Reducing Ketamine-Induced Agitation, by Midazolam or Haloperidol Premedication After Adult Procedural Sedation

Study Overview
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Brief Summary
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Ketamine is the cornerstone of procedural sedation in emergency department but ketamine induced agitation has limited its usage by many physicians. As a solution, some propose using midazolam or haloperidol before ketamine injection. In this randomized double blind clinical trial, patients who are eligible for sedation by ketamine are allocated in 3 groups. In first group, the patients will receive 0.05 mg/kg midazolam, in second group 5 mg of haloperidol and in 3rd group a placebo five minutes before receiving the sedative dose of ketamine (1 mg/kg). The patients are assessed for agitation during and after the procedure the clinician's satisfaction with sedation instrument is evaluated after the procedure.

Detailed Description
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Ketamine is the cornerstone of procedural sedation in emergency department but ketamine induced agitation has limited its usage by many physicians. As a solution, some propose using midazolam or haloperidol before ketamine injection. In this randomized double blind clinical trial, patients who are eligible for sedation by ketamine are allocated in 3 groups. In first group, the patients will receive 0.05 mg/kg midazolam, in second group 5 mg of haloperidol and in 3rd group a placebo five minutes before receiving the sedative dose of ketamine (1 mg/kg). The patients are assessed for agitation during and after the procedure the clinician's satisfaction with sedation instrument is evaluated after the procedure. The investigator will fill standard questionnaires for agitation assessment (Richmond Agitation-Sedation Scale and Pittsburgh Agitation Scale).

Official Title
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A Comparison of Midazolam or Haloperidol Premedication Versus Placebo for Reducing Ketamine Induced Agitation After Adult Procedural Sedation in the Emergency Department

Conditions
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Ketamine Induced Agitation

Intervention / Treatment
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* Drug: Midazolam
* Drug: Haloperidol
* Drug: placebo
* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patient older than 18, who need to sedate in Emergency Department Exclusion Criteria: age younger than 18 years, patients with significant cardiovascular disease,congestive heart failure (CHF) central nervous system lesions or injuries, increased intracranial pressure (ICP) ocular pathology, increased intraocular pressure (IOP) thyroid disease, acute pulmonary infections, conditions requiring stimulation of the posterior pharynx, had ingested solid food in the previous 4 hours or clear liquids in the previous 2 hours. Acute intermittent porphyria Alcoholism Hepatic Impairment Myasthenia gravis Respiratory depression allergy to haloperidol as established by direct questioning of family members and available medical history, moderate to severe dementia as documented by medical history, Parkinson's disease, corrected QTc interval (QTc) greater than 500 ms, usage of drugs prolonging QT-interval, history of torsades de pointes, history of neuroleptic malignant syndrome, family history of dystonic reactions to drugs, epilepsy or history of seizures chronic psychiatric disease, intoxication bone marrow suppression pregnancy

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>To do procedural sedation and analgesia in this group, the patients will receive 2 intravenous injections of distilled water (one 2 ml and the other 0.05 cc/kg) 5 minutes before receiving a sedative dose of 1 mg/kg IV ketamine. | Drug: placebo<br>* distilled water<br>Drug: Ketamine<br>* Ketamine is routinely used for all procedural sedation in the patients.<br>* Other names: ketalar;|
| Experimental: midazolam<br>To do procedural sedation and analgesia in this group, the patients will receive 2 intravenous injections. one will be 2 ml of distilled water and the other 0.05 mg/kg midazolam, 5 minutes before receiving a sedative dose of 1 mg/kg IV ketamine. | Drug: Midazolam<br>* Using Midazolam as a premedication for reducing ketamine-induced agitation<br>* Other names: verdes;Drug: placebo<br>* distilled water<br>Drug: Ketamine<br>* Ketamine is routinely used for all procedural sedation in the patients.<br>* Other names: ketalar;|
| Experimental: haloperidol<br>To do procedural sedation and analgesia in this group, the patients will receive 2 intravenous injections. One will be 0.05 cc/kg of distilled water and the other 5 mg of haloperidol (in 2 cc syringes), 5 minutes before receiving a sedative dose of 1 mg/kg IV ketamine. | Drug: Haloperidol<br>* Using Haloperidol as a premedication for reducing ketamine-induced agitation<br>* Other names: haldol;Drug: placebo<br>* distilled water<br>Drug: Ketamine<br>* Ketamine is routinely used for all procedural sedation in the patients.<br>* Other names: ketalar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| agitation | assessed by Pittsburgh Agitation Scale(scoring 0 to 16). Pittsburgh Agitation Scale(scoring 0 to 16) is a valid and reliable instrument to assess agitation severity of inpatients. | starts at the time of Ketamine injection through recovery period(maximum of 2 hours) | 
| level of sedation | assessed by Richmond Agitation-Sedation Scale(scoring -5 to +4). Richmond Agitation-Sedation Scale(scoring -5 to +4) is a valid and reliable instrument to assess level of sedation and agitated behavior during sedation. | 5 minutes after Ketamine injection | 
| level of sedation | assessed by Richmond Agitation-Sedation Scale(scoring -5 to +4). Richmond Agitation-Sedation Scale(scoring -5 to +4) is a valid and reliable instrument to assess level of sedation and agitated behavior during sedation. | 15 minutes after Ketamine injection | 
| level of sedation | assessed by Richmond Agitation-Sedation Scale(scoring -5 to +4). Richmond Agitation-Sedation Scale(scoring -5 to +4) is a valid and reliable instrument to assess level of sedation and agitated behavior during sedation. | 30 minutes after Ketamine injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinician's satisfaction | assessed by a Clinician Satisfaction with Sedation Instrument(CSSI) questionnaire | starts at the time of Ketamine injection through recovery period(maximum of 2 hours) |