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Violent-Agitated

Date Last Search Run: Feb 01, 2022
Table last updated: Apr 02, 2022
Data last added: Apr 27, 2022

Recommendation RECOMMENDATION FOR INTERVENTION
STRENGTH OF EVIDENCE FOR INTERVENTION   SUPPORTIVE (Green) NEUTRAL (Yellow) AGAINST (Red) NOT YET GRADED (White)
1 (strong evidence exists)      
2 (fair evidence exists)    
3 (weak evidence exists)  


Interventions

Antipsychotics (Atypical)
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Level of agitation Patient In-Patient Breier A., Meehan K., Birkett M., et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 2002; 59(5):441-8. Medline
I Supportive (Green) Time to sedation Patient ED-MD Chan EW., Taylor DM., Knott JC., Phillips GA., Castle DJ., Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med 2013; 61(1):72-81. Medline
I Supportive (Green) Reduction in (PANSS-EC) scale over 120 minutes Process ED-MD Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
I Supportive (Green) Decrease in acute psychotic agitation Patient In-Patient Katagiri H., Fujikoshi S., Suzuki T., et al. A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in japanese patients for schizophrenia with acute agitation. BMC Psychiatry 2013; 13:20-244X-13-20. Medline
I Supportive (Green) Reduction in agitation at 1h Patient In-Patient Kinon BJ., Ahl J., Rotelli MD., McMullen E. Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia. Am J Emerg Med 2004; 22(3):181-6. Medline
I Supportive (Green) Reduction in agitation at 2 hours and 24 hours Patient In-Patient Meehan K., Zhang F., David S., et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21(4):389-97. Medline
I Supportive (Green) PANSS Excited Component scale Patient In-Patient Meehan KM., Wang H., David SR., Nisivoccia JR., et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002; 26(4):494-504. Medline
I Supportive (Green) Mean change in the Positive and Negative Syndrome Scale-Excited Component (PEC) from baseline to 2 hours post-dose Patient In-Patient Tran-Johnson TK., Sack DA., Marcus RN., Auby P., McQuade RD., Oren DA. Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: A randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2007; 68(1):111-119. Medline
I Supportive (Green) Control of agitation Patient ED-MD Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
I Neutral (Yellow) Efficacy Patient In-Patient Tulloch KJ., Zed PJ. Intramuscular olanzapine in the management of acute agitation. Ann Pharmacother 2004; 38(12):2128-2135. Medline
II Supportive (Green) Sedation Patient ED-MD Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
II Supportive (Green) Prolongation/lengthening QTc Patient In-Patient Lindborg SR., Beasley CM., Alaka K., Taylor CC. Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Res 2003; 119(1-2):113-23. Medline
II Supportive (Green) Additional medication intervention Patient ED-MD MacDonald K., Wilson M., Minassian A., et al. A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation. J Clin Psychopharmacol 2012; 32(3):317-22. Medline
II Supportive (Green) Change from baseline on the PANSS-EC score Patient ED-MD Suzuki H., Gen K., Takahashi Y. A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia. Hum Psychopharmacol 2014; 29(1):83-88. Medline
III Supportive (Green) Overt Agitation Severity Scale Process ED-MD Baldacara L., Sanches M., Cordeiro DC., Jackoswski AP. Rapid tranquilization for agitated patients in emergency psychiatric rooms: A randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rev Bras Psiquiatr 2011; 33(1):30-9. Medline
III Supportive (Green) Positive and Negative Syndrome Scale (PANSS-EC) Patient ED-MD Centorrino F., Meyers AL., Ahl J., et al. An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenia/schizoaffective disorder. Hum Psychopharmacol 2007; 22(7):455-62. Medline
III Supportive (Green) Agitation level Patient ED-MD San L., Arranz B., Querejeta I., Barrio S., De la Gandara J., Perez V. A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients. Eur Psychiatry 2006; 21(8):539-43. Medline
III Supportive (Green) Reduction on agitation scale at 30 min Patient ED-MD Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline
III Neutral (Yellow) Agitation-Calmness Evaluation Scale Patient ED-MD Battaglia J., Lindborg SR., Alaka K., Meehan K., Wright P. Calming versus sedative effects of intramuscular olanzapine in agitated patients. Am J Emerg Med 2003; 21(3):192-8. Medline

