Hypertension in Pregnancy PDF

Hypertension in Pregnancy Levent TÜTÜNCÜ, MD  Background Hypertension can develop during pregnancy or can be pre-existing. Hypertensive disorders during pregnancy carry risks for the woman and her baby. The number of women with hypertensive disor...

Hypertension in Pregnancy Levent TÜTÜNCÜ, MD  Background Hypertension can develop during pregnancy or can be pre-existing. Hypertensive disorders during pregnancy carry risks for the woman and her baby. The number of women with hypertensive disorders during pregnancy is increasing.  Hypertension in Pregnancy Why worry? Common: ~ 10% of pregnancies Morbidity: fetus: 12% of preterm deliveries mother: stroke, CHF, renal injury Mortality: 12-13% of maternal mortality  Pregnancy-Related Mortality United States (1998-2005) Anesthesia (1%) Unknown (2.1%) Embolism (18%) CVA (6%) PE (10%) AFE (8%) Infection (11 %) Hemorrhage (12.5%) Cardiomyopathy (11.5%) Preeclampsia (12.3%) Other medical conditions (13.2%) Cardiovascular disease (12.4%) Obstet Gynecol 2010  Hypertension in Pregnancy (ACOG) Classification Diagnosis Management Prevention Future Implications  SUMMARY Criteria for diagnosis Classification Laboratory and fetal assessment Magnesium sulfate seizure prophylaxis Timing and place of delivery  Classification 1. Chronic hypertension 2. Gestational hypertension 3. Preeclampsia - without severe features - with severe features (severe preeclampsia) 4. Chronic hypertension with superimposed preeclampsia - without severe features - with severe features  Classification Avoid use of term mild preeclampsia (replace with preeclampsia without severe features) Severe preeclampsia = preeclampsia with severe features  Definitions Term Presentation Significant proteinuriaa Chronic hypertension Present at booking or No before 20 weeks Gestational hypertension Presenting after 20 weeks No Pre-eclampsia Presenting after 20 weeks Yes aSignificantproteinuria is > 300 mg protein in a 24-hour urine collection OR >30mg/ml in a spot urinary protein:creatinine sample  Chronic Hypert ension Wit h Measuring Blood Pressure Superimposed Preeclampsia The blood pressure levels that meet the definition criteria Definitions Preeclampsia is considered superimposed when it com- should be documented on repeat readings only after the plicates preexisting chronic hypertension. Up to 20–50% patient has rested (preferably for 10 minutes or more) and of women with chronic hypertension may develop Tab le 1. American College of Obst et ricians and Gynecologist s Def init ions of Hypert ensive Disorders Disorder Def init ion Hypert ension in pregnancy Syst olic blood pressure $ 140 mm Hg or diast olic BP $ 90 mm Hg, or bot h, measured on t w o occasions at least 4 hours apart Severe-range hypert ension Syst olic blood pressure $ 160 mm Hg or diast olic BP $ 110 mm Hg, or bot h, measured on t w o occasions at least 4 hours apart Chronic hypert ension Hypert ension diagnosed or present before pregnancy or before 20 w eeks of gest at ion; or hypert ension t hat is diagnosed for t he first t ime during pregnancy and t hat does not resolve it t he post part um period Chronic hypert ension w it h Preeclampsia in a w oman w it h a hist ory of hypert ension before pregnancy superimposed preeclampsia or before 20 w eeks of gest at ion e28 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY  Diagnosis: Hypertension Hypertension (either): SBP > 140 DBP > 90 Severe hypertension (either): SBP > 160 DBP > 110 BP > 4 hours apart  Diagnosis: Hypertension “it is recommended that a diagnosis of hypertension require at least 2 determinations at least 4 hours apart, although on occasion, especially when faced with severe hypertension, the diagnosis can be confirmed within a short interval (even minutes) to facilitate timely antihypertensive therapy.”  Blood Pressure: Technique Assessing BP (ideal): - seated, legs uncrossed, relaxed, quiet - back and arm supported - middle of cuff at level of right atrium - wait 5 minutes before first reading Improper assessment: - left lateral using upper arm - gives falsely low values  Diagnosis: Proteinuria Definition: - 24 hour* > 300 mg - timed (i.e. 12hr) > 300 mg (extrapolated) - Protein/Creatinin ratio > 0.3 - urine dipstick** > 2+ * 24 urine is preferred method ** urine dipstick used only if no other available  Chronic Hypertension: Definition Hypertension and either of the following: - present prior to pregnancy - present prior to 20 weeks Diagnosis dilemmas: - women with little care before pregnancy - women presenting after 20 weeks ported as 1.1% in women with chronic hypertension genic effect from medication. The authors of a case– (AOR 2.3; 95% CI, 1.6–3.4) compared with controls with- control study based on registry data confirmed the Risks of Chronic Hypertension out hypertension (17). The gestational age at stillbirth in above findings supporting the hypothesis that physio- pregnancies complicated by chronic hypertension has been logical changes early in pregnancy among women with Box 1. Risks of Chronic Hypert ension in Pregnancy M at ernal Fet al and Neonat al Deat h St illbirt h or perinat al deat h St roke Grow t h rest rict ion Pulmonary edema Pret erm birt h Renal insufficiency and failure Congenit al anomalies (eg, heart defect s, hypospadias, esophageal at resia) Myocardial infarct ion Preeclampsia Placent al abrupt ion Cesarean delivery Post part um hemorrhage Gest at ional diabet es  Baseline Tests for Chronic Hypertension Box 2. Test s f or Basel in e Evaluat ion f or Ch r o n ic Hyp er t en si on in Pr eg n an cy Serum aspartate aminotransferase and alanine aminotransferase Serum creatinine Serum electrolytes (specifically potassium) Blood urea nitrogen Complete blood count Spot urine protein/ creatinine ratio or 24-hour urine for total protein and creatinine (to calculate creati- nine clearance) as appropriate Electrocardiogram or echocardiogram as appropriate  Etiology Box 3. Hist or ical Feat ur es Favor ing Hyper t ension Cause Primary Hypert ension Secondary Hypert ension Gradual increase in BP, w it h slow rat e of rise in BP BP labilit y, episodic pallor, and dizziness (pheochromocyt oma) Lif est yle f act ors t hat f avor higher BP (eg, w eight Snoring or hypersomnolence (obst ruct ive sleep gain, high-sodium diet , decreased physical act ivit y, apnea) job change ent ailing increased t ravel, excessive Muscle cramps or w eakness (hypokalemia f rom consumpt ion of alcohol) primary aldost eronism or secondary aldost eronism due t o renovascular disease) Family hist ory of hypert ension Weight loss, palpit at ions, heat int olerance (hypert hyroidism) Edema, f at igue, f requent urinat ion (kidney disease or f ailure) Hist ory of coarct at ion repair (residual hypert ension associat ed w it h coarct at ion) Cent ral obesit y, f acial rounding, easy bruisabilit y (Cushing syndrome) Medicat ion or subst ance use (eg, alcohol, NSAIDS, cocaine, amphet amines) Absence of f amily hist ory of hypert ension Abbreviat ions: BP, blood pressure; NSAIDs, nonst eroidal ant iinf lammat ory drugs. Reprint ed f rom: Whelt on PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/ AHA/ AAPA/ ABC/ ACPM/ AGS/ APhA/ ASH/ ASPC/ NMA/ PCNA guideline f or t he prevent ion, det ect ion, evaluat ion, and management of  Management of pregnancy with chronic hypertension – Tell women who take angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs); - there is an increased risk of congenital abnormalities if these drugs are used in pregnancy - to discuss alternative antihypertensive treatment with their healthcare professional – Aim to keep blood pressure lower than 150/100 mmHg in women with uncomplicated chronic hypertension  Chronic Hypertension: Anti-hypertensive Therapy Anti-hypertensive medication indicated: - persistent SBP > 160 - or persistent DBP > 105 BP goals with treatment: –120-160 / 80-105 mmHg  Chronic Hypertension: Anti-hypertensive Therapy Anti-hypertensive medication not needed: - SBP < 160 and DBP < 105 - no evidence for end-organ damage  Chronic Hypertension: Oral Antihypertensive Agents Tab le 2. Comm on Oral Ant ihy pert ensive Agent s in Pregnancy Drug Dosage Comment s Labet alol 200– 2,400 mg/ d orally in t w o t o t hree Pot ent ial bronchoconst rict ive ef f ect s. divided doses. Commonly init iat ed at Avoid in w omen w it h ast hma, preexist ing 1002 200 mg t w ice daily myocardial disease, decompensat ed cardiac f unct ion, and heart block and bradycardia. Nif edipine 30– 120 mg/ d orally of an ext ended-release Do not use sublingual f orm. preparat ion. Commonly init iat ed at 302 60 Immediat e-release f ormulat ion should mg once daily (ext ended-release) generally be reserved f or cont rol of severe, acut ely elevat ed blood pressures in hospit alized pat ient s. Should be avoided in t achycardia. Met hyldopa 500– 3,000 mg/ d orally in t w o t o f our Saf et y dat a up t o 7 years of age in of f spring. divided doses. Commonly init iat ed at 250 May not be as ef f ect ive as ot her mg t w ice or t hree t imes daily medicat ions, especially in cont rol of severe hypert ension. Use limit ed by side ef f ect prof ile (sedat ion, depression, dizziness). Hydrochlorot hiazide 12.5– 50 mg daily Second-line or t hird-line agent appropriate input from maternal–fetal medicine and cardi- pregnancy excluded women with chronic hypertension or  Chronic Hypertension: Anti-hypertensive Therapy Recommended medications: - labetalol (Trandate tablet. 200 mg.) - nifedipine (Adalat 30, 60 mg tablet, Nidicard 10 mg kapsul, Nidilat 10 mg kapsul) - methyldopa (Alfamet tablet 250 mg)  Oral Anti-hypertensive Therapy Medication Dose Comments Labetalol 200-2400 mg/d (2-3 doses) caution with asthma, CHF Nifedipine 30-120 mg/d (XL) avoid SL form Methyldopa 500-3000 mg/d (2-3 doses) may not be effective with severe HTN Range Hypert ension physiologic and fetal considerations of pregnancy, the Because most existing randomized controlled trials of antihypertensive protocols used for nonpregnant individ- Anti-hypertensive Therapy for Urgent conditions acute treatment of severe-range blood pressure during uals cannot be extrapolated simply to pregnant women. Tab le 3. Ant ihyp ert ensiv e Agent s Used f or Ur gent Blood Pressure Cont rol in Pregnancy Drug Dosage Comment s Onset of Act ion Labet alol 10– 20 mg IV, t hen 20– 80 mg every Tachycardia is less common and 1– 2 minut es 10– 30 minut es t o a maximum cumu- f ew er adverse ef f ect s t han ot her lat ive dosage of 300 mg; or const ant agent s. inf usion 1– 2 mg/ min IV Avoid in w omen w it h ast hma, preexist ing myocardial disease, decompensat ed cardiac f unct ion, and heart block and bradycardia. Hydralazine 5 mg IV or IM, t hen 5– 10 mg IV every Higher or f requent dosage associat ed 10– 20 minut es 20– 40 minut es t o a maximum w it h mat ernal hypot ension, cumulat ive dosage of 20 mg; or headaches, and abnormal f et al heart const ant inf usion of 0.5– 10 mg/ hr rat e t racings; may be more common t han ot her agent s. Nif edipine 10– 20 mg orally, repeat in May observe ref lex t achycardia and 5– 10 minut es (immediat e 20 minut es if needed; t hen 10– 20 mg headaches. release) every 2– 6 hours; maximum daily dose is 180 mg Abbreviat ions: IM, int ramuscularly; IV, int ravenously. VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e35  Anti-hypertensive Therapy for Urgent conditions Recommended medications: –Labetolol –Hydralazine (Apresoline 20 mg. amp) –Nifedipine (Nidicard10 mg kapsul, Nidilat 10 mg kapsul)  Urgent Oral Nifedipine therapy Box 4. Sam p le Or der Set f or Sever e Int r ap ar t um or Post p ar t um Hyper t ension Ini t ial Fir st - line M anag em en t W it h Im m ed iat e-Release Or al Nif edip ine* † c Notify physician if systolic blood pressure (BP) is greater than or equal to 160 mm Hg or if diastolic BP is greater than or equal to 110 mm Hg. c Institute fetal surveillance if undelivered and fetus is viable. c If severe BP elevations persist for 15 minutes or more, administer immediate-release nifedipine capsules (10 mg orally).‡ c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, administer immediate-release nifedipine capsules (20 mg orally). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, administer nifedipine immediate release capsule (20 mg orally). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, administer labetalol (20 mg intravenously for more than 2 minutes) and obtain emergency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care subspecialists. c Give additional antihypertensive medication per specific order. c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour, then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours. c Institute additional BP timing per specific order. *Please note there may be adverse effects and contraindications.  Urgent Hydralazine therapy Box 5. Sam ple Or der Set f or Sever e Int r apar t um or Post par t um Hyper t ension Ini t ial Fir st -lin e M anag em en t W it h Hydr alazine* c Notify physician if systolic BP is 160 mm Hg or more or if diastolic BP is 110 mm Hg or more. c Institute fetal surveillance if undelivered and fetus is viable. c If severe BP elevations persist for 15 minutes or more, administer hydralazine (5 mg or 10 mg IV for more than 2 minutes). c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, administer hydralazine (10 mg IV for more than 2 minutes). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, administer labetalol (20 mg IV for more than 2 minutes). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 10 minutes and record results. c If either BP threshold is still exceeded, administer labetalol (40 mg IV for more than 2 minutes) and obtain emergency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care subspecialists. c Give additional antihypertensive medication per specific order. c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour, then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours. c Institute additional BP timing per specific order. Abbreviations: BP, blood pressure; IV, intravenously.  Urgent Labetalol therapy Box 6. Sam p le Or der Set f or Sever e Int r ap ar t um or Post p ar t um Hyper t ension, Ini t ial Fir st - line M anag em en t W it h Lab et alol* c Notify physician if systolic BP measurement 160 mm Hg or more or if diastolic BP measurement is 110 mm Hg or more. c Institute fetal surveillance if undelivered and fetus is viable. c If severe BP elevations persist for 15 minutes or more, administer labetalol (20 mg IV for more than 2 minutes). c Repeat BP measurement in 10 minutes and record results. c If either BP threshold is still exceeded, administer labetalol (40 mg IV for more than 2 minutes). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 10 minutes and record results. c If either BP threshold is still exceeded, administer labetalol (80 mg IV for more than 2 minutes). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 10 minutes and record results. c If either BP threshold is still exceeded, administer hydralazine (10 mg IV for more than 2 minutes). If BP is below threshold, continue to monitor BP closely. c Repeat BP measurement in 20 minutes and record results. c If either BP threshold is still exceeded, obtain emergency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care subspecialists. c Give additional antihypertensive medication per specific order. c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour, then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours. c Institute additional BP timing per specific order.  Chronic Hypertension: Fetal Assessment Ultrasound: - screen for growth restriction - timing not specified (? 28-32 weeks) Antenatal testing: - taking anti-hypertensive medication - other medical conditions - superimposed preeclampsia CHTN + fetal growth restriction: - antenatal testing - umbilical artery Doppler  Chronic Hypertension: Delivery No other additional maternal/fetal complications - delivery < 38w0d not recommended (i.e. wait until > 38w0d)  Gestational Hypertension: Definition Hypertension (onset > 20 weeks) and all of following: - absence of proteinuria - absence of severe features  Gestational Hypertension: Definition Blood Pressure ≥ 140/90mmHg on two or more occasions - in a previously normotensive patient - after 20 weeks gestation - without proteinuria - returning to normal 12 weeks after delivery Almost half of these develop preeclampsia syndrome  Gestational Hypertension: Management - serial assessment for symptoms (daily) - serial assessment of fetal movement (daily) - serial measurement of BP - 2x per week in office or - 1x per week in office and 1x at home - serial assessment for proteinuria (weekly) - platelets, LFTs, creatinine (weekly)  Gestational Hypertension: Anti-hypertensive therapy SBP < 160 and DBP < 110 - BP medication NOT be given  Gestational Hypertension: Fetal Assessment - daily kick counts ultrasound: assess growth every 3 weeks NST once weekly with AFI  Gestational Hypertension: Seizure Prophylaxis Gestational hypertension - magnesium is NOT universally needed If patients develops severe features → magnesium  Gestational Hypertension: Delivery Gestational hypertension and < 37w0d - expectant management until 37w0d - deliver sooner if other indications arise Gestational hypertension Diagnosis made > 37w0d – - deliver  Preeclampsia: Definition 1. HTN (new onset > 20 weeks) + proteinuria OR 2.* HTN (new onset > 20 weeks) + multisystemic signs - CNS - pulmonary edema - renal dysfunction - liver impairment - thrombocytopenia * Proteinuria is not required for diagnosis  Preeclampsia: Risk Factors Box 1. Risk Fact or s f or Pr eeclam psia Nulliparity Multifetal gestations Blood p Preeclampsia in a previous pregnancy c Systo Chronic hypertension diast Pregestational diabetes two week Gestational diabetes norm Thrombophilia c Systo Systemic lupus erythematosus diast (Seve Prepregnancy body mass index greater than 30 a sh Antiphospholipid antibody syndrome antih Maternal age 35 years or older and Kidney disease Proteinu Assisted reproductive technology Obstructive sleep apnea c 300 this a  Preeclampsia: Risk Factors FACTOR RISK RATIO Nulliparity 3:1 Age > 40 3:1 African American 1.5:1 Chronic hypertension 10:1 Renal disease 20:1 Antiphospholipid syndrome 10:1  Preeclampsia: Diagnostic Criteria Box 2. Diagn ost ic Cr it er ia f or Pr eeclam psia Blood pressure c Systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure c Systolic blood pressure of 160 mm Hg or more or diastolic blood pressure of 110 mm Hg or more. (Severe hypertension can be confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy). and  diastolic blood pressure of 110 mm Hg or more. (Severe hypertension can be confirmed within Preeclampsia: Diagnostic Criteria a short interval (minutes) to facilitate timely antihypertensive therapy). and Proteinuria c 300 mg or more per 24 hour urine collection (or this amount extrapolated from a timed collection) or c Protein/ creatinine ratio of 0.3 mg/ dL or more or pura, c Dipstick reading of 2+ (used only if other quan- enal titative methods not available) Or in the absence of proteinuria, new-onset hyper- nsid- tension with the new onset of any of the psia, following: it is c Thrombocytopenia: Platelet count less than si on 100,000 3 10 9/ L pre- c Renal insufficiency: Serum creatinine concen- wing trations greater than 1.1 mg/ dL or a doubling of the serum creatinine concentration in the less absence of other renal disease ndi- c Impaired liver function: Elevated blood concen- s of trations of liver transaminases to twice normal con- concentration epi- c Pulmonary edema B New-onset headache unresponsive to medi- ative cation and not accounted for by