Abstract
The physiologic changes that occur during pregnancy, labor, and the postpartum periods are profound. In addition, the fetus presents a unique component of the circulatory and metabolic systems that must be part of patient care considerations and decision-making. A thorough understanding of these physiologic alterations and fetal considerations is integral to providing safe and optimal anesthetic care for obstetric patients. The field of obstetric anesthesiology commonly uses a variety of medications that are unique within the practice of anesthesiology and require special understanding for use in the obstetric population. All medications administered to the mother have the potential to affect the fetus. A detailed understanding of drug pharmacodynamics, placental transfer, and side effects helps ensure not only optimal patient care but also improved patient counseling in both the peripartum period and for nonobstetric surgery during pregnancy. Obstetric anesthesia creates the need to care simultaneously for two patients, and a comprehensive understanding of the unique physiologic systems as well as pharmacologic management pertinent to pregnant patients will help to ensure safe and appropriate medical care.
Keywords
obstetric anesthesia, fetal anesthesia, pregnancy physiology, fetal physiology, cesarean delivery, labor analgesia, neuraxial anesthesia
Chapter Outline
Hepatic and Gallbladder Changes
Anesthesia for Cesarean Delivery
Additional Peripartum Medications and Considerations
Physiology
Hormone activity, increased metabolic demands, the gravid uterus, and biochemical changes related to the fetoplacental unit result in significant alterations in maternal physiology, anatomy, and pharmacology during pregnancy, as shown in Fig. 37.1 . These physiologic changes have a direct impact on maternal pharmacodynamics and anesthetic management considerations during the peripartum period.
Cardiovascular Changes
Pregnancy-related changes to the cardiovascular system include an increase in cardiac output, decrease in systemic vascular resistance, increase in blood volume, and presence of supine hypotension. The extent of these physiologic changes varies with gestational age (GA). A summary of these alterations at term is provided in Table 37.1 .
| Cardiovascular Component | Changes at Term (vs. Prepregnancy Values) |
|---|---|
| Cardiac output | Increased 40%–50% |
| Stroke volume | Increased 25%–30% |
| Heart rate | Increased 15%–25% |
| Vascular pressures and resistances | |
| Central venous pressure | No change |
| Femoral venous pressure | Increased 15%–50% |
| Pulmonary capillary wedge pressure | No change |
| Systemic resistance | Decreased 20% |
| Pulmonary resistance | Decreased 35% |
| Intravascular volume | Increased 35%–45% |
| Plasma volume | Increased 45%–55% |
| Erythrocyte volume | Increased 20%–30% |
Increased Cardiac Output
Maternal cardiac output increases to 35% above prepregnancy values by the end of the first trimester, with continued increases up to 50% above prepregnancy values from the end of the second trimester through term gestation. An increase in both stroke volume (by 25%–30%) and heart rate (by 15%–25%) contributes to this increased cardiac output. Further changes are also noted in labor and the postpartum period. During the first stage of labor, cardiac output increases an additional 10% to 25% above term pregnancy levels, and continues to increase to 40% above term cardiac output during the second stage of labor. Immediately after delivery there is an autotransfusion from the contracting uterus, a release of aortocaval compression with decreased systemic vascular resistance, and a return of lower extremity venous blood. These changes result in a maternal cardiac output 80% to 100% greater than prelabor values. Such a dramatic increase in cardiac output can place patients with cardiovascular pathology, such as fixed valvular stenosis, heart failure, or pulmonary hypertension, at significant risk. By approximately 24 hours postpartum, cardiac output has returned to term, prelabor levels, and by 2 weeks postpartum has continued to decline significantly toward prepregnancy values. At 3 to 6 months postpartum, maternal cardiac output has returned to normal prepregnancy levels.
