Dexmedetomidine and Fentanyl Versus Midazolam and Remifentanil for Sedation in Patients Undergoing Ablation Procedures

NCT03451227 | Terminated

• 1 other identifier: 13-6972-B
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and efficacy of dexmedetomidine and compare this to a current technique commonly used at TGH for sedation in patients undergoing ablation procedures for atrial fibrillation (AF) and atrial flutter. The investigators hypothesise that dexmedetomidine will be at least equivalent to, or more so, in terms of effectiveness and safety, when compared to midazolam and remifentanil for sedation during ablation procedures.

Conditions

Tachyarrhythmia

Keywords

Sedation, Analgesia

Outcome Measures

Primary Outcomes (2)

• Number of haemodynamic events requiring intervention

  a.Hypotension i. A decrease of 30% or more from baseline ii. Or absolute cut off values of 1. SBP \< 80mmHg 2. DBP \<40mmHg iii. Number of events and total dose of phenylephrine or ephedrine administered. b. Hypertension i. An increase in Systolic blood pressure 30% or more from baseline ii. Or an absolute cut off value of \> 180mmHg iii. Total number of events c. Bradycardia i. A decrease of 30% or more from baseline ii. Or absolute cut off values of \< 40bpm iii. Total number of events and total dose of glycopyrolate or atropine administered.

  up to 24 hours

• Number of respiratory events requiring intervention

  Respiratory events requiring intervention 1. Respiratory rate \< 6 breaths/min 2. Airway obstruction requiring manual support 3. Airway obstruction requiring guedel insertion 4. Apnoea (cessation of respiration \>10seconds) 5. Hypoxia (saturations \<90% for \>20 seconds)

  up to 24 hours

Secondary Outcomes (8)

• Intraoperative pain scores

  up to 24 hours

• Intraoperative sedation scores

  up to 24 hours

• Patient satisfaction

  up to 48 hours

• Recovery time

  up to 24 hours

• Length of stay in the recovery unit

  up to 24 hours

Study Arms (2)

Dexmedetomidine Group

EXPERIMENTAL

The study drug dexmedetomidine (PrecedexTM) is supplied as dexmedetomidine HCL 200mcg/vial (100mcg/ml). This will be added to 98 ml 0.9% NaCl to achieve a concentration of 2mcg/ml and infused at 0.2-1mcg/kg/hour from the start of the case. The infusion rate will be commenced at 1mcg/kg/hour in those less than or equal to 65 years of age, and at 0.7mcg/kg/hr in those greater than 65 years of age, and then titrated based on the intraoperative sedation scores (to achieve a Sedation and Agitation scale (SAS) score of less than or equal to 4) and cardiovascular parameters (within 30% of baseline).

Drug: Dexmedetomidine group

Remifentanil Group

ACTIVE COMPARATOR

Remifentanil HCL will be infused at 0.01-0.2 mcg/kg/min titrated to sedation level (SAS less than or equal to 4) and cardiovascular parameters (within 30% of baseline)

Drug: Remifentanil Group

Interventions

Dexmedetomidine group DRUG

The study drug dexmedetomidine (PrecedexTM) will be infused at 0.2-1mcg/kg/hour from the start of the case. The dexmedetomidine infusion will stop at completion of the procedure.

Dexmedetomidine Group

Remifentanil Group DRUG

Remifentanil HCL will be infused at 0.01-0.2 mcg/kg/min titrated to sedation level (SAS less than or equal to 4) and cardiovascular parameters (within 30% of baseline). The infusion will be stopped at the end of the procedure.

Remifentanil Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients listed for an ablation procedure for treatment of atrial fibrillation or flutter at TGH requiring sedation provided by an anesthetist
• Valid consent

You may not qualify if:

• Baseline HR \<40
• Baseline SBP \< 80mmHg
• Baseline SBP \> 180mmHg
• Second or third degree heart block unless pacemaker in situ
• Uncontrolled heart failure/severe LV dysfunction (Ejection fraction \< 40%)
• Severe hepatic dysfunction (Transaminases greater than 2 times the upper limit of normal)
• Renal dysfunction: estimated GFR \< 30ml/min, or requiring dialysis
• Allergy to any of the study drugs (dexmedetomidine, remifentanil, fentanyl, midazolam)
• Cognitive impairment precluding ability to tolerate sedation and comply with assessment methods
• Requirement for general anaesthetic for the procedure
• Pregnancy or breast feeding mothers
• Chronic use or addiction to opioids
• \< 18 years of age

