Dexmedetomidine Cycling and Sleep in the Pediatric ICU

NCT05003102 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 210478
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of mechanically ventilated pediatric intensive care unit (ICU) teenage patients and the effects of the medication dexmedetomidine on sleep, delirium, and sedation level. The Investigators will assess sleep with an 8 lead polysomnogram study and increase the medication at night for one night to see if the sleep architecture changes. The Investigators will assess their sleep with our unit's sedation protocol for an additional night.

Conditions

Critical Illness; Sedation Complication; Delirium

Keywords

dexmedetomidine; sleep

Outcome Measures

Primary Outcomes (3)

• Change in total sleep time as seen via an 8-lead polysomnogram

  quantitative measure of physiological parameter; sleep software will add all sleep time together for final value in hours and minutes

  2200 hours to 0600 hours during each study night; up to 2 study nights during the hospital admission

• Change in total time in different stages of sleep as seen via an 8-lead polysomnogram

  quantitative measure of physiological parameter; sleep study interpreter will determine time spent in stages N1, N2, N3, and Rapid Eye Movement (REM) based upon architecture of the sleep spindles and add together for final amount of time in hours and minutes spent in each stage

  2200 hours to 0600 hours during each study night; up to 2 study nights during the hospital admission

• Change in arousal index as seen via an 8-lead polysomnogram

  quantitative measure of physiological parameter; sleep study interpreter will determine the number of arousals and awakenings and divide this by the total sleep time

  2200 hours to 0600 hours during each study night; up to 2 study nights during the hospital admission

Secondary Outcomes (2)

• Incidence of Delirium

  Day 1 between 0800 hours and 1900 hours; Day 1 between 1900 hours and 0800 hours; and Day 2 between 0800 hours and 1900

• Sedation Exposure

  2200 hours to 0600 hours each study night; up to 2 study nights during the hospital admission

Study Arms (2)

Dexmedetomidine cycling then Standard Pediatric Intensive Care Unit (PICU) sedation protocol

EXPERIMENTAL

One the first night, participants receive a dexmedetomidine bolus of 0.5 mcg/kg which is then titrated at an increased drip rate of 0.3 mcg/kg/hr until a.) a targeted Richmond Agitation-Sedation Scale (RASS) state that is one level deeper than what was targeted during the day is achieved or b.) infusion is at max drip rate (dexmedetomidine 2 mcg/kg/hr). On the second night, participants receive the standard PICU Sedation Protocol of fentanyl infusion at 1 mcg/kg/hr and dexmedetomidine infusion at 0.3 mcg/kg/hr with no modifications made until goal RASS reached or at max infusion drips achieved (fentanyl 5 mcg/kg/hr and dexmedetomidine 2 mcg/kg/hr).

Drug: Dexmedetomidine Hydrochloride - Cycling; Drug: Fentanyl - PICU Standard; Drug: Dexmedetomidine Hydrochloride - PICU Standard

Standard Pediatric Intensive Care Unit (PICU) sedation protocol then Dexmedetomidine cycling

ACTIVE COMPARATOR

On the first night, participants will receive the standard PICU Sedation Protocol of fentanyl infusion at 1 mcg/kg/hr and dexmedetomidine infusion at 0.3 mcg/kg/hr with no modifications made until goal RASS reached or at max infusion drips achieved (fentanyl 5 mcg/kg/hr and dexmedetomidine 2 mcg/kg/hr). On the second night, participants receive a dexmedetomidine bolus of 0.5 mcg/kg which is then titrated at an increased drip rate of 0.3 mcg/kg/hr until a.) a targeted Richmond Agitation-Sedation Scale (RASS) state that is one level deeper than what was targeted during the day is achieved or b.) infusion is at max drip rate (dexmedetomidine 2 mcg/kg/hr).

Drug: Dexmedetomidine Hydrochloride - Cycling; Drug: Fentanyl - PICU Standard; Drug: Dexmedetomidine Hydrochloride - PICU Standard

Interventions

Dexmedetomidine Hydrochloride - Cycling DRUG

Dexmedetomidine Hydrochloride infusion at 0.5 mcg/kg titrated to 0.3 mcg/kg/hr up to a max drip rate of 2 mcg/kg/hr.

Also known as: Precedex

Dexmedetomidine cycling then Standard Pediatric Intensive Care Unit (PICU) sedation protocol; Standard Pediatric Intensive Care Unit (PICU) sedation protocol then Dexmedetomidine cycling

Fentanyl - PICU Standard DRUG

fentanyl infusion at 1 mcg/kg/hr up to a max drip rate of 5 mcg/kg/hr

Dexmedetomidine cycling then Standard Pediatric Intensive Care Unit (PICU) sedation protocol; Standard Pediatric Intensive Care Unit (PICU) sedation protocol then Dexmedetomidine cycling

Dexmedetomidine Hydrochloride - PICU Standard DRUG

Dexmedetomidine Hydrochloride infusion at 0.3 mcg/kg titrated to 0.5 mcg/kg/hr up to a max drip rate of 2 mcg/kg/hr

