a randomized comparative study between neonatal …

A RANDOMIZED COMPARATIVE STUDY BETWEEN

NEONATAL OUTCOMES OF ECLAMPTIC MOTHERS

TREATED WITH LOW DOSE MAGNESIUM SULPHATE AND

STANDARD DOSE REGIMEN FOR MANAGEMENT OF

ECLAMPSIA IN MC GANN DISTRICT TEACHING HOSPITAL,

SHIVAMOGGA

By

Dr. Sriti Hegde

Post Graduate

Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bengaluru,

Karnataka, in partial fulfillment of the requirements for the degree of

M.D. PHARMACOLOGY

Under the guidance of

Dr. Vedavathi H M.D.

Professor and Head

Department of Pharmacology

Shivamogga Institue of Medical Sciences

Shivamogga -577201

DEPARTMENT OF PHARMACOLOGY

SHIVAMOGGA INSTITUTE OF MEDICAL SCIENCES, SHIVAMOGGA

577201

2018

Scanned by CamScanner

Acknowledgement

ACKNOWLEDGEMENT

Acknowledgement is made in an attempt to recognize the person’s contribution

towards the work. I whole heartedly thank all those people who have encouraged me

right from the conception of this work till its present form.

With humble gratitude and great respect, I would like to thank my beloved teacher

and guide, Dr.Vedavathi H M.D, Professor and Head of the Department of

Pharmacology, Shivamogga Institute of Medical Sciences, Shivamogga, for being a

source of inspiration. Her constant encouragement kept me active in the academics.

Her vast experience, simplicity, knowledge, supervision, guidance, constant

inspiration and valuable advices nurtured me in completing this study successfully. I

am deeply indebted and grateful to her.

I would like to express the deepest appreciation to my co-guide, Dr. Prashant

kumar H M.S OBG, Professor and Head, Department of Obstetrics and Gynaecology,

Shivamogga Institute of Medical Sciences, Shivamogga for encouraging me in

recruitment of the subjects, ensuring the completeness of work, rendering timely

suggestions, guiding me throughout this work with his fine clinical skills and

extensive experience.

I also thank Dr. Sreenivas P Revankar Associate professor and Dr. Nagaraja

Prasad S Associate professor Department of Pharmacology for healthy discussions

regarding my academics.

My cordial and humble thanks to Dr. Dharani Devangi R, Assistant Professor,

Department of Pharmacology, Shivamogga Institute of Medical Sciences,

Shivamogga, for her support, guidance and invaluable help at several times during

this work.

Acknowledgement

I also sincerely thank Dr.Shruthi SL and Dr. Anusha SJ, Tutors Department of

Pharmacology Shivamogga Institute of Medical Sciences, Shivamogga for their

constant support, advice and help which helped me to keep up my confidence in

completion of my work.

My sincere thanks to Dr. Anirudh, Department of Community Medicine,

Shivamogga Institute of Medical Sciences, Shivamogga, for her invaluable help and

effort in making me understand the statistical part of the thesis.

I extend my thanks to my senior post graduates Dr. Jean Lourdes Murray and

Dr. Harini Manjunath for always being there and lending a helping hand in

completion of my dissertation.

I also thank my fellow postgraduates Dr. Eshanu Shastry and Dr. Abhishek C P and

for helping me at peak times and making my dissertation a successful work.

I wish to thank the interns and staff of Department of Obstetrics and Gynaecology,

Shivamogga Institute of Medical Sciences, Shivamogga for their active involvement

in the collection of the data needed for my study.

I wish to thank the interns and staff of Department of Obstetrics and Gynaecology,

Shivamogga Institute of Medical Sciences, Shivamogga for their active involvement

in the collection of the data needed for my study.

I thank DR. Lepakshi B G M.S OBG, Director, for giving me an opportunity to

undertake the present study.

I also thank Shankar G C laboratory technician, Rajesh clerk, Ranganath, Rajeshwari,

Madhusudan Raghavendra and Vinodamma non-teaching staff of the department of

Pharmacology, Shivamogga Institute of Medical Sciences, Shivamogga for their help

and co-operation rendered during my entire study period.

Acknowledgement

I am also thankful to my husband Vinayak Hegde for always believing

me and supporting me in my academics. My heartfelt thanks to my parents

Mahabaleshwar Hegde and Veena Hegde for encouraging me in my studies,

without whom it would be impossible in completion of my post graduation.

I am thankful to all my patients for participating in my study without them this

dissertation study would not have been possible and I wish them a long life and good

health.

Date: 25-11-2017 Signature of the Candidate

Place: Shivamogga Name: DR. SRITI HEGDE

ABBREVATIONS

ARM Artificial rupture of membrane

AST Asparatate

BMI Body mass index

CAT Computerized axial tomography

CNS Central nervous system

CVP Central venous pressure

DTR Deep tenodon reflexes

DBP Diastolic blood pressure

DIC Disseminated intravascular coagulation

ECG Electrocardiography

EEG Electroencephalogram

EGTA Ethylene glycol

GFR Glomerular filteration rate

HELLP Hemolysis and elevate liver enzymes and low platelet count

HR Heart rate

IL Interleukins

IM Intramuscular

IUFD Intrauterine foetal death

IUGR Intrauterine growth retardation

IV Intravenous

LBW Low birth weight

LFT Liver function test

MgSO4 Magnesium sulphate

MRI Magnetic resonance imaging

NICU Neonatal intensive care unit

NMDA N-methyl-d-asparatate

NO Nitrous oxide

O2 Oxygen

OBG Obstetrics and Gynaecology

PGI2 Prostacyclin

RCOG Royal college of Gyanaecologists

RFT Renal function test

ROS Reactive oxygen species

SBP Systolic blood pressure

SIMS Shivamogga Institute of Medical Science

TNF Tumor necrosis factor

TXA2 Thromboxane

VLBW Very low birth weight

WHO World health organization

LIST OF TABLES USED

SL. NO.

TABLES

PAGE

NO.

1. Risk factors and etiopathological factors for eclampsia 16

2. Pathophysiology and oragan dysfunctions in eclampsia 20

3. The principles of management of eclampsia 22

4. Intramuscular regimen for management of eclampsia 24

5. Maternal complications of eclampsia 28

6. Regimens of magnesium sulphate for the management of

eclampsia

37

7. Randomized control trial of magnesium sulphate with

another anticonvulsants to prevent recurrent eclamptic

convulsions

41

8. Selective vs universal magnesium sulphate prophylaxis 43

9. Representation of age distribution of eclamptic mothers

in both groups

61

10. Representation of distribution of parity among eclamptic

mothers in both groups

63

11. Representation of distribution of eclamptic mothers who

received antenatal care in both groups

65

12. Representation of distribution of eclamptic mothers from

different areas among both groups

67

13. Representation of distribution of gestational age among

eclamptic mothers in both groups

69

14. Representation of distribution of body mass index among


71

15. Representation of systolic blood pressure distribution

among eclamptic mothers in both groups

73

16. Representation of diastolic blood pressure distribution 75

among eclamptic mothers in both groups

17. Representation of distribution of no. of episodes if

seizures before the start of treatment in eclamptic

mothers among both groups

77

18. Representation of distribution of mode of delivery among


79

19. Representation of birth weight distribution in neonates of

eclamptic mothers among both groups

81

20. Representation of distribution cord blood magnesium at

the time of delivery among neonates of eclamptic

mothers in both groups

83

21. Representation of distribution of APGAR scores at 5min

among the neonates of eclamptic mothers in both groups

85

22. Representation of NICU care requirement among the

neonates of eclamptic mothers in both groups

87

23. Representation of incidence of respiratory distress among

the neonates of eclamptic mothers in both groups

89

24. Representation of incidence of hypotonia among the


91

25. Representation of incidence of bradycardia among the


92

26. Representation of serum blood magnesium at the time of

delivery among the neonates of eclamptic mothers in

both groups

93

27. Neonatal adverse events in both the groups 95

28. Maternal adverse events in both the groups 95

LIST OF FIGURES

SL.

NO. TITLE

PAGE

NO.

1. Bar diagram showing incidence of eclampsia over a decade

in India

9

2. Schematic representation of normal implantation and

defective implantation in preeclampsia and eclampsia

11

3. Schematic representation showing glomerular capillary

endotheliosis

12

4. Etiopathology of pre-eclampsia and eclampsia 13

5. Illustration showing location of cerebral haemorhages and

petechiae in women with eclampsia

15

6. Illustration of signs of eclampsia 18

7. Illustration showing extensive tongue injury following

eclamptic convulsion.

25

8. Illustration of structure of magnesium sulphate 30

9. Illustration of mechanism of action of magnesium sulphate

on myometrial cell

31

10. Comparing of serum magnesium levels in mEq/L following

intravenous and intramuscular regimens

38

11. Flow chart representing the recruitment of the patient in the study 60

12. Graphical representation of distribution of age of eclamptic

mothers among both the groups

62

13. Graphical representation of parity distribution among eclamptic

mothers among both the groups

64

14. Graphical representation of distribution of antenatal care received

between both the groups

66

15. Graphical representation of distribution of eclamptic mothers in

rural and urban areas among both the groups

68

16. Graphical representation of distribution of gestational age in

weeks of eclamptic mothers among both the groups

70

17. Graphical representation of BMI distribution of eclamptic mothers

among both the groups

72

18. Graphical representation of distribution of systolic blood pressure

of eclamptic mothers among both the groups

74

19. Graphical representation of distribution of diastolic blood pressure

in eclamptic mothers among both the groups

76

20. Graphical representation of distribution of number of convulsions

in eclamptic mothers among both the groups

78

21. Graphical representation of distribution of mode of delivery in

eclamptic mothers among both the groups

80

22. Graphical representation of distribution of birth weight in neonates

of eclamptic mothers among both the groups

82

23. Graphical representation (line diagram)of distribution of cord

blood magnesium level at the time of delivery in neonates of

eclamptic mothers among both the groups

84

24. Graphical representation of distribution of APGAR scores among

the neonates of eclamptic mothers among both the groups

86

25. Graphical representation (line diagram) correlation of cord blood

magnesium level and APGAR scores in neonates of eclamptic

mothers in both the groups

86

26. Graphical representation of distribution of NICU care requirement

in neonates of eclamptic mothers among both the groups

88

27. Graphical representation (scatter plot) correlation of cord

blood magnesium level and NICU care requirement in

neonates of eclamptic mothers among both the groups

88

28. Graphical representation of distribution of incidence of respiratory

distress in neonates of eclamptic mothers among both the groups

90

29. Graphical representation (box plot) of distribution of incidence of

respiratory distress in neonates of eclamptic mothers among both

the groups

90

30. Graphical representation of distribution of incidence of hypotonia

in neonates of eclamptic mothers among both the groups

91

31. Graphical representation of distribution of incidence of

bradycardia in neonates of eclamptic mothers among both the

groups

92

32. Graphical representation (line diagram) of distribution of serum

magnesium levels of eclamptic mothers among both the groups

94

33. Graphical representation of distribution of adverse events among

both the groups

97

34. Graphical representation (line diagram) correlation of serum

magnesium level and adverse events in eclamptic mothers among

both the groups

98

35. Graphical representation (line diagram) correlation of serum

magnesium level and adverse events in eclamptic mothers among

both the groups

98

1

ABSTRACT

BACKGROUND AND OBJECTIVE - Eclampsia is one of the preventable cause of

maternal and neonatal mortality. Magnesium sulphate is the drug of choice to control

the convulsions and prevent them. The toxic effects of magnesium sulphate like

decreased urinary output and aspiration pneumonia has discouraged many primary

and secondary health centres to use the drug. Considering the low body mass index of

women in developing countries, the use of low dose magnesium sulphate regimen

may improve the safety profile of magnesium sulphate. The objective of this study is

to compare the neonatal outcome in eclamptic mothers treated with Low-dose

magnesium sulphate regimen and Standard dose magnesium sulphate regimen.

MATERIALS AND METHODS - This is a randomised prospective open labelled

comparative study between the neonates of eclamptic mothers treated with Low dose

magnesium sulphate regimen and Standard dose magnesium sulphate regimen. The

study included 100 patients with eclampsia and divided into two groups, where group

A received low dose magnesium sulphate regimen and group B received standard

regimen. Maternal and cord blood magnesium sulphate was measured. Neonatal

outcomes of all the eclamptic patients were recorded. Maternal complications was

also assessed.

RESULTS - In this present study, NICU care was required for 28(56%) neonates in

standard regimen group compared to 8(16%) neonates in low dose regimen group.

Bradycardia and Hypotonia was significantly increased in neonates of standard

regimen group (p<0.05). APGAR scores decreased with increase in cord blood

magnesium levels. Recurrence of seizure was seen in 10% of cases in low dose

2

regimen group compared to 5% in standard dose regimen group. There was no

maternal mortality.

CONCLUSION - Neonatal complication are significantly related to increasing serum

magnesium level. Low dose magnesium sulphate regimen showed better neonatal

outcome compared to Standard dose magnesium sulphate regimen. It also showed

effective seizure control in eclamptic mothers without significant seizure recurrence.

Hence, the low-dose magnesium sulphate regimen was found to be safe in

themanagement of eclamptic mothers, without toxicity to their neonates.

KEYWORDS - Low dose magnesium sulphate regimen; Eclampsia; Neonatal

outcome

TITLE - "A randomized comparative study between neonatal outcome of

eclamptic mothers treated with low dose magnesium sulphate and standard dose

regimen for management of eclampsia in McGann teaching district hospital,

Shivamogga"

INTRODUCTION

Eclampsia is an important cause of maternal and perinatal morbidity and mortality

worldwide. Incidence in developing countries is 1 in 500 deliveries. Perinatal

mortality rate in neonates of eclamptic mothers is 30 to 50% in India.1

Magnesium sulphate is anticonvulsant drug of choice for both prevention and

treatment of eclampsia.2 Magnesium causes cerebral vasodilatation and reduction of

cerebral ischemia by calcium antagonism and relaxation of smooth muscles. Also it

has its action on peripheral vasculature and uterus.2

Dose related toxicity of magnesium sulphate is a concern. Potential hazards include

maternal hypotension, respiratory depression, respiratory arrest and decreased tendon

reflexes, decreased urinary output.3

A significant percentage of perinatal and early neonatal morbidity and mortality is

attributed to magnesium toxicity like increased still birth early neonatal death, birth

asphyxia, bradycardia, hypotonia, hyporeflexia, gastrointestinal hypomotility and

meconium plug syndrome.4 Experience with Pritchard’s magnesium sulphate regimen

showed all the above mentioned multiple toxicity and needed dose omission.

Adoption of this treatment in primary and secondary level hospital has been delayed

due to fear of toxicity of drug linked to high serum magnesium levels and can be life

threatening to both mother and neonate.5

3

Previously, no dose adjustment of magnesium sulphate were made for maternal

weight even though maternal weight is very low in low income countries than high

income ones (i.e 65kg vs 45kg).6 So low dose regimens have been described

principally due to lower BMI of Indian women and concerns about toxicity in

circumstances where facility for measurement of serum magnesium levels are not

available.7

In this study we used Bankura regimen of low dose magnesium sulphate for

administration because study with this regimen showed efficacy similar to standard

Pritchard regimen with reduced maternal and perinatal mortality.6

Normal serum concentrations of magnesium for adults are 0.75-1.25 mmol/L.

Therapeutic magnesium serum concentration recommended for the treatment of

eclamptic convulsions are 1.5-3.5mmol/L, which can be obtained by both the low

dose and standard dose regimen.7,8

Monalisa Das et al, observed the serum magnesium levels and its outcome in neonates

of eclamptic mothers treated with low dose magnesium sulphate regimen. In this cross

sectional observational study on eclampsia patients and their neonates, loading dose

and maintenance doses of magnesium sulphate were administered to eclampsia

patients by combination of intravenous and intramuscular routes. Maternal serum and

cord blood magnesium levels were estimated. Neonatal outcome was assessed.

APGAR scores decreased with increase in cord blood magnesium levels and

increasing dose of magnesium sulphate. Also other parameters like hypotonia, birth

asphyxia, intubation in delivery room, NICU care requirement were increased with

increasing dose of magnesium sulphate.6

4

Latika Sahu et al, compared low dose magnesium sulphate and standard dose regimen

for management of eclampsia. In this prospective randomized study involving two

groups of patient with eclampsia receiving either low dose group or standard

dose/control group magnesium sulphate regimen. Convulsions were controlled in 96%

of eclampsia cases with low dose magnesium sulphate regimen. There was no

maternal mortality.7

Ruchira Nautiyal et al, compared low dose magnesium sulphate regimen with

Pritchard’s regimen for eclampsia. In this prospective cross sectional study, patients

were divided into two groups. Group A received low dose magnesium sulphate

regimen group B were managed with pritchard regimen of magnesium sulphate. The

recurrence of fits, toxicity profile and feto-maternal outcome was studied. Low dose

regimen was equally effective in controlling the seizures. Incidence of loss of deep

tendon reflex compared with standard dose. Mean values of serum magnesium in both

the groups was comparable.8

Mina Abbasi Ghanavati et al, observed Neonatal effects of magnesium sulphate given

to mother. In this retrospective cohort analysis of women who received magnesium

sulphate for prevention or treatment of eclampsia magnesium sulphate was given

intravenously 6gm dose, followed by 3gm/hour infusion. The neonates were

diagnosed with hypotonia lower APGAR scores, intubation in delivery room,

admission to special nursery care, and hypotonia were all significantly increased as

maternal serum magnesium concentrations increased before birth.9

Jana N et al , studied low dose magnesium sulphate regimen for the management of

eclampsia over a decade in Indian women. A low dose of magnesium sulphate of 3gm

intravenously and 5gm intramuscularly, followed by 2.5gm intramuscularly every 4

5

hours, for 24 hours beyond the last seizure. Second phase of the study included

retrospective analysis of eclamptic mothers treated by same regimen at the same

hospital. The low dose regimen was associated with a lower seizure recurrence and

slightly lower maternal mortality compared with collaborative eclampsia trial.10

Nassar AH et al, observed adverse maternal and neonatal outcome of prolonged

course of magnesium sulphate tocolysis. They found neonatal magnesium level was

significantly higher in cases and also abnormal bone mineralization was encountered.

Maternal morbidity rate was higher with prolonged intake of tocolytic magnesium

regimen.11

Begum R et al observed low dose Dhaka magnesium regimen for eclampsia. In this

cross sectional observation study on eclampsia convulsions were controlled in 97% of

eclampsia cases and toxicity profile was less among the Dhaka regimen group

compared with standard dose.12

Neonatal outcome of low dose magnesium sulphate has rarely been studied. So we

tried to find the safety of same. Prior studies were observational studies and have not

included all the parameters which we have included in the present study, also did not

consider the correlation with serum magnesium levels. This type of study has not been

done in this region. So we tried to find the efficacy of this low dose regimen which

can be tried in our institution and also can be informed to nearby primary and

secondary centres to implement this regimen without fear of magnesium toxicity as in

standard Pritchard's regimen which can reduce the complications of eclampsia

reaching our tertiary level hospital.

6

7

OBJECTIVES

1. To compare the neonatal outcome in eclamptic mothers treated with low-dose

magnesium sulphate regimen and standard dose magnesium sulphate regimen.