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto General Hospital, Univerity health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (38)

• Verma A, Natale A. Should atrial fibrillation ablation be considered first-line therapy for some patients? Why atrial fibrillation ablation should be considered first-line therapy for some patients. Circulation. 2005 Aug 23;112(8):1214-22; discussion 1231. doi: 10.1161/CIRCULATIONAHA.104.478263. No abstract available.

  PMID: 16116072 BACKGROUND

• Di Biase L, Santangeli P, Natale A. How to ablate long-standing persistent atrial fibrillation? Curr Opin Cardiol. 2013 Jan;28(1):26-35. doi: 10.1097/HCO.0b013e32835b59bb.

  PMID: 23207492 BACKGROUND

• Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, Packer D, Skanes A, Ambrogi F, Biganzoli E. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010 Feb;3(1):32-8. doi: 10.1161/CIRCEP.109.859116. Epub 2009 Dec 7.

  PMID: 19995881 BACKGROUND

• Drabek T, Nemec J. Anesthetic management of electrophysiological procedures for heart failure. Int Anesthesiol Clin. 2012 Summer;50(3):22-42. doi: 10.1097/AIA.0b013e3182603e95.

  PMID: 22735718 BACKGROUND

• Di Biase L, Conti S, Mohanty P, Bai R, Sanchez J, Walton D, John A, Santangeli P, Elayi CS, Beheiry S, Gallinghouse GJ, Mohanty S, Horton R, Bailey S, Burkhardt JD, Natale A. General anesthesia reduces the prevalence of pulmonary vein reconnection during repeat ablation when compared with conscious sedation: results from a randomized study. Heart Rhythm. 2011 Mar;8(3):368-72. doi: 10.1016/j.hrthm.2010.10.043. Epub 2010 Nov 2.

  PMID: 21055479 BACKGROUND

• Di Biase L, Saenz LC, Burkhardt DJ, Vacca M, Elayi CS, Barrett CD, Horton R, Bai R, Siu A, Fahmy TS, Patel D, Armaganijan L, Wu CT, Kai S, Ching CK, Phillips K, Schweikert RA, Cummings JE, Arruda M, Saliba WI, Dodig M, Natale A. Esophageal capsule endoscopy after radiofrequency catheter ablation for atrial fibrillation: documented higher risk of luminal esophageal damage with general anesthesia as compared with conscious sedation. Circ Arrhythm Electrophysiol. 2009 Apr;2(2):108-12. doi: 10.1161/CIRCEP.108.815266. Epub 2009 Feb 13.

  PMID: 19808454 BACKGROUND

• Wutzler A, Rolf S, Huemer M, Parwani AS, Boldt LH, Herberger E, Hohenbichler K, Dietz R, Haverkamp W. Safety aspects of deep sedation during catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2012 Jan;35(1):38-43. doi: 10.1111/j.1540-8159.2011.03260.x. Epub 2011 Nov 6.

  PMID: 22054234 BACKGROUND

• Kottkamp H, Hindricks G, Eitel C, Muller K, Siedziako A, Koch J, Anastasiou-Nana M, Varounis C, Arya A, Sommer P, Gaspar T, Piorkowski C, Dagres N. Deep sedation for catheter ablation of atrial fibrillation: a prospective study in 650 consecutive patients. J Cardiovasc Electrophysiol. 2011 Dec;22(12):1339-43. doi: 10.1111/j.1540-8167.2011.02120.x. Epub 2011 Jun 21.

  PMID: 21692895 BACKGROUND

• Salukhe TV, Willems S, Drewitz I, Steven D, Hoffmann BA, Heitmann K, Rostock T. Propofol sedation administered by cardiologists without assisted ventilation for long cardiac interventions: an assessment of 1000 consecutive patients undergoing atrial fibrillation ablation. Europace. 2012 Mar;14(3):325-30. doi: 10.1093/europace/eur328. Epub 2011 Oct 23.

