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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 [13], the risks, benefits, and

indications during pregnancy are less well known. In addition to the usual patientrisks, 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 [49] and clinical reviews [1013]; 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 [1416].

Medications can be directly teratogenic or can indirectly cause fetal distress

secondary to effects on the mother such as cardiac arrhythmias [1720], 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

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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, exceptfor 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; [4,5,9,2635]).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

therapygastrointestinal surgeryfor active gastrointestinal bleeding or com-

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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 theileocecal 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

Table 1

Endoscopic procedures generally requiring anesthesia during pregnancy

Endoscopic procedureSelected references for

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.

sedation and analgesia during pregnancy 3


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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 patients 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 packederythrocytes 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

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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 thegastric lake during upper endoscopy, peroral aspiration as necessary to remove

oropharyngeal secretions, and placement of the patient in a decubitus position

with the patients 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 firsttrimester 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 stomachfever or sepsis

significantly abnormal vital signs

hypoxia

hypotension

angina

uncooperative patient

unable to obtain valid consent

life-threatening arrhythmias or cardiac conduction disorders

significant coagulopathyobstetric 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.

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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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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

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 procedureFetal monitoring during procedure

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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 medicationsProblem Reason

Dearth of randomized clinical trials during

pregnancy

Concern about poor outcomes and medico-legal

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

population to detect a mild, but highly

clinically significant, teratogenic effect

Statistical analysis is required to detect a

teroatogenic risk above the baseline risk of

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

guarantee fetal safety in humans

Teratogenicity may be species specific

(eg, thalidomide safe in laboratory animals)

Fetal safety may critically depend upon

maternal date of exposure

Teratogenic risk greatest during organogenesis

in the first trimester

Fetal safety may depend upon route, dosage,

duration of exposure, or diluent of

administered drug

Drug studies often lump together patients who

receive different dosages or other important

differences in drug administration duringpregnancy

Drug safety in newborn does not guarantee

safety to fetus

Very different physiologic considerations

Confounding variables that can potentiate drug

teratogenicity are typically not analyzed in

drug studies

For example, the underlying illness for which

the drug is prescribed can increase the terato-

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, orhigher-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, includingmedication 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 ananalgesic or sedative overdose

Monitor the pregnant patient by continuous pulse oximetry and

electrocardiography, and by intermittent sphygmomanometry

Consider fetal monitoring during endoscopy, if available

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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; [5557]). 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/treatment a

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,

pulse oximetry

Reversal agents for narcotics or seda-

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

anesthesiologist monitoring patient

during procedure

Terminate procedure; correct electrolyte

disorders; avoid hypoxia; antiseizure

drugs; seizure precautions

Aspiration

pneumonia

Pulse oximetry, direct observation Suction oropharynx during procedure;

place head to avoid pharyngeal aspira-

tion; consider prophylactic endotra-

cheal intubation for severe, active,

upper gastrointestinal hemorrhageAngina Electrocardiographic monitoring,

direct observation

Avoid prolonged, difficult, and painful

endoscopy; antianginal medications;

cardiac stabilization before procedure

Premature uterine

contractions

Fetal monitoring Tocolytics, avoid excessive uterine

pressure, obstetric consultation, termi-

nate difficult and painful procedures

a Severe endoscopic complications may require aborting the endoscopic procedure.



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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 drugwas 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. Thefollowing review considers the fetal risk of individual sedatives and analgesics.

Clinical studies on the overall fetal safety of endoscopy during pregnancy [49]

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.

Table 4

Food and Drug Administration categories of fetal risk from drugs administered during pregnancy

Category Fetal riskA 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.

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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 ormethadone, 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 of62 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

[62,6466]. Meperidine is preferred over morphine for obstetric analgesia be-

cause it crosses the fetal bloodbrain 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 [6974]; 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 theeffect 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, exceptfor 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 [8891]. 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, maternalserum levels [9799].

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 [101104]. 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

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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 notbeen 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 [16,107109]. 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 oralclefts [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 firsttrimester 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, 1.326.84) [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 ingestedhigh 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 [121123], 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 ofeither 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



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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 [131134], 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 areattributable 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

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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 maximalrecommended 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 anddilated 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 ofonset, 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



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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 andtransient 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 [58,154158]. 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 untowardfetal 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 increasedfrequency 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 ketamineadministration 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

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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 fetalplasma 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 thenormal 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



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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 gradeddoses 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 benzodiazepinesthat 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. Drugtransfer 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. Inanother 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

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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 [192194]. 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 tominimize 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 theenlarged 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



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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 detectearly 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

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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.