2. To determine the efficacy of low-dose magnesium sulphate regimen in

controlling and preventing the episodes of seizure.

3. To assess the maternal complications occurring due to magnesium sulphate

regimens.

4. To correlate the cord blood magnesium levels and the neonatal outcome in

eclamptic mothers.

5. To correlate the serum magnesium levels and the maternal complications in

patients of eclampsia.

8

REVIEW OF LITERATURE

Eclampsia is a multisystem disorder of unknown aetiology characterized by

development of hypertension to the extent of 140/90mmHg or more with proteinuria

after the 20th week in a previously normotensive a non proteinuric patient

complicated with generalised tonic-clonic convulsions and/coma. The basic

underlying pathology is endothelial dysfunction and vasospasm, affecting almost all

vessels, particularly those of uterus, kidney, placental bed and brain.13

EPIDEMOLOGY

Eclampsia is one of the leading causes of high maternal mortality and morbidity and

also high perinatal mortality. According to WHO, eclampsia is the cause of 12 per

cent of all maternal death globally. It accounts for 50,000 maternal deaths worldwide.

In India, reported incidence of eclampsia varies from 0.179 to 3.7 per cent. And

maternal mortality varies from 2.2 to 23 per cent of all eclamptic women. . The

estimated incidence of eclampsia in Western countries is 1 in 2000 to 3448

deliveries.14

Maternal mortality in eclampsia is very high in India and varies from 2 to 30 per cent,

much more in ruralbased hospital than in the urban counterpart. However, if treated

early and adequately, the mortality should be even less than 2 per cent.15

In India, incidence of eclampsia is high. Observation has shown that the situation is

remaining same over the decades, though in certain places reports show declining

incidence. It is observed that during the last 40 to 50 years, i.e., from 1976 to 2015

(January– February), the incidence of eclampsia in India has not changed. This trend

is evident from figure no 1. Maternal mortality from eclampsia is also remaining

highthroughout the ages.In 1982 maternal mortality was 14.12 to17.28 % and in 1992

9

it was 8.06; a death rate of 11.54% was reported in 2002. In 2010, maternalmortality

from eclampsia ranged from 2.2 to 9 %.19

Figure no 1 : Bar diagram showing incidence of eclampsia over a decade in India.

Courtesy Nobis P.N, HajongAnupama. Eclampsia in India Through the DecadesThe

Journal of Obstetrics and Gynecology of India 2016;66(1):172–176

Perinatal mortality too shows the same gloomy picture overthe decades. In 1984 the

reported figure of perinatal deathwas 45 %, in 1988 it was 32 %, in 2007 it was39.3 %

and in 2010 it ranged from 24.5 to 48 %.16

ETIOPATHOLOGY OF ECLAMPSIA

The term eclampsia is derived from a Greek word, meaning “like a flash of

lightening”. It may occur quiteabruptly, without any warning manifestations. In

majority (over 80%); however, the disease is preceded byfeatures of severe pre-

eclampsia. Pre-eclampsia when complicated with generalized tonic–clonic

convulsions and/or coma is calledeclampsia.2

The underlying pathology is endothelial dysfunction and intense vasospasm.

10

The responsible agent for endothelial dysfunction and vasospasm, still has not been

isolated precisely but it is certain that the origin is humoral.17

The following are the consideration -

• Increased circulating pressor substances.

• Increased sensitivity of the vascular system to normally circulating pressor

substances.

Trophoblast invasion and Uterine Vascular Changes : Normally, there is invasion

of the endovascular trophoblasts into the walls of the spiral arterioles of the

uteroplacental bed. In the first trimester (10-12 weeks) endovascular trophoblasts

invades up to decidual segments and in second trimester (16-18 weeks) another wave

of trophoblasts invades upto the myometrial segments. This process replaces the

endothelial lining and the muscular arterial wall by fibrinoid formation. The spiral

arterioles thereby become distended, tortuous, and funnel-shaped. This physiological

change transforms the spiral arterioles into a low resistance, low pressure, high flow

system. In eclampsia, there is failure of the second wave of endovascular trophoblast

migration and there is reduction of blood supply to the fetoplacental unit. Figure no 2

shows defective implantation characterized by inconsistence of spiral arteriolar wall

by extravilloustrophoblasts. This results in a small-caliber vessel with high resistance

flow. The magnitude ofdefective trophoblastic invasion is thought to correlate with

severity of the hypertensive disorder. Nelson and colleagues completed

placentalexamination in more than 1200 women with preeclampsia.

Theseinvestigators reported that vascular lesions including spiral arteriolenarrowing,

atherosis, and infarcts were more common in placentasfrom women diagnosed with

preeclampsia before 34 weeks.18,19

11

Figure no 2 : It is schematic representation of normal implantation and defective

implantation in preeclampsia and eclampsia.

Courtesy: Cunningham FG. Obstetrical complication: Hypertensived disorders. In:

Leveno K, editor. Williams Obstetrics 24th edition. New York: Mc Graw Hill

Education 2014: p 732

(1) There is an imbalance in different components of prostaglandins—relative or

absolute deficiency of vasodilator prostaglandin (PGI2) from vascular endothelium

and increased synthesis ofthromboxane (TXA2), a potent vasoconstrictor in platelets.

(2) There is increased vascular sensitivity to thepressor agent angiotensin-II.

Angiotensinase activity is depressed, following proteinuria with elimination of α2

globulin.

(3) Nitric oxide (NO): It is synthesized in the vascular endotheliumand

syncytiotrophoblast from L-arginine. It significantly relaxes vascular smooth muscle,

inhibits plateletaggregation and prevents intervillous thrombosis.Deficiency of nitric

oxide contributes to the development ofhypertension.

spiral arteries

12

(4) Endothelin-1 is synthesized by endothelial cells, and it is a potent vasoconstrictor

compared to angiotensin-II. Endothelin-1 also contributes to the cause of

hypertension.

(5) Inflammatory mediators:Cytokines [tumour necrosis factor (TNF-α),

interleukins (IL-6) and others] derived from activated leukocytes cause endothelial

injury

(6) Abnormal lipid metabolism—results in more oxidative stress. Lipid peroxides,

reactive oxygen species (ROS) and superoxide anion radicals — cause endothelial

injury and dysfunction. Platelet and neutrophil activation, cytokines,

superoxideradical production and endothelial damage are in a vicious cycle.

(7) Others—mutation of factor V Leiden increases the risk.20

Figure no 3: Schemation showing glomerular capillary endotheliosis.




13

EDEMA: The cause of excessive accumulation of fluids in the extracellular tissue

spaces is not clear. Probableexplanations are: Increased oxidative stress → endothelial

injury → increased capillary permeability. On thisbasis, the leaky capillaries and

decreased blood osmotic pressure are the probable explanations.

PROTEINURIA: The probable chain of events is as follows. Spasm of the afferent

glomerular arterioles →anoxic change to the endothelium of the glomerular tuft →

glomerular endotheliosis→ increased capillarypermeability → increased leakage of

proteins. Tubular reabsorption is simultaneously depressed. Albuminconstitutes 50–

60% and alpha globulin constitutes 10–15% of the total proteins excreted in the

urine.21

Figure no 4: Etiopathology of pre-eclamapsia and eclampsia.

Courtesy: Dutta DC. Hypertensive Disorders in Pregnancy. In: Konar H, editor. DC

Dutta’sText Book of Obstetrics. 8th ed. New Delhi: Jaypee Brothers Medical

Publishers(P) Ltd.; 2015. p. 268.

14

CEREBRAL PATHOLOGY:includes cortical or subcortical oedema, infarction and

haemorrhage. The neurological abnormalities areoften due to hypoxia, ischemia or

oedema. Several neurodiagnostic tests e.g. EEG, CAT, cerebral Doppler Velocimetry,

MRI, MRIangiography reveal presence of oedema and infarction. Findings are similar

to those as seen in hypertensive encephalopathy.Cerebral imaging is indicated when

there is focal neurologic deficits, prolonged coma, or atypical presentation for

eclampsia.13

CAUSE OF CONVULSION: The cause of cerebral irritation leading to convulsion is

not clear. The irritation may be provokedby:

(1) Anoxia — spasm of the cerebral vessels → increased cerebral vascular resistance

→ fall in cerebral oxygen consumption→ anoxia,

(2) Cerebral oedema — may contribute to irritation,

(3) Cerebral dysrhythmia — increases following anoxia oroedema. There is excessive

release of excitatory neurotransmitters (glutamate).

15

Figure no 5: Illustration showing location of cerebral haemorrhages and petechiae in

women with eclampsia.




Pia Arachnoid

16

Table no 1: Risk factors and etiopathological factors for eclampsia.13

RISK FACTORS FOR ECLAMPSIA ETIOPATHOLOGICAL FACTORS

Primigravida: Young or elderly (first time

exposure to chorionic villi)

Failure of trophoblast invasion

(abnormal

Placentation)

Family history: Hypertension, pre-

eclampsia

Vascular endothelial damage

Placental abnormalities:

– Hyperplacentosis: Excessive exposure to

chorionicvilli—(molar pregnancy twins,

diabetes)

– Placental ischemia.

Inflammatory mediators (Cytokines)

Dietary deficiency or excess

Obesity: BMI >35 kg/m2, Insulin

resistance.

Immunological intolerance between

maternal andfoetal tissues

Pre-existing vascular disease Coagulation abnormalities

New paternity Increased oxygen free radicals

Thrombophilias(antiphospholipidsyndrome,

protein C, Sdeficiency, Factor V Leiden)

Genetic predisposition

17

CLINICAL FEATURES OF ECLAMPSIA

An eclamptic patient always shows previous manifestations of acute fulminating

pre-eclampsia — called premonitory symptoms.

ALARMING SYMPTOMS: The following are the ominous symptoms, which may

be evident either singly or incombination. These are usually associated with acute

onset of the syndrome.

(1) Headache — either locatedover the occipital or frontal region

(2) Disturbed sleep

(3) Diminished urinary output—Urinary output of lessthan 400 ml in 24 hours is very

ominous,

(4) Epigastric pain—acute pain in the epigastric region associated withvomiting, at

times coffee colour, is due to hemorrhagic gastritis or due to subcapsular haemorrhage

in the liver,

(5) Eye symptoms—there may be blurring, scotoma, dimness of vision or at times

complete blindness. Visionis usually regained within 4–6 weeks following delivery.

The eye symptoms are due to spasm of retinal vessels(retinal infarction), occipital

lobe damage (vasogenic oedema) or retinal detachment. Reattachment of the retina

occurs following subsidence of oedema and normalization of blood pressure after

delivery.22

SIGNS

1. Abnormal weight gain: Abnormal weight gain within a short span of time probably

appears even beforethe visible oedema. A rapid gain in weight of more than 5 lb a

month or more than 1 lb a week in later monthsof pregnancy is significant.

18

2. Rise of blood pressure: The rise of blood pressure is usually insidious but may be

abrupt. The diastolicpressure usually tends to rise first followed by the systolic

pressure.

Figure no 6 : Illustration of signs of eclampsia.

Courtesy:Dutta DC. Hypertensive Disorders in Pregnancy. In: Konar H, editor. DC



3. Oedema: Visible oedema over the ankles on rising from the bed in the morning is

pathological. The oedemamay spread to other parts of the body in uncared cases

(Figno.6).

4. There is no manifestation of chronic cardiovascular or renal pathology.

5. Pulmonary oedema — due to leaky capillaries and low oncotic pressure.

6. Abdominal examination may reveal evidences of chronic placental insufficiency,

such as scanty liquoror growth retardation of the foetus.23

MARKED PEDAL OEDEMA MARKED VULVAL OEDEMA

19

Thus, the manifestations of pre-eclampsia usually appear in the following order—

rapid gain in weight →visible oedema and/or hypertension → proteinuria.

ECLAMPTIC CONVULSION OR FIT:The fits are epileptiform and consist of four

stages.

1.Premonitory stage: The patient becomes unconscious. There is twitching of the

muscles of the face,tongue, and limbs. Eyeballs roll or are turned to one side and

become fixed. This stage lasts for about 30 seconds.

2.Tonic stage: The whole body goes into a tonic spasm — the trunk-opisthotonus,

limbs are flexed andhands clenched. Respiration ceases and the tongue protrudes

between the teeth. Cyanosis appears. Eyeballsbecome fixed. This stage lasts for about

30 seconds.

3.Clonic stage: All the voluntary muscles undergo alternate contraction and

relaxation. The twitchings startin the face then involve one side of the extremities and

ultimately the whole body is involved in the convulsion.Biting of the tongue occurs.

Breathing is difficult and blood stained frothy secretions fill the mouth; cyanosis

gradually disappears. This stage lasts for 1–4 minutes.

4. Stage of coma: Following the fit, the patient passes on to the stage of coma. It may

last for a brief periodor in others deep coma persists till another convulsion. On

occasion, the patient appears to be in a confusedstate following the fit and fails to

remember the happenings.

Rarely, the coma occurs without prior convulsion.The fits are usually multiple,

recurring at varying intervals. When it occurs in quick succession, it is called

20

statuseclampticus. Following the convulsions, the temperature usually rises; pulse and

respiration rates areincreased and so also the blood pressure. The urinary output is

markedly diminished; proteinuria is pronounced,and the blood uric acid is raised.

CENTRAL NERVOUS SYSTEM ABNORMALITIES IN ECLAMPSIA

• Cerebral oedema

• Cerebral haemorrhage

• Posterior (parietal or occipital lobe) reversible encephalopathy syndrome

• Basal ganglia an brain stem lesion(rare)24

Table no 2: Pathophysiology and organ dysfunctions in eclampsia.2

ORGAN DYSFUNCTION IN PRE-ECLAMPSIA AND ECLAMPSIA

CARDIOVASCULAR

HAEMATOLOGICAL RENAL HEPATIC

Generalized vasospasm Plasma volume GFR Liver cell

damage

Peripheral vascular

resistance

Hemoconcentration Renal

plasma flow

Periportal

necrosis

CVP

Coagulation disorder Serum uric

acid

Subcapsular

haematoma

Pulmonary wedge

pressure

Blood viscosity

21

INVESTIGATIONS

Urine: Proteinuria is the last feature of pre-eclampsia to appear. It may be trace or at

times copious. There may be few hyaline casts, epithelial cells or even few red cells.

24 hours urine collection for protein measurement is done.

Ophthalmoscopic examination: In severe cases there may be retinal oedema,

constriction of the arterioles, alteration of normal ratio of vein: arteriole diameter

from 3 : 2 to 3 : 1 and nicking of the veins where crossed by the arterioles. There may

be haemorrhage.

Blood values: The blood changes are not specific and often inconsistent. A serum uric

acid level (biochemical marker of pre-eclampsia)of more than 4.5 mg/dL indicates the

presence of pre-eclampsia. Blood urea level remainsnormal or slightly raised. Serum

creatinine level may be more than 1 mg/dL. There may be thrombocytopenia

and abnormal coagulation profile of varying degrees. Hepatic enzyme levels may be

increased.

Antenatal foetal monitoring: Antenatal foetal well being assessment is done by

clinical examination, dailyfoetal kick count, ultrasonography for foetal growth and

liquor pockets, cardiotocography, umbilical artery flowvelocimetry and biophysical

profile.25

MANAGEMENT

PREDICTION AND PREVENTION: In majority of cases, eclampsia is preceded by

severe pre-eclampsia. Thus theprevention of eclampsia rests on early detection and

effective institutional treatment with judicious terminationof pregnancy during pre-

eclampsia. However, eclampsia can occur bypassing the preeclamptic state and as

22

such, it is not always a preventable condition. Eclampsia may present in atypical

ways; hence, it is at timesdifficult to predict. Use of antihypertensive drugs,

prophylactic anticonvulsant therapy and timely deliveryare important steps. Close

monitoring during labour and 24 hours’ postpartum, are also important in prevention

ofeclampsia. Magpie trial showed prophylactic use of magnesium sulphate lowers the

risk of eclampsia.Unfortunately, 30–85 percent of cases of eclampsia remained

unpreventable.26

FIRST AID TREATMENT OUTSIDE THE HOSPITAL: The patient at home or in

the peripheral healthcentres should be shifted urgently to the tertiary referral care

hospitals.Transport of an eclamptic patient to a tertiary care centre is important.27

HOSPITAL—THE PRINCIPLES OF MANAGEMENT ARE:

Table no 3 - The principles of management.28

Maintain: airway, breathing and

circulation

Hemodynamic stabilization

(control BP)

Oxygen administration 8–10 L/min Organize the investigations

Arrest convulsions Deliver by 6-8 hours

Ventilator support Prevention of complication

Prevention of injury Post partum care

23

GENERAL MANAGEMENT

Supportive care:

(i) to prevent serious maternal injury from fall, (ii) prevent aspiration, (iii) to maintain

airway and (iv) to ensure oxygenation.

Patient is kept in a railed cot and a tongue blade is inserted between the teeth. She is

kept in the lateraldecubitus position to avoid aspiration. Vomitus and oral secretions

are removed by frequent suctioning,oxygenation is maintained through a face mask

(8–10 L/min) to prevent respiratory acidosis. Oxygenation ismonitored using a

transcutaneous pulse oximeter. Arterial blood gas analysis is needed when O2

saturationfalls below 92 percent. Sodium bicarbonate is given when the pH is below

7.10. The patient should have adoctor or at least a trained midwife for constant

supervision.29

Detailed history is to be taken from the relatives, relevant to the diagnosis of

eclampsia, duration ofpregnancy, number of fits and nature of medication

administered outside.

Examination: Once the patient is stabilized, a thorough but quick general, abdominal

and vaginalexaminations are made. A self-retaining catheter is introduced and the

urine is tested for protein. The continuousdrainage facilitates measurement of the

urinary output and periodic urine analysis.

Monitoring:Half hourly pulse, respiration rates and blood pressure are recorded.

Hourly urinary outputis to be noted. If undelivered, the uterus should be palpated at

regular intervals to detect the progress of labourand the foetal heart rate is to be

monitored. Immediately after a convulsion, foetal bradycardia is common.

24

Fluid balance: Crystalloid solution (Ringer’s solution) is started as a first choice.

Total fluids shouldnot exceed the previous 24 hours urinary output plus 1000 ml

(insensible loss through lungs and skin). Infusion of balanced salt solution should be

at the rate of1 ml/kg per hour. In pre-eclampsia and eclampsia although there is

hypovolemia, the tissues are over loaded. Anexcess of dextrose or crystalline

solutions should not be used as it will aggravate the tissue overload leadingto

pulmonary oedema and adult respiratory distress syndrome. CVP monitoring is

needed for a patient with severe hypertension and reduced urineoutput.

Antibiotic: To prevent infection, Ceftriaxone 1 gm IV twice daily is given.30

SPECIFIC MANAGEMENT:

Anticonvulsant and sedative regime: The aim is to control the fits and to preventits

recurrence.

Magnesium sulphate is the drug of choice. It acts as a membrane stabilizer and

neuroprotector. It reducesmotor endplate sensitivity to acetylcholine. Magnesium

blocks neuronal calcium influx also. It induces cerebralvasodilatation, dilates uterine

arteries, increases production of endothelial prostacyclin and inhibits platelet

activation. It has no detrimental effects on the neonate within therapeutic level. It has

got excellentresult with maternal mortality of 3%. It does not control hypertension.

