Dex as Analgesic Adjuvant in OSA Patients

• ClinicalTrials.gov Identifier: NCT03613558
• Recruitment Status: Withdrawn
• First Posted: August 3, 2018
• Last Update Posted: August 3, 2018
• Sponsor: Montefiore Medical Center
• Information provided by (Responsible Party): Montefiore Medical Center

Study Description

Brief Summary:

The purpose of this study is to assess whether intravenous peri-operative Dexmedetomidine reduces opioid requirements and or improves pain control after Uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnea (OSA).

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea	Drug: Dexmedetomidine; Drug: Placebo	Phase 1; Phase 2

Detailed Description:

BACKGROUND/STUDY SIGNIFICANCE

Patients with OSA undergoing surgery have increased surgical risk compared to patients that do not have OSA . Perioperative medication such as benzodiazepines and opioids can decrease upper airway tone, inhibit central respiratory drive and inhibit upper airway reflexes. The supine position may also worsen the severity of the OSA. Additionally, this group of patients is more likely to have a higher incidence of complications, particularly post operative hypoxemia , difficult intubation , and complicated extubation course .

Uvulopalatopharyngoplasty (UPPP) along with other tongue base procedures are commonly performed surgical procedures used to help alleviate the symptoms of obstructive sleep apnea (OSA). Postoperative management of oropharyngeal pain is challenging since narcotic administration may compromise respiratory status in OSA patients. The Anesthesiology and Otorhinolaryngology communities have begun to rethink acceptable narcotic use in OSA patients especially following the recent FDA announcement highlighting serious adverse effects related to codeine consumption in children who had undergone tonsillectomies.

Dexmedetomidine (Precedex) is a sedative with minimal respiratory depression. Its mechanism is via alpha 2 agonism and has 8 times the affinity for the alpha 2 adrenoreceptor than clonidine. It has been shown to have sedative, analgesic, and anxiolytic effects. It produces a predictable and dose dependent decrease in heart rate and blood pressure. Dexmedetomidine undergoes extensive metabolism in the liver and is then eliminated as methyl and glucuronide conjugates mostly via the renal system. The pharmacokinetics are markedly affected by hepatic insufficiency .

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blinded Randomized Placebo Controlled Study Evaluating the Use of Intraoperative Dexmedetomidine in Reducing Postoperative Pain and Narcotic Requirement in Patients With Moderate to Severe OSA.
• Study Start Date: July 2014
• Estimated Primary Completion Date: June 2015
• Estimated Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dexmedetomidine Sedation; This group will receive 1mcg/kg bolus of dexmedetomidine over 15 minutes after intubation followed by an infusion of dexmedetomidine at 0.5mcg/kg/hr until approximately 30 minutes before the end of surgery.	Drug: Dexmedetomidine; Dexmedetomidine is an alpha-2 agonist that provides both sedation and analgesia; Other Name: Precedex
Placebo Comparator: Placebo; This group will receive a colorless, odorless liquid (i.e. normal saline) in order to resemble Dexmedetomidine.	Drug: Placebo; saline solution

Outcome Measures

Primary Outcome Measures :

1. Pain Score [ Time Frame: within 24 hours post-operative ]
   Patient self-reported pain scores will be measured immediately after awakening post-op using the Numerical Pain Rating Scale and opioid requirements using morphine equivalents

Secondary Outcome Measures :

1. Pain Score [ Time Frame: within 24 hours post-operative ]
   Pain score and opioid requirements will continue to be measured up to 24 hours postoperatively
2. Nausea [ Time Frame: within 24 hours post-operative ]
   participants experience of nausea will be reported
3. Hypoxia [ Time Frame: within 24 hours post-operative ]
   Number of hypoxic events will be calculated
4. Length of hospital stay [ Time Frame: from admission to discharge, up to 14 days ]
   Number of days spent in the hospital from admission to discharge will be assessed.
5. Sedation [ Time Frame: within 24 hours post-operative ]
   Ramsay Sedation Scale
6. Time to extubation [ Time Frame: from post-operative until extubation, up to 72 hours ]
   length of time from operation to removal of endotracheal tube will be measured
7. Number of participants experiencing vomiting [ Time Frame: within 24 hours post-operative ]
   participants' experiencing vomiting will be assessed and reported by care providers

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 18 or older
• Patients scheduled for UPPP
• Patients with diagnosis of OSA via polysomnography
• American Society of Anesthesiology (ASA) classification 3 or lower

Exclusion Criteria:

• Bradycardia as defined as resting heart rate <60 Beats per min (BPM) or symptomatic
• Any degree of heart block diagnosed by ECG
• Hypotension as defined as <20% from baseline or symptomatic
• Liver failure, (two fold rise in liver enzymes)
• Chronic Kidney Disease (CKD) III or greater
• History of allergy to opioids or dexmedetomidine
• ASA classification 4 or higher
• ICU or Step down admission
• Difficult airway as defined by previous history of difficult intubation or requiring a fiberoptic intubation.

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Sponsors and Collaborators

Montefiore Medical Center

Investigators

• Principal Investigator: Tracey Straker, MD; Montefiore Medical Center

More Information

Publications:

Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009 Aug;108(5):246-9.

Hillman DR, Loadsman JA, Platt PR, Eastwood PR. Obstructive sleep apnoea and anaesthesia. Sleep Med Rev. 2004 Dec;8(6):459-71. Review.

Kaw R, Pasupuleti V, Walker E, Ramaswamy A, Foldvary-Schafer N. Postoperative complications in patients with obstructive sleep apnea. Chest. 2012 Feb;141(2):436-441. doi: 10.1378/chest.11-0283. Epub 2011 Aug 25.

Siyam MA, Benhamou D. Difficult endotracheal intubation in patients with sleep apnea syndrome. Anesth Analg. 2002 Oct;95(4):1098-102, table of contents.

Reeder MK, Goldman MD, Loh L, Muir AD, Casey KR, Gitlin DA. Postoperative obstructive sleep apnoea. Haemodynamic effects of treatment with nasal CPAP. Anaesthesia. 1991 Oct;46(10):849-53.

Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000 Feb;59(2):263-8; discussion 269-70.

Farag E, Ghobrial M, Sessler DI, Dalton JE, Liu J, Lee JH, Zaky S, Benzel E, Bingaman W, Kurz A. Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. Anesthesiology. 2013 Oct;119(4):932-40. doi: 10.1097/ALN.0b013e318297d4a5.

Berger R, Hsu JC. Bioequivalence trials, intersection-union tests and equivalence confidence sets. Statis Sci. 1996;11:283-319

American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed: Diagnostic and coding manual, American Academy of Sleep Medicine, Westchester, IL 2005.

FDA. (2012, August 15) FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death. FDA.gov Retrieved August 8, 2013 from http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm#safety.

• Responsible Party: Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT03613558
• Other Study ID Numbers: 13-10-168
• First Posted: August 3, 2018
• Last Update Posted: August 3, 2018
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Montefiore Medical Center:

Dexmedetomidine

Additional relevant MeSH terms:

Sleep Apnea, Obstructive; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action