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Preeclampsia and Eclampsia: Anesthetic Management. Anita M. Backus, MD Assistant Clinical Professor Director of Obstetric Anesthesia UCLA Medical Center Los Angeles, California. Preeclampsia: Epidemiology. Incidence widely quoted at 5-7%

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Preeclampsia and eclampsia anesthetic management

Preeclampsia and Eclampsia: Anesthetic Management

Anita M. Backus, MD

Assistant Clinical Professor

Director of Obstetric Anesthesia

UCLA Medical Center

Los Angeles, California

Preeclampsia epidemiology
Preeclampsia: Epidemiology

  • Incidence widely quoted at 5-7%

    • varies greatly depending on the population

  • Remains a major cause of maternal mortality

    • U.S. (1987-90)

      • PIH: 17.6% of mat. deaths, 3rd leading cause

        • Preeclampsia (9.4%); eclampsia (7.4%)

    • Mexico (1990-95)

      • PIH: 26% of deaths (2204), 2nd leading cause

      • In the most developed and medically advanced region: 46% of deaths

Hypertension during pregnancy classification
Hypertension during Pregnancy: Classification

  • Pregnancy-induced hypertension

    • Hypertension without proteinuria/edema

    • Preeclampsia

      • mild

      • severe

    • Eclampsia

  • Coincidental HTN: preexisting or persistent

  • Pregnancy-aggravated HTN

    • superimposed preeclampsia

    • superimposed eclampsia

  • Transient HTN: occurs in 3rd trimester, mild

Preeclampsia definition
Preeclampsia: Definition

  • Hypertension

    • > 140/90

    • relative  no longer considered diagnostic

  • Proteinuria

    • > 300 mg/24 hours or  1+ on urine dipstick

    • not mandatory for diagnosis; may occur late

  • Edema (non-dependent)

    • so common & difficult to quantify it is rarely evoked to make or refute the diagnosis

Criteria for severe preeclampsia

SBP > 160 mm Hg

DBP > 110 mm Hg

Proteinuria > 5 g/24° or 3-4+ on dipstick

Oliguria < 500 cc/24°

 serum creatinine

Pulmonary edema or cyanosis

CNS symptoms (HA, vision changes)

Abdominal (RUQ) pain

Any feature of HELLP


 liver enzymes


IUGR or oligohydramnios

Criteria for Severe Preeclampsia

Preeclampsia risk factors
Preeclampsia: Risk Factors

  • Nulliparity (or, more correctly, primipaternity)

  • Chronic renal disease

  • Angiotensinogen gene T235

  • Chronic hypertension

  • Antiphospholipid antibody syndrome

  • Multiple gestation

  • Family or personal history of preeclampsia

  • Age > 40 years

  • African-American race

  • Diabetes mellitus

Etiology and prevention
Etiology and Prevention

  • Etiology is unknown.

  • Many theories:

    • genetic

    • immunologic

    • dietary deficiency (calcium, magnesium, zinc)

      • supplementation has not proven effective

    • placental source (ischemia)

Etiology and prevention1
Etiology and Prevention

  • A major underlying defect is a relative deficiency of prostacyclin vs. thromboxane

  • Normally (non-preeclamptic) there is an 8-10 fold  in prostacyclin with a smaller  in thromboxane

    • prostacyclin salutatory effects dominate

      • vasodilation,  platelet aggregation,  uterine tone

  • In preeclampsia, thromboxane’s effects dominate

    •  thromboxane (from platelets, placenta)

    •  prostacyclin (from endothelium, placenta)

Preeclampsia prophylaxis aspirin
Preeclampsia Prophylaxis: Aspirin

  • Aspirin has been extensively studied as a targeted therapy to  thromboxane production

  • CLASP study, 1994, multicenter, randomized

    CLASP Collaborative Group, Lancet 1994;343:619-29

    • 9364 women, risk factors for PIH or IUGR or who had PIH or IUGR

    • 60 mg ASA daily vs. placebo

    • Small reduction (12%) in occurrence of PIH

    • Small reduction in preterm deliveries: 20 vs 22%

    • No difference in neonatal outcome

Preeclampsia prophylaxis aspirin1
Preeclampsia Prophylaxis: Aspirin

  • NIH study of high-risk patients, randomized, 60 mg aspirin daily vs. placebo

    Caritis, et al., N Engl J Med 1998;338:701-5

    • pre-gestational DM (471 patients)

    • chronic hypertension (774 patients)

    • multifetal gestations (688 patients)

    • prior history of preeclampsia (606 patients)

  • No reduction in development of preeclampsia in any subgroup or groups in aggregate

  • No difference in perinatal death, preterm delivery, IUGR, maternal or fetal hemorrhagic complications

Preeclampsia mechanism
Preeclampsia: Mechanism

  • At this time the most widely accepted proposed mechanism for preeclampsia is:

    • global endothelial cell dysfunction

  • Redman: endothelial cell dysfunction is just one manifestation of a broader intravascular inflammatory response

    Redman, et al., Am J Obstet Gynecol 1999;180:499-506

    • present in normal pregnancy

    • excessive in preeclampsia

    • Proposed source of inflammatory stimulus: placenta

  • Pathophysiology cardiovascular
    Pathophysiology: Cardiovascular

    • In severe preeclampsia, typically hyperdynamic with normal-high CO, normal-mod. high SVR, and normal PCWP and CVP.

