Williams 34Williams 34

Hypertensive disorders in Hypertensive disorders in pregnancy (2)pregnancy (2)

부산백병원 산부인과부산백병원 산부인과R3 R3 박영미박영미

ManagementManagement

Long-term consequencesLong-term consequences

ManagementManagement

Basic management objectivesBasic management objectives Termination of pregnancy with the least Termination of pregnancy with the least

possible trauma to mother and fetuspossible trauma to mother and fetus Birth of an infant who subsequently thrivesBirth of an infant who subsequently thrives Complete restoration of health to the motherComplete restoration of health to the mother

The most important information The most important information -> Precise knowledge of the age of the fetus-> Precise knowledge of the age of the fetus

Early prenatal detectionEarly prenatal detection

The protocol of Parkland hospital The protocol of Parkland hospital

Return visits at 3 to 4 day intervals Return visits at 3 to 4 day intervals ① ① New onset diastolic blood pressure New onset diastolic blood pressure (81-89 mmHg)(81-89 mmHg) ② ② Sudden abnormal weight gain Sudden abnormal weight gain (more than 2 pounds per week during the (more than 2 pounds per week during the

third third trimester)trimester)

The protocol of Parkland hospitalThe protocol of Parkland hospital

Outpatient surveillance is continued unless superveneOutpatient surveillance is continued unless supervene

① ① Overt hypertensionOvert hypertension

② ② ProteinuriaProteinuria

③ ③ Visual disturbancesVisual disturbances

④ ④ Epigastric discomfort Epigastric discomfort

Antepartum hospital managementAntepartum hospital management

Hospitalization is consideredHospitalization is considered

New onset hypertension, especially if there is persisteNew onset hypertension, especially if there is persistent or worsening hypertensionnt or worsening hypertension

Development of proteinuriaDevelopment of proteinuria

A systemic evaluationA systemic evaluation

Daily scrutiny for clinical findings Daily scrutiny for clinical findings : headache, visual disturbances, epigastric pain, : headache, visual disturbances, epigastric pain, rapid weight gainrapid weight gain

Weight on admittance and every day thereafterWeight on admittance and every day thereafter

Analysis for proteinuria on admittance and at least eveAnalysis for proteinuria on admittance and at least every 2 days thereafterry 2 days thereafter

Blood pressure readings in the sitting position with an Blood pressure readings in the sitting position with an appropriate size cuff every 4 hoursappropriate size cuff every 4 hours

(except between midnight and morning)(except between midnight and morning)

A systemic evaluationA systemic evaluation

Measurement of plasma or serum creatinine, hematocMeasurement of plasma or serum creatinine, hematocrit, platelets, serum liver enzymesrit, platelets, serum liver enzymes

(the frequency to be determined by the severity of (the frequency to be determined by the severity of hypertension)hypertension)

Frequent evaluation of fetal size and amnionic fluid volFrequent evaluation of fetal size and amnionic fluid volume either clinically or with sonographyume either clinically or with sonography

In mild preeclampsia In mild preeclampsia

Reduced physical activity throughout much of the day iReduced physical activity throughout much of the day is beneficials beneficial

Absolute bed rest is not necessaryAbsolute bed rest is not necessary Sedatives and tranquilizers are not prescribedSedatives and tranquilizers are not prescribed Ample, but not excessive, protein and calories should Ample, but not excessive, protein and calories should

be included in the dietbe included in the diet Sodium and fluid intakes should not be limited or forcSodium and fluid intakes should not be limited or forc

eded

->-> if these observations lead to a diagnosis of if these observations lead to a diagnosis of severe preeclampsia, further management is severe preeclampsia, further management is the same as eclampsiathe same as eclampsia

Termination of pregnancyTermination of pregnancy

Delivery is the cure for preeclampsiaDelivery is the cure for preeclampsia

The prime objectivesThe prime objectives To forestall convulsionTo forestall convulsion To prevent intracranial hemorrhageTo prevent intracranial hemorrhage To prevent serious damage to vital organsTo prevent serious damage to vital organs To deliver a healthy infantTo deliver a healthy infant

▶ ▶ Indicative sign of convulsionIndicative sign of convulsion① ① HeadacheHeadache② ② Visual disturbances Visual disturbances ③ ③ Epigastric painEpigastric pain④ ④ OliguriaOliguria

▶ ▶ Severe preeclampsiaSevere preeclampsia-> Anticonvulsant-> Anticonvulsant-> Antihypertensive therapy-> Antihypertensive therapy-> Followed delivery-> Followed delivery

In milder preeclampsiaIn milder preeclampsia

Hesitation to deliver the fetus because of prematurityHesitation to deliver the fetus because of prematurity

Assesments of fetal well-being and placental functionAssesments of fetal well-being and placental function Nonstress testNonstress test Biophysical profileBiophysical profile Lecithin-sphingomyelin ratio in amnionic fluidLecithin-sphingomyelin ratio in amnionic fluid

In moderate or severe preeclampsiaIn moderate or severe preeclampsia

Delivery is usually advisableDelivery is usually advisable

Labor should be induced by intravenous oxytocinLabor should be induced by intravenous oxytocin Preinduction cervical ripening with a prostaglandin Preinduction cervical ripening with a prostaglandin

or osmotic dilator or osmotic dilator

Cesarean delivery, whenever..Cesarean delivery, whenever.. Labor induction almost certainly will not succeedLabor induction almost certainly will not succeed Attempts at induction have failedAttempts at induction have failed

Near term, milder degrees of preeclampsiaNear term, milder degrees of preeclampsia

With a soft, partially effaced cervixWith a soft, partially effaced cervix Observation is more risk to the mother and fetus thObservation is more risk to the mother and fetus th

an dose induction of labor by carefully monitored oxan dose induction of labor by carefully monitored oxytocin infusionytocin infusion

