What the s wrong with this person?

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1 Ketamine for Prehospital Management of Excited Delirium Syndrome: Is it all just a bunch of hype?!? Financial Disclosure Asa M. Margolis, DO, MPH, MS, FACEP Assistant Professor Division of Special Operation Department of Emergency Medicine Johns Hopkins University School of Medicine I have no disclosures of any financial or commercial interests or relationships to disclose Objectives Describe the clinical presentation consistent with Discuss strategies for management of ExDS Review the pharmacology of ketamine Review current literature on use of ketamine for management of ExDS in the prehospital setting Altered mental status with psychomotor and physiologic agitation leading to metabolic / electrolyte derangements and autonomic dysfunction What the (%#*;@&) s wrong with this person? Positive associations with ExDS include: Male gender, polysubstance abuse, mental health disorders, and middle age Multiple pathophysiologic changes Lactic acidosis Rhabdomyolysis Hyperthermia Arrhythmia Can be associated with sudden death, including in-custody death Typically multifactorial, including acidosis, arrhythmia, MI, hyperthermia, asphyxia Instant tranquility has been described just prior to cardiopulmonary collapse Restrained patients appear to be at high risk 1

2 Typically, ExDS is first encountered in the prehospital setting Serious challenge for first responders and EMS personnel Avoid Tunnel Vision Rapid control of these patients is paramount to successful evaluation and to ensure safety Physical restraints applied to a patient displaying ExDS may exacerbate the pathophysiology Sedation with pharmacologic agent(s) is often required, but the ideal choice has been debated Hypoglycemia Hypoxemia ICH Seizure Dementia ± Infection Environmental Thyroid disease Electrolyte derangements Feedback from EMS providers revealed a perceived lack of timely efficacy with pharmacologic options PHARMACOLOGIC MANAGEMENT OF ExDS 2

3 Ideal Pharmacologic Agent? B-52 Intramuscular administration Near-immediate onset of action High efficacy rate Predictable dose response Absence of adverse effects, including on hemodynamics, airway patency and respiratory drive Reliable duration Diphenhydramine Antipsychotics Anticholinergic properties Anticholinergic properties Haloperidol decreased seizure threshold QT prolongation Slow onset Maryland Medical Protocol 2018 Slower onset when administered IM Respiratory compromise Dose stacking Benzodiazepines 3

4 Is There Another Alternative? Is There Another Alternative? Rapid onset via IM route Predictable effectiveness when administered by IM injection Manageable side effect profile Does not negatively effect airway reflexes or respiratory drive Ketamine PHARMACOLOGY OF KETAMINE Noncompetitive antagonist of NMDA receptors, has dissociative, amnestic, & analgesic properties High lipid solubility, ketamine rapidly crosses the blood-brain barrier The elimination half-life is approximately 180 minutes; however, the sedative and analgesic effects begin to wear off quicker Adverse Effects Literature??? Clinically significant increased intracranial pressure Laryngospasm Never proven Positive pressure ventilation Increased secretions Small doses of anticholinergic Potential increases in HR and BP Emergence reaction Net effect from sedation often results in decreased HR and BP Benzodiazepines 4

5 Case PREHOSPITAL EMERGENCY CARE 2013;17: year-old male exhibiting bizarre behavior in an urban alley He was observed to be shirtless (environmental temperature was 11 F) and trying to enter a business that was closed EMS arrived and described the subject with each of the eight LEOs attempting to restrain an extremity, the head, or the buttocks, but instead being easily tossed around Prehospital Management 500 mg IM injection of ketamine 1 2 mg/kg intravenous (IV) and 4 5 mg/kg IM The EMS providers reported excellent sedation within 4 minutes after the ketamine administration Could This Change Our Management of ExDS Patients??? Quickly and definitively sedating a patient with ExDS is crucial to stopping the continued catecholamine surge and metabolic acidosis There s a New Cool Guy in Town Complications of Prehospital Ketamine Administration??? Adverse effects With maximal catecholamine surge complicating the clinical picture, will ketamine have deleterious effects? What about other sedatives commonly used such as benzodiazepines and neuroleptics? 5

6 Methods West J Emerg Med. 2014;15(7): Retrospective review of paramedic patient care reports (PCRs) from January 1, 2011 May 1, 2014 Primary endpoint: Ketamine induced sedation of sufficient duration to effectively treat and transport Secondary endpoint: Time to medical control Hemodynamic or respiratory compromise 52 Patients The use of ketamine 4 mg/kg IM by paramedics was safe 50% Received Midazolam 96% of patients were sedated 6% suffered significant respiratory depression Adverse events possibly due to polypharmacy Majority of patients were successful sedated Uncontrolled observational study Limited number of patients PCR data had missing elements Study protocol violations Prehosp Disaster Med. 2016;31(5): CLINICAL TOXICOLOGY, 2016 VOL. 54, NO. 7,

7 Study Design Primary outcome: Time to adequate sedation Prospective open label study in an urban EMS system comparing ketamine to haloperidol in patients requiring chemical sedation for acute undifferentiated agitation Secondary outcomes: Re-dosing in prehospital environment Rates of intubation Adverse medication events Results Intubations!!! Ketamine Median time to adequate sedation was 5 minutes (range 0.4 minutes 23 minutes) 95% achieved adequate sedation prior to ED arrival Haloperidol Median time to adequate sedation was 17 minutes (range 2 84 minutes) 65% achieved adequate sedation prior to ED arrival Comfort level of ED physician receiving and managing dissociated patients?? Conclusions Keep In Mind Ketamine was superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation Ketamine was associated with higher complication and intubation rates There was no randomization and blinding Study only included patients with an agitation score of +2 and +3 Majority of ExDS patients would score +4 7

8 The primary outcome: Time to adequate sedation J.B. Cole et al. / American Journal of Emergency Medicine; 2017 Secondary outcomes: Additional sedatives, intubation frequency, complications associated with ketamine, and mortality Results Median time to adequate sedation was 4.2 min (95% CI: , range 1 25 min) and 90% had adequate sedation prehospital Seven patients (14%) received a second sedative prehospital Intubation occurred in 57% (28/49) of patients Complications related to ketamine included: Hypersalivation (n = 9, 18%) Vomiting (n = 3, 6%) Emergence reaction (n = 2, 4%) One patient died from complications of septic shock on hospital day 29, likely unrelated to ketamine Conclusion In patients with prehospital profound agitation, ketamine provides rapid effective sedation when used as a primary therapy Intubation was common, but accompanied by a short duration of mechanical ventilation 8

9 Concluding Thoughts Concluding Thoughts ExDS is associated with significant morbidity and mortality Rapid control of these patients is paramount to successful evaluation and to ensure safety Management must be directed at immediate intervention, with the goal of rapid sedation to prevent further agitation, resistance, metabolic acidosis, and catecholamine surge Traditional pharmacologic agents are often required in larger doses, often involving more than one medication Ketamine administered by paramedics in the prehospital setting is a safe and effective treatment for ExDS and superior in terms of achieving time to adequate sedation Concluding Thoughts Reference Increasing comfort levels with using Ketamine in patients with ExDS will lead to decrease in adverse events Must balance potential adverse reactions associated with Ketamine with those seen when using Benzodiazepines and Neuroleptics in doses required to achieve adequate sedation Burnett AM, Watters BJ, Barringer KW, Griffith KR, Frascone RJ. Laryngospasm and hypoxia after intramuscular administration of ketamine to a patient in excited delirium. Prehosp Emerg Care. 2012;16: Cole et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clinical Toxicology Vol 54 (7) Hick JL, Smith SW, Lynch MT. Metabolic acidosis in restraint-associated cardiac arrest: a case series. Acad Emerg Med. 1999;6: Ho JD, Smith SW, Nystrom PC, et al. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013;17: Isbister GK, Calver LA, Downes MA, et al. Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Ann Emerg Med Scaggs, et al. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med Oct;31(5): Scheppke et al. Prehospital use of IM Ketamine for Sedation of Violent and agitated Patients. West J Emerg Med Nov;15(7): Vilke GM, DeBard ML, Chan TC, et al. Excited delirium syndrome (ExDS): defining based on a review of the literature. J Emerg Med. 2012;43:

10 Thank you! 10