Preeclampsia and eclampsia: enhanced detection and treatment for morbidity reduction

Abstract

Preeclampsia is a life-threatening complication that develops in 2-8% of pregnancies. It is characterized by elevated blood pressure after 20 weeks of gestation and may progress to multiorgan dysfunction, leading to severe maternal and fetal morbidity and mortality. The only definitive treatment is delivery, and efforts are focused on early risk prediction, surveillance, and severity mitigation. Anesthesiologists, as part of the interdisciplinary team, should evaluate patients early in labor in order to optimize cardiovascular, pulmonary, and coagulation status. Neuraxial techniques are safe in the absence of coagulopathy and aid avoidance of general anesthesia, which is associated with high risk in these patients. This review aims to provide anaesthesiologists with a comprehensive update on the latest strategies and evidence-based practices for managing preeclampsia, with an emphasis on perioperative care.

Introduction

Preeclampsia is a pregnancy-specific disorder characterized by new onset hypertension and proteinuria after 20 weeks of pregnancy, with multi-organ involvement and significant associated maternal and fetal morbidity and mortality [1-3]. Preeclampsia is the second most common cause of maternal mortality after postpartum hemorrhage [4]. Preeclampsia complicates between 2-5% of pregnancies globally [5, 6] and is associated with 46,000 maternal and 500,000 fetal deaths annually [7]. The incidence of preeclampsia varies markedly between countries and ethnicities. In the United States (US), the number of pregnancies complicated by preeclampsia has increased dramatically over the recent past, with a reported 11% increase between 1990 and 2019 [8]. Large prospective observational cohort studies in the United Kingdom (UK) showed the risk of preeclampsia to be significantly higher in women of Afro-Caribbean and South Asian racial origin compared with White women [9, 10]. In addition, preeclampsia is more common in low- and middle-income countries and in racial and ethnic minorities. Despite this, most of the studies in the field are performed in high-income countries and White individuals; this knowledge gap may further exacerbate the existing inequalities in care. As this condition presents significant personal and public financial costs [11] and the majority of complications are considered preventable [12], there is an urgent need to improve the care and treatment of preeclampsia.

The role of the anesthesiologist in the peripartum care of the preeclamptic parturient has been well-established in the provision of pain relief and acute management for complications [13-15]. A thorough understanding of the disease process is thus vital to the expert management of preeclampsia. This review aims to highlight the practical problems and clinical management of preeclampsia, with emphasis on the recent advances in the risk prediction, diagnosis, and treatment of preeclampsia.

Definitions and Diagnostic Criteria

Preeclampsia is a complex and heterogeneous disease, classified based on clinical symptoms and gestational age at onset. This condition is classified as part of the hypertensive disorders of pregnancy (Table 1), which are a spectrum of closely related diseases and, in addition to preeclampsia, also include gestational hypertension and chronic hypertension (Fig. 1).

Table 1.

Classification of hypertensive diseases of pregnancy. Adapted from ACOG practice bulletin 222: Gestational Hypertension and Preeclampsia.

Condition	Blood Pressures	Laboratory Testing	Symptoms
Chronic Hypertension	>140/90 mmHg on two occasions prior to 20 weeks of gestation or on antihypertensive therapy at start of pregnancy	Baseline laboratory testing should be obtained	Absent
Gestational Hypertension	> 140/90 mmHg on two occasions greater than 4 h apart after 20 weeks’ gestational	No abnormalities	Absent
Preeclampsia
Preeclampsia without Severe Features	> 140/90 mmHg on two occasions greater than 4 h apart after 20 weeks’ gestation	Elevated urine protein	Absent
Preeclampsia with severe features	(+/−) > 160/110 mmHg	(+/−) Thrombocytopenia <100x109/L, Renal insufficiency (Cr > 1.1 mg/dL or 2x baseline Cr); elevated LFTs up to twice of max normal without alternative cause	(+/−) Headache,vision changes, chest pain, pulmonary edema epigastric pain
Superimposed preeclampsia	Worsening hypertension after 20 gestational weeks with known chronic hypertension	Elevated urine protein, (+/−) abnormalities of platelets, renal, or hepatic function	(+/−) Headache,vision changes, chest pain, pulmonary edema, epigastric pain
HELLP Syndrome	(+/−) BP > 140/90 mmHg	(+/−) thrombocytopenia <100x109/L, LFT elevations more than twice of max normal without alternative cause
Eclampsia	(+/−) BP > 140/90 mmHg	(+/−) thrombocytopenia <100x109/L, Renal insufficiency (Cr > 1.1 mg/dL or 2x baseline Cr); LFTs elevations twice of max normal without alternative cause	Generalized tonic-clonic seizure

Abbreviations: BP (blood pressure), Cr (creatinine) LFT (liver function tests), HELLP, hemolysis, elevated liver enzymes, and low platelet count

Fig. 1. The spectrum of hypertensive disorders during pregnancy.