The cervix is firm and closedThe cervix is firm and closed Not likely to be the above caseNot likely to be the above case The hazards of cesarean delivery may be greater thThe hazards of cesarean delivery may be greater th

an that of allowing the pregnancy to continue under an that of allowing the pregnancy to continue under close observation until the cervix is more suitable fclose observation until the cervix is more suitable for induction or induction

Elective cesarean deliveryElective cesarean delivery

Labor induction to effect vaginal delivery has traditionaLabor induction to effect vaginal delivery has traditionally been considered to be in the best interest of the mlly been considered to be in the best interest of the motherother

Several concerns have led some practitioners to advocSeveral concerns have led some practitioners to advocate cesarean deliveryate cesarean delivery

Unfavorable cervix precluding successful induction Unfavorable cervix precluding successful induction of laborof labor

Perceived sense of urgency because of the severity Perceived sense of urgency because of the severity of preeclampsiaof preeclampsia

The need to coordinate neonatal intensive careThe need to coordinate neonatal intensive care

Antihypertensive drug therapyAntihypertensive drug therapy

Sibai (1987)Sibai (1987): Randomized study to evaluate the effectiveness of : Randomized study to evaluate the effectiveness of labetalol (200 nulliparous, 26~35 weeks)labetalol (200 nulliparous, 26~35 weeks)

Women given labetalolWomen given labetalol : Significantly lower mean blood pressures: Significantly lower mean blood pressures

Mean pregnancy prolongation, gestational age at delivMean pregnancy prolongation, gestational age at delivery, birth-weightery, birth-weight

: No differences : No differences

The cesarean delivery rates, the number of infants adThe cesarean delivery rates, the number of infants admitted to special care nurseries mitted to special care nurseries

: Similar: Similar

Growth restricted infantsGrowth restricted infants : Twice as frequent in women given labetalol : Twice as frequent in women given labetalol

## The use of ACEI during the second and third trimester The use of ACEI during the second and third trimesters should be avoideds should be avoided

: oligohydramnios: oligohydramnios: fetal growth restriction : fetal growth restriction : bony malformation: bony malformation: limb contractures: limb contractures: persistent patent ductus arteriosus: persistent patent ductus arteriosus: pulmonary hypoplasia: pulmonary hypoplasia: respiratory distress syndrome: respiratory distress syndrome: prolonged neonatal hypotension: prolonged neonatal hypotension: neonatal death: neonatal death

Delayed delivery with severe preeclampsiaDelayed delivery with severe preeclampsia

Severe preeclampsia are usually delivered without delSevere preeclampsia are usually delivered without delayay

In recent years, a different approach in the treatment In recent years, a different approach in the treatment of women with severe preeclampsia remote from termof women with severe preeclampsia remote from term

The aim of improving infant outcome without The aim of improving infant outcome without compromising the safety of the mothercompromising the safety of the mother

Careful daily, more frequent monitoring of the pregnanCareful daily, more frequent monitoring of the pregnancy in the hospital with or without drugs to control hypercy in the hospital with or without drugs to control hypertension tension

Randomized controlled trial of Sibai (1994)Randomized controlled trial of Sibai (1994)

: severe preeclampsia in 95 women, 28-32weeks: severe preeclampsia in 95 women, 28-32weeks

Expectant managementExpectant management Bed rest Bed rest Either oral labetalol or nifedipineEither oral labetalol or nifedipine

Aggressive managementAggressive management Glucocorticoid administration for fetal lung maturation Glucocorticoid administration for fetal lung maturation

-> Pregnancy was prolonged for a mean of 15.4 -> Pregnancy was prolonged for a mean of 15.4 days in the expectant management group with an days in the expectant management group with an improvement in neonatal outcomeimprovement in neonatal outcome

Vigil-De Gracia (2003)Vigil-De Gracia (2003)

: 129 women at 24 to 34 weeks with either severe or superimpose: 129 women at 24 to 34 weeks with either severe or superimposed preeclampsiad preeclampsia

Treatment with delayed deliveryTreatment with delayed delivery Bed restBed rest Magnesium sulfate for 48 hoursMagnesium sulfate for 48 hours Bolus doses of antihypertensive medications to control blood Bolus doses of antihypertensive medications to control blood

pressures exceeding 160/110 mmHgpressures exceeding 160/110 mmHg Volume expansion Volume expansion Dexamethasone to promote fetal maturationDexamethasone to promote fetal maturation

Indications for deliveryIndications for delivery Uncontrollable blood pressureUncontrollable blood pressure Fetal distressFetal distress Placental abruptionPlacental abruption Renal function deteriorationRenal function deterioration HELLP syndromeHELLP syndrome Persistent severe symptomsPersistent severe symptoms Attainment of 34 weeks gestationAttainment of 34 weeks gestation

The resultThe result The average pregnancy prolongation was 8 dayThe average pregnancy prolongation was 8 day No maternal deathNo maternal death 6 stillbirths6 stillbirths 11 placental abruptions11 placental abruptions 28 infants diagnosed with growth restriction28 infants diagnosed with growth restriction

Hall (2000)Hall (2000): 360 women with severe preeclampsia before 34wks: 360 women with severe preeclampsia before 34wks

The resultThe result Mean duration : 11 daysMean duration : 11 days Placental abruption : 20%Placental abruption : 20% Pulmonary edema : 2%Pulmonary edema : 2% Eclampsia : 1.2%Eclampsia : 1.2%

# We are reluctant to advise clinicians that it is safe to expe# We are reluctant to advise clinicians that it is safe to expectantly manage women with persistent severe hypertensictantly manage women with persistent severe hypertension, significant hematological, cerebral, liver abnormalities on, significant hematological, cerebral, liver abnormalities due to preeclampsia due to preeclampsia

