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% 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 causeIn the most developed and medically

advanced region: 46% of deaths

Hypertension during Pregnancy: Classification

Pregnancy-induced hypertension Hypertension without proteinuria/edema Preeclampsia

mildsevere

EclampsiaCoincidental HTN: preexisting or persistentPregnancy-aggravated HTN

superimposed preeclampsia superimposed eclampsia

Transient HTN: occurs in 3rd trimester, mild

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 HgDBP > 110 mm HgProteinuria > 5 g/24°

or 3-4+ on dipstickOliguria < 500

cc/24° serum creatininePulmonary edema or

cyanosis

CNS symptoms (HA, vision changes)

Abdominal (RUQ) painAny feature of HELLP

hemolysis liver enzymes thrombocytopenia

IUGR or oligohydramnios

Preeclampsia: Risk Factors

Nulliparity (or, more correctly, primipaternity)

Chronic renal diseaseAngiotensinogen gene T235Chronic hypertensionAntiphospholipid antibody syndromeMultiple gestationFamily or personal history of preeclampsiaAge > 40 yearsAfrican-American raceDiabetes mellitus

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 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

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

CLASP study, 1994, multicenter, randomizedCLASP 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: 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

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

global endothelial cell dysfunctionRedman: 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

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: 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 HgPreeclampsia: 18 mm Hg 14 mm Hg

Pathophysiology

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

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.

PathophysiologyCoagulation:

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 abruptionNeurologic:

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

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

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

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 eclampticsEclampsia 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

Evidence is strong that magnesium sulfate is indicated for seizure treatment in eclamptics seizure prophylaxis in severe

preeclampticsRole of magnesium prophylaxis in mild

preeclamptics is less clear awaits large, prospective, randomized,

placebo-controlled trial

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 prostacyclinPotential adverse effects:

toxicity from overdose (respiratory, cardiac) bleeding hypotension with hemorrhage uterine contractility

Magnesium Sulfate

Renally excretedPreeclamptics prone to renal failureMagnesium levels must be monitored

frequently either clinically (patellar reflexes) or by checking serum levels q 6-8 hours

Therapeutic level: 4-7 meq/LPatellar reflexes lost: 8-10 meq/LRespiratory depression: 10-15 meq/LRespiratory paralysis: 12-15 meq/LCardiac arrest: 25-30 meq/L

Treatment of magnesium toxicity: stop MgSO4, IV calcium, manage airway

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

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

To provide excellent labor analgesiaTo 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

Superior pain relief over parenteral narcoticsBeneficial hemodynamic effects: 20%

reduction in blood pressure with a small reduction in SVR & maintenance of CINewsome, 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 Preeclampsia

Epidural analgesia intervillous blood flow 77% in severe preeclamptics without maternal BP or FHR abnormalitiesJouppila, 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 groupLucas, et al., Anesthesiology 1998;89:A1033

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

General vs. spinal (CSE) vs. epiduralWallace, 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 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 similarCaveat: 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

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

Retrospective studyLowest intraoperative blood pressures not differentTotal ephedrine use was small & not differentSpinal group received 400 cc more IV fluid

No pulmonary edema attributable to intraop fluidMaternal & infant outcomes were similar

Regional vs. General Anesthesia in 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 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 preeclampsiaHawkins, Anesthesiology 1997;86:273

Platelets & Regional Anesthesia in 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 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 Anesthesiain 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 diseasetongue & 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 Anesthesiain 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

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 SVRPoor correlation between CVP and PCWP in PIH

However, at most centers anesthesiologists would begin with CVP & follow trendnot arbitrarily hydrate to a certain number

If poor response, change to PA catheter

Conclusions

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

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.