    • Despite normal filling pressures, intravascular fluid volume is reduced (30-40% in severe PIH)

    • Variations in presentation depending on prior treatment and severity and duration of disease

    • Total body water is increased (generalized edema)

    Pathophysiology cardiovascular1
    Pathophysiology: Cardiovascular

    • Preeclamptic patients are prone to develop pulmonary edema due to reduced colloid oncotic pressure (COP), which falls further postpartum:

      Colloid oncotic pressure:

      Antepartum Postpartum

      Normal pregnancy: 22 mm Hg 17 mm Hg

      Preeclampsia: 18 mm Hg 14 mm Hg


    • Respiratory:

      • Airway is edematous; use smaller ET tube (6.5)

      •  risk of pulmonary edema; 70% postpartum

    • Renal:

      • Renal blood flow & GFR are decreased

      • Renal failure due to  plasma volume or renal artery vasospasm

      • Proteinuria due to glomerulopathy

        • glomerular capillary endothelial swelling w/subendothelial protein deposits

      • Renal function recovers quickly postpartum

    Pathophysiology hepatic
    Pathophysiology: Hepatic

    • RUQ pain is a serious complaint

      • warrants imaging, especially when accompanied by  liver enzymes

      • caused by liver swelling, periportal hemorrhage, subcapsular hematoma, hepatic rupture (30% mortality)

    • HELLP syndrome occurs in ~ 20% of severe preeclamptics.


    • Coagulation:

      • Generally hypercoagulable with evidence of platelet activation and increased fibrinolysis

      • Thrombocytopenia is common, but fewer than 10% have platelet count < 100,000

      • DIC may occur, esp. with placental abruption

    • Neurologic:

      • Symptoms: headache, visual changes, seizures

      • Hyperreflexia is usually present

      • Eclamptic seizures may occur even w/out BP

        • Possible causes: hypertensive encephalopathy, cerebral edema, thrombosis, hemorrhage, vasospasm

    Obstetric management
    Obstetric Management

    • Classically “stabilize and deliver”

    • Medical management while awaiting delivery:

      • use of steroids X 48 hours if fetus < 34 wks

      • antihypertensives to maintain DBP < 105-110

      • magnesium sulfate for seizure prophylaxis

      • monitor fluid balance, I/O, daily weights, symptoms, reflexes, HCT, plts, LFT’s, proteinuria

    • Indications for expedited delivery:

      • fetal distress

      •  BP despite aggressive Rx

      • worsening end-organ function

      • development or worsening of HELLP syndrome

      • development of eclampsia

    Antihypertensive therapy
    Antihypertensive Therapy

    • Most commonly, for acute control: hydralazine, labetolol

    • Nifedipine may be used, but unexpected hypotension may occur when given with MgSO4

    • For refractory hypertension: nitroglycerin or nitroprusside may be used

      • Nitroprusside dose and duration should be limited to avoid fetal cyanide toxicity

      • Usually require invasive arterial pressure mon

    • Angiotensin-converting enzyme (ACE) inhibitors contraindicated due to severe adverse fetal effects

    Seizure prophylaxis treatment
    Seizure Prophylaxis & Treatment

    • Magnesium sulfate vs. phenytoin for seizure prophylaxis in preeclampsia

      Lucas, et al., N Engl J Med 1995;333:201-5.

      • 2138 patients (75% had mild PIH)

      • Maternal & fetal outcomes similar except 10 seizures in the phenytoin group (0 in MgSO4)

    • Mg vs. diazepam & Mg vs. phenytoin for preventing recurrent seizures in eclamptics

      Eclampsia Trial Collaborative Group, Lancet 1995;345:1455

      • Mg pts were 52% or 67% less likely to have a recurrent seizure than diazepam or phenytoin pts

    Seizure prophylaxis
    Seizure Prophylaxis

    • Evidence is strong that magnesium sulfate is indicated for

      • seizure treatment in eclamptics

      • seizure prophylaxis in severe preeclamptics

    • Role of magnesium prophylaxis in mild preeclamptics is less clear

      • awaits large, prospective, randomized, placebo-controlled trial

    Magnesium sulfate
    Magnesium Sulfate

    • Magnesium sulfate has many effects; its mechanism in seizure control is not clear.

