Muscle Relaxation for Pediatric Adenotonsillectomy

Tonsillectomy Clinical Trial

Official title:

Anesthesia With Neuromuscular Blockade and Reversal With Sugammadex Compared to Anesthesia Without Muscle Relaxation During Pediatric High-Risk Adenotonsillectomy: A Randomized-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06225466
• Other study ID #: STU2023-0851
• Status: Recruiting
• Phase: Phase 4
• Start date: April 10, 2024
• Est. completion date: August 1, 2025

Study information

• Verified date: April 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Proshad Efune, MD
• Phone: 214-456-7596
• Email: proshad.efune[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare general anesthesia with muscle relaxation and reversal of the relaxation at the end of surgery or without muscle relaxation in high-risk children having adenotonsillectomy surgery. The main questions it aims to answer are:

1. What is the impact of general anesthesia with muscle relaxation on opioid pain medication requirements during and after adenotonsillectomy?

2. What is the impact of general anesthesia with muscle relaxation on postoperative breathing complications and the adequacy of postoperative lung air volumes during breathing?

Participants will wear three additional, noninvasive monitors during surgery, and one additional monitor after surgery. The amount of opioid pain medication required will be tracked, and the patient will be observed postoperatively for breathing complications. Measurements will be collected from the monitor worn postoperatively.

Researchers will compare general anesthesia with muscle relaxation and reversal of relaxation at the end of surgery with general anesthesia without muscle relaxation to test the hypothesis that the approach using muscle relaxation reduces the amount of opioid pain medication required during and after surgery.

Description:

This will be a randomized, patient- and assessor-blinded, parallel arm, controlled trial assessing the efficacy of neuromuscular blockade with reversal during the anesthetic management of pediatric adenotonsillectomy (AT) to reduce intra- and postoperative opioid consumption and postoperative respiratory events in high-risk patients. Enrolled participants will be randomized by computer-generated assignment using stratified blocked randomization with a 1:1 allocation into 2 arms: neuromuscular blockade with reversal at the end of surgery and no neuromuscular blockade. Randomization will occur on the following strata: severe versus non-severe obstructive sleep apnea (OSA)/sleep disordered breathing. Patients/families, treating teams (except for the anesthesia team), and research staff/investigators responsible for measuring and adjudicating outcomes will be blinded to allocation.

Primary Efficacy Objective - Evaluate intraoperative and postoperative opioid consumption in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex.

Secondary Objectives - (1) Evaluate postoperative respiratory events in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex. The outcome of postoperative respiratory events will be a composite measure consisting of 1) airway obstruction or hypoxemia, defined as SpO2 less than 90 percent, requiring any of the following interventions: supplemental oxygen by nasal cannula or simple face mask, noninvasive positive airway pressure, or reintubation; or 2) unanticipated intensive care unit (ICU) admission. (2) Evaluate postoperative low minute ventilation (MV) episodes, defined as MV less than 40 percent predicted for at least 2 minutes and measured by a respiratory volume monitor (RVM), in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: August 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 12 Years

Eligibility

Inclusion Criteria:

• Children 2-12 years of age having tonsillectomy with or without adenoidectomy at Children's main Dallas campus

• Considered high-risk* with pre-planned overnight admission after surgery for respiratory monitoring *High-risk children have any one of the following characteristics: age < 3 years, severe obstructive sleep apnea (apnea-hypopnea index > 10 events per hour), or obesity (body mass index > 98th percentile).

Exclusion Criteria:

• Planned placement on positive airway pressure or supplemental oxygen postoperatively

• Secondary procedures under the same anesthetic, except for myringotomy tubes or auditory brainstem response testing

• Children with neuromuscular disorders such as congenital myopathies, myotonias, or myasthenia gravis

• Known rocuronium, vecuronium, or sugammadex allergy

Related Conditions & MeSH terms

• Tonsillectomy

Intervention

Drug:
• Rocuronium
After induction of anesthesia and placement of an IV, rocuronium 0.6 mg/kg (maximum dose 50mg) will be administered. Additional doses of rocuronium 0.2 mg/kg (maximum dose 15 mg) will be administered when the neuromuscular transmission monitor indicates a train of four count of 2 or greater.
• Sugammadex
When the surgery is completed, sugammadex 2 mg/kg will be administered if the neuromuscular transmission monitor indicates the train of four count is 2 or greater. Sugammadex 4 mg/kg will be administered if 1) the train of four count is 1, or 2) if the train of four count is 0 and the post tetanic count is at least 1. There is no maximum dose of sugammadex.

