Breakthrough Clinical Results

A randomized clinical trial published in JAMA Pediatrics demonstrates that EEG-guided anesthesia using Masimo SedLine® Brain Function Monitoring significantly reduces sevoflurane exposure in pediatric patients. This leads to a lower incidence of pediatric anesthesia emergence delirium (PAED), faster recovery, and earlier discharge from the post-anesthesia care unit (PACU). The study, conducted at Tokyo Women's Medical University, involved 177 children aged 1-6 undergoing elective surgery. SedLine-monitored children experienced a 14% lower rate of PAED, regained consciousness 53% faster, and were discharged 48% sooner, resulting in estimated cost savings of $240-$920 per patient. The findings suggest that current sevoflurane dosages may be excessive and highlight the potential of EEG-guided anesthesia to improve pediatric anesthesia safety and efficiency.

Completion Rate of Trials

Completion Rates and Abandonment in Pediatric Anesthesia Trials (Past 10 Years)

Determining precise completion rates for pediatric anesthesia trials specifically started in the last 10 years is challenging due to limitations in the available data. The provided research articles offer insights into pediatric anesthesia trials and trial completion/abandonment in general, but don't isolate data for this specific timeframe.

Completion Rates:

• A 2014-2015 European study (APRICOT) found a 5.2% incidence of perioperative severe critical events in children undergoing anesthesia. While not a direct measure of trial completion, it highlights potential complications that could lead to early trial termination.
• A secondary analysis of the APRICOT data focusing on Italy reported a lower incidence of severe critical events (3%), possibly due to the high expertise of anesthesiologists. This suggests that anesthesiologist experience may influence trial success and completion.
• A study analyzing Wake Up Safe data (2010-2015) found that 85% of anesthesia-related serious adverse events were deemed preventable. This implies that improving safety protocols could enhance trial completion rates.

Reasons for Trial Abandonment/Discontinuation:

The most common reasons for trial discontinuation or abandonment across various medical fields (including some related to pediatric anesthesia) are:

• Slow recruitment: Difficulty enrolling a sufficient number of participants within a reasonable timeframe is a major challenge. This is particularly relevant in pediatric research due to factors like parental consent and the rarity of some conditions.
• Operational difficulties: These can include logistical issues, protocol violations, data management problems, and unexpected adverse events.
• Lack of funding: Trials may be discontinued if funding sources are withdrawn or insufficient to cover the costs of the study.
• Futility: If interim analyses suggest that the intervention is unlikely to be effective, the trial may be stopped early to avoid exposing participants to unnecessary risks or wasting resources.

Specific to Pediatric Anesthesia:

While the provided texts don't explicitly state the most common cause of abandonment for pediatric anesthesia trials specifically, the APRICOT study highlights the importance of anesthesiologist experience in minimizing critical events. This suggests that trials involving less experienced anesthesiologists might be more susceptible to complications and subsequent discontinuation. Additionally, the Wake Up Safe data emphasizes the preventability of many adverse events, indicating that improved safety protocols could mitigate trial abandonment.

Further Research:

A dedicated study focusing on pediatric anesthesia trials initiated within the past 10 years is needed to provide more precise completion rates and identify the most common reasons for abandonment in this specific field.

Economic Burden

Drug used in other indications

Sevoflurane, primarily known for its use in pediatric anesthesia, is also being investigated for its efficacy and safety in various other clinical applications. Several studies and trials explore its use in diverse patient populations and procedures, often comparing it with other anesthetic agents. Here's a summary of some of these applications and the intervention models used in the trials:

1. Electroconvulsive Therapy (ECT):

• Intervention Model: Randomized controlled trials (RCTs) comparing sevoflurane with intravenous anesthetics like propofol, barbiturates, and ketamine.
• Findings: Sevoflurane significantly decreased EEG seizure durations compared to intravenous anesthetics, but showed no significant difference in the postictal suppression index. It also increased heart rate. The risk of adverse events was comparable between sevoflurane and intravenous anesthetics.

2. Adult Anesthesia Induction:

• Intervention Model: RCT comparing sevoflurane with halothane in adult and pediatric patients.
• Findings: Sevoflurane demonstrated faster induction and shorter intubation time compared to halothane, with better hemodynamic stability and fewer complications like coughing and breath-holding.

3. Anesthesia for Craniotomy in Patients with Supratentorial Gliomas:

• Intervention Model: Prospective, single-center, randomized parallel arm equivalent clinical trial comparing sevoflurane-remifentanil with propofol-remifentanil anesthesia.
• Hypothesis: Postoperative neurologic function is equally affected between the two regimens.
• Outcomes: Primary outcome is neurologic function change assessed by NIHSS. Secondary outcomes include hemodynamic stability, brain relaxation, emergence quality, recovery quality, cognitive function, pain, neurologic complications, and medical expenses.

4. Anesthesia for Breast Cancer Surgery:

• Intervention Model: RCT comparing propofol/remifentanil-based TIVA with sevoflurane-based inhalational anesthesia.
• Findings: Propofol/remifentanil TIVA effectively inhibited the release of VEGF-C induced by breast surgery compared to sevoflurane, but no significant difference was observed in short-term recurrence rates.

5. Anesthesia for Dilation and Evacuation (D&E) Procedures:

• Intervention Model: Randomized, double-blinded, placebo-controlled trial comparing a standardized general anesthesia protocol with and without sevoflurane.
• Findings: Sevoflurane did not significantly increase the risk of intervention for bleeding, but the study was underpowered to detect clinically important differences.

6. Anesthesia for Ankyloglossia Treatment:

• Intervention Model: Retrospective analysis of pediatric outpatients undergoing ankyloglossia treatment with sevoflurane inhalation anesthesia.
• Findings: Sevoflurane resulted in rapid onset and recovery, with few adverse reactions and significant clinical efficacy.

7. Anesthesia for MRI in Children with Neuropsychiatric Disorders:

• Intervention Model: Retrospective cohort study analyzing anesthesiologic records of children undergoing MRI under general anesthesia with sevoflurane.
• Findings: Sevoflurane-based anesthesia was feasible and safe, with a low complication rate. Specific risk factors for complications were identified.

8. Status Asthmaticus:

• Intervention Model: Case reports and case series describing the use of inhaled sevoflurane for life-threatening asthma exacerbations refractory to conventional treatment.
• Findings: Inhaled sevoflurane demonstrated significant beneficial effects in managing severe asthma attacks.

These examples highlight the diverse clinical scenarios where sevoflurane is being investigated beyond its traditional role in pediatric anesthesia. The intervention models employed in these studies, primarily RCTs and observational studies, aim to rigorously evaluate the efficacy and safety of sevoflurane in these novel applications.