Decreased Systemic Vascular Resistance
A 20% decrease in systemic vascular resistance occurs in an uncomplicated pregnancy at term, resulting in a 5% to 20% decrease in blood pressure by 20 weeks GA (with diastolic blood pressures decreasing to a greater degree than systolic). After midgestation, blood pressures begin to increase toward prepregnancy values. Although there is an increase in femoral venous pressure influenced by the gravid uterus and maternal positioning, central venous pressures and pulmonary capillary wedge pressures do not change significantly during pregnancy.
Aortocaval Compression
Supine hypotension, a decrease in blood pressure caused by aortocaval compression from the gravid uterus in the supine position, occurs in approximately 15% of term gestations. “Supine hypotension syndrome” is defined as a decrease in mean arterial pressure greater than 15 mm Hg and an increase in heart rate greater than 20 beats/min, with symptoms of diaphoresis, nausea, vomiting, and changes in mentation. Significant occlusion of the vena cava in the supine position causes a decrease in stroke volume and cardiac output by 10% to 20%, and contributes to lower extremity venous stasis, edema, varices, and increases the risk of venous thrombosis. Blood return increases through the engorged epidural, azygous, and vertebral veins. Aortoiliac arterial compression is also present in 15% to 20% of women at term.
Increased peripheral sympathetic nervous system activity is a compensatory reflex that reduces supine hypotension in the setting of aortocaval compression by increasing systemic vascular resistance in an effort to maintain blood pressure despite a reduced cardiac output. This sympathetic tone can be impaired in the setting of general or neuraxial anesthesia, resulting in an exacerbation of hypotension related to supine positioning. Maternal blood pressure measured from the upper extremities does not necessarily accurately reflect the reduced arterial pressure of the lower extremity vasculature caused by aortocaval compression. Therefore, even without measured hypotension or symptoms, uterine and placental blood flow may be significantly impaired. Prolonged impairment may lead to the development of fetal acidosis.
Because of these considerations, the supine position is avoided during neuraxial or general anesthesia. A leftward tilt helps to relieve compression of the inferior vena cava and abdominal aorta by the uterus, thus maintaining uterine and placental blood flow and lessening the degree of hypotension. An elevation of the right hip by 10 to 15 cm using a blanket, wedge, or table tilt can accomplish this.
Intravascular Volume and Hematology
Changes to the renin-angiotensin-aldosterone system during the first trimester result in sodium reabsorption and water retention. A 25% decrease in albumin and a 10% decrease in total protein are observed at term, with a resulting decrease in colloid osmotic pressure from 27 mm Hg to 22 mm Hg. The plasma volume increases approximately 50% above prepregnancy values at term, while the red cell volume increases only about 25%. This results in a “physiologic anemia” of pregnancy, with typical hemoglobin (Hb) levels decreasing toward 11 g/dL at term. Despite this physiologic anemia, total oxygen delivery is not reduced, as the increased cardiac output compensates for the decreased oxygen-carrying capacity. Plasma volume is increased by 1000 to 1500 mL at term, which offsets the 300 to 500 mL blood loss associated with a vaginal delivery or the 800 to 1000 mL blood loss with cesarean delivery. The uterine contraction after delivery results in an autotransfusion of approximately 500 mL and counteracts the delivery blood loss.
A white blood cell (WBC) count greater than 10,000 WBC/mm 3 of blood is normal in pregnancy and unrelated to infectious causes. There is often a neutrophilia at term, which can increase to more than 30,000 WBC/mm 3 during labor. These values normalize 4 to 5 days postpartum.
Pregnancy results in a hypercoagulable state. There is a 20% decrease in prothrombin time and partial thromboplastin time caused by significant increases in factor I (fibrinogen) and factor VII and less substantial increases in other factors ( Table 37.2 ). There are also decreases in factors XI and XIII and antithrombin III. Platelet levels are typically unchanged or slightly (10%) decreased at term secondary to plasma dilution, and “a routine platelet count is not necessary in the healthy parturient.” However, 6% to 10% of normal pregnancies are complicated by thrombocytopenia (platelet count <150,000/mm 3 ). The most common cause is gestational thrombocytopenia, which accounts for more than 70% of these cases. Gestational thrombocytopenia is a diagnosis of exclusion, and other clinically important pathologies such as idiopathic thrombocytopenic purpura, severe preeclampsia, and hemolysis with elevated liver enzymes and low platelet count (HELLP syndrome) should be ruled out. In cases of gestational thrombocytopenia, platelet levels typically remain above 100,000/mm 3 in the majority of cases and rarely decrease below 70,000/mm 3 .
