Chemical Restraint

Aka: Chemical Restraint, Chemical Take-Down, Sedation of the Violent Patient, Sedation in Excited Delirium

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II. Indications

  1. Dangerous and uncontrolled Violent Behavior (e.g. Agitated Delirium)

III. Precautions

  1. See Agitation (includes overall protocol)
  2. Refer to these procedures as "Sedation of the Violent Patient"
    1. Joint Commission views "Chemical Restraint" as an inappropriate term
  3. Evaluate for other causes of Agitation (see Agitated Delirium)
    1. Hypoglycemia (obtain bedside Glucose)
    2. Hypoxia
    3. Sepsis
    4. Intracranial Bleeding (if preceding Head Trauma)

IV. Monitoring

  1. Sedation requires 1:1 monitoring
  2. Vital Signs should include Pulse Oximetry, End-Tidal CO2
  3. Reassess every 15 minutes including Vital Signs
  4. Document the indications, monitoring, reassessment and the indications to continue sedation
  5. Agitation rating scales
    1. Agitated Behavior Scale
    2. Behavioral Activity Rating Scale (BARS Score)
    3. Broset Violence Checklist

V. Approach: Initial Agent Selection by Cause

  1. Excited Delirium
    1. Ketamine 5 mg/kg IM
  2. Sympathomimetic Intoxication (Methamphetamine, Cocaine, Synthetic Marijuana)
    1. Benzodiazepines (e.g. Midazolam IM)
  3. Alcohol and Psychosis
    1. Benadryl 50 mg, Haloperidol 5 mg, Midazolam 2 mg given IM (B52)
    2. Also consider other Alcohol related causes (Wernicke's Encephalopathy, hepatic encaphalopathy, Trauma)
  4. Alcohol Withdrawal and Agitation
    1. Benzodiazepines
    2. Phenobarbital (consider as alternative or adjunct to Benzodiazepines, see below)
  5. Agitation with Psychosis
    1. Second generation Antipsychotic (e.g. Olanzapine, Risperidone, Ziprasidone)
    2. Benzodiazepine (Exercise caution when used in combination with Olanzapine; see below)
    3. Dexmedetomidine Sublingual approved in 2022 for Agitation in Schizophrenia and Bipolar Disorder
      1. Preskorn (2022) JAMA 327(8): 727-36 [PubMed]
  6. Pregnancy
    1. See Neuropsychiatric Medications in Pregnancy
    2. Haloperidol
      1. Best studied Antipsychotic in pregnancy (no known Teratogenicity)
    3. Atypical Antipsychotics in observational studies appear to be safe in pregnancy without significant Teratogenicity
      1. Single exception appears to be Risperidone (see below)
      2. Huybrechts (2016) JAMA Psychiatry 73(9): 938-46 +PMID: 27540849 [PubMed]
    4. Avoid Risperidone
      1. Associated with birth malformations when used in first and second trimester
    5. Avoid Benzodiazepines in first trimester (cleft deformity) and perinatal (newborn atony, apnea)
      1. May also increase risk of preterm birth and low birth weight
      2. May consider Benzodiazepines outside of first trimester and perinatal period
      3. Consult obstetrics or maternal-fetal medicine
  7. Elderly
    1. See Agitation in Dementia
    2. Exclude secondary cause! (as with all acute Agitation, but esp. in the elderly)
    3. Follow mantra "Start low and go slow"
    4. Preferred Antipsychotics
      1. Risperidone (Risperdal) 0.5 mg orally twice daily
      2. Quetiapine (Seroquel) 25 mg orally twice daily
        1. Preferred of the Atypical Antipsychotics in Parkinson's Disease, Lewy Body Dementia
      3. Haloperidol 0.5 mg orally twice daily
        1. Consider as initial agent in acute Agitation (but greater side effects than Atypical Antipsychotics)
        2. Avoid in Parkinson's Disease
          1. Markedly impairs mobility secondary to rigidity
    5. Other Antipsychotics have had lower efficacy in elderly with Psychosis
      1. Olanzapine
      2. Ziprasidone
    6. Avoid Benzodiazepines (outside specific indications, e.g. Alcohol Withdrawal)
      1. Risk of paradoxical Agitation, respiratory depression

