Novel anesthetics in pediatric practice: is it time?

Useinovic, Nemanja; Jevtović-Todorović, Vesna

doi:10.1097/aco.0000000000001156

Cited by 8 publications

(6 citation statements)

References 91 publications

(114 reference statements)

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“…The results showed that remimazolam has a non-inferior sedative effect than propofol and might be a safer alternative ( Xin et al, 2022b ). In addition, due to the characteristics of rapid conversion to inactive metabolites, remimazolam may reduce cumulative neurotoxicity, which will benefit pediatric patients compared to other commonly used anesthetics ( Useinovic and Jevtovic-Todorovic, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial

Chu,

Zhou,

Wan

et al. 2024

Front. Pharmacol.

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Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE).Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation.Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group.Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia.Clinical trial registration:https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863

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Section: Discussionmentioning

confidence: 99%

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial

Chu,

Zhou,

Wan

et al. 2024

Front. Pharmacol.

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“…Some anesthetics drugs have also been reevaluated in different formulations, such as xenon and alphaxalone. However, their effects on brain development have yet to be established [ 58 ]. Certainly, this is another important issue for future research.…”

Section: Discussionmentioning

confidence: 99%

Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment

Colletti

Bartolomeo

Negrello

et al. 2023

JPM

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The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding “children multiple general anesthesia OR pediatric multiple general anesthesia”. Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews’ bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations.

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“…Post synaptic GABA A receptor interaction is the most common mode of action for anaesthetic and sedating drugs used in clinical anaesthesia and intensive care practice; for example, propofol, barbiturates, benzodiazepines, and inhaled drugs like isoflurane and sevoflurane. Unfortunately, those commonly used anaesthetic compounds have been shown to be neurotoxic, at least in immature brains [ 13 – 15 ], and the neurotoxic effects have been attributed to their interaction with GABA A receptors. This seems to be at odds with the fact that neurosteroids, allopregnanolone and progesterone are neuroprotective compounds even though they are sedatives and anaesthetics that interact with GABA A receptors [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial

Serrao

Goodchild

2022

BMC Anesthesiol

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Background Alfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible for maintenance of cognition and neuroprotection by activation of brain pregnane X receptors and consequent increased production of mature brain-derived neurotrophic factor (m-BDNF). Two studies are reported here: an in vitro study investigated whether alfaxalone activates human pregnane X receptors (h-PXR) as effectively as allopregnanolone; and a clinical study that measured postoperative changes in serum m-BDNF and cognition in patients after alfaxalone anaesthesia compared with propofol and sevoflurane. Methods In vitro Activation of h-PXR by allopregnanolone and alfaxalone solutions (206 - 50,000 nM) was measured using human embryonic kidney cells expressing h-PXR hybridised and linked to the firefly luciferase gene. Light emission by luciferase stimulated by each ligand binding with h-PXR was measured. Clinical A double blind prospective randomised study of patients undergoing hip arthroplasty anaesthetised with alfaxalone TIVA (n = 8) or propofol TIVA (n = 3) or propofol plus sevoflurane inhalational anaesthesia (n = 4). The doses of anaesthetics were titrated to the same depth of anaesthesia (BIS 40-60). Subjects’ cognitive performance was assessed using the Grooved Pegboard Test, Digit Symbol Substitution Test (DSST) and Mini Mental State examination (MMSE) for 7 days postoperatively. Serum m-BDNF concentrations were measured for 7 postoperative days. Results In vitro Allopregnanolone and alfaxalone both activated h-PXR, alfaxalone being more efficacious than allopregnanolone: 50,000 nM, p = 0.0019; 16,700 nM, p = 0.0472; 5600 nM, p = 0.0031. Clinical Alfaxalone treated subjects scored better than propofol and sevoflurane anaesthetised patients in the cognition tests: (MMSE p = 0.0251; Grooved Pegboard test dominant hand pre v post anaesthesia scores p = 0.8438 for alfaxalone and p = 0.0156 for propofol and propofol/sevoflurane combined). The higher cognition scores were accompanied by higher serum m-BDNF levels in the alfaxalone anaesthetised patients (p < 0.0001). Conclusions These results suggest that sedation and anaesthesia induced by the synthetic neuroactive steroid alfaxalone may be accompanied by effects normally caused by physiological actions of allopregnanolone at PXR, namely, increased secretion of m-BDNF and consequent neuroprotection and preservation of cognition. Trial registration The clinical trial was registered on 17/01/2018 with the Australian New Zealand Clinical Trials Registry: registration number ACTRN12618000064202 [Universal Trial Number U1111-1198-0412].

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Novel anesthetics in pediatric practice: is it time?

Cited by 8 publications

References 91 publications

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial

Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial

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