Table no 4: Intramuscular regimen for management of eclampsia.31

REGIMEN LOADING DOSE MAINTAINANCE DOSE

Intramuscular (Pritchard) 4 gm IV over 3–5 min

followed by 10

gm deep IM (5 gm in each

buttock)

5 gm IM 4 hourly in

alternate buttock

25

Antihypertensives and diuretics: Inspite of anticonvulsant and sedative regime, if

the blood pressureremains more than 160/110 mm Hg, antihypertensive drugs should

be administered. Drugs commonly usedare parenteral, hydralazine, labetalol, calcium

channel blockers or nitroglycerin.

Presence of pulmonary oedema requires diuretics. In such cases, the potent one

(frusemide) should beadministered in doses of 20–40 mg intravenously and to be

repeated at intervals.

Management during fit: (a) In the premonitory stage, a mouth gag is placed in

between the teeth to preventtongue bite and should be removed after the clonic phase

is over. (b) The air passage is to be cleared off themucus with a mucus sucker. The

patient’s head is to be turned to one side and the pillow is taken off. Raisingthe

footend of the bed, facilitates postural drainage of theupper respiratory tract. (c)

Oxygen is given until cyanosisdisappears.32

Figure no 7: Extensive tongue injury following an eclamptic convulsion. It occurs in

clonic stage.

Courtesy:Dutta DC. Hypertensive Disorders in Pregnancy. In: Konar H, editor. DC


Publishers(P) Ltd.; 2015. p. 268

26

OBSTETRIC MANAGEMENT: During pregnancy: In majority of cases with

antepartum eclampsia, labour startsoon after convulsions. But when labour fails to

start, the management depends on—(i) whether the fits arecontrolled or not and (ii)

the maturity of the foetus. The decision to deliver is made once the woman is stable.

• Fits controlled:

Baby mature:Delivery should be done. (a) If the cervix is favourable and there is no

contraindication of vaginaldelivery, surgical induction by low rupture of the

membranes is done. Oxytocin drip may be added, if needed.

(b) When the cervix is unfavourable, cervical ripening with PGE2 gel or pessary

could be achieved before ARM. (c)If the cervix is unfavourable and/or there is

obstetric contraindication of vaginal delivery, caesarean section is done.

Baby premature(<37 weeks): Delivery is recommended in a set up with neonatal

intensive care unit (NICU).The underlying disease process of pre-eclampsiaeclampsia

persists until the woman delivers. At times thedisease process may flare up.

Moreover, there lies the risk of recurrent convulsions and IUFD. Steroid therapy is

given when pregnancy is less than 34 weeks. Conservative management at very early

pregnancymay improve perinatal outcome but this must be carefully balanced with

maternal well-being.

Baby dead: The preeclamptic process gradually subsides and eventually expulsion of

the baby occurs.Otherwise medical method of induction is started.

Fits not controlled: If the fits are not controlled with anticonvulsant within a

reasonable period (6–8 hours),termination of pregnancy should be done. If vaginal

examination indicates a quick response to induction, lowrupture of the membranes is

27

done. Oxytocin infusion may be added. The uterus responds well to oxytocin insuch

cases. In presence of unfavourable factors, caesarean section gives a quick response.

During labour:In the absence of any contraindication to vaginal delivery, as soon as

the labour is well established,low rupture of the membranes is to be done to accelerate

the labour. The dose schedule of antihypertensive andanticonvulsant drugs may be

increased to quieten the patient. Second stage should be curtailed by forceps,

ventouseor craniotomy, if the baby is dead. Prophylactic intravenous ergometrine or

syntometrine following the deliveryof the anterior shoulder should not be given as it

may produce further rise of blood pressure. Instead, 10 units ofoxytocin IM or IV

slowly should be given.

Indications of caesarean section: (i) Uncontrolled fits in spite of therapy. (ii)

Unconscious patient and poorprospect of vaginal delivery. (iii) Obstetric indications

Follow up and prognosis: Patient should be followed up in the postnatal clinic by 6

weeks time. Persistenceof hypertension, proteinuria and abnormal blood biochemistry

necessitates further investigationand consultation with a physician.

Recurrence risk varies between 2 and 25%. 33

28

COMPLICATIONS

Table no 5 - Maternal complications of eclampsia.2

Injuries -

Tongue bite, injuries due to fallfrom bed,

bed sore.

Pulmonary complications:

Oedema—due to leaky bloodcapillaries

Pneumonia—due to aspiration,hypostatic

or infective

Adult respiratory distress syndrome

Embolism

Hyperpyrexia

Cardiac—Acute left ventricularfailure

Renalfailure

Hepatic—necrosis, Subcapsular

hematoma

Cerebral:Oedema

(vasogenic)haemorrhage

Neurologicaldeficits

Disturbed vision: Due to

retinaldetachment or occipital

lobeischemia.

Hematological

Thrombocytopenia

Disseminated intravascular

Coagulopathy

Postpartum

Shock

Sepsis

Psychosis

PROGNOSIS

MATERNAL: Immediate: Once the convulsion occurs, the prognosis becomes

uncertain. Prognosis depends on many factors and the ominous features are:

(1) Long interval between the onset of fit and commencementof treatment (late

referral).

(2) Antepartum eclampsiaespecially with long delivery interval.

(3) Number offits more than 10.

29

(4) Coma in between fits.

(5) Temperature over 102°F with pulse rate above 120/minute.

(6)Blood pressure over 200 mm Hg systolic.

(7) Oliguria (< 400 mL/24 hours) with proteinuria > 5 gm/24 hours.

(8) Nonresponse to treatment.

(9) Jaundice.

Mortality:Maternal mortality in eclampsia is very high in India and varies from 2–

30%, much more in ruralbased hospital than in the urban counterpart. However, if

treated early and adequately, the mortality shouldbe even less than 2%.

Causes of maternal deaths: (1) Cardiac failure. (2) Pulmonary oedema(3) Aspiration

and/or septic pneumonia (4) Cerebral haemorrhage (5) Acute renal failure (6)

Cardiopulmonary arrest (7) Adult respiratory distress syndrome (ARDS) (8)

Pulmonary embolism (9) Postpartum shock (10) Puerperal sepsis.

Maternalcomplications are higher in antepartum eclampsia.

Remote: If the patient recovers from acute illness, she is likely to recover rapidly

within 2–3 weeks. Recurrenceof eclampsia in subsequent pregnancies is uncommon,

although chance of pre-eclampsia is about 30%.34

FETAL: The perinatal mortality is very high to the extent of about 30–50%. The

causes are: (1) Prematurity — spontaneous or induced, (2) Intrauterine asphyxia

due to placental insufficiency arising out of infarction,retroplacental haemorrhage and

spasm of uteroplacental vasculature, (3) Effects of the drugs used to

controlconvulsions, (4) Trauma during operative delivery.35

30

SPECIFIC PHARMACOTHERAPEUTIC MANAGEMENT OF ECLAMPSIA

MAGNESIUM SULPHATE

CHEMISTRY

Magnesium sulphate USP is MgSO4·7H2O and not simple MgSO4. It is heptahydrate

sulphate mineral epsomite (MgSO4.7H20), commonly called Epsom salt. It contains

8.12 mEqper 1 g. Molar mass is MgS04 heptahydrate is 246.47g/mol.36

The generic formula of Magnesium sulphate is

Figure no 8: Illustration of structure of magnesium sulphate.

BACKGROUND AND HISTORY

In 118 a farmer by the name of Henry Wicker at Epsom in England attempted to give

his cows water from a well. They refused to drink because bitter taste of the water.

However the farmer noticed that the water seemed to heal scratches and rashes.

Eventually it was recognized to be magnesium sulphate.

Joseph Black recognized magnesium as an element in 1755. It was isolated by Sir

Humphry Davy in 1808. The name magnesium comes from Magnesia, a district of

Greece were it was first found and to this present day a lot of magnesium ore is

present in the area.13

First used anecdotally for the control of eclamptic seizures in the early 1900s,

magnesium sulphate remains one of the most commonly used medications in obstetric

practice today. Over the past 95 years, there have been countless research studies

31

investigating the efficacy of magnesium sulphate for the management of eclampsia,

preeclampsia, preterm labour, and most recently for prevention of cerebral palsy.

MECHANISM OF ACTION

Some proposed mechanisms of action include:

(1) reduced presynaptic release of the neurotransmitter glutamate,

(2) Blockade of glutamatergicN-methyl-d-aspartate(NMDA) receptors,

(3) Potentiation of adenosine action,

(4)Improved calcium buffering by mitochondria, and

(5) Blockageof calcium entry via voltage-gated channels (Arango, 2006;Wang,

2012a).13

Magnesium sulphate acts as a membrane stabilizer and neuroprotector. It reduces

motor endplate sensitivity to acetylcholine. Magnesium blocks neuronal calcium

influx also.

Figure no 9: Illustration of Mechanism of action of Magnesium sulphate on

Myometrial cell.

Courtesy:Goodman, Louis S, 19.6-2000; Gilman, Alfred, 1908-1984;Hardman, JoelG

13th ed./ editor, Laurence L.Brunton; assosciate editors Bruce A. Chabner, The

pharmacological basis of Medicine.

32

PHARMACOLOGICAL ACTIONS

Central nervous system - It depresses CNS, blocks peripheral neuromuscular

transmission and hence produces anticonvulsant effects. It promotes movement of

calcium, potassium, and sodium in a out of cells and stabilizes excitable membranes.

It also decreases amount of acetylcholine released at end-plate by motor nerve

impulse. It induces cerebral vasodilatation.37

Cardiovascular system - Slows rate of SA node impulse formation in myocardium

and prolongs conduction time.Magnesiumdecreased systemic vascular resistance and

mean arterial pressure.At the same time, it increased cardiac output withoutevidence

of myocardial depression.

Uterus - It dilates uterine arteries, increases production of endothelial prostacyclin.

Blood - inhibits platelet activation.

Respiratory system - Bronchodilator

Gastrointestinal system - Promotes osmotic retention of fluid in colon, causing

distension and increased peristaltic activity, subsequently resulting in bowel

evacuation.38

PHARMACOKINETICS

Parenterally administered magnesium is cleared almost totally by renal excretion, and

magnesium intoxication is unusual when the glomerular filtration rate is normal or

only slightly decreased. Adequate urine output usually correlates with preserved

glomerular filtration rates. Magnesium excretion is not urine flow dependent, and

urinary volume per unit time does not, per se, predict renal function. Thus,

33

serumcreatinine levels must be measured to detect a decreased glomerularfiltration

rate.

Magnesium is cleared almost exclusively by renal excretion,the dosages described

will become excessive if glomerularfiltration is substantially decreased.

Protein bound - 30%

Extracellular distribution 1-2%.39

THERAPEUTIC EFFICACY- Eclamptic convulsions are almost always prevented

orarrested by plasma magnesium levels maintained at 4 to7 mEq/L, 4.8 to 8.4 mg/dL,

or 2.0 to 3.5 mmol/L.13

DRUG INTERACTION

Magnesium sulphate binds with tetracyclines like demeclocycline, doxycycline and

minocycline

Magnesium sulphate interacts with bisphosphonates

Magnesium sulphate interacts with levothyroxine

Magnesium sulphate interacts with fluoroquinolones

USES OTHER THAN ECLAMPSIA

1. Oral magnesium sulphate preparations is used as laxative or osmotic purgative.

2. Used in replacement therapy for hypomagnesimia

3. Magnesium sulphate is aantiarrhthmic agent for torsades de pointes in cardiac

arrest under the ECC guidelines and for managing quinidine-induced arrhythmias.

4. Used as a bronchodilator in severe exacerbations of asthma.

5. It is used in agriculture, food preparation, and aquariums.39

35

ADVERSE EFFECTS AND TOXICITY PROFILE

Patellar reflexes disappear when the plasma magnesium levelreaches 10 mEq/L—

about 12 mg/dL—presumably because ofa curariform action. This sign serves to warn

of impendingmagnesium toxicity.

When plasma levels rise above 10 mEq/L,breathing becomes weakened. At 12 mEq/L

or higher levels,respiratory paralysis and respiratory arrest follow.40,41

MAGNESIUM SULPHATE - TO CONTROL CONVULSIONS

In more severe cases of preeclampsia and in eclampsia, magnesium sulphate

administered parenterally is an effective anticonvulsant that avoids producing central

nervoussystem depression in either the mother or the infant.

It has no detrimental effects on the neonate within therapeutic level. It has got

excellent result with maternal mortality of 3%. It does not control hypertension.

It may begiven intravenously by continuous infusion or intramuscularly by

intermittent injections.42

DOSAGE REGIMEN

Continuous intravenous (IV) regimen

• Give 4- to 6-g loading dose of magnesium sulphate diluted in 100 mL of IV

fluid administered over 15–20 min

• Begin 2 g/hr in 100 mL of IV maintenance infusion. Some recommend 1 g/hr

• Monitor for magnesium toxicity:

• Assess deep tendon reflexes periodically

36

• Some measure serum magnesium level at 4–6 hr and adjust infusion to

maintain levels between 4 and 7 mEq/L (4.8to 8.4 mg/dL)

• Measure serum magnesium levels if serum creatinine ≥ 1.0 mg/dL

• Magnesium sulphate is discontinued 24 hr after delivery.34

Intermittent intramuscular regimen

• Give 4 g of magnesium sulphate (MgSO4·7H2O USP) as a 20% solution

intravenously at a rate not to exceed 1 g/min

• Follow promptly with 10 g of 50% magnesium sulphate solution, one half (5

g) injected deeply in the upper outerquadrant of each buttock through a 3-inch-

long 20-gauge needle. (Addition of 1.0 mL of 2% lidocaine

minimizesdiscomfort.)

• If convulsions persist after 15 min, give up to 2 g more intravenously as a

20% solution at a rate notto exceed 1 g/min.

• If the woman is large, up to 4 g may be given slowly

• Every 4 hr thereafter, give 5 g of a 50% solution of magnesium sulphate

injected deeply in the upper outer quadrant ofalternate buttocks, but only after

ensuring that:

• The patellar reflex is present,

• Respirations are not depressed, and

• Urine output the previous 4 hr exceeded 100 mL

• Magnesium sulphate is discontinued 24 hr after delivery.35

Becauselabour and delivery is a more likely time for convulsions todevelop, women

with preeclampsia-eclampsia usually aregiven magnesium sulphate during labour and

for 24 hourspostpartum.

37

Table no 6: Regimens of magnesium sulphate for the management of eclampsia.43

REGIMENS OF MGSO4 FOR THE MANAGEMENT OF SEVERE PRE-

ECLAMPSIA AND ECLAMPSIA

Other Regimens -

Dhaka regimen - The loading dose of magnesium sulphate 4gm IV in dilution and 3

gm IM in each buttock (10gms). Followed by a maintenance dose of 2.5gm

intramuscular every 4 hourly for 24 hours after administration of the first dose.

Padhar regimen - The loading dose of magnesium sulphate 4gm IV in dilution and

3gm IM in each buttock. Followed by a maintenance dose of 4g intramuscular every

4th hourly for 24 after administration of the first dose or till the delivery whichever

comes first.

Lytic cocktail regimen - Menon in India employed the regime using chlorpromazine,

phenargan and pethidine and has got satisfactory result with reduction of maternal

mortality to 2.2%

Lean regimen (Diazepam therapy) - Diazepam is used in initial dose of 40mg IV. A

further 40mg in 500ml in 5% dextrose is infused at 30 drops per min or adjusted as

per need. Maternal mortality rate using this regimen is 5%.

REGIMEN LOADING DOSE MAINTAINANCE

DOSE

INTRAMUSCULAR

(Pritchard)

4g IV over 3-5min

followed by 10g deep IM

(5g in each buttock)

5g IM 4 hourly in alternate

buttock

INTRAVENOUS

(Zuspan or Sibai)

4-6g IV over 15-20min 1-2gm/hr IV infusion

38

Phenytoin therapy - Phenytoin is also used to control convulsions. It is given by

slow IV with monitoring. Initial dose is 10mg/kg followed by 5mg/kg two hours

later.Thereafter 200mg is given orally after 12 hours and continued until 48hours after

delivery.44

Figure no 8: Comparision of serum magnesium levels in mEq/L following

intravenous and intramuscular regimen.

Courtesy :Sibai BM, Graham JM, McCubbin JH. A comparison of intravenous and

intramuscular magnesium sulfate regimens in preeclampsia. Am J ObstetGynecol

1984;150:728–33.

In only 5 of 245 women with eclampsia atParkland Hospital was it necessary to use

supplementaryanticonvulsant medication to control convulsions. For these, an

intravenous barbiturate is given slowly.Midazolam or lorazepam may be given in a

small single dose,but prolonged use is avoided because it is associated with ahigher

mortality rate.

39

Foetal and Neonatal Effects.

Magnesium administered parenterallypromptly crosses the placenta to achieve

equilibriumin foetal serum and less so in amniotic fluid.Levels in amniotic fluid

increase with duration of maternal infusion. Current evidence supports theview that

magnesium sulphate has small but significant effectson the foetal heart rate pattern—

specifically beat-to-beat variability. At high serum magnesium levels the CNS is

depressed, neonates have profound respiratory depression requiring mechanical

ventilation. It is also associated with failure to pass meconium (meconium plug

syndrome). Hallak and coworkerscompared an infusion ofmagnesium sulphate with a

saline infusion. These investigatorsreported that magnesium was associated with a

small and clinicallyinsignificant decrease in variability. Similarly, in a

retrospectivestudy, Duffy and associates reported a lowerheart rate baseline that was

within the normal range; decreasedvariability; and fewer prolonged decelerations.

They noted noadverse outcomes.45,46

Overall, maternal magnesium therapy appears safe forperinates. For example, a recent

MFMU Network study ofmore than 1500 exposed preterm neonates found no

associationbetween the need for neonatal resuscitation and cordblood magnesium

levels. Still, there area few neonatal adverse events associated with its use. In

aParkland Hospital study of 6654 mostly term exposed newborns,6 percent had

hypotonia.In addition, exposed neonates had lower 1 and 5minute APGAR scores, a

higher intubation rate, and more admissionsto the special care nursery. The study

showed that neonataldepression occurs only if there is severehypermagnesemia

atdelivery.Observational studies have suggested a protective effect ofmagnesium

against the development of cerebral palsy in verylow-birthweight infants. Nguyen and

colleagues expanded this possibility to include term newbornneuroprotection.They

40

performed a Cochrane Database review to compareterm neonatal outcomes with and

without exposure toperipartum magnesium therapy and reported that there

wereinsufficient data to draw conclusions. Several neonatal complications are

significantly related to increasing concentration of magnesium in maternal circulation.

Long-term useof magnesium, given for several days for tocolysis, has beenassociated

with neonatal osteopenia.47-49

Maternal Safety and Efficacy of Magnesium Sulphate.

The multinational Eclampsia Trial Collaborative Group study involved 1687 women

with eclampsia randomly allocated to different anticonvulsant regimens. In one

cohort, 453 women were randomly assigned to be given magnesium sulphate and

compared with 452 given diazepam. In a second cohort, 388 eclamptic women were

randomly assigned to be given magnesium sulphate and compared with 387 women

given phenytoin. The results of these and othercomparative studies that each enrolled

at least 50 women aresummarized in Table. In aggregate, magnesium sulphatetherapy

was associated with a significantly lower incidence ofrecurrent seizures compared

with women given an alternativeanticonvulsant - 9.7 versus 23 percent. Importantly,

thematernal death rate of 3.1 percent with magnesium sulphatewas significantly lower

than that of 4.9 percent for the otherregimens.

Magnesium safety and toxicity was recently reviewed by Smith and coworkers. In

more than 9500 treatedwomen, the overall rate of absent patellar tendon reflexes

was1.6 percent; respiratory depression 1.3 percent; and calciumgluconate

administration 0.2 percent. They reported only onematernal death due to magnesium

toxicity. Our anecdotalexperiences are similar—in the estimated 50 years of its use

41

inmore than 40,000 women, there has been only one maternaldeath from an

overdose.50

Table no 7: Randomised control trial of magnesium sulphate with another.51

anticonvulsants to prevent recurrent eclamptic convulsions.

STUDY Comparing

drug

Recurrent seizures

MgSO4 (%) Other drug

(%) RR (95%CI)

Crowther52

(1990)

Diazepam

5/24

7/27

0.80

(0.29-2.2)

Bhalla53 (1994) Lytic cocktail 1/45 11/45 0.09(0.1-0.68)

Eclampsia

Trial

Colloborative

group(1995)

Phenytoin

60/453 126/452 0.48

(0.36-0.63)

Diazepam 22/388 66/387 0.33

(0.21-0.53)

TOTAL 88/910

(9.7)

210/911

(23)

0.41

(0.32-0.51)

Who Should Be Given Magnesium Sulphate?

Magnesium will prevent proportionately more seizures in women with

correspondingly worse disease. As previously discussed,however, severity is difficult

to quantify, and thus itis difficult to decide which individual woman might

benefitmost from neuroprophylaxis. The 2013 Task Force recommends that women

with either eclampsia or severe preeclampsia should be given magnesium sulphate

prophylaxis.At the same time, however, the 2013 Task Force suggests thatall women

with “mild” preeclampsia do not need magnesiumsulphate neuroprophylaxis. The

conundrum is whether or not togive neuroprophylaxis to any of these women with

“nonsevere”gestational hypertension or preeclampsia.54

In many other countries, and principally following disseminationof the Magpie Trial

Collaboration Group studyresults, magnesium sulphate is now recommended for

42

womenwith severe preeclampsia. In some, however, debate continuesconcerning

whether therapy should be reserved for women whohave an eclamptic seizure. We are

of the opinion that eclamptic seizures are dangerous.Maternal mortality rates of up to

5 percent have been reported even in recent studies. Moreover, thereare substantially

increased perinatal mortality rates in both industrializedcountries and underdeveloped

ones. Finally, the possibility of adverse long-term neuropsychologicaland vision-

related sequel of eclampsia described byAukes, Postma, Wiegman, and

theircoworkers, have raised additionalconcerns that eclamptic seizures are not

“benign.”55

Selective versus Universal Magnesium Sulphate Prophylaxis

There is uncertainty around which women with non-severe gestational hypertension

should be given magnesium sulphate neuroprophylaxis. An opportunity to address

these questions was afforded by a change in our prophylaxis protocol for women

delivering at Parkland Hospital. Before this time, Lucas and associates had found that

the risk of eclampsia without magnesium prophylaxis was approximately 1 in 100 for

women with mild preeclampsia. Up until 2000, all women with gestational

hypertension were given magnesium prophylaxis intramuscularly as first described by

Pritchard in 1955. After 2000, we instituted a standardized protocol for intravenously

administered magnesium sulphate. At the same time, we also changed our practice of

universal seizure prophylaxis for all women with gestational hypertension toone of

selective prophylaxis given only to women who met ourcriteria for severe gestational

hypertension. These criteria, shown in Table, included women with ≥ 2+ proteinuria

measured by dipstick in a catheterized urine specimen. Following this protocol

43

change, 60 percent of 6518 women with gestational hypertension during a 4½-year

period were given magnesium sulphate neuroprophylaxis.56

Table no 8:Selective versus Universal MagnesiumSulphate Prophylaxis

Selective versus Universal MagnesiumSulphate Prophylaxis: Parkland

Hospital

Criteria to Define Severity of GestationalHypertension

In a woman with new-onset proteinuric hypertension,at least one of the

following criteria is required:

Systolic BP > 160mmHg

Diastolic BP >110mmHg

Proteinuria > 2+ dipstick in a catheterized specimen

Serum creatinine >1.2mg/dL

Platelet count < 100,000/uL

AST Elevated 2 times above upper limit of normal

response

Persistent headache or scotoma

Persistent mid epigastric or right-upper quadrant pain

The remaining 40 percent with nonsevere hypertension werenot treated, and of these,

27 women developed eclamptic seizures—1 in 92. The seizure rate was only 1 in 358

for 3935women with criteria for severe disease who were given magnesiumsulphate,

and thus these cases were treatment failures.To assess morbidity, outcomes in 87

eclamptic women werecompared with outcomes in all 6431 noneclamptic

hypertensivewomen. Although most maternal outcomes were similar,almost a fourth

of women with eclampsia who underwentemergent caesarean delivery required

general anaesthesia. This isa great concern because eclamptic women have

44

laryngotrachealoedema and are at a higher risk for failed intubation, gastric

acidaspiration. Neonatal outcomes were also a concernbecause the composite

morbidity which was significantly increased tenfold in eclamptic compared

withnoneclamptic women—12 versus 1 percent, respectively.Thus, if one uses the

Parkland criteria for nonsevere gestationalhypertension, about 1 of 100 such women

who are notgiven magnesium sulphate prophylaxis can be expected to have

aneclamptic seizure. A fourth of these women likely will requireemergent caesarean

delivery with attendant maternal and perinatalmorbidity and mortality from general

anaesthesia. From this, themajor question regarding management of nonsevere

gestational hypertension remains—whether it is acceptable to avoid

unnecessarytreatment of 99 women to risk eclampsia in one? Theanswer appears to be

yes as suggested by the 2013 Task Force.57

Management of Severe Hypertension

Dangerous hypertension can cause cerebrovascular haemorrhageand hypertensive

encephalopathy, and it can trigger eclampticconvulsions in women with preeclampsia.

Other complicationsinclude hypertensive afterload congestive heart failure and

placental abruption.Because of these sequel, the National High BloodPressure

Education Program Working Group (2000) and the2013 Task Force recommend

treatment to lower systolic pressuresto or below 160 mm Hg and diastolic pressures to

orbelow 110 mm Hg. Martin and associates (2005) reportedprovocative observations

that highlight the importance of treating systolic hypertension. They described 28

selectedwomen with severe preeclampsia who suffered an associatedstroke. Most of

these were haemorrhagic strokes - 93 percentand all women had systolic pressures >

160 mm Hgbefore suffering their stroke. By contrast, only 20 percent of these same

45

women had diastolic pressures > 110 mm Hg. Itseems likely that at least half of

serious haemorrhagic strokesassociated with preeclampsia are in women with chronic

hypertension. Long-standing hypertensionresults in development of Charcot-

Bouchard aneurysmsin the deep penetrating arteries of the lenticulostriate branchof

the middle cerebral arteries. These vessels supply the basalganglia, putamen,

thalamus, and adjacent deep white matter,as well as the pons and deep cerebellum.

These unique aneurysmalweakenings predispose these small arteries to ruptureduring

sudden hypertensive episodes.54

Antihypertensive Agents

Several drugs are available to rapidly lower dangerously elevatedblood pressure in

women with the gestational hypertensive disorders.The three most commonly

employed are hydralazine,labetalol, and nifedipine. For years, parenteral hydralazine

wasthe only one of these three available. But when parenteral labetalolwas later

introduced, it was considered to be equally effectivefor obstetrical use. Orally

administered nifedipine has sincethen gained some popularity as first-line treatment

for severegestational hypertension.

Hydralazine

This is probably still the most commonly used antihypertensiveagent for treatment of

women with severegestational hypertension. Hydralazine is administered

intravenouslywith a 5 mg initial dose, and this is followed by 5 to10mg doses at 15 to

20minute intervals until a satisfactory response is achieved. Some limit the total dose

to 30 mg per treatment cycle. The target response antepartumor intrapartum is a

decrease in diastolic blood pressure to 90 to110 mm Hg. Lower diastolic pressures

46

risk compromised placentalperfusion. Hydralazine has proven remarkably effective to

prevent cerebral haemorrhage. Its onset of action can be asrapid as 10 minutes.

Although repeated administration every15 to 20 minutes may theoretically lead to

undesirable hypotension,this has not been our experience when given in these5 to

10mg increments.At Parkland Hospital, between 5 and 10 percent of allwomen with

intrapartum hypertensive disorders are given aparenteral antihypertensive agent. Mo

As with any antihypertensive agent, the tendency to give alarger initial dose of

hydralazine if the blood pressure is highermust be avoided. The response to even 5 to

10mg doses cannotbe predicted by hypertension severity. Thus, protocolis to always

administer 5 mg as the initial dose.In some cases, this foetal response to

diminisheduterine perfusion may be confused with placental abruptionand may result

in unnecessary and potentially dangerous emergentcaesarean delivery.55

Labetalol

This effective intravenous antihypertensiveagent is an α1- and nonselective β blocker.

Some preferits use over hydralazine becauseof fewer side effect. 10mg intravenously

dose is given initially. If theblood pressure has not decreasedto the desirable level in

10 minutes,then 20 mg is given. The next 10 minute incremental dose is 40mg and is

followed by another40 mg if needed. If a salutaryresponse is not achieved, then

an80mg dose is given. Sibairecommends 20 to 40 mg every10 to 15 minutes as

needed anda maximum dose of 220 mg pertreatment cycle. The AmericanCollege of

Obstetricians andGynecologistsrecommends starting with a 20mgintravenous bolus. If

not effective within 10 minutes, this is followedby 40 mg, then 80 mg every 10

minutes. Administrationshould not exceed a 220mg total dose per treatment cycle.

47

Hydralazine versus Labetalol

Comparative studies of these two antihypertensive agents show equivalent results. In

an older trial, Mabie and colleagues compared intravenous hydralazine withlabetalol

for blood pressure control in 60 peripartum women.

Labetalol lowered blood pressure more rapidly, and associatedtachycardia was

minimal. However, hydralazine loweredmean arterial pressures to safe levels more

effectively. In a latertrial, Vigil-De Gracia and associates randomly assigned

200 severely hypertensive women intrapartum to be given either:

(1) Intravenous hydralazine—5 mg, which could be given every20 minutes and

repeated to a maximum of five doses, or

(2) Intravenous labetalol—20 mg initially, followed by 40 mgin 20 minutes and then

80 mg every 20 minutes if needed upto a maximum 300mg dose.

Maternal and neonatal outcomeswere similar. Hydralazine caused significantly more

maternaltachycardia and palpitations, whereas labetalol more frequentlycaused

maternal hypotension and bradycardia. Both drugs have been associated with a

reduced frequency of foetal heart rate accelerations.13

Nifedipine

This calcium-channel blocking agent has become popularbecause of its efficacy for

control of acute pregnancy-relatedhypertension. The Royal College of Obstetricians

and Gynaecologists recommenda 10mg initial oral dose to be repeated in 30 minutesif

48

necessary. Nifedipine given sublingually is no longer recommended. Randomized

trials that comparednifedipine withlabetalol found neither drug definitively superior to

the other.However, nifedipine lowered blood pressure more quickly.56

Other Antihypertensive Agents

A few other generally available antihypertensive agents have beentested in clinical

trials but are not widely used. Belfort and associates administered the calcium

antagonistverapamilby intravenous infusion at 5 to 10 mg per hour.Mean arterial

pressure was lowered by 20 percent. Belfort andcoworkers reported that

nimodipinegiven eitherby continuous infusion or orally was effective to lower

bloodpressure in women with severe preeclampsia. Bolte and colleaguesreported good

results in preeclampticwomen given intravenous ketanserin, a selective serotonergic

(5HT2A) receptor blocker. Nitroprussideor nitroglycerineis recommendedby some if

there is not optimal response to first-lineagents. With these latter two agents, foetal

cyanide toxicity maydevelop after 4 hours. There are experimental antihypertensive

drugs that maybecome useful for preeclampsia treatment. One is calcitoningene

related peptide (CGRP),a 37amino acid potent vasodilator.Another is antidigoxin

antibody Fab (DIF) directed against endogenous digitalis-like factors, also called

cardiotonic steroids.13

Diuretics

Potent loop diuretics can further compromise placental perfusion.Immediate effects

include depletion of intravascularvolume, which most often is already reduced

compared withthat of normal pregnancy. Therefore, before delivery,diuretics are not

used to lower blood pressure.

49

In a randomised control study by Bhattacharje N et al. evaluated the efficacy of

intravenous low-dose magnesium sulphate for the management of eclampsia. A total

of 144 women with eclampsia were divided into a study group and a control group of

72 women each. The study group received 0.75 g/h of magnesium sulphate

intravenously after a loading intravenous dose of 4g and the control group was given

the standard intramuscular regimen as advocated by Pritchard. The primary outcome

measure was recurrence rate of the seizures. The secondary outcome measures were

development of magnesium toxicity if any, and maternal and perinatal outcomes. The

difference in the incidence of fit recurrence was statistically insignificant when both

groups were compared (7.46% vs 8.57%, p = 0.939). The total dose of magnesium

sulphate was significantly lower in the intravenous group (p < 0.0001), in which no

patient developed magnesium toxicity. Low-dose intravenous magnesium sulphate

was found to be as effective as the standard intramuscular regimen, while maintaining

a high safety margin.56

A prospective randomized study by Sahu L et al. of fifty eclampsia cases, treated with

magnesium sulphate (25 each with low dose regime and Pritchard regime) was carried

out from October 2010 to January 2012 at MAMC & LNH, New Delhi, India. In the

study, convulsions were controlled in 96% of eclampsia cases with low dose

magnesium sulphate regimen. One case i.e. 4% had single episode of recurrence of

convulsion, which was controlled by giving additional drugs and shifted to standard

dose regimen. There was no maternal mortality. The maternal and perinatal morbidity

and mortality in the study were comparable to those of standard Pritchard’s regimen.

The study did not find a single case of magnesium related toxicity with low dose

51

METHODOLOGY

This is a prospective, interventional study conducted

• To compare the neonatal outcome in eclamptic mothers treated with low-dose

magnesium sulphate regimen and standard dose magnesium sulphate regimen,

and

• To determine the safety, efficacy and side effect profile of magnesium

sulphate regimens. Also to determine the predisposing risk factors associated

with eclampsia.

SOURCE OF DATA - This prospective study was conducted on patients

witheclampsia in the eclampsia ward of department of obstetrics and gynaecology at

MCGANN TEACHING DISTRICT HOSPITAL SIMS (Shivamogga institute of

medical sciences), SHIVAMOGGA.

STUDY DESIGN - This is a prospective randomised comparative open labelled

single centred study.

STUDY DURATION - This study was conducted for the duration of one year from

December 2016 to January 2018.

ETHICS CLEARANCE: Ethics clearance obtained from the IEC (Institutional

Ethics committee) With the ethics clearance Reference No: SIMS/IEC/272/2016-17

MATERIALS USED IN THE STUDY -

1) Injection magnesium sulphate 2 ml ampoule.

52

2) Automated clinical chemical analyzer - for the assessment of serum and cord

magnesium levels

3) Clinical examination kit - (knee hammer, stethoscope etc)

4) Standard case record form

INCLUSION CRITERIA

1. Mothers diagnosed with eclampsia- history of generalised tonic clonic seizure

with increased blood pressure more than 140/90 mmHg, proteinuria > 1+ by

dipstick method in the absence of underlying seizure disorder >20 weeks of

pregnancy.

2. All cases of antepartum, intrapartumeclampsia presenting in obstetric

emergency, labour rooms and eclamptic wards.

3. Those who gave informed consent to participate in the study.

EXCLUSION CRITERIA:

1. Eclampsia with complications like HELLP syndrome, renal failure, severe

pulmonary oedema, respiratory failure, cardiovascular diseases, and

disseminated intravascular coagulation.

2. Patients who received magnesium sulphate before coming to hospital.

3. Patients with known seizure disorder.

4. Neonates of multiple pregnancy, very low birth weight(<1500gm), congenital

malformations.

METHODOLOGY

Totally 110 patients diagnosed with eclampsia and their neonates were screened in

obstetrics and gynaecology department of MC GANN TEACHING DISTRICT

53

HOSPITAL, SHIVAMOGGA. Out of 110, 10 patients with eclampsia and their

neonates couldn't meet the eligibility criteria, hence were excluded from the study.The

patients who met the inclusion criteria then were randomised into two groups.

Method of randomization: Patients included in the study as per the inclusion

andexclusion criteria were randomised into two groups by using block randomization

with a fixed block size 4 and allocation ratio 1:1 having equal chance of equal

distribution of patients into two groups. Computer generated random numbers in

Microsoft Excel 2007was used for allocation of block randomization.

Study procedure

Patients diagnosed with eclampsia by Obstetrics faculty in the eclampsia ward or

labour room were approached. Patient were stabilized initially by keeping them on a

railed cot and a tongue blade inserted between the teeth. They were kept in the

lateraldecubitus position to avoid aspiration. Vomitus and oral secretions were

removed by frequent suctioning, oxygenation was maintained through a face mask (8–

10 L/min) to prevent respiratory acidosis. Oxygenation was monitored using a

transcutaneous pulse oximeter. To take informed consent, their legal guardian/blood

relative were informed about the purpose of the study, study procedure, hospital staff

involved in the study, protocol of the study and about the treatment options available

to them, information about the investigations that will be carried out and the

information about the drug regimen used and their adverse effects in their own

understandable language.

54

Once explained, Informed consent(Annexure I) was taken from the patients guardian

who were willing to let their daughter/wife to participate in the study.Also once the

patient was stabilized, she was also explained in detail about the nature, purpose and

protocol of the study and Informed consent was taken from the patient too.

Patients and their guardians were explained that they can refuse or withdraw from the

study at any time and that will not affect her treatment in the hospital.

After obtaining informed consent from the patient/legal guardian of the patient

detailed history was obtained and recorded in the standard case record form.

The patients prior to their allotment into the study groups were enquired about

detailed information regarding no. of episodes of seizure before coming to the

hospital, past history of seizure disorder, last menstrual period(LMP), headache,

blurring of vision, epigastric pain, past history of preeclampsia/eclampsia in previous

pregnancy if any, similar family history and treatment taken for management of

seizure before coming to the hospital. General physical examination was conducted

including blood pressure recordings, vital signs, pallor, oedema and cyanosis.

Systemic examination included central nervous system, respiratory system and

cardiovascular system. Obstetric and pelvic examination was done by obstetrics

faculty. Routine laboratory investigations were done which included blood group and

Rh type, haemogram, platelet count, liver function tests, renalfunction tests, serum

electrolytes, coagulation profile, andurinary protein concentration.

The eligible patients were randomised into two groups

Group A (n=50) - received low dose magnesium sulphate regimen (Bankura regimen)

55

Group B (n=50) - received standard dose magnesium sulphate regimen (Pritchard's

regimen)

The patient in both the groups were admitted in eclampsia ward and examined in

detail for any complication due to eclampsia by continuous monitoring.

