Effect of interleukin 6 –174G>C gene polymorphism on opioid requirements after total hip replacement

Abstract

Objective: In recent years, increasing attention has been paid to the contribution of genetic factors to variability in patient pain threshold and the efficacy of pain management. One of the genes implicated in pain pathology and treatment response is interleukin 6 (IL6). The aim of the present study was to evaluate the association between IL6 (rs1800795: –174G>C) and opioid requirements in patients after total hip replacement (THR). Methods: A total of 196 patients eligible for the study (126 women, 70 men) were subjected to THR. The THR procedure was performed using spinal anaesthesia after implementing routine peri-operative monitoring. After the procedure each patient was individually observed, and the patient-specific chart of dynamic changes in pain perception was recorded, using the five-level Verbal Rating Scale (VRS). The multimodal analgesic treatment after THR was defined by the operating surgeons after considering indications and contraindications to the use of different groups of drugs (opioid and non-opioid analgesics). Postoperative pain was controlled by the patient-controlled analgesia method and VRS during the day-time, as well as night-time nurse-controlled analgesia. All medication adjustments were recorded in the individual patient files. In the case of moderate pain intensity (VRS-assessed), a patient was administered the non-opioid analgesic drug, and for high intensity pain the opioid. The analysis of pain relief therapy included information on the drugs applied, mode of dosing (single or multiple), daily dose, route of administration, and drug refusal due to the absence of pain recorded each study day, i.e. on the day of surgery and recovery in the postoperative room (day 0), and then daily from day 1 to day 6. Polymorphism rs1800795:G>C in the promoter region of the IL6 gene (–174G>C) was determined using the PCR–RFLP method. Results: The patients carrying at least one IL6 –174G allele (GG homozygote and GC heterozygote) were administered opioids significantly more often on days 0 (p = 0.0029), 3 (p = 0.019) and 4 (p = 0.031) after surgery compared with CC homozygous patients. Those patients also required a significantly higher opioid dose on days 3 (p = 0.029) and 4 (p = 0.030). Multivariate analysis demonstrated that the presence of the –174G allele was an independent factor predisposing patients to the administration of opioids during the first 24 h [p = 0.001, odds ratio (OR) 7.1, 95 % confidence interval (CI) 2.17–22.7], on day 3 (p = 0.01, OR 2.79, 95 % CI 1.25–6.26) and day 4 (p = 0.01, OR = 2.61, 95 % CI 1.17–5.79). Conclusion: The presence of the G allele IL6 gene (–174G>C) polymorphism was found to be an independent factor predisposing to a higher dose and more frequent administration of opioids in the first days after total hip replacement.