Endoscopy and Sedation : Official journal of the American College of Gastroenterology | ACG

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Endoscopy and Sedation

Hepner, David L. MD, MPH1; Siddiqui, Uzma D. MD, FACG2

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The American Journal of Gastroenterology 117(10S):p 33-38, October 2022. | DOI: 10.14309/ajg.0000000000001965

INTRODUCTION

A large number of pregnant patients undergo endoscopic procedures with anesthesia, with the goal of resolving or managing medical conditions. An understanding of maternal physiologic changes and how these changes alter the pharmacokinetic and pharmacodynamic properties of different medications help anesthesia providers and gastroenterologists balance potential risks with benefits.

Pregnancy represents a unique state in which dramatic physiologic alterations begin shortly after conception and progress throughout pregnancy. Although these changes are usually well tolerated by parturients, gastroenterologists performing endoscopy on pregnant patients should be aware of the impact of these changes because even subtle aberrations can have a lasting impact on both maternal and fetal health (see Supplementary Digital Content, https://links.lww.com/AJG/C659). We will review maternal physiologic and pharmacologic changes occurring during pregnancy, examine the impact of anesthetic interventions, and allow an understanding of how to minimize risks to the parturient.

Physiologic alterations during pregnancy and anesthetic considerations

Respiratory.

The physiologic changes of pregnancy have a dramatic impact on the administration of general anesthesia for endoscopic procedures, and these changes must be considered for the safety of the parturient and the developing fetus. During pregnancy, there is an increase in the metabolic demand of both, the pregnant patient and the fetus, and this, along with anatomical and hormonal influences, accounts for the relatively larger increase in maternal respiratory and cardiovascular function (1).

Pregnancy results in progressive increases in oxygen consumption and minute ventilation along with a reduced back-up oxygen supply, which comes from decreased residual volume and functional residual capacity (1). Parturients are further prone to hypoxia because of a tendency for closure of small airways in dependent areas when lung volumes fall below closing capacity (2). This decrease in functional residual capacity becomes more profound with certain body positions (e.g., supine, Trendelenburg, and lithotomy) and is further reduced by obesity and general anesthesia (3).

Anesthetic considerations

The increased metabolic demands and anatomical changes can make adequate oxygenation and perfusion of the parturient and their fetal-placental unit a constant challenge during maternal general anesthesia for endoscopic procedures. During periods of apnea or hypoventilation, the parturient is more rapidly prone to the development of hypoxia and hypercarbia. Even after adequate preoxygenation, the PaO2 in an apneic, anesthetized parturient falls by about 80 mm Hg more per minute than in nonpregnant patients (4). Furthermore, airway management by face mask, laryngeal mask, or tracheal intubation can be technically difficult because of increased anteroposterior chest wall diameter, breast enlargement, laryngeal edema, and weight gain that affect the soft tissues of the neck. Smaller endotracheal tubes, gentle laryngoscopy, and equipment to deal with difficult intubations are recommended in the care of parturients.

The induction and emergence from anesthesia with inhaled agents occurs faster in parturients than in nonpregnant patients. It is important to take this into account because a faster induction coupled with a decreased inhalational anesthetic requirement make parturients susceptible to the hypotensive effects of the volatile anesthetic agents (5).

Airway

One fundamental principle underlying the safe practice of anesthesia is to maintain a continuously patent airway to facilitate adequate pulmonary gas exchange. In excess of 85% of respiratory related, closed malpractice claims involve patient outcomes, which include brain injury or death (6–8). Estimates are that up to 30% of deaths solely attributable to anesthesia result from unsuccessful airway management (6). With increasing gestational age, maternal airway mucosa becomes edematous, abdominal contents shift with increasing uterine mass, the diaphragm rises, and the laryngeal structures shift to a more anterior position. Inability to view oral structures accounts for one-third of anesthetic-related maternal mortality and is 7 times greater than that in the general surgical population.

Cardiovascular effects

Cardiovascular function is appropriately increased during pregnancy to meet the increased metabolic demands and oxygen requirements. Cardiac output continues to increase throughout pregnancy until it reaches a level of 50% higher than in nonpregnant patients, with the majority of the increase in cardiac output during early pregnancy being a function of the increased heart rate during the first and second trimesters (9). Heart rate increases 15%–25% above prepregnancy levels and remains stable after the second trimester, but stroke volume progressively increases by 25%–30% by the end of the second trimester and remains stable until term (10,11).