Abbreviation: HELLP, hemolysis, elevated liver enzymes, and low platelet count.

Definition of preeclampsia

The diagnosis of preeclampsia is established based on the following criteria, according to the American College of Obstetricians and Gynecologists (ACOG)[1]:

Blood pressure

• Systolic blood pressure of 140 mm Hg or more, or diastolic blood pressure of 90 mm Hg or more, on two occasions at least 4 hours apart, after 20 weeks of gestation in a woman with a previously normal blood pressure.

• Single reading of systolic blood pressure of 160 mm Hg or more, or diastolic blood pressure of 110 mm Hg or more. Severe hypertension can be confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy.

Proteinuria

• 300 mg or more per 24-hour urine collection (or this amount extrapolated from a timed collection) or

• Protein/creatinine ratio of 0.3 mg/dL or more or

• Dipstick reading of 2+ (used only if other quantitative methods are not available).

Or, in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:

• Thrombocytopenia: platelet count less than 100x10⁹/L.

• Renal insufficiency: serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease

• Impaired liver function: elevated blood concentrations of liver transaminases to twice the normal concentration.

• Pulmonary edema.

• New-onset headache, unresponsive to medication and not accounted for by alternative diagnoses or presence of visual symptoms.

Preeclampsia classification based on clinical symptoms

Based on the clinical presentation (Table 1), preeclampsia is classified as preeclampsia without severe features if there is no end-organ dysfunction and the blood pressure is higher than 140/90 mmHg but lower than 160/110 mmHg [16]. If any of these symptoms are present, or the blood pressure readings are higher than 160/110 mmHg, there is preeclampsia with severe features. Some guidelines classify Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome and eclampsia as severe forms of preeclampsia with predominantly hepatic or neurologic dysfunction [17]. HELLP syndrome is characterized by severe thrombocytopenia with platelets less than 100x10⁹/L and elevated liver enzymes more than twice the normal range. It may be associated with elevated blood pressure, proteinuria, and other signs of organ damage. Eclampsia is a severe, life-threatening form of preeclampsia in which the patient develops generalized tonic-clonic seizures. As the clinical condition of patients with preeclampsia may deteriorate quickly, alternative classifications, such as those based on gestational age, are also used [17, 18].

Preeclampsia classification based on gestational age at onset

Only a small portion of the cases present at early gestational age; however, those are associated with high maternal and neonatal morbidity and mortality. The majority of preeclampsia cases present at term gestation and have a milder course. Thus, preeclampsia can be classified as preterm, associated with delivery at <37 gestational weeks; term, associated with delivery at 37 weeks or later; and postpartum preeclampsia, with onset after delivery.

Prediction of preeclampsia risk

Clinical factors associated with preeclampsia risk

Multiple risk factors associated with preeclampsia have been identified over the years. Traditional risk screening, recommended by multiple society guidelines [18, 19], is based on maternal preexisting medical conditions and obstetric history. High-risk factors include chronic renal disease, chronic hypertension, diabetes mellitus, autoimmune disease, history of preeclampsia in prior pregnancy, and multifetal gestation. Moderate risk factors include nulliparity, maternal age higher than 40 years, interpregnancy interval more than ten years, and family history of preeclampsia. These factors are readily available, and this approach is widely used in early pregnancy. However, it fails to identify 35-40% of the patients who ultimately develop preeclampsia. The positive screen rate of this approach, i.e., the patients who are predicted to be at risk and develop the disease, is only 10% [20]. In addition, a recent systematic review found that the evidence that these factors contribute to preeclampsia risk is weak [19].

Statistical and machine-learning models of preeclampsia risk

To improve risk prediction, multiple predictive models have been developed. The most commonly used and well-validated model is the competing risks model of the Maternal Fetal Medicine Foundation [20], which, in addition to the traditional clinical risk factors, also includes a serum biomarker, placental growth factor, and uterine artery pulsatility index measured by Doppler ultrasonography. While this approach can identify 75-90% of the patients with preeclampsia [19], the latter tests are not routinely performed in all patients. Recently, a number of statistical and machine-learning models have been developed. Most models utilize clinical risk factors combined with biomarkers [21, 22]; the majority of these models are also derived from well-curated datasets [21-24]. Recently, a few accurate machine-learning models based on structured data from medical records or large research datasets have been developed [23, 25-27]. These models outperformed the existing risk stratification and have shown potential to be incorporated into clinical practice and applied longitudinally throughout pregnancy.

