Download RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
Annexure-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
(To be submitted in duplicate)
1. Name of the candidate:
Address:
Dr. SHRUTHI.V. SALIAN
D/O MR.VAMAN SALIAN
No.559, 2nd MAIN,1ST CROSS
SADANANDNAGAR, NGEF(EAST),
BANGALORE -560038.
2. Name of the Institution:
M.S.RAMAIAH MEDICAL COLLEGE.
3. Course of Study and Subject:
M.S OBSTETRICS AND GYNECOLOGY
4. Date of Admission to the Course:
3rd MAY 2010
5. Title of the Topic:
A RANDOMISED CONTROL STUDY OF EFFCTIVENESS OF METHYLDOPA VERSUS
NIFEDIPINE IN MANAGEMENT OF PREECLAMPSIA.
6. Brief Resume of the Intended Work:
6.1. Need for the Study:
Hypertension is a common medical complication of pregnancy (10%) associated with
significant maternal, fetal and neonatal morbidity and mortality. The exact etiological factor
of preeclampsia is not known, though endothelial damage is found to be the pathological
change seen in this condition.
The need for an effective treatment to control preeclampsia and its effects both on the
mother and fetus is necessary. Delivery is the most appropriate therapy for the mother but
may not be so for the fetus which is remote from term. Antihypertensive treatment will
reduce the maternal complications and may help in prolonging pregnancy to enable fetal
maturity. These drugs should be safe for the fetus also.
Various antihypertensives are being used in the treatment of preeclampsia to control BP but
there is no set protocol for therapy. Hence there is a need for standardizing antihypertensive
therapy in preeclampsia. In this study, the drugs compared are methyldopa, a centrally acting
drug with nifedipine, a calcium channel blocker, which are used in the treatment of
preeclampsia.
6.2 Review of literature:
Preeclampsia is seen clinically as a syndrome ranging from indolent mild clinical hypertension
and proteinuria to a severe form of rapid fulminant endothelial disease with multiorgan
failure and death of mother and fetus.¹ Preeclampsia is associated with the release of
antiangiogenic factors, plasma volume is contracted and widespread effects on vascular
endothelium lead to the maternal syndrome of preeclampsia.²
There is little evidence to suggest that any therapy alters the underlying pathophysiology of
preeclampsia. Therapeutic efforts may be palliative, slow progression of the disorder and
permit continuation of pregnancy but they have not been shown to reverse the underlying
disorder.
When treatment is required, the ideal drug that reduces pressures to a safe level should act
quickly, reduce pressure in a controlled manner, not lower cardiac output, reverse
uteroplacental vascular constriction and result in no adverse maternal or fetal effects.³
Methyldopa is one of the most commonly used antihypertensive agent in preeclamptic
patients and it has a direct effect on sympathetic nervous system and it also decreases the
peripheral vascular spasm.⁴
Calcium antagonists generally constitute second line agents, usually administered late in
pregnancy. A prospective cohort study suggest that calcium channel blockers (especially
nifedipine) donot represent a major teratogenic risk. Nifedipine has shown to result in a lower
incidence of overshoot hypotension and to have a more rapid onset of action.⁵
6.3 Aim of the Study:
To compare and analyse the effectiveness of methyldopa versus nifedipine in treatment of
preeclampsia.
6.4 Objectives of the study:
To study the effects of methyldopa and nifedipine in terms of :
i.
the change in mean arterial pressure(MAP).
ii.
maternal and perinatal outcomes.
iii.
maximum dose required and
iv.
adverse effects of the drugs.
7. Material and Methods:
7.1 Source of data:
Preeclamptic women attending the antenatal clinic and admitted in M.S Ramaiah Hospitals
(Teaching and Memorial).
7.2 Method of collection of data:
Randomised control study of methyldopa versus nifedipine in preeclampsia.
Sample size: 168 patients will be recruited and assigned with 84 in each group.
The sample size is estimated using nMaster software based on the study as cited in ¹. Here we
considered α error as 5%, β error as 10% (90% power) and minimum expected difference
between the groups as 10 mmHg (clinically significant difference).
Procedure:
Patients randomly assigned to the two groups would receive T. methyldopa 250-2000mg in
2-4 divided doses per day or T. nifedipine 10-60mg per day as required so as to attain diastolic
BP between 90-100 mmHg. Brachial artery BP will be checked before and after administration
of the drug with the patient in lateral recumbent position using calibrated mercury
sphygmomanometer and appropriate cuff size.If the BP is not controlled with these drugs
they would then be administered other antihypertensives and these patients would be
excluded from the study.
Inclusion criterion:
i.
ii.
iii.
iv.
v.
Preeclampsia ≥140/90 mmHg on more than two occasions with or without persistent
proteinuria 30 mg/dl (≥1± dipstick) in urine samples.
All preeclamptics irrespective of parity.
Age group 18-40 years.
Singleton and multiple gestation.
Gestational age 24-40 weeks.
Exclusion criterion:
i.
ii.
iii.
History of diabetes mellitus, chronic hypertension, chronic renal disease.
Proved APLA syndrome and thrombophilias.
Proved connective tissue disorders.
7.3 Statistical analysis:
Descriptive statistics of MAP in both the groups would be analysed and expressed in mean
and SD/ median(quartile range).Independent t test/ Mann Whitney U test would be used to
compare the reduction in MAP between the two groups.
Repeated ANOVA would be used to compare the reduction in MAP at different timings in
both the groups. Chi square test would be used to compare the course of management
between the two groups.
7.4 Does the study require any investigation or intervention to be conducted on patient or
other humans or animals?
Yes, routine/ relevant blood and urine investigations.
7.5 Has ethical clearance been obtained from your institution?
Yes.
8. Duration of study:
Two years of randomized control study.
9. List of references:
1. Scardo JA, Vermillion ST, Newman RB, Chauhan SP and Hogg BB, 1999, “A randomized,
double blind, haemodynamic evaluation of nifedipine and labetalol in preeclamptic
hypertensive emergencies”, Am J Obstet Gynecol, 181,4, 858-861.
2.Khalil A, Jauniaux E and Harrington K, 2009, “Antihypertensive therapy and central
haemodynamics in women with hypertensive disorders in pregnancy”, Obstet Gynecol, 113,
646-654.
3.National High Blood pressure Education Program Working Group on High Blood Pressure in
Pregnancy, 2000, “Report of the National High Blood pressure Education Program Working
Group on High Blood Pressure in Pregnancy”, Am J Obstet Gynecol,183, S1-S22.
4.Gunenc O, Cicek N, Gorkemli H, Celik C, Acar A and Akyurek, 2002, “The effect of methyldopa
treatment on uterine, umbilical and fetal middle cerebral artery blood flows in preeclamptic
patients”, Arch Gynecol Obstet, 266, 141-144.
5.Rosenthal T and Oparil S, 2002, “The effect of antihypertensive drugs on the fetus”, Journal
of Human Hypertension, 16, 293-298.
10. Signature of the candidate:
11. Remarks of the guide:
Preeclampsia is a dreaded condition associated with maternal and fetal complications.
Delivery is the definitive treatment, but antihypertensives do have a role in prolonging
pregnancy so that fetal maturity is achieved. Various antihypertensives are used in the
management. This comparative study will help us know which of the two drugs is efficacious
and least toxic.
12. Name and designations of guides:
a. Guide:
Dr. Nandini.G
Associate Professor, Department of OB&G.
Signature:
b. Co-Guide:
Signature:
13. Name and Designations of Head of Department:
Dr. Uma Devi K
Professor and H.O.D
Signature:
14. Remarks of the Chairman and Principal:
Signature: