Management Of Mild Preeclampsia Dr . Mirzamoradi

Preeclampsia  Preeclampsia refers to the new onset of hypertension and either proteinuria or end organ dysfunction after 20 weeks of gestation in a previously normotensive woman.

Preeclampsia  In patients with new onset hypertension without proteinuria , the new onset of any of the following is diagnostic of Preeclampsia : Platlet count < 100000 Serum creatinine > 1.1 or doubling of Serum creatinine in the absence of other renal disease Liver transaminases at least twice the normal concentrations Pulmonary edema Cerebral or visual symptom

ACOG :2013 Similarly, eliminated from measures of severe preeclampsia are massive proteinuria (ie, >5 g/day) and fetal growth restriction because the extent of proteinuria does not predict morbidity, and fetal growth restriction occurs commonly in the absence of associated preeclampsia.

The new definition of severe preeclampsia includes any of the following: 1) systolic or diastolic blood pressures values ≥160 or 110 mm Hg, respectively, occurring twice, 4 hours apart at bed rest 2) thrombocytopenia (platelet counts <100,000 µL) 3) impaired liver function defined as either otherwise unexplained right-upper-quadrant-epigastric pain unresponsive to medications, or hepatic transaminase levels twice normal 4) progressive renal insufficiency 5) pulmonary edema 6) new-onset cerebral or visual disturbances.

PREVALENCE preeclampsia occurs in up to 7.5 % of pregnancies worldwide . Variations in incidence reflect, at least in part, differences in the maternal age distribution and proportion of primiparous women among populations . In these women, preeclampsia is generally mild, with the onset near term or intrapartum (75% of cases), and the condition conveys only a minimally increased risk for adverse fetal outcome.

Risk factors for Preeclampsia

OVERVIEW OF PATHOPHYSIOLOGY The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of the placental vasculature early in pregnancy, weeks to months before development of clinical manifestations of the disease, are well-documented . These abnormalities can result in placental underperfusion, and possibly hypoxia and ischemia .

OVERVIEW OF PATHOPHYSIOLOGY hypoxia and ischemia may lead to release of circulating antiangiogenic factors ([sFlt-1], [sEng]) and other substances that can cause widespread maternal systemic endothelial dysfunction (increased vascular permeability, vasoconstriction, activation of coagulation system, microangiopathic hemolysis), resulting in hypertension, proteinuria, and the other clinical manifestations of preeclampsia .

CLINICAL MANIFESTATIONS

CLINICAL MANIFESTATIONS In most women, these findings first become apparent after 34 weeks of gestation, including when the woman is in labor (ie, “ late onset preeclampsia”) In about 10 percent of women, hypertension and proteinuria develop before 34 weeks of gestation (ie, “early onset preeclampsia”) In about 5 percent, preeclampsia is first recognized postpartum, usually within 48 hours of delivery.

Atypical presentation

Atypical presentation  Atypical presentations include any of the following : Onset of signs/symptoms at <20 weeks of gestation Hypertension or proteinuria (but not both) with characteristic signs and symptoms of severe preeclampsia Delayed postpartum onset or exacerbation of disease (>2 days postpartum)

Atypical presentation Onset <20 weeks   Preeclampsia prior to 20 weeks of gestation is usually associated with a complete or partial molar pregnancy. Rarely, characteristic signs and symptoms before 20 weeks have been attributed to severe preeclampsia after other disorders with similar findings (eg, lupus nephritis, TTP,HUS , APAS, AFLP) were excluded.  In the absence of other pathology, the patient should be treated as for severe preeclampsia.

Atypical presentation Onset <20 weeks  These women should have ultrasound examination of the uterus to rule out molar pregnancy. These women should be evaluated to rule out the presence of lupus nephritis, TTP,HUS , APAS, AFLP. A diagnostic modality that is also .recommended is the measurement of uterine artery Doppler flow, which shows the classic “notching” characteristic of increased resistance in the placenta of patients with preeclampsia.

Atypical presentation Hypertension or proteinuria (not both)  Hypertension or proteinuria (but not both) with characteristic signs and symptoms of severe preeclampsia is uncommon, but may be observed in 15 percent of patients with HELLP syndrome and in some patients with eclampsia. Women with hypertension or proteinuria (but not both) may go on to develop preeclampsia.

Atypical presentation Delayed postpartum onset or exacerbation of disease  Delayed postpartum preeclampsia can be defined as signs and symptoms of the disease leading to readmission more than two days but less than six weeks after delivery , although various other definitions have been used. Of these patients, 14.5 percent developed postpartum eclampsia.

Capillary Leak Syndrome Hypertension is considered to be the hallmark for the diagnosis of preeclampsia. However, in some patients with preeclampsia, the disease may manifest as either a : capillary leak ( Facial Edema, Ascites and Pulmonary Edema, and Gestational Proteinuria ) sudden and rapid weight gain (eg, >5 pounds/week) and facial edema a spectrum of abnormal hemostasis with multiple-organ dysfunction

Isolated gestational proteinuria Significant proteinuria after 20 weeks gestation which resolved till 12 weeks post partum 30-50% may progress to preeclampsia

Gestational proteinuria CBC-plt serologic test (ANA-Anti DNA,c3,c4) HBS Ag-HIV-HCV liver enzyme PT-PTT uric acid sonography

Capillary Leak Syndrome Therefore, we recommend that women with capillary leak syndrome with or without hypertension be evaluated for platelet, liver enzyme, and renal abnormalities. Those with symptoms such as significant headache or abnormal blood tests should be considered to have atypical preeclampsia.

Antepartum Management of Mild Preeclampsia

Antepartum Management of Mild Preeclampsia Close maternal monitoring upon diagnosis of preeclampsia is important to establish disease severity and the rate of progression. Hospitalization is useful for making these assessments and facilitates rapid intervention in the event of rapid progression.

Inpatient versus outpatient care In women with mild preeclampsia at less than 37 weeks’ gestation but at more than 32 weeks, outpatient management can be considered for reliable patients with systolic BP of 150 mm Hg or less or diastolic BP of 100 mmHg or less and no increase in proteinuria if they have no symptoms and if they have normal liver enzymes and a normal platelet count (>100,000/mm3). Women who do not satisfy these criteria are hospitalized, particularly those with mild preeclampsia before 32 weeks.

Outpatient management of mild preeclampsia During ambulatory management, women are instructed to : Rest at home (restrict their activity but not to complete bedrest) Perform BP measurements daily Urine dipstick daily Prompt reporting of symptoms of severe disease

Outpatient management of mild preeclampsia Diet : these women are instructed to eat a regular diet with no salt restriction . Diuretics and antihypertensive medications are not used because of the potential to mask the diagnosis of severe disease.

Outpatient management of mild preeclampsia These women are then seen twice weekly, at which time a platelet count , Cr and liver enzyme test are performed.

Outpatient management of mild preeclampsia Fetal evaluation includes daily fetal movement count, twice-weekly NST with AFI, or BPP. Assessment of fetal growth We suggest sonographic estimation of fetal weight be at the time of diagnosis of preeclampsia and then repeated every three weeks if the initial examination is normal .

Outpatient management of mild preeclampsia Antenatal corticosteroids   Although preeclampsia may accelerate fetal lung maturation, neonatal respiratory distress remains common in premature neonates of preeclamptic pregnancies . Antenatal corticosteroids (betamethasone) to promote fetal lung maturity should be administered to women less than 34 weeks of gestation since they are at increased risk of progression to severe disease and preterm delivery.

Hospitalization If there is evidence of disease progression (significant increase in BP or proteinuria ≥2+, new onset of symptoms, or evidence of abnormal blood tests or abnormal fetal growth), these women are hospitalized for the duration of pregnancy. Women managed in the hospital receive similar maternal and fetal evaluation.

