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Gastrointest Endoscopy Clin N Am

16 (2006) 1 – 31

Sedation and Analgesia for Gastrointestinal


Endoscopy during Pregnancy
Mitchell S. Cappell, MD, PhD, FACG
Division of Gastroenterology, Department of Medicine, Albert Einstein Medical Center,
Klein Professional Building, Suite 363, 5401 Old York Road, Philadelphia, PA 19141, USA

Although gastrointestinal endoscopy is recognized as a safe, well-tolerated,


and standard procedure in the general population [1–3], the risks, benefits, and
indications during pregnancy are less well known. In addition to the usual patient
risks, endoscopy during pregnancy raises the unique issue of fetal safety.
The fetal risks of endoscopy during pregnancy have been the subject of several
clinical studies [4–9] and clinical reviews [10–13]; however, a separate review of
the fetal safety of anesthetic medications is important and timely. First, anesthetic
medications comprise an important, if not the most important, risk factor to
the fetus during endoscopy, particularly during the first trimester [14–16].
Medications can be directly teratogenic or can indirectly cause fetal distress
secondary to effects on the mother such as cardiac arrhythmias [17–20], systemic
hypotension [17], and transient hypoxia [21]. Respiratory compromise and
hypoxia, from administered anesthetic medications [22], can be compounded at
esophagogastroduodenoscopy (EGD) or endoscopic retrograde cholangiopan-
creatography (ERCP) by vagally mediated bronchospasm, laryngeal impinge-
ment during esophageal intubation [19,21,22], and pulmonary aspiration of
gastric contents [22,23]. Second, analysis of fetal risks can help the physician
avoid, restrict, or replace potentially teratogenic endoscopic medications. This is
becoming more important because of the recent introduction of several alternative
anesthetic agents for endoscopy. Third, a physician who is well informed about

E-mail address: mscappell@yahoo.com

1052-5157/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.giec.2006.01.007 giendo.theclinics.com
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the fetal risks of analgesic and sedative medications can advise and guide the
patient during informed consent. Fourth, review of standard principles and
practice guidelines can improve anesthetic safety during endoscopy (eg, by ma-
ternal assessment before endoscopy and maternal monitoring during endoscopy).
Fifth, malpractice judgments are sometimes astronomically large in cases of
poor fetal outcome [24]. Documentation of the relative safety of endoscopic
medications during pregnancy, when properly indicated and appropriately ad-
ministered, can prevent unnecessary litigation.
Knowledge about the safety of endoscopic anesthetics during pregnancy is,
however, incomplete. The published studies are retrospective. Despite current
uncertainties, the physician who evaluates a patient referred for gastrointestinal
endoscopy during pregnancy can be provided with guidelines. This article criti-
cally and comprehensively analyzes the fetal safety of endoscopic sedation
and analgesia.

Anesthesia for endoscopy

Sedation and analgesia are usually indicated for gastrointestinal endoscopic


procedures in the general population to reduce anxiety and minimize pain, except
for flexible sigmoidoscopy for which sedation and analgesia are optional. The
level of sedation varies according to the procedure; the most profound level of
sedation is needed for ERCP with sphincterotomy or other therapeutic procedures
[25]. These anesthesiologic principles also apply to endoscopy during pregnancy,
but administration of the minimal effective dose of sedative and analgesic is
emphasized. Thus, sedation and analgesia may be reasonably avoided altogether
for flexible sigmoidoscopy during pregnancy if so desired by the patient.
Various endoscopic procedures have been performed during pregnancy, par-
ticularly EGD, flexible sigmoidoscopy, and ERCP (Table 1; [4,5,9,26–35]).
Pregnant patients frequently suffer from gastrointestinal conditions that constitute
strong indications for endoscopy. More than 12,000 pregnant women per year in
America have a strong indication for EGD, such as acute upper gastrointestinal
bleeding. More than 6000 pregnant women per year have a strong indication for
sigmoidoscopy or colonoscopy, such as nonhemorrhoidal lower gastrointestinal
bleeding. About 1000 pregnant women per year have a strong indication for
therapeutic ERCP, such as complicated choledocholithiasis [7,36,37]. A prac-
ticing gastroenterologist, therefore, encounters a pregnant patient who has a
strong indication for gastrointestinal endoscopy about once a year.
Diagnostic and therapeutic endoscopy may be particularly valuable during
pregnancy because: (1) diagnosis by barium radiography is relatively contrain-
dicated because of radiation teratogenesis [38]; (2) prescription of gastrointestinal
drugs based on empirical data and without a definitive endoscopic diagnosis
is undesirable because of medication teratogenesis [39]; and (3) the alternative
therapy—gastrointestinal surgery—for active gastrointestinal bleeding or com-
sedation and analgesia during pregnancy 3

Table 1
Endoscopic procedures generally requiring anesthesia during pregnancy
Selected references for
Endoscopic procedure procedure during pregnancy
Diagnostic procedure
EGD [5]
Flexible sigmoidoscopy (anesthesia optional) [4]
Colonoscopy [4]
ERCP [26,27]
Endoscopic ultrasound [28,29]
Therapeutic procedure
EGD with variceal sclerotherapy or banding [5,30]
EGD with control of hemostasis [5,31]
EGD with endoscopic dilatation of a stricture [32]
ERCP with sphincterotomy [9]
ERCP with stent placement [33]
PEG [34,35]
Endoscopic ultrasound with drainage of a pancreatic pseudocyst [28,29]
Highly uncommon endoscopic procedures during pregnancy
ERCP with placement of a nasobiliary tube
Colonoscopy with polypectomy
Colonoscopy with endoscopic mucosal resection
EGD with endoscopic mucosal resection
Endoscopic ultrasound with celiac ganglion axis ablation
Abbreviations: EGD, esophagogastroduodenoscopy; ERCP, endoscopic retrograde cholangiopancrea-
tography; PEG, percutaneous endoscopic gastrostomy.

plicated choledocholithiasis is undesirable because of the risk of fetal wast-


age [40].