References

[1] Arrowsmith JB, Gerstman BB, Fleischer DE, et al. Results from the American Society for

Gastrointestinal Endoscopy/US Food and Drug Administration collaborative study on com-

plication rates and drug use during gastrointestinal endoscopy. Gastrointest Endosc 1991;

37:4217.

[2] Cooper GS. Indications and contraindications for upper gastrointestinal endoscopy. Gastrointest

Endosc Clin N Am 1994;4:43954.

[3] Newcomer MK, Brazer SR. Complications of upper gastrointestinal endoscopy and their

management. Gastrointest Endosc Clin N Am 1994;4:55170.

[4] Cappell MS, Sidhom O, Colon V. A study at ten medical centers of the safety and efficacy of

48 flexible sigmoidoscopies and 8 colonoscopies during pregnancy with follow-up of

fetal outcome and with comparison to control groups. Dig Dis Sci 1996;41:235360.

[5] Cappell MS, Colon V, Sidhom OA. A study of eight medical centers of the safety and clinical

efficacy of esophagogastroduodenoscopy in 83 pregnant females with follow-up of fetal

outcome and with comparison to control groups. Am J Gastroenterol 1996;91:34854.[6] Cappell MS, Sidhom O. Multicenter, multiyear study of safety and efficacy of flexible

sigmoidoscopy during pregnancy in 24 females with follow-up of fetal outcome. Dig Dis Sci

1995;40:25662.

[7] Cappell MS, Sidhom O. A multicenter, multiyear study of the safety and clinical utility of

esophagogastroduodenoscopy in 20 consecutive pregnant females with follow-up of fetal

outcome. Am J Gastroenterol 1993;88:19005.

[8] Castro LP. Reflux esophagitis as the cause of heartburn in pregnancy. Am J Obstet Gynecol

1967;98:110.

[9] Jamidar PA, Beck GJ, Hoffman BJ, et al. Endoscopic retrograde cholangiopancreatography

in pregnancy. Am J Gastroenterol 1995;90:12637.

[10] Cappell MS. Gastrointestinal endoscopy in pregnant women: risks versus benefits. NatureClinical Practice Gastroenterology & Hepatology 2005;2:376 7.

[11] Cappell MS. The safety and efficacy of gastrointestinal endoscopy during pregnancy.

Gastroenterol Clin North Am 1998;27(1):3771.

[12] Cappell MS. The fetal safety and clinical efficacy of gastrointestinal endoscopy during preg-

nancy. Gastroenterol Clin North Am 2003;32(1):12379.

[13] Frank B. Endoscopy in pregnancy. In: Karlstadt RG, Surawicz CM, Croitoru R, editors.

Gastrointestinal disorders during pregnancy. Arlington (VA)7 American College of Gastro-

enterology; 1994. p. 249.

[14] Epstein H, Waxman A, Gleicher N, et al. Meperidine-induced sinusoidal fetal heart rate pat-

tern and reversal with naloxone. Obstet Gynecol 1982;59(Suppl):225.

[15] Kim-Lo SH, Ciliberto CF, Smiley RM. Anesthesia: principles and techniques. In: Cohen WR,editor. Cherry and Merkatzs complications of pregnancy. 5th edition. Philadelphia7 Lippincott

Williams & Wilkins; 2000. p. 85371.

[16] Rosenberg L, Mitchell AA, Parsells JL, et al. Lack of relation of oral clefts to diazepam use

during pregnancy. N Engl J Med 1983;309:12825.

[17] DiSario JA, Waring JP, Talbert G, et al. Monitoring of blood pressure and heart rate during

routine endoscopy: a prospective, randomized, controlled study. Am J Gastroenterol 1991;86:

95660.



24/31

[18] Hampton KK, Grant PJ, Primrose J, et al. Haemostatic responses and vasopressin release during

colonoscopy in man. Clin Sci 1991;81:25760.

[19] Lieberman DA, Wuerker CK, Katon RM. Cardiopulmonary risk of esophagogastroduodeno-

scopy. Gastroenterology 1985;88:46872.

[20] Mathews PK, Ona FV, Damevski K, et al. Arrhythmias during upper gastrointestinal

endoscopy. Angiology 1979;30:83440.