Glucocorticoids Glucocorticoids

To enhance fetal lung maturationTo enhance fetal lung maturation

Dose not seem to worsen maternal Dose not seem to worsen maternal hypertensionhypertension

Decrease in the incidence of respiratory Decrease in the incidence of respiratory distressdistress

Improve fetal survival Improve fetal survival

The randomized clinical trial (1999)The randomized clinical trial (1999): 218 women with severe preeclampsia, 26-34wks: 218 women with severe preeclampsia, 26-34wks

The resultThe result Neonatal complications were decreased significantlNeonatal complications were decreased significantl

y when betamethasone was given compared with ply when betamethasone was given compared with placeboacebo

respiratory distressrespiratory distress intraventricular hemorrhageintraventricular hemorrhage deathdeath

ButBut 2 maternal death2 maternal death 18 stillbirths18 stillbirths

High risk pregnancy unitHigh risk pregnancy unit

In 1973, at Parkland Hospital In 1973, at Parkland Hospital

The resultThe result

The majority of women have a beneficial response The majority of women have a beneficial response by disappearance or improvement of hypertensionby disappearance or improvement of hypertension

Theses women are not “cured” Theses women are not “cured” : nearly 90% have recurrent hypertension before : nearly 90% have recurrent hypertension before

or or during laborduring labor

Provider costs are slight compared with the cost of neProvider costs are slight compared with the cost of neonatal intensive care for a preterm infantonatal intensive care for a preterm infant

Relatively simple physical facilityRelatively simple physical facility

Modest nursing careModest nursing care

No drugs other than iron and folate supplementNo drugs other than iron and folate supplement

The very few laboratory test that are essentialThe very few laboratory test that are essential

Home health careHome health care

If hypertension abates within a few daysIf hypertension abates within a few days -> Further hospitalization is not warrnated-> Further hospitalization is not warrnated

Mild to moderate hypertension, without proteinuriaMild to moderate hypertension, without proteinuria -> Managed at home-> Managed at home -> Continue as long as -> Continue as long as : the disease dose not worsen : the disease dose not worsen : fetal jeopardy is not suspected: fetal jeopardy is not suspected

Outpatient managementOutpatient management Sedentary activity throughout the greater part of the daySedentary activity throughout the greater part of the day Instructed in detail about reporting symptomsInstructed in detail about reporting symptoms Daily blood pressure monitoring Daily blood pressure monitoring Weight and spot urine protein : three times weeklyWeight and spot urine protein : three times weekly A home health nurse visited : twice weeklyA home health nurse visited : twice weekly Women were seen weekly in the clinicWomen were seen weekly in the clinic

In a study from Parkland Hospital (1995)In a study from Parkland Hospital (1995)-> Although, perinatal outcomes were similar-> Although, perinatal outcomes were similar-> the development of severe preeclampsia was -> the development of severe preeclampsia was more common in the home treated women than in more common in the home treated women than in hospitalized women hospitalized women

EclampsiaEclampsia EclampsiaEclampsia

: preeclampsia complicated by generalized tonic-clonic : preeclampsia complicated by generalized tonic-clonic convulsionsconvulsions

Major complicationsMajor complications Placental abruption (10%)Placental abruption (10%) Neurological deficits (7%)Neurological deficits (7%) Aspiration pneumonia (7%)Aspiration pneumonia (7%) Pulmonary edema (5%)Pulmonary edema (5%) Cardiopulmonary arrest (4%)Cardiopulmonary arrest (4%) Acute renal failure (4%)Acute renal failure (4%) Maternal death (1%) Maternal death (1%)

The time of onsetThe time of onset

Convulsions appear before, during, after labor -> eclaConvulsions appear before, during, after labor -> eclampsia is designated as antepartum, intrapartum, postmpsia is designated as antepartum, intrapartum, postpartumpartum

Most common in the last trimesterMost common in the last trimester

Increasingly more frequent as term approachesIncreasingly more frequent as term approaches

In more recent years, increasing shift toward the postpIn more recent years, increasing shift toward the postpartum periodartum period

Consideration with the onset of convulsions more than Consideration with the onset of convulsions more than 48hours postpartum48hours postpartum

ConvulsionConvulsion

The convulsive movements usually begin about the moThe convulsive movements usually begin about the mouth in the form of facial twitchingsuth in the form of facial twitchings

After a few seconds, the entire body becomes rigid in After a few seconds, the entire body becomes rigid in a generalized muscular contractiona generalized muscular contraction

This phase may persist for 15 to 20 secondsThis phase may persist for 15 to 20 seconds

Suddenly the jaws begin to open and close violently, aSuddenly the jaws begin to open and close violently, and soon after, the eyelids as wellnd soon after, the eyelids as well

The other facial muscles and then all muscles alternatThe other facial muscles and then all muscles alternately contract and relax in rapid successionely contract and relax in rapid succession

The muscles alternately contract and relax, may last aThe muscles alternately contract and relax, may last about a minutebout a minute

Gradually, the muscular movements become smaller aGradually, the muscular movements become smaller and less frequent, and finally the woman lies motionlesnd less frequent, and finally the woman lies motionlesss

Status epilepticusStatus epilepticus Continuous convulsion in untreated severe casesContinuous convulsion in untreated severe cases Unless treated, the first convulsion is usually the forerunner oUnless treated, the first convulsion is usually the forerunner o

f othersf others

After a seizure, coma then ensuesAfter a seizure, coma then ensues

The duration of coma after a convulsion is The duration of coma after a convulsion is variablevariable

When the convulsions are infrequent, the When the convulsions are infrequent, the woman usually recovers some degree of woman usually recovers some degree of consciousness after each attackconsciousness after each attack

