Because of a lack of universally accepted diagnostic criteria for HELLP syndrome, its incidence cannot be determined accurately. The existence of a subset of preeclampsia complicated by abnormal peripheral blood smear, abnormal liver function tests, and thrombocytopenia has been recognized for decades; in 1982, Weinstein231 described a series of 29 cases and coined the acronym HELLP. Women who do not demonstrate one or more of these clinical features are said to have “partial” HELLP syndrome.

Hemolysis, defined as the presence of microangiopathic hemolytic anemia, is the classic hallmark of HELLP syndrome; peripheral blood smear demonstrates schistocytes, burr cells, and echinocytes.232 Common histopathologic findings are periportal hepatic necrosis and hemorrhage.233 Sibai232 has proposed standardized laboratory diagnostic criteria, as outlined in Table 36-6. Maternal signs and symptoms include right upper quadrant or epigastric pain, nausea and vomiting, headache, hypertension, and proteinuria. Notably, clinical presentation varies; 12% to 18% of women may be normotensive, and proteinuria is absent in approximately 13% of affected women. Diagnosis can be especially challenging because numerous medical and surgical disorders, including acute fatty liver of pregnancy, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, and lupus, can mimic HELLP syndrome (Box 36-4). Pregnant women likely to have preeclampsia, but who demonstrate atypical symptoms, should be screened with a complete blood cell count, platelet count, and liver enzyme assessment.

In general, patients with HELLP syndrome are not considered candidates for expectant management155; however, deferred delivery for 24 to 48 hours to allow for corticosteroid administration to accelerate fetal lung maturity may be appropriate for women less than 34 weeks' gestation if the maternal and fetal condition remain stable.4 Women with HELLP syndrome who have not yet reached 34 weeks' gestation should be managed in a tertiary care facility with a neonatal intensive care unit capable of caring for a compromised preterm neonate.4 Clinical management is similar to that for severe preeclampsia and includes intravenous magnesium sulfate for seizure prophylaxis and antihypertensive medications to maintain a systolic blood pressure below 160 mm Hg and a diastolic blood pressure below 110 mm Hg.232 The first priority is to assess and stabilize the maternal condition, with particular attention given to hypertension and coagulation abnormalities. Next, the fetal condition should be assessed with FHR monitoring, Doppler ultrasonography of fetal vessels, a biophysical profile, or several of these options.

The platelet count can fall precipitously in the presence of HELLP syndrome, and it should be evaluated before the administration of neuraxial anesthesia. Women with a platelet count less than 50,000/mm3 are at significantly increased risk for bleeding,234 and general anesthesia is the method of choice for cesarean delivery. Data suggest treatment with dexamethasone may improve the platelet count in women with HELLP.207 If treatment with dexamethasone improves the patient's platelet count, the decision as to whether to use neuraxial anesthesia must weigh the risk of recurrent thrombocytopenia against the risk for a difficult airway and hypertension during induction of general anesthesia.

Platelet transfusions are indicated in the presence of significant bleeding and in all parturients with a platelet count less than 20,000/mm3. For women with a platelet count less than 40,000/mm3 who are scheduled for cesarean delivery, the preincision administration of 6 to 10 units of pooled random-donor platelets (or 1 to 2 units of apheresis platelets) has been recommended.235 The risk for postpartum hemorrhage is significantly increased in patients with HELLP syndrome; at least 2 red blood cell units should be type and crossmatched and large-bore intravenous access obtained.

Rupture of a subcapsular hematoma of the liver is a life-threatening complication of HELLP syndrome and severe preeclampsia236 that can manifest as abdominal pain, nausea and vomiting, and headaches; the pain worsens over time and becomes localized to the epigastric area or right upper quadrant. Hypotension and shock typically develop, and the liver is enlarged and tender.237 Diagnosis is confirmed with ultrasonography, computed tomography (CT), or magnetic resonance imaging of the liver (Figure 36-7). Subcapsular hematoma rupture with shock is a surgical emergency that requires immediate multidisciplinary treatment that includes intravascular volume resuscitation and blood and plasma transfusions.237 In some circumstances, selective arterial embolization by an interventional radiologist might be useful.236,238,239 Patients with fulminant hepatic failure may require liver transplantation.236 Prompt surgical intervention and refinements in surgical technique have substantially reduced the maternal mortality rate associated with spontaneous hepatic rupture to less than 20% in the past decade.236 The most common causes of death are coagulopathy and exsanguination.230,240

Conservative management is recommended for subcapsular hematoma or intraparenchymal hemorrhage without capsular rupture in stable women.235 Careful monitoring with ultrasonography or CT scan or both is required. An important component of conservative management is to avoid all potential trauma to the liver, including seizures, vomiting, and manual palpation of the abdomen. Patient transport and transfers should be conducted with care to avoid maneuvers that might result in rupture of a hematoma.

Anesthetic Management

The anesthetic management of the woman with preeclampsia without severe features differs little from the management of a healthy pregnant woman. However, the potential for rapid progression to the severe form of the disease mandates careful observation of the patient. The anesthesia provider must recognize the unpredictability of the development and progression of severe preeclampsia and should be prepared at all times for immediate cesarean delivery.

Preanesthetic Evaluation

The preanesthetic assessment of women with confirmed or suspected preeclampsia should focus on the airway examination, maternal hemodynamic and coagulation status, and fluid balance.

Airway.

Generalized edema can involve the airway and obscure visualization of anatomic landmarks at laryngoscopy.123 The anesthesia provider should anticipate the possibility of difficult airway management (see Chapter 30).

Hemodynamic Monitoring.

Systemic arterial blood pressure can change rapidly in women with severe preeclampsia, both as a result of disease progression and in response to the administration of intravenous fluids and antihypertensive drugs. In addition, preeclampsia is associated with variable degrees of intravascular volume depletion and the clinical assessment of intravascular volume status can be difficult. Therefore, the use of invasive vascular monitoring may be useful in the management of some women with severe preeclampsia.

The most frequent indications for radial artery catheter insertion are (1) poorly controlled maternal blood pressure; (2) need for frequent arterial blood gas measurements, especially in the context of pulmonary edema; (3) planned use of a rapid-acting vasodilator (e.g., sodium nitroprusside, nitroglycerin, nicardipine infusion); (4) use of calculated systolic pressure variation (SPV)241 to estimate intravascular volume status; and (5) need for continuous blood pressure monitoring during the induction of and emergence from general anesthesia in hypertensive women with severe preeclampsia.