[21] Dark DS, Campbell DR, Wesselius U. Arterial oxygen desaturation during gastrointestinal

endoscopy. Am J Gastroenterol 1990;85:1317 21.

[22] Rozen F, Fireman Z, Gilat T. The causes of hypoxemia in elderly patients during endoscopy.

Gastrointest Endosc 1982;28:243 6.

[23] Gilbert DA, Silverstein FE, Tedesco FJ. National ASGE survey on upper gastrointestinal

bleeding: complications of endoscopy. Dig Dis Sci 1981;26(Suppl):55 9.

[24] Freeman JM, Freeman AD. Cerebral palsy and the dbad babyT malpractice crisis: New York

State shines light toward the end of the tunnel. Am J Dis Child 1992;146:7257.

[25] Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphinc-

terotomy. N Engl J Med 1996;335:90918.

[26] Andreoli M, Sayegh SK, Hoefer R, et al. Laparoscopic cholecystectomy for recurrent gallstone

pancreatitis during pregnancy. South Med J 1996;89:1114 5.

[27] Wishner JD, Zolfaghari D, Wohlgemuth SD, et al. Laparoscopic cholecystectomy in pregnancy:

a report of 6 cases and review of the literature. Surg Endosc 1996;10:3148.

[28] Gyokeres T, Topa L, Marton I, et al. Endoscopic cystogastrostomy during pregnancy.


[29] Ryan ME. Endoscopic management of a pancreatic pseudocyst during pregnancy. Gastrointest

Endosc 1992;38:6058.

[30] Aggarwal N, Sawhney H, Vasishta K, et al. Non-cirrhotic portal hypertension in pregnancy.Int J Gynecol Obstet 2001;72:17.

[31] Macedo C, Carvalho L, Ribeiro T. Endoscopic sclerotherapy for upper gastrointestinal bleeding

due to Mallory-Weiss syndrome [letter]. Am J Gastroenterol 1995;90:13645.

[32] Fiest TC, Foong A, Chokhavatia S. Successful balloon dilation of achalasia during pregnancy.


[33] Farca A, Aguilar ME, Rodriguez G, et al. Biliary stents as temporary treatment for chole-

docholithiasis in pregnant patients. Gastrointest Endosc 1997;46:99 101.

[34] Koh ML, Lipkin EW. Nutrition support of a pregnant comatose patient via percutaneous

endoscopic gastrostomy. JPEN J Parenter Enteral Nutr 1993;17:3847.

[35] Serrano P, Velloso A, Garcia-Luna PP, et al. Enteral nutrition by percutaneous endoscopic

gastrojejunostomy in severe hyperemesis gravidarum: a report of two cases. Clin Nutr 1998;17:1359.

[36] Cappell MS. Gastrointestinal endoscopy in high-risk patients. Dig Dis 1996;14:228 44.

[37] Kammerer WS. Nonobstetric surgery during pregnancy. Med Clin North Am 1979;63:

115764.

[38] Brent RL. The effect of embryonic and fetal exposure to x-ray, microwaves, and ultra-

sound: counseling the pregnant and nonpregnant patient about these risks. Semin Oncol 1989;

16:34768.

[39] Steinlauf AF, Traube M. Gastrointestinal complications. In: Burrow GN, Duffy TP, editors.

Medical complications during pregnancy. 5th edition. Philadelphia7 WB Saunders; 1999.

p. 255 68.

[40] Tamir IL, Bomghard FS, Klein SR. Acute appendicitis in the pregnant patient. Am J Surg1990;160:5716.

[41] Cappell MS, Friedel D. Abdominal pain during pregnancy. Gastroenterol Clin N Am 2003;

32:158.

[42] Baer JL, Reis RA, Arens RA. Appendicitis in pregnancy with changes in position and axis of

the normal appendix in pregnancy. JAMA 1932;98:1359 64.

[43] Esposito TJ, Gens DR, Smith LG, et al. Trauma during pregnancy: a review of 79 cases.

Arch Surg 1991;126:10738.

cappell24


25/31

[44] Schwartz WJ, Thurnau CR. Iron deficiency anemia in pregnancy. Clin Obstet Gynecol

1995;38:44354.

[45] Pritchard JA. Change in the blood volume during pregnancy and delivery. Anesthesiology

1965;26:3939.

[46] Martin C, Varner MW. Physiologic changes in pregnancy: surgical implications. Clin Obstet

Gynecol 1994;37:24155.