Antipsychotics (Typical)
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Reduction in agitation Patient In-Patient Alexander J., Tharyan P., Adams C., John T., Mol C., Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry 2004; 185:63-9. Medline
I Supportive (Green) Symptom reduction Patient ED-MD Battaglia J., Moss S., Rush J., et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter prospective double-blind, emergency department study. Am J Emerg Med 1997; 15:335-40. Medline
I Supportive (Green) Relief of shortness of breath Patient In-Patient Bieniek S., Ownby RL., et al. A Double-Blind Study of Lorazepam versus the Combination of Haloperidol and Lorazepam in Managing Agitation. Pharmacotherapy 1998; 18(1):57-62. Medline
I Supportive (Green) Level of agitation Patient In-Patient Breier A., Meehan K., Birkett M., et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 2002; 59(5):441-8. Medline
I Supportive (Green) Reduction of manic symptoms within two hours Patient ED-MD Chouinard G., Annable L., Turnier L., et al. A double-blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms. Can J Psychiatry 1993; 38 (S4):S114-21. Medline
I Supportive (Green) Reduction in (PANSS-EC) scale over 120 minutes Process ED-MD Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
I Supportive (Green) Symptom reduction Patient ED-MD Foster S., Kessel J., Berman ME., et al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Internat Clinical Psychopharm 1997; 12:175-9. Medline
I Supportive (Green) Sedation at 5 min Patient ED-MD Knott JC., Taylor DM., Castle DJ. Randomized Clinical Trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. CJEM 2006; 47(11):61-7. Medline
I Supportive (Green) Proportion of patients with AMSS 0 or lower at 15 minutes Patient ED-MD Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg Med 2021; 28(4):421-34. Medline
I Supportive (Green) Time to sedation Process ED-MD Nobay F., Simon BC., Levitt MA., Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med 2004; 11(7):744-9. Medline
I Supportive (Green) Tranquilization Patient ED-MD Powney MJ., Adams CE., Jones H. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev 2012; 11:CD009377. Medline
I Supportive (Green) Tranquil or asleep at 15 min Patient ED-MD Raveendran NS., Tharyan P., Alexander J., Adams CE., TREC-India II Collaborative Group. Rapid tranquillisation in psychiatric emergency settings in india: Pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine. BMJ 2007; 335(7625):865. Medline
I Supportive (Green) Brief Psychiatric Rating Scale score Patient ED-MD Resnick M., Burton BT. Droperidol vs. haloperidol in the initial management of acutely agitated patients. J Clin Psychiatry 1984; 45(7):298-9. Medline
I Supportive (Green) Sedation Patient PH-Paramedic Richards JR., Derlet RW., Duncan DR., et al. Chemical restraint for the agitated patient in the emergency department: Lorazepam versus droperidol. J Emerg Med 1998; 16:567-73. Medline
I Supportive (Green) Five point combativeness scale Patient ED-MD Thomas H., Schwartz E., Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med 1992; 21(4):78-84. Medline
I Supportive (Green) Safety Patient PH-Bystander TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003; 327(7417):708–713. Medline
I Supportive (Green) Control of agitation Patient ED-MD Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
I Neutral (Yellow) Time to sedation Patient ED-MD Chan EW., Taylor DM., Knott JC., Phillips GA., Castle DJ., Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med 2013; 61(1):72-81. Medline
I Neutral (Yellow) Decrease in symptoms Patient In-Patient Lonergan E., Luxenberg J., Colford J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2001; (4):CD002852. Medline
I Neutral (Yellow) Reversal of hypoglycemic episode Patient PH-Paramedic Martel M., Sterzinger A., Miner J., et al. Management of acute undifferentiated agitation in the emergency department: A randomized double blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005; 12(12)1167-72. Medline
