Ketamine Versus Midazolam for Prehospital Agitation

Study Overview
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Brief Summary
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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.

Official Title
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Ketamine Versus Midazolam for Prehospital Agitation

Conditions
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Agitation

Intervention / Treatment
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* Other: Ketamine-based protocol
* Other: Midazolam-based protocol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ketamine-based Protocol<br>The first 6 month period of the study will employ a ketamine-based protocol for prehospital agitation. There will be a tiered dosing protocol based on degree of agitation. | Other: Ketamine-based protocol<br>* 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.<br>|
| Midazolam-based Protocol<br>The second 6 month period of the study will employ a midazolam-based protocol for prehospital agitation. There will again be a tiered dosing protocol based on degree of agitation. | Other: Midazolam-based protocol<br>* For profoundly agitated patients, intramuscular midazolam 15 mg will be administered. For severely agitated patients, intramuscular midazolam 5 mg will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agitation, Ketamine, Midazolam, Emergency Medical Services