What are the guidelines for ketamine dosing and administration?

Ketamine Dosing and Administration Guidelines

Primary Recommendation for Pain Management

For acute pain management in critically ill adults, use low-dose ketamine at 0.5 mg/kg IV bolus followed by 1-2 μg/kg/min continuous infusion as an adjunct to opioid therapy to reduce opioid consumption by approximately 22 mg morphine equivalents without increasing side effects. 1, 2

Dosing by Clinical Context

ICU and Postoperative Pain

• Standard ICU dosing: 0.5 mg/kg IV bolus, then 2 μg/kg/min infusion for 24 hours, followed by 1 μg/kg/min for an additional 24 hours 1
• Alternative continuous infusion: 0.5-2 mg/kg/hr (maximum 100 mg/hour), using the lowest effective dose 2
• Perioperative maximum: 0.5 mg/kg/h after anesthesia induction with continuous infusion at 0.125-0.25 mg/kg/h, stopping 30 minutes before surgery ends 3
• Microdrip maintenance: 0.1-0.5 mg/minute maintains general anesthesia in adults induced with ketamine 4

Emergency Department Acute Pain

• Low-dose range: 0.1-0.3 mg/kg IV provides effective analgesia with minimal adverse effects 5
• Higher sub-dissociative dose: 0.3 mg/kg IV offers no superior efficacy over lower doses but may increase side effects 5
• Optimal ED dosing: Start with 0.15-0.3 mg/kg IV; the 0.3 mg/kg dose sustains pain reduction up to 2 hours 6

Anesthesia Induction and Maintenance

• IV induction: 1-4.5 mg/kg IV (average 2 mg/kg produces 5-10 minutes surgical anesthesia within 30 seconds) 4
• Administer slowly over 60 seconds to avoid respiratory depression and enhanced vasopressor response 4
• IM induction: 6.5-13 mg/kg IM (9-13 mg/kg produces surgical anesthesia in 3-4 minutes, lasting 12-25 minutes) 4
• Maintenance: One-half to full induction dose as needed 4

Special Populations

• Pediatric dosing: 0.5 mg/kg as adjunct to intraoperative opioids, with optional continuous infusion of 0.1-0.2 mg/kg/hr (maximum 0.4 mg/kg/hr) 2
• Pediatric procedural sedation: 1 mg/kg or less (when combined with midazolam) successfully sedates 88% of patients 3
• Shock patients: Use reduced doses (0.5 mg/kg IV bolus followed by 1-2 μg/kg/min) with careful monitoring, as ketamine can suppress myocardial contractility when catecholamine reserves are depleted 7

Route of Administration

Route Efficacy Hierarchy

• Local infiltration: Consistently demonstrates superior analgesia compared to IV administration 2
• Subcutaneous: Provides similar analgesia to IV route 2
• Intravenous: Most commonly employed route with established safety and efficacy 1, 4
• Intramuscular: Lacks analgesic efficacy 2
• Oral: Less effective than infiltration; recommended starting dose is 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine, given 3-4 times daily 8

Preparation Requirements

• Critical: Do NOT inject the 100 mg/mL concentration IV without proper dilution 4
• Dilution for induction: Mix with equal volume of Sterile Water, Normal Saline, or 5% Dextrose 4
• Dilution for maintenance: Add 10 mL from 50 mg/mL vial or 5 mL from 100 mg/mL vial to 500 mL of 5% Dextrose or Normal Saline to create 1 mg/mL solution 4
• Use immediately after dilution 4

Timing Considerations

• Pre-operative administration provides better pain relief than postoperative dosing 2
• Discontinue infusion at end of procedure and administer longer-acting opioid to prevent analgesic gap 2
• Continuation into postoperative period increases hallucination risk without significantly enhancing analgesia 3

Monitoring and Safety Requirements

Mandatory Monitoring

• Continuous cardiac monitoring and pulse oximetry during infusion 2
• Regular assessment of sedation level, respiratory status, and hemodynamics 2, 3
• Maintain vascular access throughout procedure until patient no longer at risk for cardiorespiratory depression 3
• Care consistent with general anesthesia requirements must be provided 3
• Practitioners must be able to identify and rescue patients from unintended deep sedation or general anesthesia 3

Emergency Preparedness

• Emergency airway equipment must be immediately available 4
• If hypoxemia or hypoventilation develops, encourage deep breathing, administer supplemental oxygen, and provide positive pressure ventilation if needed 3

Side Effects Management

Psychotomimetic Effects

• Co-administer benzodiazepines to minimize dysphoria, nightmares, and hallucinations, especially at higher doses and with prolonged use 2, 3
• Administer antisialagogue prior to induction to manage salivation 4
• Sedation is the predominant side effect across multiple studies 2

Common Adverse Effects

• Agitation (7.3%) and nausea (7.0%) are most common in ED settings 5
• Dysphoria and dizziness occur more frequently with low-dose ketamine compared to opioids alone 6
• Hypotension risk exists but ketamine maintains cardiovascular stability better than propofol or dexmedetomidine in shock states 2, 7

Genitourinary Concerns

• In chronic ketamine users, genitourinary pain may occur 4
• Consider cessation if genitourinary pain continues with other genitourinary symptoms 4

Absolute Contraindications

Do not use ketamine in patients with: 3, 7

• Uncontrolled cardiovascular disease
• Pregnancy
• Active psychosis
• Severe liver dysfunction
• High intracranial or ocular pressure

Drug Interactions

• Avoid mixed agonist-antagonists (butorphanol, pentazocine) in combination with ketamine 2

Clinical Advantages

• Maintains cardiovascular stability through central NMDA blockade and preserved adrenal function, making it superior in shock states 2, 7
• Reduces postoperative respiratory impairment and agitation in recovery 2
• Strong evidence supports use in hip and knee arthroplasty to reduce opioid consumption in first 24 hours 3
• Particularly valuable for patients on long-term opioids, with opioid addiction, or opioid-naïve individuals 3
• May benefit gastritis patients by reducing opioid requirements and associated GI side effects 7

Key Clinical Pitfalls

• Purposeless and tonic-clonic movements during ketamine anesthesia do not indicate light anesthesia plane or need for additional doses 4
• Rapid IV administration causes respiratory depression and enhanced vasopressor response 4
• Higher total doses result in longer recovery times 4
• Vomiting and aspiration may occur despite active laryngeal-pharyngeal reflexes 4
• Not recommended for patients who have not followed nil per os guidelines 4