Sevoflurane/Dexmedetomidine vs. Isoflurane for Emergence Delirium

Overseen By Molly Herr, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Mayo Clinic

Disqualifiers: Severe developmental delay, TIVA, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Single session

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two different anesthesia treatments affect children upon waking after surgery, focusing on emergence delirium, a state of confusion or upset as they emerge from anesthesia. Researchers compare Isoflurane with a combination of Sevoflurane (also known as Sevorane or Ultane) and dexmedetomidine. Children aged 2-7 undergoing certain surgeries, such as tonsil removal or eye surgery, who have an IV and breathing tube during the procedure, may be suitable participants. The goal is to determine which treatment better reduces confusion and distress upon waking. As a Phase 3 trial, this study represents the final step before FDA approval, offering an opportunity to contribute to significant advancements in pediatric anesthesia care.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sevoflurane is usually well-tolerated, though some side effects have been reported. In children, it can sometimes cause temporary confusion after waking from anesthesia, known as emergence delirium, which may lead to breathing problems. An EEG, a test that measures brain activity, can help manage anesthesia and reduce these side effects by limiting exposure to sevoflurane.

Studies often focus on isoflurane's use in adults, and it is commonly used in surgeries. Both sevoflurane and isoflurane are approved anesthetics, indicating they are considered safe for humans, although they can have different side effects.

Overall, both treatments are generally safe, but like any medication, they carry some risks. Discuss any concerns with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for emergence delirium because they explore different anesthetic agents, Sevoflurane and Isoflurane, which could potentially offer varying benefits. Unlike other anesthetics, Sevoflurane is known for its rapid onset and recovery, which might reduce the duration of delirium after surgery. On the other hand, Isoflurane, while a more traditional agent, is being compared directly to see if it has any distinct advantages or drawbacks in managing this condition. This trial aims to discover if the choice of anesthetic can significantly impact patient recovery, which could lead to more tailored and effective treatment protocols.

What evidence suggests that this trial's treatments could be effective for pediatric emergence delirium?

This trial will compare the effects of Sevoflurane and Isoflurane on emergence delirium in children. Research has shown that Sevoflurane more often causes restlessness or confusion upon waking from anesthesia compared to Isoflurane. Despite this, Sevoflurane is frequently chosen due to its fewer heart-related side effects than some other anesthetics. Conversely, Isoflurane generally causes less restlessness, offering a potentially calmer recovery. Both treatments have their pros and cons, but the trial aims to determine which one better reduces post-surgery confusion in children. ^{6 7 8 9 10}

Who Is on the Research Team?

Lindsay Warner, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for children who are undergoing surgery and need anesthesia. It's designed to see if one type of anesthesia can reduce confusion or delirium when they wake up after the operation. Specific details about who can join are not provided here.

Inclusion Criteria

I am between 2 and 7 years old.

My treatment can be done as an outpatient or with a hospital stay.

I will have an IV and a breathing tube for my procedure.

Exclusion Criteria

Previous history of severe emergence delirium documented by a provider (via interventions or explicitly stated)

I have severe developmental delays and cannot interact as required.

My surgery will use total intravenous anesthesia (TIVA).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Isoflurane or Sevoflurane plus intravenous push dexmedetomidine during anesthesia

Single session

1 visit (in-person)

Recovery

Participants are monitored in the Post Anesthesia Care Unit (PACU) for emergence delirium and length of stay

0-4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Isoflurane
• Sevoflurane

Trial Overview The study compares two anesthetic approaches: Isoflurane alone versus Sevoflurane combined with a medication called dexmedetomidine. The goal is to see which method better prevents emergence delirium, a state of confusion that sometimes occurs in kids as they recover from anesthesia.

How Is the Trial Designed?

Group I: Isoflurane group Active Control 1 Intervention

Group II: Sevoflurane group Active Control 1 Intervention

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study involving 143 adult patients, sevoflurane was found to allow for a quicker recovery from general anesthesia compared to isoflurane, with shorter times for extubation, eye opening, and command response.

Both sevoflurane and isoflurane demonstrated similar safety profiles, as there were no significant differences in renal and hepatic function before and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance and recovery characteristics of sevoflurane anaesthesia in adult patients. A multicenter, randomized comparison with isoflurane. Ranieri, R., Martinelli, G., Pagani, I., et al.[2018]

In a study of 90 pediatric patients undergoing dental surgery with sevoflurane anesthesia, intranasal dexmedetomidine significantly reduced the incidence of emergence delirium (ED) compared to a control group, with a notable effect at dosages of 1 μg/kg and 2 μg/kg.

The higher dosage of 2 μg/kg not only decreased severe ED but also improved the children's acceptance of mask induction and their tolerance during separation from parents, indicating its potential for enhancing the overall anesthesia experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Intranasal Dexmedetomidine on Emergence Delirium Prevention in Pediatric Ambulatory Dental Rehabilitation Under General Anesthesia: A Randomized Clinical Trial. He, H., Cui, Q., Chen, H., et al.[2023]

In a study of 145 pediatric patients aged 3-10 undergoing anesthesia with sevoflurane, 19.3% experienced emergence delirium, which lasted an average of 6.9 minutes and often required pharmacological intervention.

Younger age and higher preoperative anxiety levels were significant risk factors for emergence delirium, with younger children being 3.3 times more likely and those with moderate to severe anxiety being 5.6 times more likely to experience this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The incidence of emergence delirium and risk factors following sevoflurane use in pediatric patients for day case surgery, Kingston, Jamaica]. Gooden, R., Tennant, I., James, B., et al.[2014]

The study found that the incidence of emergence delirium in adult patients after general anesthesia with sevoflurane is 11.8%, indicating that this condition is more common in adults than previously reported.

