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

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

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.

Study Overview

• Status: Completed
• Conditions: Ketamine Induced Agitation
• Intervention / Treatment: Drug: placebo; Drug: Ketamine; Drug: Midazolam; Drug: Haloperidol

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 4

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Sina Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; 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; distilled water; Drug: Ketamine; Ketamine is routinely used for all procedural sedation in the patients.; Other Names: ketalar
Experimental: midazolam; 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: placebo; distilled water; Drug: Ketamine; Ketamine is routinely used for all procedural sedation in the patients.; Other Names: ketalar; Drug: Midazolam; Using Midazolam as a premedication for reducing ketamine-induced agitation; Other Names: verdes
Experimental: haloperidol; 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: placebo; distilled water; Drug: Ketamine; Ketamine is routinely used for all procedural sedation in the patients.; Other Names: ketalar; Drug: Haloperidol; Using Haloperidol as a premedication for reducing ketamine-induced agitation; Other Names: haldol

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences

Publications and helpful links

General Publications

• Newton A, Fitton L. Intravenous ketamine for adult procedural sedation in the emergency department: a prospective cohort study. Emerg Med J. 2008 Aug;25(8):498-501. doi: 10.1136/emj.2007.053421.
• Sener S, Eken C, Schultz CH, Serinken M, Ozsarac M. Ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial. Ann Emerg Med. 2011 Feb;57(2):109-114.e2. doi: 10.1016/j.annemergmed.2010.09.010.
• Amr MA, Shams T, Al-Wadani H. Does haloperidol prophylaxis reduce ketamine-induced emergence delirium in children? Sultan Qaboos Univ Med J. 2013 May;13(2):256-62. doi: 10.12816/0003231. Epub 2013 May 9.
• Chudnofsky CR, Weber JE, Stoyanoff PJ, Colone PD, Wilkerson MD, Hallinen DL, Jaggi FM, Boczar ME, Perry MA. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Acad Emerg Med. 2000 Mar;7(3):228-35. doi: 10.1111/j.1553-2712.2000.tb01064.x.
• Akhlaghi N, Payandemehr P, Yaseri M, Akhlaghi AA, Abdolrazaghnejad A. Premedication With Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation With Ketamine: A Randomized Double-Blind Clinical Trial. Ann Emerg Med. 2019 May;73(5):462-469. doi: 10.1016/j.annemergmed.2018.11.016. Epub 2019 Jan 3.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): November 7, 2017
• Last Update Submitted That Met QC Criteria: November 4, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Dyskinesia Agents; Ketamine; Midazolam; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: TehranUMS-ketamine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided