Respiratory System

The respiratory system undergoes profound physiologic changes during early pregnancy. Increased progesterone concentration stimulates respiratory efforts by increasing the sensitivity of the respiratory center to carbon dioxide. Minute ventilation increases by at least 15% by 12 weeks’ gestation and by 25% by 20 weeks’ gestation. This results from an increase in tidal volume (respiratory rate is unchanged) and exceeds the increase in oxygen consumption. The result is a respiratory alkalosis with maternal arterial partial pressure of carbon dioxide decreasing to 30 to 33 mm Hg (4.0 to 4.4 kPa) by 10 to 12 weeks’ gestation. Moreover, maternal arterial partial pressure of oxygen increases to 106 to 108 mm Hg (14.1 to 14.4 kPa) in the first trimester. Decreased bicarbonate concentration partially compensates for the modest respiratory alkalosis that results from the physiologic hyperventilation, leading to a maternal pH that is slightly above normal (i.e., approximately 7.44). There is little or no change in lung capacities during the first half of pregnancy. Women in early pregnancy who undergo mechanical ventilation require increased minute ventilation.

Cardiovascular System

The cardiovascular system also undergoes profound changes early in pregnancy. During the first trimester, cardiac output increases by about 15% above prepregnancy values; by the early third trimester, cardiac output is about 30% above prepregnancy values. Systemic vascular resistance decreases 30% by 8 weeks’ gestation. Maternal mean arterial pressure decreases approximately 6  mm Hg at 16 to 24 weeks’ gestation and returns to normal near term.

In a typical pregnancy, aortocaval compression could begin to occur after 18 to 20 weeks’ gestation, when the uterine fundus reaches the umbilicus and is potentially large enough to compress the aorta and vena cava when the patient is supine. Of note, the frequency of aortocaval compression in pregnant women in the supine position has recently been questioned with a magnetic resonance imaging study showing no aortocaval compression in 10 healthy full-term pregnant women in the supine position. Nonetheless, most experts agree that when the uterine size is equivalent to an 18- to 20-week gestation, the application of left uterine displacement should be performed if possible. This can be achieved by elevating the right hip approximately 15 degrees off midline with a wedge or blankets. The need for left uterine displacement may occur earlier in gestation in the presence of multiple gestation, polyhydramnios, or gestational trophoblastic disease.

Blood volume increases throughout pregnancy. The average prepregnancy blood volume of 4350 mL (76 mL/kg) increases to 4700 mL (81 mL/kg) at 12 weeks’ gestation, to 5500 mL (89 mL/kg) at 20 weeks’ gestation, and to approximately 6600 mL (97 mL/kg) at term. The increase in blood volume is primarily the result of greater plasma volume because red blood cell volume increases to a smaller degree (27 mL/kg). Because pregnant women have an expanded blood volume, most can typically tolerate a blood loss of 500 to 1500 mL in early pregnancy without requiring blood transfusion, if the blood loss is replaced with an adequate volume of crystalloid or colloid.

Gastrointestinal System

An increased progesterone level causes relaxation of the lower esophageal sphincter tone as early as the first trimester. Fasting gastric volume is approximately 30 mL in both nonpregnant women and women in early pregnancy. Metoclopramide 10 mg, administered intravenously 15 to 30 minutes before anesthesia, can reduce this volume by 50%. Obesity does not delay gastric emptying in nonlaboring pregnant women. In a study of 100 pregnant women undergoing general anesthesia by mask at 6 to 22 weeks’ gestation, a pH electrode showed reflux of gastric contents into the esophagus in 17% of patients. Most episodes of reflux occurred in patients who experienced hiccups. Only 2% had regurgitation of gastric contents into the pharynx, and no patient demonstrated clinical evidence of pulmonary aspiration.

General anesthesia may be safely administered by means of a mask or a laryngeal mask airway (LMA) by experienced anesthesia providers in selected obstetric patients during early pregnancy. Many anesthesia providers are comfortable managing an airway without tracheal intubation until 18 to 20 weeks’ gestation, when the uterus moves out of the pelvis. The latter movement leads to anatomic and intragastric pressure changes that predispose to gastroesophageal reflux. Some anesthesia providers prefer to intubate the trachea of pregnant women who require general anesthesia as early as 12 to 14 weeks’ gestation, given that hormonal changes leading to sphincter relaxation are present early in pregnancy. Patients who receive general anesthesia during the first half of pregnancy should be intubated if they are at increased risk for gastric content aspiration (e.g., history of gastroesophageal reflux, morbid obesity, solid food ingestion within 8 hours). Pharmacologic prophylaxis (e.g., sodium citrate, a histamine-2 (H ₂ ) receptor antagonist, and/or metoclopramide) is likely to further reduce the risk for aspiration pneumonia (see Chapter 28 ). Neuraxial anesthesia is associated with a lower risk for aspiration than general anesthesia.

