Anesthetic Considerations for
Women Having Surgery While
Pregnant
Alan. C. Santos, MD, MPH
St. Luke’s-Roosevelt Hospital Center
New York, NY 10025
Contents
• Scope of the Problem
• Maternal Considerations (brief)
• Fetal Considerations
Teratogenicity
Obstetric Outcome
Long-Term Consequences?
• Nuts and Bolts
Scope of the Problem
• 0.3 to 2.2% of all pregnancies
• 87,000 in US and 115,000 in Europe
Am J OB/GYN 1980; 138:1167
Am J OB/GYN 1989; 161:1178
Breakdown by Trimester
100
First
80
Second
Third
60
%
40
20
0
Indications
• Gynecologic/Obstetric
circlage
torsion
• Other Abdominal Surgery
appendectomy
cholecystectomy
• Trauma
Maternal - Hemodynamics
• Increase in plasma volume
hemodilution - lower hematocrit
greater free fraction of drug
dilution of cholinesterase
• Increase CO/decrease SVR/±BP
• Aorta-caval compression
• Hypercoagulable state
Maternal - Respiratory
• Increase in minute ventilation
increase arterial oxygen tension
decrease in arterial carbon dioxide
Ph remains unchanged
• Decrease in FRC
• Increase in oxygen consumption
Maternal - Gastrointestinal
• Relaxation of gastroesophageal sphincter
heartburn
• Mechanical factors (growing uterus)
• Delayed gastric emptying
opioids
labor
Maternal – Induction Agents
CD50
Anesthesiology 1997;86:73
Anesth Analg 2001;93:1565
Maternal – MAC
Vol %
Anesthesiology 1994; 81:829
Anesthesiology 1996; 85:782
Maternal – Inhalational Agents
Anesthesiology 1994; 81:829
Maternal – Local Anesthetic Effect
Group
CSF
Progesterone ng.ml-1
Dermatomal Spread
Non-pregnant
0
T3-T11
1st Trimester
0.23
T3-T11
2nd Trimester
0.49
C8-T11
3rd Trimester
1.46
C7-T7
BJA 1995; 75:683
Maternal – Local Anesthetic Effect
• Epidural venous engorgement
• Reduced CSF volume
Fetal Risks
• Congenital Anomalies
• Spontaneous abortion/embryonic loss
• Premature labor
• Fetal demise
• Long term consequences???
Teratogenicity
• Structural (exposure day 15 – 55)
Congenital anomalies
Growth restriction
Enzyme deficiency
Resorptions/Death
• Behavioral (exposure late pregnancy)
Emotions
Learning
Adaptive
Teratogenicity
• Species Vulnerability
• Timing of Exposure
• Magnitude of Exposure
• Susceptibility/Genetic Predisposition
Teratogens
• Cocaine!
• Diazepam?
• Nitrous Oxide???
HOMOCYSTEINE
METHYLTERAHYDROFOLATE
Methionine
Synthetase
METHIONINE
TERAHYDROFOLATE
S-ADENOSYL
METHIONINE
ACTIVE FORMATE
FORMYLTETRAHYDROFOLATE
(FOLINIC ACID)
DEOXYURIDINE
DNA
THYMIDINE
METHYLENE
TETRAHYDROFOLATE
DIHYDROFOLATE
Nitrous Oxide Teratogenicity
• N2O 70% - fetal resorption/malformation
• N2O & Folinic – partial reversal
• N20 & Isoflurane – reversal
• N20 7 Pnenoxybenzamine - reversal
Preventing Nitrous Oxide Effects
• Limit exposure
• No benefit from folinic acid
• Combine with potent agent
CNS Growth and Development
• 2nd trimester to 2nd postnatal month:
major period of myelination
• 2nd and 3rd trimester:
neuronal proliferation and migration
region specific synaptogenesis
remodeling
• 80% of adult brain volume by age 2 years
Potential Anesthesia CNS Effects:
Cognitive:
Mechanisms:
Exposure
+ GABA
-NMDA
(+) Apoptosis
(-) Neurogenesis
∆ Cytoskeleton
∆ Dendritic spines
(-)Synapse
UNDEFINED?
CNS
Toxicity
IQ
psychomotor
memory, attention
Morbidity:
mental retardation
affective disorders
degenerative dis.
