Codeine phosphate in paediatric medicine.

Codeine is an old drug that still enjoys widespread clinical use although the logical basis for its popularity has been questioned. It is considered to be suitable for mild to moderate pain but not for more intense pain even in large doses. The World Health Organisation has devised a three-step analgesic ladder for the progressive treatment of increasing pain; on this codeine is considered a weak opioid and occupies a position on the second step (Fig. 1). A signi®cant degree of unpredictable, variable or poor response to treatment with codeine has been reported in many human and animal studies. Indeed, some single dose studies in adults, have shown no difference between codeine and placebo, 60 and a quantitative systemic review suggests that codeine 60 mg has a number needed to treat (NNT) of 18 which is very high when compared with 5.0 for paracetamol 600 mg and 3.1 for the combination. Codeine is frequently recommended for paediatric use. 37 100 A recent survey of paediatric anaesthetists in the UK showed that alongside morphine and fentanyl, codeine is the most widely prescribed opioid analgesic in paediatric anaesthetic practice. The reputedly lower incidence of opioid-related side effects has made codeine popular for the younger age groups including neonates and especially in situations where airway management and neurological assessment are critical. 69 102 106 These suggested bene®ts have been noted after single doses although they may not exist when repeated doses are used. In fact, few clinical studies of the analgesic ef®cacy or side effects of codeine in children have been undertaken, and although the incidence of side effects may be low, analgesia may be inadequate for post-operative pain in some circumstances. Pain assessment is dif®cult in paediatric populations especially neonates and preverbal children and this complicates both the study and use of analgesics particularly those with low ef®cacy or unpredictable effects. Signi®cant variability in both the pharmacokinetics and pharmacodynamics of codeine has been shown in animal and adult human laboratory experimental studies. 25 38 74 105 112 115 In this review we shall examine the reasons for this variability and unpredictability in the effects of codeine in both laboratory and clinical investigations and assess evidence for its suitability for use in preverbal infants and children.