Pethidine (meperidine)

Pethidine was introduced into obstetric practice in the 1940s. It has remained the most widely used intermittent bolused opiate worldwide. It was first made legally available in 1950 in the UK for midwives to use independently. A survey of UK practice in 2008 found that 84% of UK units still used pethidine for labour analgesia despite significant doubts to its efficacy. This is probably due to familiarity, ease of administration, low cost and lack of evidence of a superior alternative. Some women find they are more able to cope with their labour pains due to its ability to provide sedation, dysphoria and amnesia.

It is a synthetic, phenylpiperidine derivative that is an agonist at µ- and κ-opioid receptors. It is used in a dose of 50–150 mg IM, which may be repeated 4 hours later. Onset of pain relief occurs within 45 minutes and lasts 2 to 3 hours.

The Cochrane overview in 2012 found that compared to other opioids more women receiving pethidine experienced adverse effects, including impaired capacity to engage in decision-making about care, sedation, hypoventilation, hypotension, prolonged labour, urine retention, nausea, vomiting and a slowing of gastric emptying.

It rapidly crosses the placenta, equilibrating within 6 minutes, and it has been shown to cause decreased fetal heart rate variability within 25 to 40 minutes that can last for an hour. It has a maternal half-life of 2.5 to 3 hours, but a more prolonged neonatal half-life of up to 18 to 23 hours. Pethidine is metabolized in the liver to its active metabolite norpethidine, which is a potent respiratory depressant with convulsant properties, which can accumulate with repeated doses, and has a half-life in the neonate of 60 hours. It should be used with caution in women with severe pre-eclampsia and other causes of renal impairment. The babies of women who have received pethidine in labour have been shown to be sleepier, less attentive, at risk of neonatal respiratory depression and hypothermia, and less able to establish breastfeeding, despite normal Apgar scores at birth. However, about 10% of neonates will have a 1 minute Apgar score of <6 if pethidine is given 2–3 hours before delivery, as this coincides with peak fetal concentrations. The incidence is reduced if given before or after this.

Diamorphine

Diamorphine is a synthetic derivative of morphine and is widely used as a labour analgesic in the UK. In the 2008 UK survey of practice it was found that diamorphine was used in 34% of units, and more frequently than pethidine in some areas. In other surveys it is rated better than pethidine and Entonox by both midwives and parturients. It is essentially a pro-drug that is rapidly metobolized to 6-mono-acetylmorphine, an active metabolite that is more lipid soluble than morphine, before further breakdown to morphine. This increased lipid solubility accounts for its rapid onset, but also for its speed across the placenta, suggesting that infants born shortly after maternal diamorphine administration are at greater risk of respiratory depression. It is usually given in a dose of 5–7.5 mg IM. Most studies comparing pethidine and diamorphine find that neither drug works well, with almost 50% of women reporting poor pain relief and up to 40% of women requesting second-line analgesia. However, patients who receive pethidine are more likely to report no pain relief and the incidence of vomiting is lower in the diamorphine group. Pethidine was also associated with lower Apgar scores at 1 minute.