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2 cappell
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.
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.
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 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:
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
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
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
Standard
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
10 cappell
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.
12 cappell
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
Meperidine (category B)
Fentanyl (category C)
Diazepam (category D)
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
Midazolam (category D)
Lidocaine (category B)
Propofol (category B)
Ketamine (category B)
Naloxone (category B)
Flumazenil (category C)
overdose can be prevented by careful and slow titration and the administration of
the minimal dosage of benzodiazepines required for endoscopy [83].
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
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;
37:421 – 7.
[2] Cooper GS. Indications and contraindications for upper gastrointestinal endoscopy. Gastrointest
Endosc Clin N Am 1994;4:439 – 54.
[3] Newcomer MK, Brazer SR. Complications of upper gastrointestinal endoscopy and their
management. Gastrointest Endosc Clin N Am 1994;4:551 – 70.
[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;41:2353 – 60.
[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;91:348 – 54.
[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;40:256 – 62.
[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;88:1900 – 5.
[8] Castro LP. Reflux esophagitis as the cause of heartburn in pregnancy. Am J Obstet Gynecol
1967;98:1 – 10.
[9] Jamidar PA, Beck GJ, Hoffman BJ, et al. Endoscopic retrograde cholangiopancreatography
in pregnancy. Am J Gastroenterol 1995;90:1263 – 7.
[10] Cappell MS. Gastrointestinal endoscopy in pregnant women: risks versus benefits. Nature
Clinical 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):37 – 71.
[12] Cappell MS. The fetal safety and clinical efficacy of gastrointestinal endoscopy during preg-
nancy. Gastroenterol Clin North Am 2003;32(1):123 – 79.
[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. 24 – 9.
[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):22 – 5.
[15] Kim-Lo SH, Ciliberto CF, Smiley RM. Anesthesia: principles and techniques. In: Cohen WR,
editor. Cherry and Merkatz’s complications of pregnancy. 5th edition. Philadelphia7 Lippincott
Williams & Wilkins; 2000. p. 853 – 71.
[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;309:1282 – 5.
[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:
956 – 60.
24 cappell
[18] Hampton KK, Grant PJ, Primrose J, et al. Haemostatic responses and vasopressin release during
colonoscopy in man. Clin Sci 1991;81:257 – 60.
[19] Lieberman DA, Wuerker CK, Katon RM. Cardiopulmonary risk of esophagogastroduodeno-
scopy. Gastroenterology 1985;88:468 – 72.
[20] Mathews PK, Ona FV, Damevski K, et al. Arrhythmias during upper gastrointestinal
endoscopy. Angiology 1979;30:834 – 40.
[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;146:725 – 7.
[25] Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphinc-
terotomy. N Engl J Med 1996;335:909 – 18.
[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;10:314 – 8.
[28] Gyokeres T, Topa L, Marton I, et al. Endoscopic cystogastrostomy during pregnancy.
Gastrointest Endosc 2001;53:516 – 8.
[29] Ryan ME. Endoscopic management of a pancreatic pseudocyst during pregnancy. Gastrointest
Endosc 1992;38:605 – 8.
[30] Aggarwal N, Sawhney H, Vasishta K, et al. Non-cirrhotic portal hypertension in pregnancy.
Int J Gynecol Obstet 2001;72:1 – 7.
[31] Macedo C, Carvalho L, Ribeiro T. Endoscopic sclerotherapy for upper gastrointestinal bleeding
due to Mallory-Weiss syndrome [letter]. Am J Gastroenterol 1995;90:1364 – 5.
[32] Fiest TC, Foong A, Chokhavatia S. Successful balloon dilation of achalasia during pregnancy.
Gastrointest Endosc 1993;39:810 – 2.
[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;17:384 – 7.
[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;
17:135 – 9.
[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:
1157 – 64.
[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;
16:347 – 68.
[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 Surg
1990;160:571 – 6.
[41] Cappell MS, Friedel D. Abdominal pain during pregnancy. Gastroenterol Clin N Am 2003;
32:1 – 58.
[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;126:1073 – 8.
sedation and analgesia during pregnancy 25
[44] Schwartz WJ, Thurnau CR. Iron deficiency anemia in pregnancy. Clin Obstet Gynecol
1995;38:443 – 54.