Genetic risk of preeclampsia

There is significant evidence that genetics also play a role in the risk of developing preeclampsia [28]. Several genome-wide association studies (GWAS) have demonstrated that multiple genes with high population frequency and small individual effects determine the genetic contribution to preeclampsia risk [29-31]. Interestingly, preeclampsia has shared genetic architecture with both systolic and diastolic blood pressure, and body mass index [29-32]. As the effects of each gene contributing to diseases with polygenic inheritance are small, those conditions are typically studied using polygenic risk scores, which can aid disease detection. Due to the pleiotropic effect of many genes, polygenic risk scores can be applied to multiple conditions with shared genetic architecture. For example, polygenic risk scores for systolic blood pressure, hypertension, and gestational hypertension are predictive of preeclampsia [27, 33-35]. As the polygenic risk scores for multiple conditions are associated with disease risk independent of clinical and environmental risk factors, and polygenic risk scores can interact with other risk factors largely additively, all of these factors can be combined in a single model[27]. These genetic effects are small and more research in large, multiethnic cohorts is needed.

Pathophysiology and biomarkers of preeclampsia

A deeper understanding of the pathophysiology of preeclampsia has significantly advanced the potential for its prediction and early diagnosis [36]. During normal implantation, trophoblasts invade the decidualized endometrium, causing remodeling of spiral arteries and obliteration of the tunica media thereby increasing blood flow to the placenta, independent of maternal vasomotor changes. In preeclampsia, however, trophoblasts fail to differentiate into endothelial-like cells, resulting in poor trophoblast invasion and incomplete spiral artery remodeling. This leads to placental ischemia and the release of inflammatory and vasoactive mediators into the maternal circulation, triggering downstream effects such as angiogenic imbalance and endothelial dysfunction. These changes result in a vasoconstrictive state, oxidative stress, and microemboli, contributing to the involvement of multiple organ systems and manifesting as the clinical features of preeclampsia [37]. Over the past few decades, numerous clinical and biochemical methods, imaging techniques, and clinical parameters have been developed and tested, aiming to predict the onset of preeclampsia[38, 39]. Table 2 summarizes the biomarkers investigated to enable early detection of preeclampsia [40, 41].

Table 2:

Biomarkers for early detection of preeclampsia

Characteristic	Biomarker
Factors involved in trophoblast invasion	A disintegrin Metalloprotease-12 Pregnancy associated plasma protein-A (PAPP-A)
Factors involved in maternal immune modulation	Pentraxin 3
Factors involved in the transformation and remodeling of maternal vessels	Placental Protein 13 (PP13) P-selectin
Placental hormones	hCG Activin Inhibin
Placental angiogenic factors	Soluble fms-like tyrosine kinase-1 (sFlt-1) Placental growth factor (PlGF) Soluble endoglin (sEng)

Of note, none of these biomarkers meet the World Health Organization criteria for a predictive test, as they have low predictive values individually. Among the biomarkers investigated for the early detection of preeclampsia, the placental angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) have received considerable attention. A multicenter, multiracial study in the US, Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification (PRAECIS), investigated and validated an sFlt-1:PlGF ratio to stratify the short-term risk of developing preeclampsia with severe features in women with hypertension hospitalized in late pregnancy [42]. Among women hospitalized with a hypertensive disorder of pregnancy, a serum sFlt-1:PlGF ratio >40 indicated patients at greater risk of developing severe preeclampsia within the ensuing 2 weeks than those with ratios <40. Various adverse pregnancy outcomes were strongly associated with high sFlt-1:PlGF ratios, including severe hypertension requiring delivery, thrombocytopenia, eclampsia, fetal growth restriction, and fetal death [42]. These results were validated in a recent, real-world study [43].

Antepartum Management

Prophylaxis and severity mitigation

Given that no cure exists for preeclampsia aside from delivery, prevention is a vital component of reducing the incidence of preeclampsia worldwide. While several strategies have been investigated, most interventions have been unsuccessful, secondary to the multifactorial pathogenesis of the disease. Low-dose aspirin is the most useful approach currently available to prevent severe preeclampsia and delay the onset of preeclampsia in individuals at increased risk.