      • NMDA (N-methyl-D-aspartate) antagonist

      • vasodilator

        • Brain parenchymal vasodilation demonstrated in preeclamptics by Doppler ultrasonography

      • increases release of prostacyclin

    • Potential adverse effects:

      • toxicity from overdose (respiratory, cardiac)

      •  bleeding

      •  hypotension with hemorrhage

      •  uterine contractility

    Magnesium sulfate1
    Magnesium Sulfate

    • Renally excreted

    • Preeclamptics prone to renal failure

    • Magnesium levels must be monitored frequently either clinically (patellar reflexes) or by checking serum levels q 6-8 hours

      • Therapeutic level: 4-7 meq/L

      • Patellar reflexes lost: 8-10 meq/L

      • Respiratory depression: 10-15 meq/L

      • Respiratory paralysis: 12-15 meq/L

      • Cardiac arrest: 25-30 meq/L

  • Treatment of magnesium toxicity:

    • stop MgSO4, IV calcium, manage airway

  • Treatment of eclampsia
    Treatment of Eclampsia

    • Seizures are usually short-lived.

    • If necessary, small doses of barbiturate or benzodiazepine (STP, 50 mg, or midazolam, 1-2 mg) and supplemental oxygen by mask.

    • If seizure persists or patient is not breathing, rapid sequence induction with cricoid pressure and intubation should be performed.

    • Patient may be extubated once she is completely awake, recovered from neuromuscular blockade, and magnesium sulfate has been administered.

    Anesthetic goals of labor analgesia in preeclampsia
    Anesthetic Goals of Labor Analgesia in Preeclampsia

    • To establish & maintain hemodynamic stability (control hypertension & avoid hypotension)

    • To provide excellent labor analgesia

    • To prevent complications of preeclampsia

      • intracerebral hemorrhage

      • renal failure

      • pulmonary edema

      • eclampsia

    • To be able to rapidly provide anesthesia for C/S

    Benefits of regional analgesia for labor in preeclampsia
    Benefits of Regional Analgesia for Labor in Preeclampsia

    • Superior pain relief over parenteral narcotics

    • Beneficial hemodynamic effects: 20% reduction in blood pressure with a small reduction in SVR & maintenance of CI

      Newsome, Anes Anal 1986;65:31-6

    • Doppler velocimetry shows epidural analgesia reduces the S-D flow ratio in the uterine artery by 25% to levels seen in non-preeclamptics

      Ramos-Santos, et al., Obstet Gynecol 1991;77:20-6

      •  vascular resistance & relief of vasospasm

    Benefits of regional analgesia for labor in preeclampsia1
    Benefits of Regional Analgesia for Labor in Preeclampsia

    • Epidural analgesia  intervillous blood flow 77% in severe preeclamptics without maternal BP or FHR abnormalities

      Jouppila, et al., Obstet Gynecol 1982;59:158-61.

    • Large series (385) preeclamptic patients; labor epidural analgesia vs. PCIA meperidine

      • No difference in FHR abnormalities or C/S

      •  forceps in epi group but 0.125% bupi infusion

      •  naloxone use,  umb artery pH,  1 min Apgar in PCIA group

        Lucas, et al., Anesthesiology 1998;89:A1033

    Regional anesthesia preeclampsia
    Regional Anesthesia & Preeclampsia

    • One of the most important advantages of labor epidural analgesia is that it provides a route for rapid initiation of anesthesia for emergency C/S.

    • In the past there were concerns re: use of regional anesthesia for C/S in preeclamptics

      • possibility of severe  BP 2° sympathectomy in patient with volume contraction

      • risk of pulmonary edema due to excessive fluid administration with regional block

      • risk with use of pressor agents to treat  BP

    Regional vs general anesthesia for c s in severe preeclampsia
    Regional vs. General Anesthesia for C/S in Severe Preeclampsia

    • General vs. spinal (CSE) vs. epidural

      Wallace, et al., Obstet Gynecol 1995;86:193-9

      • Prospective, randomized study

      • All these types of anesthesia were used safely

      •  BP on laryngoscopy avoided by controlling hypertension pre-op with hydralazine; IV NTG & lidocaine immediately pre-intubation

      •  BP with regional avoided by 1000 cc LR pre-load & 5 mg boluses of ephedrine for SBP  100

    Regional vs general anesthesia for c s in severe preeclampsia1
    Regional vs. General Anesthesia for C/S in Severe Preeclampsia

    • BP 20% lower in regional vs general groups at skin incision only; no difference in min pressures