As the woman arouses, a semiconscious As the woman arouses, a semiconscious combative state may ensuecombative state may ensue

In very severe cases, the coma persists from In very severe cases, the coma persists from one convulsion to another, and death may one convulsion to another, and death may result before she awakensresult before she awakens

RespirationsRespirations

Throughout the seizure the diaphragm has been fixed, Throughout the seizure the diaphragm has been fixed, with respiration haltedwith respiration halted

For a few seconds the woman appears to be dying froFor a few seconds the woman appears to be dying from respiratory arrestm respiratory arrest

But the she takes a long, deep, stertorous inhalation, But the she takes a long, deep, stertorous inhalation, and breathing is resumedand breathing is resumed

After an eclamptic convulsion, respirations are usually After an eclamptic convulsion, respirations are usually increased in rate and may reach 50 or more per minutincreased in rate and may reach 50 or more per minutee

Hypercarbia from lactic acidemia, hypoxiaHypercarbia from lactic acidemia, hypoxia

Cyanosis in severe casesCyanosis in severe cases

Other signOther sign

High feverHigh fever: a very grave sign : a very grave sign : the consequence of a central nervous system hemo: the consequence of a central nervous system hemo

rrhagerrhage

ProteinuriaProteinuria: almost always present and frequently pronounced: almost always present and frequently pronounced

Urine outputUrine output: diminished appreciably, occasionally anuria : diminished appreciably, occasionally anuria

Hemoglobinuria : commonHemoglobinuria : common

Hemoglobinemia : only rarelyHemoglobinemia : only rarely

The edemaThe edema : pronounced : pronounced : at times massive, but also be absent: at times massive, but also be absent

Recovery after deliveryRecovery after delivery

An increase in urinary output An increase in urinary output : an early sign of improvement: an early sign of improvement

Proteinuria, edema Proteinuria, edema : ordinarily disappear with a week: ordinarily disappear with a week

Blood pressure Blood pressure : return to normal within a few days to 2 weeks: return to normal within a few days to 2 weeks : the longer hypertension -> the consequence of : the longer hypertension -> the consequence of chronic vascular diseasechronic vascular disease

Eclampsia and deliveryEclampsia and delivery

Antepartum eclampsia Antepartum eclampsia : Labor may begin spontaneously shortly after convulsio: Labor may begin spontaneously shortly after convulsio

n and progress rapidlyn and progress rapidly

Intrapartum eclampsiaIntrapartum eclampsia : Contractions may increase in frequency and intensity: Contractions may increase in frequency and intensity : The duration of labor may be shortened : The duration of labor may be shortened

Fetal bradycardiaFetal bradycardia

Because of maternal hypoxemia and lactic acidemiBecause of maternal hypoxemia and lactic acidemia caused by convulsionsa caused by convulsions

Usually recovers within 3 to 5 minutesUsually recovers within 3 to 5 minutes

If it persists more than about 10 minutes, another If it persists more than about 10 minutes, another cause, such as placental abruption or imminent delcause, such as placental abruption or imminent delivery must be consideredivery must be considered

Complication of eclampsiaComplication of eclampsia

Pulmonary edemaPulmonary edema Aspiration pneumonitis from inhalation of gastric coAspiration pneumonitis from inhalation of gastric co

ntentsntents Cardiac failure as the result of a combination of seCardiac failure as the result of a combination of se

vere hypertension and vigorous intravenous fluid advere hypertension and vigorous intravenous fluid administrationministration

Cerebral hemorrhageCerebral hemorrhage Sudden death due to massive hemorrhageSudden death due to massive hemorrhage Hemiplegia due to sublethal hemorrhageHemiplegia due to sublethal hemorrhage More likely in older women with underlying More likely in older women with underlying chronic hypertensionchronic hypertension

BlindnessBlindness In about 10% In about 10% Retinal detachment or occipital lobe ischemia and Retinal detachment or occipital lobe ischemia and

edemaedema The prognosis for return to normal is good and is uThe prognosis for return to normal is good and is u

sually complete within a weeksually complete within a week

Altered consciousness, persistent comaAltered consciousness, persistent coma In about 5%In about 5% Due to extensive cerebral edemaDue to extensive cerebral edema Transtentorial uncal herniation may cause deathTranstentorial uncal herniation may cause death

Psychosis, violent tendencyPsychosis, violent tendency Lasts for several days to 2 weeksLasts for several days to 2 weeks Antipsychotic medications have proved Antipsychotic medications have proved

effectiveeffective The prognosis for return to normal is good, The prognosis for return to normal is good,

provided there was no preexisting mental provided there was no preexisting mental

illnessillness

Differential diagnosisDifferential diagnosis

EpilepsyEpilepsy EncephalitisEncephalitis MeningitisMeningitis Cerebral tumorCerebral tumor CysticercosisCysticercosis Ruptured cerebral aneurysmRuptured cerebral aneurysm

-> Until other such causes are excluded, all -> Until other such causes are excluded, all pregnant women with convulsions should be pregnant women with convulsions should be considered to have eclampsia considered to have eclampsia

PrognosisPrognosis

The prognosis for eclampsia is always serious The prognosis for eclampsia is always serious

It is one of the most dangerous conditions in pregnancIt is one of the most dangerous conditions in pregnancyy

Fortunately, maternal mortality due to eclampsia has dFortunately, maternal mortality due to eclampsia has decreased ecreased

Four decades ago : 10-15 % of maternal deathFour decades ago : 10-15 % of maternal death Between 1991 and 1997 : 6% of maternal deathBetween 1991 and 1997 : 6% of maternal death

