PREECLAMPSIA AN MOTHER PRESENTING WITH IMMINENT SYMPTOMS OF ECLAMPSIA IN 3

COMPARATIVE STUDY –NORMOTENSIVE &

PREECLAMPSIA AN MOTHER PRESENTING WITH IMMINENT SYMPTOMS OF ECLAMPSIA IN 3

TRIMESTER

Dissertation submitted in

Partial fulfillment of the regulations required for the award of

M.S. DEGREE in

OBSTETRICS AND GYNAECOLOGY

REG.NO: 221716657 MAY 2020

THE TAMILNADU

DR.M.G.R.MEDICAL UNIVERSITY

GOVERNMENT THENI MEDICAL COLLEGE

TAMILNADU

CERTIFICATE

This is to certify that this dissertation titled “COMPARATIVE STUDY OF NORMOTENSIVE & PREECLAMPSIA AN MOTHER

PRESENTING WITH IMMINENT SYMPTOMS OF ECLAMPSIA IN 3RD TRIMESTER” is a Bonafide work done by Dr.S.Subalakshmi at the department of OBSTETRICS and GYNECOLOGY, Government Theni Medical College, during her postgraduate study for MS Branch II OBSTETRICS and GYNECOLOGY (2017-2020) from October 2017 to September 2019. This dissertation is submitted to Dr.MGR Medical University in partial fulfillment of the University rules and regulations for the award of MS degree in OBSTETRICS andGYNECOLOGY.

Dr.B.SHANTHI RANI, MD., DGO Dr.K.RAJENDRAN, M.S., D.Ortho

Associate Professor and HOD, The Dean

Department of Obstetrics &Gynaecology, Government Theni Medical College, Government Theni Medical College, Theni.

Theni.

CERTIFICATE

This is to certify that this dissertation work titled “COMPARATIVE STUDY OF NORMOTENSIVE & PREECLAMPSIA AN MOTHER PRESENTING WITH IMMINENT SYMPTOMS OF ECLAMPSIA IN 3RD TRIMESTER” of the candidate Dr.S.SUBALAKSHMI with Registration number: 221716657 for the award of MASTER OF SURGERY in the branch of OBSTETRICS AND GYNAECOLOGY under the guidance of

Dr.M.THANGAMANI, M.D., DGO., and Dr.A.MAHALAKSHMI, M.D.,

I personally verified the urkund.com website for the purpose of plagiarism check.

I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 12 percentage of plagiarism in the dissertation.

Signature of the guide

DECLARATION

I hereby declare that this dissertation entitled “COMPARATIVE STUDY OF NORMOTENSIVE AND PREECLAMPSIA AN MOTHER PRESENTING WITH IMMINENT SYMPTOMS ECLAMPSIA” was

prepared by me under the direct guidance and supervision of Prof. Dr.M.THANGAMANI, MD., DGO., The dissertation is submitted to the

Dr.M.G.R. Medical University in partial fulfillment of the University regulations for the award of MS degree in Obstetrics and Gynecology, Examination to be held in May 2020.

This record of work has not been submitted previously by me for the award of any degree or diploma from any other university.

Place: Theni Dr. S.SUBALAKSHMI Date:

ACKNOWLEDGEMENT

At the outset, it is with a sense of accomplishment and deep gratitude that I dedicate this Dissertation to all those who have been instrumental in its completion. First and foremost I express my heartful thanks to my esteemed and

respected HOD, Department of Obstetrics and Gynecology GTMCH Dr. B. SHANTHI RANI, MD DGO and my guide Prof. Dr.M.Thangamani

MD, Dr.C.RAJI, MD., Dr.C.NANDHINI, MD, had it not been for her whole hearted support throughout the period of this study, extending from her vast knowledge, Invaluable advice and constant motivation, I truly would not have been able to complete this dissertation topic in its present form.

I sincerely thank my Guide, Dr.A.Mahalakshmi, M.D., OG., for giving me practical suggestions and permitting me to carry out this study in their patients. I sincerely thank my Professors Dr. A. Shanthavibala, M.D., OG., and Dr.K.Kameshwari, M.D., OG., for giving me practical suggestions and permitting me to carry out this study in their Patients. I am deeply indebted to all the teaching staff and my fellow postgraduates for their helpful attitude and valuable suggestions in every stage of my study.

CONTENTS

SLNO TOPIC PAGE NO

1 Introduction 1

2 Aim of the study 3

3 Review of literature 4

4 Materials and Methods 49

5 Results 54

6 Discussion 77

7 Summary 87

8 Conclusion 89

9 Bibliography 10 Proforma 11 Master chart

12 Ethical clearance certificate 13 Plagiarism certificates

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INTRODUCTION

Every woman wishes to have a healthy pregnancy which culminates in a healthy baby and a healthy mother. Unfortunately, some women develop dreaded complications that may result in adverse obstetric outcomes. These include Pregnancy induced hypertension, Pre-eclampsia, Eclampsia and HELLP syndrome. Pre-eclampasia occurs in 5-10% of pregnancies. HELLP syndrome develops in 6-12% of women with preeclampsia or eclampsia accounting for 0.4-0.7% of all pregnancies.

Eclampsia is a Greek word meaning “shining forth”. It is an acute obstetric emergency associated with both maternal and perinatal morbidity and mortality. It is an extremely severe form of Preeclampsia which is characterized by generalized tonic clonic seizures. Eclampsia is preventable but it is still one of the common causes of maternal mortality.

Incidence of Eclampsia in developed country is 1 in 2000 to 1 in 3448.Increased in developing countries. Incidence of Eclampsia in India is 0.9 to 1.8%. 1% accounts for maternal mortality. Perinatal Mortality has been as high as 59/1000 to 214/1000 and morbidity as high as 56%. About 35% of affected women have serious complication. Major maternal complications includes placental abruption – 10%, Neurological deficit – 7%, pulmonary edema – 5%, cardiopulmonary arrest – 4% acute renal failure – 4% and 1 % maternal death. Perinatal mortality appears to be primarily related to the gestational age at the time of delivery. The most common causes of fetal death are prematurity, fetal asphyxia and acidosis.

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Severe pre-eclampsia with prodromal symptoms is called Imminent eclampsia. The prodromal symptoms are headache, epigastric pain, nausea, vomiting, oliguria and blurring of vision. Eclampsia can occur any period of pregnancy antepartum, intrapartum and postpartum.

As our hospital provides treatment facilities to large number of Preeclampsia, eclampsia and a relatively higher number of patients of HELLP syndrome, we have the opportunity to conduct such studies which can help us to determine the trend of occurrence of Imminent eclampsia, eclampsia, Pulmonary edema and HELLP syndrome, its complications and its effect on maternal and fetal outcome. This will help us in understanding better about the pathophysiology of the disease which can be applied to improve the management and thereby improve the maternal and perinatal outcome.

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AIM OF THE STUDY

 To analyze the determinants of Imminent eclampsia.

 To analyse prevalence of imminent ecampsia and complications.

 To analyse the maternal and perinatal outcome in Preeclampsia &previously normotensive presents with Imminent eclampsia

 To discuss the timely measures to prevent Eclampsia and its complication.

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REVIEW OF LITERATURE

ECLAMPSIA

Eclampsia is defined as the development of seizure and or unexplained coma during pregnancy, labour or postpartum in patients with signs and symptom of pre-eclampsia.