The beneficial effect of lower doses of aspirin (60-150 mg daily) is related to a reduction in platelet thromboxane synthesis. Preeclampsia is associated with a functional imbalance between vascular prostacyclin and thromboxane A2 production, leading to increased platelet turnover[44]. The use of low-dose aspirin is consistently associated with a decreased risk of preeclampsia in high-risk patients, with relative risks in meta-analyses of randomized controlled trials ranging from 0.57 to 0.92[45]. A 2021 meta-analysis of 23 trials of patients at highest risk of preeclampsia based on clinical risk factors demonstrated a reduction in preeclampsia incidence (absolute risk reduction −4.1 percent, 95% CI −8.4 to −1.3) and preterm birth <37 weeks (absolute risk reduction −5.7 percent, 95% CI −12.9 to −3.0). There was also no significant increase in adverse outcomes related to bleeding [46]. For patients with two moderate risk factors or one high-risk factor, ACOG recommends initiating 81 mg aspirin daily between 12 and 28 weeks of gestation, ideally prior to 16 weeks, continued until delivery [47].

No consensus exists regarding the timing of aspirin discontinuation. While some practices continue low-dose aspirin until delivery, others discontinue it at 36 weeks gestational age or 5 to 10 days before delivery to decrease the risk of bleeding at the time of delivery. However, discontinuation timing has not been linked to excessive maternal or fetal bleeding. Furthermore, low-dose aspirin use is not a contraindication to neuraxial anesthesia[48].

In addition to aspirin, strong evidence supports the recommendation of moderate-intensity exercise of at least 140 minutes per week [49] and calcium supplementation in parturients with low baseline calcium intake (less than 900 mg per day) [50].

Anti-hypertensive therapy

Effective blood pressure control is a mainstay in the management of preeclampsia to decrease maternal and fetal complications. In the absence of pre-existing chronic hypertension, antihypertensive therapy should be expedited when blood pressure reaches or exceeds 160/110 mmHg and persists after repeat measurement 15 minutes later. Intravenous hydralazine or labetalol and oral nifedipine immediate release are the three agents most commonly used to treat severe acute hypertension [1].

In those with pre-existing chronic hypertension, the Chronic Hypertension and Pregnancy (CHAP) trial in 2022, a large, multicenter, randomized trial, demonstrated that antihypertensive treatment for mild chronic hypertension in pregnancy (blood pressure <160/105 mm Hg) to a goal (<140/90 mm Hg), primarily with labetalol or nifedipine compared with no treatment (unless blood pressure was severe), reduced the composite risk of superimposed preeclampsia with severe features, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death [51]. As a result of this trial, professional societies in the US have recommended treatment of patients with chronic hypertension in pregnancy to a blood pressure goal of <140/90 mm Hg. First-line agents for long-term blood pressure control include oral beta blockers, calcium channel blockers, and alpha blockers, most commonly labetalol, nifedipine XL, and hydralazine [52]. The benefits of antihypertensive treatment must be balanced against potential risks, as overly aggressive blood pressure reduction may compromise uteroplacental perfusion, potentially leading to fetal growth restriction or distress [53]. Additionally, some antihypertensive medications such as ACE inhibitors and angiotensin receptor blockers remain contraindicated in pregnancy due to their association with fetal renal dysfunction and other congenital anomalies [54]. Therefore, careful medication selection and close monitoring of both maternal and fetal well-being are essential components of blood pressure management in preeclampsia and chronic hypertension in pregnancy.

Home blood pressure monitoring

The antihypertensive agents available for controlling blood pressure in pregnancy are limited, thus active home surveillance of blood pressure and symptoms may play a critical role in optimizing control and minimizing associated complications. The BUMP1 and BUMP2 (Blood Pressure Monitoring in High-Risk Pregnancy to Improve the Detection and Monitoring of Hypertension) trials demonstrated that home blood pressure monitoring, combined with a smartphone app for result transmission, did not lead to earlier detection of hypertension among individuals at higher risk of preeclampsia [55, 56].