VI. Medications: Adults (lower doses in the elderly)

  1. Ketamine
    1. Excellent choice for prehospital sedation of an agitated Trauma child or adult on long transport
    2. Minimal ABC suppression, and may bridge to RSI as induction agent
    3. Ketamine Bolus
      1. IV/IO: 0.5 to 1 mg/kg
      2. IM: 3-5 mg/kg (typically 5 mg/kg)
    4. Ketamine maintenance
      1. Dose: 1 to 1.5 mg/kg/hour IV
    5. Duration
      1. Recovery within 10-15 minutes of discontinuing the infusion
    6. Safe in prehospital use (including non-intubated patients)
      1. Ketamine at high dose (4-5 mg/kg) results in GCS 3, but typically maintained respiratory drive (GCS-3K)
      2. Ketamine sedated patients may be safely, closely monitored without intubation, despite low GCS
      3. Iwanicki (2014) Clin Toxicol 52:685-6 [PubMed]
      4. Swaminathan and Perlmutter in Herbert (2018) EM:Rap 18(7): 15-6
  2. Benzodiazepines
    1. Preferred fall-back agent
      1. Safest agent when potential Drug Interactions, allergies, QT Prolongation or other patient risk factors
      2. Preferred agents in Overdose patients with toxin or Unknown Ingestion (offers additional Seizure Prophylaxis)
      3. Also preferred first line agent in Agitated Delirium
      4. Consider as adjunct in patients using Sympathomimetics (e.g. Cocaine or Amphetamines)
    2. Risks
      1. Unpredictable effects (especially in tolerant drug and Alcohol Abusers) and effect may subside quickly
      2. Risk in elderly and in respiratory conditions for Hypotension and hypoventilation
      3. Maintain arway management, End-Tidal CO2 monitoring with Advanced Airway at the ready
    3. Lorazepam (Ativan)
      1. Standard Dosing
        1. Adult: 1-2 IM/IV/PO every 6 hours prn
      2. Agitated Delirium or ICU sedation
        1. Advanced Airway management as needed
        2. Dose: 0.02 to 0.4 mg/kg up to 2-4 mg IV every 2-6 hours as needed
        3. Agitated Delirium (e.g. Methamphetamine) may require 4 mg IV repeated every 10 min prn
      3. Also may be used in combination with Haloperidol (see below)
      4. Maintains a stable Half-Life regardless of underlying significant liver disease
    4. Midazolam (Versed)
      1. Preferred Benzodiazepine in short procedures due to shorter duration of action
      2. Preferred Benzodiazepine for Intramuscular Injection (most rapid absorption)
      3. Very effective with 15 min, but short-half life often requires additional doses or adjunctive agents
        1. Klein (2018) Ann Emerg Med 72(4): 374-85 [PubMed]
      4. Intravenous
        1. Child: 0.05 to 0.1 mg IV (up to 2-4 mg IV for teen) over 2 minutes
        2. Adult: 1 to 2.5 mg IV over 2 minutes and may be repeated once after 2-5 minutes
      5. Intramuscular
        1. Child: 0.1 to 0.15 mg IV (up to 5 mg IM for teen) over 2 minutes
        2. Adult: 5 mg IM and may repeat in 3-5 minutes prn
        3. Larger patients may require 10 mg IM
        4. Smaller patients or elderly may be adequately sedated with 2.5 mg IM
  3. Butyrophenones
    1. Precaution: Risk of QT Prolongation
      1. Risk with Haloperidol, Droperidol as well as all Atypical Antipsychotics
      2. Avoid these agents in higher risk comorbidities
        1. Unknown Ingestion
        2. Hypokalemia
        3. Hyomagnesemia
        4. Bradycardia
        5. Combination with other agents causing QT Prolongation
      3. Generally considered safe with low Torsades risk (despite the FDA black box warning)
    2. Haloperidol (Haldol)
      1. Haloperidol alone
        1. Child: 0.05 to 0.15 mg/kg PO/IM/IV (up to 2-5 mg for teen)
        2. Adult: 5 to 10 mg PO/IM/IV prn
        3. Consider with Benadryl 50 mg or Cogentin 1 mg to prevent Dystonic Reaction
      2. Haloperidol with Midazolam and Benadryl q30 minutes prn (Mnemonic: B52)
        1. Benadryl 50 mg (prevents Dystonia)
        2. Haloperidol 5 mg (up to 10 mg)
        3. Midazolam 2 mg (up to 4 mg) - Midazolam is preferred over Ativan for IM Benzodiazepine)
        4. Draw up the 3 agents into same syringe and deliver IM
          1. May repeat once with additional 5 mg Haloperidol and 2 mg Midazolam
    3. Droperidol (Inapsine)
      1. Unfortunately was unavailable in most regions of U.S., but is once again available as of 2020
      2. Preferred over Haloperidol due to better sedation, faster action, and shorter Half-Life
      3. Very effective in psychotic patients and those unresponsive to Benzodiazepines
      4. QT Prolongation risk appears to be very low (occurs at much higher dose than is typically used)
        1. Horowitz (2002) Acad Emerg Med 9(6): 615-8 [PubMed]
        2. Calver (2015) Ann Emerg Med 66(3): 230-8 +PMID:25890395 [PubMed]
      5. Droperidol
        1. Intravenous dose: 2.5 to 5 mg IV prn (up to 5-10 mg IV, with maximum of 20 mg IV)
        2. Intramuscular dose: 5 to 10 mg IM prn
      6. Common Combinations
        1. Droperidol (Inapsine) 5 mg with Cogentin 1 mg IV
        2. Droperidol and Midazolam mixed in same syringe (1.5 inch needle) IM
          1. Typical dose: Droperidol 5 mg with Midazolam 2 mg and may repeat once in 3-5 min
          2. Severe Agitation (violent): Droperidol 10 mg with Midazolam 5 mg
          3. Efficacy
            1. Faster onset sedation (10 min vs 30 min) than Droperidol or Olanzapine alone
            2. Minor airway management needed, but no intubations required
            3. Taylor (2017) Ann Emerg Med 69(3): 318-26 +PMID: 27745766 [PubMed]
  4. Atypical Antipsychotics
    1. Olanzapine (Zyprexa)
      1. Preferred in Psychosis (Bipolar Disorder, Schizophrenia)
      2. Contraindications
        1. Unknown Ingestion
        2. Liver disease
        3. Neuroleptic Malignant Syndrome
        4. Seizure Disorder
        5. Hypotension
      3. Dosing
        1. Child<12 years: 2.5 mg PO/IM
        2. Adults: 10 mg ODT sublingual wafer or 10 mg IM
      4. Diphenhydramine 1.25 mg/kg PO/IM/IV up to 50 mg prn Dystonia
    2. Ziprasidone (Geodon)
      1. Age <12 years old: 5 mg IM
      2. Teen or Adult: 10-20 mg IM
    3. Aripiprazole (Abilify)
      1. Child <12 years: 1-2 mg IM
      2. Teen: 2-5 mg IM
      3. Adult: 5-10 mg IM
    4. Risperidone (Risperdal)
      1. Child <12 years: 0.5 mg orally
      2. Teen: 1 mg orally
      3. Adult: 2 mg orally
  5. Miscellaneous agents (older agents)
    1. Fluphenazine (Prolixin) 5 mg IM q6h prn
    2. Chlorpromazine (Thorazine) 50 mg IM q6h (or 0.25 mg/kg IM prn in children and adolescents)
    3. Thiothixene (Navane) 5 mg PO or 10 mg IM prn
    4. Dexmedetomidine (Precedex) Sublingual
      1. IV form used in ICU for sedation on Mechanical Ventilation and in Alcohol Withdrawal
      2. Sublingual form FDA approved in 2022 for Agitation in Schizophrenia and Bipolar Disorder
      3. Mild to moderate Agitation (maximum 240 mcg in 24 hours)
        1. Start 120 mcg sublingual or buccal and repeat 60 mcg SL every 2 hours prn for up to 2 doses
      4. Severe Agitation (maximum 360 mcg in 24 hours)
        1. Start 180 mcg sublingual or buccal and repeat 90 mcg SL every 2 hours prn for up to 2 doses
    5. Phenobarbital
      1. Consider in Alcohol Withdrawal as an alternative or adjunct to Benzodiazepines
      2. Avoid IV infusion >60 mg/min
      3. Phenobarbital 5-10 mg/kg IBW up to 130 to 260 mg every 20-30 minutes titrating to light sedation
      4. Nisavic (2019) Psychosomatics 60(5):458-67 [PubMed]
      5. Nelson (2019) Am J Emerg Med 37(4):733-6 [PubMed]
      6. Tidwell (2018) Am J Crit Care 27(6):454-60 [PubMed]