1. Control of convulsion1. Control of convulsion

① ① Intravenously administered loading dose of Intravenously administered loading dose of magnesium sulfatemagnesium sulfate ② ② Followed by a continuous infusion of Followed by a continuous infusion of magnesium sulfatemagnesium sulfate

① ① Intramuscular loading dose of magnesium Intramuscular loading dose of magnesium sulfatesulfate ② ② Periodic intramuscular injections Periodic intramuscular injections

Treatment of eclampsiaTreatment of eclampsia

2. To lower blood pressure2. To lower blood pressure

Intermittent intravenous or oral administration Intermittent intravenous or oral administration of antihypertensive medication of antihypertensive medication

Whenever the diastolic pressure is considered Whenever the diastolic pressure is considered dangerously highdangerously high

Some clinicians treat at 100 mmHgSome clinicians treat at 100 mmHg Some at 105 mmHgSome at 105 mmHg Some at 110 mmHgSome at 110 mmHg

3. Fluid therapy3. Fluid therapy

Avoidance of diuretics Avoidance of diuretics

Limitation of intravenous fluid administration unless flLimitation of intravenous fluid administration unless fluid loss is excessive uid loss is excessive

Avoidance of hyperosmotic agentAvoidance of hyperosmotic agent

4. Delivery4. Delivery

Magnesium sulfate to control Magnesium sulfate to control convulsionsconvulsions

Magnesium sulfateMagnesium sulfate An effective anticonvulsant agent in severe preeclampsia, eclampAn effective anticonvulsant agent in severe preeclampsia, eclamp

siasia Without producing central nervous system depression in either thWithout producing central nervous system depression in either th

e mother or the infante mother or the infant

Usually given during labor and for 24 hours postpartum Usually given during labor and for 24 hours postpartum Because labor and delivery is more likely time for convulsion to dBecause labor and delivery is more likely time for convulsion to d

evelopevelop

Magnesium sulfate is not given to treat hypertensionMagnesium sulfate is not given to treat hypertension

Pharmacology and toxicology of Pharmacology and toxicology of magnesium sulfatemagnesium sulfate

Magnesium is cleared by renal excretionMagnesium is cleared by renal excretion

Magnesium intoxication is avoided by ensuringMagnesium intoxication is avoided by ensuring Urine output is adequateUrine output is adequate The patellar or biceps reflex is presentThe patellar or biceps reflex is present There is no respiratory depressionThere is no respiratory depression

Eclamptic convulsions are prevented by plasma magnEclamptic convulsions are prevented by plasma magnesium levels maintained esium levels maintained

at 4 to 7 mEq/L at 4 to 7 mEq/L at 4.8 to 8.4 mg/dLat 4.8 to 8.4 mg/dL at 2.0 to 3.5 mmol/L at 2.0 to 3.5 mmol/L

To establish a prompt therapeutic levelTo establish a prompt therapeutic level The initial intravenous infusion of 4 to 6 g,The initial intravenous infusion of 4 to 6 g, continuous infusion at 2 to 3 g per hourcontinuous infusion at 2 to 3 g per hour The initial intramuscular injection of 10 g,The initial intramuscular injection of 10 g, followed by 5 g every 4 hoursfollowed by 5 g every 4 hours

The plasma magnesium level reaches 10 mEq/LThe plasma magnesium level reaches 10 mEq/L Patellar reflexes disappearPatellar reflexes disappear This sign serves to warn of impending magnesium tThis sign serves to warn of impending magnesium t

oxicityoxicity

The plasma levels rise above 10 mEq/LThe plasma levels rise above 10 mEq/L Respiratory depression developsRespiratory depression develops

The plasma levels at 12 mEq/L or moreThe plasma levels at 12 mEq/L or more Respiratory paralysis and arrest followRespiratory paralysis and arrest follow

Mild to moderate respiratory depressionMild to moderate respiratory depression Treatment with calcium gluconate, 1 gTreatment with calcium gluconate, 1 g Withholding further magnesium sulfateWithholding further magnesium sulfate -> the effects of IV calcium may be short lived-> the effects of IV calcium may be short lived

Severe respiratory depression and arrestSevere respiratory depression and arrest Prompt tracheal intubationPrompt tracheal intubation Mechanical ventilationMechanical ventilation

Plasma magnesium concentration is excessive if glomPlasma magnesium concentration is excessive if glomerular filtration is decreased erular filtration is decreased

Renal function is estimated by plasma creatinineRenal function is estimated by plasma creatinine

1.3 mg/dl or higher 1.3 mg/dl or higher : only half of the maintenance intramuscular : only half of the maintenance intramuscular dosedose

Plasma magnesium levels must be checked periodiPlasma magnesium levels must be checked periodicallycally

Uterine effectsUterine effects

Magnesium ions relatively high concentration depress Magnesium ions relatively high concentration depress myometrial contractilitymyometrial contractility

The mechanisms by which Mg might inhibit uterine conThe mechanisms by which Mg might inhibit uterine contractility are not establishedtractility are not established

High concentrations of extracellular magnesium High concentrations of extracellular magnesium -> inhibit calcium entry into myometrial cells-> inhibit calcium entry into myometrial cells -> lead to high intracellular magnesium levels-> lead to high intracellular magnesium levels

Inhibition of uterine contractility appear to be dose deInhibition of uterine contractility appear to be dose dependent pendent

Serum magnesium levels of at least Serum magnesium levels of at least 8 to 10 mEq/L8 to 10 mEq/L

With the regimen described earlier, no evidence of myWith the regimen described earlier, no evidence of myometrial depressionometrial depression

Magnesium sulfate did not significantly alter Magnesium sulfate did not significantly alter oxytocin stimulation of laboroxytocin stimulation of labor admission to delivery intervalsadmission to delivery intervals route of delivery route of delivery