MEASUREMENT OF BLOOD PRESSURE

Blood Pressure is measured with the patient in sitting position in OP setup and lateral position in IP patients. It is preferable to measure the blood pressure in the right upper arm. The arm is kept at level of heart.

The cuff should be of appropriate size, the length should be 80% (1.5cm above elbow) and width should be at least cover 80% the arm circumference.

The cuff size used are

Small Adult : 22 – 26 cm Adult : 27 – 34cm Large adult : 35 – 44cm Adult thigh : 45 – 52cm

The BP cuff bladder is placed in the arm in midline over the brachial artery pulsation and lower end 2-3cm above the antecubital fossa.

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The cuff is inflated above systolic pressure (disappearance of the radial pulse) and deflated slowly. The first sound heard by auscultation (Korotkoff Phase I) is recorded as systolic BP and disappearance of sound (Korotkoff Phase V) is recorded as diastolic BP.

CLASSIFICATION OF HYPERTENSIVE DISORDER COMPLICATING PREGNANCY

NATIONAL HIGH BLOOD PRESSURE EDUCATION PROGRAMME (2000)¹.

Gestational hypertension Pre-eclampsia and eclampsia

Pre-eclampsia superimposed on chronic hypertension.

Chronic hypertension

ACOG 2017

Preeclampsia-Eclampsia Nonsevere Pre eclampsia Severe Pre eclampsia Chronic Hypertension

Chronic Hypertension with superimposed preeclampsia Gestational Hypertension

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GESTATIONALHYPERTENSION

 When the systolic BP >140mmHg and /or diastolic BP >90mmHg, measured on two occasion atleast 4 hrs apart.

 Without Proteinura.

 Diagnosed after 20 weeks of gestation and BP should return to normal before 12weeks postpartum.

NON SEVERE PRE ECLAMPSIA

 If systolic BP > 140mmHg and diastolic BP > 90mmHg after 20 wks of gestation.

 With Protenuria of +1 dipstick or >300mg/24hrs

 Often GHT accompanied by proteinuria in term as Non Severe Pre eclampsia.

SEVERE PRE-ECLAMPSIA

 If systolic BP > 160 mmHg & diastolic BP > 110mmHg on two occasions 6hrs apart.

 If Proteinuria > 5gm in 24 hrs urine sample or >3+ on two random urine sample.

 Urine output <500ml in 24hrs

 Headache and visual disturbance

 Pulmonary edema or cyanosis.

 Epigastric or right upper quadrant pain.

 Impaired liver function.

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 Fetal growth restriction

 Thrombocytopenia.

 Imminent symptoms

 Severe headache

 Blurring of vision/Flashing before eyes

 Epigastric or right upper quadrant pain

 Vomiting

 Oliguria

 Sudden swelling of the face, hands or feet (NICE guidelines : June.2019)

CHRONIC HYPERTENSION

High blood pressure detected before 20 weeks of pregnancy.

Hypertension diagnosed after 20 weeks of pregnancy but persist even after 12 weeks postpartum.

CHRONIC HYPERTENSION WITH SUPERIMPOSED PREECLAMPSIA

Women with only hypertension in early gestation who develop proteinuria after 20 weeks of gestation and Women with proteinuria before 20 weeks with any severe features.

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ECLAMPSIA

It is defined as presence of new grand mal seizures in a women with increased blood pressure

Antepartum eclampsia Intrapartum eclampsia Postpartum eclampsia TWO STAGE DISORDER

Redman² and Colleague (2015a) described pre-eclampsia as a two stage disorder. Stage 1 is preclinical caused by faulty endovascular trophoblastic remodeling of uterine arteries that downstream causes placenta hypoxia (stage 2 clinical syndrome).

Stage 2 is caused by release of placental soluble factors into maternal circulation. Can be modified by pre existing maternal condition that manifest by endothelial cell activation or inflammation.

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ETIOLOGY

 Imposing number of mechanisms have been proposed to explain the cause of preeclampsia.

 Placental implantation with Abnormal trophoblastic invasion of uterine vessels

 Immunological maladaptive tolerance between maternal, paternal (Placental), fetal tissues

 Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy

 Genetic factor including inherited predisposing genes and epigenetic influences.

ABNORMAL TROPHOBLASTIC INVASION

Fisher³ and colleagues, 2015: Normally by invasion of endovascular trophoblast, spiral arteries undergo extensive remodeling and vessel diameter increases. In pre-eclampsia due to incomplete trophoblastic invasion only superficial decidual vessels invaded and not the myometrial vessels. Hence deeper myometrial vessel do not lose their endothelial lining and musculo- elastic tissue and their mean external diameter is only half that of vessels in normal placenta.

Madazli⁴ and Anociates (2000): Severity of hypertension correlates with the magnitude of defective trophoblastic invasion.

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Khodahaeva⁵ 2016: more prevalent in women with early onset pre eclampsia.

Mac Mohan⁶ and associates (2014):lower levels of soluble antiangiogenic growth factors

Zhou⁷ 1997: endovascular trophoblasts replace the vascular endothelial and muscular linings to enlarge the vessel diameter

Redman⁸ (2012) and lee9 (2012): Placental blood flow is impaired due to abnormally narrow spiral arteriolar lumen leading to hypoxic environment.

Placental debris are released due to hypoxic environment leading to systemic inflammatory response and endothelial activation which leads to syndrome of pre-eclampsia.

De.Wolf¹⁰ 1980: Early Preeclampsia changes include endothelial damage, insiduation of plasma constituents into vessel walls, proliferation of myointimal cells, medial necrosis.

Hertig¹¹ (1945): Lipid accumulation in myointimal cells and macrophages as atherosis.

Nelson¹² 2014b: Placental findings are more common in women diagnosed as Preeclampsia before 34 wks.

Staff¹³ 2015: Acute placental vascular atherosis may also identify greater risk for later atherosclerosis and cardiovascular risk.

Brosens¹⁴, 2011:Labarrere15,2017: Nelson12 ,2014b ; Defective placentation to develop Gestational hypertension, Preeclampsia syndrome, Preterm delivery, Growth restricted fetus, Placental abruption.

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IMMUNOLOGICAL FACTORS

ERLEBACHER¹⁶ (2013); Loss of this tolerance is another cited theory for preeclampsia

Bdolah1⁷(2006); Elevated serum levels of antiangiogenic factors -soluble fms- like tyrosinekinase 1, is on chromosome 13

Strickland¹⁸ (1986); Women previously exposed to paternal antigens, such as a prior pregnancy with the same partner, are “immunized” against preeclampsia. This phenomenon is not as apparent in women with a prior abortion.

Mostello,¹⁹ (2002); Multiparas impregnated by a new consort have a greater risk of preeclampsia

Redman and colleagues² (2015a) ; role of immune maladaptation in preeclampsia pathophysiology- extravillous trophoblasts early in pregnancy express reduced amounts of immunosuppressive non classic human leukocyte antigen G (HLA G).

Loisel²⁰,( 2013); Black women more commonly have the 1597ΔC gene allele that further predisposes to preeclampsia.