Physiological changes during pregnancy: anesthesiologic and endoscopic


implications

Abdominal assessment during pregnancy is modified by displacement of ab-


dominal viscera by the expanding gravid uterus [41]. In the nonpregnant patient,
external compression and detection of endoscopic transillumination in the right
lower quadrant help verify cecal intubation during colonoscopy. These signs can
be unreliable during advanced pregnancy because the cecum is displaced by the
enlarged gravid uterus [42]. However, visualization of the appendix and of the
ileocecal valve remain as reliable markers of cecal intubation during pregnancy.
In the nonpregnant patient, colonic overdistention from excessive air insufflation
during colonoscopy manifests as abdominal distention. This sign may be difficult
to recognize during advanced pregnancy because of the enlarged gravid uterus. In
the nonpregnant patient, external abdominal compression is often applied during
colonoscopy to facilitate cecal intubation. This compression should be applied
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gently and away from the uterus in patients who are in advanced pregnancy to
avoid uterine trauma.
The fetus is particularly sensitive to maternal hypoxia and hypotension [37].
For example, maternal hypotension from bleeding during pregnancy leads
to maternal cathecholamine release, which produces uterine vasoconstriction,
placental hypoperfusion, and potential fetal injury [43]. A relatively normal
maternal blood pressure does not guarantee fetal perfusion, and maternal tolerance
of transient hypoxia or hypotension does not guarantee fetal well being [43].
Maternal hypotension and hypoxia should, therefore, be avoided and aggres-
sively treated during endoscopy. Measures to avoid maternal hypotension during
endoscopy include adequate hydration before the procedure, transfusion of
packed erythrocytes (as necessary) for patients who present with gastrointestinal
bleeding, limited use of medications that can produce dehydration such as
diuretics, limited use of antihypertensive medications before the procedure, use of
the minimal effective dose of analgesics and sedatives during the procedure, and
avoidance of colonic overdistention during colonoscopy. Patients who receive
colonic lavage for colonoscopy should receive adequate hydration preprocedure.
Hypotension during the procedure should be treated by (1) prompt intravenous
hydration with normal saline or a similarly high osmolar solution, (2) a change to
the patient’s position to help drain blood from the lower extremities to perfuse
the vital organs, (3) restricted use of analgesics and sedatives, and (4) con-
sideration of aborting the endoscopic procedure. In particular, the colonoscopist
may be well advised to terminate a difficult and painful colonoscopy dur-
ing pregnancy.
The hematocrit is not a reliable indicator of bleeding severity in the general
population because of the lag between blood loss and hematocrit decline. The
hematocrit is an even less reliable indicator during pregnancy because of the
conflicting effects of intravascular fluid accumulation and increased total
erythrocyte mass during normal pregnancy [44,45]. The central venous pressure
is usually lower in the pregnant woman. Fluid, including transfusions of packed
erythrocytes when indicated, should be aggressively administered to pregnant
patients who undergo endoscopy for gastrointestinal bleeding because of the
extraordinary fetal sensitivity to hypoperfusion, the difficulty in assessing volume
status during pregnancy, and the usually satisfactory cardiac function of preg-
nant patients.
In the general population, patients are often placed in the supine position
during colonoscopy. The physician should avoid placing the pregnant patient
with gastrointestinal bleeding in the supine position during colonoscopy because,
in this position, the enlarged gravid uterus compresses the inferior vena cava,
decreases venous return, exacerbates maternal hypotension, and decreases uterine
perfusion [46]. Simply turning the patient to the left side to displace the uterus
may relieve this compression, improve venous return, and normalize the blood
pressure [41,46].
Maternal hypoxia during endoscopy is prevented by the administration of
supplemental oxygen by nasal cannulae, use of the minimal effective dose of
sedation and analgesia during pregnancy 5

sedatives and analgesics, optimization of cardiac and pulmonary status before the
procedure, avoidance of colonic overdistention during colonoscopy, avoidance
of oropharyngeal trauma during upper endoscopic intubation, aspiration of the
gastric lake during upper endoscopy, peroral aspiration as necessary to remove
oropharyngeal secretions, and placement of the patient in a decubitus position
with the patient’s head slightly elevated to prevent pulmonary aspiration.
Nasogastric aspiration in patients who have active upper gastrointestinal bleeding
before EGD helps prevent pulmonary aspiration during endoscopy and helps
clear the endoscopic field. This maneuver is particularly important during preg-
nancy because the pregnant state promotes nausea and vomiting, particularly
during the first trimester, as a result of the effects of gestational sex hormones
and gastric compression by the gravid uterus [47].
To reduce the risk of preterm uterine contractions or premature labor, avoid
mechanical trauma to the uterus during endoscopy, especially from looping
during colonoscopy, and avoid ischemic insult to the uterus from maternal
hypotension or hypoxia. Premature uterine contractions during endoscopy may
require tocolytics, such as magnesium sulfate or terbutaline [48,49].

Team approach

The endoscopic management of complicated gastrointestinal disease during


pregnancy, particularly symptomatic cholelithiasis, is improved by the formation
of a team that may include a gastroenterologist, obstetrician, anesthesiologist,
surgeon, and radiation physicist. Such a team is ideally located at tertiary medical
centers where the requisite experience and expertise is available. Pregnant pa-
tients who present to community hospitals with complicated gastrointestinal
disease may be referred to these tertiary medical centers.

Preprocedure anesthesiologic evaluation

Although gastroenterologists routinely administer sedation and analgesia for


endoscopy without anesthesiologic assistance in the general population, gastro-
enterologists should consider anesthesiologic consultation for pregnant patients
because of concern about medication teratogenicity. Anesthesiologic assistance
is recommended during pregnancy when the endoscopy is performed in the first
trimester because of the increased teratogenic risk; in the late third trimester or
with impending delivery because of the risk of premature labor; in a high-risk
pregnancy; for high-risk, invasive, and prolonged endoscopic procedures such as
therapeutic ERCP; and in a pregnant patient who has severe gastrointestinal
bleeding, choledocholithiasis complicated by ascending cholangitis, or other life-
threatening endoscopic indications.
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The anesthesiologist should obtain a brief history, perform a directed physical


examination, and check the critical laboratory tests to evaluate the safety of the
procedure and of sedative and analgesic medications (Box 1).
In the absence of an anesthesiologist, the endoscopist performs this directed
evaluation during the routine preprocedure patient evaluation. This evaluation is
used to exclude or identify contraindications to endoscopy, such as

severe electrolyte disorders


hypoglycemia
severe hyperglycemia
food in the stomach
blood in the stomach
fever or sepsis
significantly abnormal vital signs
hypoxia
hypotension
angina
uncooperative patient
unable to obtain valid consent
life-threatening arrhythmias or cardiac conduction disorders
significant coagulopathy
obstetric instability
preterm uterine contractions.