Anesthetic considerations

Maternal blood flow and pressure are directly linked to fetal perfusion through the placenta, and uterine blood flow represents about 10% of maternal cardiac output. Prompt treatment of hypotension is also very important because uteroplacental blood flow is not autoregulated, and a decrease in maternal blood pressure will ultimately cause a decrease in blood flow to the fetus. Neo-synephrine intravenously (40–80 mcg) should be the vasopressor of choice used to treat maternal hypotension unless contraindicated or not effective. In such a situation, ephedrine intravenously (5–10 mg) is an alternative option. Careful attention to the volume status of the parturient is imperative during endoscopy cases. Aggressive volume hydration, the normal decrease in colloid oncotic pressure that occurs during pregnancy, the decrease in colloid oncotic pressure postpartum, and the use of tocolytic agents, such as magnesium and beta agonists, may all predispose the parturient to pulmonary edema.

Hematology/coagulation

Blood volume is increased by 35% by the second and third trimesters of pregnancy (12). Red blood cell volume increases in response to the increased erythropoietin levels, which are also affected by hormonal changes in progesterone, prolactin, and placental lactogen. The increase in plasma volume exceeds the increase in red blood cell volume, leading to a drop in the hemoglobin (Hgb) and hematocrit (Hct) concentrations by midgestation (physiologic anemia).

Pregnancy is a state associated with increased coagulability. This hypercoagulable state reflects the increased platelet aggregation, elevated plasma coagulation factors, decreased coagulation inhibitors (protein C and S), and decreased fibrinolysis. Appropriate measures should be taken to prevent venous thrombosis associated with pregnancy and immobility after surgical procedures.

Anesthetic considerations

The parturient has lowered hemoglobin and hematocrit values as a result of the greater increase in plasma volume than in red blood cell volume, and higher values may signify preeclampsia or dehydration.

Postsurgical parturient immobility combined with the hypercoagulable state of pregnancy requires that measures, such as pneumatic boots, subcutaneous heparin prophylaxis, and ambulation, be taken to prevent venous thrombosis in the postoperative period.

Gastrointestinal system

The gastrointestinal system undergoes important physiological changes. These changes have critical implications for the parturient undergoing general anesthesia for endoscopic procedures because these changes may predispose to acid aspiration syndrome. Although the overall incidence of aspiration is low, 73% of maternal deaths related to anesthesia in parturients are the result of aspiration in the setting of difficult intubations (13). Reductions in the incidence of this complication are attributed, in part, to prophylactic measures taken to reduce the risk and attention to the physiologic changes.

The gravid uterus slowly causes the stomach to be displaced upward toward the left hemidiaphragm. There is an axis rotation of 45° to the right from the normal vertical position, and the intra-abdominal section of the esophagus is displaced into the thorax. These anatomical shifts cause a reduction in lower esophageal sphincter tone throughout pregnancy, predisposing to esophageal reflux and aspiration (14). Progesterone may also have an influence in relaxing the lower esophageal sphincter tone and reducing esophageal peristaltic time. The incidence of reflux increases with gestational age, with 72% of pregnant patients reporting symptoms by the third trimester. Gastroesophageal reflux is more common with advanced maternal age and correlates with increasing parity (15). There is no correlation with race, body mass index, or weight gain during pregnancy (15). Studies have confirmed that the acid content of the stomach is not increased during gestation and is in fact associated with a decreased plasma gastrin concentration (16). Gastric acid secretory rates are decreased during early gestation, reach their lowest levels at 30 weeks' gestation, and increase to normal by term (16). In addition, there is no change in gastric volume in the second and third trimesters of pregnancy when compared with controls (17). There are no significant pH differences when comparing nonpregnant patients undergoing anesthesia for surgery and parturients having elective cesarean sections (17). Studies using various techniques including ultrasound, applied potential tomography, dye techniques, and gastric impedance techniques have not been able to show a significant delay in gastric emptying during the second or third trimester of pregnancy when compared with nonpregnant controls (18–20).

The most recent guidelines of the American Society of Anesthesiologists have become more liberal on the issue of clear liquids before procedures (21). These changes reflect recent data showing that, during the stress of labor, while feeding results in a significant increase in gastric residual volume, clear liquids are rapidly emptied from the stomach. The gastric emptying of water and isotonic sports drinks are not delayed at term or during labor (22,23). On the other hand, opioid drugs given parenterally cause a marked delay in gastric emptying (24).