A systematic review and meta-analysis showed that home blood pressure monitoring during the antenatal period was associated with reduced risk of induction of labor, prenatal hospital admissions, and diagnosis of preeclampsia. There were no significant differences between home blood pressure monitoring and conventional care regarding composite maternal, fetal, or neonatal outcomes when used during the antenatal period. However, the study was limited due to significant clinical heterogeneity [57, 58]. While home blood pressure monitoring shows promise in improving hypertension management during pregnancy, it should be used as a complement to, rather than a replacement for, regular antenatal care and clinical assessments. There is also growing evidence and increasing utilization of monitoring of blood pressure postpartum in individuals with a history of hypertension in pregnancy. A systematic review from 2023 demonstrated that home blood pressure monitoring improves the collection of blood pressure readings needed for early detection of hypertension in the postpartum period and may even work towards decreasing racial disparities seen in clinic-based blood pressure follow-up postpartum [58].

At this time, there is insufficient evidence to conclude that home blood pressure monitoring reduces severe maternal morbidity or mortality or reduces racial disparities in clinical outcomes [58].

Seizure prophylaxis with magnesium

Intravenous magnesium sulfate is a cornerstone in the management of preeclampsia with severe features and eclampsia, primarily for seizure prophylaxis and fetal neuroprotection. The landmark MAGPIE Trial (2002) demonstrated that magnesium sulfate halves the risk of eclampsia in women with preeclampsia [59]. For seizure prophylaxis, magnesium sulfate infusion begins at the start of labor or induction, or prior to cesarean delivery and continues for 12- 24 hours postpartum. Additionally, in patients with severe features undergoing expectant management, magnesium is initiated in the setting of clinical instability, usually upon initial presentation, such as for persistent severe range blood pressures, and may be discontinued with stabilization [1]. While the exact mechanism of seizure prophylaxis is unknown, magnesium’s efficacy is postulated to result from its role as a central nervous system depressant by blocking N-methyl-D-aspartate (NMDA) receptors and calcium channels[60]. Careful monitoring is crucial due to the narrow therapeutic index of magnesium. The therapeutic range of magnesium is 4.8-8.4 mg/dL, however data supporting these values are limited [61]. The most common regimen for achieving a therapeutic level expeditiously while also minimizing adverse effects consists of an intravenous 4-6 g loading bolus over 20-30 min, followed by a maintenance dose of 1-2 g/h. When IV access is not feasible, magnesium sulfate can be given intramuscularly (IM) at a dose of 10 g (5 g IM in each buttock) and then 5 g every 4 hours. In order to reduce pain with IM injection, magnesium can be mixed with 1 mL of lidocaine 2% solution [1].

In the setting of renal insufficiency, there is a higher risk of magnesium toxicity given magnesium is almost exclusively renally excreted. In these situations, the maintenance infusion dose may need to be reduced from 2g/h to 1g/h or may need to be discontinued altogether with the plan to administer boluses as needed based on serum magnesium levels checked every 4-6 hours.

Individuals receiving magnesium for seizure prophylaxis may experience nausea, vomiting, flushing, drowsiness, weakness, and confusion[59]. Physical examination, including vital signs, urine output, mental status, and deep tendon reflexes, should be evaluated at regular intervals to screen for signs of toxicity. Serum laboratory tests, including a complete blood count and comprehensive metabolic profile, are obtained at regular intervals with the inclusion of hemolysis tests and coagulation factors if clinically warranted. Magnesium levels are not routinely obtained but may be obtained to confirm therapeutic range. The magnesium infusion should be discontinued if a magnesium serum level exceeds 9.6 mg/dL (8 mEq/L), and the level should be checked every 2 h with reinitiation of the infusion when serum levels fall below 8.4 mg/dL (7 mEq/L). Hypermagnesemia is treated with intravenous calcium gluconate 10% solution, 10 mL over 3 minutes. Magnesium toxicity should be suspected, ruled out, and rapidly treated in parturients who suffer cardiac arrest with ongoing or recent magnesium therapy, particularly if no other etiologies are confirmed. Important considerations for when magnesium is contraindicated include myasthenia gravis, hypocalcemia, moderate to severe renal failure, acute myocardial infarction, heart block, or myocarditis. In these cases, benzodiazepines or levetiracetam can be used for alternative seizure prophylaxis[16].

Timing and mode of delivery

Patients with preeclampsia without severe features may be expectantly managed until 37 weeks’ gestation when delivery is indicated. Delivery for preeclampsia with severe features is indicated at 34 weeks’ gestation[16]. Expectant management is contraindicated in the setting of severe-range hypertension unresponsive to antihypertensive regimens, HELLP syndrome, acute kidney injury (serum creatinine twice baseline, or greater than 1.1 mg/dL), pulmonary edema, eclampsia, placental abruption, refractory headache or epigastric pain. Mode of delivery is based on standard obstetric indications. Patients may undergo induction of labor with cervical ripening, and the diagnosis of severe preeclampsia does not indicate the need for cesarean delivery, given there is a reasonable likelihood of vaginal delivery even when induction occurs before 34 weeks gestation. Prolonged induction of labor should, however, be avoided due to the lower likelihood of success [62].

