Comparative evaluation of the analgesic, opioid-sparing, and anti-inflammatory effects of multimodal regimens based on paracetamol and a fixed combination of diclofenac with orphenadrine in the early postoperative period in cardiac surgery patients

Introduction. The surgical stress response in patients undergoing cardiac surgery is the primary cause of systemic inflammatory response syndrome (SIRS) development and requires investigation of methods for its modulation, including the development of optimal postoperative analgesia regimens.

The objective was to conduct a comparative evaluation of the analgesic, opioid-sparing and anti-inflammatory effects of paracetamol and a fixed combination of diclofenac with orphenadrine in the early postoperative period in cardiac surgery patients.

Materials and methods. The study included 60 patients undergoing cardiopulmonary bypass surgery. The group 1 (group N) included 30 patients who received Neodolpasse infusion; intravenous paracetamol was administrated to 30 patients in group 2 (group P). Both groups received patient-controlledanalgesia (PCA) with morphine. The intensity of the pain syndrome was assessed with a 100 mm visual-analog scale (VAS). The daily opioid requirement was determined, and blood samples for proinflammatory markers were collected; interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). These samples were assessed before analgesia and at 24 and 48 hours post-procedure.

Results. With initially high VAS scores observed throughout the study, group N demonstrated a significantly more pronounced analgesic effect compared to group P. The requirement for additional morphine bolus infusions in group N was 2.7 times lower than in group P. Adverse events characteristics of the opioid analgesic morphine were significantly more frequent in group P. Cytokine analysis at 6 hours postoperatively revealed a 30-fold or greater increase in IL-6 levels. During the second phase, only group N demonstrated a trend toward IL-6 reduction. A significant increase in C-reactive protein (CRP) was observed only by the end of the first 24 hours, averaging 93 [68–129.5] mg/L in group N and 110.3 [82.7–151.6] mg/L in group P. By 48 hours, group N (fixed combination group) showed statistically significant CRP reduction, while group P maintained elevated CRP levels. No significant IL-8 elevation was detected, and TNF-α and IL-1β levels remained within normal reference throughout the observation period.

Conclusion. The fixed combination of nonsteroidal anti-inflammatory drug (NSAID) diclofenac and centrally acting muscle relaxant orphenadrine demonstrates clinical advantages over intravenous paracetamol, providing superior analgesic efficacy, reducing PCA morphine requirements, and attenuating systemic response manifestations.

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