| Procoagulant factors | |
| Increased | I, VII, VIII, IX, X, XII, von Willebrand factor |
| Decreased | XI, XIII |
| Unchanged | II, V |
| Anticoagulant factors | |
| Increased | None |
| Decreased | Antithrombin III, protein S |
| Unchanged | Protein C |
Patients with inherited disorders of coagulation (e.g., factor V Leiden, von Willebrand disease) may have significant changes in their clotting profile during pregnancy, and multidisciplinary management with an anesthesiologist, obstetrician, and hematologist is essential for optimal care.
Clinical Examination and Evaluation
The physiologic changes of pregnancy on the cardiovascular system result in changes in clinical findings and studies. Often a benign, grade 2/6 systolic ejection murmur is appreciated over the left sternal border secondary to mild tricuspid regurgitation from annular dilation and increased intravascular volume. Cardiac auscultation demonstrates an accentuated S 1 as well as increased splitting because of the dissociated closures of the tricuspid and mitral valves. An S 3 is often noted in the third trimester, and an S 4 is heard in a minority of patients owing to increased volume and turbulent flow. Neither the S 3 or S 4 typically has clinical significance. Changes in the electrocardiogram and echocardiography are outlined in later text ( Table 37.3 ). Pregnant patients with chest pain, syncope, severe arrhythmias, high-grade murmurs, or clinically significant shortness of breath should undergo appropriate clinical evaluation and workup. In addition, patients with preexisting cardiac disease should have consultation with a multidisciplinary care team including an anesthesiologist and cardiologist early in pregnancy to optimize their care and minimize risk.
| Clinical Examination in Pregnancy | Findings |
|---|---|
| Electrocardiography |
|
| Echocardiogram |
|
Respiratory Changes
Increases in minute ventilation and oxygen consumption, decreased lung reserve, and upper airway changes are seen in normal pregnancies ( Table 37.4 ).
| Pulmonary Component | Changes at Term (vs. Prepregnancy Values) |
|---|---|
| Minute ventilation | Increased 45%–50% |
| Tidal volume | Increased 40%–45% |
| Respiratory rate | Increased 0–15% |
| Oxygen consumption | Increased 20% |
| Lung capacities and volumes | |
| Total lung capacity | Decreased 0–5% |
| Vital capacity | No change |
| Functional residual capacity | Decreased 20% |
| Expiratory reserve volume | Decreased 20%–25% |
| Reserve volume | Decreased 15%–20% |
Minute Ventilation and Oxygenation
Minute ventilation is increased by 45% to 50% by the end of the first trimester to compensate for the increased oxygen demand and carbon dioxide production by the fetus and placenta. The respiratory rate is only minimally increased, whereas an increase in tidal volume contributes significantly to the increased minute ventilation. Despite a decrease in maternal arterial partial pressure of carbon dioxide (Pa co 2 ) to 30 mm Hg during the first trimester as a result of these respiratory changes, arterial pH is only slightly alkalotic, at 7.42 to 7.44, because of a compensatory increase in renal excretion of bicarbonate (HCO 3 − 20–21 mEq/L) at term. The increased maternal ventilation results in a room air arterial partial pressure of oxygen (Pa o 2 ) slightly greater than 100 mm Hg early in gestation. However, later during the pregnancy, Pa o 2 returns toward prepregnancy values secondary to small airway collapse and intrapulmonary shunting.
These respiratory changes occur during an increased maternal oxygen consumption of 20% at term. During the first stage of labor oxygen consumption increases 40% above term prelabor values, and during the second stage it increases 75% above prelabor values.
