Propofol and thiopental for intravenous induction in neonates: Study protocol for a dose-finding trial.

BACKGROUND: Propofol and thiopental are commonly used induction agents in neonatal anesthesia. Even though both hypnotics have been used off-label for many years, pharmacological knowledge regarding these agents is scarce in neonates. The significant variability in neonates' body composition, organ function, and maturation makes pharmacological studies highly relevant albeit challenging. As a result, there is currently limited data about the anesthetic induction dose of thiopental and propofol in neonates. In addition, a knowledge gap exists concerning the pharmacodynamics of induction doses. OBJECTIVE: To determine the median effective anesthetic induction dose of propofol and thiopental in neonatal patients of different gestational and postnatal ages and evaluate the pharmacodynamics of the anesthesia induction doses on the neonatal systemic and cerebral hemodynamics. METHODS: This is a single-center, prospective, open-label, interventional, dose-finding study, including neonatal patients from birth up to 28 postnatal days undergoing general anesthesia for surgical or diagnostic procedures. The patients will be stratified according to their gestational and postnatal age and allocated to one of the two trial arms: anesthesia induction with propofol or anesthesia induction with thiopental. We will use Dixon's up-and-down method to estimate the median effective anesthesia induction dose of both agents in neonates of different gestational and postnatal ages. In addition, we will study the relationship between anesthesia induction doses and changes in systemic and cerebral hemodynamics. DISCUSSION: Alterations in the systemic and cerebral regional hemodynamics secondary to anesthesia induction may be harmful in neonates, especially premature and critically ill newborns, due to their immature organ systems, reduced physiological reserves, and impaired cerebral autoregulation. Perfusion homeostasis is considered one of the significant and modifiable determinants of anesthesia-related neurocognitive outcomes. Therefore, dose-finding and safety pharmacological studies of the anesthetic induction agents in neonates are urgently needed and acknowledged as a high priority by the European Medicine Agency. Estimating adequate induction doses to ensure optimal depth of anesthesia while avoiding systemic and cerebral hemodynamic disturbances will help ensure safe anesthesia and potentially improve anesthesia-related outcomes in this group of patients. TRIAL REGISTRATION: EudraCT (EudraCT Identifier: 2019-001534-34), 05.07.2022.

Perioperative anaesthetic management and short-term outcome of neonatal repair of oesophageal atresia with or without tracheo-oesophageal fistula in Europe: A sub-analysis of the neonate and children audit of anaesthesia practice in Europe (NECTARINE) prospective multicenter observational study.

BACKGROUND: Oesophageal atresia with or without a tracheo-oesophageal fistula is a congenital abnormality that usually requires surgical repair within the first days of life. OBJECTIVE: Description of the perioperative anaesthetic management and outcomes of neonates undergoing surgery for oesophageal atresia with or without a tracheo-oesophageal fistula, included in the 'neonate and children audit of anaesthesia practice in Europe' (NECTARINE) database. DESIGN: Sub-analyses of prospective observational NECTARINE study. SETTING: European multicentre study. PATIENTS: Neonates who underwent surgery for oesophageal atresia with or without a tracheo-oesophageal fistula in the NECTARINE cohort were selected. MAIN OUTCOME MEASURES: Incidence rates with 95% confidence intervals were calculated for peri-operative clinical events which required a predetermined intervention, postoperative complications, and mortality. RESULTS: One hundred and three neonates undergoing a first surgical intervention for oesophageal atresia with or without a tracheo-oesophageal fistula repair were identified. Their median gestational age was 38 weeks with a median birth weight of 2840 [interquartile range 2150 to 3150] grams. Invasive monitoring was used in 66% of the procedures. The incidence of perioperative clinical events was 69% (95% confidence interval 59 to 77%), of 30-day postoperative complications 47% (95% confidence interval 38 to 57%) and the 30- and 90 days mortality rates were 2.1% and 2.6%, respectively. CONCLUSION: Oesophageal atresia with or without a tracheo-oesophageal fistula repair in neonates is associated with a high number of perioperative interventions in response to clinical events, a high incidence of postoperative complications, and a substantial mortality rate.

Practical and societal implications of the potential anesthesia-induced neurotoxicity: The safetots perspective.

