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CARDIOVASCULAR ANESTHESIA

Propacetamol as Adjunctive Treatment for Postoperative Pain After Cardiac Surgery

Pasi Lahtinen, MD^*, Hannu Kokki, MD PhD^*, Heikki Hendolin, MD PhD^*, Tapio Hakala, MD, and Markku Hynynen, MD PhD

*Department of Anesthesia and Intensive Care and Department of Surgery, Kuopio University Hospital, Kuopio; and Department of Anesthesia and Intensive Care, Helsinki University Central Hospital, Jorvi Hospital, Espoo, Finland

Address correspondence and reprint requests to Pasi Lahtinen, MD, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, FIN-70210 Kuopio, Finland. Address e-mail to pasi.lahtinen{at}kuh.fi

Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1–42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7–20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group.

IMPLICATIONS: This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.

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