With pregnancy, there is an increase in the maternal oxygen partial pressure associated with 50% Hb saturation (P 50 ) from 27 mm Hg to 30 mm Hg as shown in Fig. 37.2 . This right shift in the maternal Hb oxygen dissociation curve, combined with the relatively left-shifted fetal P 50 of 18 mm Hg, facilitates oxygen transfer from the mother to the fetus.
Lung Volumes
As the uterus enlarges during pregnancy, the diaphragm is forced cephalad, resulting in similarly decreased expiratory reserve volume and residual lung volume. These changes cause a decrease in functional residual capacity (FRC) starting after the first trimester, with a 20% decrease in FRC present at term (see Table 37.4 ). Because closing capacity (CC) remains unchanged, there is a reduced FRC/CC ratio with more small airway closure, reduced lung volumes, and increased propensity for atelectasis in the supine position. Decreased FRC with increased minute ventilation results in a faster rate of alveolar gas exchange and a more rapid change in inhaled anesthetic concentration. Additionally, upon induction of general anesthesia, desaturation occurs more rapidly in a pregnant patient because of decreased oxygen reserve (decreased FRC) as well as increased oxygen consumption. Preoxygenation with 100% oxygen for 3 minutes or four maximal volume breaths immediately before induction is necessary to minimize the chance of significant hypoxia secondary to these physiologic changes.
Airway
Vascular engorgement of the oropharyngeal, laryngeal, and tracheal mucosa results in increased tissue friability and edema, thereby increasing the risk of bleeding with upper airway manipulation and difficulty in intubation and ventilation. Attempts at laryngoscopy should be minimized, and a smaller cuffed endotracheal tube (6.0–6.5 mm) should be used. Suctioning and placement of airways should be done with care to prevent bleeding, and nasal instrumentation should generally be avoided. In patients with preeclampsia, upper respiratory tract infections, and those who have been actively pushing in the second stage of labor, airway edema is often more severe as a result of increased venous pressure. Additionally, the weight gain and increased breast tissue make laryngoscopy more challenging. Positioning should be optimized before laryngoscopy, and backup airway equipment should be immediately available. A recent multiinstitutional database review found the rate of failed intubation for cesarean delivery with general anesthesia to be 1 : 533.
Gastrointestinal Changes
Beyond midgestation the maternal stomach and pylorus are shifted cephalad by the enlarged uterus, thus repositioning the intraabdominal esophagus in the thoracic cavity and decreasing the competence of the esophageal sphincter. Progesterone and estrogen levels contribute to a reduced esophageal sphincter tone. Gastrin is secreted by the placenta, resulting in increased gastric hydrogen ion secretion and decreased gastric pH. These physiologic changes and the increased gastric pressure from the gravid uterus increase the frequency of acid reflux during pregnancy, the risk of aspiration of gastric contents, and development of acid pneumonitis upon induction of general anesthesia. Additionally, gastric emptying is impaired with the onset of labor as well as with pain, anxiety, and opioid administration. The use of epidural local anesthetics alone does not slow gastric emptying, but the use of bolus doses of epidural fentanyl does. Although delayed after delivery gastric emptying returns to prepregnancy function by 18 hours postpartum.
Because of the delayed gastric emptying seen in labor, as well as the physiologic changes detailed above, all women in labor are considered to have a full stomach and are at increased risk for pulmonary aspiration of stomach contents upon induction of general anesthesia. Metoclopramide can significantly decrease gastric volume within 15 minutes of administration. However, prior opioid administration decreases this effect. Some physicians advocate for the use of H 2 -histamine receptor blockers, which increase gastric pH within an hour in pregnant women. The combination of antacids and H 2 -histamine receptor antagonists is more effective in reducing gastric pH than antacids alone or no pharmacologic intervention. Current American Society of Anesthesiologists guidelines for obstetric anesthesia state “…before surgical procedures (e.g., cesarean delivery or postpartum tubal ligation), consider the timely administration of nonparticulate antacids, H 2 -receptor antagonists, and/or metoclopramide for aspiration prophylaxis.”