Anesthetic considerations

The data presented above would suggest that transit times and acid levels may not be significantly different between pregnant and nonpregnant patients. However, the anatomical changes associated with a gravid uterus and a decreased lower esophageal sphincter tone may predispose the parturient to a potentially life-threatening acid aspiration pneumonia. It is for this reason that solids are avoided for 8 hours, the use of antacids and gastric promotility drugs is encouraged, and a rapid sequence induction is used for parturients undergoing general anesthesia. Fasting guidelines range from 6 hours for a light nonfat meal to 8 hours for other type of foods. There is emerging evidence that clear liquids until 2 hours before surgery increase gastric motility. Nonparticulate antacids are recommended because the pH of the inhaled contents is an important factor in limiting lung damage should acid aspiration occur (25). Metoclopramide is helpful not only by increasing transit time but also by increasing lower esophageal sphincter tone (26).

Renal system

Pregnancy is accompanied by an increase in renal function. Renal blood flow increases 70%–85% and the glomerular filtration rate (GFR) increases 40%–50% over nonpregnant values. The increased GFR leads to lower serum creatinine and blood urea nitrogen values, with creatinine levels of 0.5–0.6 mg/dL and blood urea nitrogen levels of 8–9 mg/dL being normal in pregnancy. Even a slight elevation in these values may indicate renal dysfunction in the pregnant patient. There is no change in urinary protein values with pregnancy, but an aminoaciduria does occur. Plasma bicarbonate levels are decreased approximately 4 meq/L to compensate for the progesterone-induced respiratory alkalosis.

A maternal adaptation to pregnancy includes resetting of the volume and osmoreceptors, induced by a reduction in the vascular tone leading to early changes in plasma osmolality and GFR. After this initial adaptation, other volume-regulating mechanisms such as the renin-angiotensin-aldosterone system, pregnancy hormones, and atrial natriuretic peptide adapt to the rising blood volume (27). Maternal estrogen and progesterone production is thought to be responsible for enhanced plasma renin and aldosterone activity, respectively (renin-angiotensin-aldosterone system), which increases sodium absorption and water retention.

Anesthetic considerations

Pregnant patients have lower serum creatinine and blood urea nitrogen levels, and even modest increases to the high end of normal should be a cause for concern because they may indicate a degree of renal failure and lead to a prolongation of the effect of renally excreted drugs. Pharmacologic changes during pregnancy, in part mediated by physiologic renal changes during pregnancy, are discussed in the following section.

PHARMACOLOGIC CHANGES DURING PREGNANCY

Physiologic changes in pregnancy can lead to altered pharmacokinetics and pharmacodynamics of many anesthetic drugs. Absorption of orally administered medications can be altered because of changes in gastric emptying times. An increase in total body water and adipose tissue and a decrease in plasma protein levels can alter many drugs' volume of distribution. Although an increased renal blood flow and GFR can enhance the elimination of renally excreted drugs, hepatic metabolism of drugs may be inhibited by a competition with steroid hormones during pregnancy.

Induction agents

The blood concentration of propofol required in early pregnancy (6–12 weeks) at which parturients would not respond to a verbal command was not different from nonpregnant controls, indicating that early pregnancy does not alter the propofol pharmacokinetics (28). Propofol does cross the placenta, and neonatal blood levels can be clinically significant if delivery occurs within 10 minutes of administration, although delivery is not typically a planned event immediately after endoscopy (29).

Neuromuscular blocking agents

Although serum cholinesterase activity decreases 30% during pregnancy, recovery from a dose of 1 mg/kg of succinylcholine is not prolonged in pregnant patients (30). Succinylcholine has a very low placental transfer because of its low lipid solubility and high degree of ionization (30).

Pregnant patients may be more sensitive to the action of nondepolarizing agents, with the administration of vecuronium resulting in a more rapid onset and delayed recovery of neuromuscular block when compared with nonpregnant control patients (31). This prolonged action of vecuronium persists into the postpartum period for at least 4 days and has been explained by physiologic changes in hepatic blood flow and competition for hepatic uptake by pregnancy hormones interfering with the clearance of vecuronium (32). Unlike the limited clinical relevance of pregnancy on induction agents, the clinical duration of vecuronium in term and postpartum patients is twice that in nonpregnant patients (33).

Volatile anesthetics

Pregnant patients are more sensitive to the anesthetic action of the volatile agents (34). This may lead to a deeper level of anesthesia than predicted during endoscopic procedures and a relative overdose associated with maternal cardiac depression and hypotension.

Volatile anesthetic agents are known to produce uterine relaxation with increasing levels of volatile inhalation agents producing a greater degree of uterine relaxation (35).

PROCEDURE-RELATED CONSIDERATIONS

Anatomic changes of pregnancy

The expanding uterus creates a mechanical effect, usually starting during the middle of the second trimester. It can lead to aortocaval compression by impeding blood flow in major vascular structures and displace the intra-abdominal structures (e.g., shifts and rotates the stomach up into the thorax). Left uterine displacement is recommended to minimize aortocaval compression and associated hypotension (Table 1).