  PMID: 22024600 BACKGROUND

• Bhananker SM, Posner KL, Cheney FW, Caplan RA, Lee LA, Domino KB. Injury and liability associated with monitored anesthesia care: a closed claims analysis. Anesthesiology. 2006 Feb;104(2):228-34. doi: 10.1097/00000542-200602000-00005.

  PMID: 16436839 BACKGROUND

• Candiotti KA, Bergese SD, Bokesch PM, Feldman MA, Wisemandle W, Bekker AY; MAC Study Group. Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial. Anesth Analg. 2010 Jan 1;110(1):47-56. doi: 10.1213/ane.0b013e3181ae0856. Epub 2009 Aug 27.

  PMID: 19713256 BACKGROUND

• Khan ZP, Ferguson CN, Jones RM. alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999 Feb;54(2):146-65. doi: 10.1046/j.1365-2044.1999.00659.x.

  PMID: 10215710 BACKGROUND

• Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology. 1992 Dec;77(6):1125-33. doi: 10.1097/00000542-199212000-00013.

  PMID: 1361310 BACKGROUND

• Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000 Mar;90(3):699-705. doi: 10.1097/00000539-200003000-00035.

  PMID: 10702460 BACKGROUND

• Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000 Aug;93(2):382-94. doi: 10.1097/00000542-200008000-00016.

  PMID: 10910487 BACKGROUND

• Ryu JH, Lee SW, Lee JH, Lee EH, Do SH, Kim CS. Randomized double-blind study of remifentanil and dexmedetomidine for flexible bronchoscopy. Br J Anaesth. 2012 Mar;108(3):503-11. doi: 10.1093/bja/aer400. Epub 2011 Dec 15.

  PMID: 22174346 BACKGROUND

• Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg. 2004 Jan;98(1):153-158. doi: 10.1213/01.ANE.0000093225.39866.75.

  PMID: 14693611 BACKGROUND

• Cortinez LI, Hsu YW, Sum-Ping ST, Young C, Keifer JC, Macleod D, Robertson KM, Wright DR, Moretti EW, Somma J. Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004 Nov;101(5):1077-83. doi: 10.1097/00000542-200411000-00006.

  PMID: 15505442 BACKGROUND

• Kaygusuz K, Gokce G, Gursoy S, Ayan S, Mimaroglu C, Gultekin Y. A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: a randomized controlled trial. Anesth Analg. 2008 Jan;106(1):114-9, table of contents. doi: 10.1213/01.ane.0000296453.75494.64.

  PMID: 18165564 BACKGROUND

• Angst MS, Ramaswamy B, Davies MF, Maze M. Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans. Anesthesiology. 2004 Sep;101(3):744-52. doi: 10.1097/00000542-200409000-00024.

  PMID: 15329600 BACKGROUND

• Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, Mangano DT. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology. 1995 Mar;82(3):620-33. doi: 10.1097/00000542-199503000-00003.

  PMID: 7879930 BACKGROUND

• Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg. 2002 Aug;95(2):461-6, table of contents. doi: 10.1097/00000539-200208000-00042.

  PMID: 12145072 BACKGROUND

• Hogue CW Jr, Talke P, Stein PK, Richardson C, Domitrovich PP, Sessler DI. Autonomic nervous system responses during sedative infusions of dexmedetomidine. Anesthesiology. 2002 Sep;97(3):592-8. doi: 10.1097/00000542-200209000-00012.

  PMID: 12218525 BACKGROUND

• Venn M, Newman J, Grounds M. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. 2003 Feb;29(2):201-7. doi: 10.1007/s00134-002-1579-9. Epub 2002 Nov 22.

  PMID: 12594584 BACKGROUND

• Jalowiecki P, Rudner R, Gonciarz M, Kawecki P, Petelenz M, Dziurdzik P. Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology. 2005 Aug;103(2):269-73. doi: 10.1097/00000542-200508000-00009.

  PMID: 16052108 BACKGROUND

• Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, Young CC, Wright DR, Macleod DB, Somma J. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004 Nov;101(5):1066-76. doi: 10.1097/00000542-200411000-00005.

  PMID: 15505441 BACKGROUND

• Alhashemi JA. Dexmedetomidine vs midazolam for monitored anaesthesia care during cataract surgery. Br J Anaesth. 2006 Jun;96(6):722-6. doi: 10.1093/bja/ael080. Epub 2006 Apr 4.

