Preeclampsia and Eclampsia: Anesthetic ManagementHarfah, NsAssistant Clitical Specialist NursingDirector of Anesthesia and ReanimationUniv of Indonesian

Preeclampsia: EpidemiologyIncidence widely quoted at 5-7%varies greatly depending on the populationRemains a major cause of maternal mortalityU.S. (1987-90)PIH: 17.6% of mat. deaths, 3rd leading causePreeclampsia (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: ClassificationPregnancy-induced hypertensionHypertension without proteinuria/edemaPreeclampsiamildsevereEclampsiaCoincidental HTN: preexisting or persistentPregnancy-aggravated HTNsuperimposed preeclampsiasuperimposed eclampsiaTransient HTN: occurs in 3rd trimester, mild

Preeclampsia: DefinitionHypertension> 140/90relative no longer considered diagnosticProteinuria> 300 mg/24 hours or 1+ on urine dipsticknot mandatory for diagnosis; may occur lateEdema (non-dependent)so common & difficult to quantify it is rarely evoked to make or refute the diagnosis

Criteria for Severe PreeclampsiaSBP > 160 mm HgDBP > 110 mm HgProteinuria > 5 g/24 or 3-4+ on dipstickOliguria < 500 cc/24 serum creatininePulmonary edema or cyanosisCNS symptoms (HA, vision changes)Abdominal (RUQ) painAny feature of HELLPhemolysis liver enzymesthrombocytopeniaIUGR or oligohydramnios

Preeclampsia: Risk FactorsNulliparity (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:geneticimmunologicdietary deficiency (calcium, magnesium, zinc)supplementation has not proven effectiveplacental source (ischemia)

Etiology and PreventionA major underlying defect is a relative deficiency of prostacyclin vs. thromboxaneNormally (non-preeclamptic) there is an 8-10 fold in prostacyclin with a smaller in thromboxaneprostacyclin salutatory effects dominatevasodilation, platelet aggregation, uterine toneIn preeclampsia, thromboxanes effects dominate thromboxane (from platelets, placenta) prostacyclin (from endothelium, placenta)

Preeclampsia Prophylaxis: AspirinAspirin has been extensively studied as a targeted therapy to thromboxane productionCLASP study, 1994, multicenter, randomizedCLASP Collaborative Group, Lancet 1994;343:619-299364 women, risk factors for PIH or IUGR or who had PIH or IUGR60 mg ASA daily vs. placeboSmall reduction (12%) in occurrence of PIHSmall reduction in preterm deliveries: 20 vs 22%No difference in neonatal outcome

Preeclampsia Prophylaxis: AspirinNIH 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 aggregateNo difference in perinatal death, preterm delivery, IUGR, maternal or fetal hemorrhagic complications

Preeclampsia: MechanismAt 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;180:499-506present in normal pregnancyexcessive in preeclampsiaProposed source of inflammatory stimulus: placenta

Pathophysiology: CardiovascularIn 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 diseaseTotal body water is increased (generalized edema)

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

Colloid oncotic pressure:AntepartumPostpartumNormal pregnancy:22 mm Hg17 mm HgPreeclampsia:18 mm Hg14 mm Hg

PathophysiologyRespiratory:Airway is edematous; use smaller ET tube (6.5) risk of pulmonary edema; 70% postpartumRenal:Renal blood flow & GFR are decreasedRenal failure due to plasma volume or renal artery vasospasmProteinuria due to glomerulopathyglomerular capillary endothelial swelling w/subendothelial protein depositsRenal function recovers quickly postpartum

Pathophysiology: HepaticRUQ pain is a serious complaintwarrants imaging, especially when accompanied by liver enzymescaused 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 fibrinolysisThrombocytopenia is common, but fewer than 10% have platelet count < 100,000DIC may occur, esp. with placental abruptionNeurologic:Symptoms: headache, visual changes, seizuresHyperreflexia is usually presentEclamptic seizures may occur even w/out BPPossible causes: hypertensive encephalopathy, cerebral edema, thrombosis, hemorrhage, vasospasm

Obstetric ManagementClassically stabilize and deliverMedical management while awaiting delivery:use of steroids X 48 hours if fetus < 34 wksantihypertensives to maintain DBP < 105-110magnesium sulfate for seizure prophylaxismonitor fluid balance, I/O, daily weights, symptoms, reflexes, HCT, plts, LFTs, proteinuriaIndications for expedited delivery:fetal distress BP despite aggressive Rxworsening end-organ functiondevelopment or worsening of HELLP syndromedevelopment of eclampsia

Antihypertensive TherapyMost commonly, for acute control: hydralazine, labetololNifedipine may be used, but unexpected hypotension may occur when given with MgSO4For refractory hypertension: nitroglycerin or nitroprusside may be usedNitroprusside dose and duration should be limited to avoid fetal cyanide toxicityUsually require invasive arterial pressure monAngiotensin-converting enzyme (ACE) inhibitors contraindicated due to severe adverse fetal effects