Other:
• Anesthesia without neuromuscular blockade
Anesthesia without rocuronium or sugammadex

Locations

Country	Name	City	State
United States	Children's Health Dallas	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & Publications (24)

Allareddy V, Martinez-Schlurmann N, Rampa S, Nalliah RP, Lidsky KB, Allareddy V, Rotta AT. Predictors of Complications of Tonsillectomy With or Without Adenoidectomy in Hospitalized Children and Adolescents in the United States, 2001-2010: A Population-Based Study. Clin Pediatr (Phila). 2016 Jun;55(7):593-602. doi: 10.1177/0009922815616885. Epub 2015 Nov 24. — View Citation

Baldo BA, Rose MA. Mechanisms of opioid-induced respiratory depression. Arch Toxicol. 2022 Aug;96(8):2247-2260. doi: 10.1007/s00204-022-03300-7. Epub 2022 Apr 26. — View Citation

Brown KA, Laferriere A, Moss IR. Recurrent hypoxemia in young children with obstructive sleep apnea is associated with reduced opioid requirement for analgesia. Anesthesiology. 2004 Apr;100(4):806-10; discussion 5A. doi: 10.1097/00000542-200404000-00009. — View Citation

Chisholm AG, Sathyamoorthy M, Seals SR, Carron JD. Does intravenous acetaminophen reduce perioperative opioid use in pediatric tonsillectomy? Am J Otolaryngol. 2019 Nov-Dec;40(6):102294. doi: 10.1016/j.amjoto.2019.102294. Epub 2019 Sep 9. — View Citation

Cote CJ, Posner KL, Domino KB. Death or neurologic injury after tonsillectomy in children with a focus on obstructive sleep apnea: houston, we have a problem! Anesth Analg. 2014 Jun;118(6):1276-83. doi: 10.1213/ANE.0b013e318294fc47. — View Citation

Dalesio NM, Lee CKK, Hendrix CW, Kerns N, Hsu A, Clarke W, Collaco JM, McGrath-Morrow S, Yaster M, Brown RH, Schwartz AR. Effects of Obstructive Sleep Apnea and Obesity on Morphine Pharmacokinetics in Children. Anesth Analg. 2020 Sep;131(3):876-884. doi: 10.1213/ANE.0000000000004509. Erratum In: Anesth Analg. 2022 Feb 1;134(2):e12. — View Citation

Efune PN, Longanecker JM, Alex G, Saynhalath R, Khan U, Rivera K, Jerome AP, Boone W, Szmuk P. Use of dexmedetomidine and opioids as the primary anesthetic in infants and young children: A retrospective cohort study. Paediatr Anaesth. 2020 Sep;30(9):1013-1019. doi: 10.1111/pan.13945. Epub 2020 Jul 26. — View Citation

Efune PN, Saynhalath R, Blackwell JM, Steiner JW, Olomu PN, Szmuk P. The Truview PCD video laryngoscope for nasotracheal intubation in pediatric patients: A subset analysis from a prospective randomized controlled trial. Paediatr Anaesth. 2020 Oct;30(10):1157-1158. doi: 10.1111/pan.14005. Epub 2020 Sep 6. No abstract available. — View Citation

Goldman JL, Baugh RF, Davies L, Skinner ML, Stachler RJ, Brereton J, Eisenberg LD, Roberson DW, Brenner MJ. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope. 2013 Oct;123(10):2544-53. doi: 10.1002/lary.23926. Epub 2013 Apr 17. — View Citation

Gozal D, Burnside MM. Increased upper airway collapsibility in children with obstructive sleep apnea during wakefulness. Am J Respir Crit Care Med. 2004 Jan 15;169(2):163-7. doi: 10.1164/rccm.200304-590OC. Epub 2003 Oct 2. — View Citation

Hamilton TB, Thung A, Tobias JD, Jatana KR, Raman VT. Adenotonsillectomy and postoperative respiratory adverse events: A retrospective study. Laryngoscope Investig Otolaryngol. 2020 Jan 3;5(1):168-174. doi: 10.1002/lio2.340. eCollection 2020 Feb. — View Citation

Johnson RF, Zhang J, Chorney SR, Kou YF, Lenes-Voit F, Ulualp S, Liu C, Mitchell RB. Estimations of Inpatient and Ambulatory Pediatric Tonsillectomy in the United States: A Cross-sectional Analysis. Otolaryngol Head Neck Surg. 2023 Aug;169(2):258-266. doi: 10.1002/ohn.268. Epub 2023 Feb 5. — View Citation

Kou YF, Sakai M, Shah GB, Mitchell RB, Johnson RF. Postoperative respiratory complications and racial disparities following inpatient pediatric tonsillectomy: A cross-sectional study. Laryngoscope. 2019 Apr;129(4):995-1000. doi: 10.1002/lary.27405. Epub 2018 Nov 9. — View Citation