Mortality:
early death
Courtesy: Lena Sun
Early Exposure to Anesthetics
• ANIMALS: Sprague-Dawley rat pups day 7
• METHODS:
Control: DMSO
Study: 6 hour exposure to mock GA
N2O in oxygen
midazolam in DMSO
isoflurane
J Neurosci 2003; 23:876
Neuroapoptosis
Courtesy Lena Sun
Behavioral Effects
CNS Effects
• Atlanta Birth Defects Case-Control Database
• Infants born with major CNS defects
No anesthesia
General Anesthesia
Am J Public Health 1994; 84:1757
st
1
Trimester & CNS Effects
*
Anesthesia for Cesarean Delivery
and Learning Disabilities
• Deliveries in Olmsted County, 1976-1982
• Cohort review:
Vaginal Delivery
Cesarean Delivery – GEA
Cesarean Delivery – Regional
• Assessment of Learning
Anesthesiology 2009; 111:302
Cumulative Learning Disabilities
Isoflurane Exposure In Utero
• Animals:
Pregnant rats at day 14
• Methods:
Exposure to:
isoflurane in 100% oxygen
100% oxygen
• Results:
impaired spatial memory
reduced anxiety
Anesthesiology 2011; 114:521
Hyperoxia is also bad!
• J Neurosci 2008; 28:1236
• J Neurosci Res 2006; 84:306
• Cell Death Differ 2006; 13:1097
• Neurobiol Dis 2004; 17:273
What Are the Limitations?
• Species: Rats vs Lambs vs Humans
• Study Design: Retrospective
• Dose and Magnitude of Exposure
• Specificity: All Drugs Equal All the Time?
The Studies We Need
• Large scale, national studies
• Agents and exposure
• Timing
An Academic Exercise?
• Surgery during pregnancy is undertaken
only if absolutely necessary
• Mothers will require an anesthetic
is regional better than general?
• Children requiring surgery need anesthesia
Prevention
• Lithium
• Hypothermia
• Are some agents better than others
Any inhalational agent better:
desflurane-isoflurane-sevflurane?
• Animals:
Neonatal mice
• Methods:
Determine MAC in littermates
Study: 0.6 MAC for 6 H
Control: 6 h fast in RA
Euthanize – caspase-3 neurons
• Results:
No differences among the 3 agents
Anesthesiology 2011; 114;578
What Are the Important
Determinants of Fetal Outcome?
• Maternal Disease
• Site of Surgery
Obstetric
Pelvic
Abdominal
Peripheral
Reproductive Outcome After Anesthesia
and Surgery During Pregnancy
• All women delivering in Sweden 1973-1981
• Linked Registries:
Birth registry
Congenital Anomalies
Hospital Discharges
AJOG 1989; 161:1178
Results
• Deliveries
880,000
• Non-Ob Surgery
5,404
• Incidence
0.75%
Outcomes
*
*
Anesthetic Technique
When Is the Best Time?
TERATOGENICITY
PREMATURE LABOR
Appendectomy During Pregnancy
• All women delivering in Sweden 1973-1981
*appendectomy
• Linked Registries:
Birth registry
Congenital Anomalies
Hospital Discharges
Obstet Gynecol 1991; 77:835
Appendectomy During
Pregnancy
• Prior to 24 weeks – no effect
• Of women at 24 to 36 weeks delivered:
day of
16%
day after
5%
within 1 week
22%
Laparoscopy During Pregnancy
• Subjects: Women having abd/pelvic surgery
Sweden – 1973-1993
• Method: Linked registries:
Birth registry
Congenital Anomalies
Hospital Discharges
Am J OB/GYN 1997; 177:673
Obstetric Outcome
Relative Risk
Pregnant Patient
Elective Surgery
Delay until postpartum
Essential Surgery
1st trimester
Emergency Surgery
2nd/3rd trimester
If no minimal increased risk
to mother, consider delaying
until mid-gestation.
If greater than minimal
increased risk to mother,
proceed with surgery.
Proceed with optimal anesthetic for mother,
modified by considerations for maternal
physiologic changes and fetal well being.
Consider consulting a perinatologist or an
obstetrician.
Intraoperative and postoperative fetal and
uterine monitoring may be useful.
Nuts and Bolts (1)
• Timing as discussed
• Pre-anesthesia assessment:
surgical disease
co-morbidities
gestational age
risk of aspiration
physiologic alterations
fetal assessment
Nuts and Bolts (2)
• Prior to fetal viability:
confirmation of FHR by Doppler
• At fetal viability:
hospital that can manage obstetric issues
obstetrician to assume care
continuous fetal monitoring????
Nuts and Bolts (3)
• Second trimester on:
avoid aorta-caval compression
oxygenation and ventilation
maintain blood pressure
• Choice of Anesthesia
based on maternal condition
avoid hyperoxia
regional vs general??????
Nuts and Bolts (4)
• Post-operative care:
vigilance and monitoring
assess fetal status
assess/prevent/treat preterm labor
treat pain and discomfort aggressively