alternative cen- diagnoses or visual symptoms erum enal  Preeclampsia with Severe Features Bo x 3. Sever e Feat u r es c Systolic blood pressure of 160 m m Hg or m ore, or diastolic blood pressure of 110 m m Hg or m ore on tw o occasions at least 4 hours apart (unless antihypertensive therapy is initiated before this tim e) c Throm bocytopenia (platelet count less than 9 100,000 3 10 / L) c Im paired liver function as indicated by abnorm ally elevated blood concentrations of liver enzym es (to tw ice the upper lim it norm al concentration), and severe persistent right upper quadrant or epigastric pain unresponsive to m edication and not accounted for by alternative diagnoses c Renal insufficiency (serum creatinine concentra- tion m ore than 1.1 m g/ dL or a doubling of the serum creatinine concentration in the absence of other renal disease) c Pulm onary edem a c New -onset headache unresponsive to m edication and not accounted for by alternative diagnoses c Visual disturbances  Old classification New classification Name Severe preeclampsia Preeclampsia with severe features BP BP > 160 or > 110 (6 hr) BP > 160 or > 110 (4 hrs apart) Platelets < 100,000 < 100,000 Liver increased LFTs increased LFTs RUQ/epigastric pain RUQ/epigastric pain Renal creatinine not used creatinine > 1.1 mg or doubling oliguria not used > 5000 mg protein not used Lungs pulmonary edema pulmonary edema CNS persistent Headache persistent Headache visual changes persistent visual changes Fetus growth restriction not used  Pathogenesis of Preeclampsia Pre-eclampsia is a pregnancy specific disorder. It can occur in absence of the fetus. The disease is cured by the removal of the placenta. 47  Pathophysiology Vasospasm Uterine vessels Hemostasis Prostanoid balance Endothelium-derived factors Lipid peroxide, free radicals and antioxidants  Pathophysiology Vasospasm ◦ Predominant finding in gestational hypertension and preeclampsia  Uterine vessels  Hemostasis  Prostanoid balance  Endothelium-derived factors  Lipid peroxide, free radicals and antioxidants  Pathophysiology  Vasospasm Uterine vessels ◦ Inadequate maternal vascular response to trophoblastic mediated vascular changes ◦ Endothelial damage  Hemostasis  Prostanoid balance  Endothelium-derived factors  Lipid peroxide, free radicals and antioxidants  Pathophysiology  Vasospasm  Uterine vessels Hemostasis ◦ Increase platelet activation resulting in consumption ◦ Increased endothelial fibronectin levels ◦ Decreased antithrombin III and α2-antiplasmin levels ◦ Allows for microthrombi development with resultant increase in endothelial damage  Prostanoid balance  Endothelium-derived factors  Lipid peroxide, free radicals and antioxidants  Pathophysiology  Vasospasm  Uterine vessels  Hemostasis Prostanoid balance ◦ Prostacyclin (PGI2):Thromboxane (TXA2) balance shifted to favor TXA2 ◦ TXA2 promotes:  Vasoconstriction  Platelet aggregation  Endothelium-derived factors  Lipid peroxide, free radicals and antioxidants  Pathophysiology  Vasospasm  Uterine vessels  Hemostasis  Prostanoid balance Endothelium-derived factors ◦ Nitric oxide is decreased in patients with preeclampsia  As this is a vasodilator, this may result in vasoconstriction  Lipid peroxide, free radicals and antioxidants  Pathophysiology  Vasospasm  Uterine vessels  Hemostasis  Prostanoid balance  Endothelium-derived factors Lipid peroxide, free radicals and antioxidants ◦ Increased in preeclampsia ◦ Have been implicated in vascular injury Pathogenesis of Preeclampsia  Pathophysiologic Changes Cardiovascular effects Hematologic effects Neurologic effects Pulmonary effects Renal effects Fetal effects  Pathophysiologic Changes Cardiovascular effects ◦ Hypertension ◦ Increased cardiac output ◦ Increased systemic vascular resistance  Hematologic effects  Neurologic effects  Pulmonary effects  Renal effects  Fetal effects  Pathophysiologic Changes  Cardiovascular effects Hematologic effects ◦ Volume contraction/Hypovolemia ◦ Elevated hematocrit ◦ Thrombocytopenia ◦ Microangiopathic hemolytic anemia ◦ Third spacing of fluid ◦ Low oncotic pressure  Neurologic effects  Pulmonary effects  Renal effects  Fetal effects  Pathophysiologic Changes  Cardiovascular effects  Hematologic effects Neurologic effects ◦ Hyperreflexia ◦ Headache ◦ Cerebral edema ◦ Seizures ◦ Findings of PRES on radiologic imaging  Pulmonary effects  Renal effects  Fetal effects  Pathophysiologic Changes  Cardiovascular effects  Hematologic effects  Neurologic effects Pulmonary effects ◦ Capillary leak ◦ Reduced colloid osmotic pressure ◦ Pulmonary edema  Renal effects  Fetal effects  Pathophysiologic Changes  Cardiovascular effects  Hematologic effects  Neurologic effects  Pulmonary effects Renal effects ◦ Decreased glomerular filtration rate ◦ Glomerular endotheliosis ◦ Proteinuria ◦ Oliguria ◦ Acute tubular necrosis  Fetal effects  Pathophysiologic Changes  Cardiovascular effects  Hematologic effects  Neurologic effects  