Drugs used for TIVA in the obstetric population

Point to note: “Guidelines for the safe practice of TIVA” – Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia

In the section relating to obstetrics it is important to note

• No recommendation on the routine use of TIVA in obstetric anaesthesia is made
• This is an area which requires further research.
• In situations where TIVA is required (e.g. the transfer of an anaesthetised patient to the ICU), the principles in this guideline apply.

Propofol

• PK: Propofol is highly bound to albumin. Maternal albumin levels are lower in pregnancy. Increased free concentration.
• PD: Hepatic clearance is maximal outside of pregnancy, increased hepatic blood flow does not alter propofol metabolism.
• Dosing/Model:
  • 2mg/kg induction dosing.
  • Expected maintenance dosing is similar to non-pregnant population 100 – 200mcg/kg/minute
  • Marsh (with actual body weight)
• F/M ratio: Between 0.7 and 1.3
• Benefits:
  • Suitable for use when uterine tone needs to be preserved eg haemorrhage
  • Use where volatile contraindicated, eg MH
  • No difference in neonatal depression has been found when propofol was used for induction of general anaesthesia compared to thiopental
• Caution: If there is a delay from anaesthetic induction to delivery of the fetus, neonatal ventilation may be required until the drug can be metabolised and the fetus wakes from general anaesthesia.

Remifentanil

• PK: Due to a larger volume of distribution and higher clearance, after administration the plasma concentration of remifentanil in a pregnant woman is half that of the non-pregnant woman.
• PD: Rapidly metabolised
• Dosing/Model:
  • PCA dosing: The initial PCA bolus is set at 0.25 to 0.5 mcg/kg (ideal body weight) with a lock-out interval of two minutes.
  • Minto model recommended
• F/M ratio: Consistently <1
• Benefits:
  • Can be used as a PCA on labour ward.
  • Can be used to blunt sympathetic response to laryngoscopy.
• Cautions: Transient neonatal respiratory depression is possible.

Dexmedetomidine

• PK: Human PK studies of dexmedetomidine in pregnancy are lacking.
• PD: Human PD studies of dexmedetomidine in pregnancy are lacking.
• F/M ratio: The fetal to maternal index is described as <1 (0.7–0.8) even after infusion for >30 minutes.
• Benefits:
  • Low placental transfer
  • Does not cause uterine relaxation. May augment uterine contraction.
• Cautions: Limited studies on safety in pregnancy.

Fentanyl

• PK: Human PK studies of fentanyl in pregnancy are lacking.
• PD: Human PD studies of fentanyl in pregnancy are lacking.
• Dosing/Model: Doses ranging from 10 to 100 mcg IV are used to treat painful contractions of labour.
• F/M ratio: 0.5 to 0.9
• Benefits: Used at general anaesthesia to blunt the sympathetic responses to laryngoscopy and intubation, and to provide rapid onset of analgesia.
• Cautions: If administered repeatedly, or as an infusion, note fentanyl’s context sensitive half-time increases substantially after prolonged administration.

Midazolam

• PK:
  • It is metabolised by CYP3A4, a liver enzyme that is induced in pregnancy.
  • Peak concentration of midazolam is reduced after both oral and parenteral administration of midazolam in pregnancy.
  • The half-life is unchanged.
• PD: Pregnant women have decreased albumin concentration resulting in a markedly increased free fraction of midazolam.
• Dosing/Model: Pregnant women generally require reduced doses of midazolam for anxiolysis.
• F/M ratio: 0.15 to 0.66
• Benefits: Little effect on uterine contractility
• Cautions:
  • Benzodiazepines not recommended in early pregnancy due to suggestion of a two-fold increase in oral cleft with exposure during the first trimester of pregnancy.
  • Prolonged use of benzodiazepines near term is contra-indicated because of neonatal toxicity and withdrawal symptoms.
  • May impair maternal memory if used at the time of delivery.