Redman2,( 2012, 2015a): T-helper (Th) lymphocytes during normal pregnancy are produced so that type 2 activity is increased in relation to type 1—so-called type 2 bias (Th2 cells promote humoral immunity, whereas Th1 cells stimulate inflammatory cytokine secretion). Beginning in the early second trimester in women who develop preeclampsia, Th1 action is increased.

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American journal²¹ of obstetrics and gynaecology: (Vol. 180, issue 2 Feb.1999, Page 499 - 506) Pre-eclampsia is due to immunological maladaptive tolerance between maternal, paternal and fetal tissue

ENDOTHELIAL CELL ACTIVATION

Davidge²², (2015); Inflammatory changes are believed to be a continuation of stage 1 alterations. In response to ischemia or other inciting causes, placental factors are released and begin a cascade of events.

Faas²³, (2000); Gervasi24, (2001); Endothelial cell dysfunction may result from an extreme activated state of leukocytes in the maternal circulation.

Manten²⁵, (2005); Reactive oxygen species and free radicals that lead to formation of self-propagating lipid peroxides. These peroxides in turn generate highly toxic radicals that injure systemic vascular endothelial cells, modify nitric oxide production by these cells, and interfere with prostaglandin balance.

Oxidative stress include production of the lipid-laden macrophage foam cells seen in placental atherosis, activation of systemic microvascular coagulation manifested by thrombocytopenia, and greater systemic capillary permeability reflected by edema and proteinuria.

Nutritional factor

John²⁶ and coworker 2002: Diet having antioxidant is associated with decreased blood pressure.

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Zhang²⁷ and Associates (2002):Dietary intake of ascorbic acid <85mg/day has double the risk to develop pre-eclampsia.

Villar²⁸ and Associates (2006): Calcium supplementation to low dietary calcium intake population has no effect on incidence of pre-eclampsia.

GENETIC FACTORS

Nilsson^29,( 2004): Multifactorial, polygenic disorder

Ward and Taylor³⁰ (2015) : Incident risk for preeclampsia of 20 to 40 percent for daughters of pre eclamptic mothers; 11 to 37 percent for sisters of preeclamptic women; and 22 to 47 percent for twins.

Shahabi³¹, (2013).Ethno racial factors are important, lower incidence because of interactions of American Indian and white race genes.

Triche³²,(2014). Both maternal and paternal—that control myriad enzymatic and metabolic functions throughout every organ system.

Mackenzie³³, (2012).Plasma-derived factors may induce some of these genes in preeclampsia.

Yang³⁴, (2013); Clinical manifestation in preeclampsia syndrome will occupy a spectrum. Phenotypic expression will differ among similar genotypes depending on interactions with environmental components

Buurma³⁵, (2013); Sakowicz36, (2016); Ward30, (2015); Hundreds of genes have been studied for their possible association with preeclampsia

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Pathogenesis: Vasospasm:

Volhard³⁷ (1918) The concept of vasospasm was studied as early as.

Suzuki³⁸ (2003) Wang39( 2002):Systemic endothelial cell injury promotes interstitial leakage, and blood constituents, including platelets and fibrinogen, are deposited subendothelially. Endothelial junctional proteins are also disrupted, and the subendothelial region of resistance arteries undergoes ultrastructural change.

Seven of these are widely investigated. They are:

Chromosome Gene Biological association 1p 36.3 MTHFR (C677T) Vascular disease

1q 23 F5(Leiden) Thrombophilia

1q42, q43 AGT (M235T) Blood pressure regulation (Angiotensinogen)

6q 21.3 HLA (Various) Immunity

7q 36 NO53 (alu298 Asp) Vascular endothelial function

11p 11q 12 F2(G20210A) Prothrombin (factor 11) 17q23 ACE (1/ D^at intron 16) Blood pressure regulation

CTLA4 Cytotoxic t lymphocyte

associated protein

LPL Lipoprotein lipase

SERPINE 1 Serine peptidase inhibitor GNA promoter Decreased methylation

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Zeeman ⁴⁰ (2009): With diminished blood flow because of maldistribution from vasospasm and interstitial leakage, ischemia of the surrounding tissues can lead to necrosis, hemorrhage, and other end-organ disturbances characteristic of the syndrome.

ENDOTHELIAL CELL INJURY

Davidge⁴¹, 2015: Injury to systemic endothelial cells is now a centerpiece of preeclampsia pathogenesis.

Myers⁴², 2007; Walsh⁴³, 2009: Multiple factors in the plasma of preeclampticwomen combine to exert these vasoactive effects.

Grundmann⁴⁴ and Associates (2008): Reported that circulating endothelial cells are fourfold elevated in pre-eclamptic women.

INCREASED PRESSOR RESPONSE

Raab⁴⁵, (1956); Talledo⁴⁶, (1968). Women with early preeclampsia, however, have enhanced vascular reactivity to infused norepinephrine and angiotensin II Gant⁴⁷, (1974): Increased sensitivity to angiotensin II clearly precedes the onset of gestational hypertension.

Chase⁴⁸, (2017): Women who develop preterm preeclampsia have lower circulating levels of angiotensin II

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Role of Prostaglandin

Davidge⁴¹, (2015): Compared with normal pregnancy, endothelial prostacyclin (PGI2) production is lower in preeclampsia.This action appears to be mediated by phospholipase A2 .

Spitz⁴⁹, (1988): Thromboxane A2 secretion by platelets is increased, and the prostacyclin: thromboxane A2 ratio declines. The net result favours greater sensitivity to infused angiotensin II and, ultimately, vasoconstriction.

Chavarria⁵⁰, (2003): Changes are apparent as early as 22 weeks’ gestation in gravidas who later develop preeclampsia.

Nitric oxide:

Myatt⁵¹, (1992): Weiner⁵²,(1992): Inhibition of nitric oxide synthesis raises mean arterial pressure, lowers heart rate, and reverses the pregnancy-induced refractoriness to vasopressors. In humans, nitric oxide likely is the compound that maintains the normal low-pressure vasodilated state characteristic of fetoplacental perfusion

Davidge⁴¹, (2015): Syndrome is associated with decreased endothelial nitric oxide synthase expression, thus resulting in lower nitric oxide activity

Endothelin

Karumanchi⁵³, (2016b): Endothelin-1 (ET-1) is the primary isoform produced by human endothelium

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Ajne⁵⁴, (2003). Plasma ET-1 levels are elevated in normotensive pregnant women, but women with preeclampsia have even higher levels

Taylor and Roberts⁵⁵ (1999): Placenta is not the source of increased ET-1 concentrations: arise from systemic endothelial activation.

Sagsoz⁵⁶ (2003): Treatment of preeclamptic women with magnesium sulfate lowers ET-1 concentrations

Gillis⁵⁷(2016): Sildenafil reduces ET-1 concentrations Angiogenic and antiangiogenic factor

Karumanchi⁵⁸, (2016a): Angiogenic imbalance describes excessive amounts of antiangiogenic factors, which are thought to be stimulated by worsening hypoxia at the uteroplacental interface. Trophoblast of women destined to develop preeclampsia overproduces at least two antiangiogenic peptides that enter the maternal circulation.

Maynard⁵⁹, (2003): Elevated maternal sFlt-1 levels inactivate and reduce circulating free placental growth factor (PlGF) and VEGF concentrations, leading to endothelial dysfunction

Haggerty⁶⁰, (2012): Highlevels in the second trimester are associated with a doubling of the risk for preeclampsia.

