Neuroanesthesia During Pregnancy

Cardiovascular System

Pregnancy is a state of high cardiac output. Cardiac output is elevated by 35% to 40% by the end of the first trimester, increases to 50% above baseline by 28 to 30 weeks’ gestation, and peaks with uterine contraction immediately after delivery. Output is increased through a combination of increased stroke volume (25%–30% increase) and heart rate (15%–25%). Echocardiography demonstrates eccentric left ventricular hypertrophy; increased diameters of the mitral, tricuspid, and pulmonic valves; and elevated ejection fraction. The increase in cardiac output during pregnancy is crucial to meet the increased oxygen demands of the body and the developing fetus, and to allow for the intravascular volume expansion that accompanies pregnancy. Despite an elevated cardiac output, blood pressure tends to decrease modestly during pregnancy secondary to diminished systemic vascular resistance. Of importance to the neuroanesthesia provider, cerebral blood flow (CBF) does not change with pregnancy. Thus the elevated cardiac output in pregnancy does not typically affect intracranial compliance or pressure.

Aortocaval compression refers to occlusion of the inferior vena cava (IVC) and aorta by the gravid uterus. IVC compression can be evident as early as 13 to 16 weeks gestation. In the supine parturient at term, there is near-complete blockage of IVC venous return, a 10% to 20% decrease in cardiac output, and a corresponding drop in blood pressure. This phenomenon has important implications when positioning pregnant patients for neurosurgical procedures, as maternal hypotension can contribute to decreased placental, fetal, and maternal organ perfusion (including cerebral perfusion pressure in the neurosurgical patient with elevated intracranial pressure [ICP]). IVC compression can be attenuated by providing left uterine displacement, whether by placing a wedge underneath the right side of the patient, tilting the operating table, or performing surgery in the lateral position if possible.

Pulmonary System and Airway

During pregnancy, minute ventilation increases, resulting in a mild respiratory alkalosis. Ventilation increases secondary to increased CO ₂ production and hormonal influences resulting in a leftward shift of the carbon dioxide ventilation response curve, as well as the hemoglobin-oxygen dissociation curve. The elevated minute ventilation stems almost entirely from increased tidal volume with no to minimal change in respiratory rate. Because vital capacity remains unchanged in pregnancy, the larger tidal volume carves into the expiratory reserve volume, which drops by 25%. In addition, there is a 15% decrease in residual volume. Together, these decreases in the expiratory reserve and residual volumes contribute to a 20% decrease in functional residual capacity (FRC). This is an important consideration for the anesthesiologist, as the size of the FRC is related to the amount of oxygen reserve a patient has at induction of anesthesia. The combination of diminished FRC and an increased oxygen consumption with pregnancy leads to a rapid fall in oxygen saturation with apnea. Moreover, pregnant patients have the potential to become more difficult to intubate when compared with their prepregnancy baseline. Airway edema is common during pregnancy secondary to vascular engorgement such that visualization of the vocal cords during laryngoscopy may be impaired, or it may prove challenging to place a standard-size endotracheal tube in the context of laryngeal swelling. The weight gain and engorged breasts at term represent additional technical challenges. With this potentially dangerous combination of rapid desaturation and a potentially difficulty airway, careful attention to preoxygenation, patient positioning, and a comprehensive intubation plan is essential.

As mentioned, hyperventilation during pregnancy leads to a primary respiratory alkalosis. Correspondingly, the arterial Pa co ₂ falls from 40 to 30 mm Hg in an otherwise heathy parturient. There is compensatory excretion of bicarbonate by the kidneys, with a decrease in serum HCO ₃ ⁻ to 20 mEq/L. The net effect of these changes is a mild alkalemia with a pH of 7.44.