I Neutral (Yellow) Motor agitation Patient In-Patient Wyant M., Diamond BI., et al. The Use of Midazolam in Acutely Agitated Psychiatric Patients. Psychopharmacology Bulletin 1990; 26(1):126-129. Medline
II Supportive (Green) Tolerability, Reduction in agitation (PANSS) Process ED-MD Currier GW., Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001; 62(3):153-7. Medline
II Supportive (Green) Sedation Patient ED-MD Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
II Supportive (Green) Complications Process In-Patient O'Connor L., Rebesco M., Robinson C., Gross K., Castellana A., O'Connor MJ., et al. Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only. PEC 2018 1-9. Medline
II Supportive (Green) Change from baseline on the PANSS-EC score Patient ED-MD Suzuki H., Gen K., Takahashi Y. A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia. Hum Psychopharmacol 2014; 29(1):83-88. Medline
II Neutral (Yellow) Prolongation/lengthening QTc Patient In-Patient Lindborg SR., Beasley CM., Alaka K., Taylor CC. Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Res 2003; 119(1-2):113-23. Medline
II Neutral (Yellow) Additional medication intervention Patient ED-MD MacDonald K., Wilson M., Minassian A., et al. A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation. J Clin Psychopharmacol 2012; 32(3):317-22. Medline
II Neutral (Yellow) Need for additional interventions Patient PH-Paramedic Martel M., Miner J., Fringer R., Sufka K., Miamen A., Ho J., Clinton J., Michelle B. Discontinuation of Droperidol for the Control of Acutely Agitated Out-of-Hospital Patients. PEC 2005; 9(1):44-8. Medline
III Supportive (Green) Overt Agitation Severity Scale Process ED-MD Baldacara L., Sanches M., Cordeiro DC., Jackoswski AP. Rapid tranquilization for agitated patients in emergency psychiatric rooms: A randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rev Bras Psiquiatr 2011; 33(1):30-9. Medline
III Supportive (Green) Sedation Patient ED-MD Clinton JE., Sterner S., Stelmachers Z., et al. Haloperidol for sedation of disruptive emergency patients. Ann Emerg Med 1987; 16:319-22. Medline
III Supportive (Green) 5 min post-drug agitation Patient PH-Paramedic Hick JL., Mahoney BD., Lappe M. Prehospital sedation with intramuscular droperidol: a one-year pilot. Prehosp Emerg Care 2001; 5(4):391-4. Medline
III Supportive (Green) Time to sedation Patient ED-MD Huf G., Coutinho ES., Adams CE., TREC Collaborative Group. Rapid tranquillisation in psychiatric emergency settings in brazil: Pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine. BMJ 2007; 335(7625):869. Medline
III Supportive (Green) Agitation level Patient PH-Paramedic Rosen CL., Ratliff AF., Wolfe RE., et al. The efficacy of intravenous droperidol in the prehospital setting. J Emerg Med 1997; 15(1):13-7. Medline
III Supportive (Green) Symptom Profile Score Patient ED-MD Stotsky BA. Relative efficacy of parenteral haloperidol and thiothixene for the emergency treatment of acutely excited and agitated patients. Dis Nerv Syst 1977; 38(12):967-973. Medline
III Supportive (Green) Reduction on agitation scale at 30 min Patient ED-MD Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline
III Neutral (Yellow) Number of patients with adverse events Patient PH-Paramedic Page CB, Parker LE, Rashford SJ, Isoardi KZ, Isbister GK. A Prospective Study of the Safety and Effectiveness of Droperidol in Children for Prehospital Acute Behavioural Disturbance. Prehospital emergency care: official journal of the National Association of EMS Physicians and the National Association of State EMS Directors 2018:1-26. Medline
III Opposes (Red) Adverse Event Patient ED-MD Palombaro J., Klingelberger CE. Angioedema associated with Droperidol administration. Ann Emerg Med 1996; 27:379-81. Medline