Disparities in care and global health and preeclampsia

According to the World Health Organization (WHO), the incidence of preeclampsia ranges between 2% and 10% of pregnancies worldwide. About 1.8-16.7% of the cases are reported in developing countries, while in developed countries, the rate is 0.4%[63]. Maternal mortality is increasing in the US, particularly among Black, Hispanic, and Indigenous populations [64]. Hypertensive disorders are associated with severe maternal morbidity, with the greatest impact among Black individuals [65]. The adverse outcomes are associated with limited access to antenatal care, diagnostic resources, and effective treatments in many regions. Addressing these disparities requires a multifaceted approach, including improved access to quality prenatal care, increased awareness, and education, research into the biological mechanisms underlying racial differences in preeclampsia risk, and policy changes to address systemic inequities in healthcare delivery.

Anesthetic management of the patient with preeclampsia

The role of the anesthesiologist in the management of patients with preeclampsia is crucial to ensure a safe outcome for both the mother and neonate [66, 67]. It is essential that anesthesiologists understand the pathophysiology of this multisystem disease, as patients with severe features may present with rapid deterioration in their clinical picture [66]. Recent studies of point-of-care ultrasound (POCUS) suggest that early perioperative assessment of cardiac, lung, and cerebral dysfunction may enhance the detection of severe features of preeclampsia [68-71]. In addition, an obstetric airway management registry has provided evidence that preeclamptic patients are at increased risk of hypoxemia and guidance for anesthesia in the presence of thrombocytopenia [72, 73]. In this regard, we will discuss two clinical scenarios to explain the various anesthesia considerations for a patient with preeclampsia with severe features.

Anesthesia for the patient with preeclampsia with severe features

Clinical scenario 1:

A 26-year-old parturient with early onset severe preeclampsia at 34 weeks’ gestation has been admitted for induction of labor. Her sFlt-1:PlGF ratio was >40 when checked the week prior to when she first developed preeclampsia. The obstetrics team has asked for assistance with analgesia. She is obese, with a body mass index (BMI) of 45 kg/m². The patient’s vital signs are as follows:

• Blood pressure 180/110 mmHg

• Heart rate 90 beats per minute

• Oxygen saturation: 98% on room air

Prior to analgesia, the obvious first step in the management of this patient includes blood pressure control to reduce the risk of stroke, and seizure prophylaxis [66]. While neuraxial analgesia can further facilitate the control of maternal blood pressure, adequate platelet count should first be confirmed. Diastolic dysfunction is the hallmark of cardiovascular dysfunction in preeclampsia [66, 74]. Neuraxial anesthesia is associated with sympathetic blockade and modest afterload reduction, both of which are beneficial for blood pressure control and diastolic dysfunction. Therefore, in the absence of contraindications, epidural analgesia should be initiated wherever possible and as early as possible in women with preeclampsia in active labor. This technique also avoids potential airway difficulties associated with urgent cesarean delivery in preeclampsia, particularly in obese patients. In their analysis of an obstetric airway registry, Smit et al. found that clinically significant oxygen desaturation during airway management occurred twice as often in patients with hypertensive disorders of pregnancy, compounded by increasing body mass index [72].

There are a number of considerations when evaluating the risk of neuraxial anesthesia. Coagulopathy associated with preeclampsia, particularly in patients with HELLP syndrome or thrombocytopenia, may increase the risk of epidural hematoma, and thus, the use of neuraxial analgesia is relatively contraindicated. Historically, societal guidelines specify a higher risk of this complication with platelet counts of < 70 x 10⁹/L. Recently amended guidelines from the Society for Obstetric Anesthesia and Perinatology propose a more liberal range [75] Two studies of combined 1,995 patients with thrombocytopenia receiving neuraxial anesthesia did not report any epidural hematomas with 95% CI to 0.19%, 2.6%, and 9% at platelet counts between 70,000 and 100,000 × 10⁶/L, 50,000 and 69,000 × 10⁶/L, and <50,000 × 10⁶/L, respectively [76, 77] . Prompt and serial assessment for thrombocytopenia is essential in these patients to enable the safe provision of neuraxial techniques. If thrombocytopenia is present, the platelet count should be checked before spinal, epidural placement, and epidural catheter removal.