Serum levels of sEng also begin to rise months before clinical preeclampsia develops

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Doubling of expressions of sFlt-1 and sEng increased the preeclampsia risk by 39 and 74 percent.The cause of placental overproduction of antiangiogenic proteins remains an enigma

Vatten⁶¹, (2012): Divergence from normal levels appears to develop even sooner with early-onset preeclampsia.

Herraiz⁶², (2012). Pregnancies complicated by fetal-growth restriction Brownfoot⁶³, (2016). Metformin reduces antiangiogenic secretion.

Widmer⁶⁴, (2007) : Third-trimester elevation of sFlt-1 levels and lower PlGF concentrations correlate with preeclampsia development after 25 weeks’gestation.

Yang⁶⁵, (2016): Racial-ethnic difference in their secretion

Staff⁶⁶, (2007): Concentrations of the soluble forms are not higher infetal circulation or amnionic fluid of preeclamptic women, and their levels in maternal blood dissipate after delivery.

Thadhani⁶⁷, (2016): Antiangiogenic proteins in the prediction and diagnosis.

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RISK FACTOR FOR PRE-ECLAMPSIA

Gustaff Dekker⁶⁸ Bartsch⁶⁹ 2016

 Primi paternity

 Extremes of maternal age>3oyrs

 Multifetal gestation

 Obesity

 Pre-eclampsia in the family

 Pre-eclampsia in previous pregnancy.

 Chronic hypertension and or renal disease.

 Maternal chronic inflammatory condition (rheumatologic disease, SLE, APA)

 Prior stillbirth

 Prior abruption

 Male foetus (Jaskolka⁷⁰ 2017)

 Pregnancy after donor insemination

IMMINENT SYPMTOMS Headache:

Sibai⁷¹ 2005; Zwart⁷²2008 Stefan⁷³C.Kane et al 2013:

The headache may be throbbing pain, needle / knife like sensation generalized pressure. Headache may be mild to severe & intermittent to constant. Headache has poor response to non-opoid analgesic. Frequently

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relieved after magnesium administration.75% cases have headache preceding eclamptic convulsions. Transcranial Doppler Ultrasound shows strong association between abnormal cerebral perfusion pressure and headache.

EPIGASTRIC PAIN OR RIGHT UPPER QUADRANTPAIN

It frequently accompanies hepatocellular necrosis, ischemia and edema that stretch glisson capsule.

NAUSEA ANDVOMITTING It is due to liver changes.

VISUAL DISTURBANCE

Sibai⁷¹ 2005; Zwart⁷² 2008 Stefan⁷³C.Kane et al 2013:

20-30% visual changes preceding eclamptic convulsions. Visual disturbance may be scotoma, photopsia, blurring vision, diplopia ae common.

Usually improves with magnesium sulfate therapy or lowering of blood pressure.

Cunningham⁷⁴ 1995; Blindness is rare but complicates in 15% cases Chambers⁷⁵ 2004; Blindness can develop upto one week after delivery.

Handor⁷⁶ 2014; Roos⁷⁷ 2012; The pathological lesions may be ischaemia, infarction & detachment.

Cunningham⁷⁴ 1995; Amaurosis (occipital blindness)- extensive vasogenic edema. Blindness lasted for 4hrs to 8days but completely resolved in all cases.

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Rare entities

Purtscher retinopathy- Blindness from retinal lesions ( serous retinal detachment or retinal infarction)

Saito⁷⁸ 1998; usually unilateral & asymptomatic; blindness will improve Lara torre⁷⁹ 2002; Moose⁸⁰ 2002; Roos⁷⁷ 2012

Central retinal vein occlusion - Vision permanently impared.

OLIGURIA

Gustaaf Dekker⁶⁸

 Oliguria or anuria may be due to combination of glomelular

endotheliosis, intrarenal vasoconstriction and hypovolemia. The excess SFLT-1 play major role in glomerular endotheliosis.

ATYPICAL PRE-ECLAMPSIA /ECLAMPSIA

M.Sibiai⁸¹ et al., Diagnosis and management of atypical pre-eclampsia and eclampsia Am J obstet Gynecol. 2009, 200: 481e1 –481e7.

Classical presentation in pre-eclampsia is hypertension and proteinuria at >20wks of gestation and or <48hrs after delivery. Atypical pre-eclampsia presents without these classical finding and / or outside the time periods. They may develop before 20wks or after 48hrs postpartum and may have signs of pre-eclampsia without the usual hypertension or proteinuria

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Ayptical Pre-Eclampsia

 Gestational hypertension plus >1 of following items:

o Symptoms of Pre-eclampsia o Haemolysis

o Elevated liver enzymes( 2times upper limit) o Thrombocytopenia.(<1 lakh)

 Gestational Proteinuria plus > 1 of the following:

o Pre-eclampsia symptoms o Thrmbocytopenia

o Elevated liver enzyme

 Early sign and symptom of Pre-eclampsia– Eclampisa at less than 20 weeks of gestation.

 Late postpartum pre-eclampsia–eclampsia >48hours after delivery.

LABARATORY TESTS

 Persistent proteinuria >300mg/24hrs.

 Platelet count < 1,00,000/mm³

 Liver enzymes two times the upper normal limit.

 Serum creatinine > 1.2mg/dl.

 Lactic dehydrogenase > 2 times the upper limit of normal.

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PREDICTIVE TESTS FOR DEVELOPMENT OF THE PREECLAMPSIA

Conde – Agudelo& Associates, 2009.

PLACENTAL PERFUSION/ VASCULAR RESISTANCE

Roll-over test, isometric handgrip or cold pressor test, angiotensin-II infusion, midtrimester mean arterial pressure, platelet angiotensin-II binding,renin, 24-hour ambulatory blood pressure monitoring, uterine artery or fetal transcranial Doppler velocimetry

FETEL-PLACENTAL UNIT ENDOCRINE DYSFUNCTION

Human chronic gonadotropin (hCG), alpha-fetoprotein (AFP), estriol, pregnancy associated protein A (PAPP A), inhibin A, activin A, placental protein13, corticotrophin releasing hormone

RENAL DYSFUNCTION

Serum uric acid, microalbuminuria, urinary calcium or kallikrein, microtransferrinuria, N-acetyl-β-glucosaminidase

ENDOTHELIAL DYSFUNCTION/ OXIDANT STRESS

Platelet count and activation, fibronectin, endothelial adhesion molecules, prostaglandin, thromboxane, C-reactive protein, cytokines, endothelin, neurokinin B, homocysteine, lipids, antiphospholipid antibodies, plasminogen activator inhibitor (PAI), leptin, p-selectin, angiogenic factors to

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include placental growth factor (PIGF), vascular endothelial growth factor (VEGF). fms-like tyrosine kinase receptor-1 (sFIt-1), endoglin.

ECLAMPSIA

Eclampsia is defined as the development of seizures that cannot be attributed to other causes and/ or unexplained coma during pregnancy or puerperium in a women with preeclampsia. `

Eclampsia usually occur anytime from IInd trimester to puerperium.