Fetal effectsFetal effects

Magnesium administered to the mother Magnesium administered to the mother -> promptly crosses the placenta -> promptly crosses the placenta -> to achieve equilibrium in fetal serum and in -> to achieve equilibrium in fetal serum and in amnionic fluidamnionic fluid

Neonatal depression occurs only if there is severe hypNeonatal depression occurs only if there is severe hypermagnesemia at deliveryermagnesemia at delivery

Neonatal compromise has not been reportedNeonatal compromise has not been reported

Whether magnesium sulfate affects the fetal heart ratWhether magnesium sulfate affects the fetal heart rate pattern is controversiale pattern is controversial

Magnesium was associated with a small but clinicaMagnesium was associated with a small but clinically insignificant decrease in heart rate variability lly insignificant decrease in heart rate variability (Hal(Hallak, 1999)lak, 1999)

Crowther (2003)Crowther (2003)-> 1062 women, younger than 30 weeks for -> 1062 women, younger than 30 weeks for whom birth was planed within 24 hours were whom birth was planed within 24 hours were randomly assigned to receive Mg or placeborandomly assigned to receive Mg or placebo

Mortality and cerebral palsyMortality and cerebral palsy

: less frequent for infants exposed to : less frequent for infants exposed to

magnesium, but the differences were not magnesium, but the differences were not

significantsignificant

Substantial gross motor dysfunctionSubstantial gross motor dysfunction

: reduced significantly in the magnesium : reduced significantly in the magnesium groupgroup

Importantly, no serious harmful effects from Importantly, no serious harmful effects from magnesium were observed magnesium were observed

Clinical efficacy of magnesium sulfate Clinical efficacy of magnesium sulfate therapytherapy

The multinational Eclampsia Trial Collaborative GroupThe multinational Eclampsia Trial Collaborative Group

Magnesium sulfate : DiazepamMagnesium sulfate : Diazepam 50% reduction in recurrent seizures in Mg therapy50% reduction in recurrent seizures in Mg therapy Reduced maternal deaths in Mg therapy (3.8% : 5.1%)Reduced maternal deaths in Mg therapy (3.8% : 5.1%)

Magnesium sulfate : PhenytoinMagnesium sulfate : Phenytoin 67% reduction in recurrent seizures in Mg therapy67% reduction in recurrent seizures in Mg therapy Maternal mortality was lower in Mg therapy (2.6% : 5.2%)Maternal mortality was lower in Mg therapy (2.6% : 5.2%)

Women allocated to Mg therapy (than phenytoin)Women allocated to Mg therapy (than phenytoin) Less likely to be artificially ventilatedLess likely to be artificially ventilated Less likely to develop pneumoniaLess likely to develop pneumonia Less likely to be admitted to ICULess likely to be admitted to ICU

Neonates of women given Mg therapy Neonates of women given Mg therapy (than phenytoin)(than phenytoin)

Less likely to required intubation at delivery Less likely to required intubation at delivery Less likely to be admitted to the neonatal ICULess likely to be admitted to the neonatal ICU

Prevention of eclampsiaPrevention of eclampsia

Magnesium sulfate therapy is superior in preventing eclaMagnesium sulfate therapy is superior in preventing eclamptic seizuremptic seizure

10 convulsion in 1089 women given phenytoin compared with no 10 convulsion in 1089 women given phenytoin compared with no convulsion in 1049 women given magnesium sulfate (Lucas, 199convulsion in 1049 women given magnesium sulfate (Lucas, 1995)5)

The rate of eclampsia was more than threefold higher for nimodipThe rate of eclampsia was more than threefold higher for nimodipine group (Belfort, 2003)ine group (Belfort, 2003)

699 severe preeclampsia was allocated to magnesium sulfate or 699 severe preeclampsia was allocated to magnesium sulfate or to saline placebo, eclampsia developed in 1 of 30 women given sto saline placebo, eclampsia developed in 1 of 30 women given saline (Coetzee,1988)aline (Coetzee,1988)

Debate about whether magnesium sulfate prophyDebate about whether magnesium sulfate prophylaxis should be given routinely to all hypertensive laxis should be given routinely to all hypertensive womenwomen

With mild preeclampsia, the estimated risk of eclampsWith mild preeclampsia, the estimated risk of eclampsia without magnesium prophylaxis is ia without magnesium prophylaxis is

1 in 100 or less1 in 100 or less

Convulsion due to eclampsia doses no immediate greConvulsion due to eclampsia doses no immediate great harm to most mothers and fetusesat harm to most mothers and fetuses

Magnesium sulfate dose not appear to alter the progrMagnesium sulfate dose not appear to alter the progression of mild preeclampsia to severe preeclmapsiaession of mild preeclampsia to severe preeclmapsia

Alexander (2003) Alexander (2003) Eclamptic seizures increased when mildly hypertenEclamptic seizures increased when mildly hyperten

sive women were not given magnesiumsive women were not given magnesium The rate tripled from 2.9 to 9.3 per 1000The rate tripled from 2.9 to 9.3 per 1000 However, neonatal outcomes were similar However, neonatal outcomes were similar

Parkland Hospital emphasize two caveatsParkland Hospital emphasize two caveats

Severe maternal morbidity due to eclampsia in mild hySevere maternal morbidity due to eclampsia in mild hypertension is uncommonpertension is uncommon

The women who developed eclampsia at Parkland The women who developed eclampsia at Parkland hospital were in a labor-delivery unit with hospital were in a labor-delivery unit with considerable experience in the management of considerable experience in the management of eclampsiaeclampsia

-> At Parkland hospital, we currently do not give -> At Parkland hospital, we currently do not give magnesium sulfate for seizure prophyaxis in mild magnesium sulfate for seizure prophyaxis in mild hypertensionhypertension

