Tocolytics

Tocolytics

1. Definition, scope & therapeutic rationale

• Tocolytics (uterine relaxants) are drugs that decrease uterine (myometrial) motility; clinically they are used to delay or postpone labour, arrest threatened abortion, and (historically) in dysmenorrhoea (KDT 8e Ch.23, pp.358–9).
• Preterm birth is defined as delivery before 37 completed weeks of gestation; it occurs in >10% of pregnancies (US data, rising in frequency) and is the dominant context for tocolysis (G&G 14e Ch.48, p.980).
• Preterm birth carries major neonatal complications — neonatal respiratory distress syndrome (RDS), pulmonary hypertension, and intracranial haemorrhage — and the more premature the baby, the greater the risk, which is what drives efforts to interrupt preterm labour (G&G 14e Ch.48, p.980).
• Risk factors for preterm labour: multifetal (multiple) gestation, premature rupture of the membranes (PROM), intrauterine infection, and placental insufficiency (G&G 14e Ch.48, p.980).
• The therapeutic objective of tocolysis is to delay delivery, NOT to prevent prematurity — the delay is used to:
  • transfer/transport the mother in utero to a regional/tertiary centre with proper neonatal facilities (G&G 14e Ch.48, p.980; KDT 8e Ch.23, p.358);
  • buy time to administer antenatal glucocorticoids to stimulate fetal lung maturation (G&G cross-references Ch.50; KDT cross-references its glucocorticoid section, p.316) (G&G 14e Ch.48, p.980; KDT 8e Ch.23, p.358);
  • allow co-administration of supportive agents such as antibiotics (e.g., erythromycin, ampicillin) to reduce neonatal group B β-haemolytic Streptococcus infection — reserved for PROM with evidence of infection, NOT given indiscriminately (G&G 14e Ch.48, p.980).
• Critical efficacy caveat (the central exam point): tocolytic agents delay delivery in ~80% of women (G&G) / ~70% of cases (KDT, ritodrine), but they neither prevent premature birth nor improve adverse fetal outcomes such as RDS — no clearly satisfactory drug is available since none has been shown to improve fetal outcome (G&G 14e Ch.48, p.981; KDT 8e Ch.23, p.358).
• Despite numerous clinical trials, the superiority of any one tocolytic over another has not been established (G&G 14e Ch.48, p.981).

1.1 Conditions / patient-selection rules for tocolysis (KDT)

• An attempt to delay premature labour is likely to succeed only if cervical dilatation is < 4 cm and "taking up" (effacement) of the lower segment is minimal (KDT 8e Ch.23, p.358).
• Measures to delay labour should NOT be undertaken if (contraindications to attempting tocolysis):
  • membranes have ruptured (PROM);
  • antepartum haemorrhage is occurring;
  • severe toxaemia of pregnancy (severe pre-eclampsia/eclampsia);
  • intrauterine infection; or
  • fetal death (KDT 8e Ch.23, p.358).