The evaluation is also used to guide triage decisions about the endoscopy
(Box 2).
The anesthesiologic evaluation concludes with a patient discussion about the
fetal risks, patient benefits, and patient choices regarding sedation and analgesia
during endoscopy, including:

known risks of anesthesiologic medications


unknown (potential) teratogenic risks of medications
alternatives to anesthesia during endoscopy
desired level of sedation and analgesia during endoscopy
written, signed, and witnessed consent.

The patient should be informed of the benefits and the small potential
teratogenic risks of endoscopic medications, but should be advised that the
potential fetal risks are incompletely characterized. This discussion is docu-
mented by a separate signed informed consent for anesthesia when performed by
an anesthesiologist, but is documented in the usual informed consent form for
endoscopy when performed by an endoscopist. Although the mother legally
makes all decisions concerning her endoscopy, the father may be apprised and
informed of the endoscopic decisions and findings, as appropriate.
sedation and analgesia during pregnancy 7

Box 1. Preprocedure anesthesiologic evaluation*

Medication & social history

Allergies to medications
Other allergies
Prescription medications
Nonprescription (over-the-counter) medications
Unregulated/alternative medications (herbal medicines)
Illicit medications (drug abuse)
Alcoholism

Medical history

Liver disease
Easy bruisability/coagulopathy
Respiratory illnesses
Cardiovascular diseases
Anesthesiologic/surgical history
Obstetric history

Physical examination

Vital signs
Oxygen saturation
Oropharyngeal airway
Respiratory status
Cardiac examination
Abdominal examination
Mental status & neurologic evaluation

Laboratory tests

Routine electrolytes
Hematocrit
Coagulation profile

Classification

American Society of Anesthesiology class


(Mallampati) airway class

* Performed by an anesthesiologist when in attendance at the en-


doscopic procedure or performed by a gastroenterologist, as part of
the routine preprocedure evaluation, when an anesthesiologist is not
in attendance.
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Box 2. Anesthesiology-related triage decisions for endoscopic


procedures

Anesthesiologist consultation for procedure


Obstetric consultation before procedure
Site of endoscopy: office-based endoscopy, versus ambulatory
surgery or endoscopy unit, versus in-hospital endoscopy
suite, versus intensive care unit
Timing of endoscopy: prompt (as scheduled) versus delayed
(until after patient stabilizes)
Preprocedure correction of electrolyte disorders
Preprocedure vitamin K administration
Preprocedure transfusion of packed erythrocytes
Preprocedure transfusion of other blood products
Preprocedure intravenous hydration
Preprocedure antibiotic prophylaxis
Ventilation: supplemental oxygen administration by nasal
cannulae, versus ventimask, versus continuous positive
airway pressure (CPAP), versus endotracheal intubation
Sedation and analgesia versus general anesthesia for procedure
Central venous pressure (CVP) monitoring during procedure
Fetal monitoring during procedure

Monitoring during endoscopy

Sedation and analgesia are rendered safer when the patient is monitored during
endoscopy (Box 3).
For example, pulse oximetry makes endoscopy safer by identifying hypoxic
patients (who should avoid endoscopy), by identifying patients who require
supplemental oxygen administration or endotracheal intubation before endos-
copy, and by alerting physicians to respiratory decompensation during endoscopy
[50]. Fetal monitoring is recommended during intra-abdominal surgery in the
third trimester [51,52]. Fetal monitoring is preferable during endoscopy, if
available, when fetal heart sounds become detectable [5]. The ambulatory
pregnant patient should be monitored postprocedure until the medication effects
wear off.

Medication teratogenicity

Medication teratogenicity is an inexact science. Safety in animal models does


not assure safety in humans because of species specificity, a lesson unfortunately
sedation and analgesia during pregnancy 9

Box 3. Recommended patient monitoring for endoscopy during


pregnancy

Standard

Continuous pulse oximetry


Intermittent (periodic) sphygmomanometry
Continuous respiratory rate monitoring
Continuous pulse monitoring
Continuous electrocardiographic monitoring

Optional/nonstandard

Fetal monitoring

Table 2
Difficulties assessing fetal safety of anesthetic medications
Problem Reason
Dearth of randomized clinical trials during Concern about poor outcomes and medico-legal
pregnancy liability by physicians, drug companies, and
patients
Generally small and retrospective clinical trials Study medications often avoided during
pregnancy unless absolutely required
Drug studies have to be performed on a large Statistical analysis is required to detect a
population to detect a mild, but highly teroatogenic risk above the baseline risk of
clinically significant, teratogenic effect 1% to 3% [55,56]
Potential late toxicity from fetal exposure Fetal side effects may only manifest many years
after birth (eg, vaginal adenocarcinoma from
diethylstilbestrol exposure manifests after
puberty [57]; subtle neurodevelopmental
toxicity may manifest after starting school)
Fetal safety in animals does not necessarily Teratogenicity may be species specific
guarantee fetal safety in humans (eg, thalidomide safe in laboratory animals)
Fetal safety may critically depend upon Teratogenic risk greatest during organogenesis
maternal date of exposure in the first trimester
Fetal safety may depend upon route, dosage, Drug studies often lump together patients who
duration of exposure, or diluent of receive different dosages or other important
administered drug differences in drug administration during
pregnancy
Drug safety in newborn does not guarantee Very different physiologic considerations
safety to fetus
Confounding variables that can potentiate drug For example, the underlying illness for which
teratogenicity are typically not analyzed in the drug is prescribed can increase the terato-
drug studies genic rate above the baseline spontaneous
teratogenic rate
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Box 4. General principles and precautions concerning sedation and


analgesia for gastrointestinal endoscopy during pregnancy

Use smallest effective dose


Minimize procedure time to minimize the need for anesthetics
and sedatives
Substitute less invasive and shorter procedure, if possible, to
decrease intraprocedural medication use (eg, flexible
sigmoidoscopy for colonoscopy)
Terminate poorly tolerated procedures to avoid excessive
sedative or analgesic doses
Preferably use pregnancy category B instead of pregnancy
category C drugs, unless there is no effective alternative to
the category C drug
Avoid category D drugs
Do not use category X drugs
Avoid optional drugs
Contact pharmacologist or perform literature review as
necessary regarding drug teratogenicity
Consider anesthesiologist referral for administering analgesia
and sedation, particularly in more complicated, longer, or
higher-risk procedures (eg, therapeutic endoscopic
retrograde cholangiopancreatography)
Avoid use of drugs during the first trimester if possible (ie, defer
endoscopy when possible until after the first trimester)
Avoid use of drugs during active labor if possible (ie, defer
endoscopy to postpartum when possible)
Consider performing endoscopy in a hospital endoscopy suite
rather than private office during pregnancy to facilitate
treatment of procedure complications, including
medication side effects
Obtain fully informed and written consent that includes fetal risks
of procedure because of medications or other causes. Involve
patients in decisions on potentially fetotoxic medications
Refer patient who has a complicated clinical course and a very
high-risk endoscopy to an experienced endoscopist at a
tertiary medical center
Avoid antagonists to analgesic or sedative drugs. Use these
antagonists only when strongly indicated to treat an
analgesic or sedative overdose
Monitor the pregnant patient by continuous pulse oximetry and
electrocardiography, and by intermittent sphygmomanometry
Consider fetal monitoring during endoscopy, if available
sedation and analgesia during pregnancy 11