Time Of Delivery In Mild Preeclampsia Experts consistently recommend delivery of women with mild preeclampsia at ≥37 weeks of gestation . Cervical ripening agents should be used in women with unfavorable cervices.

Mode of Delivery A plan for vaginal delivery should be attempted in all women with mild disease without other indications for cesarean delivery.

INTRAPARTUM MANAGEMENT  There are no evidence-based standards for the optimal approach. Continuous maternal-fetal monitoring is indicated intrapartum to identify : Worsening hypertension Deteriorating maternal hepatic, renal, cardiopulmonary, neurological, or hematologic function Abruptio placentae Nonreassuring fetal heart rate tracing The presence of uterine tachysystole or recurrent fetal heart rate decelerations may be the first sign of abruptio placentae in these women.

INTRAPARTUM MANAGEMENT Some women with mild hypertension-preeclampsia progress to severe disease as a result of changes in cardiac output and stress hormones during labor. Therefore, women with gestational hypertension-preeclampsia should have BP recordings every hour and should be assessed for symptoms suggestive of severe disease.

INTRAPARTUM MANAGEMENT Fluids — Fluid balance should be monitored closely to avoid excessive administration, since women with severe disease are at risk of pulmonary edema and significant third-spacing. Maintenance fluids of 80 mL/hour ( 60-125 cc RL ) are often adequate in the absence of ongoing fluid loss, such as bleeding. Diuretics are only indicated for treatment of pulmonary edema.

Anesthesia: Neuraxial techniques  Neuraxial techniques are generally safe and effective in preeclamptic women . In preeclampsia, the two major anesthesia-related concerns with use of neuraxial techniques are : (1) the potential for a large drop in blood pressure due to depleted intravascular volume and sympathetic blockade (2) peridural hematoma in women with severe thrombocytopenia The former can be minimized by appropriate adjustments in pre-hydration, drug choice, drug dosing, and drug delivery by the anesthesiologist.

General Anesthesia  The major concerns associated with general anesthesia (for cesarean delivery) are : A marked increases in systemic and cerebral pressures during intubation and extubation (response to noxious stimuli). Hypotension (from reduction in cardiac output and systemic vascular resistance) Difficult or failed intubation because of oropharyngeal edema . general anesthesia carries the risk for aspiration.

General Anesthesia  Given these issues, early patient assessment by the anesthesia team is desirable. Women with airway or laryngeal edema may require awake intubation under fiberoptic observation with the availability of immediate tracheostomy . Changes in systemic and cerebral pressures may be attenuated by pretreatment with labetalol or nitroglycerine injections.

Analgesia Maternal pain relief during labor and delivery can be provided by either systemic opioids or segmental epidural anesthesia. Epidural analgesia is considered to be the preferred method of pain relief in women with mild gestational hypertension and mild preeclampsia. The use of either epidural, spinal, or combined techniques of regional anesthesia is considered by most obstetrical anesthesiologists to be the method of choice during cesarean delivery.

Seizure prophylaxis  Based upon data from randomized trials, we administer intrapartum magnesium sulfate seizure prophylaxis to women with mild or severe preeclampsia.

Seizure prophylaxis  It is important to emphasize that seizure prophylaxis does not prevent progression of disease unrelated to convulsions. Approximately 10 to 15 percent of women in labor with mild preeclampsia will develop signs of severe preeclampsia or abruptio placenta, whether or not they receive magnesium therapy.

Magnesium regimen and monitoring  There is no consensus on the optimal magnesium regimen, when it should be started and terminated, or route of administration . The drug is usually initiated at the onset of labor or induction, or prior to cesarean delivery .

Magnesium regimen and monitoring Dosing — Although published dosage regimens for magnesium sulfate vary widely (loading dose of 4 to 6 grams /IV and maintenance dose of 1 to 3 grams per hour), the most common regimen, is a loading dose of 6 grams /IV over 15 to 20 minutes followed by 2 grams per hour as a continuous infusion . An alternative regimen is 5 grams /IM into each buttock (total of 10 grams) followed by 5 grams /IM every four hours. However, this method is associated with more side effects, particularly pain at the injection site.

