Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia.

BACKGROUND: The 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. AIMS: To 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. METHODS: Nineteen 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®. RESULTS: After 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. CONCLUSION: The 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.

Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds): study protocol and statistical analysis plan for a multicentre international observational cohort study.

INTRODUCTION: Surgery is a cost-effective public health intervention. Access to safe surgery is a basic human right. However, there are still significant disparities in the access to and safety of surgical and anaesthesia care between low-income and middle-income countries and high-income countries. The Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds) is an international, observational, 14-day cohort study to investigate the incidence of 30-day in-hospital complications following elective or emergency paediatric surgery in Latin American countries. METHODS AND ANALYSIS: LASOS-Peds is a prospective, international, multicentre observational study of paediatric patients undergoing both elective and non-elective surgeries and procedures, inpatient and outpatient, including those performed outside the operating room. The primary outcome is the incidence of in-hospital postoperative complications up to 30 days after surgery. Secondary outcomes include intraoperative complications and the need for intensive care unit admission. ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board of the coordinating centre (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo) as well as from all the participating centres. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT05934682.

Anestesia obstétrica en Chad. Volviendo a los orígenes / Obstetric Anesthesia in Chad. Back to basics

BACKGROUND: Most maternal deaths occur in low- and middle-income countries, with Chad being one of the countries with the most alarming figures. There aren't many reports of anesthetic management for cesarean delivery in these countries. AIM: To report the obstetrical anesthetic experience in a hospital in Chad, Africa in the context of an international cooperation project to reduce the global shortage of anesthesiologists. MATERIAL AND METHODS: Case series of pregnant woman who were admitted to the ward of the Good Samaritan University Hospital Complex. RESULTS: Thirty-two cesarean sections were performed, all using spinal anesthesia. The median age was 22 years, seven of them being adolescents. In two cases sedation with ketamine was used due to insufficient level and in one case general anesthesia with halothane was converted due to total spinal diagnosis. In twelve patients the interruption was due to immediate maternal/fetal vital risk (emergency cesarean section), the main causes being fetal bradycardia and placental abruption. Three patients presented uterine inertia refractory to medical treatment and resolved with the B-Lynch technique. Two patients decided to have immediate skin-to-skin contact. Three neonates had to be resuscitated with positive pressure ventilation, one of them died. No operative deaths were reported in the patients who underwent c-section, but there was one maternal death due to severe preeclampsia and postpartum hemorrhage after vaginal delivery. No epidural analgesia was requested for labor. CONCLUSIONS: This individual report provides insight into a particular reality with very limited staff and resources.

IMPORTANCIA: La mayoría de las muertes maternas se producen en países de bajos y medianos ingresos, siendo Chad uno de los países con cifras más alarmantes. No existen muchos reportes del manejo anestésico para la operación cesárea en estos países. OBJETIVO: Relatar la experiencia anestésica obstétrica en un hospital de Chad, África, en el contexto de un proyecto de cooperación internacional para reducir el déficit global de anestesistas. MATERIAL Y MÉTODOS: Serie de casos de mujeres embarazadas que ingresaron al Complejo Hospitalario Universitario del Buen Samaritano, en el mes de diciembre de 2017. RESULTADOS: Treinta y dos cesáreas se realizaron, en todas se usó anestesia raquídea. La mediana de edad fue 22 años, siendo siete de ellas adolescentes. En dos casos se ocupó sedación con ketamina por nivel insuficiente y en un caso se convirtió a anestesia general con halotano por diagnóstico de espinal total. En doce pacientes la interrupción fue por riesgo vital materno / fetal inmediato (cesárea de emergencia), siendo las principales causas bradicardia fetal y desprendimiento de placenta. Tres pacientes presentaron inercia uterina refractaria a tratamiento médico resolviéndose con técnica de B-Lynch. Dos pacientes decidieron tener contacto piel con piel inmediato. Hubo que reanimar con ventilación a presión positiva a tres neonatos, falleciendo uno de ellos. No se reportaron muertes operatorias en las pacientes operadas de cesárea, pero hubo una muerte materna por preeclampsia severa y hemorragia posparto luego de un parto vaginal. No se solicitó analgesia peridural para trabajo de parto. CONCLUSIONES: Este reporte individual otorga una visión de una realidad particular con personal y recursos muy limitados.