Epidural analgesia, especially with high doses of local anesthetic, may not be a safe option in patients with severe systolic dysfunction occasionally associated with preeclampsia [68]. POCUS, most commonly performed by the anesthesiologist, offers a reliable method of assessing cardiovascular dysfunction using transthoracic echocardiography and lung ultrasound [66, 68, 70, 71]. Yagani et al. concluded that pulmonary interstitial syndrome is found on ultrasound in more than half of women with early onset preeclampsia with severe features, and this could be a precursor to the development of cardiovascular deterioration [71]. Ortner et al. revealed that there is a high prevalence of ultrasound abnormalities in women presenting with late-onset preeclampsia, and, thus, the value of POCUS examination in these patients is high [68, 70].

The sFlt-1:PlGF ratio is used as a screening tool to predict the development of severe preeclampsia over the next two weeks. Her ratio was elevated the week before her initial presentation with preeclampsia, and she then progressed to severe preeclampsia in the next week. The use of this test is becoming increasingly prevalent in clinical practice. It is also used in stratifying which patients with preeclampsia could be managed inpatient versus outpatient, depending on their risk of progressing to severe preeclampsia in the next two weeks.

Anesthesia for the patient with eclampsia and COVID-19

Clinical scenario 2:

A 24-year-old woman with eclampsia at 38 weeks’ gestation is scheduled for a cesarean section for a category II fetal heart tracing. She has had a single seizure two hours ago. The patient has the following features:

• BMI 40 kg/m2

• A swollen, bitten tongue

• Blood pressure 188/110 mmHg

• Heart rate 110 bpm

• Dyspnea, with oxygen saturation of 94% on room air

• Glasgow Coma Scale 14

• Recent platelet count 90 x 10⁹/L

• SARS-CoV-2 positive

Such complex clinical presentations, common in limited-resource environments, pose serious challenges in deciding anesthetic techniques. Risks and benefits of spinal versus general anesthesia require careful and often urgent consideration in such patients.

After urgent blood pressure reduction to prevent stroke, goals of general anesthesia in the patient with preeclampsia or eclampsia include attenuation of the hypertensive response to intubation and optimal oxygenation to prevent critical desaturation. Prior to induction of anesthesia, either in the ward or, if necessary, in theatre, a targeted reduction of systolic blood pressure to < 160 mmHg can be achieved. Various agents, including beta-blockers, vasodilators, and even small doses of induction agents such as propofol, may be used [66, 78].

Low oxygen saturation and dyspnea in this patient could be due to SARS-CoV-2 infection in an obese patient or cardiac dysfunction with pulmonary congestion. After chest radiography and arterial blood gas analysis, this would best be assessed with POCUS using cardiac and lung ultrasound [68, 70, 71]. The reliability of the measurement of optic nerve sheath diameter to assess intracranial pressure in preeclampsia and eclampsia remains controversial [69].

The attenuation of the hypertensive response to intubation can be achieved using one or a combination of several drugs [78]. The first is magnesium sulfate, which can be given to obtund catecholamine release as a bolus of 30 mg/kg IV immediately after induction of anesthesia in magnesium-treated patients and 45 mg/kg if the patient is magnesium naïve [79]. Other options include beta-blockers (esmolol or labetalol), vasodilators (nitroglycerine), opiates (fentanyl, remifentanil or alfentanil), alpha-2 agonists (dexmedetomidine) and lidocaine [66, 78, 80]. All these drugs have risks and benefits. The appropriate choice of an induction agent, such as propofol, can also have a significant impact on the attenuation of the hemodynamic response [78].

Hypoxemia in patients with hypertensive disorders of pregnancy is twice as likely compared to normotensive patients [72]. Other factors that worsen hypoxemia are obesity and the presence of pulmonary edema [66]. Apneic oxygenation using high-flow nasal oxygenation has been shown to prolong the time to desaturation in non-obstetric patients, and although studies showing preoxygenation with such techniques in the obstetric population have been disappointing, further studies on apneic oxygenation are awaited [81, 82]. In a recent trial, pre-oxygenation using high-flow nasal oxygen was not inferior to pre-oxygenation using a face mask; the latter did not achieve the preoxygenation targets in 50% of the individuals [83]. Additional methods to reduce the incidence of hypoxemia stem from the first principles of preparing for a difficult airway and securing the airway as safely and quickly as possible with the use of video laryngoscopy [84].