Pulmonary effects  Renal effects Fetal effects ◦ Placental abruption ◦ Fetal growth restriction ◦ Oligohydramnios ◦ Fetal distress ◦ Increased perinatal morbidity and mortality  Organ Specific changes of Preeclampsia Cardiovascular Renal Generalized vasospasm Proteinuria Increased peripheral resistance Decreased glomerular filtration rate Reduced central venous/ Decreased urate excretion pulmonary pressure Hepatic Organ Specific Changes associated with Periportal necrosis Pre-eclampsia Subscapular hematoma Hematological Central Nervous System Platelet activation and depletion Cerebral oedema Coagulopathy Cerebral haemorrhages Decreased plasma volume Increased blood viscosity  Organ Specific changes of Preeclampsia Organ Damage utero-placenta IUGR Hematological Epistaxis, DIC like features, hemoconcentration CNS Cerebral edema, cerebral hge →seizures Heart Subendothelial hge , focal necrosis & hge, cardiomyopathy, heart failure Lungs Pulmonary edema, hemorrhagic brochopneumonia Kidneys glomerular endotheliosis, oliguria liver Subcapsular hematoma, ischaemia→periportal necrosis, HELLP  Preeclampsia: Management The ultimate cure is delivery Assess gestational age Assess cervix Fetal well-being Laboratory assessment Rule out severe disease!!  Preeclampsia: Management Without severe features: - serial assessment for symptoms (daily) - serial assessment of fetal movement (daily) - serial measurement of BP (2x per week) - platelets, LFTs, creatinine (weekly)  Preeclampsia: Anti-hypertensive therapy SBP < 160 and DBP < 110 - BP medication NOT be given SBP > 160 or DBP > 110 - BP medication is recommended  Criteria for Treatment Diastolic BP > 105-110 Systolic BP > 160 Avoid rapid reduction in BP Do not attempt to normalize BP Goal is DBP < 105 not < 90 May precipitate fetal distress  Characteristics of Severe HTN Crises are associated with hypovolemia Clinical assessment of hydration is inaccurate Unprotected vascular beds are at risk, eg, uterine  Key Steps Using Vasodilators 250-500 cc of fluid, IV Avoid multiple doses in rapid succession Allow time for drug to work Maintain LLD position Avoid over treatment  Other Complications Pulmonary edema Oliguria Persistent hypertension DIC  Pulmonary Edema Fluid overload Reduced colloid osmotic pressure Occurs more commonly following delivery as colloid oncotic pressure drops further and fluid is mobilized  Treatment of Pulmonary Edema Avoid over-hydration Restrict fluids Lasix 10-20 mg IV Usually no need for albumin or Hetastarch (Hespan)  Oliguria 25-30 cc per hour is acceptable If less, small fluid boluses of 250-500 cc as needed Lasix is not necessary Postpartum diuresis is common  Persistent Hypertension BP may remain elevated for several days Diastolic BP less than 100 do not require treatment By definition, preeclampsia resolves by 6 weeks  Disseminated Intravascular Coagulopathy Rarely occurs without abruption Low platelets is not DIC Requires replacement blood products and delivery  HELLP Syndrome He-hemolysis EL-elevated liver enzymes LP-low platelets  HELLP Syndrome Is a variant of severe preeclampsia Platelets < 100,000 LFT’s - 2 x normal May occur against a background of what appears to be mild disease 4-12% of pt. with severe preeclampsia and eclampsia develop HELLP syndrome  Preeclampsia: Fetal Assessment Preeclampsia without severe features: - daily fetal kick counts - ultrasound to assess growth (q 3 weeks) - antenatal testing twice weekly Preeclampsia with fetal growth restriction: - antenatal testing - umbilical artery Doppler  Preeclampsia: Delivery Preeclampsia without severe features and < 37w0d - deliver > 37w0d - deliver sooner if other indications arise Preeclampsia without severe features Diagnosis at > 37w0d - deliver Preeclampsia with severe features > 34w0d - deliver Preeclampsia with severe features < 34w0d and stable maternal/fetal status - expectant management at tertiary center  Preeclampsia: Delivery Preeclampsia with severe features Prior to fetal viability (23-24 weeks) - deliver (not candidates for expectant management) Deliver if any of following at any gestational age - uncontrollable severe hypertension - eclampsia - pulmonary edema - abruption - DIC - nonreassuring fetal status  Preeclampsia: Delivery Deliver in 48 hours (after steroids) if stable: - PROM, labor - Thrombocytopenia (platelets < 100,000) - elevated LFTs - IUGR (EFW < 5th percentile) - Oligohydramnios (AFI < 5 cm) - abnormal umbilical artery Doppler (Reverse end-diastolic flow) - new onset/worsening renal dysfunction  Preeclampsia: Expectant management Preeclampsia with severe features and 23w0d- 33w6d Expectant management candidates: - severe hypertension, if controllable - transient lab abnormalities (LFTs, platelets)  Timing of Delivery >38 0/7 weeks – Chronic hypertension >37 0/7 weeks – Gestational hypertension – Preeclampsia without severe features >34 0/7 weeks – Preeclampsia with severe features  Route of