Nervous System

During early pregnancy, the nervous system is more sensitive to general and local anesthetic agents. The minimum alveolar concentration (MAC) for volatile anesthetic agents is decreased by approximately 30%, although the underlying mechanism for this change is unclear. A study that compared patients undergoing cesarean delivery with nonpregnant patients undergoing elective gynecologic surgery found no difference between groups in electroencephalographic (EEG) measures during general anesthesia with similar end-tidal concentrations of sevoflurane. Because it is well-proven that MAC decreases in pregnancy, this study implies that MAC in pregnant women may not correlate well with depth of anesthesia. Conversely, another study found that pregnant women with elevated baseline serum progesterone concentrations had lesser sevoflurane consumption when the anesthetic was titrated to vital signs and a bispectral index (BIS) value. Further research is needed to clarify the effects of pregnancy and progesterone on MAC and depth of anesthesia as measured by BIS or EEG.

Clinical Presentation

The clinical presentation of the patient with an ectopic pregnancy depends on the gestational age, site of implantation, and extent of hemorrhage. Before rupture, the signs and symptoms are often subtle. Classic clinical signs of impending rupture or a ruptured tubal pregnancy include abdominal or pelvic pain (95%), delayed menses (75% to 95%), and vaginal bleeding (60% to 80%). Vaginal bleeding results from the breakdown and shedding of the decidual lining of the uterine wall, which is probably associated with decreased hormone production by the corpus luteum and inadequate human chorionic gonadotropin (hCG) production by the ectopic trophoblast. Pain often precedes vaginal bleeding. Patients with hemorrhage (with or without tubal rupture) may experience dizziness or syncope, may have the urge to defecate because of the effect of blood in the cul-de-sac, and may have shoulder pain from diaphragmatic irritation by intra-abdominal blood.

Physical findings include abdominal tenderness with or without rebound (80% to 95%), a uterus that is smaller than expected for dates (30%), and a tender adnexal mass (30% to 50%). A bulging cul-de-sac suggests hemoperitoneum. With significant hemorrhage, there may be signs of shock, but some patients may appear hemodynamically stable despite a hemoperitoneum volume of 1000 to 1500 mL. As with many young women, compensation for blood loss can occur with minimal symptoms initially followed by rapid decompensation.

Diagnosis

Ectopic pregnancy should be excluded in any patient who has pelvic pain and a positive pregnancy test. In a woman of reproductive age, the symptoms of ectopic pregnancy must be differentiated from (1) a threatened, inevitable, or incomplete pregnancy loss; (2) infection after attempted abortion; (3) pelvic inflammatory disease; (4) a degenerating fibroid; (5) appendicitis and other gastrointestinal diseases; (6) ovarian torsion; (7) a ruptured or bleeding ovarian cyst; (8) a trapped retroverted uterus in pregnancy; and (9) nephrolithiasis.

Pregnancy of unknown location (PUL) exists when the hCG is positive and presumed due to pregnancy but the site of implantation has yet to be determined. Ultrasonography can reliably confirm the presence of an intrauterine pregnancy; however, the ectopic pregnancy itself may be difficult to visualize. Transvaginal ultrasonography is the current modality of choice. A gestational sac with a yolk sac is the earliest confirmation of an intrauterine pregnancy, while ultrasonographic visualization of an adnexal mass and free fluid with absence of an intrauterine pregnancy is specific for ectopic pregnancy. Unfortunately, ultrasonographic visualization of an ectopic pregnancy has poor sensitivity.

