The analgesic concentration of oxycodone with co-administration of paracetamol -- a dose-finding study in adult patients undergoing laparoscopic cholecystectomy.

We have previously shown that paracetamol has an opioid-sparing effect in tonsillectomy, and now, we evaluated the analgesic efficacy of paracetamol i.v. in early post-operative pain after laparoscopic cholecystectomy (LCC). Twenty-four patients with LCC were randomized to receive paracetamol i.v. 1 g (group 1) or 2 g (group 2) at the end of surgery. All patients were provided 0.1 mg/kg of oxycodone i.v. 15 min. before the end of surgery. At the recovery room when the wound pain at rest was ≥ 3/10 and/or ≥ 5/10 during the wound compression, plasma sample was taken for the determination of oxycodone (minimum effective concentration, MEC), its metabolites and paracetamol. After that the patients were titrated with further doses of oxycodone i.v. to wound pain < 3/10 at rest and < 5/10 during wound compression, plasma sample was taken for the determination of minimum effective analgesic concentration (MEAC) of oxycodone. The total oxycodone dose needed for pain relief was similar, about 0.3 mg/kg (range 0.2-0.5), in both groups (p = 0.80). At the onset of pain, P-oxycodone (MEC) was similar in both groups, 25 ng/ml (19-32) in group 1 and 24 ng/ml (16-34) in group 2. The pain relief (MEAC) was achieved in group 1 with P-oxycodone 70 ng/ml (30-131) and in group 2 with 62 ng/ml (36-100) (p = 0.48). In conclusion, in the early-phase after LCC, there was no significant difference between the effect of paracetamol doses of 1 g and 2 g i.v. on the need of i.v. oxycodone.

Analgesic concentrations of oxycodone--a prospective clinical PK/PD study in patients with laparoscopic cholecystectomy.

The analgesic concentrations of oxycodone in acute post-operative pain management have not been established. Here, we have evaluated the minimum effective concentration (MEC) and the minimum effective analgesic concentration (MEAC) of oxycodone in pain after laparoscopic cholecystectomy (LCC) in 23 adult patients. The patients were provided with 0.1 mg/kg of oxycodone i.v. 10-15 min. before the end of surgery. After surgery, when the wound pain at rest was ≥3/10 and/or ≥5/10 during wound compression, a first blood sample was obtained (MEC). A second blood sample was obtained after titration with 2 mg i.v. of oxycodone to wound pain <3/10 at rest and <5/10 during wound compression (MEAC). A third blood sample was obtained at the recurrence of the wound pain (the second MEC), and the final blood sample when pain relief was obtained a second time (the second MEAC). At the first onset of pain (MEC), mean P-oxycodone was 21 ng/mL (95% CI 13-29 ng/mL). At the first pain relief (MEAC), P-oxycodone was 55 ng/mL (19-91 ng/mL). The second MEC was 34 ng/mL (11-57 ng/mL), and the second MEAC was 47 ng/mL (14-80 ng/mL). In conclusion, the estimated MEC, 20-35 ng/mL, and MEAC, 45-50 ng/mL, values of P-oxycodone in patients after LLC were significantly higher than those proposed previously. Early pain after LCC appeared to be a feasible method to estimate the analgesic efficacy of oxycodone in acute pain management.