Atypical eclampsia: Occurs before 20wks, in molar preganancy

Types of Eclampsia

 Antepartum eclampsia is 38% to 53%,

 Intrapartum eclampsia is 18% to36%,

 Postpartum eclampsia is 11% to24%.

PATHOGENESIS OF SEIZURE

Contemporary clinical management of cerebral complications of pre-eclampsia: (Obster Gynecol Int. 2013)⁸⁴

Two hypothesis have been proposed:

 Cerebral over-regulation resulting in vasospasm causes ischemia and intracellular (cytotoxic) edema.

 Loss of auto regulation of cerebral blood flow due to high systemic blood pressure results in hyperperfusion, endothelial damage and extracellular (vasogenic) edema.

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CLINICAL FEATURES

SEIZURES

 Characteristic of seizure is usually generalized, tonic – clonic seizures.

Seizure is usually self limiting, lasts for 60-75 sec and seldom last longer than 3 –4min.

TONIC PHASE

 Last for 10 – 20 sec.

 Sudden loss of consciousness and posture. Eyes deviate upwards and therein brief flexion of arms followed by extension of head, neck, arms and legs.

CLONIC PHASE

 Lasts for 30 – 90seconds

 There will be brief violent and generalized flexor contraction altering with progressively longer muscle relaxation.

 Tongue biting, foamy salivation, loss of bladder and bowel control can occur.

 It ends with deep inspiration.

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RECOVERY PHASE

 Convulsion subsides, respiration resumes and patient may have coma of variable duration.

 Patient has mild confusion, headache, muscle soreness and fatigue in post ictal phase

FETAL

During and immediately after an seizure fetal bradycardia occur which lasts for atleast 3 – 5mintues. By stabilizing the mother, fetus usually recovers.

DIFFERENTIALDIAGNOSIS

 Epilepsy

 Hemorrhage or central thrombosis causing cerebrovascular accident.

 Infection like meningitis, encephalitis and cerebral malaria

 Metabolic disturbances.

COMPLICATIONS OF ECLAMPSIA MATERNAL

 Maternal injury

 Aspiration pneumonia

 Placental abruption

 Status epileptius

 Cardio pulmonary arrest

 Acute renal failure

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 HELLP Syndrome

 Retinal detachment

 Cerebral hemorrhage

 PRES syndrome

 Pulmonary edema

 Postpartum psychosis

 Coma

FETAL

 Fetal distress/ bradycardia

 Hypoxic ischemic encephalopathy

 Intrauterine death

CEREBROVASCULAR ACCIDENT

Stroke in women with Pre-eclampsia may be either ischemic or hemorrhagic. Hemorrhagic is more common and it is the common cause of maternal death.

Pre-eclamptic and eclamptic women with stroke has main correlation with systolic blood pressure than diastolic blood pressure.

VISUAL DISORDER

Arias⁸³: Blindness can occur in patient with severe pre-eclampsia and eclampsia, due to multiple micro hemorrhages and microinfarcts in the

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occipital lobe. Diplopia may occur due to functional impairment of sixth nerve palsy. Visual disturbance usually resolves after delivery.

PRES (POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME)

PRES is characterized by variable association of seizures activity, conscious impartment, headaches, visual abnormalities, nausea/ vomiting, and focal neurological signs. It is clinicoradiological condition diagnosed by appearance of symmetrical lesion of vasogenic edema, predominantly in parieto-occipital lobes. Coexistent ischemia / infarction has been reported due to vasoconstriction secondary to pressure from edema. PRES is not unique either to pregnancy or eclampsia and occur in any hypertensive state.

ABRUPTION PLACENTA

About 7% of all patient with eclampsia have premature separation of placenta. It is often an unexpected finding at time of delivery.

ACUTE RENAL FAILURE

Oliguria is common in patient with severe pre-eclampsia mainly due to volume depletion which respond to fluid challenge.

In rare case, oliguria may be due to ATN that occur in severe pre- eclampsia patient complicated by abruption and DIC.

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PULMONARY EDEMA

 Accumulation of fluid in the pulmonary interstitial spaces & alveoli which prevents adequate diffusion of both oxygen & CO2. Incidence 3% in pregnancy , 1:500. Most commonly seen in postpartum period.

 Profound respiratory distress

 Severe hypoxaemia

 Diffuse bilateral rales on auscultation

 No history of heart disease

2 main causes

 Cardiogenic / hydrostatic edema

o caused by high pulmonary capillary hydrastatic pressure

 Non cardiogenic/ permeability edema

o caused by capillary endothelial & alveolar epithelial damage, more common type

 Most common precipitating factor- Resuscitation for haemorrhage and vigorous treatment of preterm labour.

Clinical presentation

 Severe hypoxaemia

 Bilateral diffuse rales on auscultation.

 Young women without previous history of heart disease

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 Profound respiratory distress,

 Normal ECG

 Without cardiomegaly on Chest X Ray /ECHO

Management

 Propped up position

 O2 administration by nasal prongs

 Restriction of intravenous & oral fluids

 Furosemide 80-120mg followed by 20- 40mg IV 4-6hrs till symptomatic improvement.

 Aggressive use results in profound diuresis and improvement of respiratory symptoms.

 ACOG – CVP of swan Ganz cathetar monitoring in Severe preeclampsia women with cardiac, renal, in case of refractory hypertension, oliguria and pulmonary edema.

HELLP SYNDROME

INCIDENCE OF HELLP SYNDROME

Overall incidence of HELLP Syndrome is one in thousand pregnancies.

Incidence in preeclamptic and eclamptic mother is 4 to 12 %⁸⁵. 30 % occur in postpartum period 70 % occurs in antepartum period in the third trimester and often associated in Caucasian multiparous women aged about 25 years. Of the two thirds of women who are first diagnosed with HELLP syndrome

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antepartum, 10% will be identified before 27 weeks, 20% in pregnancies beyond 37 weeks, and the majority 70% occurring between 27 and37 weeks gestation.

Esan et al (1997)⁸⁶ reported that HELLP syndrome can occur after a normal delivery in a woman whose blood pressure has remained normalthroughout the antenatal period.

Donaldson (1978): Reported that some may experience visual disturbances.

Neurological affection can also result.

Jaundice is a rare complication and hyperbilirubinemia may result froma combination of hemolysis and liver cell necrosis. However it is unusual foricterus to be clinically apparent.

Woods et al (1992)⁸⁷: Maternal ascitis is frequently found at Caesarean delivery in 65% of patients with HELLP syndrome.

Cunningham et al. (1993)⁸⁸:The risk of opportunistic infections may be increased in patients with HELLP syndrome, because of generalised (Both B&T Cell) immunosuppression and profound decrease in monocyte phagocytic and bactericidal activity.