[47] Depue RH, Bernstein L, Ross RK, et al. Hyperemesis gravidarum in relation to estradiol levels,

pregnancy outcome, and other maternal factors: a seroepidemiologic study. Am J Obstet

Gynecol 1987;156:1137 41.

[48] Eichenberg BJ, Vanderlinden J, Miguel L, et al. Laparoscopic cholecystectomy in the third

trimester of pregnancy. Am Surg 1996;62:8747.

[49] Kort B, Katz VL, Watson WJ. The effect of nonobstetric operation during pregnancy. Surg

Gynecol Obstet 1994;177:3716.

[50] Berg JC, Miller R, Burkhalter E. Clinical value of pulse oximetry during routine diagnostic

and therapeutic endoscopic procedures. Endoscopy 1991;23:328 30.

[51] Gianopoulos JG. Establishing the criteria for anesthesia and other precautions for surgery

during pregnancy. Surg Clin North Am 1995;75:3345.

[52] Katz JD, Hook R, Barash PG. Fetal heart rate monitoring in pregnant patients undergoing

surgery. Am J Obstet Gynecol 1996;125:2679.

[53] Gardner-Medwin JM, Powell RJ. Thalidomide: the way forward. Postgrad Med J 1994;

70:8602.

[54] Newman LM, Johnson EM, Staples RE. Assessment of the effectiveness of animal de-

velopmental toxicity testing for human safety. Reprod Toxicol 1993;7:359 90.

[55] US Department of Health and Human Services. Vital statistics of the United States 1989: Vol I.

Natality. Hyattsville (MD)7

National Center for Health Statistics; 1993.[56] US Bureau of the Census. Statistical abstract of the United States 1993: the national data book.

113th edition. Washington7 US Bureau of the Census; 1993.

[57] Jefferies JA, Robboy SJ, OBrien PC, et al. Structural anomalies of the cervix and vagina in

women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project. Am J Obstet Gynecol

1984;148:5966.

[58] Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to

fetal and neonatal risk. 7th edition. Philadelphia7 Lippincott, Williams & Wilkins; 2005.

[59] Heinonen OP, Stone D, Shapiro S. Birth defects and drugs in pregnancy. Boston7

John Wright; 1982.

[60] Szeto HH, Zervoudakis IA, Cederquist LL, et al. Amniotic fluid transfer of meperidine

from maternal plasma in early pregnancy. Obstet Gynecol 1978;52:5962.[61] Savona-Ventura C, Sammut M, Sammut C. Pethidine blood concentrations at time of birth.

Int J Gynaecol Obstet 1991;36:1037.

[62] Hawkins JL. Obstetric anesthesia and analgesia. In: Scott JR, Gibbs RS, Karlan BY, et al,

editors. Danforths obstetrics and gynecology. 9th edition. Philadelphia7 Lippincott Williams &

Wilkins; 2003. p. 57 73.

[63] Kopecky EA, Koren G. Maternal drug abuse: effects on the fetus and neonate. In: Polin RA,

Fox WW, Abman SH, editors. Fetal and neonatal physiology. 3rd edition. Philadelphia7

Saunders; 2004. p. 234 49.

[64] Fairlie FM, Marshall L, Walker JJ, et al. Intramuscular opioids for maternal pain relief in

labour: a randomized controlled trial comparing pethidine with diamorphine. Br J Obstet

Gynaecol 1999;106:1181 7.[65] Olofsson C, Ekblom A, Ekman-Ordeberg G, et al. Lack of analgesic effect of systemically

administered morphine or pethidine on labour pain. Br J Obstet Gynaecol 1996;103:96872.

[66] Sheikh A, Tunstall ME. Comparative study of meptazinol and pethidine for the relief of pain

in labour. Br J Obstet Gynaecol 1986;93:2649.

[67] Belfrage P, Boreus LO, Hartvig P, et al. Neonatal depression after obstetrical analgesia with

pethidine: the role of injection-delivery time interval and the plasma concentrations of

pethidine and norpethidine. Acta Obstet Gynecol Scand 1981;60:439.



26/31

[68] Mattingly JE, DAlessio J, Ramanathan J. Effects of obstetric analgesics and anesthetics on

the neonate: a review. Paediatr Drugs 2003;5:61527.

[69] Belsey EM, Rosenblatt DB, Lieberman BA, et al. The influence of maternal analgesia on

neonatal behavior. I. Pethidine. Br J Obstet Gynaecol 1981;88:398406.

[70] Borgstedt AD, Rosen MG. Medication during labor correlated with behavior and EEG of

the newborn. Am J Dis Child 1968;115:21 4.

[71] Hodgkinson R, Bhatt M, Grewal G, et al. Neonatal neurobehavior in the first 48 hours

of life: effect of the administration of meperidine with and without naloxone in the mother.

Pediatrics 1978;62:294 8.

[72] Hodgkinson R, Bhatt M, Wang CN. Double-blind comparison of the neurobehaviour

of neonates following the administration of different doses of meperidine to the mother.

Can Anaesth Soc J 1978;25:40511.

[73] Kulmert BR, Lirm PL, Kennard MJ, et al. Effects of low doses of meperidine on neonatal

behavior. Anesth Analg 1985;64:335 42.

[74] Nissen E, Lilja G, Matthiesen AS, et al. Effects of maternal pethidine on infants developing

breast feeding behaviour. Acta Paediatr 1995;84:1405.

[75] Hodgkinson R, Husain FJ. The duration of effect of maternally administered meperidine on

neonatal neurobehavior. Anesthesiology 1982;56:512.

[76] Buck C. Drugs in pregnancy [letter]. Can Med Assoc J 1975;112:1285.

[77] Buck C, Gregg R, Stavraky K, et al. The effect of single prenatal and natal complications

upon the development of children of mature birth weight. Pediatrics 1969;43:9425.

[78] Golding J, Greenwood R, Birmingham K, et al. Childhood cancer, intramuscular vitamin K,

and pethidine given during labour. BMJ 1992;305:3416.

[79] Barrett JM, Boehm FH. Fetal heart rate responses to meperidine alone and in combination

with propiomazine. South Med J 1983;76:14803.[80] Petrie RH. Influence of meperidine on fetal movements and heart rate beat-to-beat variability

in the active phase of labor. Am J Perinatol 1988;5:306.

[81] Cunningham FG, Gant NF, Leveno KJ, et al. Analgesia and sedation. In: Williams Obstetrics.

21st edition. New York7 McGraw-Hill; 2001. p. 53763.

[82] Sosa CG, Balaguer E, Alonso JG, et al. Meperidine for dystocia during the first stage of labor:

A randomized controlled trial. Am J Obstet Gynecol 2004;191:12128.

[83] Freeman ML. Sedation and monitoring for gastrointestinal endoscopy. In: Yamada T, Alpers DH,

Kaplowitz N, et al, editors. Textbook of gastroenterology. 4th edition. Philadelphia7 Lippincott

Williams & Wilkins; 2003. p. 281224.

[84] Martin LV, Jurand A. The absence of teratogenic effects of some analgesics used in anaesthesia:

additional evidence from a mouse model. Anaesthesia 1992;47:4736.[85] Anonymous. Physicians desk reference. 59th edition. Montvale (NJ)7 Thomson Healthcare;

2005.

[86] Cooper J, Jauniaux E, Gulbis B, et al. Placental transfer of fentanyl in early human pregnancy

and its detection in fetal brain. Br J Anaesth 1999;82:92931.

[87] Shannon C, Jauniaux E, Gulbis B, et al. Placental transfer of fentanyl in early human preg-

nancy. Hum Reprod 1998;13:231720.

[88] Fernando R, Bonello E, Gill P, et al. Neonatal welfare and placental transfer of fentanyl and

bupivacaine during ambulatory combined spinal epidural analgesia for labour. Anaesthesia

1997;52:51724.

[89] Morley-Forster PK, Reid DW, Vandeberghe H. A comparison of patient-controlled analgesia

fentanyl and alfentanil for labour analgesia. Can J Anaesth 2000;47:1139.[90] Nelson KE, Rauch T, Terebuh V, et al. A comparison of intrathecal fentanyl and sufentanil for

labor analgesia. Anesthesiology 2002;96:1070 3.

[91] Rayburn W, Rathke A, Leuschen MP, et al. Fentanyl citrate analgesia during labor. Am J Obstet

Gynecol 1989;161:2026.

[92] Pace MC, Aurilio C, Bulletti C, et al. Subarachnoid analgesia in advanced labor: a comparison

of subarachnoid analgesia and pudendal block in advanced labor: analgesic quality and obstet-

ric outcome. Ann N Y Acad Sci 2004;1034:35663.

cappell26


27/31

[93] Porter J, Bonello E, Reynolds F. Effect of epidural fentanyl on neonatal respiration. Anes-

thesiology 1998;89:79 85.