[45] Pritchard JA. Change in the blood volume during pregnancy and delivery. Anesthesiology
1965;26:393 – 9.
[46] Martin C, Varner MW. Physiologic changes in pregnancy: surgical implications. Clin Obstet
Gynecol 1994;37:241 – 55.
[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;62:874 – 7.
[49] Kort B, Katz VL, Watson WJ. The effect of nonobstetric operation during pregnancy. Surg
Gynecol Obstet 1994;177:371 – 6.
[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;75:33 – 45.
[52] Katz JD, Hook R, Barash PG. Fetal heart rate monitoring in pregnant patients undergoing
surgery. Am J Obstet Gynecol 1996;125:267 – 9.
[53] Gardner-Medwin JM, Powell RJ. Thalidomide: the way forward. Postgrad Med J 1994;
70:860 – 2.
[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, O’Brien PC, et al. Structural anomalies of the cervix and vagina in
women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project. Am J Obstet Gynecol
1984;148:59 – 66.
[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;52:59 – 62.
[61] Savona-Ventura C, Sammut M, Sammut C. Pethidine blood concentrations at time of birth.
Int J Gynaecol Obstet 1991;36:103 – 7.
[62] Hawkins JL. Obstetric anesthesia and analgesia. In: Scott JR, Gibbs RS, Karlan BY, et al,
editors. Danforth’s 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;103:968 – 72.
[66] Sheikh A, Tunstall ME. Comparative study of meptazinol and pethidine for the relief of pain
in labour. Br J Obstet Gynaecol 1986;93:264 – 9.
[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;60:43 – 9.
26 cappell
[68] Mattingly JE, D’Alessio J, Ramanathan J. Effects of obstetric analgesics and anesthetics on
the neonate: a review. Paediatr Drugs 2003;5:615 – 27.
[69] Belsey EM, Rosenblatt DB, Lieberman BA, et al. The influence of maternal analgesia on
neonatal behavior. I. Pethidine. Br J Obstet Gynaecol 1981;88:398 – 406.
[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;25:405 – 11.
[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;84:140 – 5.
[75] Hodgkinson R, Husain FJ. The duration of effect of maternally administered meperidine on
neonatal neurobehavior. Anesthesiology 1982;56:51 – 2.
[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;43:942 – 5.
[78] Golding J, Greenwood R, Birmingham K, et al. Childhood cancer, intramuscular vitamin K,
and pethidine given during labour. BMJ 1992;305:341 – 6.
[79] Barrett JM, Boehm FH. Fetal heart rate responses to meperidine alone and in combination
with propiomazine. South Med J 1983;76:1480 – 3.
[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. 537 – 63.
[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;191:1212 – 8.
[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. 2812 – 24.
[84] Martin LV, Jurand A. The absence of teratogenic effects of some analgesics used in anaesthesia:
additional evidence from a mouse model. Anaesthesia 1992;47:473 – 6.
[85] Anonymous. Physician’s 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;82:929 – 31.
[87] Shannon C, Jauniaux E, Gulbis B, et al. Placental transfer of fentanyl in early human preg-
nancy. Hum Reprod 1998;13:2317 – 20.
[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;52:517 – 24.
[89] Morley-Forster PK, Reid DW, Vandeberghe H. A comparison of patient-controlled analgesia
fentanyl and alfentanil for labour analgesia. Can J Anaesth 2000;47:113 – 9.
[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;161:202 – 6.
[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;1034:356 – 63.
sedation and analgesia during pregnancy 27
[93] Porter J, Bonello E, Reynolds F. Effect of epidural fentanyl on neonatal respiration. Anes-
thesiology 1998;89:79 – 85.
[94] Carrie LE, O’Sullivan GM, Seegobin R. Epidural fentanyl in labour. Anaesthesia 1981;36:
965 – 9.
[95] Lindemann R. Respiratory muscle rigidity in a preterm infant after use of fentanyl during
caesarean section. Eur J Pediatr 1998;157:1012 – 3.
[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;107:570 – 2.
[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:
353 – 62.
[98] Jauniaux E, Jurkovic D, Lees C, et al. In-vivo study of diazepam transfer across the first
trimester human placenta. Hum Reprod 1996;11:889 – 92.
