Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
The acutely agitated patient Brian Levine, MD Program Director Emergency Medicine Residency Christiana Care Health System Department of Emergency Medicine Associate Professor of Emergency Medicine Jefferson Medical College Objectives To update healthcare providers regarding current issues in the acute psychiatric setting, including Historical use of pharmacotherapy in the acute psychiatric setting Predictors of involuntary return to acute psychiatric services and increasing frequency of acute psychiatric events Importance of initial assessment for development of a treatment plan Treatment guidelines and considerations in acute psychiatric settings and ongoing care Benefits of early intervention Overview Definition of an acute psychiatric event Historical use of pharmacotherapy and restraint in the acute psychiatric setting Predictors and frequency of presentation to acute psychiatric settings Medication nonadherence Diagnoses associated with acute psychiatric events Initial assessment during an acute psychiatric event Treatment guidelines and considerations during acute agitation Definition and Historical Use of Interventions During an Acute Psychiatric Event Defining an Acute Psychiatric Event An acute disturbance of thought, mood, behavior, or social relationship that requires an immediate intervention as defined by the patient, family, or community A set of circumstances in which the Behavior or condition of an individual is perceived by someone, often not the identified individual, as having the potential to rapidly eventuate in a catastrophic outcome Resources available to understand and deal with the situation are not available at the time and place of the occurrence APA. Report and Recommendations Regarding Psychiatric Emergency and Crisis Services. Arlington, VA: APA; 2002. Historical Use of Pharmacotherapy Sedative use was widespread and nonspecific aimed at controlling disturbed behavior whatever the cause1,2 Introduction of antipsychotics to treat psychosis and acute mental disorders3 Sedation is increasingly considered an adverse effect that should be avoided especially when treating disorders such as anxiety or depression4 Antiquity 1800 Ethanol, opium tinctures, and herbals2 1850 1900 Bromide2 Barbiturates2 1950 2000 Benzodiazapines2 Chlorpromazine3 1. Lader M. Introduction to Psychopharmacology. London, UK: SCOPE; 1983:56; 2. Adapted from Charney DS, Mihic SJ, Harris RA. Hypnotics and Sedatives. In: Eds. Hardman JG, Limbird LE. Goodman & Gilman’s: The Pharmacologic Basis of Therapeutics. New York, NY: McGraw-Hill; 2001:400; 3. López-Muñoz F et al. Ann Clin Psychiatry. 2005;17:113-135; 4. Bourin M, Briley M. Hum Psychopharmacol Clin Exp. 2004;19:135-139. Historical Use of Restraint During an Acute Psychiatric Event Management policies in psychiatry began minimizing the use of restraint by the 1940s1 In 1998, estimates of 50 to 150 deaths per year by restraint or seclusion in the US2 Use of restraint is an extraordinary practice and should only be considered as a last resort when2,3 All less restrictive measures have failed3 Severely aggressive or destructive behavior places the patient or others in immediate danger3 1. Lader M. Introduction to Psychopharmacology. London, UK: SCOPE; 1983:8. 2. Currier GW, Allen MH. Psychiatr Serv. 2000;51:717-719. 3. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88. Predictors, Frequency, and Diagnoses Associated With Acute Psychiatric Events Estimated Annual Hospitalization Rates (%) Medication Nonadherence Is Associated With Higher Hospitalization Rates in Patients With Schizophrenia 40 Psychiatric Medical 35 30 † 25 20 * 15 10 * 5 0 ‡ Nonadherent Partially Adherent Adherent Excess Filler N=2801 patient years among Medicaid beneficiaries with schizophrenia. *P<.001 vs nonadherent and excess filler groups. †P<.001 vs adherent group. ‡Excess filling of medications may occur due to actual overuse or loss/theft of medications. Adapted from Gilmer TP et al. Am J Psychiatry. 2004;161:692-699. Patients Reporting Barrier (%) Barriers to Medication Adherence in Patients With Schizophrenia 50 45 40 35 30 25 20 15 10 5 0 Modified from Hudson TJ et al. J Clin Psychiatry. 