[94] Carrie LE, OSullivan GM, Seegobin R. Epidural fentanyl in labour. Anaesthesia 1981;36:

9659.

[95] Lindemann R. Respiratory muscle rigidity in a preterm infant after use of fentanyl during

caesarean section. Eur J Pediatr 1998;157:10123.

[96] Regan J, Chambers F, Gorman W, et al. Neonatal abstinence syndrome due to prolonged

administration of fentanyl in pregnancy. Br J Obstet Gynaecol 2000;107:5702.

[97] Bakke OM, Haram K. Time-course of transplacental passage of diazepam: influence of

injection-delivery interval on neonatal drug concentrations. Clin Pharmacokinet 1982;7:

35362.

[98] Jauniaux E, Jurkovic D, Lees C, et al. In-vivo study of diazepam transfer across the first

trimester human placenta. Hum Reprod 1996;11:88992.

[99] Kanto J, Sjovall S, Erkkola R, et al. Placental transfer and maternal midazolam kinetics. Clin

Pharmacol Ther 1983;33:78691.

[100] Shepard TH. Catalog of teratogenic agents. 6th edition. Baltimore7 Johns Hopkins University

Press; 1989. p. 2036.

[101] Saxen I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol

1975;4:3744.

[102] Saxen I. Epidemiology of cleft lip and palate: an attempt to rule out chance correlations. Br J

Prev Soc Med 1975;29:10310.

[103] Saxen I, Saxen L. Association between maternal intake of diazepam and oral clefts. Lancet

1975;2:498.

[104] Rivas F, Hernandez A, Cantu JM. Acentric craniofacial cleft in a newborn female prenatally

exposed to a high dose of diazepam. Teratology 1984;30:17980.[105] Safra MJ, Oakley Jr GP. Association between cleft lip with or without cleft palate and prenatal

exposure to diazepam. Lancet 1975;2:47880.

[106] Safra MJ, Oakley Jr GP. Valium: an oral cleft teratogen? Cleft Palate J 1976;13:198 200.

[107] Czeizel A. Diazepam, phenytoin, and etiology of cleft lip and/or cleft palate. Lancet 1976;

1:810.

[108] Lakos P, Czeizel E. A teratological evaluation of anticonvulsant drugs. Acta Paediatr Acad Sci

Hung 1977;18:14553.

[109] Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy. N Engl J Med 1984;

311:919.

[110] Czeizel A. Lack of evidence of teratogenicity of benzodiazepine drugs in Hungary. Reprod

Toxicol 198788;1:1838.[111] Bergman U, Rosa FW, Baum C, et al. Effects of exposure to benzodiazepine during fetal life.

Lancet 1992;340:694 6.

[112] McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod

Toxicol 1994;8:461 75.

[113] Yankowitz J. Teratology and drugs in pregnancy. In: Scott JR, Gibbs RS, Karlan BY, et al,

editors. Danforths obstetrics and gynecology. 9th edition. Philadelphia7 Lippincott Williams &

Wilkins; 2003. p. 12941.

[114] Bracken MB, Holford TR. Exposure to prescribed drugs in pregnancy and association with

congenital malformations. Obstet Gynecol 1981;58:336 44.

[115] Rothman KJ, Fyler DC, Goldblatt A, et al. Exogenous hormones and other drug exposures

of children with congenital heart disease. Am J Epidemiol 1979;109:4339.[116] Courtens W, Vamos E, Hainaut M, et al. Mobius syndrome in an infant exposed in utero

to benzodiazepines. J Pediatr 1992;121:8334.

[117] Ornoy A, Arnon J, Shechtman S, et al. Is benzodiazepine use during pregnancy really

teratogenic? Reprod Toxicol 1998;12:511 5.

[118] Dolovich LR, Addis A, Vaillancourt JMR, et al. Benzodiazepine use in pregnancy and major

malformations or oral cleft: meta-analysis of cohort and case-controlled studies. BMJ 1998;

317:83943.



28/31

[119] Laegreid L, Olegard R, Wahlstrom J, et al. Abnormalities in children exposed to benzo-

diazepines in utero [letter]. Lancet 1987;1:1089.

[120] Laegreid L, Olegard R, Wahlstrom J, et al. Teratogenic effects of benzodiazepine use during

pregnancy. J Pediatr 1989;114:126 31.

