Aubrun F, et al. - Whether four single nucleotide polymorphisms (SNP) [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics impact morphine dose requirements and adverse events in the postoperative period, was determined. Researchers found no major link between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period.

Methods

• This is a single centre prospective study conducted at University Hospital, Paris, France, from 2 January 2007 to 15 November 2011.
• This study included a total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia, excluding those receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, those with pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction.
• Researchers performed assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide).
• They analysed common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)].
• Morphine was titrated by staff in the postanaesthesia care unit (PACU).
• Patient-controlled intravenous analgesia was used for 24 h in the ward.
• They assessed the dose of morphine needed to achieve pain relief and the impact of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements.
• The concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events were also assessed.

Results

• Data showed that a total of 404 patients completed the study to final analysis.
• In the PACU and during patient-controlled intravenous administration, the observed mean ± SD morphine dose to achieve pain relief was 15.8 ± 8.8 mg and 22.7 ± 18.6 mg, respectively.
• In 37%, the occurrence of morphine-related adverse events was reported.
• Researchers found no association between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level.
• They also observed that P-glycoprotein polymorphisms (ex-21; ex-26) were significantly related to morphine concentration in the PACU only but the prediction of the model was poor (R² = 0.04)