Physiologic hyperventilation during pregnancy has important management implications for the neuroanesthesiologist. Mechanical ventilator settings must account for the low baseline arterial CO ₂ pressure, as ventilating to a “normal” end-tidal CO ₂ of 35 to 40 would actually be relative hypoventilation, resulting in respiratory acidosis and a rise in CBF and potential increase in ICP, which can be detrimental. At the same time, because pregnant patients have a lower baseline Pa co ₂ , there is a reduced margin of safety to acutely reduce ICP through hyperventilation. Although further hyperventilation will reduce CBF and ICP, Pa co ₂ <25 mm Hg may result in uterine artery vasoconstriction and a leftward shift of the maternal oxyhemoglobin dissociation curve, both of which could contribute to decreased placental oxygen delivery, resulting in fetal hypoxia and acidosis. In addition, prophylactic hyperventilation in brain-injured patients to Pa co ₂ less than 25 mm Hg has been associated with poor outcomes, so this strategy is not recommended. Overall, perioperative ventilation should target a Pa co ₂ of 25 to 30 mm Hg in pregnant patients undergoing neurosurgical procedures.

Hematology

Pregnancy is marked by a significantly expanded intravascular volume. Total blood volume increases 45%, with expansion in both plasma and red blood cell quantities. Plasma volume increases by a greater percentage than red blood cell mass, resulting in a dilutional anemia. This increase in blood volume and oxygen-carrying capacity enables the parturient to transport more oxygen to meet the increased metabolic demands of pregnancy. In addition, volume expansion and dilution allow the pregnant woman to tolerate significant blood loss while maintaining hemodynamic stability and adequate oxygen-carrying capacity, as may accompany childbirth.

Along with red blood cell dilution, pregnancy also results in a dilution of plasma albumin and other proteins. Albumin levels drop from an average of 4.5 g/dL to 3.9 g/dL in the first trimester and down to 3.3 g/dL by term. The decrease in albumin and colloid oncotic pressure have some implications for the anesthetic management. Low plasma oncotic pressure predisposes toward development of edema in the airway and extremities, although much less so intracranially, which is more influenced by the osmotic pressure than oncotic pressure, and albumin contributes little to the osmotic pressure. In the setting of traumatic brain injury or symptomatic brain tumor, low serum osmolality can have detrimental effects on brain swelling and contribute to increases in ICP. Perioperative intravenous fluid therapy should therefore consist of isotonic solution to reduce the risk of further brain swelling. Administration of albumin solution has been observed to increase both short- and long-term mortality in traumatic brain injury, although its influence in the context of pregnant patients is unknown.

Another important hematologic change during pregnancy occurs in the coagulation system. Pregnancy is a hypercoagulable state, characterized by elevations in fibrinogen and factors VII, VIII, IX, X, and XII. Prothrombin time (PT) and partial thromboplastin time are decreased, and thromboelastography (TEG) demonstrates increased coagulability and decreased fibrinolysis. With a tendency toward clot formation, the pregnant patient is at increased risk for deep venous thrombosis (DVT). DVT prophylaxis is an essential element of perioperative care, and lower extremity pneumatic compression devices should be used with any anesthetic. The anesthesiologist should have a high index of suspicion for thromboembolic disease when working up perioperative hypoxia or acute hemodynamic instability. Postoperative pharmacologic prophylaxis must balance the risks of bleeding against the risk of thromboembolism and requires consensus of the entire care team.

Even though pregnant patients are most frequently hypercoagulable, it is important to recognize that certain gestational conditions can be associated with thrombocytopenia or disseminated intravascular coagulation (DIC). Preeclampsia may be associated with thrombocytopenia, with or without other manifestations of DIC. Other conditions that may predispose to development of DIC include intrauterine fetal demise, amniotic fluid embolism, sepsis, and placental abruption. The latter is particularly relevant when caring for patients with traumatic brain injury, as trauma is a major risk factor for placental abruption, as well as a risk factor for coagulopathy. Thrombocytopenia and DIC can be devastating in the setting of intracranial hemorrhage and should be managed with replacement of platelets and clotting factors accordingly. The anesthesiologist should have a low threshold to check platelet count, fibrinogen levels, and results of coagulation studies including TEG in the setting of intracranial bleeding or trauma during pregnancy.

