Preeclampsia: a Perioperative Medical Challenge for the Anesthesiologist

Anesthesia practice is based on an understanding of the relevant pathophysiology. Current theory suggests that in preeclampsia there is failure of the usual vascular remodeling of the spiral arteries by invasion by the cytotrophoblast. There is resultant activation of clotting pathways, release of cytokines and antiangiogenic proteins, endothelial dysfunction, vasoconstriction, and finally reduced organ perfusion, with its associated symptoms and signs. It has also been postulated that the mechanisms of abnormal placentation may be different in early and late-onset disease.

The anesthesiologist therefore needs to have a keen understanding of cardiopulmonary function, as well as cerebrovascular dysfunction, in preeclampsia and eclampsia, and must be able to assess disease severity in order to predict, prevent, and treat life-threatening complications.

The assessment of cardiac function in preeclampsia has been considerably advanced in recent years, with anesthesiologists playing a leading role in this field. Transthoracic echocardiography has been a major research tool in the elucidation of central hemodynamics and as a point-of-care tool for assessment of severity of cardiac dysfunction in preeclampsia.

The prevalence of point-of-care ultrasound (POCUS) abnormalities was established using transthoracic echocardiography, lung ultrasound, and ONSD in late onset severe preeclampsia, as well as the association with serum albumin and brain natriuretic peptide (BNP).

There should be a low threshold for arterial line placement in preeclampsia, particularly in the setting of poorly controlled hypertension, renal failure, hemorrhage, pulmonary edema, and mechanical ventilation. Transthoracic echocardiography is a useful point-of-care tool for assessment of intravascular volume status, ventricular function, and comorbidities such as valvular heart disease.

ANESTHESIA MANAGEMENT

Regional Anesthesia

Using the pulmonary artery catheter there was only mild afterload reduction during epidural analgesia for labor in women with severe preeclampsia and receiving magnesium sulfate. Blood pressure and cardiac output were well preserved. From first principles, epidural anesthesia should therefore be initiated wherever possible in women with preeclampsia in active labor, because the analgesia forms part of blood pressure control.

Using minimally invasive cardiac output monitoring in severe preeclampsia, it has been shown that SA is associated with only mild afterload reduction and that preload is not the major concern in the absence of hemorrhage or other comorbidities. Sympathetic blockade, and modest afterload reduction with only minor changes in preload, are textbook management for diastolic dysfunction, which is the hallmark of cardiovascular dysfunction in preeclampsia.

The vasopressor used should be based on maternal hemodynamic status. Phenylephrine is the first-line vasopressor if systolic function is preserved. In the authors' view, noradrenaline is contraindicated in the routine management of spinal hypotension in preeclampsia, because even minor dose errors using this potent vasoconstrictor could cause precipitous hypertension in these patients, with potential associated severe morbidity; this is especially true in under resourced environments, where anesthesia providers may be inexperienced, with little supervision.

There is no definitive literature on specific contraindications to SA in severe preeclampsia, other than the presence of hypovolemia and thrombocytopenia.

Thrombocytopenia and the Risks of Regional Anesthesia

The lower limit of the platelet count for safe performance of regional anesthesia in preeclampsia remains controversial. A recent SOAP Task Force performed a systematic review and a Delphi process and concluded that the risk of spinal epidural hematoma associated with a platelet count ≥ 70 x 10⁹ /L would be low in hypertensive disorders of pregnancy; factors to be considered with relevance to preeclampsia include airway status, available equipment, and the risk of GA, which to some extent would be determined by the experience of the anesthesia provider. All these factors should also be considered when deciding on the method of anesthesia in women with preeclampsia or eclampsia who have thrombocytopenia or when a platelet count is not available.

In HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) thrombocytopenia occurs more frequently, and the platelet count may decrease precipitously to less than 75 x 10⁹ /L. In these parturients it is essential that one follows the trend in platelet counts closely.38 In contrast with the SOAP consensus guidelines, the NICE guidelines do not recommend a specific platelet threshold that precludes neuraxial blockade. Instead, they suggest an individualized approach, where one takes into consideration the risk of bleeding and opportunity for correction, the use of anticoagulants, anticipated difficulty of the procedure, as well as the proposed method (epidural or SA).

Current guidance recommends that pregnant women hospitalized with SARS-CoV-2 infection receive prophylactic anticoagulation, generally with low-molecular-weight heparins, in the absence of contraindications. The choice of anticoagulant and its dosing in undelivered patients with preeclampsia and SARS-CoV-2 should take into consideration the likelihood of residual anticoagulation should a category 1 or 2 emergency CS become indicated. It is prudent to have a recent platelet count available, as each of the conditions and the heparin anticoagulants may be associated with thrombocytopenia.