Invasive central monitoring has been advocated in the assessment of oliguria and to monitor patient responses to fluid administration, but in practice it is rarely used. When invasive central monitoring is desired, a central venous pressure (CVP) catheter is adequate in the majority of cases; a pulmonary artery catheter is generally only used in patients with severe cardiac disease. The placement of an invasive CVP or pulmonary artery catheter is not a benign procedure. Well-recognized risks include arterial trauma, pneumothorax, venous air embolism, neuropathy, and cardiac arrhythmias. Additional risks for an indwelling pulmonary artery catheter include potentially fatal pulmonary artery hemorrhage, thromboembolism, sepsis, and endocardial damage.242

The 1991 to 1993 Report on Confidential Enquiries into Maternal Deaths in the United Kingdom described the postpartum death of a woman after several unsuccessful attempts at internal jugular line placement and a likely carotid artery puncture.243 Despite digital pressure and application of a pressure dressing after vessel puncture, she developed neck tightness and dyspnea 4 hours later. Attempts at reintubation and resuscitation were unsuccessful, and she died. In the 2003 to 2005 CEMACH report, an anesthesia-related maternal death occurred in a woman with fulminant preeclampsia and HELLP syndrome who developed a large right hemothorax after a subclavian line insertion.221 Because both immediate and delayed244 maternal deaths have been attributed to the use of invasive central catheters, insertion of these catheters should be done only after careful consideration of risks and benefits.

Further, the timing of the use of invasive central monitoring is important and requires clinical judgment. Many patients are better served by immediate transfer to the operating room for delivery rather than delaying delivery for central line placement. In one study of a critical care unit in an academic hospital, the time from the decision to proceed with placement of a pulmonary artery catheter until the first pressure measurement was obtained was always more than 45 minutes.245 Insertion time would likely exceed 45 minutes in most labor and delivery settings where the procedure is rarely performed and qualified assistance may not be available. In the majority of cases, the preoperative placement of an invasive central line will not change the intraoperative anesthetic management. Many obstetric care providers prefer to proceed immediately to delivery in women with persistent oliguria and to optimize fluid status after delivery.

Transthoracic echocardiography (TTE) can be used in place of invasive monitoring to quantify cardiac function and volume status.138 In the hands of experienced practitioners, TTE may be useful in guiding fluid management for women with severe preeclampsia at risk for pulmonary edema and with oliguria.246 Lung ultrasonography may also be useful in severe preeclampsia to diagnosis the presence of pulmonary edema.247 Pulse waveform analysis has been suggested as a minimally invasive method to measure cardiac output in patients with severe preeclampsia; cardiac output measurements using this approach closely match those obtained from thermodilution in preeclamptic patients.248

In summary, the presence of severe preeclampsia per se is not an indication for CVP or pulmonary artery pressure monitoring. There is no indication for central hemodynamic monitoring that is unique to preeclampsia. Preeclampsia is a disorder of the peripheral circulation, not the central circulation. Indications for invasive central monitoring are similar to those in other multisystem disorders such as severe sepsis, multisystem organ dysfunction, pulmonary edema, congenital heart disease, and cardiomyopathy. TTE and arterial waveform monitoring may provide less invasive means of assessing hemodynamic parameters in these patients. Some women will require transfer to an intensive care unit for specialized nursing care and management directed by a critical care medicine specialist.

Neuraxial Analgesia for Labor and Delivery

During labor, early administration of neuraxial analgesia is recommended for several reasons: (1) to avoid general anesthesia and the possibility of airway catastrophe and marked hypertension with laryngoscopy in the event of emergency cesarean delivery, (2) to optimize the timing of epidural catheter placement in the setting of a declining platelet count, and (3) to obtain the beneficial effects of neuraxial analgesia on uteroplacental perfusion.

Continuous lumbar epidural analgesia or combined-spinal epidural (CSE) analgesia are the preferred methods of pain management during labor in women with preeclampsia. Advantages include (1) provision of high quality analgesia, which attenuates the hypertensive response to pain249; (2) a reduction in levels of circulating catecholamines and stress-related hormones250; (3) possible improvement in intervillous blood flow251; and (4) provision of a means for administration of local anesthetic for emergency cesarean delivery, thus obviating the need for general anesthesia with its attendant risks.

One disadvantage of the CSE technique is that epidural catheter function cannot be fully evaluated until after resolution of the intrathecal analgesia. For this reason, some anesthesia providers avoid the CSE technique in favor of a standard epidural technique in women with severe preeclampsia who have an increased risk for emergency cesarean delivery. Use of a standard epidural technique allows for verification of catheter function within 15 to 20 minutes.

Continuous epidural infusion of local anesthetic has been used in the antepartum period to optimize uteroplacental blood flow in the hope of prolonging pregnancy and avoiding preterm delivery in preeclamptic women remote from term. Kanayama et al.252 studied 20 severely preeclamptic women at 28 to 32 weeks' gestation who were assigned by physician choice to receive either long-term epidural bupivacaine combined with routine supportive management or routine supportive management alone. Gestational age at delivery and birth weight were greater in the treatment group, and maternal blood pressure and platelet count were also improved, compared with the routine management group. Although promising, this technique remains unproven, and randomized controlled trials are needed to verify that antepartum epidural local anesthetic infusion may facilitate expectant management of women with preeclampsia remote from term.

For the most part, the clinical administration of epidural analgesia to women with preeclampsia does not differ from that in healthy pregnant women without preeclampsia (see Chapter 23). The choice of local anesthetic, method of epidural space identification, and maintenance of analgesia are not affected by the presence of preeclampsia. However, four special considerations exist in preeclamptic women: (1) assessment of coagulation status, (2) intravenous hydration before the epidural administration of a local anesthetic, (3) treatment of hypotension, and (4) use of epinephrine-containing local anesthetic solutions.

Coagulation Status.

