The only agent licensed for inhaled analgesia in the UK is Entonox, which is a mixture of 50% nitrous oxide and 50% oxygen. Its advantages are that it is inexpensive, is almost universally available (including for use in the community), has a long record of safety, and is acceptable to many mothers and midwives; it is used in almost two-thirds of deliveries in the UK. Its low blood solubility means that blood levels rapidly reach a maximum after inhalation and fall once a contraction has passed and inhalation has ceased. It does not appear to have any detrimental effect on the fetus. The main disadvantage of Entonox is that it provides only limited pain relief.
Volatile anaesthetic agents such as methoxyflurane and trichloroethylene have been used for analgesia in labour, but these drugs have been withdrawn for non-obstetric reasons. They were administered using a draw-over vaporiser and breathing system and provided analgesia of slow onset because of their high blood solubility, with residual effects between contractions. Other volatile agents, including sevoflurane and desflurane, have also been studied, but none is widely used. A premixed preparation of isoflurane and Entonox (Isoxane) has been described, but this too is not widely available.
Problems and special considerations
Entonox is presented as a premixed agent, available in cylinders for community use and piped from central tanks in hospital maternity units. The mixture is stable under most conditions, but at very low temperatures the constituent gases separate out. This is relevant for community midwives practising in parts of the UK in winter, who must be aware that they need to invert Entonox cylinders several times before use to ensure adequate mixing.
Nitrous oxide is a relatively weak analgesic that exerts its effect through N-methyl- D-aspartate (NMDA) antagonism, thus benefiting 30-50% of mothers who use it, but with little effect on actual pain scores. Some women report benefit through distraction and concentration on breathing technique. Use of more than 50% nitrous oxide improves analgesic efficacy, but at the cost of increased maternal sedation and decreased inspired concentration of maternal oxygen. The use of the 50:50 mixture of nitrous oxide and oxygen represents a compromise between analgesic efficacy and maternal and fetal safety.
The efficacy of Entonox can be improved with good technique. About 45 seconds of use is required to achieve maximal effect, so the mother should be instructed to start inhaling as soon as she becomes aware of a contraction, and to continue inhalation until the contraction subsides. It is also important to ensure that if a facemask is used it is applied firmly to the face to avoid entraining air.
The mother administers the gas to herself from a demand valve via either facemask or mouthpiece. Maternal sedation may occur even with 50% nitrous oxide, especially if systemic opioids such as pethidine have been given, and it is therefore important that Entonox is self-administered, not administered by the midwife or by the woman’s partner. The mother should also take a break from Entonox when not having a contraction. Overzealous use can lead to hyperventilation, hypocapnia, alkalosis and vasoconstriction.
Some mothers find inhalation of dry gases unpleasant, and in asthmatics this may provoke bronchospasm. Entonox also causes unacceptable nausea in a small number of women, and dizziness is common.
Although Entonox crosses the placenta readily, it is excreted by the neonatal lungs after delivery. Entonox does not have adverse effects on the fetus, but the maternal hyperventilation associated with its use may cause placental vasoconstriction and impair fetal oxygenation. Similarly, the combination of pethidine and Entonox has been associated with a high incidence of maternal arterial oxygen desaturation and should be avoided if there is evidence of fetal compromise.
There has been recent concern about the pollutant effects of Entonox. Many labour wards do not have any means of scavenging exhaled Entonox, and this is increasingly considered unacceptable. Scavenging equipment is available but obviously has resource implications.
Volatile anaesthetic agents cause dose-dependent uterine relaxation, although this can be overcome at low concentrations (< 0.5 MAC) by oxytocic drugs. They also have cardiorespiratory side effects, although these are usually minimal at low concentrations.
Key points
• Entonox provides acceptable (but incomplete) analgesia to up to half of the mothers who use it. It is appropriate for low-risk mothers in uncomplicated labour and for mothers awaiting regional analgesia.
• Entonox should not be recommended for high-risk mothers or as a supplement to inadequate systemic analgesia.
Further reading
Likis FE, Andrews JC, Collins MR, et al. Nitrous oxide for the management of labor pain: a systematic review. Anesth Analg 2014; 118: 153-67.
Richardson MG, Lopez BM, Baysinger CL. Should nitrous oxide be used for labouring patients? Anesthesiol Clin 2017; 35: 125-43.
Sutton CD, Butwick AJ, Riley E, Carvalho B. Nitrous oxide for labor analgesia: utilization and predictors of conversion to neuraxial analgesia. J Clin Anaesth 2017; 40: 40-5.