learned with thalidomide [53,54], and because physicians are reluctant to perform
and patients are reluctant to enroll in therapeutic clinical trials during pregnancy
(Table 2; [55–57]). Despite outstanding contributions by Briggs and coworkers
[58], and by Heinonen and colleagues [59], clinical studies of drug teratogenicity
during the first trimester, when available, are usually small and retrospective.
Historically, teratogenic effects have been appreciated late, unless they were large
or highly unusual. Thalidomide teratogenicity took years to appreciate despite
an extremely large (one in three) and highly unusual (phocomelia) teratogenic
effect [58].
Nonetheless, the existing data, even though mostly retrospective, nonrandom-
ized, and poorly controlled, provide crude estimates of drug teratogenicity. A

Table 3
Common complications related to anesthesia for endoscopy
Complication Identification Prevention/treatmenta
Hypotension Periodic sphygmomanometry Gradually administer narcotics and
sedatives with dosage titrated to effect;
administer fluids; transfuse as neces-
sary before endoscopy; avoid colonic
overdistention during colonoscopy
Hypoxia Pulse oximetry Gradually administer narcotics and
sedatives with dosage titrated to effect;
administer supplemental oxygen by
nasal cannulae; endotracheal intubation;
position head by manual pressure
on lower jaw
Hypoventilation Respiratory rate monitoring, Reversal agents for narcotics or seda-
pulse oximetry tives; stimulate patient; carefully
observe patient
Bradycardia Electrocardiographic monitoring Avoid colonic overdistention with air
during colonoscopy; avoid excessive
sedation or analgesia
Seizures Direct observation by nurse or Terminate procedure; correct electrolyte
anesthesiologist monitoring patient disorders; avoid hypoxia; antiseizure
during procedure drugs; seizure precautions
Aspiration Pulse oximetry, direct observation Suction oropharynx during procedure;
pneumonia place head to avoid pharyngeal aspira-
tion; consider prophylactic endotra-
cheal intubation for severe, active,
upper gastrointestinal hemorrhage
Angina Electrocardiographic monitoring, Avoid prolonged, difficult, and painful
direct observation endoscopy; antianginal medications;
cardiac stabilization before procedure
Premature uterine Fetal monitoring Tocolytics, avoid excessive uterine
contractions pressure, obstetric consultation, termi-
nate difficult and painful procedures
a
Severe endoscopic complications may require aborting the endoscopic procedure.
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Table 4
Food and Drug Administration categories of fetal risk from drugs administered during pregnancy
Category Fetal risk
A Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester
(and there is no evidence of a risk in later trimesters), and the possibility of fetal harm
appears remote.
B Either animal reproduction studies have not demonstrated a fetal risk but there are no
controlled studies in pregnant women, or animal-reproduction studies have shown an
adverse effect (other than a decrease in fertility) that was not confirmed in controlled
studies in women in the first trimester (and there is no evidence of a risk in later
trimesters).
C Either studies in animals have revealed adverse effects on the fetus (teratogenic,
embryocidal, or other) and there are no controlled studies in women, or studies in
women and animals are not available. Drugs should be given only if the potential
benefit justifies the potential risk to the fetus.
D There is positive evidence of human fetal risk, but the benefits from use in pregnant
women may be acceptable despite the risk (eg, if the drug is needed in a life-
threatening situation or for a serious disease for which safer drugs cannot be used or
are ineffective).
X Studies in animals or humans have demonstrated fetal abnormalities, or there is
evidence of fetal risk based on human experience or both, and the risk of the use of
the drug in pregnant women clearly outweighs any possible benefit. The drug is
contraindicated in women who are or may become pregnant.

large, retrospective study that shows no teratogenicity strongly suggests that the
studied drug is not a major teratogen. Several concurring studies strengthen this
conclusion. Even a large study that shows a small, but statistically significant,
increase in congenital malformations after in utero drug exposure can suggest
that the drug is not a major teratogen: the reported association may be caused
by confounding variables, such as the underlying illness for which the drug
was administered.
General considerations about drug administration to the pregnant patient dur-
ing endoscopy are summarized in Box 4.
The identification and treatment of common endoscopic complications related
to anesthesia are summarized in Table 3. The Food and Drug Administration
(FDA) provides a useful classification of fetal risk of medications (Table 4). The
simplicity of this classification often belies the underlying complex, conflicting,
and controversial animal and clinical data. This classification should be used in
conjunction with clinical experience and knowledge of the relevant literature. The
following review considers the fetal risk of individual sedatives and analgesics.
Clinical studies on the overall fetal safety of endoscopy during pregnancy [4–9]
are omitted here, even though the overall endoscopic risks include the risks of
medications; these studies are reviewed in other articles. The reader is also
referred to the article on upper endoscopy during pregnancy for a review of
antibiotic prophylaxis for endoscopy during pregnancy.
sedation and analgesia during pregnancy 13

Sedative and analgesic medications administered by endoscopists

Meperidine (category B)

