Preeclampsia and Eclampsia: Anesthetic Management

1
Preeclampsia and Eclampsia Anesthetic Management

• Anita M. Backus, MD
• Assistant Clinical Professor
• Director of Obstetric Anesthesia
• UCLA Medical Center
• Los Angeles, California

2
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

3
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

4
Preeclampsia Definition

• Hypertension
• gt 140/90
• relative ? no longer considered diagnostic
• Proteinuria
• gt 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

5
Criteria for Severe Preeclampsia

• SBP gt 160 mm Hg
• DBP gt 110 mm Hg
• Proteinuria gt 5 g/24 or 3-4 on dipstick
• Oliguria lt 500 cc/24
• ? serum creatinine
• Pulmonary edema or cyanosis

• CNS symptoms (HA, vision changes)
• Abdominal (RUQ) pain
• Any feature of HELLP
• hemolysis
• ? liver enzymes
• thrombocytopenia
• IUGR or oligohydramnios

6
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 gt 40 years
• African-American race
• Diabetes mellitus

7
Etiology and Prevention

• Etiology is unknown.
• Many theories
• genetic
• immunologic
• dietary deficiency (calcium, magnesium, zinc)
• supplementation has not proven effective
• placental source (ischemia)

8
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, thromboxanes effects dominate
• ? thromboxane (from platelets, placenta)
• ? prostacyclin (from endothelium, placenta)

9
Preeclampsia Prophylaxis Aspirin

• Aspirin has been extensively studied as a
  targeted therapy to ? thromboxane production
• CLASP study, 1994, multicenter, randomized
• CLASP Collaborative Group, Lancet
  1994343619-29
• 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

10
Preeclampsia Prophylaxis Aspirin

• NIH study of high-risk patients, randomized,
  60 mg aspirin daily vs. placebo
• Caritis, et al., N Engl J Med 1998338701-5
• 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

11
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
  1999180499-506
• present in normal pregnancy
• excessive in preeclampsia
• Proposed source of inflammatory stimulus placenta

12
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)

13
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

14
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

15
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.

16
Pathophysiology

• Coagulation
• Generally hypercoagulable with evidence of
  platelet activation and increased fibrinolysis
• Thrombocytopenia is common, but fewer than 10
  have platelet count lt 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

17
Obstetric Management

• Classically stabilize and deliver
• Medical management while awaiting delivery
• use of steroids X 48 hours if fetus lt 34 wks
• antihypertensives to maintain DBP lt 105-110
• magnesium sulfate for seizure prophylaxis
• monitor fluid balance, I/O, daily weights,
  symptoms, reflexes, HCT, plts, LFTs, proteinuria
• Indications for expedited delivery
• fetal distress
• ? BP despite aggressive Rx
• worsening end-organ function
• development or worsening of HELLP syndrome
• development of eclampsia

18
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

19
Seizure Prophylaxis Treatment

• Magnesium sulfate vs. phenytoin for seizure
  prophylaxis in preeclampsia
• Lucas, et al., N Engl J Med 1995333201-5.
• 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
  19953451455
• Mg pts were 52 or 67 less likely to have a
  recurrent seizure than diazepam or phenytoin pts

20
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

21
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

22
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

23
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.

24
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

25
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 19866531-6
• 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 19917720-6
• ? vascular resistance relief of vasospasm

26
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 198259158-61.
• 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 199889A1033

27
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

28
Regional vs. General Anesthesia for C/S in Severe
Preeclampsia

• General vs. spinal (CSE) vs. epidural
• Wallace, et al., Obstet Gynecol 199586193-9
• 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

29
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

30
Epidural vs. Spinal Anesthesia for C/S in Severe
Preeclampsia

• Hood, et al., Anesthesiology 1999901276-82
• 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

31
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

32
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 preeclampsia
• Hawkins, Anesthesiology 199786273

33
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
  gt100K, many would proceed at 80-100K, lt80K some
  would proceed (esp. spinal)

34
Platelets Regional Anesthesia in Preeclampsia

• When placing a regional block in a patient with a
  platelet count lt 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
  1990161-30
• Low-dose aspirin is not a contraindication to
  regional anesthesia in preeclampsia
• CLASP study 1422 women on aspirin received
  epidurals without any bleeding complications

35
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 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

36
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.

37
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 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

38
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.

39
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.