Hepatic and Gallbladder Changes
During pregnancy, aspartate aminotransferase, alanine aminotransferase, and bilirubin levels rise to the upper limits of normal, while plasma protein concentrations are reduced. The decreased protein concentrations can cause elevated free serum levels of highly protein-bound drugs. Alkaline phosphatase levels will double in pregnancy secondary to placental production. Of note, incomplete gallbladder emptying and changes in bile composition increase the risk of gallbladder disease during pregnancy. Although acute cholecystitis is not more common in pregnancy, gallstones are reported in 1% to 3% of pregnant patients and about 0.1% of pregnant patients develop acute cholecystitis.
Butyrylcholinesterase (pseudocholinesterase), which is produced by the liver, is decreased in activity by 25% to 30% starting at the 10th week of gestation through 6 weeks postpartum. This decreased activity is not likely to cause a significant prolongation of neuromuscular blockade achieved with succinylcholine, although muscle strength should be thoroughly assessed before extubation.
Renal Changes
By the end of the first trimester, renal blood flow and glomerular filtration rate are increased by 50% to 60% and remain elevated for 3 months postpartum. The upper limits of blood urea nitrogen and serum creatinine values are about 50% lower during pregnancy, as the clearance of creatinine, urea, and uric acid is increased. Urine protein and urine glucose levels are often elevated from decreased renal tubular resorption capacity, and 300 mg protein or 10 g glucose in a 24-hour urine collection is considered the upper limits of normal during pregnancy.
Neurologic Changes
Pregnant women are considered to have a decreased minimum alveolar concentration (MAC) for inhalational anesthetics, as evidenced by a 40% MAC reduction in animal studies and a 28% MAC reduction in humans during the first trimester. The etiology of this reduction in MAC is unknown but is potentially related to progesterone. In contrast to these findings, an electroencephalographic study suggests that anesthetic effects of sevoflurane on the brain are similar between pregnant and nonpregnant patients. In addition, rates of intraoperative awareness are increased during cesarean delivery with general anesthesia compared with other general anesthesia cases, and reducing standard anesthetic levels in stable obstetric patients may not be prudent.
Pregnant patients are also more sensitive to local anesthetics, and a reduced amount is required for neuraxial anesthesia. Anatomic changes to the nervous system during pregnancy include engorgement of the epidural veins, decreased size of the epidural space, and decreased volume of cerebrospinal fluid. The lower volume of these spaces may result in greater spread of local anesthetics. However, research suggests that the decreased local anesthetic requirements observed during pregnancy occur in the first trimester, before significant anatomic changes in the neuraxial system are seen, suggesting a biochemical role for the increased nerve sensitivity. Cerebral spinal fluid pressure remains unchanged until labor, at which point it is increased with contractions and pushing in the second stage.
Uteroplacental Physiology
The placenta, composed of both maternal and fetal tissues, is the means by which physiologic exchange between mother and fetus occurs. It is made up of basal and chorionic plates separated by the intervillous space, into which maternal blood is delivered via the uterine arteries and then the spiral arteries as shown in Fig. 37.3 . Two umbilical arteries return fetal blood to the placenta and then become umbilical capillaries that cross the chorionic villi. After placental exchange occurs at the chorionic villi, nutrient-rich and waste-free blood is returned from the placenta to the fetus via an umbilical vein.
