What is the role of ketamine in treating acute behavioral disturbance, including indications, dosing, potential complications, and alternative medications, particularly in patients with a history of substance use disorders, elderly patients, or those with dementia?

Ketamine for Acute Behavioral Disturbance

Ketamine is an effective rescue sedation agent for severe acute behavioral disturbance when first-line agents fail, administered intramuscularly at 4-5 mg/kg (typically 300 mg for adults), with sedation achieved within 8-20 minutes in 98% of patients, though adverse events occur in approximately 38% of cases. 1, 2

Indications

Ketamine should be reserved as rescue sedation for patients with severe acute behavioral disturbance who have failed initial sedation attempts with droperidol or benzodiazepines. 2

• The primary indication is severe agitation requiring parenteral sedation where first-line agents (typically droperidol 10-30 mg or benzodiazepines) have proven ineffective 2
• Most commonly used in prehospital settings and emergency departments for patients with substance-induced (39%) or alcohol-induced (33%) behavioral disturbance 1
• Police involvement is common (41% of cases), indicating the severity of presentations requiring ketamine 2
• Ketamine has shown promise in elderly patients with major neurocognitive disorder and severe agitation unresponsive to haloperidol plus lorazepam, though this represents limited evidence from case reports 3

Dosing Protocols

The recommended intramuscular dose is 4-5 mg/kg, typically 300 mg for adults, with doses below 200 mg associated with treatment failure. 2

• Standard IM dosing: 200-300 mg (median 200-300 mg across studies), with higher doses (300-500 mg) showing better efficacy 1, 2
• Doses less than 200 mg are specifically associated with treatment failure—4 of 5 treatment failures occurred with ≤200 mg 2
• Time to sedation: median 8 minutes (IQR 5-13 minutes) in prehospital settings and 20 minutes (IQR 10-30 minutes) in emergency departments 1, 2
• Success rate: 98% achieve sedation, though 42% require no additional sedation or adverse events, while 58% experience complications or need further medication 1

Important Dosing Caveat

The FDA label indicates ketamine IM dosing of 10 mg/kg produces surgical anesthesia, which is substantially higher than the 4-5 mg/kg used for behavioral sedation 4. The lower doses used for acute behavioral disturbance represent off-label use with a different therapeutic goal (chemical sedation rather than anesthesia).

Complications and Adverse Events

Adverse events occur in 38-40% of patients but are generally manageable with supportive care. 1

Common Adverse Events (in order of frequency):

• Over-sedation: 15% of patients 1
• Intubation required: 16% of patients 1
• Vomiting: 4-6% 1, 2
• Hypoxia: 4% 1
• Bradypnea: 3% 1
• Hypersalivation: 2% 1
• Emergence phenomena: 2% 1
• Laryngospasm and airway obstruction: rare but documented 1

Critical Safety Considerations:

The need for advanced airway management (endotracheal intubation or supraglottic airway) occurs in approximately 11-12% of patients receiving ketamine for acute behavioral disturbance, similar to midazolam (12%). 5

• Respiratory depression and apnea may occur with overdosage or rapid administration 4
• Cardiovascular effects include changes in heart rate and blood pressure requiring monitoring 4
• In elderly patients, dose selection should start at the low end of the dosing range due to decreased hepatic, renal, or cardiac function 4

Special Population Concerns:

Patients with substance use disorders represent the majority (51%) of acute behavioral disturbance cases, and individuals with drug abuse history may be at greater risk for ketamine abuse and misuse. 1, 4

• Ketamine is a Schedule III controlled substance with abuse potential 4
• Physical dependence and withdrawal symptoms (craving, fatigue, poor appetite, anxiety) have been reported with prolonged high-dose use 4
• In elderly patients with dementia, a single case report showed dramatic de-escalation with 200 mg IM ketamine within minutes, with no adverse effects, though this represents extremely limited evidence 3

Alternative Medications

First-line agents should always be attempted before ketamine, with droperidol and benzodiazepines representing standard initial therapy. 2

First-Line Alternatives:

• Droperidol: 10 mg IM initially, with repeat doses of 5-10 mg (most patients in studies received 20-30 mg total before ketamine was needed) 2
• Midazolam: comparable efficacy to ketamine with similar intubation rates (12% vs 11%) but should be used as first-line rather than rescue 5
• Haloperidol plus lorazepam: traditional combination for acute agitation 3

When First-Line Agents Fail:

The evidence shows that 33 patients received droperidol 20 mg, 11 received 30 mg, and some received combinations with benzodiazepines before requiring ketamine rescue 2. This demonstrates that ketamine fills a critical gap when standard agents prove inadequate.

Midazolam and ketamine show equivalent outcomes for advanced airway management (12% vs 11%), emergency department intubation (14% vs 11%), and mortality (2% vs 1%), suggesting either can be used, though ketamine is typically reserved for rescue. 5

Clinical Implementation Algorithm

1. Initial sedation attempt: Droperidol 10 mg IM or midazolam 5-10 mg IM 2, 5
2. If inadequate response at 15-20 minutes: Repeat droperidol 10 mg or midazolam dose 2
3. If still inadequate after 20-30 mg droperidol or equivalent benzodiazepine: Consider ketamine 4-5 mg/kg IM (300 mg for average adult) 2
4. Avoid doses <200 mg due to high failure rates 2
5. Monitor for: Respiratory depression, over-sedation, vomiting, and prepare for potential airway management 1
6. Additional sedation: 39% of patients require further sedation within 1 hour of hospital arrival despite initial ketamine success 1

Key Pitfall to Avoid:

Do not use inadequate ketamine doses—the single most common cause of treatment failure is dosing below 200 mg. 2 When ketamine is chosen as rescue sedation, commit to an adequate dose (4-5 mg/kg or 300 mg minimum for adults) rather than tentative under-dosing.