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Drugs used for TIVA in the obstetric population

How do the drugs we commonly use for TIVA work 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.
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Introduction to Using Total Intravenous Anaesthesia (TIVA)

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