Significant risk factors for emergence delirium included being over 65 years old, undergoing emergency surgery, being of African ethnicity, having longer surgery durations, and the number of intubation attempts, suggesting that these factors should be monitored to reduce the risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Emergence delirium following sevoflurane anesthesia in adults: prospective observational study]. Ramroop, R., Hariharan, S., Chen, D.[2022]

In a study of 88 children aged 2-6 undergoing cataract surgery, both desflurane and sevoflurane anesthesia resulted in similar rates of postoperative emergence delirium (ED), with 18.18% in the sevoflurane group and 20.45% in the desflurane group, indicating that both anesthetics are comparably safe in this regard.

Desflurane allowed for faster emergence from anesthesia compared to sevoflurane, suggesting it may be more efficient for recovery, although both drugs had similar effects on ED as measured by the Pediatric Anesthesia Emergence Delirium (PAED) scale.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative emergence delirium in pediatric patients undergoing cataract surgery--a comparison of desflurane and sevoflurane. Sethi, S., Ghai, B., Ram, J., et al.[2022]

In a study of 60 patients undergoing intracranial surgery, sevoflurane (SEVO) was found to provide a significantly faster recovery time compared to isoflurane (ISO), with patients emerging from anesthesia and responding to commands more quickly.

The faster recovery with SEVO, demonstrated by earlier Glasgow coma scale scores, is clinically important for timely neurological assessments in neurosurgical patients, especially after long-duration surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sevoflurane provides faster recovery and postoperative neurological assessment than isoflurane in long-duration neurosurgical cases. Gauthier, A., Girard, F., Boudreault, D., et al.[2019]

In a systematic review of 66 studies involving 5257 pediatric patients, the use of dexmedetomidine with sevoflurane significantly reduced the incidence of emergence delirium compared to sevoflurane alone (9.1% vs. 40%).

However, while dexmedetomidine reduced emergence delirium, it was associated with a higher incidence of postoperative nausea and vomiting (PONV), indicating that clinical decisions should weigh the risks of both outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine vs. total intravenous anaesthesia in paediatric emergence delirium: A network meta-analysis. Petre, MA., Levin, DN., Englesakis, M., et al.[2021]

In a study of 46 children undergoing elective ear-nose-throat surgery, there was no significant difference in the incidence of emergence delirium (ED) between those receiving sevoflurane and those receiving desflurane for anesthesia maintenance.

Both anesthetics showed similar safety profiles, with no increase in adverse events like nausea or vomiting, suggesting that desflurane can be safely used in this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing incidence of emergence delirium between sevoflurane and desflurane in children following routine otolaryngology procedures. Driscoll, JN., Bender, BM., Archilla, CA., et al.[2019]

In a study of 117 children recovering from general anesthesia, the Pediatric Anesthesia Emergence Delirium (PAED) scale identified emergence delirium (ED) in 32% of cases, while the Watcha and Cravero scales identified 26% and 35%, respectively, indicating variability in detection rates among the scales.

The PAED scale showed improved sensitivity and specificity for detecting ED when a score greater than 12 was used, while the Watcha scale was noted for its simplicity and potentially higher overall sensitivity and specificity in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of emergence delirium scales following general anesthesia in children. Bajwa, SA., Costi, D., Cyna, AM.[2022]

Citations

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Incidence of emergence agitation in children undergoing ... The risk of emergence agitation in children after maintenance anesthesia with sevoflurane is significantly greater than with isoflurane.

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Emergence delirium following sevoflurane anesthesia in ... The incidence of emergence delirium in adults after general anesthesia using sevoflurane is significant and has not been adequately reported.

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Emergence agitation in paediatric patients using ... An increased incidence of EA was observed with sevoflurane maintenance anaesthesia, particularly during the initial 10–20 min of the postoperative period.

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Prevention of Sevoflurane Delirium and Agitation With Propofol Sevoflurane is advantageous because it does not cause significant cardiac depression and dysrhythmias compared to halothane. Inhalation induction and ...

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Effects of sevoflurane versus other general anaesthesia on ... We also wanted to know whether treatments can be given to reduce the rate of emergence agitation when sevoflurane is used. Study characteristics.

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Emergence delirium following sevoflurane anesthesia in adults The incidence of emergence delirium was 11.8%. The factors significantly associated with emergence delirium included elderly age (>65) (p = 0.04) ...

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Delirium in older patients given propofol or sevoflurane ... Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery.

8. jamanetwork.com jamanetwork.com/journals/jamapediatrics/article-abstract/2832986

EEG-Guided Titration of Sevoflurane and Pediatric ... EEG-guided management of general anesthesia reduced sevoflurane exposure and pediatric anesthesia emergence delirium in children.

9. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1115124/full

Association of volatile anesthesia exposure and depth with ... Transient agitation/delirium from sevoflurane anesthesia can lead to a variety of adverse events, such as airway spasm, shedding or displaced tracheal tube, ...

10. www2.pedsanesthesia.org www2.pedsanesthesia.org/meetings/2004winter/pdfs/mason_Pitfalls.pdf

Emergence Delirium - Society for Pediatric Anesthesia Oral premedication with the midazolam syrup 0.2 mg/kg had an incidence of emergence agitation that was seen in 47% of patients as compared to 81% who received a ...