Uterine Blood Flow
In the nonpregnant state, uterine blood flow is approximately 100 mL/min. At term, uterine blood flow reaches 700 mL/min, or about 10% of the cardiac output. At term, about 80% of uterine blood flow perfuses the intervillous spaces within the placenta, while the other 20% supports the myometrium. Autoregulation of uterine blood flow is minimal, as the uterine vessels are fully dilated throughout pregnancy. Therefore maternal cardiac output, uterine vascular resistance, and uterine perfusion pressure dictate uterine and placental blood flow. A decrease in systemic vascular resistance, from either general or neuraxial anesthesia, or maternal hypotension from aortocaval compression or hypovolemia, may result in a decreased placental perfusion pressure. In the absence of maternal hypotension, neuraxial anesthesia does not affect uterine blood flow. There may also be a decrease in uterine perfusion pressure from venocaval compression in the supine position, prolonged or frequent contractions, prolonged Valsalva maneuver during pushing, or significant hypocapnia (Pa co 2 < 20 mm Hg) from hyperventilation associated with pain. Decreases in uterine perfusion may result in placental hypoperfusion and cause fetal hypoxemia and acidosis.
Placental Exchange
Oxygen Transfer
In addition to uterine and fetal blood flow, oxygen delivery from mother to fetus is affected by the oxygen partial pressure gradient, diffusion capacity of the placenta, acid-base status of maternal and fetal blood (Bohr effect), and maternal and fetal Hb concentrations and oxygen affinities. Fetal Hb has a greater affinity for oxygen compared with maternal Hb, as shown in Fig. 37.2 . These differences create an oxygen transfer gradient to the fetus. The oxygen delivery to the fetus is primarily dependent on the rate of blood flow on each side of the placenta rather than barriers to diffusion. Fetal Pa o 2 is typically 20 to 40 mm Hg but can reach up to 60 mm Hg if the mother is breathing 100% oxygen, although typical fetal tissue arterial Hb saturation remains below 65% even with maternal inspired oxygen near 100%. This is the maximal fetal Pa o 2 because a substantial amount of oxygen is extracted from maternal blood before arrival at the fetoplacental unit. Concern has been expressed for potential fetal harm from generation of free radicals based on chemical markers in the fetal umbilical circulation with maternal hyperoxia. However, further studies have noted this concern to be unwarranted, with free radical activity independent of inspired oxygen, but dependent on the labor course and mode of delivery. In the setting of decreased oxygen delivery to the fetus, fetal oxygen consumption is maintained by increased oxygen extraction until maternal oxygen delivery is approximately 50% of expected. In cases of nonreassuring fetal heart rate patterns, use of maternal supplemental oxygen has been demonstrated to significantly increase fetal oxygenation (based on fetal pulse oximetry) and is likely beneficial, but no randomized clinical trials have addressed the use of maternal oxygen treatment for fetal distress.
Drug Transfer
Drugs and other molecules in the maternal circulation smaller than approximately 1000 Da are primarily exchanged with the fetus by diffusion. The rate of transfer depends on maternal-to-fetal concentration gradients, maternal protein binding, molecular weight, lipid solubility, and ionization. The degree of fetal transfer for a specific drug is typically presented as a ratio of concentration in the umbilical vein to the maternal artery. Although all drugs transfer across the placenta to some degree, a few are significantly limited. Nondeloparizing neuromuscular blockers have high molecular weights and are poorly lipid-soluble, thus limiting their capacity for crossing the placenta and reaching the fetus. Succinylcholine has a low molecular weight but is also highly ionized and poorly lipid-soluble, which limits its ability to cross the placenta unless given in large doses. Similarly, unfractionated heparin, low-molecular-weight heparins, and glycopyrrolate are highly ionized and do not cross the placenta in significant amounts. In contrast, volatile anesthetic agents, benzodiazepines, local anesthetics, and opioids all have relatively low molecular weights and readily cross the placenta.
Fetal blood has a lower pH than maternal blood. When weakly basic drugs, such as local anesthetics and certain opioids, cross the placenta in a non-ionized state, they can become ionized in the relatively acidic fetal circulation. These newly ionized molecules are unable to readily diffuse back to the maternal circulation via the placenta, thus accumulating in the fetal circulation and potentially reaching levels higher than the maternal concentration. This is called “ion trapping” and can be more extreme during fetal distress, when the fetal pH is lower than normal. Unintended intravascular injection of local anesthetics can cause extremely high fetal concentrations of these drugs, which may result in bradycardia, ventricular arrhythmias, acidosis, and severe cardiac depression. The upcoming sections “Labor Analgesia” and “Anesthesia for Cesarean Delivery” further discuss placental transfer and fetal uptake considerations of specific agents.
