Ketamine Versus Midazolam for Prehospital Agitation

Agitation Clinical Trial

Official title:

Ketamine Versus Midazolam for Prehospital Agitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03554915
• Other study ID #: HSR #17-4306
• Status: Completed
• Start date: August 1, 2017
• Est. completion date: September 24, 2018

Study information

• Verified date: April 2019
• Source: Minneapolis Medical Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This research study is being done to figure out the best approach to treatment of pre-hospital agitation. It will compare two tiered dosing treatment protocols, one ketamine-based and one midazolam-based. Agitation is a state of extreme emotional disturbance where patients can become physically aggressive or violent, endangering themselves and those who are caring for them. Often chemical substances or severe mental illness are involved in this level of agitation. Specifically, the investigators are interested in studying agitation that is treated in the prehospital setting by paramedics. This study's hypothesis is a ketamine-based protocol will achieve a faster time to adequate sedation than a midazolam-based protocol for treatment of agitation in the prehospital environment. This study will observe the natural history of an emergency medical services standard operating procedure change from a ketamine-based protocol to a midazolam-based protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: September 24, 2018
• Est. primary completion date: June 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 or older

• Severe agitation (AMSS +2 or +3) or profound agitation (AMSS +4) requiring chemical sedation

• Transport to Hennepin County Medical Center

Exclusion Criteria:

• Obviously gravid women

• Patients known or suspected to be less than 18 years of age

• Patients in which stopwatch activation, for safety reasons, is unable to occur

Related Conditions & MeSH terms

• Agitation
• Psychomotor Agitation

Intervention

Other:
• Ketamine-based protocol
For profoundly agitated (physically violent) patients, intramuscular ketamine 5 mg/kg will be administered first line. For severely agitated patients, intramuscular ketamine 3 mg/kg will be administered first line.
• Midazolam-based protocol
For profoundly agitated patients, intramuscular midazolam 15 mg will be administered. For severely agitated patients, intramuscular midazolam 5 mg will be administered.

Locations

Country	Name	City	State
United States	Hennepin County Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Minneapolis Medical Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (24)

Buckland DM, Crowe RP, Cash RE, Gondek S, Maluso P, Sirajuddin S, Smith ER, Dangerfield P, Shapiro G, Wanka C, Panchal AR, Sarani B. Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States. Prehosp Disaster Med. 2018 Feb;33(1):23-28. doi: 10.1017/S1049023X17007142. Epub 2017 Dec 21. — View Citation

Burnett AM, Peterson BK, Stellpflug SJ, Engebretsen KM, Glasrud KJ, Marks J, Frascone RJ. The association between ketamine given for prehospital chemical restraint with intubation and hospital admission. Am J Emerg Med. 2015 Jan;33(1):76-9. doi: 10.1016/j.ajem.2014.10.016. Epub 2014 Oct 22. — View Citation

Cole JB, Driver BE, Klein LR, Moore JC, Nystrom PC, Ho JD. In reply: Ketamine is an important therapy for prehospital agitation - Its exact role and side effect profile are still undefined. Am J Emerg Med. 2018 Mar;36(3):502-503. doi: 10.1016/j.ajem.2017.12.014. Epub 2017 Dec 7. — View Citation

Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, Harrington J, Ho JD. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med. 2018 May;36(5):789-796. doi: 10.1016/j.ajem.2017.10.022. Epub 2017 Oct 7. — View Citation

Cole JB, Moore JC, Nystrom PC, Orozco BS, Stellpflug SJ, Kornas RL, Fryza BJ, Steinberg LW, O'Brien-Lambert A, Bache-Wiig P, Engebretsen KM, Ho JD. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016 Aug;54(7):556-62. doi: 10.1080/15563650.2016.1177652. Epub 2016 Apr 22. — View Citation

Cong ML, Humble I. A Ketamine Protocol and Intubation Rates for Psychiatric Air Medical Retrieval. Air Med J. 2015 Nov-Dec;34(6):357-9. doi: 10.1016/j.amj.2015.07.007. — View Citation

Gonin P, Beysard N, Yersin B, Carron PN. Excited Delirium: A Systematic Review. Acad Emerg Med. 2018 May;25(5):552-565. doi: 10.1111/acem.13330. Epub 2017 Nov 27. — View Citation

Hick JL, Ho JD. Ketamine chemical restraint to facilitate rescue of a combative "jumper". Prehosp Emerg Care. 2005 Jan-Mar;9(1):85-9. — View Citation

Ho JD, Smith SW, Nystrom PC, Dawes DM, Orozco BS, Cole JB, Heegaard WG. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013 Apr-Jun;17(2):274-9. doi: 10.3109/10903127.2012.729129. Epub 2012 Dec 11. — View Citation

Hollis GJ, Keene TM, Ardlie RM, Caldicott DG, Stapleton SG. Prehospital ketamine use by paramedics in the Australian Capital Territory: A 12 month retrospective analysis. Emerg Med Australas. 2017 Feb;29(1):89-95. doi: 10.1111/1742-6723.12685. Epub 2016 Oct 3. — View Citation

Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010 Oct;56(4):392-401.e1. doi: 10.1016/j.annemergmed.2010.05.037. — View Citation

Isenberg DL, Jacobs D. Prehospital Agitation and Sedation Trial (PhAST): A Randomized Control Trial of Intramuscular Haloperidol versus Intramuscular Midazolam for the Sedation of the Agitated or Violent Patient in the Prehospital Environment. Prehosp Disaster Med. 2015 Oct;30(5):491-5. doi: 10.1017/S1049023X15004999. Epub 2015 Sep 1. — View Citation

Keseg D, Cortez E, Rund D, Caterino J. The Use of Prehospital Ketamine for Control of Agitation in a Metropolitan Firefighter-based EMS System. Prehosp Emerg Care. 2015 January-March;19(1):110-115. Epub 2014 Aug 25. — View Citation

Linder LM, Ross CA, Weant KA. Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting. Pharmacotherapy. 2018 Jan;38(1):139-151. doi: 10.1002/phar.2060. Epub 2017 Dec 22. Review. — View Citation

Martel M, Miner J, Fringer R, Sufka K, Miamen A, Ho J, Clinton J, Biros M. Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients. Prehosp Emerg Care. 2005 Jan-Mar;9(1):44-8. — View Citation

Martel M, Sterzinger A, Miner J, Clinton J, Biros M. Management of acute undifferentiated agitation in the emergency department: a randomized double-blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med. 2005 Dec;12(12):1167-72. Epub 2005 Nov 10. Erratum in: Acad Emerg Med. 2006 Feb;13(2):233. — View Citation

Melamed E, Oron Y, Ben-Avraham R, Blumenfeld A, Lin G. The combative multitrauma patient: a protocol for prehospital management. Eur J Emerg Med. 2007 Oct;14(5):265-8. — View Citation

Miner JR. Ketamine is a good first-line option for severely agitated patients in the prehospital environment. Am J Emerg Med. 2018 Mar;36(3):501-502. doi: 10.1016/j.ajem.2017.12.015. Epub 2017 Dec 7. — View Citation

Olives TD, Nystrom PC, Cole JB, Dodd KW, Ho JD. Intubation of Profoundly Agitated Patients Treated with Prehospital Ketamine. Prehosp Disaster Med. 2016 Dec;31(6):593-602. Epub 2016 Sep 19. — View Citation

Page CB, Parker LE, Rashford SJ, Bosley E, Isoardi KZ, Williamson FE, Isbister GK. A Prospective Before and After Study of Droperidol for Prehospital Acute Behavioral Disturbance. Prehosp Emerg Care. 2018 Nov-Dec;22(6):713-721. doi: 10.1080/10903127.2018.1445329. Epub 2018 Mar 20. — View Citation

Parsch CS, Boonstra A, Teubner D, Emmerton W, McKenny B, Ellis DY. Ketamine reduces the need for intubation in patients with acute severe mental illness and agitation requiring transport to definitive care: An observational study. Emerg Med Australas. 2017 Jun;29(3):291-296. doi: 10.1111/1742-6723.12763. Epub 2017 Mar 20. — View Citation

Scaggs TR, Glass DM, Hutchcraft MG, Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med. 2016 Oct;31(5):563-9. doi: 10.1017/S1049023X16000662. Epub 2016 Aug 12. — View Citation

Scheppke KA, Braghiroli J, Shalaby M, Chait R. Prehospital use of i.m. ketamine for sedation of violent and agitated patients. West J Emerg Med. 2014 Nov;15(7):736-41. doi: 10.5811/westjem.2014.9.23229. Epub 2014 Nov 11. — View Citation

TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ. 2003 Sep 27;327(7417):708-13. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from injection of drug to adequate sedation, defined as a score of +1 or less on the AMSS	The Altered Mental Status Scale (AMSS) is an integral ordinal scale evaluating both agitation and sedation with scores from -4 to +4. It was developed at our institution and has been internally and externally validated. This scale is a modified version of the Behavioral Activity Rating Scale with additional data points from the Observer's Assessment of Alertness Scale. Effectiveness of sedation will be defined as an AMSS score less than or equal to +1.; AMSS will be determined by the treating paramedic, who will undergo training as a research associate prior to commencement of the study. Participants will be followed for the duration of agitation, an expected average of 2 hours.	2 hours
Secondary	Number of participants intubated	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient is intubated.	2 hours
Secondary	Number of participants experiencing hypersalivation	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences hypersalivation.	2 hours
Secondary	Number of participants experiencing apnea	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences apnea, defined as 6 seconds of absent EtCO2 waveform.	2 hours
Secondary	Number of participants experiencing nausea/vomiting	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if the patient experiences nausea/vomiting	2 hours
Secondary	Number of participants experiencing laryngospasm	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if laryngospasm occurs.	2 hours
Secondary	Number of participants needing rescue sedation	Participants will be followed for the duration of agitation, an expected average of 2 hours. Enrolling paramedics or research associates in the Emergency Department will record if additional sedatives are needed in the prehospital or ED environment.	2 hours