Take a chill pill: An approach to the agitated ED patient Alan Sazama, MD Avera Medical Group Emergency Medicine Sioux Falls, SD

Disclosures None

Objectives Differentiate causes of acute agitation in the ED Discuss pharmacologic treatment options for agitated patients Review evidence behind treatment of agitated patients Discuss treatment of special populations of agitation patients

Agitation: Excessive verbal and/or motor behavior in addition to feelings of unease Loss of impulse control Involuntary behaviors Potential to hurt self or others Citrome, L. Postgrad Med. 2002

Who is agitated? Waiting patients Psychiatric history Toxins(drugs/alcohol/withdrawal) Patients in trouble with the law Medical patients (hypoxia, infection, medications)

Why do we care? Patient safety Staff safety Government regulations It’s common!

Medical causes

Can’t miss diagnoses Infection Toxins Meningitis/encephalitis UTI Sepsis Toxins Drugs Withdrawal Carbon monoxide

Can’t miss diagnoses Hypoxia Trauma CNS Metabolic Electrolytes (sodium, calcium) Hepatic encephalopathy Uremia Hypothermia/hyperthermia

What do we need to work up? H&P of most importance Labs unless directed by H&P are usually unhelpful (ACEP clinical policy Level B recommendation) Urine drug screens

Strategy

Project Beta Best Practices for Evaluation and Treatment of Agitated Patients Series of 6 articles in the Western Journal for Emergency Medicine Excellent resource for information on treating agitated patients

Verbal De-escalation

The verbal de-escalation 10 commandments

The verbal de-escalation 10 commandments 1. Thou shall be non-provocative 2. Thou shall respect personal space 3. Thou shall establish verbal contact 4. Thou shall be concise 5.Thou shall identify wants and feelings

The verbal de-escalation 10 commandments 6. Thou shall lay down the law 7. Thou shall listen 8. Thou shall agree or agree to disagree 9. Thou shall have a moderate show of force and be prepared to use it 10. Thou shall debrief with patients and staff

Chemical restraints

Considerations Indications Side effects Toxicities Medical Hx of patient Drug interactions Time of onset

Important ED factors Time of onset Reliability of delivery Interaction with other medications Patient preference

Side effects Antipsychotics Movement disorders (acute dystonia) Sedation Dysphoria Postural hypotension QTc prolongation

Side effects Benzodiazepines Sedation, ataxia, dysarthria Dysphoria, euphoria Hypotension Abuse potential Respiratory depression

Benzodiazepines Versed (midazolam), Ativan (lorazepam), Valium (diazepam) are the most common used in the acute setting Fast onset Multiple mechanisms of delivery

Benzodiazapines Drug Onset Peak Duration Versed (Midazolam) IN: 5 min IM: 15 min IV: 1.5-5 min 10 min 30-60 min rapid 2-6 hr Ativan (Lorazepam) PO: 15-60 min IM: 30-60 min IV: 15-30 min 1-6 hr 1-2 hr 15-20 min 8-12 hr Valum (Diazepam) PO: 30-60 min IM: 20 min IV 1-5 min 30 min-1.5 hr 15-30 min Up to 24 hr Unknown 15-60 min

Droperidol

Haloperidol Titratable (2 mg/5mg increments) Can be combined with ativan for synergism Works in 15-30 min Dopamine blocker– extrapyramidal side effects

Atypical Antipsychotics Olanzapine (zyprexa), ziprazadone (geodon), aripiprazole (abilify), quetiapine (seroquel), risperdone (risperdal) Effects seen in about 25 minutes Comparable QTc effects Less extrapyramidal side effects

Antipsychotics Drug Onset Peak Duration Haloperidol PO: 2 hr IM: 20-30 min IV: seconds 2-6 hrs 30-45 min immediate 8-12 hrs 4-8 hrs 4-6 hrs Olanzapine PO: 60 min IM: rapid 6 hrs 15-45 min 10-15 hrs 2-4 hrs Quetiapine PO: 10-15 min 1.5 hrs 7-12 hrs Ziprasidone PO: hours 1-3 days 60 minutes unknown

Ketamine

Ketamine NMDA receptor antagonist Dissociates cortical activity from brain stem activity vs just depressing CNS VS maintained as well as airway reflexes BP, pulse can increase Can be a weak bronchodilator

Ketamine IV: 1-2 mg/kg IM: 4-5 mg/kg Onset 1 minute, lasts 20-30 minutes Can titrate IM: 4-5 mg/kg Onset 5 min, lasts 30-45 min

Ketamine Side effects Increased secretions Emergence reaction Nausea, vomiting Laryngospasm

Primary outcome: respiratory depression Secondary outcomes: additional doses of sedative, Qtc, time to nadir sedation, adverse events, physician assessment of efficacy. 784 patients

Conclusion (per authors): These data suggest that, with proper monitoring, administration of olanzapine, both intramuscular and intravenous, is safe for several indications in the ED

Prospective open label study patient in urban EMS system A prospective study of ketamine versus haloperidol for severe prehospital agitation JCole J, et al Prospective open label study patient in urban EMS system Paramedics received training on altered mental status scale 2 six month periods where ketamine or haldol was first line therapy

A prospective study of ketamine versus haloperidol for severe prehospital agitation J Cole et al Primary outcome time to adequate sedation Secondary outcomes adverse medication events 146 subjects 64 ketamine 82 haldol Ketamine sedation: 5 minutes Haldol sedation: 17 minutes

A prospective study of ketamine versus haloperidol for severe prehospital agitation J Cole et al 49% complications ketamine vs 5% haldol Ketamine complications Hypersalivation 38% Emergence reaction 10% Vomiting 9% Laryngospasm 5% 39 % intubated on ketamine vs 4% haldol

Special populations

No official evidence based management guidelines exist for pediatric population Lorazepam, Olanzapine often featured in hospital policies. Similar to adults, verbal de-escalation and avoiding restraints is stressed in many guidelines

Tough population with respect to increased medical causes, co morbid conditions, and polypharmacy Haldol and olanzapine with some evidence Oral risperdal has good evidence in dementia patients Benzodiazpines have a role, but must be used in caution in the elderly

Summary It’s common to encounter agitation Must rule out organic causes Verbal de-escalation and pharmacology are good strategies Ketamine and IV olanzapine hold promise for the future care of our patients

References Cole JB, Moore JC, Dolan BJ, et al. A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department. Annals of Emergency Medicine. 2017;69 (3) 327-336. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicology 2016;54(7):556–62. Hilt, RJ, Woodward, TA. Agitation Treatment for Pediatric Emergency Patients. The Journal of American Academic Child Adolescent Psychiatry. 47(2): 132-8. 2008 Feb. Levine, B. The acutely agitated patient. Christiana health care system. http://christianacare.org/ documents/ APNPharmacologyUpdate/Agitation.pdf Lukens, TW. et al. Clinical Policy: Critical Issues in the Diagnosis and Management of the Adult Psychiatric Patient in the Emergency Department. Annals of Emergency Medicine. 47(1): 79-99. 2006 Jan. Nassisi, D, Korc, B, Hahn, S, et al. The Evaluation and Management of the Acutely Agitated Elderly Patient. The Mount Sinai Journal of Medicine 2006; 73 (7). 976-984 Zeller, S. Project Beta. Best Practices for Evaluation and Treatment of Agitated Patients.

Questions/comments Alan.sazama@gmail.com