-> In other setting in which eclampsia is rare, -> In other setting in which eclampsia is rare, prevention of eclampsia in mild hypertension may prevention of eclampsia in mild hypertension may be preferred as compared with treatment of the be preferred as compared with treatment of the convulsing woman convulsing woman

Hydralazine to control severe hypertensionHydralazine to control severe hypertension

HydralazineHydralazine: remarkably effective in the prevention of cerebral hemorrhage: remarkably effective in the prevention of cerebral hemorrhage

IndicationIndication

At Parkland HospitalAt Parkland Hospital The systolic blood pressure ≥ 160 mmHgThe systolic blood pressure ≥ 160 mmHg The diastolic blood pressure ≥110 mmHgThe diastolic blood pressure ≥110 mmHg

The Working group of the NHBPEP (2000)The Working group of the NHBPEP (2000) The systolic pressure exceeding 160 mmHgThe systolic pressure exceeding 160 mmHg The diastolic pressure exceeding 105 mmHgThe diastolic pressure exceeding 105 mmHg

The regimensThe regimens

5 to 10 mg doses at 15 to 20 minute intervals 5 to 10 mg doses at 15 to 20 minute intervals until a satisfactory response is achieveduntil a satisfactory response is achieved

A satisfactory response A satisfactory response Decrease in diastolic BP to 90 to 100 mmHgDecrease in diastolic BP to 90 to 100 mmHg But, no lower lest placental perfusion be But, no lower lest placental perfusion be

compromisedcompromised

The initial dose : 5mgThe initial dose : 5mg

The tendency to give a larger initial dose of hydralazinThe tendency to give a larger initial dose of hydralazine when the blood pressure is higher must be avoidede when the blood pressure is higher must be avoided

The response to even 5 to 10 mg doses cannot be preThe response to even 5 to 10 mg doses cannot be predicted by the level of hypertensiondicted by the level of hypertension

Labetalol Labetalol

αα1 and nonselective 1 and nonselective ββ-blocker-blocker

Used to treat acute hypertension of pregnancyUsed to treat acute hypertension of pregnancy

Compared with hydralazine (Mabie, 1987)Compared with hydralazine (Mabie, 1987) Lowering BP more rapidlyLowering BP more rapidly Minimal tachycardiaMinimal tachycardia But, hydralazine lowered mean arterial pressure to But, hydralazine lowered mean arterial pressure to

safe levels more effectivelysafe levels more effectively

At parkland hospitalAt parkland hospital Initially : 10 mg IVInitially : 10 mg IV If the BP has not decreased to the desirable level in 10 If the BP has not decreased to the desirable level in 10

minutes : 20 mg minutes : 20 mg The next 10 minute : 40 mg, followed by another 40mgThe next 10 minute : 40 mg, followed by another 40mg If a salutary response is not yet achieved : 80 mgIf a salutary response is not yet achieved : 80 mg

NHBPEP (2000)NHBPEP (2000) Initially : 20 mg IVInitially : 20 mg IV If not effective within 10 minutes : 40 mgIf not effective within 10 minutes : 40 mg Every 10 minutes : 80 mgEvery 10 minutes : 80 mg But, not to exceed a 220 mg total dose per episode But, not to exceed a 220 mg total dose per episode

treatedtreated

Other antihypertensive agentsOther antihypertensive agents

NifedipineNifedipine

10 mg oral to be repeated in 30 minutes10 mg oral to be repeated in 30 minutes

Aali and Nejad (2002)Aali and Nejad (2002) Compared with hydralazineCompared with hydralazine -> fewer doses were required to achieve BP -> fewer doses were required to achieve BP control without increased adverse effectscontrol without increased adverse effects

Mabie (1988)Mabie (1988)

Potent and rapid antihypertensive effectsPotent and rapid antihypertensive effects

Two women developed worrisome hypotensionTwo women developed worrisome hypotension

Similar effects in nonpregnant patients Similar effects in nonpregnant patients -> cerebrovascular ischemia -> cerebrovascular ischemia -> myocardial infarction-> myocardial infarction -> conduction disturbances-> conduction disturbances -> death -> death

NitroprussideNitroprusside

Not recommended by the NHBPEP unless there is no rNot recommended by the NHBPEP unless there is no response to hydralazine, labetalol, nifedipineesponse to hydralazine, labetalol, nifedipine

A continuous infusion is begun with a dose of 0.25 ugA continuous infusion is begun with a dose of 0.25 ug/kg/min increased as necessary to 5 ug/kg/min/kg/min increased as necessary to 5 ug/kg/min

Fetal cyanide toxicity may occur after 4 hoursFetal cyanide toxicity may occur after 4 hours

Persistent immediate severe Persistent immediate severe postpartum hypertensionpostpartum hypertension

After delivery, early in the puerperiumAfter delivery, early in the puerperium

A problem in controlling severe hypertensionA problem in controlling severe hypertension IV hydralazine is being used repeatedly IV hydralazine is being used repeatedly => Other regimens=> Other regimens

IM hydralazine, 10-25 mg at 4-6 hour intervalsIM hydralazine, 10-25 mg at 4-6 hour intervals Once repeated BP remain near normal, Once repeated BP remain near normal, hydralazine is stopped hydralazine is stopped

The persistence or refractoriness of hypertensionThe persistence or refractoriness of hypertension

1. Underlying chronic hypertension1. Underlying chronic hypertension 2. Mobilization of edema fluid with redistribution 2. Mobilization of edema fluid with redistribution into the intravenous compartmentinto the intravenous compartment

=> Effective treatment=> Effective treatment LabetalolLabetalol Diuretics Diuretics

Plasma exchangePlasma exchange

Atypical syndromeAtypical syndrome Severe preeclampsia-eclampsia persists despite delivery Severe preeclampsia-eclampsia persists despite delivery