Platelets contribute to coagulation and hemostasis in two important ways. First, their adhesive and cohesive functions lead to the formation of the hemostatic plug. Second, they activate the coagulation process by exposing a phospholipid surface and acting as a catalytic site for subsequent coagulation and consolidation of the initial platelet plug. Activated platelets release adenosine diphosphate, serotonin, thromboxane A2, and other adhesive proteins, coagulation factors, and growth factors.253

Women with preeclampsia without severe features are usually hypercoagulable relative to women with an uncomplicated pregnancy and should not be denied neuraxial labor analgesia.140 Women with severe preeclampsia (particularly those with HELLP syndrome) may develop thrombocytopenia, which increases the risk for bleeding into the epidural or spinal space with a neuraxial procedure (see Chapter 32). Neuraxial hematoma formation can result in permanent neurologic sequelae. Therefore, documentation of the platelet count is necessary before provision of epidural analgesia in women with severe preeclampsia. The incidence of neuraxial hematoma cannot be precisely determined because not all cases are reported and because there is no accurate method to determine the denominator of all preeclamptic women who have received neuraxial anesthesia. That said, the incidence of epidural hematoma in contemporary obstetric anesthesia practice is exceptionally low.254

In the past, a platelet count greater than or equal to 100,000/mm3 was considered necessary for the safe administration of neuraxial anesthesia. This threshold probably originated from the results of a 1972 study that correlated platelet counts with bleeding times.255 Critical appraisal of 1,083 human studies concluded that the bleeding time is not a reliable method of assessing the risk for bleeding for a single individual.256 Coagulopathy is rare in preeclamptic women with a platelet count exceeding 100,000/mm3, and in the absence of other risk factors for coagulopathy, neuraxial block placement is considered safe without further coagulation testing.156

Currently, many anesthesiologists agree that neuraxial procedures may be initiated in pregnant women without other risk factors if the platelet count is higher than 80,000/mm3.234 There is general consensus among anesthesia providers that a platelet count less than 50,000/mm3 precludes the administration of neuraxial anesthesia. For women with a platelet count between 50,000 and 80,000/mm3, the risks and benefits of neuraxial anesthesia must be weighed against the risks of general anesthesia for the individual patient if emergency cesarean delivery is required, including whether anatomic features of the patient's airway are favorable. Two additional considerations include the trend in the platelet count and any coexisting coagulopathy.

In certain cases, the platelet count decreases rapidly and the nadir in the platelet count cannot be identified prospectively. If serial platelet counts are stable and remain in the normal range, platelet count measurement every 24 to 48 hours is adequate to monitor women undergoing expectant management of severe preeclampsia remote from term.4,161 Once a decision is made to induce labor, platelet count determination at least every 6 hours will ensure a timely measurement has been obtained at the time of request for neuraxial analgesia. If the platelet count is low (80,000 to 100,000/mm3), early epidural catheter insertion is recommended in anticipation of worsening thrombocytopenia. If an epidural catheter is inserted before labor pain becomes significant, dilute solutions of local anesthetic may be infused at a low rate.

If the platelet count is less than 100,000/mm3, other hemostatic abnormalities, including prolonged PT and aPTT and hypofibrinogenemia, may be present.156 Further coagulation studies may be useful, particularly if risk factors for DIC are present (e.g., placental abruption, HELLP syndrome).156 Thus, in the presence of thrombocytopenia or abnormal results of liver function tests, the PT and aPTT should be assessed before the initiation of neuraxial anesthesia.257

Viscoelastic monitors of coagulation may expedite decision-making about neuraxial block administration for women with preeclampsia-related hemostatic dysfunction. Although thromboelastography (TEG) has shown some promise in the assessment of coagulation status in pregnant patients with thrombocytopenia,140 it has been criticized for its inability to diagnose specific coagulation defects, particularly for impairments in primary hemostasis.258 Platelet function analysis (PFA-100) appears to be more sensitive to coagulation dysfunction in severe preeclampsia.142 However, with both TEG and PFA, the ability to predict the risk for epidural hematoma after the administration of neuraxial anesthesia is unproven and requires further study.259

The risk for epidural hematoma formation exists not only at the time of epidural catheter placement but also at the time of its removal. In patients with thrombocytopenia, the catheter should not be withdrawn from the epidural space until there is evidence of an acceptable (and increasing) platelet count. A platelet count of 75,000 to 80,000/mm3 seems reasonable for epidural catheter removal. The platelet count in women with HELLP syndrome usually reaches a nadir on the second or third postpartum day and then gradually returns to the patient's normal baseline.

If the decision is made to proceed with a neuraxial technique when the platelet count is less than 100,000/mm3, the following suggestions may help reduce the risk for epidural hematoma and its sequelae:

Treatment of Hypotension.

A retrospective study found that parturients with severe preeclampsia were more susceptible to hypotension after initiation of epidural labor analgesia than healthy parturients.261 The hypotension was associated with an increase in FHR abnormalities,261 suggesting the need for close attention to maternal blood pressure at the time of initiation of analgesia. Women with preeclampsia may be treated with phenylephrine or ephedrine (although the latter is no longer the agent of choice in healthy women—see Chapter 26). There is an often-expressed concern that severely preeclamptic women may have an exaggerated response to vasopressors that might result in a sharp increase in blood pressure.262,263 However, supportive data are lacking. The anesthesia provider should initiate treatment with low doses of phenylephrine (25 to 50 µg) or ephedrine (5 to 10 mg) to assess maternal blood pressure response before administration of a larger dose. With careful dosing, increased sensitivity to vasopressors is rarely a clinical problem.

Epinephrine.

It has been suggested that local anesthetic solutions containing epinephrine (including the standard epinephrine-containing test dose) should be avoided during the administration of epidural analgesia in preeclamptic women. This concern arises from observations that preeclamptic women exhibit an increased sensitivity to vasopressors, including angiotensin II,264,265 norepinephrine and epinephrine,133,266 and a thromboxane A2-mimetic agent.267 In addition, clinical studies have demonstrated that smaller doses of ephedrine and phenylephrine are required to restore maternal blood pressure during spinal anesthesia in preeclamptic women compared with healthy women.262,263,268,269 One case report described a hypertensive crisis in a preeclamptic woman after the incremental administration of 30 mL of freshly mixed 2% lidocaine with epinephrine 5 µg/mL for planned cesarean delivery.270 However, the onset and duration of hypertension were atypical and a drug error could not be excluded.270 In contrast, several other case series have used the same solution without adverse effects in women with preeclampsia.271,272

No randomized controlled trials have assessed the effects of epidural epinephrine in women with severe preeclampsia. In the absence of malignant hypertension, epinephrine is unlikely to pose a significant risk for hypertensive crisis, given the absence of confirmed reports after decades of its use in obstetric anesthesia practice. Although not necessarily harmful for women with preeclampsia, the use of epinephrine in epidural test doses or analgesic solutions may not be particularly helpful. Patients who have received beta-adrenergic receptor antagonists (e.g., labetalol) do not demonstrate the typical tachycardic response to intravascular administration of epinephrine.273 This lack of response will decrease the sensitivity of the epinephrine test dose to detect intravascular administration of local anesthetic solution, and alternative testing strategies to detect intravascular catheter location may be preferred.274 The addition of epinephrine to local anesthetic solutions results in a modest local anesthetic-sparing effect, at best,275 and increases the density of motor blockade.276 Finally, consideration should be given to the consequences of an unintentional intravascular injection of an epinephrine-containing test dose in a patient with baseline hypertension.

