Background and objectives: The combination of non-steroidal anti-inflammatory drugs and paracetamol is widely used for pediatric postoperative pain management, although the evidence of superiority of a combination over either drug alone is insufficient. We aimed to find out if intravenous (i.v.) paracetamol in a dose of 60 mg kg⁻¹ 24 h⁻¹, given in addition to i.v. ketoprofen (4.5 mg kg⁻¹ 24 h⁻¹), improves analgesia, physical recovery, and satisfaction with postoperative well-being in children and adolescents following moderate and major general surgery. Materials and Methods: Fifty-four patients were randomized to receive either i.v. paracetamol or normal saline as a placebo in adjunct to i.v. ketoprofen. For rescue analgesia in patients after moderate surgery, i.v. tramadol (2 mg kg⁻¹ up two doses in 24 h), and for children after major surgery, i.v. morphine-patient-controlled analgesia (PCA) were available. The main outcome measure was the amount of opioid consumed during the first 24 h after surgery. Pain level at 1 and over 24 h, time until the resumption of normal oral fluid intake, spontaneous urination after surgery, and satisfaction with postoperative well-being were also assessed. Results: Fifty-one patients (26 in the placebo group and 25 in the paracetamol group) were studied. There was no difference in required rescue tramadol doses (n = 11 in each group) or 24-h morphine consumption (mean difference (95% CI): 0.06 (–0.17; 0.29) or pain scores between placebo and paracetamol groups. In patients given morphine-PCA, time to normal fluid intake was faster in the paracetamol than the placebo subgroup: median difference (95% CI): 7.5 (1.3; 13.7) h, p = 0.02. Parental satisfaction score was higher in the paracetamol than the placebo group (mean difference: –1.3 (–2.5; –0.06), p = 0.04). Conclusions: There were no obvious benefits to opioid requirement or analgesia of adding regular intravenous paracetamol to intravenous ketoprofen in used doses. However, intravenous paracetamol may contribute to faster recovery of normal functions and higher satisfaction with postoperative well-being.

Fractional tissue oxygen extraction (FTOE) by means of cerebral near-infrared spectroscopy (NIRS) provides information about oxygen uptake in the brain. Experimental animal data suggest that sedative agents decrease cerebral oxygen demand. The aim of the present study was to investigate the association between the cerebral FTOE and the use of pre and intraoperative sedative agents in infants aged 1–90 days. Cerebral NIRS was continuously applied during open major non-cardiac surgery in 46 infants. The main outcomes were the mean intraoperative FTOE and the percentage (%) of time of intraoperative hyperoxia_FTOE relative to the total duration of anesthesia. Hyperoxia_FTOE was defined as FTOE ≤ 0.1. Cumulative doses of sedative agents (benzodiazepines and morphine), given up to 24 h preoperatively, correlated with the mean intraoperative FTOE (Spearman’s rho = −0.298, p = 0.0440) and were predictive for the % of time of intraoperative hyperoxia_FTOE (β (95% CI) 47.12 (7.32; 86.92)) when adjusted for the patients’ age, type of surgery, preoperative hemoglobin, intraoperative sevoflurane and fentanyl dose, mean intraoperative arterial blood pressure, and end-tidal CO₂ by multivariate 0.75 quantile regression. There was no association with 0.5 quantile regression. We observed the suggestive positive association of decreased fractional cerebral tissue oxygen extraction and the use of sedative agents in neonates and infants undergoing surgery.

Studies report the link between exposure to major neonatal surgery and the risk of later neurodevelopmental disorders. The aim of this study was to find out the behavioral problem scores of 2.5–5 years old children who had undergone median/major non-cardiac surgery before the age of 90 days, and to relate these to intraoperative cerebral tissue oxygenation values (rSO₂), perioperative duration of mechanical ventilation (DMV) and doses of sedative/analgesic agents. Internalizing (IP) and externalizing problems (EP) of 34 children were assessed using the CBCL for ages 1½–5. Median (range) IP and EP scores were 8.5 (2–42) and 15.5 (5–33), respectively and did not correlate with intraoperative rSO₂. DMV correlated and was predictive for EP (β (95% CI) 0.095 (0.043; 0.148)). An aggregate variable “opioid dose per days of ventilation” was predictive for EP after adjusting for patients’ gestational age and age at the day of psychological assessment, after further adjustment for age at the day of surgery and for cumulative dose of benzodiazepines (β (95% CI 0.009 (0.003; 0.014) and 0.008 (0.002; 0.014), respectively). Neonatal/infantile intraoperative cerebral oxygenation was not associated with later behavioral problems. The risk factors for externalizing problems appeared to be similar to the risk factors in preterm infant population.