CLASSIFICATION

 Classification system are of two types based on platelet count and LDH level which reflect the senility of disease process and rapidity of recovery from HELLP Syndrome

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The Mississippi Triple Class System further classifies the syndrome based on the platelet count:

 Class I (severe thrombocytopenia): platelet count below 50,000/mm3

 Class II (moderate thrombocytopenia): platelet count between 50,000 and 100,000/mm3

 Class III (AST . 40 IU/L, mild thrombocytopenia): platelet count between 100,000 and 150,000/mm3

Tennessee System also classifies HELLP into complete syndrome if there is presence of all three parameters abnormal (AST/ALT, LDH, Platelets) and incomplete syndrome if there are one or two of the three as abnormal Sibai proposed strict diagnostic criteria for HELLP syndrome

1. Intravascular hemolysis diagnosed by abnormal peripheral blood 1. smear

2. Increased serum bilirubin ≥20.5 μmol/l or ≥1.2mg/100ml 3. Elevated LDH levels (>600 units/l)

4. Platelet count of < 1,00,000/microlitre 5. Serum AST (SGOT) levels > 70 IU/l 6. Low serum haptoglobin level

7. Drop in Hb% level unrelated to blood loss

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OTHER CLASSIFICATIONS OF HELLP SYNDROME Sibai et al ; Platelet Count < 1,00,000/mm3

AST > 70 IU/L LDH > 600 IU/L Van Pampus; Platelet Count < 1,00,000/mm3 AST > 50 IU/L LDH >600 IU/L Visser and Wallenburg < 1,00,000mm3 AST > 30 IU/L

DIFFERENTIAL DIAGNOSIS FOR THE HELLP SYNDROME

Different types of thrombocytopenia

 Benign thrombocytopenia of pregnancy

 Immunologic thrombocytopenia (ITP)

 Thrombocytopenia due to folate deficiency

 Systemic lupus erythematosus

o Thrombotic thrombocytopenic purpura (TTP) o Hemolytic uremic syndrome (HUS)

 Acute fatty liver of pregnancy

 Infectious and inflammatory disease o Urinary tract infections

o Acute pancreatitis

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o Gastritis and gastric ulcers o Cholecystitis or cholangitis o Hepatitis

Investigation

 Haematocrit, hemoglobin, peripheral smear, urine albumin, 24 hrs urinary protein, renal function test, liver function test, serum uric acid and platelet.

 If platelet count or liver enzymes are abnormal, coagulation studies and testing for hemolysis are indicated.

MANAGEMENT PROTOCOL FOR HELLP SYNDROME

 Refer to Tertiary Medical Centre.

 Admit in labor ward

 Do laboratory investigation.

 Prevent seizures with injection Magnesium sulphate.

 Control of blood pressure with anti-hypertensive.

 ^{Bed rest.}

 Fluid and electrolyte correction.

Hemotherapy with blood and blood products.

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MATERNAL MORTALITY

Maternal mortality due to eclampsia varies from 1 to5%.

Cause of death in eclampsia is

 Cerebral haemorrhage

 DIC

 Acute renal failure

 Cardio pulmonary arrest

 HELLP syndrome

PERINATAL MORTALITY

 The perinatal mortality is due to prematurity, hypoxia and effects of drugs.

ECLAMPSIA PROPHYLAXIS:

 80-90% of eclampsia has prodromal symptoms.

 When patient has imminent symptoms, she should be kept in quiet room and sedation can be given if necessary.

 Antihypertensive therapy should be initiated and blood pressure to be controlled.

 Magnesium sulphate is given to preventseizure.

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MANAGEMENT OF ECLAMPSIA

 General Management

 Controlling seizures

 Controlling the blood pressure.

 Termination of pregnancy

CLEARING THE AIRWAYS

 Patient nursed in left lateral position and suction of secretions done to prevent aspiration.

 Airway or padded tongue blade placed between teeth to avoid tongue bite and maintain airway. O2 is given at rate of 8 – 10l/min.

CONTROL OF SEIZURES

MAGNESIUM SULPHATE: CATEGORY A DRUG

 MgSo4 is drug of choice for prevention and treatment of eclampsia.

Magnesium Sulphate is MgSo4.7H2O.

 Magnesium sulphate injection was first used to prevent eclamptic seizures in 1906 by Horn in Germany, who injected it intrathecally.

 In 1925 and 1926 MgSO4 was used intravenous and intramuscularly to control convulsions.

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MECHANISMOF ACTION– Mgso4

Neuromuscular junction– It blocks the NMDA(N-methyl D-asparate) receptors and inhibits the release of excitatory neurotransmitter such as glutamate and acetylcholine and increasing the seizure threshold.

Vasodilator action-It increases blood flow to the brain by producing endothelial vasodilator prostacyclin.It acts on the vascular calcium ion channels and decreasing calcium and causes vasodilatation.

PHARMACOKINETICS

 Administered INTRAVENOUSLY or INTRAMUSCULARLY.

 Half life of MgSO4 5-6 Hrs

 IV route – immediate action and lasting for 30 minutes

 IM route – action within 1-2hrs and lasting for 6hrs.

 25-30% protein binding.

 Crosses the placenta.

 Serum therapeutic concentration 4 -7 mEq/L.

 Excreted by kidney

REGIMENS

 Pritchard regimen

 Zuspan regimen

 Sibai regimen

 Sardesai regimen

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 Sokoto regimen

 Dhaka regimen

PRITCHARD REGIMEN

INTRAVENOUSLOADINGDOSE: 4g of 20% magnesium sulphate i.e. 20ml slow IV for 15mins. one ampoule of 50% magnesium sulphate contain 1g = 2ml of drug. To make a concentration of 20% , 4 ampoules(8ml) are taken and dilute with distilled water12ml in a 20cc syringe.

4ampoules (4g=8ml)+12ml distilled water=20mlof20%MgSO4

IF CONVULSION RECUR AFTER 15MINS, 2g of 20% MgSO4 IS GIVEN IV OVER 5MINS.

INTRAMUSCULARLOADINGDOSE: 5g(10ml) of 50% MgSO4 deep intramuscular injection 3 inch in the upper outer quadrant of each buttock using 20 gauge needle.

MAINTENANCEDOSE- INTRAMUSCULARLY: 5g (10ml) of 50%

MgSO4 deep IM injection in alternate buttock every 4hrs continued upto 24hrs after delivery or after last convulsion whichever is later.

ZUSPAN REGIMEN⁸⁹:

 LOADING DOSE: 4g of IVMgSO4 in 100ml of normal saline given over 15mins.

 MAINTENANCE DOSE: 1g/ 50ml of normal saline/hr is given for 24hrs after delivery or convulsion whichever is later..

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SIBAI REGIMEN⁸⁹

 LOADING DOSE: 6g of IV MgSO4 in100ml of normal saline given over 15mins.

 MAINTENANCE DOSE: 2g/100ml of normal saline/hr is given for 24hrs after delivery or convulsion whichever is later

SIDE EFFECTS

 Feeling of warmth

 Facial flushing

 Lethargy

 ^Sweating

 Confusion

MONITORING FOR MAGNESIUM SULPHATE TOXICITY

 Deep tendon reflexes should be present

 Respiratory rate should be >16breaths/min

 Urine output should be atleast 30ml/hr

 Pulse oximetry SpO2 should be >96%.

TOXICITY

 Disappearance of patellar reflex is the First Impending Toxicity of MgSO4.

 Best marker of magnesium toxicity is Pulseoximetry O2 saturation – begins to drop before the evidence of respiratory depression.

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Monitoring during IV infusion:

 Magnesium toxicity is monitored

 Assessing the deep tendon reflex periodically.

Serum Magnesium level can be measured at 4 – 6hrs and infusion is adjusted to maintain the level of 4 – 7meq/l (THERAPEUTIC LEVEL)

Patellar reflex is lost if MgSO4 level 8-10meq Respiratory depression if MgSo4 level > 12meq Cardiac arrest if MgSo4 >30 meq

Serum Magnesium level is measured if serum creatinine is > 1.0mg/dl.