T1
Table 1.:
Procedure-related considerations

The increased anterior-posterior diameter of the chest and weight gain may affect positioning and airway management, and soft-tissue edema increases the risk for nerve entrapment and for a difficult airway. Nasal intubation should be avoided because of the increased vascularity of mucous membranes with the potential for epistaxis.

Timing of endoscopy

Any elective nonobstetric procedure should be delayed until after delivery to limit maternal and fetal risks. Nonemergent (but nonelective) procedures should be performed in the 2nd trimester, if possible. Emergent procedures should be performed according to the maternal disease process because the primary goal is to preserve the life of the pregnant patient. The diagnosis of pregnant patients requiring nonobstetric procedures is specific for the disease process requiring intervention. The diagnosis of abdominal conditions is often delayed during pregnancy, increasing the risk of maternal and fetal morbidity.

Prophylaxis

It is important to provide thromboprophylaxis, aspiration prophylaxis, and antibiotic prophylaxis when indicated. The following antibiotics are relatively contraindicated during pregnancy: tetracyclines are avoided because of the suppression of fetal bone growth and staining of teeth; fluoroquinolones are avoided because of animal studies showing adverse effects on cartilage development; trimethoprim is generally avoided early in pregnancy because of concerns of congenital malformations and aminoglycosides carry a risk of ototoxicity and nephrotoxicity but are still considered relatively safe (36). Intraoperative anesthetic management focuses on preventing maternal hypoxia, maintaining maternal pH in a normal range, treating hypotension quickly and aggressively, using a left uterine displacement to avoid aortocaval compression, using regional anesthesia when feasible, preparing for the possibility of a difficult airway, and providing thromboprophylaxis, aspiration prophylaxis, and antibiotic prophylaxis when warranted.

Maternal monitoring

The American Society of Anesthesiologists standard monitors and capnography should be used, and supplemental oxygen should be provided. Continual monitoring for the presence of expired carbon dioxide shall be performed unless invalidated by the nature of the patient, procedure, or equipment. Quantitative monitoring of the volume of expired gas is strongly encouraged.

Fetal monitoring

Whenever a pregnant patient undergoes nonobstetric procedures, communications between the obstetrical provider, proceduralist, anesthesiologist, and neonatologist are important to coordinate management. Surgery should be performed in the 2nd trimester when possible, and fetal monitoring should be performed when appropriate and when personnel are available to interpret the results (37). At a minimum, the fetal heart rate and uterine activity should be monitored both before and after surgery. Continuous fetal monitoring should be used for all fetuses of viable age if technically feasible and agreed to by the patient. The decision to use intraoperative fetal monitoring should be individualized to each patient and procedure. Fetal monitoring can assist in optimizing maternal positioning and cardiorespiratory management, even if the fetus in nonviable. If used, appropriately skilled persons to interpret the fetal heart monitor should be present. It can be difficult to distinguish changes in the fetal heart rate caused by anesthetic drugs from changes due to fetal hypoxia. If used to influence a decision to deliver the fetus, appropriately skilled persons should be available to perform emergent cesarean delivery, if indicated.

Maternal and fetal effects of medications given for sedation during endoscopy

Deep sedation can be safely used for selected pregnant patients undergoing endoscopy procedures. Clinical doses of midazolam, fentanyl, and propofol have not been associated with congenital malformations. No anesthetic agents have been identified as having teratogenic potential in humans when clinical doses are used. Short exposure to anesthesia in utero has not been shown to cause future learning disabilities in humans. Propofol and etomidate have a long history of safety during pregnancy. Induction agents are rapidly transferred across the placenta, but healthy fetuses metabolize single doses of induction agents quickly. Induction doses of propofol do not need to be reduced in early pregnancy. No evidence supports the teratogenicity of opioids in humans, specifically in infants exposed in utero throughout pregnancy. All opioids cross the placental barrier and have effects on the fetus (e.g., respiratory depression). Opioids and induction agents can decrease fetal heart rate variability. This most often is a result of an anesthetized fetus and should not be a source of concern if no other abnormalities are present.

The current consensus is that benzodiazepines as a group are not teratogenic, and a single dose during anesthesia is safe, with midazolam being the preferred choice in this class (38). A review of drug therapy in pregnancy showed that although benzodiazepines (specifically diazepam) were initially thought to cause oral clefts, this class of medication has subsequently been proven safe for use in pregnancy (39). Muscle relaxants have no effect on uterine relaxation. These agents are large, charged molecules that do not readily cross the placental barrier. Pregnant patients are more sensitive to nondepolarizing neuromuscular blocking drugs, despite increased hepatic clearance. Neostigmine and glycopyrrolate are quaternary ammonium compounds that have minimal placental transfer and have been used effectively in combination during pregnancy (40).