Group ‘A’received low dose magnesium sulphate -Bankura regimen. This comprised

of a loading dose of 3 grams magnesium sulphate prepared from, 6ml of magnesium

sulphate solution diluted with 5% dextrose solution and made upto 15ml, given

intravenously slowly at the rate of 1ml/min and 2.5 grams(5ml) of magnesium

sulphategiven intramuscular in each buttock. Followed by a maintenance dose of

2.5grams given 4 hourly in alternate buttock.

Group B received magnesium sulphate as per Pritchard’s regimen. This included a

loading dose of 4 grams of magnesium sulphate prepared from 8ml of magnesium

sulphate solution diluted with 5% dextrose solution and made upto 20ml given slowly

intravenously at the rate of 1ml/min and 5 grams (10ml) of magnesium sulphate deep

intramuscularly in each buttock. Followed by maintenance dose of 5 grams given 4th

hourly in alternate buttock.

After stabilization of the patient, artificial rupture of membrane and oxytocin

administration was used to induce labour, in patients who did not have a spontaneous

onset of labour, with dinoprostone gel used only occasionally when cervix was

unfavourable. Steroid therapy was given when delivery was less than <34weeks

Caesarean section was performed for obstetrical indications.

All obstetrical interventions were at the discretion of attending obstetric faculty.

56

The patients were monitored every 4th hourly till the delivery for adverse effect due

to magnesium sulphate regimens like loss of deep tendon reflexes, urinary output,

pulmonary crepitations, pulse rate, and blood pressure.

Recurrence of seizure if occurred in Group A in low dose magnesium sulphate

regimen, the patient was given immediately standard dose magnesium sulphate

regimen. If seizure recurred in Group B, they were treated with another dose of

Magnesium sulphate also when it was refractory general anaesthetic was used.

Maternal serum was collected from eclamptic mothers after giving induction of labour

and serum magnesium level was assessed in the hospital laboratory by automated

chemical analyzer. The clinical chemical analyzer used dye binding assay method for

estimation of magnesium level in the sample. Magnesium ion reacted with xylidyl

blue in an alkaline medium to form a water soluble purple-red chelate, the colour

intensity of which was proportional to concentration of magnesium in the sample.

Interference of calcium was excluded from the reaction by complexing it with

ethylene glycol tetraacetic acid (EGTA).

After the delivery the cord blood was collected either by the nursing staff or by intern

and sent to the laboratory for the assessment of magnesium level.

Neonatal birth weight, APGAR scores at 5 min was recorded. Presence of respiratory

depression, requirement of intubation in delivery room, NICU care requirement,

bradycardia and hypotonia was recorded. Monitoring of all the above mentioned

parameters in neonates was done for 24 hours. Still births and early neonatal deaths

were also noted.

57

Neonatal birth weight, APGAR score at 1, 5 min wererecorded. A maximum score of

10 and minimum score of 0was assigned to the neonates. The respiratory depression

was defined as apnoea at birth for more than 20seconds, bradycardia was defined as <

90 beats/min for > 5 s in duration. Neonatal hypotonia was diagnosed if neonate was

limp or flaccid and exhibited reduced activity. Neonatal resuscitation in the labour

room and NICU was at the decision of attending paediatric and faculty. Early neonatal

death was defined as death during first 15 days of life.

Maternal height and weight was recorded on 3rd and 4th day after delivery or when

patient was ambulatory.

Phone number was taken from the patient and follow up was also done on the 16th

day of the neonate for any adverse drug reaction. Also to enquire about any

recurrence of seizure in the mother.

The investigators phone number was also given to the patient and their guardians for

they were asked to inform if any reactions occur or convulsions develop during the 15

days of study follow up period.

STATISTICAL ANALYSIS

The data collected from the study was tabulated in Microsoft excel Microsoft Excel

2007.

Few selected data were given codes for statistical analysis in SPSS software version

20.0. (Annexure-IV). The demographic data was analysed with descriptive statistics

and compared with chi square test. All the demographic data analysed was considered

significant with a p value ≤ 0.05.

58

Pearson Correlation Coefficient was used to determine correlation between

APGARscore and cord blood magnesium level.

The Chisquare/Fisher’s exact test was used to determine whether there was

statistically significant difference between the groups with respect to primary study

parameters.

P ≤ 0.05 were considered significant

SAMPLE SIZE CALCULATION

Sample size was calculated with power of 80%. Alpha as 0.05% and expecting the

largest mean difference between two groups with 0.22 and anticipated complication

rates 8% and 30% from previous studies.12,13 Thus the sample size "n" required per

group was n=49. But n=50 patients in each group will be recruited for the study. The

total participants recruited for the study will be N=100.

59

RESULTS

There were total 110 eclampsia cases were screened during the study period and after

exclusion only 100 cases met the inclusion criteria.

9 patients were excluded from the study due to the following reasons (Fig No):

• 6 neonates had low birth weight

• 2 mothers had eclampsia with elevated liver enzymes and complication

• 1 patient had received magnesium sulphate before coming to the hospital

• 1 patient had multiple pregnancy

100 patients were randomized into two groups of 50 patients each as follows:

GROUP ‘A’ (CASE): n=50 patients and their neonates were included in the group

and analyzed in the study

GROUP ‘B’ (CONTROL): n=50 patients and their neonates were included in the

group and analyzed in the study

60

Figure no 11 : Flow chart representing the recruitment of the patients in the study.

110 patients diagnosed with

eclampsia were screened

4 patients were excluded

from the study

2 mothers -eclampsia with

complication

1 patient - received

magnesium sulphate before

coming to the hospital

1 patient - multiplepregnancy

N = 106 were randomised in two

groups

n = 53 were included

Group A

n = 53 were included in

Group B

n = 50 mothers and neonates

were analyzed who received

low dose magnesium sulphate

regimen

n = 50 mothers and neonates

were analyzed who received

standard dose magnesium

sulphate regimen

4 patients were

excluded - VLBW

neonate

2 patients were

excluded - VLBW

neonate

61

DEMOGRAPHIC PROFILE OF THE PATIENTS IN BOTH GROUP

1. AGE DISTRIBUTION

Table no. 9 - Representation of age distribution of eclamptic mothers in both

groups

AGE IN

YEARS

GROUP ᵡ2 p-value

Standard dose

group

n (%)

Low dose

group

n (%)

df= 3

4.97

0.17

18-22 23 (46) 32 (64)

23-27 17 (50) 8 (16)

28-32 7 (14) 8 (16)

32-36 3 (6) 2 (4)

Mean (+)SD 24.36+3.48 24.1+3.89

Median 26 26

IQR 4.75 9.5

Table no 9 represents the age distribution of eclamptic mothers among the two

groups. The mean age of mother for the standard dose regimen group is 24.36+3.48

and low dose regimen group is 24.1+3.89. Proportion of patients were more in the age

group between 18-22 in the standard dose regimen group and low dose regimen group

with frequency of 23 and 32 constituting 46% and 64% respectively. The minimum

and maximum age distributed among standard dose regimen group and low dose

regimen group are 20, 33 and 19, 34 respectively. There was no significant difference

in the age distribution among groups with ᵡ2(chi-square value) = 4.97 and p value

of 0.17.

62

Figure No 12: Graphical representation of distribution of age of eclamptic mothers

among both the groups.

0

5

10

15

20

25

20 - 2425 - 29

30 - 35

NO

.OF

PA

TIEN

TS

AGE IN YEARS

Standard dose

Low dose group

63

2. PARITY DISTRIBUTION

Table no 10 - Representation of distribution of parity among the mothers of both

group

GRAVIDA

STATUS/PARITY

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 1

1.08

0.29

Primigravida 39 (78) 43 (86)

Multigravida 11 (22) 7 (14)

Table no 10 represents the distribution of parity of eclamptic mothers between two

groups. The frequency (proportion) of Primigravida distributed among standard dose

regimen group and low dose regimen group is 39(78%) and 43(86%) respectively.

The frequency (proportion) of Multigravida distributed among standard dose regimen

group and low dose regimen group is 11(22%) and 7(14%) respectively. There was no

significant difference between parity distribution between groups with

x2 = 1.08 and p value of 0.29.

64

Figure No 13: Graphical representation of parity distribution among eclamptic

mothers in both the groups.

0

5

10

15

20

25

30

35

40

45

primi gravida

multigravida

NO

. OF

PATI

ENTS

GRAVIDA STATUS

Standard dose group

Low dose group

65

3. DISTRIBUTION OF ANTENATAL CARE

Table no 11 : Representation of distribution of mothers who received antenatal

care in both the groups

ANTENATAL

CARE

GROUP ᵡ2 p-value

Standard

dose group

n(%)

Low dose

group

n(%)

df = 1

0.21

0.63

Booked cases 13 (26) 11 (22)

Unbooked cases 37 (74) 39 (78)

Table no 11 represents the distribution of patients diagnosed with eclampsia who

received antenatal care in both standard dose regimen group and low dose regimen

group. The frequency of unbooked mothers in both the groups were higher with 37

patients constituting of 74% in standard dose regimen group and 39 patients in low

dose regimen group constituting of 78%. The frequency (proportion) of eclamptic

patients was least both in standard dose regimen group and low dose regimen group

with frequency of 13 patients constituting 26% and 11 patients constituting 22%

respectively. There was no significant difference in distribution of booked and

unbooked mothers between groups with x2 =0.21and p value of 0.63.

66

Figure no 14: Graphical representation distribution of antenatal care received between

both the groups.

0

5

10

15

20

25

30

35

40

Booked cases

Unbooked cases

NO

.OF

PATI

ENTS

Standard dose group

Low dose group

67

4. DISTRIBUTION OF AREAS

Table no 12: Representation of distribution of eclamptic mothers from the

different areas among both the groups

AREA

GROUP ᵡ2 p-value

Standard

dose group

n(%)

Low dose

group

n(%)

df = 1

0.79

0.37

RURAL 38(76) 34(68)

URBAN 12(24) 16(32)

Table no 12 represents the distribution of rural and urban population between two the

two groups. The frequency (proportion) of mothers from rural areas distributed among

standard dose regimen group and low dose regimen group is 38(76%) and 34(68%)

respectively. The frequency (proportion) of mothers from urban areas distributed

among standard dose regimen group and low dose regimen group is 12(24%) and

16(32%) respectively. There was no significant difference between rural and urban

population between groups with x2 = 0.79 and p value of 0.37.

68

Figure No 15: Graphical representation of distribution of eclamptic mothers in rural

and urban areas among both the groups.

0

5

10

15

20

25

30

35

40

Rural population Urban population

NO

.OF

PATI

ENTS

Standard dose regimen

Low dose regimen

69

5. GESTATIONAL AGE DISTRIBUTION

Table no 13 - Representation of distribution of gestational age among the

eclampticmothers of both the groups

PERIOD OF

GESTATION

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 3

0.24

0.96 <33 WEEKS 3 (6) 3 (6)

33-35 WEEKS 11 (22) 12 (24)

35-37 WEEKS 33 (66) 31 (62)

>37 WEEKS 3 (6) 4 (8)

MEAN(+)SD 36.44+2.78 36.2+2.32

Median 33.5 34

IQR 5 5

Table no 13 represents the distribution of period of gestation among mothers

diagnosed with eclampsia in both standard dose regimen group and low dose regimen

group. The mean period of gestation for the standard dose regimen group is

36.44+2.78 and low dose regimen group is 36.2+2.32. Proportion of patients were

more in 35-37 weeks of gestation in both the standard dose regimen group and low

dose regimen group with frequency of 33 and 31 constituting 66% and 62%

respectively. The minimum and maximum period of gestation distributed among

standard dose regimen group and low dose regimen group are 31, 37 weeks and 32,

37. There was no significant difference in the period of gestation distribution among

groups with ᵡ2(chi-square value) = 0.24 and p value of 0.96.

70

Figure No 16 : Graphical representation of distribution period of gestation in weeks of

eclamptic mothers among both the groups.

0

5

10

15

20

25

30

35

40

45

50

Standard dose group Low dose group

PR

OP

OR

TIO

N O

F P

ATI

ENTS

> 36 weeks

32 - 36 weeks

28 - 31 weeks

<28 weeks

71

6. BMI DISTRIBUTION

Table no 14 : Representation of distribution body mass index in both groups

among mothers

BODY MASS

INDEX

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 2

1.63

0.44

<19 kg/m2 15 (30) 10 (20)

20 - 25kg/m2 32 (64) 35 (70)

>25kg/m2 3 (6) 5 (10)

MEAN(+)SD 20.97+2.72 19.42+2.80

Median 19.97 21.22

IQR 3.73 4.01

Table no 14 represents the distribution of body mass index among mothers diagnosed

with eclampsia in both standard dose regimen group and low dose regimen group. The

mean body mass index for the standard dose regimen group is 20.97+2.72 and low

dose regimen group is 19.42+2.80. Proportion of patients were more with BMI 20 to

22 kg/m2 in both the standard dose regimen group and low dose regimen group with

frequency of 32 and 35 constituting 64% and 70% respectively. The minimum and

maximum body mass index distributed among standard dose regimen group and low

dose regimen group are 18, 26 kg/m2 and 17, 28kg/m2 respectively. There was no

significant difference in the body mass index distribution among groups with

ᵡ2(chi-square value) = 0.51 and p value of 0.77.

72

Figure No 17: Graphical representation of body mass index distribution in eclamptic

mothers among both the groups.

0

5

10

15

20

25

30

35

< 19 kg/m2 20 - 25 kg/m2 >25 kg/m2

NO

.OF

PA

TIEN

TS

Standard dosegroup

Low dosegroup

73

7. SYSTOLIC BLOOD PRESSURE DISTRIBUTION

Table no 15 - Representation of systolic blood pressure distribution among

mothers of both group

SYSTOLIC

BLOOD

PRESSURE

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df =2

2.31

0.31

130-150mmHg 8 (16) 10 (20)

150-170mmHg 35 (70) 28 (56)

>180mmHg 7 (14) 12 (24)

MEAN(+)SD 161.48+13.12 160+13.87

Median 159 160

IQR 7.74 6

Table no 15 represents the distribution of systolic blood pressure among mothers


group. The mean systolic blood pressure for the standard dose regimen group is

161.48+13.12 and low dose regimen group is 160+13.87. Proportion of patients were

more with systolic blood pressure 150 to 170mmHg in both the standard dose regimen

group and low dose regimen group with frequency of 35 and 28 constituting 70% and

56% respectively. The minimum and maximum systolic blood pressure distributed

among standard dose regimen group and low dose regimen group are 150, 200mmHg

and 150, 180mmHg respectively. There was no significant difference in the systolic

blood pressure distribution among groups with ᵡ2(chi-square value) = 2.31 and p

value of 0.31

74

.

Figure No 18: Graphical representation of distribution of systolic blood pressure of


0

5

10

15

20

25

30

35

130 - 150mmHg 150 - 170mmHg > 180mmHg

NO

OF

PA

TIEN

TS

Standard dosegroup

75

8. DIASTOLIC BLOOD PRESSURE DISTRIBUTION

Table no 16: Representation of distribution of diastolic blood pressure among

mothers of both groups

DIASTOLIC

BLOOD

PRESSURE

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 2

0.72

0.69

<90mmHg 18 (36) 22 (44)

100mmHg 27 (54) 23 (46)

>110mmHg 5 (10) 5 (10)

MEAN(+)SD 97.4+6.32 100+6.58

Median 100 100

IQR 10 10

Table no 16 represents the distribution of diastolic blood pressure among mothers


group. The mean diastolic blood pressure for the standard dose regimen group is

97.4+6.32 and low dose regimen group is 100+6.58. Proportion of patients were more

with diastolic blood pressure 100mmHg in both the standard dose regimen group and

low dose regimen group with frequency of 27 and 23 constituting 54% and 46%

respectively. The minimum and maximum diastolic blood pressure distributed among

standard dose regimen group and low dose regimen group are 90,100 mmHg and 90,

100mmHg respectively. There was no significant difference in the diastolic blood

pressure distribution among groups with ᵡ2(chi-square value) = 0.72 and p value

of 0.69.

76

Figure No 19: Graphical representation of distribution of diastolic blood pressure of


0

5

10

15

20

25

30

<90mmHg100mmHg

>100mmHg

NO

. OF

PA

TIEN

TS

Standard doseregimen

Low doseregimen

77

9. EPISODES OF SEIZURE DISTRIBUTION

Table no 17 - Representation of distribution of no. of episodes of seizures before

the start of treatment in eclamptic mothers among both the groups

NO.OF

CONVULSSIONS

GROUP ᵡ2 p-value

Standard

dose group

n(%)

Low dose

group

n(%)

df = 3

2.24

0.52

<3 16 (32) 19 (38)

3 - 5 22 (44) 15 (30)

5 - 7 10 (20) 14 (28)

>7 2 (4) 2 (4)

Mean 4.3+1.59 4.24+2.0

Median 3 4

IQR 2 3

Table no 17 represents the distribution of number of seizures among mothers


group. The mean number of seizures for the standard dose regimen group is 4.3+1.59

and low dose regimen group is 4.24+2.0. Proportion of patients were more with

number of seizures between 3 to 5 in both the standard dose regimen group and low

dose regimen group with frequency of 22 and 15 constituting 44% and 30%

respectively. The minimum and maximum number of episodes of seizure distributed

among standard dose regimen group and low dose regimen group are 1, 9 and 1, 8

respectively. There was no significant difference in the number of seizures before the

start of treatment distribution among groups with ᵡ2(chi-square value) = 2.24 and p

value of 0.52.

78

Figure No 20: Graphical representation of distribution of number of convulsions

before admission in eclamptic mothers among both the groups.

0

5

10

15

20

25

<3 3 to 5 5 to 7 > 7

Standard dosegroup

79

10. MODE OF DELIVERY DISTRIBUTION

Table no 18 : Representation of distribution of mode of delivery in mothers

among both groups

MODE OF

DELIVERY

GROUP ᵡ2 p-value

Standard

dose group

n(%)

Low dose

group

n(%)

df = 1

1.41

0.23

Vaginal delivery 36(72) 41(82)

Caesarean section 14 (28) 9 (18)

Table no 18 represents the distribution of mode of delivery in patients diagnosed with

eclampsia in both standard dose regimen group and low dose regimen group. The

frequency of vaginal delivery in eclamptic mothers in both the groups were higher

with 36 patients constituting of 72% in standard dose regimen group and 41 patients

in low dose regimen group constituting of 82%. The frequency (proportion) of

eclamptic patients who underwent caesarean section was least both in standard dose

regimen group and low dose regimen group with frequency of 14 patients constituting

28% and 9 patients constituting 18% respectively. There was no significant difference

in distribution of mode of delivery in eclamptic mothers between the groups with

x2 =1.41and p value of 0.23.