Despite the challenges of early diagnosis of ectopic pregnancy, prompt treatment decreases morbidity and mortality. If concern exists for ectopic pregnancy with a PUL, serial hCG measurements spaced 48 hours apart can help clarify the viability of the pregnancy regardless of location. For a viable pregnancy, the increase in hCG over 48 hours should be at least 53%. A decrease in hCG by at least 10% suggests a nonviable pregnancy. In these scenarios, the decision to intervene or manage the nonviable pregnancy conservatively is based on the clinical situation and the woman’s preference. An abnormal rise (< 53% in 48 hours) or a plateau in the hCG value often indicates a nonviable pregnancy, but can also be seen with a vanishing twin where a viable pregnancy remains. Serial hCG measurements and transvaginal ultrasonography along with symptoms are considered when determining viability versus nonviability of a PUL.

A serum progesterone concentration greater than 25 ng/mL is usually associated with a viable pregnancy. A concentration less than or equal to 5 ng/mL usually indicates a nonviable pregnancy but cannot distinguish a spontaneous pregnancy loss from an ectopic pregnancy. Most ectopic pregnancies are associated with progesterone levels between 5 and 25 ng/mL, a fact that limits the usefulness of this test.

Uterine curettage can be performed when nonviability of a PUL is established. Identification of trophoblastic villi confirms loss of an intrauterine pregnancy. Absence of villi signals either a complete spontaneous pregnancy loss (confirmed by rapidly decreasing hCG concentration) or an ectopic pregnancy. Culdocentesis has been replaced in most all instances by transvaginal ultrasonography for detection of hemoperitoneum.

Obstetric Management

Management options for ectopic pregnancy are expectant, medical, and surgical. Management choice depends on the “activity” of the ectopic pregnancy, which is determined by symptoms and diagnostic findings.

Expectant management is preferred in “very less active” ectopic pregnancy or PUL with no symptoms, an hCG less than 1500 mIU/mL, and a plateauing trend in hCG values. Treatment with methotrexate does not improve resolution and is reserved for women in whom hCG levels fail to resolve. Very low positive hCG levels can have etiologies other than pregnancy. Very less active ectopic pregnancy may be difficult to localize surgically.

Medical management with methotrexate is a preferred option in “less active” ectopic pregnancy. Less active ectopic pregnancy is characterized by an hCG less than 5000 mIU/L and no fetal cardiac activity in an asymptomatic woman who is hemodynamically stable. Methotrexate , a folate antagonist, interrupts DNA synthesis and thus inhibits the growth of trophoblastic cells. It can be administered intramuscularly in one or more injections to women who screen negative for kidney, liver, and hematologic disease.

From day 4 to day 7 after methotrexate treatment, a decrease in hCG level of 15% must be present to consider the treatment successful. Otherwise, repeat methotrexate treatment or surgical intervention is required. Follow-up and close monitoring until the hCG level reaches nonpregnant values is imperative because of the risk for rupture and hemorrhage. Side effects of methotrexate can be severe and include abdominal pain, vomiting, stomatitis, severe neutropenia, and pneumonitis. Compared with surgical management, medical management of ectopic pregnancy provides no difference in overall tubal preservation, tubal patency, risk for repeat ectopic pregnancy, or success of future pregnancies.

Surgical management depends on the location of the pregnancy, the hemodynamic stability of the patient, the availability of equipment, and the surgeon’s expertise. Most often, laparoscopy is performed to confirm the diagnosis by locating the ectopic pregnancy and then proceeding with treatment. For tubal ectopic pregnancies, a salpingostomy, salpingotomy, or salpingectomy (usually partial) is performed by means of laparoscopy or laparotomy. To aid hemostasis during laparoscopic removal of the ectopic pregnancy, some obstetricians inject dilute vasopressin into the surface of the fallopian tube. This agent causes marked blanching of the tube and results in a relatively bloodless surgical field. If the vasopressin is mixed incorrectly or accidentally injected intravenously, a marked increase in maternal blood pressure may occur.

A laparotomy is indicated if the surgeon is not trained in operative laparoscopy, laparoscopic removal is anticipated to be difficult (e.g., tube diameter greater than 6 cm or an interstitial location of the ectopic pregnancy), or there is uncontrolled bleeding. Laparotomy should be performed immediately if there is hemodynamic instability; these cases often require a partial or total salpingectomy. If a partial salpingectomy is performed, tubal repair may be performed primarily or during a second operation. Although some experts have noted that outcomes from randomized trials comparing salpingostomy and salpingectomy are lacking, the risk for persistent ectopic pregnancy may be higher after salpingostomy than after salpingectomy.