Anesthesia for Cesarean Delivery

The administration of neuraxial anesthesia for cesarean delivery in women with preeclampsia does not differ greatly from administration in healthy pregnant women (see Chapter 26). Hepatic dysfunction can result in reduced drug clearance but has little clinical impact on choice of anesthetic or analgesic agents.

The choice of local anesthetic, method of epidural space identification, and maintenance of anesthesia are not affected by the presence of preeclampsia. However, there are three special considerations in preeclamptic women undergoing cesarean delivery: (1) choice of anesthetic technique, (2) technique for induction of general anesthesia, and (3) the interaction between magnesium sulfate and nondepolarizing muscle relaxants.

Neuraxial Anesthesia.

In the Seventh and Eighth Reports of the Confidential Enquiries into Maternal Deaths from the United Kingdom,212,221 the leading cause of death in women with preeclampsia was intracranial hemorrhage. Disadvantages of general anesthesia in the presence of preeclampsia include the risk for intracranial hemorrhage from the hypertensive response to both tracheal intubation and extubation. In a study involving more than 300,000 women in Taiwan, general anesthesia for cesarean delivery was associated with a greater than twofold increase in the risk for stroke after adjusting for confounders compared with neuraxial anesthesia.277 Neuraxial anesthesia also avoids the possibility of difficult tracheal intubation secondary to airway edema. Therefore, neuraxial anesthesia is preferred whenever clinical circumstances permit its use.

The traditional view was that spinal anesthesia is relatively contraindicated in severe preeclampsia because of the possibility of marked hypotension as a result of the rapid onset of spinal anesthesia–induced sympathetic blockade. However, data that have emerged over the past decade suggest that this concern is not supported by evidence, and that both spinal and epidural anesthesia are reasonable anesthetic modalities for women with severe preeclampsia. Wallace et al.278 randomized 80 women with severe preeclampsia who required cesarean delivery to receive general, epidural, or CSE anesthesia. Notably, the initial spinal dose in the CSE group (hyperbaric bupivacaine 11.25 mg) is a dose comparable to that often used for a single-shot spinal technique. There was no significant difference between the CSE and epidural anesthesia groups in maternal mean arterial pressure over time. Another small prospective study randomized women with severe preeclampsia to receive either spinal or epidural anesthesia, with similar results.279 Hood and Curry280 retrospectively reviewed cesarean delivery records for 138 women with severe preeclampsia who received either spinal or epidural anesthesia and found that the lowest mean blood pressure measurements did not differ between groups. Because of the retrospective study design, the possibility that the groups were dissimilar cannot be excluded (i.e., the anesthesia providers may have chosen to administer epidural anesthesia to the more severely ill women). Nonetheless, the expected marked hypotension after spinal anesthesia did not occur. These studies lend support to the safety of spinal anesthesia in women with severe preeclampsia.

In two prospective cohort studies of women undergoing cesarean delivery, Aya et al.262,268 compared women with severe preeclampsia to healthy pregnant women (both preterm and at term) and found that the risk for significant spinal anesthesia–induced hypotension (defined as requiring the administration of ephedrine) was significantly lower in the preeclampsia group than in the control groups. The authors speculated that the known increased vascular sensitivity to vasoconstrictors may explain the infrequent incidence of hypotension after spinal anesthesia and the ease with which mean arterial blood pressure can be restored to baseline with small doses of vasopressor.

A randomized multicenter study281 comparing the hemodynamic effects of spinal anesthesia with epidural anesthesia for cesarean delivery in women with severe preeclampsia found that significantly more women in the spinal anesthesia group experienced hypotension. However, the duration of hypotension was less than 1 minute in both groups and, although there was more ephedrine use in the spinal group than the epidural group, hypotension was easily treated in both groups. In addition, there was no significant difference in neonatal outcome between infants whose mothers received spinal anesthesia compared with those whose mothers received epidural anesthesia.282 Another study suggested that spinal anesthesia has little effect on cardiac output in severely preeclamptic women.263 These data, taken together, suggest that the use of spinal anesthesia for cesarean delivery in women with severe preeclampsia is appropriate.

General Anesthesia.

General anesthesia is less desirable than neuraxial anesthesia because of (1) the possibility of difficult tracheal intubation secondary to airway edema and (2) the transient but severe hypertension that accompanies tracheal intubation and extubation. Nonetheless, there are situations in which general anesthesia is the best anesthetic option. Clinical indications include severe ongoing maternal hemorrhage, sustained fetal bradycardia with a reassuring maternal airway examination, and severe thrombocytopenia or other coagulopathy, or a combination of these indications. The platelet count can fall dramatically with rapidly progressing severe preeclampsia or HELLP syndrome and may mandate administration of general anesthesia. Major placental abruption, intrauterine fetal demise, and preeclampsia all increase the risk for DIC. The safe administration of general anesthesia in women with preeclampsia requires an advanced state of readiness and careful preparation.

Once the decision has been made to proceed with general anesthesia, the anesthesia provider faces three specific challenges: (1) the potential difficulty of securing the airway, (2) the hypertensive response to direct laryngoscopy and tracheal intubation, and (3) the effects of magnesium sulfate on neuromuscular transmission and uterine tone. A suggested technique for the administration of general anesthesia is outlined in Box 36-5.

Box 36-5

A Suggested Technique for Administration of General Anesthesia in Women with Severe Preeclampsia

1. Place a radial arterial cannula for continuous blood pressure monitoring in women with severe hypertension.

2. Place an additional large-bore intravenous catheter given the increased risk for postpartum hemorrhage.

3. Verify that smaller-sized endotracheal tubes and supraglottic airway devices are immediately available. Equipment needed for difficult airway management should also be immediately available.

4. Consider the administration of an H2-receptor antagonist and metoclopramide IV between 30 and 60 minutes before induction of anesthesia.

5. Administer 0.3 M sodium citrate 30 mL by mouth less than 30 minutes before induction of anesthesia.

6. Denitrogenate (3 minutes of tidal-volume breathing or 8 vital capacity breaths with an FIO2 of 1.0 and a tight-fitting facemask).