RECURRENCE OF FIT

If convulsion persist 15mins after initial dose give 2gm of MgSo4 iv as 20% solution at a rate not to exceed1gm/min.

ANTIDOTE FOR MgSO4 TOXICITY

INTRAVENOUS CALCIUM GLUCONATE, 10ml (1g) of a 10% solution given over 10 minutes.

• Action: Calcium anatagonizes the effect of magnesium by increasing the amount of acetylcholine at the neuromuscular junction.

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INDICATION: RESPIRATORY DEPRESSION CONTRAINDICATION: 1.Mysthenia Gravis 2.Renal Failure.

THE INITIAL LOADING DOSE OF 4g CAN BE SAFELY ADMINISTERED REGARDLESS OF RENAL FUNCTION

 The MAGPIE¹ trial was a large multi centric randomised trial, proved beyond doubt the effectiveness of magnesium sulphate in proplylaxis and its safety.

 Simth⁹⁰ JM et al.,: The study is done for the confirmation of safety profile of MgSo4. The side effects were found at low rate. In their study the side effect of absent patellar reflex is 1.6%, respiratory depression is1.3% and use of Calcium gluonate to reverse the effect of MgSo4is

<0.2%.

 The Multinational Eclampsia Trial Collaborative Group Study (1995)¹ Magnesium Sulphate has lower incidence of recurrent seizure and maternal death rate compared to phenytoin and diazepam.

Magnesium Sulphate is more effective in controlling seizure than lyticcocktail.

 Baha⁹¹M.Sibai et al: MgSo4 is equally effective in preventing recurrent seizure in all the three regimen (Pitchard, Zupan and Sibai).

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 Singh⁹⁰ et al: Magnesium sulphate given by Pitchard and Sibai regimen was 100% effective in controlling recurrent seizure and 98% in Zupan regimen.

Maternal consideration

When serum magnesium level is relatively high myometrial contractility is depressed. However the therapeutic dose given has no effect on myometrial contractility. Levno⁹² and colleagues (1998) showed MgSo4 did not alter the need for oxytocin stimulation of labour, admission-delivery interval and mode of delivery. For inhibition of uterine contractility at least serum magnesium level should be 8 to 10meq/l.

Fetal consideration:

 When parenterally administered it crosses the placenta and increase the fetal level. It remains controversial whether MgSo4 reduces fetal heart variability andreactivity.

 Williams¹: MgSo4has NeuroProtective effect against cerebral palsy in very low-birth weight infants.

Phenytoin

It was synthesized in 1908 as a barbiturate analogue.

Mechanism

By prolonging the inactivated state of voltage sensitive neuronal Na⁺ channel, phenytoin has stabilizing influence on neuronal membrane.

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Maternal consideration

Clearance is increased during pregnancy, dose adjustment should be based on clinical symptom and not solely on serum drug concentration.

Side effects

Gingival hyperplasia, Megaloblastic anaemia, Hirsutism, Osteomalacia Leucopenia, Agranulocytosis, Exfolative dermatitis, Polyarteritis nodosa, Steven Johnson Syndrome, SLE.

Fetal consideration

Phenytoin crosses the human placenta. If given in 1^st trimester causes fetal hydantion syndrome – hypoplastic phalangx, microcephaly, cleft palate and hare lip.

Control of Blood pressure: Labetalol:

MECHANISM OF ACTION

 First drug developed to block both alpha & beta receptors

 Selective alpha 1, non selective beta 1 & beta 2 adrenergic receptors blocker

 Acts by decreasing peripheral vascular resistance with little or no effect on cardiac output

 Ratio of alpha to beta blockade is 1:7 for intravenous form

 Has no intrinsic sympathomimetic activity.

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PHARMACOKINETICS

 Onset of action-5 mins

 Peak action-10-15mins

 Duration of action-45mins to 6 hours

 Has first pass metabolism in liver

Dose: Labetolol-200-400mg/day in 2 divided doses.

Maximum dose 2400mg¹ Pregnancy Category C.

Labetolol is considered as drug of choice to control blood pressure (NICE guidelines).

LABETALOL INJECTION

 Labetalol hydrochloride ampoule-100mg/20ml

 Each ml contains 5mg

 Store below 30 degrees

 Protect from light

INDICATION OF USE

 Primary medicine of choice of severe hypertension in pregnancy

 Systolic BP>160 mmhg, diastolic BP>110 mmhg

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INTRAVENOUS LABETOLOL

• Labetalol 20mg iv bolus over 2mins

• Increase dose of labetalol to 40mg after 10mins

• Increase dose of labetalol to 80mg after 10mins

• Repeat dose of labetalol 80mg again after 10mins

LABETOLOL INFUSION

500mg (100ml) of labetalol added to 400ml of normal saline solution (1mg/ml) Administered at initial rate of 20mg/hr(20ml/hr)

• If blood pressure does not fall into expected range in 20 mins , dose is doubled every 20mins duration

• Continued to double till an expected range is obtained or maximum dose of 220mg/hour is given

MAXIMUM DOSE 220MG¹

CONTRAINDICATIONS

 Asthma/ COPD

 Bradycardia

 Severe hypotension

 Shock

 Heart failure

 Hypersensitivity to labetalol

 Studies related to intravenous labetalol

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RCOG -2019

 Oral Nifedipine versus intravenous labetalol for acute blood pressure control in hypertensive emergencies.

 Both drugs are equally effective in controlling acute emergencies of GHT.

MEDLINE-2006

 Compares the efficacy of labetalol vs hydralazine

 Both were found to have equal effect

Nifedipine

 Calcium channel blocker

 Dose: 10-20mg three to four times daily, 10-20mg once or twice daily in extended release tablet

 Maximum dose that can be given is120mg/day.

Pregnancy Category C Maternal Consideration:

 Proven safe and effective. In maternal cerebral blood flow there is reduction in middle cerebral artery flow velocities but there is no change in uteroplacental flow.

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FETAL CONSIDERATION

 Nifidipine crosses the human placenta. Newborn exposed to nifedipine has lower NICU admission rates, lower incidences of RDS, intracranial bleeding and neonatal jaundice.

OBSTETRIC MANAGEMENT

 Termination of pregnancy is cure for Imminent eclampsia and eclampsia.

 The mode of delivery depends on gestational age, fetal presentation and cervical scoring.

 Timing of delivery affects the outcome of both mother and baby. A rushed delivery in unstable patient and delay in delivery in sick patient may cause maternal mortality.

 Vaginal delivery is preferred route after eclamptic seizure. Following seizure labour starts spontaneously or can be induced to improve Bishop Score. Prolonged induction is however beavoided.

 In current obstetrical practice the majority of eclamptic women are delivered by cesarean section. Liberalization of cesarean section for eclamptic women is done inorder to reduce the maternal morbidity.

Cesarean is done for term fetus with unfavourable cervix, poor progression of labour and fetal distress..

 Anesthesia of choice is regional, spinal or epidural.

 In postpartum period first 24 - 48hrs is crucial as BP fluctuate and patient is at risk of developing complication.