General Anesthesia

Should GA be required, it is of great importance to obtund the hypertensive response to tracheal intubation, thus avoiding potential cerebrovascular complications. The most effective pharmacologic technique for this purpose remains controversial. The authors recommend esmolol or nitroglycerine.

Intubation of the eclamptic patient with a bitten tongue poses a particular challenge for induction of GA. Logically, the worst of the lingual trauma and swelling is situated anterior in the buccal cavity, but the possibility of blood and edema deeper in the upper airway must be recognized.

In general, patients are managed and delivered according to the status of their preeclampsia; however, earlier delivery may be indicated should there be respiratory compromise, particularly if prone ventilation or extracorporeal membrane oxygenation is required as part of SARS-CoV-2 therapy. Where the patient's respiratory status and coagulation status allow it, neuraxial anesthesia is strongly preferred.

The Use of Uterotonic Agents

Specific work on the effects of uterotonic agents in preeclampsia is especially relevant given the increased risk of postpartum hemorrhage. A slowly administered oxytocin bolus dose, in line with current international consensus recommendations, has been shown to cause similar short-lived vasodilatation and hypotension as in healthy parturients at CS, although the hemodynamic response may be more variable in severe preeclampsia. There are growing data suggesting that carbetocin is a safe and efficacious alternative oxytocic, even though its manufacturing license lists preeclampsia as a contraindication to its use. Second-line uterotonic agents remain largely limited to prostaglandins such as misoprostol, because the ergot alkaloids may provoke a pronounced hypertensive response.

Postcesarean Analgesia

Adequate analgesia, as during labor, is not only a patient's right but also a crucial component of blood pressure management after CS. A multimodal approach is typically recommended, but there has been limited work done on postoperative analgesia in preeclamptic women. Dennis and colleagues demonstrated lower pain scores and analgesic requirements in the early postoperative period in preeclamptic women after SA for CS and postulated that this may be due to the effects of peripartum magnesium sulfate infusion and the higher neuraxial local anesthetic dose administered for the delivery of growth-restricted, preterm fetuses. The use of nonsteroidal antiinflammatory drugs (NSAIDs) remains controversial, with concerns around the propensity of these drugs to impair renal and platelet function and control of hypertension in preeclamptic women.

ECLAMPSIA

Eclampsia remains a major challenge for the anesthesiologist. Progression to eclamptic seizures may be associated with cytotoxic edema and cerebral infarction and/or vasogenic edema, with loss of cerebral autoregulation and increased capillary permeability, placing the patient at risk of intracerebral hemorrhage.

Current clinical opinion is that patients with eclampsia with a Glasgow Coma Scale score (GCS) < 14 and a high likelihood that there is elevated ICP should receive GA for CS with similar considerations as in neuroanaesthesia. These include normoxia and normocarbia, control of blood pressure so that cerebral perfusion is maintained in the setting of elevated ICP, and postoperative ventilation with careful sedation until neurologic recovery is achieved, in an intensive care unit. In limited-resource environments, the capacity for postoperative ventilation is often not available.

In view of the undoubted risk associated with GA in women with eclampsia, careful consideration should be given to the use of SA in all women with a GCS < 14. In patients who have had several seizures, focal neurologic signs, and/or HELLP syndrome, GA should be provided. Major audits of anesthesia practice in high- and low-income environments would be useful, so that one could plan optimal management depending on resources available.

Anesthesiologists have for many years been at the forefront of research whose goal has been the establishment of safe regional anesthesia in preeclampsia, both epidural anesthesia for labor and SA for CS. Advances in GA in this field include an understanding of the mechanisms of hypoxemia, and the introduction of sophisticated aids to tracheal intubation. More recently, anesthesiologists have become proficient in the use of echocardiography and other ultrasound modalities, which has led to research elucidating cardiac function, and point-of-care identification of many aspects of cardiac and pulmonary function. The close involvement of the anesthesiologist in the perioperative interdisciplinary team including nurses, obstetricians, physicians, and cardiologists has improved the prediction of severity of disease and will likely improve safety in patients with complicated preeclampsia with severe features.

CLINICS CARE POINTS

• Point-of-care lung ultrasound is useful to identify those patients with preeclampsia with IPE, who would benefit from judicious fluid restriction and afterload reduction, to avoid progression to life-threatening alveolar edema.
• Point-of-care transthoracic echocardiography is useful to delineate the cause of pulmonary edema and allows differentiation between diastolic dysfunction, systolic hypofunction, and preexisting valvular heart disease.
• In the absence of contraindications, SA is a well-tolerated technique for urgent CS, with less hypotension than in normotensive women.
• Induction of GA requires skilled administration of agents to control peri-induction hypertension and an awareness of the propensity for rapid desaturation and airway edema.
• Anesthesiologists should be aware of the long-term cardiovascular effects of preeclampsia, many of which influence the choice of technique and detailed practice of anesthesia