[99] Kanto J, Sjovall S, Erkkola R, et al. Placental transfer and maternal midazolam kinetics. Clin
Pharmacol Ther 1983;33:786 – 91.
[100] Shepard TH. Catalog of teratogenic agents. 6th edition. Baltimore7 Johns Hopkins University
Press; 1989. p. 203 – 6.
[101] Saxen I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol
1975;4:37 – 44.
[102] Saxen I. Epidemiology of cleft lip and palate: an attempt to rule out chance correlations. Br J
Prev Soc Med 1975;29:103 – 10.
[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;30:179 – 80.
[105] Safra MJ, Oakley Jr GP. Association between cleft lip with or without cleft palate and prenatal
exposure to diazepam. Lancet 1975;2:478 – 80.
[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;18:145 – 53.
[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 1987–88;1:183 – 8.
[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. Danforth’s obstetrics and gynecology. 9th edition. Philadelphia7 Lippincott Williams &
Wilkins; 2003. p. 129 – 41.
[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;109:433 – 9.
[116] Courtens W, Vamos E, Hainaut M, et al. Mobius syndrome in an infant exposed in utero
to benzodiazepines. J Pediatr 1992;121:833 – 4.
[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;
317:839 – 43.
28 cappell
[145] Kileff ME, James III FM, Dewan DM, et al. Neonatal neurobehavioral responses after epi-
dural anesthesia for cesarean section using lidocaine and bupivacaine. Anesth Analg 1984;63:
413 – 7.
[146] Levy BT, Bergus GR, Hartz A, et al. Is paracervical block safe and effective? A prospec-
tive study of its association with neonatal umbilical artery pH values. J Fam Pract 1999;48:
778 – 84.
[147] Gowda RM, Khan IA, Mehta NJ, et al. Cardiac arrhythmias in pregnancy: clinical and
therapeutic considerations. Int J Cardiol 2003;88:129 – 33.
[148] Rex DK. The science and politics of propofol. Am J Gastroenterol 2004;99:2080 – 3.
[149] Lazzaroni M, Porro GB. Preparation, premedication, and surveillance. Endoscopy
2005;37:101 – 9.
[150] Alon E, Ball RH, Gillie MH, et al. Effects of propofol and thiopental on maternal and fetal
cardiovascular and acid-base variables in the pregnant ewe. Anesthesiology 1993;78:562 – 76.
[151] Dailland P, Cockshott ID, Lirzin JD, et al. Intravenous propofol during cesarean section:
placental transfer, concentrations in breast milk, and neonatal effects—a preliminary study.
Anesthesiology 1989;71:827 – 34.
[152] Sanchez-Alcaraz A, Quintana MB, Laguarda M. Placental transfer and neonatal effects of
propofol in caesarean section. J Clin Pharm Ther 1998;23:19 – 23.
[153] Celleno D, Capogna G, Tomassetti M, et al. Neurobehavioral effects of propofol on the neonate
following elective caesarean section. Br J Anaesth 1989;62:649 – 54.
[154] Abboud TK, Zhu J, Richardson M, et al. Intravenous propofol vs thiamylal-isoflurane for
caesarean section: comparative maternal and neonatal effects. Acta Anaesthesiol Scand 1995;
39:205 – 9.
[155] Cheng YJ, Wang YP, Fan SZ, et al. Intravenous infusion of low dose propofol for conscious
sedation in cesarean section before spinal anesthesia. Acta Anaesthesiol Sin 1997;35:79 – 84.
[156] Gregory MA, Gin T, Yau G, et al. Propofol infusion anaesthesia for caesarean section. Can J
Anaesth 1990;37:514 – 20.
[157] Gin T, O’Meara ME, Kan AF, et al. Plasma catecholamines and neonatal condition after
induction of anaesthesia with propofol or thiopentone at caesarean section. Br J Anaesth
1993;70:311 – 6.
[158] Gin T. Propofol during pregnancy. Acta Anaesthesiol Sin 1994;32:127 – 32.
[159] Yau G, Gin T, Ewart MC, et al. Propofol for induction and maintenance of anaesthesia
at caesarean section: a comparison with thiopentone/enflurane. Anaesthesia 1991;46:20 – 3.