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 Antihypertensive is continued throughout the labour and required for 24 - 48hrs and need to be gradually decreased.

Postnatal assessment

 If hypertension or proteinuria persist after 6weeks postpartum, it is necessary to investigate further.

 It is important to counsel patient for early booking in future pregnancies.

 Long term prognosis and counselling for future pregnancies (including contraception) should be discussed.

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MATERIALS AND METHODS

SOURCE OF DATA: The study was carried out in the department of Obstetrics and Gynaecology, Government Theni Medical College during the period of October 2017 to September 2019.

STUDY DESIGN: Prospective study was conducted on patient admitted for imminent symptoms & complications.

STUDY CASES: 100 Antenatal mother were selected for the study.

 Group A-50 known case of Preeclampsia presented with severe symptoms.

 Group B-50 previously Normotensive patients present with imminent symptoms of eclampsia.

PLACE OF STUDY: Govt Theni Medical College DURATION OF STUDY: One year

CONSENT : Consent obtained from patients & attenders.

The purpose of this study is to analyse the determinants of imminent eclampsia and eclampsia like age, parity, socio economic status, booking status, referral status, parity, gestational age, prodromal symptoms, blood pressure, measures taken, convulsion details, mode of delivery maternal and perinatal complications were analysed.

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INCLUSION CRITERIA

1) All Pregnant Women With Imminent Symptoms

2) All Pregnant Women With Antepartum Eclampsia preceded with Imminent Symptoms

EXCLUSION CRITERIA

Antenatal Patient presented as eclampsia or Post ictal Phase in admission- without prodromal symptoms

Other causes of convulsion in pregnancy

 Epilepsy

 Trauma (headinjury)

 Metabolic disorder (anaemia, electrolyte imbalance, hepatic / renal failure, hypogylcemia)

 Poisoning (Strychnine, CNS stimulant)

 Infection (Meningitis, Encephalitis, Cerebral Malaria)

 Functional

HISTORY

History was elicited from patient and if patient is unconscious or in postictal state, history was elicited from attender. A detailed history of the patient regarding age, parity, socio-economic status, booking status, gestational age, prodromal symptoms, details about imminent symptoms, convulsions,

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referral and treatment (including MgSo4 administration) at referral centre were noted down. Details about previous obstetric history were recorded. (recurrent cause).

EMERGENCY CARE

When the patient with convulsion is received, Patient nursed in left lateral position and suction of secretions done to prevent aspiration. The bedside rails is elevated to prevent maternal injury. Mouth gag is placed to prevent tongue bite. Oxygen by mask is given at rate of 8-10 litre/minute. IV lifeline started. Stabilize the patient ABC.

CLINICAL EVALUATION

Detailed general examination and obstetric examination were done. On general examination conscious level, anaemia, pedal edema, facial puffiness, jaundice, BMI, Blood pressure, pulse rate, respiratory rate, temperature, thyroid, fundus and nature of fits were recorded. RS, CVS, CNS were examined.

For all cases were started on T.Labetalol 100mg bd is started and dose adjusted according to BP. If diastolic BP is >110mmHg.T.nifedipine 10mg TDS started. For patient who had uncontrolled BP, IV labetalol given. Dose of IV labetalol is 20mg IV bolus given initially. If the blood pressure does not decrease to the expected range (80-110 diastolic) in 10 minutes, additional dose of 40mg, then 80mg may be administered every 10 minutes as needed to a maximum of 220mg. For continuous IV administration, one 20-ml vial

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containing 100mg labetalol is added to 400ml of lactated Ringers solution. The resultant solution will contain 1mg/ml, the initial dose is 20mg/hour. This dose can be doubled every 20 minutes up to a maximum of 220mg/hour. The therapeutic range is usually between 50 and 200mg/hour. Once the blood pressure reaches the desired level, the IV solution is discontinued and the patient started an oral labetalol, 100-400mg every 6 -12 hours upto max of 2400mg.

Loading dose MgSo4 given as prophylactically in all patients with imminent symptoms and therapeutically in eclampsia. MgSo4 was given according to Pritchard regimen.

OBSTETRIC MANAGEMENT

After stabilizing the patient, mode of delivery was planned according to gestational age, presentation, viability of fetus, cervical scoring and pelvic assessment.

Vaginal delivery is preferred and induction done with PGE2 gel for patient who was not in labour. When patient was in labour, acceleration was done with aminotomy and oxytocin infusion. LSCS was done for maternal, fetal indication and when PGE2 induction failed.

Immediately after delivery of baby 10 units of oxytocin given intramasucular. The patient was carefully monitored anticipating complication like postpartum hemorrhage and postpartum ecalmpsia.

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The patient was observed for 48 hours in eclampsia room. Blood pressure was monitored and antihypertensives continued. MgSo4 was continued 4^th hourly till 24hours after delivery by monitoring patellar reflex, respiratory rate and urine output. After 48hours patient shifted to postnatal or postoperative ward respectively.

Neonate

Details of baby such as birth weight, maturity, sex and complication like prematurity, IUGR, birth asphyxia and mortality were recorded. Baby was followed up till discharge.

Postpartum care

Postnatally antihypertensive drugs continued till 12weeks¹ and slowly tapered when blood pressure return to normal. While discharge patient was advised for contraception and review after a week. Patient was advised about early booking in next pregnancy.

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OBSERVATION AND RESULTS

For period of 1 year from September 2018- September 2019

Total number of deliveries during the period of September 2018- September 2019 in our hospital is 8076

Incidence of Imminent eclampsia & complications

 Incidence of Imminent eclampsia – 1.2%

 Incidence of Eclampsia -0.1%

 Incidence of HELLP– 0.04%

 Incidence of Pulmonary Oedema -0.06%

 Incidence of PRES– 0.07%

 Incidence of Abruption – 0.14%

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TABLE 1: AGE DISTRIBUTION

AGE GROUP A % GROUP B %

<20yrs 7 14 14 28

20- 25yrs 20 40 19 38

25- 30yrs 15 30 11 22

30-35yrs 7 14 5 10

>35yrs 1 2 1 2

MEAN`

SD

25.42 4.7

24.3 6.0

P Value 0.1 P>0.05

 60% imminent eclampsia occurred in age < 25yrs.

 21 % imminent eclampsia occurred in age <20yrs.

 28% in group B presented with imminent eclampsia in <20yrs. In Group A14% presented with imminent symptoms in < 20yrs.

 P value >0.05 , statistically not significant

FIGURE 1: AGE DISTRIBUTION

7

20

15

7

1 14

19

11

5

1 0

5 10 15 20 25

<20YRS 21-25 26-30 30-35 >35

GROUP A GROUP B

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TABLE 2: PARITY

 59 % imminent eclampsia occurred in primigravida. 41% in multigravida.

 32 out 50 were primi in Group B, 27 out 50 were primi in Group A.

 P value is 0.01, statistically significant.

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FIGURE 2 (PARITY)

PRIMI

MULTIGRAVIDA

PARITY GROUP A GROUP B

P Value

PRIMIGRAVIDA 27 32

0.01

MULTIGRAVIDA 23 18

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TABLE 3: SOCIO ECONOMIC CLASS

Class GROUP A GROUP B

P Value P>0.05 (0.3)

I - -

II - -

III 9 8

IV 20 20

V 21 22