Delivery Determined by: – Gestational age – Fetal presentation – Cervical status – Maternal condition – Fetal condition Bo x 4. Co n d i t i o n s Pr ecl u d i n g Ex p ect an t M an ag em en t ∗ Maternal c Uncontrolled severe-range blood pressures ( per- sistent systolic blood pressure 160 m m Hg or m ore or diastolic blood pressure 110 m m Hg or m ore not responsive to antihypertensive m edication c Persistent headaches, refractory to treatm ent c Epigastric pain or right upper pain unresponsive to repeat analgesics c Visual disturbances, m otor deficit or altered sensorium c Stroke c Myocardial infarction c HELLP syndrom e c New or w orsening renal dysfunction ( serum cre- atinine greater than 1.1 m g/ dL or tw ice baseline) c Pulm onary edem a c Eclam psia c Suspected acute placental abruption or vaginal bleeding in the absence of placenta previa c Pulmonary edema c Eclampsia c Suspected acute placental abruption or vaginal bleeding in the absence of placenta previa Fetal c Abnormal fetal testing c Fetal death c Fetus without expectation for survival at the time of maternal diagnosis (eg, lethal anomaly, extreme prematurity) c Persistent reversed end-diastolic flow in the umbilical artery Abbreviation: HELLP, hemolysis, elevated liver enzymes, and low platelet count. ∗In some cases, a course of antenatal steroids can be considered depending on gestational age and maternal severity of illness. Data from Balogun OA, Sibai BM. Counseling, manage- ment, and outcome in women with severe preeclampsia  Preeclampsia: Seizure Prophylaxis Preeclampsia without severe features - magnesium is NOT universally needed  Preeclampsia: Seizure Prophylaxis Preeclampsia without severe features - monitor closely during labor - magnesium if progression to severe disease - BP > 160/110 - symptoms Some providers may elect to use magnesium for patients without severe features  Preeclampsia: Seizure Prophylaxis Preeclampsia with severe features or eclampsia - magnesium sulfate Quality of evidence: High Recommendation: Strong If Cesarean → continue magnesium intraoperatively  Magnesium Sulfate Is not a hypotensive agent Works as a centrally acting anticonvulsant Also blocks neuromuscular conduction 4-6 g bolus 1-2 g/hour Monitor urine output and DTR’s With renal dysfunction, may require a lower dose Serum levels: 6-8 mg/dL are considered therapeutic  Magnesium Sulfate: Toxicity Respiratory rate < 12 DTR’s not detectable Altered sensorium Urine output < 25-30 cc/hour Antidote: 10 ml of 10% solution of calcium gluconate iv over 3 minutes consultation with an anesthesiologist, maternal–fetal ACOG Advise; medicine subspecialist, or critical care subspecialist to discuss second-line intervention is recommended. Magnesium sulfate is not recommended as an antihypertensive agent, but magnesium sulfate re- mains the drug of choice for seizure prophylaxis for women with acute-onset severe hypertension during pregnancy and the postpartum period. Starting magnesium should not be delayed in the setting of acute severe hypertension; it is recommended regardless of whether the patient has gestational hypertension with severe features, preeclampsia with severe features, or eclampsia.  Magnesium Sulfate Table 2. Serum Magnesium Concent rat ion and Toxicit ies Serum Magnesium Concent rat ion mmol/ L mEq/ L mg/ dL Ef f ect 2–3.5 4–7 5–9 Therapeut ic range. 3.5. 7.9 Loss of pat ellar reflexes. 5. 10. 12 Respirat ory paralysis. 12.5. 25. 30 Cardiac arrest Dat a from Duley L. Magnesium sulphat e regimens for women wit h eclampsia: messages from t he Collaborat ive Eclampsia Trial. Br JObst et Gynaecol 1996;103:103–5 and Lu JF, Night ingale CH. Magnesium sulfat e in eclampsia and preeclampsia: pharmacokinet ic principles. Clin Pharmacokinet 2000;38:305–14. emergency correction with calcium gluconate 10% solu- oral nifedipine are the three agents most commonly tion, 10 mL IV over 3 minutes, along with furosemide used for this purpose (see Table 3). A recent Cochrane intravenously to accelerate the rate of urinary excretion. systematic review that involved 3,573 women found  Eclampsia: Defination new onset of seizures or unexplained coma during pregnancy in patients with pre-existing preeclampsia and without pre-existing neurological disorder.  Eclampsia: Defination addition of convulsions in a woman with preeclampsia occurs in 0.5-4% of deliveries 25% have eclamptic seizures before labour, 50% during labour, and 25% after delivery. Seizure/ Eclampsia Preeclampsia Convulsion/ Coma  Treatment of Eclampsia Few people die of seizures Protect patient Avoid insertion of airways and padded tongue blades IV access MGSO4 4-6 bolus, if not effective, give another 2 g THE FIRST THING TO DO AT A SEIZURE IS TO TAKE YOUR OWN PULSE!  