Preventing Nitrous Oxide Effects Limit exposure No benefit from folinic acid Combine with potent agent
CNS Growth and Development 2 nd trimester to 2 nd postnatal month: major period of myelination 2 nd and 3 rd 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 CNS Toxicity 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 N 2 O in oxygen midazolam in DMSO isoflurane J Neurosci 2003; 23:876
Neuroapoptosis Courtesy Lena Sun
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
1 st Trimester & CNS Effects *
Anesthesia for Cesarean Delivery and Learning Disabilities Deliveries in Olmsted County, Cohort review: Vaginal Delivery Cesarean Delivery – GEA Cesarean Delivery – Regional Assessment of Learning Anesthesiology 2009; 111:302
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 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 * *
When Is the Best Time? TERATOGENICITY PREMATURE LABOR
Appendectomy During Pregnancy All women delivering in Sweden *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 – Method: Linked registries: Birth registry Congenital Anomalies Hospital Discharges Am J OB/GYN 1997; 177:673
Obstetric Outcome Relative Risk
Pregnant Patient Elective SurgeryEssential SurgeryEmergency Surgery Delay until postpartum1 st trimester2 nd /3 rd 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