Interstitial, cervical, cesarean scar, and abdominal ectopic pregnancies as well as early placenta accreta may present significant diagnostic and therapeutic challenges, resulting in delay of diagnosis and treatment. There is potential for massive hemorrhage because of disruption of organs and adjacent tissues. The desire to preserve fertility may result in greater blood loss as tissue and organ preservation are attempted.

Interstitial pregnancy often goes unrecognized and may manifest as uterine wall rupture, massive hemorrhage, and shock. Conservative surgery (e.g., cornual resection) may be attempted, but hysterectomy may be required if uterine damage is severe.

Cervical pregnancy can result in massive hemorrhage because of the inability of the cervix to contract. In the past, most cervical pregnancies necessitated hysterectomy to control hemorrhage. More current management options that are more likely to maintain fertility include (1) methotrexate therapy; (2) local excision; (3) cerclage and tamponade; (4) ligation of the hypogastric arteries or the cervical branches of the uterine arteries; and (5) angiographic embolization of the uterine arteries followed by a dilation and curettage procedure (see later discussion).

Cesarean scar pregnancy occurs when a gestational sac implants in the uterine scar defect (niche) at the site of a previous cesarean delivery. Cesarean scar pregnancy has a high complication rate. Although relatively rare, its incidence is rising with increasing cesarean delivery rates and currently may be as high as 1 in 1800 pregnancies. Jurkovic et al. described two types of cesarean scar pregnancies: (1) implantation on the scar with enlargement into the uterine cavity and (2) implantation into a scar defect with growth into the myometrium. Depending on its progression, the former type may grow normally or may be treated medically. Scar implantation results in an increased risk for early uterine rupture and severe hemorrhage at delivery. Growth into the myometrium may lead to eventual rupture and bleeding in the first trimester; prompt surgical intervention is preferred over medical management in this situation.

The incidence of early placenta accreta is also rising because of increasing cesarean delivery rates. It is defined as penetration of the placenta into the myometrium, which is discovered in the first or early second trimester. Because of similarities in pathogenesis, it is thought—although not confirmed—that early placenta accreta may develop from cesarean scar pregnancy. A review found that 15 of 47 (32%) patients with early placenta accreta had spontaneous uterine rupture, in most cases followed by bleeding and shock, which resulted in laparotomy, hysterectomy, or uterine artery embolization. Although the gestational age is early, it is imperative that the anesthesia team is aware of the risk for hemorrhage during surgical intervention for cesarean scar pregnancy and early placenta accreta.

Abdominal pregnancy is defined as implantation in the peritoneal cavity, not including the fallopian tubes, ovaries, or ligaments, and is associated with a high incidence of maternal morbidity and fetal demise. In a series of advanced extrauterine pregnancies, Worley et al. identified 10 women who presented with extrauterine pregnancies beyond 18 weeks’ gestation, of whom three met the diagnostic criteria for abdominal pregnancy. All patients had difficult surgery, nine patients required blood transfusion, and only five fetuses survived after complicated courses.

Diagnosis of abdominal pregnancy can be difficult, historically being missed in as many as one of nine cases. The diagnosis was missed before delivery in four of the ten cases in the series of Worley et al. Abdominal pain, vaginal bleeding, symptoms consistent with partial bowel obstruction, shock, or death may be the first indication of this unusual type of pregnancy. Ultrasonography is useful but may miss the diagnosis in more than 50% of cases. Magnetic resonance imaging may prove to be a more sensitive diagnostic tool.

If an extrauterine pregnancy is suspected in early gestation, laparoscopy can be used to diagnose and remove gestational products. If the extrauterine pregnancy is not identified until late gestation, it is associated with decreased placental perfusion (which typically results in fetal growth restriction) and oligohydramnios (which often results in pulmonary hypoplasia and anatomic deformities). In 1993, Stevens reviewed published cases of abdominal pregnancy since 1809 and found that 63% of infants survived when born after 30 weeks’ gestation.

Management of an advanced extrauterine pregnancy consists of laparotomy and delivery of the fetus. Once the fetus is delivered, management of the placenta is controversial and fraught with hazard. Removal of the placenta is associated with massive hemorrhage, prolonged and complicated surgery (e.g., bowel resection), and an increased risk for maternal mortality. A decision to leave the placenta in situ results in a higher risk for infectious morbidity as well as a potential greater need for additional surgery. In the series of Worley et al., the placenta was left in situ in two patients, both of whom developed serious complications. The site of placental implantation and the ability to adequately ligate the blood supply often dictates the obstetrician’s decision about management of the placenta.