Meperidine, an opiate analgesic, has been commonly administered during


gastrointestinal endoscopy. Meperidine is rapidly transferred across the human
placenta after intramuscular injection [60], or intravenous administration [58].
Peak cord blood concentrations average about 75% of maternal plasma levels
[61]. Meperidine is metabolized in humans to normeperidine, which has a long
half-life. Repeated, high-dose, and prolonged administration of meperidine can
cause progressive accumulation of normeperidine, and produce toxic effects of
maternal respiratory depression and seizures [62]. Meperidine, unlike heroin or
methadone, has not been associated with an acute opioid withdrawal syndrome in
neonates born to addicted mothers, a syndrome that is characterized by irritability,
tremors, hypertonicity, altered gastrointestinal function, respiratory distress, and
occasionally seizures [63].
Two large studies revealed no teratogenicity from meperidine administration
during the first trimester. In the Collaborative Perinatal Project, meperidine
was not teratogenic in a study of 268 mothers who were exposed in the first
trimester, except that six of the infants with in utero exposure had inguinal
hernias [59]. In a surveillance study of Michigan Medicaid recipients, 3 of
62 newborns who had been exposed in utero during the first trimester had major
congenital defects; the unexposed control group had the same rate of congenital
defects [58].
Physicians have extensive experience prescribing meperidine during labor
[62,64–66]. Meperidine is preferred over morphine for obstetric analgesia be-
cause it crosses the fetal blood–brain barrier much more slowly [62]. Maternal
meperidine administration during delivery depresses neonatal respiration for
several hours thereafter because normeperidine, its active metabolite, is slowly
metabolized [67,68]. Meperidine may impair neonatal neuropsychologic func-
tions, such as attention and social responsiveness, during the first few weeks of
life [69–74]; these effects disappear with time [75]. Children whose mothers
received meperidine during labor had similar psychological, physical, and
intellectual parameters at 5 years of age as compared with children without in
utero exposure [76,77]. In utero meperidine exposure during labor does not
increase the risk of childhood cancer [78].
Meperidine can cause diminished fetal heart beat variability for about 1 hour
after maternal intravenous administration [79,80]. Generally, diminished cardiac
variability is a sign of fetal distress, such as fetal acidosis or hypoxemia, but the
effect produced by a single small-to-medium dose of meperidine is reversible,
transient, and not a poor prognostic indicator [81]. In one recent study of
407 pregnant women, women who received meperidine during delivery had a
worse neonatal outcome than pregnant women who received placebo, as mea-
sured by neonatal Apgar scores, umbilical artery acidosis, and neonatal intensive
care unit admission [82].
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Meperidine is rated a category B drug during pregnancy, except for a rating of


D when used for prolonged periods and at high doses at term [58]. It is preferred
to diazepam or midazolam as an endoscopic medication during pregnancy.
Meperidine dosage should be titrated to produce calmness, relaxation, and mild
analgesia without somnolence. Dosage should be restricted to 50 or 75 mg during
routine endoscopy.

Fentanyl (category C)

Fentanyl, a potent synthetic narcotic agonist, is increasingly used as an alter-


native to meperidine during endoscopy because of a faster onset of action and a
shorter recovery time [83]. Fentanyl was not teratogenic, but was embryocidal, in
rats who were administered 0.3 times the maximal human equivalent dose for
prolonged periods [84,85]. In humans, fentanyl crosses the placenta to the fetus
[86,87].
In numerous clinical studies, maternal fentanyl administration during labor
produced no neonatal toxicity [88–91]. For example, one study that compared
137 women who were administered fentanyl during labor with 112 women who
did not require any epidural or narcotic analgesia during labor, reported no
differences in newborn outcomes such as neonatal respiratory rate, Apgar score,
heart rate, blood pressure, neurologic status, and overall health [91]. In multiple
studies, addition of fentanyl to bupivacaine for spinal anesthesia during delivery
revealed no adverse effects on neonatal respiratory rate or neurobehavioral scores
[92,93].
In single case reports, fentanyl has, however, been associated with respiratory
depression [94], respiratory muscle rigidity [95], or opiate withdrawal that lasted
for several days after birth in an addicted mother [96]. Fentanyl, like meperidine,
can decrease fetal heart rate variability without causing fetal hypoxia [15,62].
Fentanyl is rated a risk category C during pregnancy, except for a rating of D if
used for prolonged periods or high doses at term [58,85]. The accumulated data
suggest that fentanyl may be used in low dosage for endoscopy during pregnancy.

Diazepam (category D)

Benzodiazepines, including diazepam and midazolam, are commonly admin-


istered before gastrointestinal endoscopy to reduce anxiety, induce brief amnesia,
and produce muscle relaxation. Diazepam rapidly crosses the placenta and
accumulates in the fetal circulation at levels equal to, or higher than, maternal
serum levels [97–99].
Diazepam administration to pregnant mice was associated with cleft palates in
their offspring [100]. Several studies suggested an association between diazepam
use during pregnancy and neonatal cleft lips or palates in humans [101–104]. For
example, in 1975, Safra and Oakley [105] reported in a retrospective study of
278 mothers, that mothers of children who had a cleft lip or palate had a fourfold
sedation and analgesia during pregnancy 15

increased rate of diazepam use during the first trimester as compared with
mothers of children with other congenital defects. These same investigators,
however, concluded from a review of the literature in 1976 that diazepam had not
been proven to cause oral clefts, and even if this relationship existed, the risk of
neonatal oral clefts from in utero exposure was only about 0.4% [106].
More recent studies have demonstrated no association between diazepam and
oral clefts [16,107–109]. No association was detected in a study that compared
611 infants who had oral clefts with 2498 infants who had other congenital
defects [16], or in a study that compared 355 infants who had oral clefts with
11,073 healthy infants [110]. No oral clefts occurred in the offspring of
80 mothers who used frequent, high-doses of diazepam during pregnancy [111].
The current consensus is that diazepam does not cause a significant risk of oral
clefts [112,113].
Other studies raised a possible association between diazepam exposure and
other congenital abnormalities. An association with congenital inguinal hernia
was reported in two studies [114,115]; cardiac defects and pyloric stenosis were
reported in a study that compared the rate of diazepam exposure among 1427
malformed newborns with 3001 healthy controls [115]; and Mobius syndrome
(sixth and seventh nerve palsies) was reported after in utero diazepam exposure in
one case report [116]. These associations are unconfirmed. In a study from the
Israeli Teratogen Service, 11 (3.1%) of 355 infants who experienced in utero first
trimester exposure to a benzodiazepine, including diazepam in 25% of cases, had
major congenital malformations compared with 10 (2.6%) of 382 unexposed
control infants [117]. A meta-analysis of nine cohort studies revealed no as-
sociation of diazepam with major malformations; whereas, a meta-analysis of
nine case-controlled studies showed an association with major malformations
(odds ratio 3.01, 95% confidence interval, 1.32–6.84) [118].
Several reports raised a possible association between frequent, high-dose
diazepam administration during pregnancy and neonatal mental retardation or
neurologic defects. For example, in one study, seven mothers who had ingested
high doses of diazepam during pregnancy had mentally retarded infants
[119,120]. Several investigators reported that high doses of diazepam adminis-
tered during labor may cause the floppy infant (overdose) syndrome characterized
by hypotonia, lethargy, and sucking difficulties [121–123], and a neonatal
withdrawal syndrome characterized by intrauterine growth retardation, tremors,
impaired temperature homeostasis, irritability, hypertonicity, diarrhea, vomiting,
and vigorous sucking [124,125]. This neonatal withdrawal syndrome seems to be
biologically plausible because chronically habituated pregnant women can
develop similar symptoms after abrupt diazepam cessation [126]. The risk of
either neonatal syndrome is increased by prolonged diazepam use. Generally,
infants gradually recover from the floppy infant syndrome as diazepam is
metabolized and disappears from the neonatal circulation.
Diazepam is categorized as a class D drug during pregnancy, and its use
should be carefully restricted during endoscopy, particularly during the first
trimester [58]. However, some recent experience suggests that it may be safer
16 cappell

during pregnancy than previously appreciated when administered at a low dose


for a brief period [127].