2004;65:211-216. Involuntary Return to the Acute Psychiatric Setting 29% of patients treated in the acute psychiatric setting returned within 12 months Primary predictors of an involuntary return to the acute psychiatric setting included patients who were Psychotic (increased likelihood of return by 241%) Deemed more dangerous Deemed less treatable Involuntary returnees and nonreturnees did not differ in age, gender, racial composition, or their substance abuse involvement N=417 patients admitted due to an acute psychiatric event; 66% of patients presented with a psychotic diagnosis (56% of those had a schizophrenic condition, 22% had an affective disorder, 22% had another psychotic condition), and 33% had a condition complicated by substance abuse. Segal SP et al. Soc Work Health Care. 2002;1/2:591-603. Increased Frequency of Emergency Department Visits Due to Psychosis Emergency Department Visits Due To Psychosis Acute psychiatric events represent 5.4% (~4.3 million) of total ED visits, which has increased by 15%* 2000 Values 1992 Values 0 10 20 Percent *National probability sample of adults comparing rates in 1992 vs 2000. 26% patients seen for neuroses in the ED. ED=emergency department. Hazlett SB et al. Acad Emerg Medicine. 2004;11:193-195. 30 Incidence (%) Diagnoses of Schizophrenia and Psychosis Account for Majority of Involuntary Admissions to a Psychiatric Unit 50 45 40 35 30 25 20 15 10 5 0 48 N=1755* 16.8 8.4 8.9 6.5 4.4 3 3.2 d S O ic er ia on D/ O man mixe ty D/ essi s NO sord hren i i i r l p s O O d p a / / u se o o e l n z D D e a h i o D t c c h s e e n y r c n S ta Ps Pe me cti v cti v subs an i c r af fe r af fe e g a a l l r v i o o t O Bip Bip h o ac Psyc 0.9 r Ot he *Study included 2200 consecutive admissions to an intensive psychiatric treatment unit of a university hospital over an 18-month period; 34.5% admissions represented multiple admissions to the unit. D/O=disorder; NOS=not otherwise specified. Adapted from Sanguineti VR et al. Am J Psychiatry. 1996;153:392-396. Who is agitated? Anyone who waits a while to get seen in the ED! Hx of psychiatric problems: BPD, personality disorders, psychotics, mania drugs/alcohol/intoxication/withdrawal medical (sepsis, hypoxia, med rxn) fighting with the law Well known that sudden cardiac death can occur in healthy patient who are struggling and never received tranquilization Altered MS (to the EP) Infection meningitis/encephalitis sepsis UTI/pneumonia Toxic drugs (including ETOH and withdrawal) Environmental exposure (CO) Altered MS Metabolic electrolyte (Na, Ca) endocrine (glycemia, adrenal, thyroid) hepatic encephalopathy uremia environmental (hypothermia) Hypoxia CHF, PE, COPD Altered MS Cerebrovascular trauma (SDH) CVA CNS vasculitis HTN encephalopathy CNS - other trauma space occupying lesions seizures and postictal states Altered MS Psychiatric Severe depression Functional psychosis schizophrenia Assessment Is Key to Appropriate Intervention Effective and appropriate treatments are based on accurate, relevant diagnostic and clinical assessments1 Initial assessment clearly plays a key role in selecting the most appropriate intervention during an acute psychiatric event2 During an acute psychiatric event, reductions in symptoms without sedation allow the patient to participate in further assessment and treatment3 1. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004. 2. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88. 3. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108. Calming Versus Sedating During an Acute Psychiatric Event Time-limited sedation may be preferred in situations where there is no pharmacologic treatment for the underlying disorder1 Calming the patient rather than sedating them may be the appropriate end point of interventions for acute psychiatric events1 These recommendations from the Treatment of Behavioral Emergencies Expert Consensus Guideline (2005) are consistent with the Clinical Guideline on Schizophrenia from the National Institute for Clinical Excellence (NICE) in the United Kingdom2 1. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108. 2. National Institute for Health and Clinical Excellence (NICE). Clinical Guideline 1: Schizophrenia: Core interventions in the treatment and management of schizophrenia in primary and secondary care. London: National Institute for Clinical Excellence; December 2002. APA Treatment Guidelines for Patients With Schizophrenia and Bipolar Disorder Schizophrenia1 Prevent harm Control disturbed behavior Reduce the severity of psychosis and associated symptoms Formulate short- and long-term treatment plans Develop an alliance with the patient and family Effect a rapid return to the best level of functioning Connect the patient with appropriate aftercare in the community Bipolar Disorder2 Rapid control of agitation, aggression, and impulsivity Ensure the safety of patients and those around them Stabilization of the acute episode Achieve remission Defined as a complete return to baseline level of functioning and a virtual lack of symptoms Strategies with a narrow focus that determine short-term outcomes may do so at the cost of relationship issues that influence long-term outcomes3 1. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004. 2. APA. Am J Psychiatry. 2002;159(suppl 4):1-50. 3. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88. Our role Protect the patient from harm Protect the staff from the patient Select the appropriate mechanism for restraint talk them down (occasionally works) physical chemical Determine the etiology (“medically clear”) Chemical Restraints The EP must think carefully about every medicine we order and give: indications side-effects toxicities medical hx of pt drug interactions Considerations When Choosing an Antipsychotic Following Diagnosis Patient’s Prior Treatment Response Adverse Effects of Medications General Medical Problems Patient Preferences Optimal Clinical Management Short-term Goals Favorable Long-term Outcomes Modified from Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88; APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004. Considerations When Choosing an Antipsychotic Some important factors to consider1 Speed of onset Reliability Patient of delivery preference Interactions with other medications Overarching treatment plans should serve the patient's short- and long-term needs2 1. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108. 2. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004. Benzodiazepines Ativan (lorezepam), Valium (diazepam) and Versed (midazalam) are the only three we basically use fast onset (minutes) effective sedation few side-effects (can get hypotension/resp depression) can be titrated/combined/IM/IV Haloperidol Butyrophenone (like poor old Droperidol) titratable (2mg or 5mg increments) often combined with Ativan for synergism (911) works in 15-30min, can last an hour or two dopamine blocker - leading to side effects extrapyramidal (dystonia, akisthisia, anticholinergic effects, Parkinsonism, cardiovascular- Tordsades, hypotension) Thus the search…. For a quality antipsychotic agent with sedating qualities for use in the ED need easy route of administration for the acutely agitated/psychotic agent (IM or IV) few side effects few interactions predictable Atypical antipsychotics Fewer adverse effects than haloperidol comparable QTc at max concentrations no significant cardiac toxicity Effects seen within 25 min (8-12); lasts 4 hours minimal drug interactions For ED use: olanzapine (Zyprexa), ziprazadone (Geodon), aripiprazole (Abilify), asenapine (Saphris) Study 050: ABILIFY Injection Rapidly Controls Agitation in Schizophrenia Time After First Intramuscular (IM) Injection (min) 0 15 30 45 60 75 90 105 120 PANSS™-EC *P.05 vs placebo -1 Improvement Mean Change in PANSS™-EC Score 0 -2 -3 -4 -5 * -6 -7 -8 * * * * * * * Significant reduction of agitation at primary endpoint (2 hours) vs placebo Placebo (n=62) ABILIFY 5.25 mg (n=63) * * * * * ABILIFY 9.75 mg (n=57) * * * Uncooperativeness Poor impulse control Hostility Excitement Tension ** Haloperidol 7.5 mg (n=60) ABILIFY 15 mg (n=58) Baseline scores ranged