80

Figure No 21: Graphical representation of distribution of mode of delivery in


0

10

20

30

40

50

60

Vaginal delivery Caesarean section


Low dose regimen

81

OUTCOME MEASURES

1. BIRTH WEIGHT DISTRIBUTION

Table no 19 - Representation of distribution of birth weight among the neonates

of eclamptic mothers in both the groups

BIRTH

WEIGHT

(in grams)

GROUP ᵡ2 p-value

Standard

dose group

n(%)

Low dose

group

n(%)

df = 2

0.95

0.62

<2500 30(60) 31(62)

2500 - 3500 18(36) 15(30)

>3500 2(4) 4(8)

Mean 2624+505.30 2610+549.30

Median 2500 2500

IQR 700 700

Table no 19 represents the distribution of birth weight among mothers diagnosed with

eclampsia in both standard dose regimen group and low dose regimen group. The

mean birth weight for the standard dose regimen group is 2624+505.30 and low dose

regimen group is 2610+549.30. Proportion of patients were more with birth weight

less than 2500gm in both the standard dose regimen group and low dose regimen

group with frequency of 30 and 31 constituting 60% and 62% respectively. The

minimum and maximum birth weight distributed among standard dose regimen group

and low dose regimen group are 1800, 2000 and 3800, 3500 respectively. There was

no significant difference in the birth weight distribution among groups with

ᵡ2(chi-square value) = 0.95 and p value of 0.62.

82

Figure No 22: Graphical representation of distribution of birth weight in neonates of


0

5

10

15

20

25

30

35

< 2500 2500 - 3500 > 3500

NO

.OF

NEO

NA

TES

BIRTH WEIGHT

Standard regimen

Low dose regimen

83

2. CORD BLOOD MAGNESIUM LEVEL DISTRIBUTION

Table no 20:Representation of distribution of cord blood magnesium at time of

delivery among the neonates of eclamptic mothers in both groups

CORD BLOOD

MAGNESIUM IN

MMOL/L

GROUP

Standard dose group

n(%)

Low dose group

n(%)

1.5 - 1.8 0 3(6)

1.8 - 2.1 0 10(20)

2.1 - 2.4 0 23(46)

2.4 - 2.7 3(6) 11(22)

2.7 - 3.0 7(14) 3(6)

3.0 -3.3 15(30) 0

3.3 - 3.6 21(42) 0

3.6 - 3.9 4(8) 0

MEAN(+)SD

3.28+0.16 2.20+0.26

MEDIAN

3.25 2.2

IQR

0.2 0.37

MIN

3.0 1.7

MAX

3.8 2.7

Table no 20 represents the distribution of cord blood magnesium level among mothers


group. The mean cord blood magnesium level for the standard dose regimen group is

3.28+0.16 and low dose regimen group is 2.20+0.26. The minimum and maximum

level of cord blood magnesium distributed among standard dose regimen group and

low dose regimen group are 2.6, 3.8 mmol/l and 1.7, 2.8 mmol/l respectively.

84

Figure no 23: Graphical representation (Line diagram) of distribution of cord blood

magnesium level at the time of delivery of neonates of eclamptic mothers among both

the groups.

0

5

10

15

20

25

1.5 1.8 2.1 2.4 2.7 3 3.3 3.6 3.9

DISTRIBUTION OF CORD BLOOD MAGNESIUM LEVEL AMONG BOTH THE GROUPS

Standard dose regimen group Low dose regimen group

x axis - No. of neonates

y axis - Cord blood magnesium level

85

Table no 21 - Representation of APGAR scores at 5 min among the neonates of


APGAR

SCORE

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 2

7.56

0.02

<3 6 (12) 1 (2)

3 - 7 17 (34) 10 (20)

>7 27 (54) 39 (78)

MEAN(+)SD 6.62+2.23 8.9+1.46

Median 8 9

IQR

3.75 1

MIN

3 3

MAX

10 10

As per Table no 21 Chi square test showed that over all there is statistically

significant difference in APGAR score at 5 min between the two groups with

χ2 = 7.56 and p = 0.02, with a mean APGAR score at 5 min in standard dose regimen

group 6.62+2.23 and in low dose regimen group 8.9+1.46. The Interquartile range

between the standard dose regimen group is 3.75 and in low dose regimen group is

1.APGAR scores decreased significantly with increase in cord blood magnesium

levels. Cord blood magnesium level of severely depressed neonates (APGAR score ≤

3), was in the range of 3.5–3.9 mmol/L. This is depicted in figure no. which shows

spikes (APGAR score < 3) at cord blood magnesium level of 3.5 to 3.9 and another

spikes (APGAR score between 3-7) at cord blood magnesium level of 3.3 to

3.5mmol/L. The pearson correlation coefficient for cord blood magnesium level and

APGAR score was = -0.79, which is statistically significant.

86

Figure No 24: Graphical representation of distribution of APGAR scores of neonates

of eclamptic mothers among both the groups.

Figure No 25: Graphical representation (line diagram) of correlation of cord blood

magnesium level and APGAR scores in neonates of eclamptic mother in both the

groups

0

5

10

15

20

25

30

35

40

< 3 3 to 7

> 7

NO

. OF

NEO

NA

TES

APGAR SCORES

Standard doseregimen group

Low dose regimengroup

0

1

2

3

4

5

6

7

8

9

10

1.5 1.7 1.9 2.1 2.3 2.5 2.7 2.9 3.1 3.3 3.5 3.7 3.9

No

. of

ne

on

ate

s

CORRELATION

< 3

3 TO 7

87

4. NICU CARE DISTRIBUTION

Table no : 22 - Representation of requirement of NICU care among the neonates

of eclamptic mothers in both groups

INCIDENCE

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 1

17.36

<0.001

NICU care

required 28(56) 8(16)

NICU care not

required 22(44) 42(84)

As per Table no 22 The Chi square test showed that over all there is statistically

significant difference in NICU care requirement between the two groups with

χ2 = 17.36 and p = <0.001, with a proportion of neonates who required NICU care in

standard dose regimen group were 56% and low dose regimen group were 16%.

NICU care requirement increased significantly with increase in cord blood

magnesium levels. The number of neonates who required NICU care were more when

they had cord blood magnesium level in the range of 3.5 to 3.8 mmol/l. This is

depicted in the figure no. which shows a scatter plot, where the neonates admission in

the NICU is seen to be scattered more with the higher level of cord blood

magnesium. Proportion of neonates admitted in NICU varied from 70 - 100% at the

cord blood magnesium level between 3.5 - 3.8mmol/l.

88

Figure No 26 : Graphical representation of distribution of NICU care requirement in

neonates of eclamptic mothers among both the groups.

Figure No 27: Graphical representation of distribution of NICU care requirement in

neonates of eclampticmothers scattered among both the groups.

0

5

10

15

20

25

30

35

40

45

50

Standard dose groupLow dose group

NICU care not required

NICU care required

0

20

40

60

80

100

120

0 1 2 3 4 5

Pe

rce

nta

ge o

f ad

mis

sio

n

Cord blood magnesium level

NICU care requirement


89

5. RESPIRATORY DISTRESS DISTRIBUTION

Table no 23 - Representation of incidence of respiratory distress among the


GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 1

5.74

0.01 Respiratory

distress

13(26) 4(8)

No respiratory

distress

37(74) 46(92)


significant difference in incidence of respiratory distress between the two groups with

χ2 = 5.74 and p = 0.01, with a proportion of neonates who had respiratory distress in

standard dose regimen group was 26% and low dose regimen group was 8%.

90

Figure No 28: Graphical representation of distribution of incidence of respiratory

distress in neonates of eclamptic mothers among both the groups.

Figure No 29: Graphical representation (box plot) of distribution of incidence of

respiratory distress in neonates of eclamptic mothers in the box plot form among both

the groups.

0

5

10

15

20

25

30

35

40

45

50

Respiratory distress Normal breathing

NO

.OF

PA

TIEN

TS

StandardDose group

Low dosegroup

0

10

20

30

40

50

60

Standard dose regimen Low dose regimen

91

6. HYPOTONIA DISTRIBUTION

Table no 24 - Representation of incidence of hypotonia among the neonates of


GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 1

13.22

0.0002

Presence of

Hypotonia

27 4

No Hypotonia 23 46


significant difference in incidence of hypotonia between the two groups with

χ2 = 17.36 and p = <0.001, with a proportion of neonates who had hypotonia in


Figure No 30: Graphical representation of distribution of incidence of hypotonia in


0

5

10

15

20

25

30

35

40

45

50

Hypotonia Normal muscle tone


Low dose regimen

92

7. BRADYCARDIA DISTRIBUTION

Table no 25 - Representation of incidence of bradycardia among the neonates of


INCIDENCE

GROUP ᵡ2 p-value

Standard dose

group

n(%)

Low dose

group

n(%)

df = 1

9.49

0.002 Bradycardia 13(26) 2(4)

No

Bradycardia

37(74) 44(88)


significant difference in incidence of bradycardia between the two groups with

χ2 = 9.49 and p = 0.002, with a proportion of neonates who had bradycardia in


Figure No 31: Graphical representation of distribution of incidence of bradycardia in


0

5

10

15

20

25

30

35

40

45

Bradycardia

Normal heart rate

NO

. OF

PA

TIEN

TS

Standard dosegroup

Low dosegroup

93

SAFETY PARAMETERS

1. SERUM MAGNESIUM LEVEL DISTRIBUTION

Table no 26 - Representation of serum magnesium level at the time of delivery in

eclamptic mothers among both groups

SERUM MAGNESIUM

LEVEL IN M MOL/L

GROUP

Standard dose group

n(%)

Low dose group

n(%)

1.8 - 2.1 0 10(20)

2.1 - 2.4 0 21(42)

2.4 - 2.7 0 11(22)

2.7 - 3.0 0 19(38)

3.0 -3.3 6(12) 0

3.3 - 3.6 38(76) 0

3.6 - 3.9 6(12) 0

MEAN(+)SD

3.40+0.16 2.31+0.26

MEDIAN

3.4 2.3

IQR

0.2 0.3

MIN

3.1 1.8

MAX

3.9 2.8

Table no 26 represents the distribution of serum magnesium level among mothers


group. The mean serum magnesium level for the standard dose regimen group is

3.40+0.16 and low dose regimen group is 2.31+0.26. The minimum and maximum

level of cord blood magnesium distributed among standard dose regimen group and

low dose regimen group are 3.1, 3.9 mmol/l and 1.8, 2.8 mmol/l respectively.

94

Figure no 32. Graphical representation (Line diagram) of distribution of serum

magnesium level at the time of delivery of eclamptic mothers among both the groups.

0

5

10

15

20

25

30

35

1.8 2.1 2.4 2.7 3 3.3 3.6 3.9

Standard group

Low dose group

x axis - No. of neonates

y axis - serum magnesium level (at the time of delivery)

95

Table no 27 - Adverse effects of the magnesium sulphate regimens used in the

study.

NEONATAL ADVERSE EVENTS

ADVERSE

DRUG

EVENTS

GROUPS

ᵡ2 p value

Standard dose

regimen, n

Low dose

regimen, n

Still birth 2 1 0.34 0.55

Early neonatal

death 0 0

MATERNAL ADVERSE EVENTS

ADVERSE

DRUG

REACTIONS

GROUPS

ᵡ2 p value

Standard dose

regimen, n

Low dose

regimen, n

Aspiration

pneumonia 2 0 2.04 0.15

Oliguria 8 1 8.69 0.003

Seizure

recurrance 3 5 0.54 0.46

Loss of DTR 13 2 14.94 <0.0001

Maternal

mortality 0 0

96

In the study the neonatal adverse drug event observed was still birth, which was seen

in one case in low dose magnesium sulphate group compared to two cases in standard

dose regimen group, and the result did not show any statistical significance. There

was no early neonatal mortality documented in the study.

In the study the adverse drug events observed in mothers were loss/decreased deep

tendon reflexes, oliguria, seizure recurrence and aspiration pneumonia. In low dose

magnesium sulphate regimen group the proportion of adverse event observed were

loss of deep tendon reflex (4%), oliguria (2%), seizure recurrence(10%). There was

no aspiration pneumonia and maternal mortality reported in the low dose group. In the

standard dose magnesium sulphate regimen group the proportion of adverse event

observed were loss of deep tendon reflex (26%), oliguria (16%), seizure recurrence

(6%) and aspiration pneumonia (4%). There was no maternal mortality reported in the

standard dose regimen group. Low dose magnesium sulphate regimen group showed

statistical significant less number of adverse events loss/decreased deep tendon reflex

and oliguria.

The figure no depicts correlation between serum magnesium level in mothers at the

time of delivery and adverse events loss of DTR and oliguria. Both show statistical

significant higher adverse events at the range of 3.3-3.9mmol/l. The graphs no depicts

spikes at the serum magnesium level of 3.4 to 3.9mmol/l representing higher number

of cases with adverse events.

The figure no depicts correlation between serum magnesium level in mothers at the

time of delivery and adverse events aspiration pneumonia and seizure recurrence.

Both did not show statistical significant higher or lower adverse events.

97

Figure no 33. Graphical representation of distribution of adverse events in eclamptic

mothers among both the groups.

0

2

4

6

8

10

12

14

Standard doseregimenLow doseregimen

98

Figure no 34. Graphical representation of correlation of serum magnesium level and

adverse events in eclamptic mothers among both the groups.

Figure no 35. Graphical representation of correlation of serum magnesium level and

adverse events in eclamptic mothers among both the groups.

0

1

2

3

4

5

6

7

8

1.5 1.7 1.9 2.1 2.3 2.5 2.7 2.9 3.1 3.3 3.5 3.7 3.9

loss of DTR

Oliguria

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

1.5 1.7 1.9 2.1 2.3 2.5 2.7 2.9 3.1 3.3 3.5 3.7 3.9

Aspiration pneumonia

Seizure recurrance

99

DISCUSSION

The present study was conducted among the neonates of eclamptic mothers in the

Obstetrics and Gynaecology department at Mc Gann Teaching District Hospital,

Shivamogga Institute of Medical Sciences, Shivamogga. Total 110 patients were

screened out of which 100 patients and their neonates were included and analyzed in

the study.

In our study 100 patients with eclampsia were analyzed for neonatal outcome who

were treated with magnesium sulphate regimens. The two regimens of magnesium

sulphate used in the study are Standard dose magnesium sulphate regimen (Pritchard's

regimen) and Low dose magnesium sulphate regimen (Bankura regimen). The study

was done to compare and assess safety of Low dose magnesium sulphate regimen and

Standard dose magnesium sulphate regimen in neonates of eclamptic mothers treated

with this regimen.58

In the present study the mean age of mothers included in the study was 24.36+3.48 in

Standard dose magnesium sulphate regimen group and 24.1+3.89 in Low dose

magnesium sulphate regimen group which is in accoradance with Mahajan N et al

where the mean age of mothers diagnosed with eclampsia was 23.64. WhereasBangal

V et al. Shilva et al. reported that 44% and 46% of cases respectively below 20 years

of age which is much lower age group than our study. In our study primigravida

constituted larger proportions of patients in both the groups with 78% of primigravida

in Standard dose magnesium sulphate regimen group and 86% primigravida in Low

dose magnesium sulphate regimen group. Similar studies by Sardesai et al. Pritchard

et al. and Begum R et al. observed 80%, 75%, and 79% of eclampsia cases in

primigravidas respectively. These observations are similar to our study.59

100

In the present study the number of eclamptic mothers who got antenatal care were

very less with only 26% in Standard dose magnesium sulphate regimen group and

22% in Low dose magnesium sulphate regimen group. In a similar study by Sardesai

et al. shows 23.4% of eclamptic mothers got antenatal care which is similar to our

study. In another identical study by Stone S R et al. shows only 8% of mothers who

were diagnosed with eclampsia had got antenatal care which is much lower than our

study. This difference may be due to larger middle class and educated population in

our area who are eager to receive antenatal care. Eclampsia is a sequel of

preeclampsia with uncontrolled blood pressure hence regular antenatal checkups,

screening and treatment of preeclampsia are major factors that contributes to prevent

the morbidity and mortality associated with eclampsia. So lesser the mothers receives

the antenatal care more chances of incidence of eclampsia.60

In our study majority of patients diagnosed with eclampsia were from rural areas with

76% in Standard dose magnesium sulphate regimen group and 68% in Low dose

magnesium sulphate regimen group. This implies there was very little accessibility for

antenatal care and continuous monitoring of the blood pressure, and even many of the

patients were not diagnosed with preeclampsia. Our observations are similar to the

study done by Shamsuddin L et al. who reported 80% of patients diagnosed with

eclampsia were from rural communities in their study.61

The average period of gestation of mothers who presented with eclampsia at our

hospital was 36.44+2.78 weeks in Standard dose magnesium sulphate regimen group

and 36.2+2.32 weeks in Low dose magnesium sulphate regimen group. In an

identical study by LatikaSahu et al. observed the mean weeks of gestation in mothers

who presented with eclampsia was 34 weeks which is very similar to our study. Also

101

other studies by Altman D et al. and Begum R et al. observed mean weeks of

gestation to be 33.3 weeks and 35.8 weeks respectively.62

In the present study mean body mass index of eclamptic mothers was 20.97+2.72 in

Standard dose magnesium sulphate regimen group and 19.42+2.80 in low dose

magnesium sulphate regimen group. These values are indicating towards the lower

range of BMI in our study area among mothers. This indicates the lower body mass

index in developing communities which warrants usage of magnesium sulphate in

lower dose to prevent the toxicity due to hypermagnesimia. In resembling studies by

Sibai B M et al, Bangal V et al and Sardesai et al. the mean BMI of the eclamptic

mothers was 20.64 ± 1.24, 20.75 ± 1.33 and 22.83 ± 2.53 respectively which is similar

to our study. All the above studies done in developing countries are therefore

indicating lower range of BMI among mothers receiving less antenatal care.63

In our study we found the mean systolic blood pressure of the mothers with eclampsia

was 161.48 +13.12 in Standard dose magnesium sulphate regimen group and

160+13.87 in the Low dose magnesium sulphate regimen group. The elevated blood

pressure shows the need of administering the magnesium sulphate regimen as

mentioned in the treatment of eclampsia is recommended (MAGPIE Trial-2002). In a

similar study by Duley et al. the mean systolic blood pressure among the eclamptic

mothers was 164 ± 14.14 which corresponds to our study value. The severe

hypertension (>160mmHg) among the mothers indicates that delivery should be

considered irrespective of the gestational age, which was done accordingly in our

study.64

In our study we observed the mean of diastolic blood pressure of eclamptic mothers

was 97.4+6.32 in Standard dose magnesium sulphate regimen group and 100+6.58 in

102

Low dose magnesium sulphate regimen group. These values are little higher than

normal showing the fulminant eclamptic state of the mother. Both systolic blood

pressure and diastolic blood pressure are showing the need of treating the mother

immediately with anticonvulsants to prevent recurrent seizures and to start appropriate

antihypertensive. In similar study by Jana N et al. and Mahajan N et al the mean

diastolic blood pressure was 118.8 ± 4.01 and 104.8 ± 9.48 respectively which is in

accordance to our study.65

In the present study the average number of convulsions the mother suffered before the

admission in our hospital was 4.3+1.59 in Standard dose magnesium sulphate regimen

group and 4.24+2.0 in Low dose magnesium sulphate regimen group. This indicating

the potential morbidity and mortality in both mother and the foetus. In identical

studies by Malapaka S V et al. and Bangal V et al. show the higher numbers with

average number of convulsions before admissions 6.08+2.81 and 6.83+1.33. This is

due to better use of transportation facility by the nearby population of our hospital

under jananisurakshayojana and also the awareness among the community for better

healthcare facility.66

In the present study the proportion of caesarean section done among eclamptic

mothers was 28% in Standard dose magnesium sulphate regimen group and 18% in

Low dose magnesium sulphate regimen group which was comparable with similar

studies by Nautiyal R et al. and Seth S et al. who showed proportion to be 16% and

20% respectively. There was no maternal mortality seen in our study among both the

groups. The patient with complications before admission were not included in the

study which might be the reason for better outcome in our study. If complication

developed the both treating gynaecologist and physician shifted the patient to

103

intensive care unit (ICU) and managed accordingly. And mother who developed

complications due to eclampsia were also excluded from the study. This is similar to

the study by Sardesai et al. and Shilva et al which also reported no maternal mortality.

