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; 138:1167Am J OB/GYN 1989; 161:1178

Breakdown by Trimester

0

20

40

60

80

100

First

Second

Third

%

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;86:73Anesth Analg 2001;93:1565

Maternal – MAC

Vol %

Anesthesiology 1994; 81:829Anesthesiology 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???

METHYLTERAHYDROFOLATEHOMOCYSTEINE

METHIONINE TERAHYDROFOLATE

S-ADENOSYLMETHIONINE

ACTIVE FORMATE

FORMYLTETRAHYDROFOLATE(FOLINIC ACID)

FORMYLTETRAHYDROFOLATE(FOLINIC ACID)

MethionineSynthetaseMethionineSynthetase

METHYLENE TETRAHYDROFOLATE

DIHYDROFOLATETHYMIDINEDNA

DEOXYURIDINE

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:

Exposure+ GABA-NMDA

Cognitive: IQ psychomotor memory, attention

Morbidity: mental retardation affective disorders degenerative dis.

Mortality: early death

CNSToxicity

Mechanisms:(+) Apoptosis

(-) Neurogenesis ∆ Cytoskeleton

∆ Dendritic spines(-)Synapse

UNDEFINED?

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

1st 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 Essential Surgery Emergency Surgery

Delay until postpartum 1st trimester 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