Midazolam (category D)

Many endoscopists prefer midazolam to diazepam for endoscopy because of


faster onset time and faster recovery time, more intense transient antegrade
amnesia, and lower risk of thrombophlebitis [128]. Administration of 10 and
5 times the maximal recommended human equivalent dose in pregnant rats and
rabbits, respectively, revealed no teratogenicity [85]. Midazolam crosses the
human placenta, but fetal serum levels rise to only one-third to two-thirds of
maternal serum levels after oral, intramuscular, or intravenous maternal ad-
ministration [129,130].
Several studies suggested that maternal midazolam administration during
parturition transiently depresses neonatal respiration [131–134], and neuro-
behavioral responsiveness [133]. Three of 19 infants whose mothers had received
midazolam during cesarean section had transient neurobehavioral abnormalities
in body temperature, body tone, and arm recoil [133]. In a controlled study of
52 infants, the infants who were exposed to midazolam during cesarean section
had lower Apgar scores at 1 minute after birth compared with unexposed controls
[131]. Another study confirmed these results [135]. These sedative effects are
attributable to direct neonatal effects of midazolam and should disappear after
drug elimination. Two other studies, however, reported no adverse effects in
30 and 20 newborns whose mothers received midazolam during parturition
[136,137].
Other than endoscopic studies [4,5], no published reports have analyzed the
effects of first or second trimester fetal exposure [58]. Midazolam was, however,
successfully used for patient sedation during intrafallopian gamete transfer with
subsequently normal pregnancies in a small clinical series [138]. This
benzodiazepine has not been associated with oral clefts.
This drug is classified a risk factor D during pregnancy [85], but seems to be
preferable to diazepam because of the potential, albeit unlikely, association
between diazepam and oral clefts and neonatal neurobehavioral abnormalities.
Because of a similar mechanism of action as diazepam, midazolam should be
used cautiously and in low doses during pregnancy, particularly during the first
trimester. Dosage should be titrated to an end point of relaxation and calmness
without somnolence.

Lidocaine (category B)

Lidocaine, an aminoethylamide local anesthetic, is often applied topically to


the oropharynx before EGD or ERCP to decrease the gag reflex and alleviate
oropharyngeal discomfort during endoscopic intubation. Lidocaine is occasion-
ally applied topically to the anus to relieve pain from anal conditions, especially
hemorrhoids, during flexible sigmoidoscopy or colonoscopy. Anesthesiologists
sedation and analgesia during pregnancy 17

sometimes use intravenous lidocaine in combination with intravenous propofol


for sedation and analgesia.
No fetal harm occurred after pregnant rats received 6.6 times the maximal
recommended equivalent human dose [85]. Lidocaine rapidly crosses the
placenta in humans [139]. Epidural lidocaine administration during parturition
resulted in mild transient neurologic depression of the newborn in some studies
[140], but not others [141]. The neurologic depression at birth, as evidenced by
low Apgar scores, was associated with very high neonatal serum levels of
lidocaine after maternal exposure during delivery [142]. Six cases of fetal
bradycardia or tachycardia were noted after 12 women received paracervical
lidocaine block during delivery [143]. Accidental lidocaine injection into the fetal
scalp during attempted local infiltration for episiotomy led to apnea and fixed and
dilated pupils 15 minutes after birth, and convulsions 1 hour after birth [144]. The
infant subsequently developed normally.
The current consensus is that lidocaine block during parturition is safe to the
fetus [145,146]. In the Collaborative Perinatal Project, lidocaine was generally
not associated with fetal malformations among 293 infants who were exposed in
utero during the first trimester [59]. Lidocaine is classified as a risk factor B
during pregnancy [85]. Intravenous lidocaine has been administered to mothers
with ventricular arrhythmias with good fetal outcomes [147]. Although the
teratogenic potential of oral lidocaine is small, topical application is often unnec-
essary for endoscopy during pregnancy. The pregnant patient who is administered
topical lidocaine should be instructed to gargle and spit out, rather than swallow,
the preparation to minimize systemic absorption. Lidocaine should be adminis-
tered intravenously only at low dose when deemed necessary by an anesthesi-
ologist for endoscopy.

Sedative and analgesic medications administered by anesthesiologists

Propofol (category B)

Anesthesiologists increasingly use propofol, a short-acting parenteral anes-


thetic, for endoscopy, but gastroenterologists have traditionally avoided using
propofol because of a narrow therapeutic index, potential respiratory depression,
and legal restrictions in certain states [83]. A large study has reported no
significant risks from nurse-administered propofol during endoscopy under
the supervision of an attending gastroenterologist [148]. Potential advantages
of propofol over conventional endoscopic anesthetics include a shorter time of
onset, greater depth of sedation, shorter recovery time, and earlier patient
discharge [149].
Administration of six times the maximal recommended human equivalent dose
in pregnant rats or rabbits revealed no teratogenicity [85]. Administration of
moderately high doses of propofol to pregnant sheep did not adversely affect
maternal uterine blood flow, maternal or fetal arterial pressure and heart rate, fetal
18 cappell

heart rate variability, or pregnancy outcome [150]. Propofol rapidly transfers


across the placenta near term in humans [151,152]. In one study, 20 infants who
were exposed to propofol during parturition had depressed Apgar scores and
transient neurologic depression at birth compared with unexposed controls, but
the neurologic depression rapidly reversed postpartum [153]. In contrast,
numerous other studies that involved hundreds of patients reported no neonatal
toxicity from propofol administered during parturition [58,154–158]. However,
most studies agree that very high doses of propofol administered during
parturition may transiently depress neonatal neurobehavioral function [159].
Propofol is rated a risk factor B and is considered relatively safe during preg-
nancy, but the safety of first trimester exposure has been inadequately studied
[85,158].