7. Give labetalol (10-mg bolus doses) IV to titrate systolic blood pressure to 140/90 mm Hg before the induction of anesthesia.

8. Continue to monitor the FHR during labetalol administration.

9. Consider alternative antihypertensive agents for patients who do not respond to labetalol (or those with a contraindication to labetalol). Alternatives include hydralazine or nicardipine, sodium nitroprusside, or nitroglycerin infusion. Consider remifentanil infusion at 0.05 µg/kg/min. (See Table 36-4.)

10. Perform rapid-sequence induction with propofol 2.0 to 2.8 mg/kg and succinylcholine 1.0 to 1.5 mg/kg (avoid ketamine as an induction agent given its sympathomimetic properties). Consider the administration of a bolus dose of labetalol, esmolol, nitroglycerin, sodium nitroprusside, or remifentanil to blunt the hemodynamic response to laryngoscopy.

11. Maintain anesthesia with a volatile halogenated agent and 100% oxygen before delivery. After delivery, decrease the concentration of the volatile halogenated agent to prevent uterine atony and consider using nitrous oxide or a propofol infusion and administering an opioid with or without a benzodiazepine. Avoid giving additional muscle relaxants; if absolutely required, administer a low dose of a short-acting nondepolarizing muscle relaxant because of the exaggerated effect of these medications when coadministered with magnesium.

12. At the end of surgery, reverse neuromuscular blockade and give labetalol 5 to 10 mg IV bolus, titrated to effect, to prevent hypertension during emergence and tracheal extubation.

FHR, fetal heart rate; IV, intravenously.

Modified from Ramanathan J, Bennett K. Pre-eclampsia: fluids, drugs, and anesthetic management. Anesthesiol Clin North Am 2003; 21:145-63.

Airway Considerations.

Before proceeding with general anesthesia, careful airway examination is mandatory. Airway edema may be present even with a relatively reassuring airway examination; thus, many anesthesia providers try to avoid emergency administration of general anesthesia if there is any suspicion of a difficult airway. Endotracheal tubes in various sizes and difficult airway equipment should be immediately available (see Chapter 30). In unusually difficult situations, it may be prudent to have a surgeon immediately available to establish a surgical airway, if needed. One of the dangers of repeated tracheal intubation attempts is the risk for traumatic bleeding in the airway, which may make ventilation difficult or even impossible. It is wise to avoid repeated attempts and proceed with insertion of a supraglottic airway device (e.g., laryngeal mask airway) before the airway is irretrievably lost. Because the supraglottic airway devices do not protect the patient from pulmonary aspiration of gastric contents, the obstetrician should be encouraged to complete the procedure as quickly as possible.

If indicated, an awake fiberoptic tracheal intubation should be used to secure the airway. Ideally, invasive blood pressure monitoring should be initiated before tracheal intubation and the induction of general anesthesia in patients with severe preeclampsia so that hypertension can be promptly recognized and treated. Effective topical anesthesia of the airway with nebulized or atomized lidocaine can enhance patients' comfort and decrease the hypertensive response to airway manipulation. Airway injections (including glossopharyngeal nerve blocks and transtracheal injections) are usually best avoided because of coagulopathy in this population.

Hypertensive Response to Laryngoscopy.

The hemodynamic instability associated with rapid-sequence induction and tracheal intubation presents a serious problem. The transient but severe hypertension that may accompany tracheal intubation can result in cerebral hemorrhage or pulmonary edema, both potentially fatal complications. Continuous arterial blood pressure monitoring is required for severely hypertensive women to monitor the effects of antihypertensive drugs administered before and after tracheal intubation and to allow rapid detection of adverse hemodynamic responses to laryngoscopy.

Medications that have been used to blunt the hemodynamic response to laryngoscopy include labetalol, esmolol, nitroglycerin, sodium nitroprusside, and remifentanil.283-287 The goal of treatment is to reduce the arterial blood pressure to approximately 140/90 mm Hg before the induction of general anesthesia and to maintain the systolic blood pressure between 140 to 160 mm Hg and the diastolic blood pressure between 90 to 100 mm Hg throughout laryngoscopy and tracheal intubation.166 If possible, the FHR should be monitored during intravenous antihypertensive therapy.

Most anesthesia providers consider labetalol to be the drug of choice for attenuating the hypertensive response to laryngoscopy in women with severe preeclampsia. Ramanathan et al.285 compared intravenously administered labetalol with no treatment in a randomized study of preeclamptic women who received general anesthesia for cesarean delivery. Mean arterial blood pressure increased after tracheal intubation in both study groups, but the hypertensive response was significantly less pronounced in the labetalol group. Women in the control group also developed tachycardia (in response to laryngoscopy and tracheal intubation), which did not occur in the labetalol group. Labetalol can be administered using either a bolus technique or a continuous intravenous infusion, or both.

There is also evidence of safe short-term administration of esmolol in this setting. A randomized double-blind study of 80 hypertensive women presenting for cesarean delivery demonstrated that intravenous esmolol—in doses as high as 2 mg/kg—can be safely used to dampen the hemodynamic response to laryngoscopy and tracheal intubation.288

Nitroglycerin has many desirable properties for blunting the hypertensive response to tracheal intubation. It is a direct vasodilator with a rapid onset, is rapidly metabolized, and has no apparent maternal or fetal toxicity. In a randomized controlled trial, Hood et al.284 administered intravenous nitroglycerin (200 µg/mL), which decreased mean arterial blood pressure by approximately 20%, before the induction of general anesthesia. Compared with women who did not receive nitroglycerin, the maximal blood pressure with tracheal intubation was significantly lower in the nitroglycerin group. Both Apgar scores and umbilical cord blood gas and acid-base measurements were similar in the two groups.

Sodium nitroprusside infusions have also been used to attenuate hemodynamic responses to tracheal intubation in women with severe preeclampsia. An intravenous infusion can be initiated at 0.5 µg/kg/min and titrated to blood pressure response. Short-term infusions are considered safe for the fetus.