  PMID: 16595611 BACKGROUND

• Vann MA, Ogunnaike BO, Joshi GP. Sedation and anesthesia care for ophthalmologic surgery during local/regional anesthesia. Anesthesiology. 2007 Sep;107(3):502-8. doi: 10.1097/01.anes.0000278996.01831.8d.

  PMID: 17721254 BACKGROUND

• Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007 Nov;62(11):1132-8. doi: 10.1111/j.1365-2044.2007.05230.x.

  PMID: 17924894 BACKGROUND

• Sichrovsky TC, Mittal S, Steinberg JS. Dexmedetomidine sedation leading to refractory cardiogenic shock. Anesth Analg. 2008 Jun;106(6):1784-6. doi: 10.1213/ane.0b013e318172fafc.

  PMID: 18499610 BACKGROUND

• McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg. 2006 Mar;102(3):668-75. doi: 10.1213/01.ane.0000197777.62397.d5.

  PMID: 16492813 BACKGROUND

• Rozet I, Muangman S, Vavilala MS, Lee LA, Souter MJ, Domino KJ, Slimp JC, Goodkin R, Lam AM. Clinical experience with dexmedetomidine for implantation of deep brain stimulators in Parkinson's disease. Anesth Analg. 2006 Nov;103(5):1224-8. doi: 10.1213/01.ane.0000239331.53085.94.

  PMID: 17056959 BACKGROUND

• Okawa K, Ichinohe T, Kaneko Y. A comparison of propofol and dexmedetomidine for intravenous sedation: a randomized, crossover study of the effects on the central and autonomic nervous systems. Anesth Analg. 2010 Feb 1;110(2):415-8. doi: 10.1213/ANE.0b013e3181c88ba0. Epub 2009 Dec 10.

  PMID: 20007736 BACKGROUND

• Tsai CJ, Chu KS, Chen TI, Lu DV, Wang HM, Lu IC. A comparison of the effectiveness of dexmedetomidine versus propofol target-controlled infusion for sedation during fibreoptic nasotracheal intubation. Anaesthesia. 2010 Mar;65(3):254-9. doi: 10.1111/j.1365-2044.2009.06226.x. Epub 2010 Jan 22.

  PMID: 20105150 BACKGROUND

• Dupanovic M, Lakkireddy D, Emert MP, Krebill R. Utility of dexmedetomidine in sedation for radiofrequency ablation of atrial fibrillation. J Perianesth Nurs. 2013 Jun;28(3):144-50. doi: 10.1016/j.jopan.2012.10.005.

  PMID: 23711310 BACKGROUND

• Prachanpanich N, Apinyachon W, Ittichaikulthol W, Moontripakdi O, Jitaree A. A comparison of dexmedetomidine and propofol in Patients undergoing electrophysiology study. J Med Assoc Thai. 2013 Mar;96(3):307-11.

  PMID: 23539933 BACKGROUND

• Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999 Jul;27(7):1325-9. doi: 10.1097/00003246-199907000-00022.

  PMID: 10446827 BACKGROUND

• Dexter F, Aker J, Wright WA. Development of a measure of patient satisfaction with monitored anesthesia care: the Iowa Satisfaction with Anesthesia Scale. Anesthesiology. 1997 Oct;87(4):865-73. doi: 10.1097/00000542-199710000-00021.

  PMID: 9357889 BACKGROUND

MeSH Terms

Conditions

Tachycardia; Agnosia

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Study Officials

• George Djaiani, MD

  Toronto General Hospital, University Health Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Patients will be randomly allocated (computer generated) to receive either a dexmedetomidine infusion or a remifentanil infusion. The patient, interventional cardiologist and data analyser will be blinded to the drugs given. The anaesthesia care provider will not be blinded
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Manager Anesthesia Research

Model Details: This is a prospective, single blind, randomised controlled study looking at the feasibility of dexmedetomidine for sedation during ablation procedures at Toronto General Hospital.

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: March 1, 2018
• Study Start: December 1, 2017
• Primary Completion: March 12, 2018
• Study Completion: May 14, 2019
• Last Updated: May 16, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)