    • Regional pts received 800 cc more IV fluid

      • 2200 cc vs. 1500 cc

      • No associated pulmonary edema

    • Infant outcomes were similar

    • Caveat: cases were not urgent; none for non-reassuring FHR pattern

      • In an urgent situation there might not be time to adequately control hypertension pre-op prior to inducing general anesthesia

    Epidural vs spinal anesthesia for c s in severe preeclampsia
    Epidural vs. Spinal Anesthesia for C/S in Severe Preeclampsia

    • Hood, et al., Anesthesiology 1999;90:1276-82

    • Retrospective study

    • Lowest intraoperative blood pressures not different

    • Total ephedrine use was small & not different

    • Spinal group received 400 cc more IV fluid

      • No pulmonary edema attributable to intraop fluid

    • Maternal & infant outcomes were similar

    Regional vs general anesthesia in preeclampsia
    Regional vs. General Anesthesia in Preeclampsia Preeclampsia

    • Epidural anesthesia would probably be preferred by many anesthesiologists in a severely preeclamptic pt in a non-urgent setting

    • For urgent cases it is reassuring to know that spinal is also safe

    • This allows us to avoid general anesthesia with the potential for encountering a swollen, difficult airway and/or labile hypertension

    Regional vs general anesthesia in preeclampsia1
    Regional vs. General Anesthesia in Preeclampsia Preeclampsia

    • General anesthesia is a well-known hazard in obstetric anesthesia:

      • 16X more likely to result in anesthetic-related maternal mortality

      • Mostly due to airway/respiratory complications, which would only be exaggerated in preeclampsia

        Hawkins, Anesthesiology 1997;86:273

    Platelets regional anesthesia in preeclampsia
    Platelets & Regional Anesthesia in Preeclampsia Preeclampsia

    • Prior to placing regional block in a preeclamptic it is recommended to check the platelet count.

    • No concrete evidence at to the lowest safe platelet count for regional anesthesia in preeclampsia

    • Any clinical evidence of DIC would contraindicate regional

    • In the absence of such signs, most anesthesiologists would proceed at plt count >100K, many would proceed at 80-100K, <80K some would proceed (esp. spinal)

    Platelets regional anesthesia in preeclampsia1
    Platelets & Regional Anesthesia in Preeclampsia Preeclampsia

    • When placing a regional block in a patient with a platelet count < 100K, the most important thing is to monitor resolution of block closely

    • Bleeding time has been discredited as an indicator of epidural bleeding risk and is not indicated.

      Channing-Rogers, Semin Thromb Hemost 1990;16:;1-30

    • Low-dose aspirin is not a contraindication to regional anesthesia in preeclampsia

      • CLASP study: 1422 women on aspirin received epidurals without any bleeding complications

    Hazards of general anesthesia in preeclampsia
    Hazards of General Anesthesia Preeclampsiain Preeclampsia

    • Airway edema is common

      • Mandatory to reexamine the airway soon before induction

      • Edema may appear or worsen at any time during the course of disease

        • tongue & facial, as well as laryngeal

    • Laryngoscopy and intubation may  severe BP

      • Labetolol & NTG are commonly used acutely

      • Fentanyl (2.5 mcg/kg), alfentanil (10 mcg/kg), lidocaine may be given to blunt response

    Hazards of general anesthesia in preeclampsia1
    Hazards of General Anesthesia Preeclampsiain Preeclampsia

    • Magnesium sulfate potentiates depolarizing & non-depolarizing muscle relaxants

      • Pre-curarization is not indicated.

      • Initial dose of succinylcholine is not reduced.

      • Neuromuscular blockade should be monitored & reversal confirmed.

    Invasive central hemodynamic monitoring in preeclampsia
    Invasive Central Hemodynamic Monitoring in Preeclampsia Preeclampsia

    • Usually reserved for patients with complications

      • oliguria unresponsive to modest fluid challenge (500 cc LR X 2)

      • pulmonary edema

      • refractory hypertension

        • may have increased CO or increased SVR

    • Poor correlation between CVP and PCWP in PIH

      • However, at most centers anesthesiologists would begin with CVP & follow trend

        • not arbitrarily hydrate to a certain number

      • If poor response, change to PA catheter

    Conclusions Preeclampsia

    • Preeclampsia is a serious multi-organ system disorder of pregnancy that continues to defy our complete understanding.

    • It is characterized by global endothelial cell dysfunction.

    • The cause remains unknown.

    • There is no effective prophylaxis.

    Conclusions Preeclampsia

    • Delivery is the only effective cure.

    • Magnesium sulfate is now proven as the best medication to prevent and treat eclampsia.

    • Epidural analgesia for labor pain management & regional anesthesia for C/S have many beneficial effects & are preferred.