Postoperative pain control is a key concern following percutaneous nephrolithotomy (PCNL). While intravenous (IV) paracetamol is widely used, evidence comparing its effectiveness with oral paracetamol remains limited. This study aimed to compare oral and IV paracetamol for pain control after PCNL and to explore factors associated with pain outcomes.

A total of 54 patients undergoing PCNL were randomized to receive either oral (n = 30) or IV (n = 24) paracetamol. PCNL was done under spinal anesthesia and a 26 Fr nephroscope. Pain was assessed using the Numeric Rating Scale (NRS) at 1, 4, 8, 12, 16, 20, and 24 hours postoperatively. Overall pain burden was quantified using the area under the curve (AUC) of NRS values. Bivariate and multivariable analyses were conducted to evaluate predictors of pain.

Baseline characteristics were comparable between groups. The mean AUC was 50.78 ± 26.09 in the oral group and 44.92 ± 30.23 in the IV group, with no statistically significant difference (Mann-Whitney U = 407.00, p = 0.418). Pain scores at each time point were also similar between groups (p > 0.05). In bivariate analysis, postoperative fever was significantly associated with higher AUC (p = 0.036), while stone burden showed a non-significant trend (p = 0.081). Hemoglobin decline and leukocyte count were not associated with pain. However, in the multivariable regression model adjusting for paracetamol route, age, sex, stone burden, and fever, none of the variables were independently associated with overall pain. Fever was no longer significant after adjustment (p = 0.435).

Oral and IV paracetamol provided comparable analgesic effects following PCNL. Although postoperative fever appeared to influence pain in unadjusted analysis, this effect did not persist after multivariable adjustment.