Dexmedetomidine vs Midazolam for Intraoperative Sedation

Minimally Conscious State Clinical Trial

Official title:

Dex vs Dazzle: Dexmedetomidine vs Midazolam for Intraoperative Sedation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02878837
• Other study ID #: IAMSPE
• Status: Completed
• Phase: Phase 4
• First received: August 10, 2016
• Last updated: August 17, 2017
• Start date: January 2016
• Est. completion date: May 2017

Study information

• Verified date: August 2017
• Source: Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, open clinical trial sought to compare the use of Midazolam and Dexmedetomidine during surgery in patients under regional anesthesia.

The primary objective was to determine the superiority of either drug during the intraoperative period regarding: 1- Depth of sedation and 2- incidence of complications.

Secondary objectives included the determination of superiority regarding the postoperative period.

For that, patients were randomized into two groups and sedated with either Midazolam or Dexmedetomidine.

Description:

This study was a randomized, open clinical trial.

Patients undergoing surgery under regional (neuraxial or brachial plexus block) anesthesia were randomly assigned into one of two groups.

Patients in one of the groups (called MDZ) were initially sedated with a 0.05mg/Kg bolus dose of Midazolam.

The ones in the other group (called DEX) were initially sedated with a loading dose of 1 µg/Kg of Dexmedetomidine over 10 minutes, followed by continuous infusion at 0.2 to 0.8 µg/Kg/h.

In order to achieve a Richmond Agitation-Sedation Scale (RASS) score between -3 and -1, the following breakthrough doses were used as necessary:

MDZ: 0.02 mg/Kg bolus dose of Midazolam plus 0.5µg/Kg bolus dose of Fentanyl DEX: 0.5µg/Kg bolus dose of Fentanyl

Depth of sedation and incidence of complications were recorded during surgery, in the Post Anesthesia Care Unit (PACU) and in the Ward for two days following surgery,

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Undergoing surgery under regional anesthesia

Exclusion Criteria:

• The presence of any Bradyarrhythmia;

• New York Heart Association (NYHA) Functional Classes III and IV Heart Failure and/or Left Ventricle Ejection Fraction under 30%;

• Respiratory Failure, Glasgow Coma Scale score 8 or under, and Liver Failure - due to the increased risk of sedation in patients with these conditions (d) refusal to participate in the study or withdrawal of consent at any moment.

Related Conditions & MeSH terms

• Failed Moderate Sedation During Procedure
• Minimally Conscious State
• Persistent Vegetative State

Intervention

Drug:
• Dexmedetomidine

• Midazolam

Locations

Country	Name	City	State
Brazil	Hospital do Servidor Publico Estadual	Sao Paulo	Sao Paulo SP

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (26)

Abdalla MI, Al Mansouri F, Bener A. Dexmedetomidine during local anesthesia. J Anesth. 2006;20(1):54-6. — View Citation

Alexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, Georgopoulos D. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014 Oct;121(4):801-7. doi: 10.1097/ALN.0000000000000361. — View Citation

American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002 Apr;96(4):1004-17. — View Citation

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. — View Citation

Bailey PL, Pace NL, Ashburn MA, Moll JW, East KA, Stanley TH. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology. 1990 Nov;73(5):826-30. — View Citation

Bajwa SJ, Gupta S, Kaur J, Singh A, Parmar S. Reduction in the incidence of shivering with perioperative dexmedetomidine: A randomized prospective study. J Anaesthesiol Clin Pharmacol. 2012 Jan;28(1):86-91. doi: 10.4103/0970-9185.92452. — View Citation

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. — View Citation

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. — View Citation

Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol. 2008 May;4(5):619-27. doi: 10.1517/17425255.4.5.619 . Review. — View Citation

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. — View Citation

Elbaradie S, El Mahalawy FH, Solyman AH. Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically ventilated patients. J Egypt Natl Canc Inst. 2004 Sep;16(3):153-8. — View Citation

Gerlach AT, Murphy CV. Dexmedetomidine-associated bradycardia progressing to pulseless electrical activity: case report and review of the literature. Pharmacotherapy. 2009 Dec;29(12):1492. doi: 10.1592/phco.29.12.1492. — View Citation

Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001 Jan;14(1):13-21. — View Citation

Grosu I, Lavand'homme P. Use of dexmedetomidine for pain control. F1000 Med Rep. 2010 Dec 17;2:90. doi: 10.3410/M2-90. — View Citation

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. — View Citation

Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, Scheinin H, Scheinin M, Meriläinen P, Himanen SL, Jääskeläinen S. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol — View Citation

Kettner SC, Willschke H, Marhofer P. Does regional anaesthesia really improve outcome? Br J Anaesth. 2011 Dec;107 Suppl 1:i90-5. doi: 10.1093/bja/aer340. Review. — View Citation

Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic review. JAMA. 2000 Mar 15;283(11):1451-9. Review. — View Citation

Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critica — View Citation

Shir Y, Raja SN, Frank SM. The effect of epidural versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing radical prostatectomy. Anesthesiology. 1994 Jan;80(1):49-56. — View Citation

Taghinia AH, Shapiro FE, Slavin SA. Dexmedetomidine in aesthetic facial surgery: improving anesthetic safety and efficacy. Plast Reconstr Surg. 2008 Jan;121(1):269-76. doi: 10.1097/01.prs.0000293867.05857.90. — View Citation

Takrouri MS, Seraj MA, Channa AB, el-Dawlatly AA, Thallage A, Riad W, Khalaf M. Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anaesthesiol. 2002 Oct;16(6):587-95. — View Citation

Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010 Jun;36(6):926-39. doi: 10.1007/s00134-010-1877-6. Epub 2010 Apr 8. Review. — View Citation

Usta B, Gozdemir M, Demircioglu RI, Muslu B, Sert H, Yaldiz A. Dexmedetomidine for the prevention of shivering during spinal anesthesia. Clinics (Sao Paulo). 2011;66(7):1187-91. — View Citation

Venn RM, Grounds RM. Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth. 2001 Nov;87(5):684-90. — View Citation

Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care. 2000;4(5):302-8. Epub 2000 Jul 31. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depth of Sedation	Number of breakthrough doses necessary to achieve RASS score between -3 and -1	Intraoperative
Primary	Respiratory depression	Use of supplemental oxygen flow greater than 2L/min or endotracheal intubation for mechanical ventilation	Intraoperative
Primary	Bradycardia	Heart Rate < 50 heartbeats per minute	Intraoperative
Primary	Hypotension	Mean Arterial Pressure < 55mmHg	Intraoperative
Secondary	Residual Sedation	RASS score < -1 in Post Anesthesia Care Unit	Up to 2 hours after surgery
Secondary	Shivering	Self-described by the patient	Up to 2 hours after end of surgery
Secondary	Pain	Pain, described by the patient, according to the Analog Scale. Necessity of breakthrough doses of analgesics.	2 days
Secondary	Quality of Sleep	Self-described.	2 days
Secondary	Delirium	Incidence of Delirium according to CAM-ICU algorithm	2 days
Secondary	Length of Hospital Stay	Length of time between surgery and discharge from Hospital, in days	Until Discharge, up to 30 days