There are shared risk factors for the development of preeclampsia and severe SARSCoV-2 disease [66]. In general, patients are managed and delivered according to the status of their preeclampsia. However, earlier delivery may be indicated as part of COVID-19 therapy to improve respiratory compromise. Neuraxial anesthesia is the preferred mode of anesthesia for patients with COVID-19 disease if their respiratory status and coagulation status allow it [85]. It has the advantage of avoiding airway manipulation in the patient who already has a respiratory compromise and has been shown to be hemodynamically favorable, including a milder degree of spinal hypotension compared with normotensive controls.

Spinal anesthesia, in the absence of labor epidural analgesia, is the technique of choice in preeclamptic patients, especially in limited-resource settings. Although associated with some degree of spinal hypotension, the main cardiovascular consequence is sympathetic blockade and mild afterload reduction, which is ideal for these patients [66, 74]. In fact, a randomized controlled trial in women with severe preeclampsia showed that spinal hypotension was associated with an increase in cardiac index in patients with preeclampsia [86]. In eclampsia, a recent audit of practice suggested that spinal anesthesia is safe in women with a GCS >14 and less than two previous seizures and avoids both difficult tracheal intubation in the setting of a bitten tongue in an obese patient, as well as the hypertensive response to intubation [87]. A recent analysis of data from an airway management registry suggested that a platelet count <75x10⁹/L is uncommon in patients with isolated severe hypertension, in which case one might consider spinal anesthesia without the availability of a platelet count [73]. In the present complicated case, the platelet count was known, which simplified the decision. Considering the above arguments, spinal anesthesia was performed on this patient, with a favorable outcome. No postoperative ventilation was required.

The above cases clearly demonstrate that hypertensive disorders of pregnancy pose unique and onerous challenges for the anesthesiologist, which require diligent attention to recent evidence in the literature and prompt escalation of care, in direct communication with the obstetric team.

Postpartum management and complications

In patients with preeclampsia diagnosed in the ante- and intrapartum periods, the main postpartum efforts are focused on managing elevated blood pressure[16]. Home blood pressure monitoring is effective in maintaining normal blood pressure. In 0.3%-27.5% of the patients, preeclampsia develops postpartum, and commonly, those patients may be readmitted for blood pressure control and magnesium prophylaxis [88]. A few studies have suggested that non-steroidal anti-inflammatory analgesics, commonly prescribed for pain control after delivery, may elevate preeclampsia risk by inhibiting prostaglandin-mediated vasodilation and increased sodium retention. However, the results of clinical trials are inconclusive [89, 90] and cannot justify a change in practice. Short- and long-term patients with a history of preeclampsia are at significant risk for future cardiovascular disease [36, 91].

Conclusion

Patients with preeclampsia, especially preeclampsia with severe features, have complex medical care needs and are best managed by multidisciplinary teams in tertiary care facilities. Significant progress has been made to enhance risk stratification, prophylaxis, and surveillance. As a care team member, the anesthesiologist’s role is to recognize preoperative risk, inform patients of the benefits of early neuraxial analgesia, facilitate prompt control of severe-range blood pressure, and optimize the management of critically ill patients to improve maternal and neonatal outcomes.

Practice Points.

• Patients with preeclampsia should be managed by a multidisciplinary care team, including obstetricians, maternal-fetal medicine specialists, obstetric anesthesiologists, neonatologists, and other specialists as needed.

• Screening for the presence of risk factors should be performed early in pregnancy. In those at high risk, aspirin prophylaxis, moderate intensity exercise and calcium supplementation if low intake, should be recommended.

• A novel serum test, sFlt-1:PlGF ratio, if >40, can predict the risk of developing severe preeclampsia in the subsequent 2 weeks.

• Most patients, especially those with severe preeclampsia, should be managed in a tertiary care center.

• Early consultation with an anesthesiologist and establishing early neuraxial analgesia is preferred in patients in labor; general anesthesia is associated with higher risk in patients with preeclampsia.

• There is an increasing role of point of care ultrasound evaluation of cardiac, lung, and cerebral dysfunction in preeclampsia.

• SARS-CoV-2 infection and preeclampsia may be associated with a higher risk for pulmonary and cardiovascular complications.

Research agenda.

• Future studies should focus on personalized risk prediction and developing novel prevention strategies.

• Research should continue to elucidate the mechanisms of preeclampsia and aid the development of therapeutic agents.

• A better understanding of and mitigation strategies for disparities in the diagnosis and management of patients with preeclampsia is needed.