In the present study the mean birth weight of neonates was found to be 2624+505.30

grams in Standard dose magnesium sulphate regimen group and 2610+549.30 grams

in Low dose magnesium sulphate regimen group. The neonatal birth weight did not

vary significantly among the groups in our study which is in accordance with the

study by Das M et al. Also similar studies by Stone S R et al. and Donovan E F et al.

showed similar observations.67,68

In the present study the mean cord blood magnesium level was 3.28+0.16 mmol/l in

Standard dose magnesium sulphate regimen and 2.20+0.26mmol/l in Low dose

magnesium sulphate regimen. The greater proportion of cord blood magnesium levels

were in the desired therapeutic range of 2.0-3.5mmol/l. Only 4(8%) neonates had

levels exceeding 3.8mmol/l. These findings are in accordance with identical studies

by Riaz M et al and Rasch D K et al which reported the mean cord blood magnesium

level to be 3.36 and 3.19mmol/l respectively. The dose of magnesium sulphate in Low

dose magnesium sulphate regimen group was 40% lower than in

ColloborativeEclampsia Trial, using standard Pritchard regimen (40g vs 23.9g, p <

0.001).6,7

In the present study the APGAR score of the neonates at 5 min was primary endpoint

and it showed a statistical significance between the groups. The mean APGAR score

was 6.62+2.23 in Standard dose magnesium sulphate regimen group and 8.9+1.46 in

Low dose magnesium sulphate regimen group. Neonates with severely depressed

APGAR score were significantly more in Standard dose magnesium sulphate regimen

104

group compared to Low dose magnesium sulphate regimen group. There was

significant decrease in APGAR scores with corresponding increase in the cord blood

magnesium level. APGAR scores were decreased as the cord blood magnesium level

increased from 2.5 to 3.5 mmol/l. The neonatal effects of magnesiumion that we

observed occurred primarily within the therapeuticrange of magnesium sulphate in

mothers. Similar studies by Das M et al. and Green K W et al showed significant

correlation between the APGAR scores and cord blood magnesium level. They found

higher proportion of neonates had severely depressed APGAR scores where in

mothers were treated with Prtichard regimen compared to Low dose regimen.

However identical studies by Regmi M C et al. and Bhattacharjee et al. did not show

statistical significance in decrease of APGAR scores between neonates of eclamptic

mothers in Standard dose magnesium sulphate regimen group and Low dose

magnesium sulphate regimen groups. This may be due to the lesser sample size and

less emphasis on neonatal parameters.8

In the present study neonates who required NICU care were significantly more in

Standard dose magnesium sulphate regimen group compared to Low dose magnesium

sulphate regimen group. Also there was significant correlation between the number of

NICU admissions and cord blood magnesium level. Number of NICU admission

increased with the cord blood magnesium level increase. Higher proportion of

neonates were admitted with cord blood magnesium level in the range of 3.5-3.8

mmol/l compared to lower range <3.5mmol/l of cord blood magnesium level. These

findings are in accordance with similar studies by Latikasahu and Monalisa Das who

showed significant increase in rate of admission in NICU among neonates of mothers

treated with standard dose regimen group compared to lower dose regimens. However

105

other identical studies by Mahajan NN and Jana N showed no significance in neonatal

parameters among neonates of eclamptic mothers.9

In our study we found incidence of respiratory distress, hypotonia and bradycardia to

be significantly more among neonates of eclamptic mother who were treated with

Standard dose magnesium sulphate regimen compared to neonates of eclamptic

mothers who were treated with Low dose magnesium sulphate regimen. These

findings are in accordance with similar studies by Abbassi-Ghanavati and Das M who

showed significant increase in rate of admission in NICU among neonates of mothers

treated with Standard dose magnesium regimen compared to lower dose regimens.

However other identical studies by Shilva andBangal V there was no significance in

neonatal parameters among neonates of eclamptic mothers.10

In the present study the proportion of still birth among eclamptic mothers was 1% in

Standard dose magnesium sulphate regimen group and 0.5% in Low dose magnesium

sulphate regimen group which was much lower compared to similar studies by Begum

R et al. and Sardesai et al. who showed proportion to be 30% and 15% respectively.

This might be due to the exclusion criteria considered in our study which excluded

eclamptic mothers with complication. Our results did not show any statistical

significance in still births among both the groups which is in accordance with Begum

R et al which showed no significance difference in still births among both the groups.

In an identical study by Das M et al. there was statistical significance difference in

still births among both the groups which is in contrast to our study.11

There was no early neonatal death in our study. If complication developed in the

neonates attending paediatric faculty shifted the neonate to neonatal intensive care

106

unit (NICU) and managed accordingly. This is similar to the study by Sardesai et al.

and Shilva et al which also reported no early neonatal mortality.12

In the present study the seizure recurrence after administration of magnesium sulphate

regimens was seen in 6% among eclamptic mothers in Standard dose magnesium

sulphate regimen group and 10% in Low dose magnesium sulphate regimen group.

There was no statistical significance in seizure recurrence in both the groups. The

eclamptic mothers with seizure recurrence were treated accordingly with the protocol

decided in the study. Our findings were in accordance with the study by Sahu L et al.

where the seizure recurrence in the low dose regimen group was 4% and zero cases in

standard dose regimen group.62

In the present study significant less number of adverse effects or adverse events were

observed in Low dose magnesium sulphate regimen group which wereloss of deep

tendon reflexes, aspiration pneumonia and oliguria. In Standard dose magnesium

sulphate regimen group higher number of adverse events reported compared to Low

dose regimen group such as ,n (%) loss of deep tendon reflexes 13(26%), constituting

the highest adverse effect, which lasted for hours, followed by oliguria 8(16%) and

aspiration pneumonia 2(4%). Adverse events in mothers were statistically related to

higher serum magnesium levels. Standard dose magnesium sulphate regimen safety

and efficacy have been documented in study by Pritchard J A et al. who evaluated 245

cases of eclampsia and found magnesium sulphate alone effectively controlled

convulsions in great majority of cases with very few and rare adverse events like renal

failure, pulmonary oedema and only one case of respiratory arrest.63

In our study we have evaluated the neonatal outcomes of eclamptic mothers treated

with Low dose magnesium sulphate regimen and Standard dose magnesium sulphate

107

regimen for management of eclampsia. Our results highlighted the largely forgotten

observations on neonatal outcome of eclamptic mothers treated with magnesium

sulphate which was made several decades ago. Further studies with larger size needed

for documentation of neonatal adverse events due to hypermagnesimia. The results

are clinically relevant to health care facilities in developing countries, where maternal

height and weight are almost always low.64

The present study results have implications -

• Firstly, following the Low dose magnesium sulphate regimen decreases the

risk of magnesium toxicity to mothers and newborns and hence increased

safety of the drug.

• Secondly with a lesser toxicity, magnesium sulphate treatment is likely to

become acceptable at primary health centres. Recent similar studies in

Bangladesh by Shamshuddin L et al. suggests that administering the drug at

primary health centres significantly reduces the recurrence of seizures,

maternal deaths and improves perinatal outcome.

108

CONCLUSION

This study was conducted to compare the neonatal outcome in eclamptic

mothers treated with low-dose magnesium sulphate regimen and standard dose

magnesium sulphate regimen. We concluded that

• Neonatal outcome were better in eclamptic mothers treated with low dose

magnesium sulphate regimen compared to the eclamptic mothers treated with

standard dose magnesium sulphate regimen.

• Low dose magnesium sulphate regimen has comparable efficacy as standard

dose magnesium sulphate regimen to control convulsions in management of

eclampsia.

• Low dose magnesium sulphate regimen had less magnesium toxicity and fewer

maternal adverse events and achieved serum magnesium levels within

therapeutic range for control of convulsons in eclampsia compared to standard

dose magnesium sulphate regimen.

• APGAR scores decreased with increase in cord blood magnesium levels and

NICU care requirement increased with increase in cord blood magnesium

levels.

• Our analysis indicates that several neonatal outcomes are significantly related

to increasing concentration of magnesium ion in the maternal circulation.

• Maternal adverse events increased with increase in serum magnesium levels of

the eclamptic mothers after loading dose.

109

STRENGTHS

• This was a comparative study on neonatal outcomes of eclamptic mothers were

assessed who were treated with magnesium sulphate regimens.

• Several neonatal and maternal parameters which were not considered in the

previous studies were highlighted in this study.

• The correlation of neonatal parameters with cord blood magnesium level were

done and correlation of maternal parameters with serum magnesium level was

done. So the results could be elaborated to the health facilities were no facilities

for monitoring the therapeutic concentration of magnesium level were present.

• The result of the study can be can be implemented in the nearby primary and

secondary centres without fear of magnesium toxicity as in standard Pritchard's

regimen which can reduce the complications of eclampsia while reaching our

tertiary care hospital.

LIMITATIONS

• Larger sample size, including multi institution would give more power to the

study and would help in assessment of several other neonatal and maternal

parameters.

• Facilities for continuous electrocardiographic monitoring of all newborn not

available in our hospital, so bradycardia and subtle ECG changes due to

neonatal hypermagnesimia could not be monitored.

110

SUMMARY

• This interventional prospective randomized open labelled study was done

between neonatal outcomes of eclamptic mothers treated with low dose

magnesium sulphate regimen treated with standard dose magnesium sulphate

regimen for management of eclampsia.

• Eclampsia is a multisystem disorder of unknown aetiology characterized by

development of hypertension to the extent of 140/90mmHg or more with

proteinuria after the 20th week in a previously normotensive an non

proteinuric patient complicated with generalised tonic-clonic convulsions

and/coma.

• In severe cases of preeclampsia and in eclampsia,magnesium sulphate

administered parenterally is an effectiveanticonvulsant that avoids producing

central nervoussystem depression in either the mother or the infant.

• Magnesium sulphate acts as a membrane stabilizer and neuroprotector. . It

reduces motor endplate sensitivity to acetylcholine. Magnesium blocks

neuronal calcium influx also byblockadeof calcium entry via voltage-gated

channels.

• Magnesium sulphate may begiven intravenously by continuous infusion or

intramuscularlyby intermittent injection.

• Magnesium sulphate is attributed to dose related toxicity which is a major

concern. Possible maternal adverse effects include reduced urinary output,

respiratory depression, aspiration pneumonia, hypotension, decreased or loss

of deep tendon reflexes. A significant percentage of perinatal and early

111

neonatal morbidity and mortality has been recorded due to neonatal

hypermagnesimia.

• Pritchard in 1984 suggested that the dose of magnesium sulphate may be

reduced for women with low BMI in Asia as administering Pritchard’s

regimen might prove to be hazardous for them due to dose related toxicity.

Various low dose magnesium sulphate regimens have been described

principally because of low BMI of Indian women & concern about toxicity in

circumstances where facility for measurement of serum level of magnesium is

not available. Low dose magnesium sulphate regimen has shown promise in

terms of decrease in side effects without a significant decrease in its

therapeutic benefits.

• Low-dosemagnesium sulphate for administration, showed efficacy similar to

standard Pritchardregimen with reduced maternal and perinatal mortality in

previous studies. However, neonatal outcome has rarely been studied

withlowdose magnesium sulphate regimen.

• The primary end point of the study was to assess the neonatal outcome by the

assessment of APGAR scores at 5min. Secondary end points of the study were

to assess neonatal parameters in terms of birth weight, respiratory depression,

NICU care requirement, bradycardia and hypotonia. Also to study the

correlation of neonatal outcomes with cord blood magnesium level. And to

assess the safety and efficacy of low dose magnesium sulphate regimen.

• In the present study the neonates with severely depressed APGAR score were

significantly more in standard dose regimen group compared to low dose

regimen group. There was significant decrease in APGAR scores with

corresponding increase in the cord blood magnesium level.

112

• Neonatal parameters like NICU care requirement, incidence of respiratory

distress, bradycardia and hypotonia showed significant decrease in Low dose

magnesium sulphate regimen group compared to Standard dose magnesium

sulphate regimen group.

• Low dose magnesium sulphate regimen had less number of adverse events

reported among eclamptic mothers and it had decreased maternal morbidity

compared to standard dose magnesium sulphate regimen. Also it was effective

in controlling convulsion in eclamptic mothers similar to Pritchard's regimen.

• Low dose magnesium sulphate regimen can be used by nearby primary and

secondary centres and implement this regimen without fear of magnesium

toxicity as in standard Pritchard's regimen which can reduce the complications

of eclampsia while reaching our tertiary care hospital.

• Larger trials with multiple institutional trials should be undertaken to find the

lowest effective dose of magnesium sulphate for convulsion control.

113

REFERENCES

1. World Health Organisation International. Collaborative Study of Hypertensive

Disorders of pregnancy. Geographic Variation in the incidence of hypertension in

pregnancy. Am J ObstetGynecol1958;158:80-3.

2. Dutta DC. Hypertensive Disorders in Pregnancy. In: Konar H, editor. DC Dutta’s

Text Book of Obstetrics. 8th ed. New Delhi: Jaypee Brothers Medical


3. Altura BM, Altura BT, Carella A, Gebrewold A, Murakawa T, Nishio A. Mg2+-

Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic

calcium channel blockers on myogenic tone and agonist-induced responsiveness

of blood vessels. Can J PhysiolPharmacol 1987;65:729-45.

4. Idama TO, Lindow SW. Magnesium sulphate: A review of clinical pharmacology

applied to obstetrics. Br J ObstetGynaecol1998;105:260-8.

5. Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Memorial Hospital

protocol for treatment of eclampsia: Evaluation of 245 cases. Am J

ObstetGynecol1984;148:951-63.

6. Das M, Patralekha Ray Choudri, Badal C. Assessment of serum magnesium levels

and its outcome in neonates of eclamptic mothers treated with low dose

magnesium sulphate regimen. Indian journal of pharmacology 2015:55(4):757-

761.

7. Sahu L, Singh S, Tempe A, Koner BC. A randomized comparative study between

low-dose magnesium sulphate and standard dose regimen for management of

eclampsia. International Journal Reproduction Contraception Obstetrics and

Gynaecology 2014;3:79-86.

114

8. RuchiraNautiyal, Akansha Srivastava, Nidhi Chauhan, Hemant Kumar Nautiyal,

Feasibility of low dose magnesium sulphate for eclampsia – a randomized study

Indian Journal of Obstetrics and Gynaecology Research 2016;3(2):121-125.

9. Abbassi-Ghanavati M, Alexander JM, McIntire DD, Savani RC, Leveno KJ.

Neonatal effects of magnesium sulphate given to the mother. American Journal of

Perinatolgy2012;29:795-9.

10. Jana N, Dasgupta S, Das AK, Santra D, Samanta B. Experience of a low-dose

magnesium sulphate regimen for the management of eclampsia over a decade.

International Journal of Gynaecology and Obstetrics 2013;122:13-7.

11. Nassar AH, Sakhel K, Maarouf H, Naassan GR, Usta IM. Adverse maternal and

neonatal outcome of prolonged course of magnesium sulfatetocolysis.

ActaObstetGynecolScand2006;85:1099-103.

12. Begum R, Begum A, Johanson R, Ali MN, Akhter S. A low dose ("Dhaka")

magnesium sulphate regime for eclampsia. ActaObstetGynecolScand

2001;80:998-1002.

13. Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et

al., editors. Hypertensive Disorders. In: Williams Obstetrics. 24th ed. New York:

McGraw–Hill Education; 2014. p. 728-9.

14. K.Park.Preventive medicine in obstetrics, pediatrics and geriatrics. Park textbook

of Preventive and Social Medicine. 23rd edition. Jabalpur: M/s BanarsidasBhanot

Publishers.2015; 532-5.

15. Nobis P N, Hajong A et al. Eclampsia in India Through Decades.The Journal of

Obstetrics and Gynaecology of India (September–October 2016) 66(S1):S172–

S176.

115

16. Ministry of Health and Family Welfare, India. Annual Report. New Delhi: 2005:

105-111. Available at:

http://mohfw.nic.in/WriteReadData/l892s/6960144509Annual%20Report%20to%

20the%20People%20on%20Health.pdf. Accessed December 2011.

17. Chesley LC. Hypertensive Disorders in Pregnancy. New York: Appleton-Century-

Crofts; 1978.

18. Fernando Arias. Hypertensive disorder in pregnancy; Practical Guide to High

Risk pregnancy and delivery.3rd ed. New Delhi: Elsevier publishers;2008:397-

437.

19. Bhargava A, Pant R, Chutani I, Singh S R. In search for accelerated recovery from

eclampsia. J Obstet and Gynecol India. 2006;56:402-5.

20. Duley L. The Eclampsia Trial collaborative Group. Which Anticonvulsant for

women with Eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet

1995;345:1455-63.

21. Euser AG, Bullinger L, Cipolla MJ. Magnesium sulphate treatment decreases

blood-brain barrier permeability during acute hypertension in pregnant rats.

ExpPhysiol2008;93:254-61.

22. American College of Obstetricians and Gynecologists: Diagnosis and

management of preeclampsia and eclampsia. Practice Bulletin No. 33, January

2002.

23. Shokry M, Elsedfy GO, Bassiouny MM, Anmin M, Abozid H. Effects of antenatal

magnesium sulphate therapy on cerebral and systemic hemodynamics in preterm

newborns. ActaObstetricaetGynaecologica. 2010;8(6)9:801-6.

http://mohfw.nic.in/

116

24. Fisher S, Roberts JM: The placenta in normal pregnancy and preeclampsia.

InTaylor RN, Roberts JM, Cunningham FG (eds): Chesley’s Hypertensive

Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2014

25. Hallak M, Berman RF, Irtenkauf SM, Janusz CA, Cotton DB. Magnesium sulfate

treatment decreases N-methyl-D-aspartate receptor binding in the rat brain: An

autoradiographic study. J SocGynecolInvestig 1994;1:25-30.

26. Montan S. Medical prevention of pre-eclampsia. ActaObstetGynaecolScand

Suppl. 1997;76(164):111-5.

27. Witlin AG: Prevention and treatment of eclamptic convulsions.

ClinObstetGynecol1999;42:507–518.

28. Helmin R H J. Prevention of eclampsia and preeclampsia. Lancet 1952;1:64.

29. Altman D, Carroli G, Duley L, Farrell B, Moodley J, Neilson J, et al. Do women

with pre-eclampsia, and their babies, benefit from magnesium sulphate? The

magpie trial: A randomised placebo-controlled trial. Lancet 2002;359:1877-90.

30. Lipsitz PJ. The clinical and biochemical effects of excess magnesium in the

newborn. Pediatrics1971;47:501-9.

31. Sibai BM. Magnesium sulfate is the ideal anticonvulsant in preeclampsia –

eclampsia. Am J Obstet Gynecol. 1990;162(5):1141-5.

