What are the typical routes of administration for ketamine?

Routes of Administration for Ketamine

Ketamine is administered via multiple routes, with intravenous (IV) and intramuscular (IM) being the primary parenteral routes in clinical practice, though oral, intranasal, subcutaneous, rectal, topical, and infiltration routes are also utilized depending on the clinical context. 1

Primary Parenteral Routes

Intravenous Administration

• IV ketamine is the most commonly employed route and is considered the optimal method for procedural sedation based on available evidence 2
• Dosing for IV administration:
  • Induction of anesthesia: 1-2 mg/kg (average 2 mg/kg produces 5-10 minutes of surgical anesthesia within 30 seconds) 1, 3
  • For brief procedures: 1-1.5 mg/kg (with 1.5 mg/kg being more effective, requiring additional doses in only 5.5% of patients) 3
  • Perioperative pain management: bolus <0.35 mg/kg, followed by continuous infusion at 0.125-0.25 mg/kg/h (maximum 0.5 mg/kg/h) 4, 5
• Onset of action: 1 minute with duration of 15-30 minutes 3
• Critical administration requirement: The 100 mg/mL concentration must be diluted with an equal volume of Sterile Water, Normal Saline, or 5% Dextrose before IV injection 1
• Administer slowly over 60 seconds; rapid administration causes respiratory depression and enhanced vasopressor response 1

Intramuscular Administration

• IM ketamine provides an alternative when IV access is difficult or unavailable 2
• Dosing for IM administration:
  • Standard dose: 4 mg/kg for wound repair, burn care, or lumbar puncture 4, 3
  • Lower dose: 2.5 mg/kg for laceration repair (superior to intranasal midazolam with 100% vs 70% cooperation during suturing) 4, 3
  • Combined therapy: 3 mg/kg with midazolam 0.05 mg/kg for dental procedures or lacerations 3
• Onset of action: 3-5 minutes (average 4 minutes 42 seconds, range 60 seconds to 15 minutes) 3
• Duration: 12-25 minutes of anesthetic effect with doses of 9-13 mg/kg 1
• Safety and efficacy are broadly similar between IV and IM routes, though trends favor IV administration 2

Alternative Routes of Administration

Local Infiltration

• Peritonsillar ketamine infiltration is consistently effective for reducing pain and analgesic requirements after tonsillectomy in children 4
• Infiltration demonstrated superior pain relief compared to IV ketamine in one direct comparison 4
• Combination with bupivacaine provides superior analgesia compared to either drug alone 4

Oral Administration

• Oral ketamine has poor bioavailability (only 20-25% reaches bloodstream), requiring appropriately higher doses 6
• Doses range from 0.25 to 7 mg/kg or 50-300 mg per occasion 6
• Less effective than infiltration for procedural sedation 4
• Well-tolerated with 25 years of experience in acute and chronic pain management 6

Intranasal Administration

• Intranasal ketamine has been studied but shows inferior efficacy compared to IM ketamine for procedural sedation 4
• An intranasal formulation is currently undergoing clinical trials 7

Subcutaneous Administration

• Subcutaneous ketamine provides similar analgesia to the IV route 4
• Bolus administration is safe and effective via this route 8
• Warrants further study for clinical practicability 8

Other Routes

• Rectal administration: One study found no differences between peritonsillar, IV, or rectal ketamine in children undergoing tonsillectomy 4
• Topical administration: Limited evidence with mixed results 4
• Transdermal: A formulation is under patent review 7

Critical Safety Considerations

Monitoring Requirements

• Care consistent with general anesthesia must be provided when ketamine is used for moderate procedural sedation 5
• Practitioners must be able to identify and rescue patients from unintended deep sedation or general anesthesia 5
• Maintain vascular access throughout the procedure until the patient is no longer at risk for cardiorespiratory depression 5
• Emergency airway equipment must be immediately available 1

Common Pitfalls

• The 100 mg/mL concentration cannot be given IV without dilution - this is a critical safety issue 1
• Rapid IV administration causes respiratory depression and enhanced vasopressor response; always administer over 60 seconds 1
• Combination with midazolam increases risk of respiratory depression, requiring particular care in monitoring 4
• Emergency reactions (hallucinations, delirium) occur in 10-30% of adults; consider benzodiazepine co-administration 3

Contraindications

• Uncontrolled cardiovascular disease, active psychosis, severe hepatic dysfunction, or elevated intracranial/ocular pressure 3, 5
• Not recommended for patients who have not followed nil per os guidelines due to aspiration risk 1

Adjunctive Medications

• Administer an antisialagogue prior to induction to manage excessive salivation 1
• Benzodiazepines (particularly midazolam) are effective in reducing ketamine's adverse side effects and preventing neuropsychological manifestations during emergence 9, 1