What are the uses and dosing guidelines for ketamine in medical settings, including anesthesia and pain management?

Ketamine: Clinical Uses and Dosing Guidelines

Primary Medical Applications

Ketamine serves three FDA-approved and guideline-supported roles: general anesthesia induction and maintenance, acute perioperative pain management as an opioid-sparing agent, and treatment-resistant depression (esketamine formulation). 1

Anesthesia

• Induction dosing: 1-4.5 mg/kg IV (average 2 mg/kg produces 5-10 minutes of surgical anesthesia within 30 seconds) or 9-13 mg/kg IM (produces surgical anesthesia within 3-4 minutes lasting 12-25 minutes) 1
• Maintenance: Repeat half to full induction dose as needed, or continuous infusion at 0.1-0.5 mg/minute 1
• Administer IV doses slowly over 60 seconds to prevent respiratory depression and enhanced vasopressor response 1
• Critical advantage: Maintains cardiovascular stability through central NMDA blockade and preserved adrenal function, making it superior to propofol or dexmedetomidine in shock states 2, 3
• Produces bronchodilation, making it the agent of choice for patients with life-threatening asthma or acute bronchial constriction 4

Acute Pain Management

For perioperative pain, use sub-anesthetic doses of 0.5 mg/kg IV bolus followed by 1-2 μg/kg/min infusion, which reduces opioid requirements by approximately 22 mg morphine equivalents without increasing side effects. 2

Specific Dosing Protocols:

• Intraoperative: Maximum 0.5 mg/kg/h after anesthesia induction, with continuous infusion at 0.125-0.25 mg/kg/h; discontinue 30 minutes before end of surgery and administer longer-acting opioid to prevent analgesic gap 2, 5
• ICU setting: 0.5-2 mg/kg/hr continuous infusion (maximum 100 mg/hour), using lowest effective dose 2
• Pediatric patients: 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
• Breakthrough pain in PACU: 0.5 mg/kg titrated to effect 2

Route-Specific Efficacy:

• Local infiltration (particularly peritonsillar) consistently demonstrates superior analgesia compared to IV administration and effectively reduces pain and analgesic requirements 6
• Subcutaneous administration provides similar analgesia to IV route 6
• Intramuscular route lacks analgesic efficacy 6
• Oral administration is less effective than infiltration 6

Specialized Pain Applications

• Cancer-related neuropathic pain: IV ketamine recommended when other modalities fail, though data suggest only modest analgesic potential for opioid-refractory cancer pain 2
• ICU patients with refractory pain: Ketamine helps prevent or reduce opioid tolerance and provides relief when pain is unresponsive to opioids and other agents 6
• Pre-operative administration provides better pain relief than postoperative dosing 6

Critical Safety Considerations

Monitoring Requirements

When administering ketamine for procedural sedation, provide care consistent with general anesthesia standards, including ability to identify and rescue patients from unintended deep sedation. 5

• Maintain vascular access throughout procedure until patient is no longer at risk for cardiorespiratory depression 5
• Continuous cardiac monitoring and pulse oximetry during infusion 2
• Regular assessment of sedation level, respiratory status, and hemodynamics 2, 5

Side Effects Management

• Emergence reactions (postoperative confusional states, agitation, vivid imagery, hallucinations) occur in approximately 12% of patients 1
• Psychotomimetic effects (dysphoria, nightmares, hallucinations) occur especially at higher doses; co-administration with benzodiazepines minimizes these effects 6, 2, 1
• Administer benzodiazepine during induction and maintenance to prevent neuropsychological manifestations during emergence 1
• Minimize verbal, tactile, and visual stimulation during recovery period 1
• Sedation was the predominant side effect in multiple studies 6
• Continuation of ketamine into postoperative period increases hallucination risk without significantly enhancing analgesia 5

Absolute Contraindications

• Uncontrolled cardiovascular disease (contraindicated when significant blood pressure elevation would constitute serious hazard) 2, 5, 1
• Pregnancy 2, 5
• Active psychosis 5
• Severe liver dysfunction 5
• High intracranial or ocular pressure 5
• Known hypersensitivity to ketamine or excipients 1

Special Populations

Patients with Hemodynamic Instability

• Ketamine maintains cardiovascular stability better than alternatives, but can still suppress myocardial contractility in patients with depleted catecholamine reserves 3
• Start at lower end of dosing range (0.5 mg/kg IV bolus) and titrate carefully in significant hemodynamic compromise 3
• Monitor for transient increases in blood pressure, heart rate, and cardiac index, as well as potential decreases in blood pressure, arrhythmias, and cardiac decompensation 1

Pediatric Procedural Sedation

• Combination of ketamine and midazolam shows fewer complications compared to midazolam/meperidine regimens 5
• 88% of pediatric patients successfully sedated at initial doses of 1 mg/kg or less 5

Preparation and Administration

• Do not inject 100 mg/mL concentration IV without proper dilution 1
• For induction: Dilute with equal volume of Sterile Water, Normal Saline, or 5% Dextrose; use immediately after dilution 1
• For maintenance infusion: 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 1
• When fluid restriction required: Add to 250 mL infusion to provide 2 mg/mL concentration 1
• Inspect for particulate matter and discoloration before administration; discard if present 1

Key Clinical Pearls

• Avoid mixed agonist-antagonists (butorphanol, pentazocine) in combination with ketamine 2
• Strong evidence supports IV ketamine in perioperative period to reduce opioid use in first 24 hours after hip and knee arthroplasty 5
• Purposeless and tonic-clonic movements of extremities may occur during ketamine anesthesia; these do not indicate light anesthesia plane or need for additional doses 1
• Ketamine provides analgesia while reducing opioid requirements, potentially beneficial in patients with gastritis at risk for opioid-induced gastrointestinal side effects 3