between 18.84 and 19.45. LOCF=last observation carried forward. PANSS™-EC=Positive and Negative Syndrome Scale–Excited Component. Daniel D et al. Presented at: 157th Annual Meeting of the American Psychiatric Association; May 1-6, 2004; New York, NY. Please see IMPORTANT SAFETY INFORMATION, including Boxed WARNING, and INDICATIONS for ABILIFY (aripiprazole) on slides 25-31. Long-Term Stabilization Begins With Acute Management of Psychiatric Events Acute Episode Symptoms Increasing Stability Prolonged Stability Time Adapted from APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004. Your ED, 0330 A disheveled, combative patient is thrown onto the stretcher in CT-2 by PD and the constables. He’s fighting the police, screaming, kicking; he has a cut on his lip and is spitting blood at anyone who gets near. He bit a chunk out of the arm of a constable at triage. He’s singing Creed’s “With Arms Wide Open” and screaming that he’s Jesus Christ. What do you do? What do you order? Does your order change if: He’s a known PCP user? He’s a known schizophrenic? He’s a known alcoholic? He’s a 75 year-old man? He’s a 14 year-old? Did you ever wonder if there was any method to your madness? me neither Agitated/Combative Patients in the ER What medications are best for safe, effective, quick sedation? Are there different populations where different drugs should be used? What evidence (if any) exists in the literature? Yes, we’re talking about psych literature. Archives of General Psychiatry, May 2002 Study objective: To determine if Olanzapine (Zyprexa) will demonstrate a dose dependant decrease in agitation To compare efficacy to haloperidol (Haldol) and placebo Patient population: Hospitalized patients 18 and older, clinically diagnosed with schizophrenia, schizophreniform disorder, or schizoaffective disorder. Acutely agitated, but “not so agitated that they were unable to provide written consent or cooperate with the requirements of the study.” Methods 270 patients randomized to: IM olanzapine 2.5mg IM IM olanzapine 5.0mg IM IM olanzapine 7.5mg IM IM olanzapine 10mg IM IM haloperidol 7.5mg IM IM placebo Conducted at: 4 sites in Croatia 1 site in Italy 3 patients 3 sites in Romania 69 patients 82 patients 6 sites in South Africa 116 patients Results There was a statistically significant dose-dependant improvement in agitation when compared with placebo. There was no significant difference when compared with haloperidol. Most common side effect encountered was hypotension in each group. Zero cases of dystonia in olanzapine group Higher doses of olanzapine trended towards better agitation control. 2/40 haloperidol patients No incidence of QTc prolongation greater than 500 milliseconds in any group Conclusion: Olanzapine has a dose-dependant sedative effect, is safe to use, and may be safer than haloperidol. Limitations Sponsored by Eli Lilly Multi-center, multi-country study Additional benzodiazepine administration allowed in all groups Olanzapine IM was not yet FDA approved in US Noted in article that there was no difference of use in any group except placebo, data not reported Low numbers in all groups Patients had to be calm enough to sign consent Journal of Clinical Psychopharmacology, February 2004 Study Objective: To examine the effect on QTc of six commonly used antipsychotic agents Patient population: Patients aged 18-59 years who required chronic treatment of a psychotic disorder Patients had not had an exacerbation of psychosis in the past 3 months Multiple exclusion criteria: BMI limits, resting heart rate, substance abuse, use of other medications within the past 3 months, congenital long QT, pregnant, smoking more than 40 cigarettes per day, unable to give written informed consent Methods/Results Prospective, randomized, parallel-group study Drugs studied: Haloperidol, Ziprasadone, Quetiapine, Olanzapine, Risperidone, Thioridazine 300 patients screened 183 randomized 164 completed the study 7 discontinued due to adverse drug events (not QTc related) 12 for “other reasons” Conclusion: No clinically significant prolongation of QTc in any group Heart rate increased in all groups