Ketamine (category B)

Anesthesiologists sometimes use ketamine for endoscopy because of its rapid


action of onset and short duration of effects [160], particularly in patients who are
expected to experience insufficient sedation from propofol. Multiple studies have
demonstrated no teratogenic effects in rats, mice, rabbits, and dogs that were
administered high doses during organogenesis or near delivery [161]. Exposure
of five pregnant monkeys to ketamine during pregnancy resulted in no untoward
fetal effects, but high dose exposure during delivery resulted in profound,
but transitory, neonatal respiratory depression [162]. Exceedingly high dose
administration of ketamine to neonatal mice can cause degeneration of neurons,
loss of cerebral cortex, and decreased learning ability in maze trials in adult-
hood [163].
Ketamine rapidly crosses the placenta to the fetus in humans [164]. It is
commonly used clinically for intrapartum anesthesia. Ketamine administration
during delivery occasionally causes maternal dysphoria [62]. Ketamine has
oxytocic effects, causes an increased basal uterine tone as well as increased
frequency and amplitude of uterine contractions [165], and can increase the blood
pressure in the mother [166]. Both the uterine and blood pressure effects are
transient, short lasting, and dose-dependent. Maternal ketamine administration
just before delivery does not adversely affect neonatal blood pressure [165,167].
Ketamine administration during delivery can cause transient neonatal
depression, reflected in lower initial Apgar scores and the need for neonatal
resuscitation [168]. This phenomenon is most evident with high dose admin-
istration and prolonged induction-to-delivery times [168]. The neurobehavioral
depression may last for up to 2 days after delivery [169]. Maternal ketamine
administration during labor, however, appears to cause less neonatal respiratory
depression than other sedatives [62]. High doses of ketamine administered to the
mother during delivery can transiently increase neonatal muscle tone [170].
Ketamine has not been associated with teratogenicity [171]. However, ketamine
administered during the first trimester has not apparently been reported. Ketamine
is rated as a class B drug during pregnancy, but carries the caveats that fetal safety
sedation and analgesia during pregnancy 19

during organogenesis is unstudied in humans, and extremely high or prolonged


administration during pregnancy might be unsafe.

Sedative and analgesic reversal agents

Naloxone (category B)

Naloxone, a rapidly acting opiate antagonist, is sometimes administered after


endoscopy to reverse the effects of narcotics that were administered during
endoscopy. It does not produce narcotic effects or respiratory depression at
clinically used dosages [172]. It rapidly crosses the placenta, and appears in fetal
plasma within 2 minutes of intravenous maternal injection [58,173]. Fetal serum
levels peak at about one-half of maternal levels after maternal intravenous
injection [173]. Naloxone administered at up to 50 times the maximal equivalent
human dose in pregnant mice and rats was not fetotoxic, but rat pups that were
exposed to naloxone during lactation developed long-lasting hyperalgesia
[85,174].
Naloxone administration has been analyzed during the third trimester.
Intravenous infusion of 0.4 mg of naloxone in 27 healthy pregnant women at
37 to 39 weeks of gestation led to an increase in fetal gross movements,
respiratory movements, and heart rate acceleration, without subsequent neonatal
toxicity [175]. Infant neurobehavioral scores were similar after their mothers had
received meperidine alone or meperidine plus naloxone during labor [169,176].
Naloxone was safely administered to newborns immediately postpartum to
reverse narcotic depression, including depressed respiration or, somnolence that
followed administration of narcotics to the mother during labor [177,178].
In one study, eight otherwise normal fetuses with decreased heartbeat vari-
ability intrapartum, were administered naloxone to increase the heartbeat
variability based on the theory that elevated fetal endorphin levels depress the
normal fetal heart rate and depress the normal fetal heartbeat variability. One of
the infants developed fatal respiratory failure and convulsions soon after the drug
was administered [179].
Naloxone administration is contraindicated for pregnant patients who are
dependent on opiates. Naloxone administration can precipitate the opiate
withdrawal syndrome in the mother and can precipitate a similar withdrawal syn-
drome in the neonate because of transplacental opiate transfer. Neonatal symptoms
include restlessness, anxiety, insomnia, irritability, hyperalgesia, nausea, and
muscle cramps [63,180]. One newborn, whose mother was opioid-dependent,
suffered convulsions that were precipitated by naloxone administration [181].
Naloxone is rated a category B drug during pregnancy [85]. Naloxone is not
recommended for routine use after endoscopy during pregnancy because of one
reported fatality associated with neonatal administration. Patients should be
monitored in a recovery unit with intravenous access and electrocardiographic
monitoring until they recover from narcotic-induced drowsiness. Naloxone
20 cappell

administration should be restricted to pregnant patients who suffer signs of


potential narcotic toxicity, such as respiratory depression, systemic hypotension,
or unresponsiveness, and should be administered, in these cases, in small graded
doses that are titrated to the desired effect. Naloxone overdose should be avoided.
It can cause maternal myocardial infarction, pulmonary edema, or severe hyper-
tension [62].

Flumazenil (category C)

Flumazenil rapidly reverses the central effects of benzodiazepines [182]. It is


used after endoscopy to reverse the effects of oversedation with benzodiazepines
that were administered during endoscopy [183]. The administration of flumazenil
to pregnant rats and rabbits during or after organogenesis at several hundred
times the maximal recommended human dose revealed no teratogenicity [85].
Flumazenil was not embryocidal when administered at 60 times the recom-
mended human dose in pregnant rabbits, but was embryocidal at 200 times the
recommended human dose [85]. Prolonged, high-dose administration to pregnant
rats in late gestation may result in subtle neurobehavioral changes in their male
offspring [184].
Little is known about flumazenil safety during pregnancy in humans. Drug
transfer across the human placenta to the fetus is unstudied. Transplacental
transfer is theoretically likely because of the low molecular weight of the
compound, but this transfer is likely to be small from a single drug bolus because
of the short drug half-life. One somnolent pregnant patient at 36 weeks of
gestation developed fetal cardiotocographic abnormalities of a decreased basal
fetal heart rate, decreased beat-to-beat cardiac variability, and absent cardiac
accelerations after a diazepam overdose. The patient rapidly awoke and the fetal
cardiotocographic abnormalities rapidly reversed after intravenous flumazenil
administration [185]. The mother delivered a healthy infant 2 weeks later. In
another case report, a healthy infant was born after in utero exposure to
flumazenil just before cesarean section [186]. In a third case, administration of
flumazenil in the third trimester was not associated with fetal toxicity [187].
Little is also known about flumazenil toxicity in neonates. Flumazenil was
successfully used to reverse recurrent apnea in two newborn infants whose
mothers had taken high doses of diazepam during late pregnancy [188,189].
Intravenous flumazenil was also successfully used to reverse unresponsiveness
and hypotonicity in a 4-month-old infant after intravenous midazolam sedation
[190]. The infant subsequently did well.
Flumazenil is rated a category C drug during pregnancy [85]. Flumazenil
should be used only to reverse benzodiazepine overdose during pregnancy be-
cause the fetal risks are unknown [85]. For this indication, the known maternal
benefits should greatly outweigh the unknown, but unlikely, fetal risks.
Flumazenil overdose can cause maternal seizures, particularly when administered
to patients who are chronically habituated to benzodiazepines [191]. This
sedation and analgesia during pregnancy 21