[160] Gilger MA, Spearman RS, Dietrich CL, et al. Safety and effectiveness of ketamine as a sedative
agent for pediatric GI endoscopy. Gastrointest Endosc 2004;59:659 – 63.
[161] El-Karum AHA, Benny R. Embryotoxic and teratogenic action of ketamine. Ain Shams Med J
1976;27:459 – 63.
[162] Eng M, Bonica JJ, Akamatsu TJ, et al. Respiratory depression in newborn monkeys at
caesarean section following ketamine administration. Br J Anaesth 1975;47:917 – 21.
[163] Fredriksson A, Archer T, Alm H, et al. Neurofunctional deficits and potentiated apoptosis by
neonatal NMDA antagonist administration. Behav Brain Res 2004;153:367 – 76.
[164] Nishijima M. Ketamine in obstetric anesthesia: special reference to placental transfer and its
concentration in blood plasma. Acta Obstet Gynaecol Jpn 1972;19:80 – 93.
[165] Marx GF, Hwang HS, Chandra P. Postpartum uterine pressures with different doses of
ketamine. Anesthesiology 1979;50:163 – 6.
[166] Maduska AL, Hajghassemali M. Arterial blood gases in mothers and infants during ketamine
anesthesia for vaginal delivery. Anesth Analg 1978;57:121 – 3.
[167] Marx GF, Cabe CM, Kim YI, et al. Neonatal blood pressures. Anaesthesist 1976;25:318 – 22.
[168] Baraka A, Louis F, Dalleh R. Maternal awareness and neonatal outcome after ketamine
induction of anaesthesia for caesarean section. Can J Anaesth 1990;37:641 – 4.
[169] Hodgkinson R, Bhatt M, Kim SS, et al. Neonatal neurobehavioral tests following cesarean
section under general and spinal anesthesia. Am J Obstet Gynecol 1978;132:670 – 4.
[170] Corssen G. Ketamine in obstetric anesthesia. Clin Obstet Gynecol 1974;17:249 – 58.
[171] Friedman JM. Teratogen update: anesthetic agents. Teratology 1988;37:69 – 77.
30 cappell
[172] Fukuda K. Intravenous opioid anesthetics. In: Miller RD, editor. Miller’s anesthesia. 6th edition.
Philadelphia7 Churchill Livingstone; 2005. p. 379 – 437.
[173] Hibbard BM, Rosen M, Davies D. Placental transfer of naloxone. Br J Anaesth 1986;58:45 – 8.
[174] De-Castro RM, Cabral-Filho JE, Costa JA, et al. Neonatal treatment with naloxone causes
permanent hyperalgesia in rats. Braz J Med Biol Res 1993;27:747 – 51.
[175] Arduini D, Rizzo G, Dell’Acqua S, et al. Effect of naloxone on fetal behavior near term. Am J
Obstet Gynecol 1987;156:474 – 8.
[176] Brookshire GL, Shnider SM, Abboud TK, et al. Effects of naloxone on the mother and neonate
after intrathecal morphine for labor analgesia [abstract]. Anesthesiology 1983;59:A417.
[177] Bonta BW, Gagliardi JV, Williams V, et al. Naloxone reversal of mild neurobehav-
ioral depression in normal newborn infants after routine obstetric analgesia. J Pediatr
1979;94:102 – 5.
[178] Welles B, Belfrage P, de Chateau P. Effects of naloxone on newborn infant behavior after
maternal analgesia with pethidine during labor. Acta Obstet Gynecol Scand 1984;63:617 – 9.
[179] Goodlin RC. Naloxone and its possible relationship to fetal endorphin levels and fetal distress.
Am J Obstet Gynecol 1981;139:16 – 9.
[180] American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics
1998;101:1079 – 88.
[181] Gibbs J, Newson T, Williams J, et al. Naloxone hazard in infant of opioid abuser. Lancet 1989;
2:159 – 60.
[182] Hoffman EJ, Warren EW. Flumazenil: a benzodiazepine antagonist. Clin Pharm 1993;12:
641 – 56.
[183] Dunk AA, Norton AC, Hudson M, et al. The value of flumazenil in the reversal of midazolam-
induced sedation for upper gastrointestinal endoscopy. Aliment Pharmacol Ther 1990;4:35 – 42.