Gastrointestinal, Hepatic, Endocrine Systems

Hormonal and physical changes during pregnancy have important effects on the gastrointestinal (GI) system. Increased circulating progesterone contributes to decreased lower esophageal sphincter tone, with 30% to 50% of pregnant women experiencing symptomatic gastroesophageal reflux disease (GERD). As pregnancy progresses, the competence of the lower esophageal sphincter is further compromised by the gravid uterus, which displaces the stomach up and to the left. Beyond 20 weeks’ gestation, parturients are considered to be at an increased risk for aspiration during anesthetic induction. Accordingly, they should be treated with preoperative nonparticulate antacid (when possible, assuming the patient can tolerate oral medications); when general anesthesia is required, a rapid sequence induction should be performed to minimize aspiration risk.

Hepatic size and blood flow do not change with pregnancy. Plasma bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) may increase toward the upper limits of normal, and alkaline phosphatase activity increases secondary to placental production. There is an increased risk for gallbladder disease secondary to biliary stasis during pregnancy. Overall, there is little change in hepatic synthetic function, and effects on anesthetic management are negligible. Of note, pseudocholinesterase is produced by the liver, and its activity decreases by about 25% during pregnancy. This change is not clinically significant, and the duration of neuromuscular blockade from succinylcholine is not prolonged in pregnancy.

The important endocrine consideration for the anesthesiologist is an increase in insulin resistance. Postprandial blood glucose levels are elevated in pregnancy, and perioperative hyperglycemia can be difficult to manage.

Renal System

Renal blood flow and glomerular filtration rate are elevated during pregnancy. Accordingly, creatinine clearance increases and both blood urea nitrogen and creatinine are decreased. There is an increase in the excretion of albumin and other proteins, contributing to the hypo-oncotic state seen in the parturient.

The increased glomerular filtration rate may affect the clearance of certain medications. Of particular importance in the neurosurgical patient population are anticonvulsant medications, which are often prescribed to patients with intracranial masses to suppress seizure activity. Consideration should be given to consulting neurology or pharmacy colleagues for dosing and monitoring recommendations.

Nervous System

There are multiple CNS changes that influence the administration of both general and regional anesthesia during pregnancy. With pregnancy, the minimal alveolar concentration (MAC) for inhaled anesthetics decreases by up to 40%. Therefore pregnant patients are more sensitive to the sedative-hypnotic effects of volatile anesthetics, and a reduced dose may be used to minimize side effects such as hypotension or interference with neurological monitoring (such as motor evoked potentials or somatosensory evoked potentials). The susceptibility to general anesthetics should also be taken into account during emergence at the conclusion of a neurosurgical case. With the decreased MAC of the parturient, even trace levels of residual anesthetic might contribute to delayed awakening and the ability to perform a thorough postoperative neurological assessment.

In addition to an increased sensitivity to volatile anesthetics, pregnant patients are also more sensitive to the effects of local anesthetics, and effective epidural and spinal anesthesia doses are reduced in the parturient, particularly at later gestational ages. As pregnancy progresses, epidural veins become engorged, occupying more of the epidural space. Consequently, a given volume of epidural local anesthetic will spread further, effecting blockade at more dermatomes than in the nonpregnant patient. The increased volume of epidural veins also exerts a compressive force on the spinal column, reducing cerebrospinal fluid volume such that spinal local anesthetic injection results in enhanced spread during pregnancy. Despite the reduction in volume, CSF pressure remains normal during pregnancy and there is no change in ICP. Spinal and epidural anesthesia are seldom used for neurosurgical procedures, but there are case reports of urgent lumbar disk decompression being performed with epidural anesthesia.

The autonomic nervous system plays an enhanced role in the maintenance of normal blood pressure during pregnancy. Blockade of sympathetic innervation via neuraxial or general anesthesia can result in more profound hypotension during pregnancy. It is important for the anesthesiologist to anticipate potential hemodynamic instability and take measures to attenuate blood pressure drops or treat them rapidly, especially in the setting of elevated ICP, when maintenance of cerebral perfusion pressure is crucial.