Magnesium regimen and monitoring There does not appear to be a clear threshold concentration for insuring the prevention of convulsions, although a therapeutic range of 4.8 to 8.4 mg/dL (2.0 to 3.5 mmol/L) has been recommended based on retrospective data . Loading doses less than 6 grams are more likely to result in subtherapeutic magnesium levels (less than 4.5 mg/dL)

Magnesium regimen and monitoring Since magnesium sulfate is excreted by the kidneys, dosing should be adjusted in women with renal insufficiency (defined as a serum creatinine greater than 1.0 mg/dL). Such women should receive a standard loading dose but a reduced maintenance dose and close monitoring of their serum magnesium level every six hours. No maintenance dose if the serum creatinine is greater than 2.5 mg/dL

Magnesium regimen and monitoring The maintenance phase is given only if : A patellar reflex is present (loss of reflexes being the first manifestation of symptomatic hypermagnesemia) Respirations exceed 12 per minute urine output exceeds 100 mL per four hours Following serum magnesium levels is not required if the woman's clinical status is closely monitored for evidence of potential magnesium toxicity The maintenance dose should be decreased if there is clinical evidence of magnesium toxicity.

Duration of therapy  Magnesium sulfate is usually continued for 24 hours postpartum . Timing of drug discontinuation has been arbitrary; there are no high quality data to guide therapy. In women who have only mild preeclampsia, discontinuation of therapy after 12 hours may be safe . In women with severe preeclampsia or eclampsia, seizure prophylaxis is generally continued for 24 to 48 hours postpartum, after which the risk of recurrent seizures is low.

Contraindication of Magnesium sulfate Hypersensitivity to any component of the formulation Myasthenia gravis Heart block Myocardial damage because of its anti-inotropic effects Neuromuscular blockade and hypotension due to concurrent use of magnesium sulfate and calcium channel blockers have been described in case reports, but the risk appears to be minimal.

Magnesium toxicity Magnesium toxicity is related to serum concentration: loss of deep tendon reflexes occurs at 9.6 to 12.0 mg/dL (4.0 to 5.0 mmol/L) Respiratory paralysis at 12.0 to 18.0 mg/dL (5 to 7.5 mmol/L) Cardiac arrest at 24 to 30 mg/dL (10 to 12.5 mmol/L)  Calcium gluconate (1 gram intravenously over 5 to 10 min in 50 mL of 5 percent dextrose or saline) should be administered only to counteract life-threatening symptoms of magnesium toxicity (such as cardiorespiratory compromise). The calcium should not be given more rapidly, because of the risk of serious cardiac dysfunction, including systolic arrest.

POSTPARTUM MANAGEMENT

Postpartum Management There are no evidence-based standards for the optimal approach to postpartum monitoring and follow-up. During the immediate postpartum period, women with preeclampsia should receive close monitoring of BP and of symptoms consistent with severe disease and accurate measurements of fluid intake and urinary output. We monitor vital signs every two hours while the patient remains on magnesium sulfate  and we repeat laboratory tests until two consecutive sets of data are normal.

Postpartum Management ACOG SUGGESTS MONITORING blood pressures in postpartum patients with gestational hypertension, preeclampsia, and superimposed preeclampsia for 72 hours in hospital and after 7 to 10 days postpartum.

Postpartum Management Careful evaluation of the amount of intravenous fluids, oral intake, blood products, and urine output, as well as monitoring by pulse oximetry and chest auscultation, are advised.

ACOG recommend using low-dose aspirin for prophylaxis in pregnant women with prior preterm preeclampsia or 2 or more previously affected pregnancies. Finally, they make common-sense—though non-evidence-based—recommendations that women with a history of preeclampsia lose weight, exercise, not smoke and have their blood pressure, fasting glucose, and lipid levels followed yearly to mitigate their risks of subsequent cardiovascular mortality

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