overdose can be prevented by careful and slow titration and the administration of
the minimal dosage of benzodiazepines required for endoscopy [83].

Future trends: anesthesiologic monitoring

Automated electroencephalogram monitors that use the bispectral (BIS) index


(Aspect Medical Systems, Natick, Massachusetts) or Narcotrend (Monitor
Technik, Germany), are being tested to quantitatively define the level of anes-
thesia [192–194]. This technology might reduce anesthesia requirements for
endoscopy during pregnancy and thereby decrease fetotoxicity. The fetus is
routinely monitored during surgery in the third trimester to rapidly detect fetal
distress. Fetal monitoring may, likewise, improve fetal safety during endoscopy,
particularly for therapeutic ERCP [5].

Alternatives to conventional endoscopy

Alternatives to gastrointestinal endoscopy, including an upper gastrointestinal


series, barium enema, abdominal roentgenogram, mesenteric angiogram,
computerized tomography, and virtual colonoscopy, are useful in the general
population and are theoretically desirable for preganant patients because they
require minimal or no anesthesiologic medications. But these tests are generally
contraindicated because of radiation teratogenicity [12]. Likewise, bleeding scans
are relatively contraindicated during pregnancy because of the fetal risks from
ionizing radiation.
Ultranarrow upper gastrointestinal endoscopes may permit gastrointestinal
intubation with minimal anesthesia and with reduced mechanical pressure on the
uterus [195]. These benefits are especially attractive during pregnancy to
minimize exposure to potentially teratogenic anesthetic medications and to avoid
endoscopic trauma to the uterus. These endoscopes have not been studied dur-
ing pregnancy.
Videocapsule endoscopy is currently used to examine the small bowel beyond
the ligament of Treitz, because this area is relatively inaccessible to conventional
tube endoscopy [196]. Videocapsule endoscopy has theoretical advantages during
pregnancy: the examination does not require sedation and does not cause
mechanical pressure on the uterus. The safety of videocapsule endoscopy during
pregnancy is currently unstudied and unknown. Intestinal compression by the
enlarged gravid uterus might theoretically retard videocapsule progression, but
this may not be a significant practical problem. Technical innovations could
render videocapsule endoscopy a viable alternative to EGD or colonoscopy dur-
ing pregnancy. In string videocapsule endoscopy of the esophagus, a string is
attached to the videocapsule for retrieval of the videocapsule after esophageal
passage and esophageal videophotography [197]. This test has the theoretical
22 cappell

advantages during pregnancy of minimal test invasiveness and lack of need for
anesthesia, but test safety has not been evaluated during pregnancy.
Fecal or serologic molecular markers are being used experimentally to detect
early colon cancer. In a preliminary study, a multitarget molecular assay for
mutations in the p53 and APC genes, microsatellite instability, and other mo-
lecular markers had a sensitivity of 91% and a specificity of 100% for colon
cancer [198]. Recent studies have demonstrated a much lower test sensitivity
(only 18.2%) and specificity for detection of advanced colonic adenomatous
polyps [199]. Such a test could be used to screen for suspected colon cancer to
limit colonoscopy during pregnancy to patients who have a positive result on the
screening test, provided that the test sensitivity is improved by adding more
markers to the test array.
Although virtual colonoscopy that uses computerized tomography has no
foreseeable role in pregnancy because of radiation teratogenicity [200], virtual
colonoscopy that uses magnetic resonance imaging (MRI) would theoretically
be attractive during pregnancy because MRI is apparently much safer than
radiation during pregnancy. In MRI, multifrequency pulses are applied in the
presence of a magnetic field gradient to excite hydrogen ions. MRI without
contrast has no known harmful effects in nonpregnant humans, except in patients
with metallic foreign bodies or with implanted electronic devices, such as cardiac
pacemakers [201].
Magnetic resonance cholangiopancreatography (MRCP) is increasingly
supplanting diagnostic ERCP in the general population [202]. MRCP is a par-
ticularly attractive alternative to diagnostic ERCP during pregnancy because it
avoids radiation teratogenicity and does not require sedation and analgesia [203].
MRI is being used increasingly to evaluate the abdomen and retroperitoneum
during pregnancy. Short-term exposure to electromagnetic radiation from MRI
does not produce harmful fetal effects [204,205].

Summary

Endoscopy during pregnancy raises the unique issue of fetal safety. Endo-
scopic medications comprise a significant component of fetal endoscopic risks.
Before endoscopy, the gastroenterologist or anesthesiologist should evaluate the
potential fetal risks of sedation and analgesia, identify any contraindications to
endoscopy, stabilize the maternal medical status as necessary, and correct
maternal hypoxia or hypotension. The mother should be informed about the
potential teratogenic risks of endoscopic medications during pregnancy, espe-
cially during organogenesis during the first trimester. Patients who receive
sedation and analgesia should be monitored during endoscopy by continuous
electrocardiography, continuous pulse oximetry, and intermittent sphygmoma-
nometry, as well as by the pulse and respiratory rate. General principles of seda-
tion and analgesia during pregnancy include use of the minimal effective dose,
avoidance of unnecessary medications, and preferable use of FDA category B
sedation and analgesia during pregnancy 23

medications. Medications used for sedation and analgesia during pregnancy


include meperidine (category B), fentanyl (category C), midazolam (category D),
lidocaine (category B), propofol (category B), and ketamine (category B).
Endoscopy can be performed with sedation and analgesia during pregnancy, with
appropriate precautions, for strong endoscopic indications.

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