Alternate Anticonvulsants Have not been shown to be as efficacious as magnesium sulfate and may result in sedation that makes evaluation of the patient more difficult – Diazepam 5-10 mg IV – Sodium Amytal 100 mg IV – Pentobarbital 125 mg IV – Dilantin 500-1000 mg IV infusion  After the Seizure Assess maternal labs Fetal well-being Effect delivery Transport when indicated No need for immediate cesarean delivery  Chronic Hypertension with Superimposed Preeclampsia Hypertension (onset < 20 weeks) and new findings: Without severe features: - hypertension and proteinuria only - proteinuria: new onset or worsening With severe features - hypertension +/- proteinuria + severe features  CHTN with Superimposed Preeclampsia: Seizure Prophylaxis Without severe features - magnesium sulfate is not necessary With severe features - magnesium sulfate is recommended  CHTN with Superimposed Preeclampsia: Delivery Without severe features - stable maternal and fetal status - delivery > 37w0d With severe features < 34w0d and stable maternal/fetal status - expectant management at tertiary center Preeclampsia with severe features > 34w0d - deliver  CHTN with Superimposed Preeclampsia: Delivery Deliver if any of following at any gestational age - uncontrollable severe hypertension - eclampsia - pulmonary edema - abruption - DIC - non-reassuring fetal status  Postpartum Preeclampsia: Seizure Prophylaxis Postpartum diagnosis - new onset hypertension with CNS symptoms - or preeclampsia with severe hypertension - magnesium sulfate (24 hr)  Management: Postpartum Gestational hypertension or preeclampsia - BP monitored for 72 hours - in hospital - equivalent outpatient surveillance - Repeat BP assessment 7-10 days postpartum - Repeat BP earlier in women with symptoms  Management: Postpartum Persistent hypertension - SBP > 150 or DBP > 100 (2 readings > 4 hrs) - treat with anti-hypertensive - SBP > 160 or > 110 - treat within 1 hour  Prevention Women with history of: - early-onset preeclampsia and PTD < 34w0d - history preeclampsia in more than 1 pregnancy Treatment: - daily low-dose aspirin (60-80 mg) - begin in late first trimester day) aspirin for preeclampsia prophylaxis initiated were no differences in the rates of term preeclampsia between 12 weeks and 28 weeks of gestation (optimally between study groups. Of note, as a possible study before 16 weeks of gestation) and continuing until deliv- ery (Table 1). Aspirin Use for prevention limitation, the prevalence of preterm preeclampsia in the placebo group was one half of that expected for Tab le 1. Clinical Risk Fact or s and Asp ir in Use * Level of Risk Risk Fact or s Recommendat ion High† Hist ory of preeclampsia, especially w hen Recommend low -dose aspirin if t he pat ient accompanied by an adverse out come has one or more of t hese high-risk f act ors Mult if et al gest at ion Chronic hypert ension Type 1 or 2 diabet es Renal disease Aut oimmune disease (ie, syst emic lupus eryt hemat osus, t he ant iphospholipid syndrome) Moderat e z Nulliparit y Consider low -dose aspirin if t he pat ient has Obesit y (body mass index great er t han 30) more t han § one of t hese moderat e-risk f act ors Family hist ory of preeclampsia (mot her or sist er) Sociodemographic charact erist ics (Af rican American race, low socioeconomic st at us) Age 35 years or older Personal hist ory f act ors (eg, low birt h w eight or small f or gest at ional age, previous adverse pregnancy out come, more t han 10-year pregnancy int erval) Low Previous uncomplicat ed f ull-t erm delivery Do not recommend low -dose aspirin *Includes only risk f act ors t hat can be obt ained f rom t he pat ient ’s medical hist ory. Clinical measures, such as ut erine art ery Doppler ult rasonogr aphy, are not included. † Single risk f act ors t hat are consist ent ly associat ed w it h t he great est risk of preeclampsia. The preeclampsia incidence rat e w ould be approximat ely 8% or more in a pregnant w oman w it h one or more of t hese risk f act ors. z A combinat ion of mult iple moderat e-risk f act ors may be used by clinicians t o ident if y w omen at high risk of preeclampsia. These risk f act ors are independent ly associat ed w it h moderat e risk of preeclampsia, some more consist ent ly t han ot hers. § Moderat e-risk f act ors vary in t heir associat ion w it h increased risk of preeclampsia. Modif ied f rom LeFevre, ML. U.S. Prevent ive Services Task Force. Low -dose aspirin use f or t he prevent ion of morbidit y and mort alit y  Prevention Consider for women with high-baseline risk (~20%) - chronic hypertension - previous preterm preeclampsia - diabetes Needed to treat to prevent 1 case preeclampsia: 50  Prevention Not recommended: - vitamin C - vitamin E - salt restriction - bed rest - physical activity restriction  Future Implications Preeclampsia in pregnancy - increased risk cardiovascular disease - overall: 2x increase risk - < 34 week delivery: 8-9x increase risk  Future Implications What can be done to lower cardiovascular risk? Preterm birth < 37 weeks from preeclampsia consider yearly assessment of: - BP - lipids - fasting glucose - BMI