Heterotopic pregnancy describes the simultaneous occurrence of an ectopic and an intrauterine pregnancy. Historically, it was thought to occur in 1 in 30,000 spontaneous pregnancies. However, in patients utilizing assisted reproductive technologies, 0.2% to 3% of pregnancies may be heterotopic. Difficulty visualizing the entire fallopian tube on ultrasonography, combined with normal or slightly elevated hCG measurements (i.e., low serum levels from the ectopic pregnancy combined with normal levels from the intrauterine pregnancy), make the early diagnosis of heterotopic pregnancy difficult. This diagnosis should be suspected in cases in which clinical signs of an ectopic pregnancy and a confirmed intrauterine pregnancy coexist. In most cases, the ectopic pregnancy is removed surgically. Alternatively, transvaginal ultrasonography-guided injection of potassium chloride into the ectopic pregnancy has been performed successfully; however, as many as 55% of patients may require subsequent surgery. The patient often retains the normal intrauterine pregnancy to term. Patients with ectopic pregnancies who are Rh-negative should receive Rh ₀ (D) immune globulin.

Anesthetic Management

Patients with an unruptured tubal pregnancy usually have normal intravascular volume, minimal bleeding before and during surgery, and low anesthetic and surgical risk. Anesthetic considerations for laparoscopy or laparotomy are summarized in Box 16.1 . Although most patients may prefer general anesthesia, neuraxial anesthesia with an upper sensory level to at least T4 may be an alternative in selected patients. Shoulder pain from diaphragmatic irritation may occur and can be treated with intravenous analgesics (e.g., fentanyl 1 to 2 µg/kg).

Box 16.1

Suggested Anesthetic Techniques for Laparoscopy or Laparotomy for Patients with Ectopic Pregnancy

General Considerations

• •
  

  Blood typing and antibody screening

  
  
• •
  

  Aspiration prophylaxis if patient has a full stomach

  
  
• •
  

  Routine noninvasive monitors

  
  
• •
  

  Large-bore peripheral intravenous catheter

  
  
• •
  

  Urinary catheter

  
  
• •
  

  If major bleeding has occurred or is expected to occur (e.g., ruptured tubal, interstitial, cervical, uterine scar, or abdominal ectopic pregnancy):

  
  
  
  
  • •
    

    Two or more intravenous catheters

    
    
  • •
    

    Typing and cross-matching of blood

    
    
  • •
    

    Consideration of invasive hemodynamic monitoring (e.g., arterial catheter, central venous catheter)

    
    
  • •
    

    Consideration of intraoperative cell salvage

  
  
  
  
• •
  

  Although general anesthesia is usually preferred, neuraxial (spinal or epidural) anesthesia may be considered for hemodynamically stable patients with a low likelihood of significant hemorrhage (i.e., unruptured tubal pregnancy):

  
  
  
  
  • •
    

    Intravenous fluids, vasopressors, supplemental oxygen, and minimal sedation given as clinically indicated.

  
  

General Anesthesia

• •
  

  Rapid-sequence induction with cricoid pressure if the patient has a full stomach

  
  
• •
  

  Induction: propofol or thiopental (ketamine or etomidate should be considered if patient is hemodynamically unstable)

  
  
• •
  

  Muscle relaxant

  
  
• •
  

  Tracheal intubation

  
  
• •
  

  Maintenance: volatile or intravenous anesthetic agents

  
  
• •
  

  Placement of an oral gastric tube, performance of suctioning, and removal of the tube

  
  
• •
  

  Reversal of neuromuscular blockade and extubation when the patient is awake and responds to verbal commands

Spinal Anesthesia

• •
  

  Single injection with a small-gauge pencil-tip spinal needle: hyperbaric bupivacaine 12 mg with fentanyl 10 to 25 µg to achieve T4 sensory blockade

Epidural Anesthesia

• •
  

  Placement of mid-lumbar epidural needle and catheter

  
  
• •
  

  Lidocaine 2% with epinephrine 5 µg/mL (1 : 200,000), approximately 20 mL, and fentanyl 100 µg, injected incrementally, to achieve T4 sensory blockade

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