Seizure Prophylaxis & TreatmentMagnesium 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;345:1455Mg pts were 52% or 67% less likely to have a recurrent seizure than diazepam or phenytoin pts

Seizure ProphylaxisEvidence is strong that magnesium sulfate is indicated for seizure treatment in eclampticsseizure prophylaxis in severe preeclampticsRole of magnesium prophylaxis in mild preeclamptics is less clearawaits large, prospective, randomized, placebo-controlled trial

Magnesium SulfateMagnesium sulfate has many effects; its mechanism in seizure control is not clear.NMDA (N-methyl-D-aspartate) antagonistvasodilatorBrain parenchymal vasodilation demonstrated in preeclamptics by Doppler ultrasonographyincreases release of prostacyclinPotential adverse effects:toxicity from overdose (respiratory, cardiac) bleeding hypotension with hemorrhage uterine contractility

Magnesium SulfateRenally excretedPreeclamptics prone to renal failureMagnesium levels must be monitored frequently either clinically (patellar reflexes) or by checking serum levels q 6-8 hoursTherapeutic 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/LTreatment of magnesium toxicity:stop MgSO4, IV calcium, manage airway

Treatment of EclampsiaSeizures 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 PreeclampsiaTo establish & maintain hemodynamic stability (control hypertension & avoid hypotension)To provide excellent labor analgesiaTo prevent complications of preeclampsiaintracerebral hemorrhagerenal failurepulmonary edemaeclampsiaTo be able to rapidly provide anesthesia for C/S

Benefits of Regional Analgesia for Labor in PreeclampsiaSuperior pain relief over parenteral narcoticsBeneficial hemodynamic effects: 20% reduction in blood pressure with a small reduction in SVR & maintenance of CINewsome, Anes Anal 1986;65:31-6Doppler 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 PreeclampsiaEpidural 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 meperidineNo 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 & PreeclampsiaOne 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 preeclampticspossibility of severe BP 2 sympathectomy in patient with volume contractionrisk of pulmonary edema due to excessive fluid administration with regional blockrisk with use of pressor agents to treat BP

Regional vs. General Anesthesia for C/S in Severe PreeclampsiaGeneral vs. spinal (CSE) vs. epiduralWallace, et al., Obstet Gynecol 1995;86:193-9Prospective, randomized studyAll 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 PreeclampsiaBP 20% lower in regional vs general groups at skin incision only; no difference in min pressuresRegional pts received 800 cc more IV fluid2200 cc vs. 1500 ccNo associated pulmonary edemaInfant outcomes were similarCaveat: cases were not urgent; none for non-reassuring FHR patternIn 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 PreeclampsiaHood, et al., Anesthesiology 1999;90:1276-82Retrospective studyLowest intraoperative blood pressures not differentTotal ephedrine use was small & not differentSpinal group received 400 cc more IV fluidNo pulmonary edema attributable to intraop fluidMaternal & infant outcomes were similar

Regional vs. General Anesthesia in PreeclampsiaEpidural anesthesia would probably be preferred by many anesthesiologists in a severely preeclamptic pt in a non-urgent settingFor urgent cases it is reassuring to know that spinal is also safeThis allows us to avoid general anesthesia with the potential for encountering a swollen, difficult airway and/or labile hypertension

Regional vs. General Anesthesia in PreeclampsiaGeneral 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 PreeclampsiaPrior 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 preeclampsiaAny clinical evidence of DIC would contraindicate regionalIn the absence of such signs, most anesthesiologists would proceed at plt count >100K, many would proceed at 80-100K,

Platelets & Regional Anesthesia in PreeclampsiaWhen placing a regional block in a patient with a platelet count < 100K, the most important thing is to monitor resolution of block closelyBleeding time has been discredited as an indicator of epidural bleeding risk and is not indicated.Channing-Rogers, Semin Thromb Hemost 1990;16:;1-30Low-dose aspirin is not a contraindication to regional anesthesia in preeclampsiaCLASP study: 1422 women on aspirin received epidurals without any bleeding complications

Hazards of General Anesthesiain PreeclampsiaAirway edema is commonMandatory to reexamine the airway soon before inductionEdema may appear or worsen at any time during the course of diseasetongue & facial, as well as laryngealLaryngoscopy and intubation may severe BPLabetolol & NTG are commonly used acutelyFentanyl (2.5 mcg/kg), alfentanil (10 mcg/kg), lidocaine may be given to blunt response

Hazards of General Anesthesiain PreeclampsiaMagnesium sulfate potentiates depolarizing & non-depolarizing muscle relaxantsPre-curarization is not indicated.Initial dose of succinylcholine is not reduced.Neuromuscular blockade should be monitored & reversal confirmed.

Invasive Central Hemodynamic Monitoring in PreeclampsiaUsually reserved for patients with complicationsoliguria unresponsive to modest fluid challenge (500 cc LR X 2)pulmonary edemarefractory hypertensionmay 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 numberIf poor response, change to PA catheter

ConclusionsPreeclampsia 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.

ConclusionsDelivery 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.