VII. Medications: Children

  1. Precautions
    1. Avoid combining intramuscular Olanzapine with Benzodiazepines
      1. Risk of Hypotension and Bradycardia
    2. Limit Antipsychotic doses to half dose or less for children under age 9 years old
  2. Benzodiazepines (esp. Lorazepam)
    1. Preferred agents in suspected ingestion or Intoxication
    2. Paradoxical Agitation may occur
      1. Avoid Benzodiazepines if possible in Autism spectrum disorder and Developmental Delay
    3. Lorazepam 0.05 mg/kg IV/IM/PO up to 2 mg per dose
  3. Olanzapine (Zyprexa)
    1. Contraindicated in Unknown Ingestion, liver disease, Neuroleptic Malignant Syndrome and Seizure Disorder
    2. Dose for age 6-10 years old: 2.5 mg ODT or IM Injection
    3. Dose for age >10 years old: 5 mg ODT or IM Injection
    4. Dose for adult weight: 10 mg ODT or IM Injection
    5. Observe for Dystonic Reaction
      1. Diphenhydramine 1.25 mg/kg PO/IM/IV up to 50 mg prn Dystonia
  4. Haloperidol
    1. Age 6-12 years: 1-3 mg IM every 4-6 hours as needed (max: 0.15 mg/kg/day)
    2. Administer with Benadryl 5 mg/kg/day divided IV/IM every 6 hours as needed
    3. Frequently used in combination with Lorazepam
  5. Other agents that may be considered in acute presentations
    1. Diphenhydramine
  6. Other agents that may be considered longer term (reactive children)
    1. Clonidine
    2. Guanafacine

VIII. References

  1. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
  2. Mason, Mallon and Colwell in Herbert (2018) EM:Rap 18(10): 11-2
  3. Orman in Herbert (2012) EM: Rap 12(8): 3-5
  4. Orman and McCollum in Herbert (2016) EM:Rap 16(1): 12-14
  5. Shanks, Ginsburg and Leaf (2023) Crit Dec Emerg Med 37(9): 4-10

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