The short-acting opioid remifentanil is rapidly metabolized by both mother and neonate by nonspecific blood and tissue esterases and has been administered to preeclamptic women. A clear advantage of remifentanil compared with other opioids is the rapid onset and short duration of the drug; the limited duration of action should not interfere with the resumption of spontaneous ventilation if tracheal intubation is unsuccessful. Ngan Kee et al.287 randomly allocated 40 pregnant women without preeclampsia who required general anesthesia for cesarean delivery to receive either a one-time intravenous dose of remifentanil 1 µg/kg or saline immediately before induction of anesthesia. The primary outcome was the maximum increase in systolic blood pressure (compared with a baseline measurement). Administration of remifentanil significantly decreased the maximum increase in systolic blood pressure. However, remifentanil crosses the placenta, and two neonates in the remifentanil group required naloxone administration for poor respiratory effort. Park et al.289 randomized 48 patients with severe preeclampsia to receive remifentanil 0.5 µg/kg or 1 µg/kg before tracheal intubation. Both doses prevented a hypertensive response, but three patients treated with the higher dose required ephedrine to treat hypotension. Apgar scores and umbilical cord blood gas measurements were comparable in both groups. The lower remifentanil dose, 0.5 µg/kg, is therefore likely preferable.

Effects of Magnesium Sulfate.

Most severely preeclamptic women will present to the operating room after receiving magnesium sulfate for seizure prophylaxis. The magnesium infusion should continue throughout surgery to minimize the risk of eclampsia.4 The primary anesthetic considerations for women receiving magnesium sulfate are (1) interaction with nondepolarizing muscle relaxants, (2) effects on uterine tone, and (3) interaction with calcium entry–blocking agents.

Magnesium inhibits the release of acetylcholine at the neuromuscular junction, decreases the sensitivity of the neuromuscular junction to acetylcholine, and depresses the excitability of the muscle fiber membrane. Magnesium sulfate increases the potency and duration of vecuronium, rocuronium, and mivacurium.290-292 Several case reports have described a requirement for overnight mechanical ventilation after administration of routine doses of vecuronium in women receiving magnesium sulfate.290,293 Thus, if nondepolarizing muscle relaxants are used, they should be administered in very small doses and the response should be monitored carefully with a peripheral nerve stimulator. Many practitioners avoid the use of depolarizing neuromuscular blocking agents in this setting because of the concern for residual postoperative neuromuscular blockade, which can lead to respiratory complications. Because of abdominal wall distention in the term parturient, neuromuscular blockade is rarely required to facilitate surgical closure after cesarean delivery.

Even though succinylcholine mimics acetylcholine at the nerve terminal, the onset and duration of a single intubating dose is not prolonged when administered concurrently with a magnesium sulfate infusion294; a routine intubating dose of 1 to 1.5 mg/kg should be used during rapid-sequence induction of anesthesia.

Used for many years as a tocolytic agent, magnesium depresses smooth muscle contractions and inhibits CNS catecholamine release.295-297 Therefore, it seems intuitive that the risk for uterine atony and excessive blood loss might be increased in women receiving magnesium sulfate.193 However, studies193,203 have not found an increased risk for blood loss in women receiving magnesium sulfate. A blood sample for a type and screen should be sent to the blood bank before cesarean delivery, and uterotonic agents should be immediately available. Although some reports have suggested that coadministration of a calcium entry–blocking agent and magnesium may cause hypotension and/or neuromuscular blockade,176-179 more recent information suggests that these medications can be used safely together.180

Postoperative Analgesia.

Options for postoperative analgesia are the same as for healthy pregnancies and include patient-controlled intravenous opioids, neuraxial opioids (single injection), and continuous epidural infusion of analgesic agents. Many anesthesia providers prefer neuraxial opioid administration for postcesarean analgesia (see Chapter 28). For women whose postpartum hypertension persists longer than one day, the ACOG has suggested that nonsteroidal anti-inflammatory medications be replaced by alternative analgesics, as nonsteroidal anti-inflammatory drugs may contribute to hypertension.4 In the rare case of a woman with continuing severe refractory hypertension, continuous epidural analgesia is attractive for its blood pressure–modulating properties.

Regardless of the postoperative analgesic technique, all women should be carefully monitored with pulse oximetry for signs of respiratory depression or airway obstruction.

Postpartum Management

The risks of severe preeclampsia do not end with delivery. Postpartum women are at significant risk for pulmonary edema, sustained hypertension, stroke, venous thromboembolism, airway obstruction, and seizures and should receive close monitoring of blood pressure, fluid intake, and urinary output. In addition, severe preeclampsia, the HELLP syndrome, and eclampsia can present for the first time in the postpartum period, with delayed presentation as late as 4 weeks after delivery.4 A study of almost 4000 women diagnosed with preeclampsia found that the incidence of postpartum onset of disease was 5.7%,116 and hypertension is the leading indication for postpartum hospital readmission.298

The risk for pulmonary edema is also highest in the postpartum period. The resolution of preeclampsia usually occurs within 5 days of delivery and is heralded by a marked diuresis that follows mobilization of extracellular fluid and an increase in the intravascular volume. As a consequence, women with severe preeclampsia, particularly those with early-onset disease, renal insufficiency, or pulmonary capillary leak, are at increased risk for the development of postpartum pulmonary edema.163

In contrast to women with gestational hypertension, who typically become normotensive within a week of delivery, women with severe preeclampsia may have a longer duration of hypertension; the risk for cerebrovascular accident is highest during this time.168,208,209,299,300 Given the increased risk of postpartum cerebrovascular accident, the ACOG recommends antihypertensive therapy in the postpartum period when systolic blood pressure persistently exceeds 150 mm Hg or diastolic blood pressure exceeds 100 mm Hg.4 Antihypertensive therapy should be continued, started, or resumed for these women, and blood pressure should be closely monitored. For women in the postpartum period who develop new-onset hypertension associated with headaches or other neurologic symptoms, or new-onset severe hypertension, a 24-hour course of magnesium sulfate administration may help prevent eclampsia or a cerebrovascular accident.4

Postpartum venous thromboembolism (VTE) has an estimated incidence of 1 to 18 per 1000 cesarean deliveries301,302 and is a leading cause of maternal mortality in pregnancy.303 The risk factors for antepartum and postpartum events differ, suggesting a different pathophysiology for each.304 Both cesarean delivery304-307 and preeclampsia304,305 are independent risk factors for postpartum VTE. An emergency cesarean delivery doubles the risk for VTE compared with a nonemergent cesarean delivery.308

The 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend that women with a risk for postcesarean VTE greater than 3% receive either pharmacologic thromboprophylaxis or mechanical prophylaxis (elastic stockings or intermittent pneumatic compression) during hospitalization after cesarean delivery.301 Preeclampsia in the absence of fetal growth restriction is considered a minor risk factor for VTE. VTE prophylaxis is indicated in patients with two or more minor risk factors (e.g., BMI > 30 kg/m2, use of > 10 cigarettes per day, multiple pregnancy, emergency cesarean delivery, postpartum hemorrhage > 1 L) (see Box 39-4).301 Preeclampsia with fetal growth restriction is considered a major risk factor (with risk for VTE > 3%), such that all patients with this condition merit VTE prophylaxis after cesarean delivery.301 The ACOG recommends pneumatic compression devices for all patients undergoing cesarean delivery.309

Preeclampsia has been associated with increased upper airway resistance and an increased risk of obstructive sleep apnea.310,311 A review of anesthesia-related maternal deaths in Michigan312 described a series of postoperative and postpartum deaths attributed to airway obstruction or hypoventilation, including the death of one women with severe preeclampsia and sleep-disordered breathing who likely experienced opioid-related respiratory depression while receiving patient-controlled intravenous analgesia after cesarean delivery. Such findings highlight the need for close monitoring and consistent vigilance in the postoperative care of women with severe preeclampsia—particularly those with generalized edema, known airway swelling, snoring, and obesity.