Postoperative management

The postoperative management of pregnant patients having undergone nonobstetric procedures depends on gestational age and may include fetal heart rate and uterine activity monitoring during the postoperative recovery. Adequate analgesia should be obtained with acetaminophen, opioids (oral or parenteral), local anesthetics, or a combination of these. Nonsteroidal inflammatory agents should be avoided or used with caution in the third trimester because of their propensity to constrict and possibly close the ductus arteriosus. Venous thromboprophylaxis should be considered in all patients, especially those with limited mobility.

Sedation during lactation

The risks of sedation in lactating patients are similar to those for any adult, but consideration must be given to the use of sedative medications because they are transferred to the milk. Most procedural sedatives can be safely used in lactating patients because they are short acting and quickly cleared from lactating patients' circulation, achieving clinically insignificant quantities in milk. It is acceptable to breastfeed after procedural sedation provided the lactating patient is awake, alert, and able to feed. There is no need to pump and discard breastmilk. No interruption in breastfeeding is needed for fentanyl or propofol, but lactating patients should consider waiting at least 4 hours after receiving midazolam before breastfeeding (41–44). Some guidelines indicate that breastfeeding can be resumed after a single dose of midazolam as long as the woman has recovered from the sedation, given that blood levels are expected to be low after a small dose of midazolam (41).

NATIONAL GUIDELINES

The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice Guidelines for Nonobstetric Surgery During Pregnancy has produced guidelines for nonobstetric procedures that reiterate the main points already stated in this review (45).

CONCLUSION

A large number of patients undergo anesthesia and endoscopy during pregnancy and lactation periods for nonobstetric conditions. Fetal risks associated with procedures include spontaneous abortion, preterm labor, growth restriction, and low birth weight. Clinical studies suggest that anesthesia and procedures during pregnancy do not increase the risk of congenital abnormalities. Elective procedures should be postponed until after delivery. Nonemergent procedures should ideally be performed in the second trimester with special attention to aspiration prophylaxis, thromboprophylaxis, left uterine displacement, and fetal monitoring. The anesthetic management of the pregnant surgical patient should focus on the avoidance of hypoxemia, hypotension, acidosis, and hyperventilation.

Supplementary oxygen must always be given during vulnerable periods to maintain oxygenation. End-tidal CO2 should be maintained at 32–34 mm Hg. Excessive hyperventilation may impair uterine blood flow, whereas hypoventilation may increase the risk of fetal acidosis. Uterine displacement to relieve aortocaval compression should be used whenever possible to maintain uterine blood flow by placing the patient in a left lateral position (e.g., wedge under the right hip).

Aspiration prophylaxis is recommended preoperatively at all stages of pregnancy and may include a clear nonparticulate antacid (e.g., sodium citrate), a histamine (H2) receptor blocker, and dopamine receptor antagonist that stimulates gastric motility and increases lower esophageal sphincter tone (e.g., metoclopramide). Antibiotic prophylaxis should be administered according to the guidelines for the procedure.

Close communication between colleagues in the fields of obstetrics, anesthesiology, and gastroenterology is essential. Although there are no clear guidelines for the exclusion of candidates for endoscopic procedures, any maternal coexisting disease that would place the patient at a greater risk for morbidity or mortality would be excluded from consideration.

CONFLICTS OF INTEREST

Guarantor of the article: David L. Hepner, MD, MPH.

Financial support: This article appeared as part of the ACG Monograph on GI Diseases and Endoscopy in Pregnancy and Postpartum Period. Unrestricted educational grants to support the monograph have been provided to the ACG Institute for Clinical Research & Education from UCB, Inc., Ferring Pharmaceuticals, Inc., and Janssen Biotech, Inc.

Potential competing interests: U.D.S. is a consultant for Medtronic, Boston Scientific, and Olympus America. D.L.H. has no conflicts of interest.

BEST PRACTICE RECOMMENDATIONS

  • ✓ Clinical studies suggest that anesthesia and procedures during pregnancy do not increase the risk of congenital abnormalities.
  • ✓ Elective procedures should be postponed until after delivery.
  • ✓ Nonemergent procedures should ideally be performed in the second trimester with special attention to aspiration prophylaxis, thromboprophylaxis, left uterine displacement, and fetal monitoring.
  • ✓ The anesthetic management of the pregnant surgical patient should focus on the avoidance of hypoxemia, hypotension, acidosis, and hyperventilation.
  • ✓ Close communication between colleagues in the fields of obstetrics, anesthesiology, and gastroenterology is essential.

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