Fetal Circulation and Physiology
Fetal circulation is significantly different from that of a newborn ( Fig. 37.4 ). Oxygen-rich blood from the placenta passes through the umbilical vein directly to the fetal liver, where the circulation splits and flows into both the ductus venosus (20%–30% of flow) and portal sinus circulation. It then passes into the inferior vena cava and enters the right atrium. The majority of this blood flows through the foramen ovale, into the left atrium, then the left ventricle, and empties into the aorta (a small portion travels through the pulmonary arteries to perfuse lung tissue). This shunted portion traveling through the foramen ovale has the highest oxygen levels and directly perfuses the brain (carotid arteries) and heart (coronary arteries). Fetal deoxygenated blood returning from the superior vena cava and lower extremities is directed toward the right ventricle and pulmonary trunk. The majority of this blood flow passes through the ductus arteriosus, into the descending aorta, and perfuses the lower extremities and hypogastric arteries. Deoxygenated fetal blood returns to the placenta via two umbilical arteries.
Two-thirds of fetal blood volume is within the placenta. During the second and third trimesters, the fetal blood volume is approximately 110 to 160 mL/kg, and after midgestation can be estimated from GA: Estimated fetal blood volume (mL) = 11.2 × GA − 209.4. Hemoglobin F (HbF) is the primary oxygen carrier in the developing fetus, with a gradual shift from HbF to adult Hb (HbA) production starting at 32 weeks’ gestation. Hb levels in the fetus typically increase from 11 g/dL (17 weeks GA) to about 18 g/dL in a term newborn.
The fetal heart rate is the primary determinant of fetal cardiac output, as the fetal myocardium is less compliant than adult myocardium, operating near the upper end of the Frank-Starling curve and less responsive to changes in preload. Normal fetal cardiac output is 425 to 550 mL/kg/min throughout gestation.
The fluid-filled lungs of the fetus may potentially impair ventricular filling, thus preventing an increase in cardiac output after an increase in preload. Fetal lung epithelium produces more than 100 mL/kg per day of fluid that facilitates pulmonary development. This pulmonary fluid leaves via the trachea and is either swallowed by the fetus or becomes part of the amniotic fluid.
The immature fetal liver is able to synthesize coagulation factors, the concentration of which increases with GA. These coagulation factors do not cross the placenta into maternal circulation, and are not as effective at clot formation compared with those factors found in adults. About 75% of umbilical venous blood initially passes through the fetal liver. Drugs in the umbilical blood thus undergo initial hepatic metabolism (first-pass metabolism) before these substances reach the fetal brain or heart. Although these fetal metabolic enzymes are less functional that those of adults, most drugs are still significantly metabolized. Additionally, drugs entering the fetal circulation enter the inferior vena cava via the ductus venosus. This blood is mixed with the venous blood returning from the lower extremities and pelvic viscera of the fetus, thus further diluting any concentrations of drugs passed through the placenta.
By 18 weeks’ gestation, the fetus exhibits a neuroendocrine stress response to noxious stimuli. This response occurs at the level of the spinal cord and brainstem, as thalamocortical connections necessary for the perception of pain are not present until after 24 to 26 weeks’ gestation. During fetal surgery, opioids are directly administered to the fetus to decrease the physiologic stress from the procedure.
Preeclampsia
Preeclampsia is a pathophysiologic disease specific to pregnancy that affects approximately 5% of pregnant women in the United States. Although the exact underlying cause remains unknown, it is characterized by endothelial dysfunction and an upregulation of cytokines. These changes affect the physiology of all organ systems and is associated with numerous maternal and fetal complications. Diagnostic criteria for preeclampsia with and without severe features are shown in Fig. 37.5 .