Also known as: Precedex

Dexmedetomidine cycling then Standard Pediatric Intensive Care Unit (PICU) sedation protocol; Standard Pediatric Intensive Care Unit (PICU) sedation protocol then Dexmedetomidine cycling

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients who are intubated and ages 12 years and 0 days old to 17 years and 364 days old who are admitted to the Pediatric intensive care unit and who are on the sedation protocol with use of at least an intravenous dexmedetomidine infusion
• Patients will be selected from those admitted from the emergency room for traumas and critical illness as well as those admitted for post-operative care
• Prematurity, history of permanent neurological damage, autism spectrum disorder, presence of genetic conditions will not preclude enrollment

You may not qualify if:

• Patients taking clonidine daily prior to admission
• Those with allergy to dexmedetomidine
• Those on non-intravenous forms of dexmedetomidine
• Those on a ketamine, propofol, pentobarbital, or paralytic infusions
• Those with a diagnosis of refractory status epilepticus
• Patients with vision loss
• Those admitted for care following a cardiac arrest
• Those with a history of hemodynamic instability with dexmedetomidine infusion and lack of a permanent pacemaker or implantable cardioverter-defibrillator
• Those with International Normalized Ratio (INR) \>3.2 (due to concerns for reduction in clearance by 50% in pediatric patients at that level of coagulopathy)
• Those on antiarrhythmics (due to association with cardiac arrest with dexmedetomidine and amiodarone and concerns with administration while on digoxin)
• Those with a Glascow Coma Scale (GCS) of 3T or less at presentation
• Those on sedation for end of life comfort

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Related Publications (12)

• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.

  PMID: 15082703 BACKGROUND

• Figueroa-Ramos MI, Arroyo-Novoa CM, Lee KA, Padilla G, Puntillo KA. Sleep and delirium in ICU patients: a review of mechanisms and manifestations. Intensive Care Med. 2009 May;35(5):781-95. doi: 10.1007/s00134-009-1397-4. Epub 2009 Jan 23.

  PMID: 19165463 BACKGROUND

• Faraut B, Boudjeltia KZ, Vanhamme L, Kerkhofs M. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev. 2012 Apr;16(2):137-49. doi: 10.1016/j.smrv.2011.05.001. Epub 2011 Aug 10.

  PMID: 21835655 BACKGROUND

• Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Follett H, Kales A, Chrousos GP. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab. 2004 May;89(5):2119-26. doi: 10.1210/jc.2003-031562.

  PMID: 15126529 BACKGROUND

• Kudchadkar SR, Yaster M, Punjabi AN, Quan SF, Goodwin JL, Easley RB, Punjabi NM. Temporal Characteristics of the Sleep EEG Power Spectrum in Critically Ill Children. J Clin Sleep Med. 2015 Dec 15;11(12):1449-54. doi: 10.5664/jcsm.5286.

  PMID: 26194730 BACKGROUND

• Kamdar BB, Shah PA, King LM, Kho ME, Zhou X, Colantuoni E, Collop NA, Needham DM. Patient-nurse interrater reliability and agreement of the Richards-Campbell sleep questionnaire. Am J Crit Care. 2012 Jul;21(4):261-9. doi: 10.4037/ajcc2012111.

  PMID: 22751369 BACKGROUND

• Hoey LM, Fulbrook P, Douglas JA. Sleep assessment of hospitalised patients: a literature review. Int J Nurs Stud. 2014 Sep;51(9):1281-8. doi: 10.1016/j.ijnurstu.2014.02.001. Epub 2014 Feb 15.

  PMID: 24636444 BACKGROUND

• Richardson A, Crow W, Coghill E, Turnock C. A comparison of sleep assessment tools by nurses and patients in critical care. J Clin Nurs. 2007 Sep;16(9):1660-8. doi: 10.1111/j.1365-2702.2005.01546.x. Epub 2007 Apr 24.

  PMID: 17459137 BACKGROUND

• Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7.

  PMID: 28105598 BACKGROUND

• Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.

  PMID: 12552203 BACKGROUND

• Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018 May 1;197(9):1147-1156. doi: 10.1164/rccm.201710-1995OC.

  PMID: 29498534 BACKGROUND

• Hong KS, Kim NR, Song SH, Hong G. Cycling of Dexmedetomidine May Prevent Delirium After Liver Transplantation. Transplant Proc. 2018 May;50(4):1080-1082. doi: 10.1016/j.transproceed.2017.11.076.

  PMID: 29731070 BACKGROUND

Related Links

• FDA Sheet for Dexmedetomidine Hydrochloride (Reference ID: 3836249)

MeSH Terms

Conditions

Critical Illness; Delirium

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Chiara N Foster, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Sleep study interpreters will not know which night had dexmedetomidine preferentially increased
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Critical Care Medicine Fellow

Model Details: randomized crossover trial

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 12, 2021
• Study Start: February 20, 2023
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)