Key elements for safe and high-quality care in pediatric anesthesia are personal and institutional competence, perioperative maintenance of physiological homeostasis, prevention, prompt recognition, and appropriate treatment of critical situations as well as the reassurance of the parents and respecting the children's rights. Training in pediatric anesthesia should take place within the framework of harmonized curricular structures. International quality assessment and improvement projects should be encouraged and supported by collaborations. Healthy communication and providing information in a balanced way to the public and all stakeholders is an important task for pediatric anesthesia societies and individuals. The Safetots.org initiative was established to emphasize the role of the conduct of anesthesia to prevent harm, promote quality in the perioperative period, and provide safe and high-quality clinical care. This initiative considers that the prevention of complications and other well-known risk factors of perioperative care, as well as the quality of anesthesia management, have a far more important impact on outcomes following anesthesia and surgery than anesthetic drugs themselves.

[Interhospital transport of sick newborns in Denmark].

Interhospital transport of sick newborn infants is dangerous, but the risk of adverse events can be reduced, when transport is being performed by trained neonatal retrieval teams. In this review, we describe the current organisation of neonatal retrieval service in Denmark. The services are based at the neonatal intensive care units of the four university hospitals. Improved cooperation and harmonisation of operations between the teams is needed, as this is a prerequisite for the development of a national clinical consensus guideline and national quality metrics enabling benchmarking both within Denmark and abroad.

No impact of surgery on cognitive function: a longitudinal study of middle-aged Danish twins.

PURPOSE: To examine the association between exposure to surgery and 10-year change in cognitive functioning. METHODS: Among 2351 middle-aged twins, a 10-year change in composite cognitive scores derived from five cognitive tests was compared between 903 (38%) twins exposed to surgery classified as major, minor, knee and hip replacement, and other, and a reference group of 1448 (62%) twins without surgery, using linear regression models adjusted for socioeconomic factors. Genetic and shared environmental confounding was addressed in intrapair analyses of 48 monozygotic and 74 dizygotic same-sexed twin pairs. RESULTS: In individual-level analyses, twins with major surgery (mean difference, -0.37; 95% CI, -0.76 to 0.02) or knee and hip replacement surgery (mean difference, -0.54; 95% CI, -1.30 to 0.22) had a tendency of a negligibly higher rate of decline in cognitive score than the reference group. In the intrapair analyses, the surgery-exposed twin had a higher rate of cognitive decline than the co-twin in 55% (95% CI, 45% to 63%) of the pairs. The mean difference in cognitive decline within pairs was -0.21 (95% CI, -0.81 to 0.39). CONCLUSIONS: No significant associations were found between exposure to surgery and change in cognitive score either in individual-level or in intrapair analyses.

Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery: A randomized controlled study comprising four different anaesthetic techniques.

BACKGROUND: Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens. METHODS: Young (21-days) and adult (2 months) male Sprague-Dawley rats were randomized to 150 min exposure to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic profiles were evaluated in the cortex, thalamus and hippocampus (CA1 and CA3) at the end of the procedure in each experimental group. RESULTS: Significant perturbations of systemic homeostasis were found under all anaesthetic regimens. Hyperglycemia and decreased heart rate were particularly relevant in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery-induced neuroapoptosis was found between young and adult rats in several brain regions. Combination of sevoflurane and dexmedetomidine resulted in the highest number of caspase-3 positive cells, although the extent of cell death remained relatively low in all experimental groups. CONCLUSION: Combination of anaesthesia and surgery induces significant perturbations of physiological parameters in both young and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups, the overall extent of neuronal cell death remained very low under all conditions questioning, thereby, the physiological significance of apoptotic neurodegeneration in the context of anaesthesia and surgery.

[Congenital hyperinsulinism--diagnosis and treatment]. / Kongenit hyperinsulinisme--diagnostik og behandling.

Congenital hyperinsulinism (CHI) is a rare and heterogeneous disease with a challenging diagnostic process and a need of individualised treatment of each patient. In severe, neonatal or infant CHI, differentiation between the focal and diffuse form by rapid genetics, 18F-fluoro-L-dihydroxyphenylalanine positron emission tomography/computed tomography and peroperative microscopy of frozen section allows surgeons to resect the focal lesion instead of performing subtotal pancreatectomy. Milder CHI, sometimes difficult to diagnose, is treated conservatively. In spite of all improvements, cerebral complications are still frequently seen.