Lammers CR, Schwinghammer AJ, Hall B, Kriss RS, Aizenberg DA, Funamura JL, Senders CW, Nittur V, Applegate RL 2nd. Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. Anesth Analg. 2021 Dec 1;133(6):1568-1576. doi: 10.1213/ANE.0000000000005678. — View Citation

Marcus CL, McColley SA, Carroll JL, Loughlin GM, Smith PL, Schwartz AR. Upper airway collapsibility in children with obstructive sleep apnea syndrome. J Appl Physiol (1985). 1994 Aug;77(2):918-24. doi: 10.1152/jappl.1994.77.2.918. — View Citation

Mitchell RB, Archer SM, Ishman SL, Rosenfeld RM, Coles S, Finestone SA, Friedman NR, Giordano T, Hildrew DM, Kim TW, Lloyd RM, Parikh SR, Shulman ST, Walner DL, Walsh SA, Nnacheta LC. Clinical Practice Guideline: Tonsillectomy in Children (Update). Otolaryngol Head Neck Surg. 2019 Feb;160(1_suppl):S1-S42. doi: 10.1177/0194599818801757. — View Citation

Rossi NA, Spaude J, Ohlstein JF, Pine HS, Daram S, McKinnon BJ, Szeremeta W. Apnea-hypopnea index severity as an independent predictor of post-tonsillectomy respiratory complications in pediatric patients: A retrospective study. Ear Nose Throat J. 2021 Dec 1:1455613211059468. doi: 10.1177/01455613211059468. Online ahead of print. — View Citation

Saynhalath R, Alex G, Efune PN, Szmuk P, Zhu H, Sanford EL. Anesthetic Complications Associated With Severe Acute Respiratory Syndrome Coronavirus 2 in Pediatric Patients. Anesth Analg. 2021 Aug 1;133(2):483-490. doi: 10.1213/ANE.0000000000005606. — View Citation

Shen F, Zhang Q, Xu Y, Wang X, Xia J, Chen C, Liu H, Zhang Y. Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2225473. doi: 10.1001/jamanetworkopen.2022.25473. — View Citation

Smith DF, Spiceland CP, Ishman SL, Engorn BM, Donohue C, Park PS, Benke JR, Frazee T, Brown RH, Dalesio NM. Admission Criteria for Children With Obstructive Sleep Apnea After Adenotonsillectomy: Considerations for Cost. J Clin Sleep Med. 2017 Dec 15;13(12):1463-1472. doi: 10.5664/jcsm.6850. — View Citation

Templeton TW, Goenaga-Diaz EJ, Downard MG, McLouth CJ, Smith TE, Templeton LB, Pecorella SH, Hammon DE, O'Brien JJ, McLaughlin DH, Lawrence AE, Tennant PR, Ririe DG. Assessment of Common Criteria for Awake Extubation in Infants and Young Children. Anesthesiology. 2019 Oct;131(4):801-808. doi: 10.1097/ALN.0000000000002870. — View Citation

von Ungern-Sternberg BS, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, Hall GL. Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: The REACT Randomized Clinical Trial. JAMA Pediatr. 2019 Jun 1;173(6):527-533. doi: 10.1001/jamapediatrics.2019.0788. — View Citation

Voss T, Wang A, DeAngelis M, Speek M, Saldien V, Hammer GB, Wrishko R, Herring WJ. Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study. Paediatr Anaesth. 2022 Mar;32(3):436-445. doi: 10.1111/pan.14370. Epub 2021 Dec 17. — View Citation

Waters KA, McBrien F, Stewart P, Hinder M, Wharton S. Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol (1985). 2002 May;92(5):1987-94. doi: 10.1152/japplphysiol.00619.2001. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative intra- and postoperative opioid consumption	Continuous outcome of intravenous morphine milligram equivalents (MME) per kg of body weight	From surgery start to discharge home, up to 24 hours
Secondary	Number of participants with postoperative respiratory events	Composite binary outcome consisting of 1) airway obstruction or hypoxemia, defined as SpO2 <90%, requiring any of the following interventions: supplemental oxygen by nasal cannula or simple face mask, noninvasive positive airway pressure, or reintubation; or 2) unanticipated ICU admission.	From post-anesthesia care unit admission to discharge home, up to 24 hours
Secondary	Number of low minute ventilation (MV) events in the post-anesthesia care unit	Count outcome of distinct episodes of MV less than 40 percent predicted for at least 2 minutes	From post-anesthesia care unit admission to transfer to the postoperative ward, up to 8 hours