Long-Term Outcomes

Women with a history of preeclampsia are at increased risk for chronic hypertension and cardiovascular disease, including ischemic heart disease and stroke, later in life,59,61,313-316 and an earlier onset of cardiovascular disease than women with healthy pregnancies.60,317,318 Risks for ischemic heart disease and stroke are elevated approximately twofold.61

In addition, there is evidence of a dose-response relationship between preeclampsia and cardiovascular disease. Women with severe and/or early-onset preeclampsia, and whose pregnancies are complicated by both preeclampsia (the maternal syndrome) and fetal growth restriction (the fetal syndrome) are at higher risk than women with preeclampsia without severe features or gestational hypertension.59 Women with preeclampsia in both their first and second pregnancies are at even greater risk for future ischemic heart disease.318

The mechanism of increased risk for cardiovascular disease in preeclampsia is unclear. It is possible that preeclampsia causes permanent damage to the endothelium and hastens the onset of cardiovascular disease. Women with a history of preeclampsia have persistent impairment of brachial artery endothelium-dependent vascular relaxation at 1 to 3 years after delivery compared with healthy control women.319,320 A more likely explanation is that preeclampsia and cardiovascular disease have a common pathogenesis because of shared risk factors. Common risk factors for preeclampsia and atherosclerosis include hypertension, obesity, insulin resistance, advanced age, hypercholesterolemia, and dyslipidemia.317,321,322 Cigarette smoking is the notable exception in that it is an established risk factor for cardiovascular disease but is protective against preeclampsia.67,68 Preeclampsia may be a cardiovascular risk marker in women with an underlying predisposition to vascular disease; the hemodynamic and metabolic stress of pregnancy causes the predisposition to manifest as preeclampsia. After pregnancy, women return to a normal state until the threshold for disease development is exceeded in later life.

Regardless of the mechanism of increased risk, these observations represent a potential opportunity for primary disease prevention and risk factor modification. In a 2004 multinational study, 90% of the risk for a first myocardial infarction was attributed to potentially modifiable risk factors.323 Possible interventions include earlier cardiovascular disease screening and individual counseling regarding the importance of smoking cessation, regular exercise, and a diet low in saturated fat and high in antioxidants.

In contrast to the increased risk for cardiovascular disease, a history of preeclampsia has been associated with a decreased risk for cancer. Several earlier studies have suggested that women who have been diagnosed with preeclampsia have a slightly lower risk for breast cancer in later life compared with other parous women.324,325 However, a 2007 systematic review and meta-analysis of almost 200,000 women with a history of preeclampsia found no association between preeclampsia and future cancer risk.61

Evidence indicates that preeclampsia may also result in psychological sequelae. A woman with a history of severe preeclampsia (particularly with early-onset disease and preterm delivery) has experienced a serious complication that threatened her life and the life of her child. In one study, approximately one fourth of women developed post-traumatic stress disorder (PTSD) after early-onset preeclampsia.326 This association may be mediated by the condition of the offspring after preterm delivery.327-329 Further research is required to characterize women at risk for PTSD and to investigate strategies for PTSD prevention and intervention.

Eclampsia

Eclampsia is defined as the new onset of seizures or unexplained coma during pregnancy or the postpartum period in a woman with signs and symptoms of preeclampsia and without a preexisting neurologic disorder.330-333

Epidemiology

Findings from population-based studies in the past 10 years suggest that the incidence of eclampsia varies from 0.1 to 5.9 per 10,000 pregnancies in developed countries.9,38,334-338 The variation in rates of eclampsia among studies likely reflects reporting differences among countries or differences in treatment for severe preeclampsia.335,339 On average, studies have shown a decrease in the incidence of eclampsia in developed countries over time; this decrease is likely attributable to an increase in the use of magnesium for seizure prophylaxis.335,337,338

Eclampsia can occur suddenly at any point in the puerperium; however, most seizures occur intrapartum or within the first 48 hours after delivery. Late eclampsia is defined as seizure onset from 48 hours after delivery to 4 weeks postpartum.331,340 The majority of eclamptic women have evidence of severe preeclampsia, but in 10% to 15% of cases, hypertension is absent or modest and/or proteinuria is not detected.340 Reported risks include young maternal age, nulliparity, multiple gestation, molar pregnancy, triploidy, preexisting hypertension, renal or cardiac disease, previous severe preeclampsia or eclampsia, nonimmune hydrops fetalis, and systemic lupus erythematosus.338,341 Major maternal complications of eclampsia include pulmonary aspiration, pulmonary edema, cerebrovascular accident, cardiopulmonary arrest, venous thromboembolism, acute renal failure, and death.333-335,338 Eclampsia is associated with a high perinatal death rate and has also been associated with placental abruption, severe fetal growth restriction, and extreme prematurity.330,334,335,338

Clinical Presentation and Diagnosis

Any of the pathophysiologic changes of preeclampsia can be present in eclampsia. About 80% of patients will have premonitory neurologic symptoms, the most common of which are headache and visual disturbances.342 Other premonitory signs and symptoms can include photophobia, epigastric or right upper quadrant pain, hyperreflexia, and altered mental status330,340; these symptoms can occur before or after the onset of seizures.330

Seizures have an abrupt onset, typically beginning as facial twitching that is followed by a tonic phase that persists for 15 to 20 seconds. This phase progresses to a generalized clonic phase characterized by apnea, which lasts approximately 1 minute. Breathing generally resumes with a long stertorous inspiration, and the patient enters a postictal state with a variable period of coma. Cardiorespiratory arrest and pulmonary aspiration of gastric contents can complicate a seizure. Although the definitive diagnosis for eclampsia is a sudden seizure in a pregnant woman who has signs and symptoms of preeclampsia, a woman who lapses into coma without witnessed convulsions can also be classified as eclamptic.330

