HARRY SINGH, MD DEPT. OF ANESTHESIOLOGY UTMB Preterm Labor 9.5%-1982 Preterm Labor 11%-1994 69%-83% Neonatal deaths Despite improved care the incidence of preterm delivery remains greater than 11% in US Current areas of research: Determination of causes Early identification of women at risk Optimal recognition and treatment Preterm infant : 20-37 weeks gestation or 3 weeks before expected date of delivery SGA: Small for gestational age Infant weight < 2500 gms at birth-LBW Infant weight < 1500 gms at birth-VLBW ↑Survival rate with ↑gestational age and birth weight 70%-80% survival in infants weighing 750 to 1000 gms High mortality rate with weight < 750 gms 24 weeks-Survival 43% 25 weeks-Survival 74% 26 weeks-Survival 83% Greatest gain achieved by prolonging pregnancy beyond 24 weeks gestation Survival exceeds 90% by 30 weeks gestation 90% Preterm births: 30-36 weeks gestation Morbidity primary concern at this gestational age ↓ Morbidity from RDS > 36 weeks gestation ↓ Morbidity from IVH (grade III and IV) > 27 weeks gestation ↓ Morbidity from necrotizing enterocolitis and patent ductus arteriosus > 32 weeks gestation History of preterm delivery History of diethylstilbestrol exposure History of second trimester abortion Young age<18 years Low socioeconomic status Acute or chronic systemic disease Trauma Abdominal surgery during pregnancy Infections: Untreated syphilis, Neisseria gonorrhoeae, asymptomatic group B streptococcus, acute pyelonephritis, cervicovaginal infections Smoking Drug abuse Overdistention of cavity: multiple gestation, polyhydramnios Abnormal cavity: uterine anomaly, fibroids Foreign body: intrauterine device Cervical incompetence Trauma to cervix Faulty placentation: placenta previa, placental abruption Genetic abnormality Fetal death Premature rupture of membranes Iatrogenic-50% 20%-25% Preterm deliveries don’t follow preterm labor Elective delivery: Severe preeclampsia Non reassuring fetal heart rate Preterm labor vs. false labor Criteria for Diagnosis: Gestational age between 20-37 weeks At least 4 documented uterine contractions in 20 minutes or 8 in 60 minutes Cervical dilation of at least 2 cm Cervical effacement of 80% Physical examination Intravenous hydration Bed rest Fetal heart rate monitoring Ultrasonography for gestational age and weight Amniocentesis for fetal lung maturity and to rule out infection Speculum examination to rule out PPROM Gestational age between 20 and 34 weeks Fetal weight < 2500 gms Absence of fetal distress Benefits:↓Neonatal morbidity and mortality Risks: Maternal and/or fetal sepsis Maternal side effects of tocolytics Further compromise of a distressed fetus Indicated for the following scenarios: To facilitate transport from a small community hospital to a tertiary center To delay delivery for 24-48 hours allowing administration of glucocorticoids to accelerate fetal lung maturity Fetal resuscitation in utero in fetal distress Reduced incidence of respiratory distress syndrome Reduced incidence of intraventricular hemorrhage Reduction of neonatal morbidity and mortality ABSOLUTE: Fetal death Fetal anomalies incompatible with life Fetal distress warranting immediate delivery Chorioamnionitis/fever of unknown origin Severe hemorrhage Severe chronic HTN and/or PIH RELATIVE: Cervical dilation > 4 cm Ruptured membranes β-adrenergic agents: Ritodrine* Terbutaline Magnesium sulfate Prostaglandin synthetase inhibitor: Indomethacin Calcium channel blockers: Nifedipine * Ritodrine is only FDA approved tocolytic, however, terbutaline, magnesium sulfate, nifedipine and indomethacin are widely used in US. During labor and delivery, preterm infant at high risk of acidosis and has high incidence of intracranial hemorrhage High incidence of CD due to fetal distress Preterm infant more sensitive to depressant effects of analgesic and anesthetic drugs. Regional anesthesia technique of choice to avoid depressant effects of anesthetic drugs. Epidural prevents precipitous vaginal delivery and rapid decompression of vulnerable fetal head Ritodrine and terbutaline commonly used agents May delay delivery for 24-48 hrs; however, not in substantial prolongation of pregnancy Contraindicated in severe cardiac or pulmonary disease Reported incidence of side effects vary from 0.54% to 9% as per different studies Side effects include hypotension, tachycardia, cardiac arrhythmias, myocardial ischemia, pulmonary edema, hyperglycemia, hypokalemia and fetal tachycardia Side effects dose related Consider delaying administration of anesthesia where feasible until maternal side effects have subsided Extensive experience for use of seizure prophylaxis in preeclamptic women Little scientific evidence of efficacy of MgSO4 for tocolysis Many clinicians consider MgSO4 to be tocolytic of choice in patients at high risk of bleeding (P. Previa) Less frequent and less severe side effects than β- adrenergic agents Side effects include chest pain, palpitations, nausea, transient hypotension, blurred vision, sedation and pulmonary edema Can attenuate compensatory response to hemorrhage Some concern about possible increase in perinatal mortality May increase risk of hypotension during regional Loading dose 4 gm over 15-20 min Followed by infusion at 1-4 gm/hr Serum levels of 5-7 mg/dl required for tocolysis 8-10 mg/dl; loss of tendon reflexes 10-15 mg/dl: respiratory depression >10-15 mg/dl: cardiac conduction defects Potentiates both depolarizers and non-depolarizers Causes sedation, ↓MAC and ↓analgesic requirements Modest prolongation of bleeding time due to effect on platelet aggregation by antagonizing the effects of Ca++ Acts by inhibiting cyclo-oxygenase Dose: 50 mg PO followed by 25 mg PO 4-6 hr Limit course of therapy to less than 72 hr and administer only before 32 week gestation to minimize neonatal side effects No cardiovascular side effects like other agents ↓ thromboxane A2 →↓platelet aggregation Does not necessitate assessment of coagulation status prior to regional due to transient reversible effect on platelet function Can cause premature closure of ductus arteriosus in utero resulting in persistent fetal circulation if administered after 32 weeks gestation Other side effects include oligohydramnios and neonatal necrotizing enterocolitis Reduced side effect profile compared to β- adrenergic agonists Some investigators suggest as first line tocolytic compared to others Can arrest labor for 48 hrs or longer Can be administered orally or sublingually Dose: 10-20 mg PO every 4-6 hours More effective with fewer side effects than β-adrenergic agents and better neonatal outcome However, adverse fetal effects as per some animal studies Usually mild maternal side effects like flushing Potential to cause vasodilatation, hypotension, myocardial depression and conduction defects when used in combination with volatile agents Studies in progress for agents with fewer maternal and fetal side effects Oxytocin antagonist: Atosiban Anticytokine agents: Urinary trypsin inhibitor Cytokines: Promote production of oxytocin and corticotropin, corticotropin stimulates prostaglandin release Nitric oxide donors Muir HA, Chestnut DH. Preterm Labor and Delivery in Principles and Practice of Obstetric Anesthesia, Editor David H Chestnut, Elsevier Mosby, PA.