrolyte balance. Neonatal Intensive
Nursing Care 2nd edn, pg 258.
19. Cloherty JP, Eichenwald EC, Hansen AR, Stark AR. Manual of Neonatal Care 7th ed.
pg 313-322.
17