Martin (1995)Martin (1995) Single or multiple plasma exchange for 18 womenSingle or multiple plasma exchange for 18 women 3L of plasma (13 to 15 donors) were exchanged three times befo3L of plasma (13 to 15 donors) were exchanged three times befo

re a response was forthcomingre a response was forthcoming

Forster (2002)Forster (2002) Plasma exchange was performed in postpartum women with HELPlasma exchange was performed in postpartum women with HEL

LP syndromeLP syndrome

Diuretics and hyperosmotic agentsDiuretics and hyperosmotic agents

Potent diureticsPotent diuretics Intravascular volume depletionIntravascular volume depletion Compromise placental perfusionCompromise placental perfusion

Not used to lower blood pressureNot used to lower blood pressure Enhance the intensity of maternal hemoconcentration Enhance the intensity of maternal hemoconcentration Enhance adverse effects on the mother and the fetusEnhance adverse effects on the mother and the fetus

Limited antepartum use of furosemideLimited antepartum use of furosemide: Identified or strongly suspected pulmonary edema: Identified or strongly suspected pulmonary edema

Once delivery is accomplishedOnce delivery is accomplished

Spontaneous diuresis Spontaneous diuresis : begins within 24 hours: begins within 24 hours

Disappearance of excessive extravascular fluid Disappearance of excessive extravascular fluid : over the next 3 to 4 days: over the next 3 to 4 days

Infusion of hyperosmotic agentsInfusion of hyperosmotic agents

Appreciable intravascular influx of fluidAppreciable intravascular influx of fluid

Subsequent escape of intravascular fluid in the form oSubsequent escape of intravascular fluid in the form of edema into vital organs (lung, brain)f edema into vital organs (lung, brain)

Osmotically active agent leaks through capillaries into Osmotically active agent leaks through capillaries into lungs and brain -> accumulation of edema lungs and brain -> accumulation of edema

Most importantly, a sustained beneficial effect use haMost importantly, a sustained beneficial effect use has not been demonstrateds not been demonstrated

Fluid therapyFluid therapy

Routine administrationRoutine administration Lactated ringer solution at the rate of 60 ml to no more than 125 Lactated ringer solution at the rate of 60 ml to no more than 125

ml per hour ml per hour Unless unusual fluid loss from vomiting, diarrhea, diaphoresis, exUnless unusual fluid loss from vomiting, diarrhea, diaphoresis, ex

cessive blood loss at deliverycessive blood loss at delivery

Infusion of large fluid volumesInfusion of large fluid volumes Enhance the maldistribution of extravascular fluidEnhance the maldistribution of extravascular fluid Increased the risk of pulmonary and cerebral edemaIncreased the risk of pulmonary and cerebral edema

Plumonary edemaPlumonary edema

In normal term pregnancyIn normal term pregnancy Decreased plasma oncotic pressureDecreased plasma oncotic pressure : because of decreases in serum albumin: because of decreases in serum albumin

In women with preeclampsiaIn women with preeclampsia Even more decreased plasma oncotic pressureEven more decreased plasma oncotic pressure Increased extravascular fluid oncotic pressureIncreased extravascular fluid oncotic pressure -> capillary fluid extravasation-> capillary fluid extravasation

Vigorous volume expansion Vigorous volume expansion : associated with high incidence of pulmonary edema: associated with high incidence of pulmonary edema

HemoconcentrationHemoconcentration Reduced central venous and pulmonary capillary wedge pressuresReduced central venous and pulmonary capillary wedge pressures

Attempts to expand blood volume Attempts to expand blood volume -> to relieve vasospasm -> to relieve vasospasm -> to reverse organ deterioration-> to reverse organ deterioration

Infusion of various fluids (colloid and crystalloid), starch polymerInfusion of various fluids (colloid and crystalloid), starch polymers, albumins, albumin

Serious complication : pulmonary edemaSerious complication : pulmonary edema

Invasive hemodynamic monitoringInvasive hemodynamic monitoring

Invasive monitoring Invasive monitoring : flow-directed pulmonary artery chatheter: flow-directed pulmonary artery chatheter

IndicationIndication Intrinsic heart diseaseIntrinsic heart disease Advanced renal diseaseAdvanced renal disease -> cause pulmonary edema-> cause pulmonary edema

DeliveryDelivery

To avoid maternal risks from cesarean deliveryTo avoid maternal risks from cesarean delivery -> Steps to effect vaginal delivery are used initially -> Steps to effect vaginal delivery are used initially in women with eclampsiain women with eclampsia

After an eclamptic seizureAfter an eclamptic seizure Labor often ensues spontaneously Labor often ensues spontaneously Labor can be induced successfully even in women rLabor can be induced successfully even in women r

emote from termemote from term

Blood loss at deliveryBlood loss at delivery

Severe preeclmapsia-eclampsia womenSevere preeclmapsia-eclampsia women : Less tolerant of blood loss than are : Less tolerant of blood loss than are normotensive pregnant womennormotensive pregnant women

HemoconcentrationHemoconcentration

Lack of normal pregnancy induced hypervolemiaLack of normal pregnancy induced hypervolemia

Appreciable fall in BP very soon after deliveryAppreciable fall in BP very soon after delivery Excessive blood lossExcessive blood loss Not sudden dissolution of vasospasmNot sudden dissolution of vasospasm

When oliguria follows deliveryWhen oliguria follows delivery

Frequent hematocrit evaluationFrequent hematocrit evaluation -> To help detect excessive blood loss-> To help detect excessive blood loss

If identifiedIf identified -> Should be treated appropriately -> Should be treated appropriately by careful blood transfusionby careful blood transfusion

Analgesia and anesthesiaAnalgesia and anesthesia