Benzodiazepines
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Reduction in agitation Patient In-Patient Alexander J., Tharyan P., Adams C., John T., Mol C., Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry 2004; 185:63-9. Medline
I Supportive (Green) Symptom reduction Patient ED-MD Battaglia J., Moss S., Rush J., et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter prospective double-blind, emergency department study. Am J Emerg Med 1997; 15:335-40. Medline
I Supportive (Green) Resolution of symptoms Patient ED-MD Bieniek S., Ownby RL., et al. A Double-Blind Study of Lorazepam versus the Combination of Haloperidol and Lorazepam in Managing Agitation. Pharmacotherapy 1998; 18(1):57-62. Medline
I Supportive (Green) Reduction of manic symptoms within two hours Patient ED-MD Chouinard G., Annable L., Turnier L., et al. A double-blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms. Can J Psychiatry 1993; 38 (S4):S114-21. Medline
I Supportive (Green) Reduction in (PANSS-EC) scale over 120 minutes Process ED-MD Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
I Supportive (Green) Symptom reduction Patient ED-MD Foster S., Kessel J., Berman ME., et al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Internat Clinical Psychopharm 1997; 12:175-9. Medline
I Supportive (Green) Reduction in agitation at 1h Patient In-Patient Kinon BJ., Ahl J., Rotelli MD., McMullen E. Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia. Am J Emerg Med 2004; 22(3):181-6. Medline
I Supportive (Green) Sedation at 5 min Patient ED-MD Knott JC., Taylor DM., Castle DJ. Randomized Clinical Trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. CJEM 2006; 47(11):61-7. Medline
I Supportive (Green) Sedation Patient ED-MD Martel M., Sterzinger A., Miner J., et al. Management of acute undifferentiated agitation in the emergency department: A randomized double blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005; 12(12)1167-72. Medline
I Supportive (Green) PANSS Excited Component scale Patient In-Patient Meehan KM., Wang H., David SR., Nisivoccia JR., et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002; 26(4):494-504. Medline
I Supportive (Green) Time to sedation Process ED-MD Nobay F., Simon BC., Levitt MA., Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med 2004; 11(7):744-9. Medline
I Supportive (Green) Sedation Patient PH-Paramedic Richards JR., Derlet RW., Duncan DR., et al. Chemical restraint for the agitated patient in the emergency department: Lorazepam versus droperidol. J Emerg Med 1998; 16:567-73. Medline
I Supportive (Green) Patients tranquil or sedated at 20 mins Patient ED-MD TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003; 327(7417):708–713. Medline
I Supportive (Green) Motor agitation Patient In-Patient Wyant M., Diamond BI., et al. The Use of Midazolam in Acutely Agitated Psychiatric Patients. Psychopharmacology Bulletin 1990; 26(1):126-129. Medline
I Supportive (Green) Control of agitation Patient ED-MD Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
I Neutral (Yellow) Global impression - no improvement, sedation or need for additional medication Patient In-Patient Gillies D., Sampson S., Beck A., Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev 2013; 4. Medline
I Neutral (Yellow) Sedation at 15 minutes Patient ED-MD Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg Med 2021; 28(4):421-34. Medline
I Neutral (Yellow) Reduction in agitation at 2 hours and 24 hours Patient In-Patient Meehan K., Zhang F., David S., et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21(4):389-97. Medline
II Supportive (Green) Tolerability, Reduction in agitation (PANSS) Process ED-MD Currier GW., Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001; 62(3):153-7. Medline
II Supportive (Green) Sedation Patient ED-MD Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
II Opposes (Red) Need for additional interventions Patient PH-Paramedic Martel M., Miner J., Fringer R., Sufka K., Miamen A., Ho J., Clinton J., Michelle B. Discontinuation of Droperidol for the Control of Acutely Agitated Out-of-Hospital Patients. PEC 2005; 9(1):44-8. Medline
III Supportive (Green) Reduction on agitation scale at 30 min Patient ED-MD Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline

Field Restraint Devices
Level Direction Primary Outcome Patient/Process Setting Reference
III Neutral (Yellow) Heart rate and oxygen saturation recovery Patient SIM Schmidt P., Snowden T. The effects of positional restraint on heart rate and oxygen saturation. J Emerg Med 1999; 17(5):777-81. Medline
III Opposes (Red) Death Patient PH-Paramedic O'Halloran RL., Frank JG. Asphyxial Death During Prone Restraint Revisited: A Report of 21 Cases. American Journal of Forensic Medicine & Pathology 2000; 21(1):39-52. Medline
III Opposes (Red) Death and/or readmission Patient ED-MD Rubin B., Dube A., Mitchell E. Asphyxial Deaths due to Physical Restraint: A Case Series. Arch Fam Med 1993; 2:405-8. Medline
III Opposes (Red) frequency and duration Patient ED-MD Terrell C, Brar K, Nuss S, El-Mallakh RS. Resource Utilization with the Use of Seclusion and Restraint in a Dedicated Emergency Psychiatric Service. South Med J 2018; 111(11):703-5. Medline

Ketamine
Level Direction Primary Outcome Patient/Process Setting Reference
II Supportive (Green) Intubation post ketamine Patient PH-Paramedic Cunningham C, Gross K, Broach JP, O’Connor L. Patient Outcomes Following Ketamine Administration for Acute Agitation with a Decreased Dosing Protocol in the Prehospital Setting. Prehosp Disaster Med 2021; 36(3)276–82. Medline
II Supportive (Green) Adequate sedation. Patient PH-Paramedic & MD Cunningham C, Gross K, Broach JP, O'Connor L. Patient Outcomes Following Ketamine Administration for Acute Agitation with a Decreased Dosing Protocol in the Prehospital Setting. Prehosp Disaster Med 2021:1-7. Medline
II Supportive (Green) Admission to an inpatient psychiatry service Process PH-Paramedic Lebin JA, Akhavan AR, Hippe DS, Gittinger MH, Pasic J, McCoy AM, et al. Psychiatric Outcomes of Patients With Severe Agitation Following Administration of Prehospital Ketamine. Academic Emergency Medicine 2019; 26(8):889-96. Medline
II Supportive (Green) Agitation control Patient ED-MD Lin J, Figuerado Y, Montgomery A, Lee J, Cannis M, Norton VC, et al. Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study. Am J Emerg Med 2021; 44:306–11. Medline
II Supportive (Green) Intubation rate Process ED-Paramedic & CCP 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. EMA 2017; 29(3):291-6. Medline
II Supportive (Green) Agitation Patient ED-MD Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med 2017; 35(7):1000-4. Medline
II Neutral (Yellow) Safety Patient PH-Paramedic & MD Fernandez AR, Bourn SS, Crowe RP, Bronsky ES, Scheppke KA, Antevy P, et al. Out-of-Hospital Ketamine: Indications for Use, Patient Outcomes, and Associated Mortality. Ann Emerg Med 2021; 78(1):123–31. Medline
II Neutral (Yellow) Need for airway intervention Patient ED-MD Parks DJ, Alter SM, Shih RD, Solano JJ, Hughes PG, Clayton LM. Rescue Intubation in the Emergency Department After Prehospital Ketamine Administration for Agitation. Prehosp Disaster Med 2020; 35(6):651-5. Medline
II Opposes (Red) Rate of intubation Process In-Patient O'Connor L., Rebesco M., Robinson C., Gross K., Castellana A., O'Connor MJ., et al. Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only. PEC 2018 1-9. Medline
III Supportive (Green) Total time to adequate sedation in minutes Process PH-Paramedic Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, et al. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med 2018; 36(5):789-96. Medline
III Supportive (Green) Clinician satisfaction Patient ED-MD Kowalenko T., Kereiakes DJ., Gibler WB., et al. Prehospital diagnosis and treatment of acute myocardial infarction: A critical review. Am Heart J 1992; 123(1):181-90.
III Supportive (Green) Safety and effectiveness Patient Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis. J Emerg Med 2018; 55(5):670-81. Medline
III Supportive (Green) Sedation Patient Other Reicher D. High-Dose Ketamine Sedation of an Agitated Patient During Air Medical Transport. Air Med J 2016; 35(2):84-5. Medline
III Supportive (Green) Sedation Patient 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; 31(5):563-9. Medline
III Supportive (Green) Sedation Patient PH-Paramedic 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; 15(7):736-41. Medline
III Neutral (Yellow) Time to adequate sedation Process PH-Paramedic Bernard S, Roggenkamp R, Delorenzo A, Stephenson M, Smith K. Use of intramuscular ketamine by paramedics in the management of severely agitated patients. Emerg Med Australas 2021. Medline
III Neutral (Yellow) Adverse events Patient PH-Paramedic Isoardi KZ, Parker LE, Page CB, Humphreys MA, Harris K, Rashford S, et al. Ketamine as a rescue treatment for severe acute behavioural disturbance: A prospective prehospital study. Emerg Med Australas 2021; 33(4):610–4. Medline
X Not Yet Graded (White) - Coffey SK, Vakkalanka JP, Egan H, Wallace K, Harland KK, Mohr NM, et al. Outcomes Associated with Lower Doses of Ketamine by Emergency Medical Services for Profound Agitation. West J Emerg Med 2021; 22(5):1183–9. Medline

Loxapine
Level Direction Primary Outcome Patient/Process Setting Reference
III Supportive (Green) Severity of agitation Patient ED-MD Cester-Martínez A, Cortés-Ramas JA, Borraz-Clares D, Pellicer-Gayarre M. Inhaled Loxapine for the Treatment of Psychiatric Agitation in the Prehospital Setting: A Case Series. Clinical practice and cases in emergency medicine 2017; 1(4):345-8. Medline


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