Limitations Lead author works for Pfizer (Geodon) Not powered to determine differences between agents Small numbers per group Not blinded About 10% of patients dropped out of the study, some for unknown reasons For our purposes, not exactly what we want Psychopharmacology, June 2001 Study objective: To compare ziprasidone IM 2mg and 20mg in the acute control and short-term management of agitated psychotic patients Patient population: Admitted patients over the age of 18 who had acute agitation in association with either schizophrenia, schioaffective disorder, bipolar disorder with psychotic features or “another psychotic disorder” Excluded if ETOH or substance positive (except marijuana or benzodiazepines), suicidal, unable to give written consent, pregnant, EKG abnormalities Methods/Results Prospective, randomized, doubleblinded study 99 patients screened Fewer patients in the 20mg cohort required more than two doses Statistically significant decrease in agitation in both groups 79 patients randomized to 2mg IM or 20mg IM 20mg cohort significantly better than 2mg Only ADE was a priapism that resolved spontaneously (2mg) No significant QTc change Conclusion: Ziprasadone is an effective, safe agent for sedation of an agitated patient with psychosis. Limitations No comparisons to other treatment modalities Only studied the calm, cooperative psychotic patient Sponsored by Pfizer Small numbers But what about the kids? Journal of American Academic Child and Adolescent Psychiatry, February 2008 Study Objective: To review the current literature and develop guidelines for emergency medicine use Review article focused on medication use and dosage (No official guidelines exist for this population) 2006 ACEP recommendations: No Level A recommendations Level B: Use a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic (haloperidol or droperidol) as effective monotherapy in the acutely agitated undifferentiated patient in the ED. If rapid sedation required, use droperidol instead of haloperidol. Use an antipsychotic (typical or atypical) as effective monotherapy for both management of agitation and initial drug therapy for the patient with known psychiatric illness. Use a combination of oral benzodiazepine and an oral antipsychotic for agitated but cooperative patients. Level C: The combination of a parenteral benzodiazepine and haloperidol may produce more rapid sedation than monotherapy in the acutely agitated psychiatric patient in the ED. What about Droperidol? Droperidol is a butyrophenone antipsychotic; antiemetic effect is a result of blockade of dopamine stimulation of the chemoreceptor trigger zone Other effects include alpha-adrenergic blockade, peripheral vascular dilation, and reduction of the pressor effect of epinephrine resulting in hypotension and decreased peripheral vascular resistance; may also reduce pulmonary artery pressure What about Droperidol? Dose 1.25-2.5 mg IV/IM Uses Antiemetic, agitation, migraine/headache Administration Rate no faster than 2.5 mg /min What about Droperidol? Monitor Blood pressure, respiration and EKG Adverse Reactions Cardiovascular: cardiac arrest, hypertension, hypotension (especially orthostatic), QTc prolongation (dose dependent), tachycardia, torsade de pointes, ventricular tachycardia Central nervous system: Anxiety, chills, depression (postoperative, transient), dizziness, drowsiness (postoperative) increased, dysphoria, extrapyramidal symptoms (akathisia, dystonia, oculogyric crisis), hallucinations (postoperative), hyperactivity, neuroleptic malignant syndrome (NMS) (rare), restlessness Respiratory: Bronchospasm, laryngospasm Miscellaneous: Anaphylaxis, shivering Precautions [U.S. Boxed Warning]: Cases of QT prolongation and torsade de pointes, including some fatal cases, have been reported. Use extreme caution in patients with bradycardia (<50 bpm), cardiac disease, concurrent MAO inhibitor therapy, Class I and Class III antiarrhythmics or other drugs known to prolong QT interval, and electrolyte disturbances (hypokalemia or hypomagnesemia), including concomitant drugs which may alter electrolytes (diuretics). May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention) May cause extrapyramidal symptoms (pseudoparkinsonism, acute dystonic reactions, akathisia, tardive dyskinesia). Risk of dystonia (and possibly other EPS) may be greater with increased doses Neuroleptic malignant syndrome Orthostatic hypotension Sedation What about Droperidol? Pharmacodynamics/kinetics Onset: 3-10 mins (peak effect ~30 min) Duration 2-4 hours Patients require continuous EKG monitoring for at least three hours after the drug is administered What about Ketamine? The Combative Multi-Trauma Patient: A Protocol for Prehospital Management Melamed E, et al, Euro J Emerg Med 2007;14(5):265 Israel, 11 patients – access to Ketamine and benzos, retrospective Traumatic injuries – mean time almost 2 hours Successful in all attempts Ketamine “the safest anesthetic in the world” “the lights are on and nobody’s home” dissociates cortical activity from the brainstem rather than depressing CNS function: sedative/analgesic VS maintained, airway reflexes intact increase BP, pulse weak bronchodilator Ketamine (con’t) IM: 4-5mg/kg IV: 1-2mg/kg onset 5 minutes, lasts 30-45 min (can take over 1 hour for recovery) onset 1 minute, lasts 20-30 minutes can titrate with an additional dose Most studies show same effects on discharge, satisfaction. AVOID IV? Ketamine: adverse effects Increased oral/bronchial secretions emergence effect = nightmares, greatest under the age of 5 – 22% vs 12% N, V (5-10%-most at home), ↑ICP laryngospasm: rare, may need a minute of bagging (<1%) Bronchorrhea: atropine recommended for under 5yo Abnormal gait up to 1/3 Roving eyes, The Exorcist Ketamine for adults Some literature support people fear emergence reactions adjunctive sedation controls/prevents versed Most studies show for children, versed adds NOTHING, except added sedation Contraindications to Ketamine <3 months pulmonary/tracheal disease significant CAD Glaucoma/globe injury (↑IOP) psychiatric illness? recently ate? Summary Acute psychiatric events include disturbances of thought, mood, behavior, or social relationship that require an immediate intervention Treatment nonadherence and psychotic symptoms are predictors of future psychiatric hospitalizations Calming the patient rather than sedating them may be the appropriate end point of interventions for acute psychiatric events Acute treatment should attempt to return the patient to the best level of functioning while considering the long-term treatment goals of the patient and caregiver Choice of therapy is complex and involves numerous factors Clinical judgment, early intervention, and maintenance treatment may help prevent relapse References 1. 2. 3. 4. 5. 6. 7. 8. 9. Breier A. et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Archives of General Psychiatry. 59(5):441-8, 2002 May. Harrigan EP. et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. Journal of Clinical Psychopharmacology. 24(1):62-9, 2004 Feb. Nobay F. et al. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Academic Emergency Medicine. 11(7):744-9, 2004 Jul. MacDonald K. et al. A retrospective analysis of intramuscular haloperidol and intramuscular olanzapine in the treatment of agitation in drug- and alcohol-using patients. General Hospital Psychiatry. 32(4):443-5, 2010 Jul-Aug. Daniel DG. et al. Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial. Psychopharmacology. 155(2):128-34, 2001 May. Wilson, MP. et al. A Comparison of the Safety of Olanzapine and Haloperidol in Combination with Benzodiazepines in Emergency Department Patients with Acute Agitation. The Journal of Emergency Medicine. 5(1): 1-8, 2011 Jan. Baldacara, L. et al. Rapid Tranquilization for Agitated Patients in Emergency Psychiatric Rooms: A Randomized Trial of Olanzapine, Ziprasadone, Haloperidol plus Promethazine, Haloperidol plus Midazolam and Haloperidol Alone. Brazilian Review of Psychiatry. 33(1): 30-9. 2011 Mar. Hilt, RJ, Woodward, TA. Agitation Treatment for Pediatric Emergency Patients. The Journal of American Academic Child Adolescent Psychiatry. 47(2): 132-8. 2008 Feb. 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. Questions?