32. Chinayon P. Clinical management and outcome of eclampsia at Rajavithi

Hospital. J Med Assoc Thai.1998;81(8):579-85.

33. Bhargava A, Pant R, Chutani I, Singh SK: In search for accelerated recovery from

eclampsia. J ObstetGynecol India 2006;56:402–405.

117

34. Regmi MC, Aggrawal A, Pradhan T, Rijal P, Sabdi A. Loading dose versus

standard regimen of magnesium sulphate in eclampsia-a randomized trial. Nepal

Med Coll J. 2010;12(4):244-7.

35. Chowdhury JR, Chaudhuri S, Bhattacharyya N, et al: Comparison ofintramuscular

magnesium sulfate with low dose intravenous magnesiumsulfate regimen for

treatment of eclampsia. J ObstetGynaecol Res 35:119, 2009

36. Ekele BA, Muhammed D, Bello L N, Namadina IM. Magnesium sulfate therapy

in Eclampsia : the Sokoto (ultra short) regimen. BMC Res Notes. 2009;2:165.

37. Duley LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate

for women at risk of preterm birth for neuroprotection of the fetus. Cochrane

Database Syst Rev. 2009 Jan;21(1):CD004661.

38. Ekele BA, Muhammed D, Bello LN, Namadina IM. Magnesium sulphate therapy

in eclampsia: the Sokoto (ultra short) regimen. BMC Res Notes. 2009;2:165-8.

39. Magpie Trial Collaboration Group: Do women with pre-eclampsia, and

theirbabies, benefit from magnesium sulphate? The Magpie Trial: a

randomisedplacebo-controlled trial. Lancet 359:1877, 2002

40. Laurence L, Bruton. Antiarrhytmic drugs In: Goodman and Gilman’s The

Pharmacological Basis of Therapeutics.13th edition. New York: McGraw-Hill

Education; 2011.p.842.

41. Maternal anthropometry and pregnancy outcomes. A WHO Collaborative Study:

Introduction. Bull World Health Organ 1995;73 Suppl:1-6.

42. Duley L. Magpie Trial Follow up Collaborative group. The Magpie Trial: A

randomized trial comparing magnesium sulphate with placebo for preeclampsia:

Outcome for children at 18 months. Br J ObstetGynaecol. 2007;114(3):289-99.

118

43. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy

in Africa, Asia, Latin America and the Carribean. Br J ObstetGynaecol

1992;99(7):547-53.

44. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with

eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet

1995;345:1455-63.

45. Gastrich MD, Gandhi SK, Pantazopoulos J, et al: Cardiovascular outcomesafter

preeclampsia or eclampsia complicated by myocardial infarction or stroke.

ObstetGynecol120(4), 823, 2012

46. Kleigman, Behram, Jenson, Stanton et al, editors. Electrolytes and acid base

disorders. In: Nelson textbook of Pediatrics Volume 1. 18th edition. New Delhi:

Reed Elsevier India Private Limited 2010.p.287.

47. Stone SR, Pritchard JA. Effect of maternally administered magnesium sulfate on

the neonate. ObstetGynecol 1970;35:574-7.

48. Donovan EF, Tsang RC, Steichen JJ, Strub RJ, Chen IW, Chen M. Neonatal

hypermagnesemia: Effect on parathyroid hormone and calcium homeostasis.

JPediatr1980;96:305-10.

49. Lipsitz PJ, English IC. Hypermagnesemia in the newborn infant.

Pediatrics1967;40:856-62.

50. Rasch DK, Huber PA, Richardson CJ, L'Hommedieu CS, Nelson TE, Reddi

R.Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr

1982;100:272-6.

51. Green KW, Key TC, Coen R, Resnik R. The effects of maternally administered

magnesium sulfate on the neonate. Am J ObstetGynecol 1983;146:29-33.

119

52. Riaz M, Porat R, Brodsky NL, Hurt H. The effects of maternal magnesium sulfate

treatment on newborns: A prospective controlled study. J Perinatol 1998;18:449-

454.

53. Alexander JM, McIntire DD, Leveno KJ, et al: Selective magnesium sulfate

prophylaxis for the prevention of eclampsia in women with

gestationalhypertension. ObstetGynecol 108:826, 2006

54. Crowther CA, Bouwmeester AM, Ashurst HM: Does admission to hospitalfor bed

rest prevent disease progression or improve fetal outcome in pregnancy

complicated by non-proteinuric hypertension? Br J ObstetGynaecol 99:13, 1992

55. Abalos E, Duley L, Steyn DW, et al: Antihypertensive drug therapy for mild to

moderate hypertension during pregnancy. Cochrane Database Syst Rev

1:CD002252, 2007

56. Duffy CR, Odibo AO, Roehl KA, et al: Effect of magnesium sulfate on fetalheart

rate patterns in the second stage of labor. ObstetGynecol 119(6):1129, 2012

57. Hallak M, Martinez-Poyer J, Kruger ML, et al: The effect of magnesium sulfateon

fetal heart rate parameters: a randomized, placebo-controlled trial. Am J

ObstetGynecol 181:1122, 1999

58. Sardesai S, Maira S, Patil A. Low dose Magnesium Sulphate therapy for

Eclampsia and imminent Eclampsia ─ regimen tailored for Indian women. J

ObstetGynecol India 2003;53:546-550.

59. Shilva, Saha SC, Kalra J, Prasad R. Safety and efficacy of low-dose MgSO4 in the

treatment of eclampsia. Int J GynaecolObstet 2007;97:150-1.

60. Bangal V, Kwatra A, Raghav S, Jadhav S. Low dose magnesium sulphate regime

for Eclampsia. Pravara Med Rev 2009;4:13-5.

INFORMED CONSENT (GUARDIAN)

SHIVAMOGGA INSTITUTE OF MEDICAL SCIENCES

I have been briefed on the foregoing study being conducted by Dr. Sriti Hegde and it has

been conveyed to me about the treatment regimen, need for the blood test and the need for the

observation of new born in my own language. I have had the opportunity to ask questions

about it and any questions that I have asked have been answered to my satisfaction. I consent

on behalf of my ________________( relation ) _____________ (name).

Name :

Relation with the participant :

Signature :

Date:

If illiterate

I have accurately read the consent form to the relative of the participant and the individual

has had the opportunity to ask questions. I confirm that the individual has given the consent.

Sign :

Name of the relative of the participant

Relation with the participant

Left thumb impression :

Date :

INFORMED CONSENT

SHIVAMOGGA INSTITUTE OF MEDICAL SCIENCES

I have been briefed on the foregoing study being conducted by Dr. Sriti Hegde and it has

been conveyed to me about the treatment regimen, need for the blood test and the need for the

observation of new born in my own language. I have had the opportunity to ask questions

about it and any questions that I have asked have been answered to my satisfaction. I consent

voluntarily to participate.

Name of the participant :

Signature :

Date:

If illiterate

I have accurately read the consent form to the relative of the participant and the individual

has had the opportunity to ask questions. I confirm that the individual has given the consent.

Sign :

Name of the participant

Left thumb impression :

Date :

M¦àUÉ ¥ÀvÀæ (¸ÀA§A¢üPÀgÀÄ) ²ªÀªÉÆUÀÎ ªÉÊzÀQÃAiÀÄ «eÁÕ£ÀUÀ¼À ¸ÀA¸ÉÜ ²ªÀªÉÆUÀÎ

(ªÉÄÃ°éZÁgÀPÀgÀÄ eÉÆÃ¥Á£À ªÀiÁqÀÄªÀÅzÀÄ)

qÁ. ±ÀÈw ºÉUÀqÉ gÀªÀgÀ G£ÀßvÀ ªÉÊzÀåQÃAiÀÄ ªÁå¸ÀAUÀPÉÌ ¸ÀºÀPÀj¸À®Ä M¦àUÉ ¤ÃrgÀÄvÉÛ£É F PÀÄjvÀÄ CªÀgÀÄ £À£Àß

ªÀiÁvÀÈ ¨sÁµÉAiÀÄ°è G¥ÀAiÉÆÃV¸ÀÄwÛgÀÄªÀ OµÀ¢ü ¥ÀzÀÞwÛAiÀÄ §UÉÎ CzÀjAzÀ ¸ÁzsÀåªÁUÀ§ºÀÄzÁzÀ ¥ÀæAiÉÆÃd£ÀUÀ¼ÀÄ

ºÁUÀÄ CqÀØ¥ÀjuÁªÀÄUÀ¼À §UÉÎ gÀPÀÛ ¥ÀjÃPÉëAiÀÄ CUÀvÀåvÉ ºÁUÀÄ ªÀÄUÀÄªÀ£ÀÄß ¤UÁzÀ°è EqÀÄªÀ CUÀvÀåvÉAiÀÄ §UÉÎ

«ªÀj¹gÀÄvÁÛgÉ £Á£ÀÄ F PÀÄjvÀÄ PÉÃ½zÀ ¥ÀæwAiÉÆÃAzÀÄ ¥Àæ±ÉßUÀ½UÉ £À£ÀUÉ vÀÈ¦ÛAiÀiÁUÀÄªÀ jÃwAiÀÄ°è GvÀÛgÀUÀ¼À£ÀÄß

¤ÃrgÀÄvÁÛgÉ.

F §UÉÎ £Á£ÀÄ AiÀiÁgÀ MvÁÛAiÀÄ«®èzÉ À̧é-EZÉÑ¬ÄAzÀ £À£Àß ……………… CzÀ …………………………………………………… ¥ÀgÀªÁV

M¦àUÉ ¤ÃrgÀÄvÉÛÃ£É.

ºÉ¸ÀgÀÄ:

D¨sÀåyðAiÉÆA¢UÉ ¸ÀA§AzsÀ:

¸À»

¢£ÁAPÀ:

C£ÀPÀëgÀ¸ÀÜgÁzÀgÉ

£Á£ÀÄ M¦àUÉ ¥ÀvÀæzÀ°ègÀÄªÀ J¯Áè ªÀiÁ»wUÀ¼À£ÀÄß C¨sÀåyðAiÀÄ ¸ÀA§A¢üUÉ «ªÀgÀªÁV w½¹gÀÄvÉÛÃ£É. CzÀgÀ §UÉÎ

¥Àæ±ÉßUÀ¼À£ÀÄß PÉÃ¼ÀÄªÀÅzÀPÉÌ CªÀPÁ±À PÀ°à¹zÀÄÝ, CzÀgÀ §UÉÎ ªÀiÁ»wAiÀÄ£ÀÄß w½zÀÄ, D¨sÀåyðAiÀÄ ¸ÀA§A¢ü

M¦àUÉAiÀÄ£ÀÄß ¤Ãr ºÉ̈ ÉânÖ£À À̧» ºÁQgÀÄvÁÛgÉ.

ºÉ¸ÀgÀÄ:

D¨sÀåyðAiÉÆA¢UÉ ¸ÀA§AzsÀ:

ºÉ̈ ÉânÖ£À UÀÄgÀÄvÀÄ :

¢£ÁAPÀ:

M¦àUÉ ¥ÀvÀæ

²ªÀªÉÆUÀÎ ªÉÊzÀQÃAiÀÄ «eÁÕ£ÀUÀ¼À ¸ÀA¸ÉÜ ²ªÀªÉÆUÀÎ

(ªÉÄÃ°éZÁgÀPÀgÀÄ eÉÆÃ¥Á£À ªÀiÁqÀÄªÀÅzÀÄ)

qÁ. ±ÀÈw ºÉUÀqÉ gÀªÀgÀ G£ÀßvÀ ªÉÊzÀåQÃAiÀÄ ªÁå À̧AUÀPÉÌ À̧ºÀPÀj¸À®Ä M¦àUÉ ¤ÃrgÀÄvÉÛ£É F PÀÄjvÀÄ CªÀgÀÄ £À£Àß

ªÀiÁvÀÈ s̈ÁµÉAiÀÄ°è G¥ÀAiÉÆÃV¸ÀÄwÛgÀÄªÀ OµÀ¢ü ¥ÀzÀÞwÛAiÀÄ §UÉÎ CzÀjAzÀ ¸ÁzsÀåªÁUÀ§ºÀÄzÁzÀ ¥ÀæAiÉÆÃd£ÀUÀ¼ÀÄ

ºÁUÀÄ CqÀØ¥ÀjuÁªÀÄUÀ¼À §UÉÎ gÀPÀÛ ¥ÀjÃPÉëAiÀÄ CUÀvÀåvÉ ºÁUÀÄ ªÀÄUÀÄªÀ£ÀÄß ¤UÁzÀ°è EqÀÄªÀ CUÀvÀåvÉAiÀÄ §UÉÎ

«ªÀj¹gÀÄvÁÛgÉ £Á£ÀÄ F PÀÄjvÀÄ PÉÃ½zÀ ¥ÀæwAiÉÆÃAzÀÄ ¥Àæ±ÉßUÀ½UÉ £À£ÀUÉ vÀÈ¦ÛAiÀiÁUÀÄªÀ jÃwAiÀÄ°è GvÀÛgÀUÀ¼À£ÀÄß

¤ÃrgÀÄvÁÛgÉ. F §UÉÎ £Á£ÀÄ AiÀiÁgÀ MvÁÛAiÀÄ«®èzÉ ¸Àé-EZÉÑ¬ÄAzÀ s̈ÁUÀªÀ»¸ÀÄvÉÛ£É ºÁUÀÄ M¦àUÉ ¤ÃrÃgÀÄvÉÛÃ£É.

ºÉ¸ÀgÀÄ :

¸À» ;

¢£ÁAPÀ :

C£ÀPÀëgÀ¸ÀÜgÁzÀgÉ £Á£ÀÄ M¦àUÉ ¥ÀvÀæzÀ°ègÀÄªÀ J¯Áè ªÀiÁ»wUÀ¼À£ÀÄß C¨sÀåyðUÉ «ªÀgÀªÁV w½¹gÀÄvÉÛÃ£É. CzÀgÀ §UÉÎ ¥Àæ±ÉßUÀ¼À£ÀÄß

PÉÃ¼ÀÄªÀÅzÀPÉÌ CªÀPÁ±À PÀ°à¹zÀÄÝ, CzÀgÀ §UÉÎ ªÀiÁ»wAiÀÄ£ÀÄß w½zÀÄ, D¨sÀåyðAiÀÄÄ M¦àUÉAiÀÄ£ÀÄß ¤Ãr ºÉ¨ÉânÖ£À

¸À» ºÁQgÀÄvÁÛgÉ.

¸À» : ºÉ¸ÀgÀÄ : ºÉ¨ÉânÖ£À UÀÄgÀÄvÀÄ : ¢£ÁAPÀ :

ANNEXURE III

CASE REPORT FORM

DATE -

NAME :

AGE

GENDER MALE / FEMALE

IP/OP NO.

PHONE NUMBER

OCCUPATION

ADDRESS

INFORMANT

RELATION OF INFORMANT WITH THE PATIENT

SOCIOECONOMIC STATUS

HISTORY OF PRESENT ILLNESS:

G__P__L__A__D__ with ________ weeks of amenorrhea with history of generalised tonic clonic seizures

LMP

EDD

HISTORY OF PRESENT PREGNANCY

I TRIMESTER

II TRIMESTER

III TRIMESTER

OBSTETRICS HISTORY

YEAR PREGNANCY LABOUR PEURPERIUM BABY

MENSTRUAL HISTORY

AGE OF MENARCHE DURATION

CYCLE AMOUNT OF BLOOD FLOW

PAST HISTORY

CONVULSION HISTORY

HYPERTENSION

ENDOCRINE DISORDERS (DIABETES/THROID ABNORMALITY)

CHRONIC KIDNEY DISEASE

CORTICOSTEROID MEDICATION

OTHERS SPECIFY

FAMILY HISTORY

SIMILAR HISTORY IN THE FAMILY

OTHERS

PERSONAL HISTORY -

CONTRACEPTIVE USE

IMMUNIZATION STATUS

SMOKING

ALCOHOL

ALLERGY

GENERAL PHYSICAL EXAMINATION

GLASSGOW COMA SCALE

(GCS)

HEIGHT

HR WEIGHT

BP BREAST

RR PALLOR

TEMP ICTERUS

BUILD CYANOSIS

NUTRITION PEDAL OEDEMA

OBSTETRICS EXAMINATION

ABDOMEN

CERVIX

LABORATORY VALUES -

Hb gm% ALT IU/L

RBC million/mL ALP IU/L

PLATELET thousands/mL AST IU/L

TLC thousands/mL S. sodium

BLOOD GROUP S. potassium

RBS gm/dL S.creatinine

BILLIRUBIN TOTAL

mg/dL

REGIMEN USED

0 hour

at time of delivery

cord blood

serum magnesium

MONITORING OF MAGNESIUM TOXICITY

DTR Urine output

Pedal oedema

Pulmonary crepitations

Blood pressure

Oxygen saturation

4 h

8h

12h

16h

20h

24h

CONTROL OF SEIZURE BY THE ABOVE REGIMEN

RECURRENCE OF SEIZURE

SHIFTED TO PRITCHARD'S REGIMEN

TERMINATION OF PREGNANCY

METHOD USED

OUTCOME OF PRESENT PREGNANCY

NEONATAL PARAMETERS

BIRTH WEIGHT

APGAR SCORE (1min)

APGAR SCORE (5min)

RESPIRATORY DISTRESS

INTUBATION IN DELIVERY ROOM

BRADYCARDIA

HYPOTONIA


TIME TO FIRST STOOL

TIME TO FIRST VOID

FEEDING INTOLERANCE

STILL BIRTH

EARLY NEONATAL DEATH

ANNEXURE IV

KEY TO MASTER CHART

COLUMN HEADING CODE

A Patient ID number

B Age in years

C Gravida status of mother 0 - multigravida

1 - primigravida

D Antenatal care required 0 - booked cases

1 - unbooked cases

E Areas 0 - rural

1 - urban

F Gestation period in weeks

G Body mass index in kg/m2

H Systolic blood pressure

I Diastolic blood pressure

J No. of seizures before admission

K Mode of delivery 0 - Vaginal delivery

1 - Caesarean section

L Deep tendon reflexes 0 - Deep tendon reflex

1 - Loss of DTR

M Pulmonary crepitations 0 - Normal breathing

1 - Pulmonary crepitation

N Urinary output 0 - Normal urine output

1 - Oliguria

O Seizure recurrence 0 - No recurrence of

seizure

1 - Recurrence of seizure

P Birth weight

Q APGAR scores at 5 min

R NICU admissions 0 - NICUcare not required

1 - NICU care required

S Respiratory distress 0 - Respiratory distress

1 - Normal breathing

T Hypotonia 0 - Normal muscle tone

1 - Hypotonia

U Bradycardia 0 - Normal heart rate

1 - Bradycardia

V Still birth 0 - Live birth

1 - Still birth

W Early neonatal death 0 - Healthy neonates

1 - Neonatal death

X Regimen followed 0 - Low dose regimen

1 - Standard dose regimen

Y Maternal serum magnesium level

Z Cord blood magnesium level

ANNEXURE V

IMAGES

Illustration of automated clinical chemical analyzer for estimation of serum and cord

blood magnesium

Illustration of reagents used for estimation of serum and cord blood magnesium

a randomized comparative study between neonatal …

Documents