[121] Gillberg C. Floppy infant syndrome and maternal diazepam. Lancet 1977;2(8031):244.

[122] Haram K. Floppy infant syndrome and maternal diazepam. Lancet 1977;2(8038):612 3.

[123] Speight AN. Floppy-infant syndrome and maternal diazepam and/or nitrazepam [letter]. Lancet

1977;1:878.

[124] Backes CR, Cordero L. Withdrawal symptoms in the neonate from presumptive intra-uterine

exposure to diazepam: report of a case. J Am Osteopath Assoc 1980;79:5845.

[125] Rementeria JL, Bhatt K. Withdrawal symptoms in neonates from intrauterine exposure to

diazepam. J Pediatr 1977;90:1236.

[126] Einarson A, Selby P, Koren G. Abrupt discontinuation of psychotropic drugs during pregnancy:

fear of teratogenic risk and impact of counseling. J Psychiatry Neurosci 2001;26:448.

[127] Einarson A, Selby P, Koren G. Discontinuing antidepressants and benzodiazepines upon

becoming pregnant. Beware of the risks of abrupt discontinuation. Can Fam Physician 2001;47:

48990.

[128] Macken E, Gevers AM, Hendrickx A, et al. Midazolam versus diazepam in lipid emulsion as

conscious sedation for colonoscopy with or without reversal of sedation with flumazenil.


[129] Bach V, Carl P, Ravjo O, et al. A randomized comparison between midazolam and thiopental

for elective cesarean section anesthesia: III. Placental transfer and elimination in neonates.

Anesth Analg 1989;68:23842.

[130] Kanto JH. Use of benzodiazepines during pregnancy, labour and lactation, with particular

reference to pharmacokinetic considerations. Drugs 1982;23:354 80.[131] Bland BAR, Lawes EG, Duncan PW, et al. Comparison of midazolam and thiopental for rapid

sequence anesthetic induction for elective cesarean section. Anesth Analg 1987;66:11658.

[132] Crawford ME, Carl P, Bach V, et al. A randomized comparison between midazolam and

thiopental for elective cesarean section anesthesia. I. Mothers. Anesth Analg 1989;68:229 33.

[133] Ravlo O, Carl P, Crawford ME, et al. A randomized comparison between midazolam and

thiopental for elective cesarean section anesthesia. II. Neonates. Anesth Analg 1989;68:2347.

[134] Wilson CM, Dundee JW, Moore J, et al. A comparison of the early pharmacokinetics of

midazolam in pregnant and nonpregnant women. Anaesthesia 1987;42:105762.

[135] Celleno D, Capogna G, Emanuelli M, et al. Which induction drug for cesarean section? A

comparison of thiopental sodium, propofol, and midazolam. J Clin Anesth 1993;5:2848.

[136] Kanto J, Sjovall S, Erkkola R, et al. Placental transfer and maternal midazolam kinetics. ClinPharmacol Ther 1983;33:78691.

[137] Tucker AP, Mezzatesta J, Nadeson R, et al. Intrathecal midazolam II: combination with

intrathecal fentanyl for labor pain. Anesth Analg 2004;98:15217.

[138] Padilla SL, Smith RD, Dugan K, et al. Laparascopically assisted gamete intrafallopian transfer

with local anesthesia and intravenous sedation. Fertil Steril 1996;66:4047.

[139] Phillipson EH, Kuhnert BR, Syracuse CD. Maternal, fetal, and neonatal lidocaine levels

following local perineal infiltration. Am J Obstet Gynecol 1984;149:4037.

[140] Scanlon JW, Brown Jr WU, Weiss JB, et al. Neurobehavioral responses of newborn infants after

maternal epidural anesthesia. Anesthesiology 1974;40:121 8.

[141] Abboud TK, David S, Costandi J, et al. Comparative maternal, fetal and neonatal effects

of lidocaine versus lidocaine with epinephrine in the parturient. Anesthesiology 1984;61(Suppl.):A405.

[142] Shnider SM, Way EL. Plasma levels of lidocaine (Xylocaine) in mother and newborn following

obstetrical conduction anesthesia: clinical applications. Anesthesiology 1968;29:9518.

[143] Liston WA, Adjepon-Yamoah KK, Scott DB. Foetal and maternal lignocaine levels after

paracervical block. Br J Anaesth 1973;45:7504.

[144] Kim WY, Pomerance JJ,

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