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BackgroundThe Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration.AimsTo evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia.MethodsNineteen children, 5.3 (4.1–6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 μg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5‐, 15‐, and 30‐min post‐fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®.ResultsAfter the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) −12(−18–−6) and 100 ± 10 vs. 102 ± 10; −2(−4–−0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5–18) and 102 ± 10 vs. 91 ± 11; 11 (7–16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight‐scaled, 3‐compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect‐site equilibration half‐time of 1.69 (0.4–2.9) min. The estimated fentanyl C50 was 1.93 (0.73–4.2) ng/mL.ConclusionThe Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception‐antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.
BackgroundThe Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration.AimsTo evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia.MethodsNineteen children, 5.3 (4.1–6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 μg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5‐, 15‐, and 30‐min post‐fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®.ResultsAfter the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) −12(−18–−6) and 100 ± 10 vs. 102 ± 10; −2(−4–−0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5–18) and 102 ± 10 vs. 91 ± 11; 11 (7–16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight‐scaled, 3‐compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect‐site equilibration half‐time of 1.69 (0.4–2.9) min. The estimated fentanyl C50 was 1.93 (0.73–4.2) ng/mL.ConclusionThe Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception‐antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.
Background and objectives Pediatric thoracic surgery has unique considerations due to the immaturity of the respiratory system anatomically and physiologically, which presents technical and pharmacological considerations, including the very common technique of one-lung ventilation (OLV), which causes serious complications in children. Therefore, we investigated the effects of dexmedetomidine on oxygenation and pulmonary shunt fraction (Qs/Qt) in high-risk pediatric patients undergoing OLV for thoracic surgery. This randomized controlled trial aimed to investigate dexmedetomidine's effect on the partial pressure of arterial oxygen (PaO 2 ) and pulmonary shunt fraction (Qs/Qt). Methods A total of 63 children underwent thoracic surgery with OLV and were divided into two groups. The dexmedetomidine group (group Dex, n = 32) received dexmedetomidine (0.4 μg/kg/hour), and the placebo group (group placebo, n = 31) received normal saline. Two arterial and central venous blood samples were taken for arterial and venous blood gas analysis at four time points: T1 (10 minutes after mechanical ventilation of total lung ventilation), T2 (10 minutes after OLV), T3 (60 minutes after OLV), and T4 (20 minutes after the end of OLV). At these intervals, the following parameters were measured: PaO 2 , Qs/Qt, mean arterial pressure (MAP), heart rate (HR), and peak inspiratory pressure (PIP). Results The two groups had no significant differences in FEV1/FVC and baseline pulmonary shunt fraction (Qs/Qt). Dexmedetomidine significantly improved PaO 2 compared with placebo during OLV (T2 and T3). There was a significant decrease in Qs/Qt compared with placebo during OLV (T2, T3, and T4). There was a decrease in PIP compared with placebo during OLV (T2 and T3). No statistically significant differences in MAP or HR were observed between the groups. Conclusion Infusion of dexmedetomidine during OLV in high-risk pediatric thoracic surgery reduces shunt and pulmonary shunt fraction Qs/Qt, improves PaO 2 and body oxygenation, reduces PIP and pressure load, and maintains hemodynamic stability (MAP, HR).
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