[184] Cagiano R, de Salvia MA, Giustino A, et al. Behavioral changes produced in rats by devel-
opmental exposure to flumazenil, a benzodiazepine receptor antagonist. Prog Neuropsycho-
pharmacol Biol Psychiatry 1993;17:151 – 9.
[185] Stahl MMS, Saldeen P, Vinge E. Reversal of fetal benzodiazepine intoxication using
flumazenil. Br J Obstet Gynaecol 1993;100:185 – 8.
[186] Shibata T, Kubota N, Yokoyama H. A pregnant woman with convulsion treated with diazepam
which was reversed with flumazenil just prior to cesarean section. Masui 1994;43:572 – 4.
[187] Bailey B. Are there teratogenic risks associated with antidotes used in the acute management
of poisoned pregnant women? Birth Defects Res A Clin Mol Teratol 2003;67:133 – 40.
[188] Richard F, Autret E, Bardol J, et al. The use of flumazenil in a neonate. J Toxicol Clin Toxicol
1991;29:137 – 40.
[189] Dixon JC, Speidel BD, Dixon JJ. Neonatal flumazenil therapy reverses maternal diazepam.
Acta Paediatr 1998;87:225 – 6.
[190] Collins S, Carter JA. Resedation after bolus administration of midazolam to an infant and its
reversal by flumazenil. Anaesthesia 1991;46:471 – 2.
[191] Brogden RN, Goa KL. Flumazenil. A reappraisal of its pharmacological properties and
therapeutic efficacy as a benzodiazepine antagonist. Drugs 1991;42:1061 – 89.
[192] Kreuer S, Biedler A, Larsen R, et al. The Narcotrend: a new EEG monitor designed to measure
the depth of anaesthesia. A comparison with bispectral index monitoring during propofol-
remifentanil-anaesthesia. Anaesthetist 2001;50:921 – 5.
[193] Ortolani O, Conti A, di Filippo A, et al. EEG signal processing in anaesthesia: use of a neural
network technique for monitoring depth of anaesthesia. Br J Anaesth 2002;88:644 – 8.
[194] Schultz B, Grouven U, Schultz A. Automated classification algorithms of the EEG monitor
Narcotrend for routinely recorded EEG data from general anaesthesia: a validation study.
Biomed Tech (Berl) 2002;47:9 – 13.
[195] Campo R, Montserrat A, Brullet E. Transnasal gastroscopy compared to conventional
gastroscopy: a randomized study of feasibility, safety and tolerance. Endoscopy 1998;30:
448 – 52.
[196] Appleyard M, Glukhovsky A, Swain P. Wireless-capsule diagnostic endoscopy for recurrent
small-bowel bleeding. N Engl J Med 2001;344:232 – 3.
sedation and analgesia during pregnancy 31
[197] Ramirez FC, Shaukat MS, Young MA, et al. Feasibility and safety of string, wireless capsule
endoscopy in the diagnosis of Barrett’s esophagus. Gastrointest Endosc 2005;61:741 – 6.
[198] Ahlquist DA, Shuber AP. Stool screening for colorectal cancer: evolution from occult blood
to molecular markers. Clin Chim Acta 2002;315:157 – 68.
[199] Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versus fecal occult blood for
colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704 – 14.
[200] Lefkovitz Z, Shapiro R, Koch S, et al. The emerging role of virtual colonoscopy. Med Clin
North Am 2005;89:111 – 38.
[201] American College of Radiology. MR safety and sedation. In: 1998 American College of
Radiology Standards. Reston (VA)7 American College of Radiology; 1998. p. 457.
[202] Chan YL, Chan AC, Lam WW, et al. Choledocholithiasis: comparison of MR cholangiography
and endoscopic retrograde cholangiography. Radiology 1996;200:85 – 9.
[203] Seidman DS, Heyman Z, Ben-Ari G, et al. Use of magnetic resonance imaging in pregnancy
to diagnose intussusception induced by colon cancer. Obstet Gynecol 1992;79:822 – 3.
[204] Colletti PM, Sylvestre PB. Magnetic resonance imaging in pregnancy. Magn Reson Imaging
Clin N Am 1994;2:291 – 307.
[205] Kanal E, Borgstede JP, Barkovich AJ, et al. American College of Radiology white paper
on MR safety. AJR 2002;178:1135 – 47.