The mechanism of eclamptic seizures remains poorly understood.332 It may involve a loss of the normal cerebral autoregulatory mechanism, resulting in hyperperfusion and leading to interstitial or vasogenic cerebral edema and decreased cerebral blood flow.213,214,332 Neuroradiologic studies suggest that eclampsia might be a form of PRES.121,122

Until proven otherwise, the occurrence of seizures during pregnancy should be considered eclampsia. Conditions simulating eclampsia include seizure disorder, stroke, hypertensive encephalopathy, ischemia or hypoxia, cerebral space-occupying lesion, systemic disease (e.g., systemic lupus erythematosus, sickle cell anemia), infection (e.g., meningitis, encephalitis), electrolyte and endocrine disturbances, PRES, vasculitis or angiopathy, amniotic fluid embolism, medications (withdrawal, illicit drug use), and organ failure.330,331

Obstetric Management

Immediate goals are to stop convulsions, establish a patent airway, and prevent major complications (e.g., hypoxemia, aspiration). Further obstetric management includes antihypertensive therapy, induction or augmentation of labor, and expeditious (preferably vaginal) delivery. Fetal bradycardia typically begins during or immediately after a seizure but does not mandate immediate delivery unless it is persistent.

Resuscitation and Seizure Control

During the seizure, oxygenation may prove impossible but supplemental oxygen should be delivered by means of a facemask (Box 36-6). Attempts to insert an oral airway should be withheld until the seizure abates. As soon as breathing resumes, ventilation may be gently augmented with a bag-mask device. Pulse oximetry should be used to assess maternal oxygenation. Blood pressure and the electrocardiogram should be monitored to identify hypertension, arrhythmia, or cardiac arrest. While initial resuscitation is underway, an assistant should establish intravenous access, which may be difficult in a combative postictal woman. Judicious sedation might be required to allow further treatment in some patients.

Magnesium sulfate is the preferred drug for the prevention of further seizures in eclampsia.189,190 The administration of magnesium sulfate in eclamptic women is associated with significantly lower maternal death rates. An initial intravenous bolus of 4 to 6 g is administered, followed by an infusion at 1 to 2 g/h, assuming the patient has adequate renal function.343 Recurrent convulsions should prompt administration of an additional bolus of 2 to 4 g, infused over 5 to 10 minutes.343 The patient should be carefully monitored for signs of magnesium toxicity.

Anesthetic Management

The preanesthetic management of an eclamptic woman parallels that of a patient with severe preeclampsia. Considerations330,344 specific to the woman with eclampsia are as follows:

The anesthetic plan is tailored to each individual case. In conscious, eclamptic women with no evidence of increased intracranial pressure and whose seizures are well controlled, neuraxial analgesia/anesthesia can be considered. In a retrospective review of 66 stable eclamptic South African women, Moodley et al.345 found no difference in maternal and neonatal outcomes in women who received epidural anesthesia compared with general anesthesia for cesarean delivery.

Eclamptic seizures are likely associated with an increase in intracranial pressure. In the rare instance of requirement for immediate delivery in a woman with ongoing seizures, a technique similar to that used for neuroanesthesia in patients with increased intracranial pressure should be considered. Intravenous induction agents such as propofol346 or thiopental347 will reduce the cerebral metabolic rate and cerebral blood flow, with a consequent decrease in cerebral blood volume and intracranial pressure. These agents are also effective in terminating seizures.348,349 Because hyperventilation reduces cerebral blood flow without a reduction in cerebral metabolic rate, it should be employed with caution. On the other hand, hypoventilation is associated with hypercarbia, which can lower the seizure threshold. To prevent further neurologic injury, it is important not to be overly aggressive in the reduction of systemic pressure because cerebral perfusion pressure is the difference between mean arterial pressure and intracranial pressure.350 Avoidance of hypoxia, hyperthermia, and hyperglycemia is also important in avoiding an exacerbation of neurologic injury.351 The tracheas of patients who have not recovered neurologically should remain intubated, and these patients should be monitored in an intensive care unit. If unconsciousness persists, further neurologic evaluation with electroencephalography and brain imaging to rule out persistent seizures and/or other underlying neurologic problems should be performed.

Long-Term Outcomes

Neurologic abnormalities occurring in patients with eclampsia (e.g., cortical blindness, focal motor deficits, coma) do not usually result in permanent neurologic deficits.330 However, recent studies suggest that formerly eclamptic women had significantly poorer neurocognitive function as well as an increase in visual impairment years after the index pregnancy, both of which may be attributable to permanent white matter changes caused by eclampsia.352-354

Key Points

• Preeclampsia is a multisystem disorder of pregnancy characterized by a maternal syndrome with or without a fetal syndrome.

• Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide, particularly in developing countries.

• Disease pathophysiology involves superficial placentation related to abnormal angiogenesis leading to placental hypoxia and the release of soluble substances toxic to vascular endothelium.

• Management of preeclampsia is supportive, and delivery of the fetus and placenta is the only definitive cure.

• Antihypertensive drugs should be used when systolic blood pressure is 160 mm Hg or higher, or the diastolic blood pressure is 110 mm Hg or higher.

• Preeclampsia likely consists of more than one disease; early-onset disease (earlier than 34 weeks' gestation) carries a worse prognosis than late-onset disease.

• Systemic disease manifestations result from widespread maternal vascular endothelial dysfunction.

• Complications of severe preeclampsia include severe refractory hypertension, cerebrovascular accident, pulmonary edema, placental abruption, renal failure, and the HELLP syndrome.

• Important hematologic changes in severe preeclampsia include the potential for thrombocytopenia and disseminated intravascular coagulation.

• There are no indications for invasive central monitoring unique to preeclampsia; indications are similar to those in other multisystem disorders such as severe sepsis or multisystem organ dysfunction.

• Preeclamptic women are at risk for airway edema. The anesthesia provider should anticipate the possibility of difficult airway management.

• The hypertensive response to direct laryngoscopy and tracheal intubation can cause intracranial hemorrhage in women with severe preeclampsia.

• Spinal anesthesia is acceptable for women with severe preeclampsia, especially as an alternative to general anesthesia for emergency cesarean delivery.

• The risks for pulmonary edema, cerebrovascular accident, and venous thromboembolism are increased in the postpartum period.

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