What is the recommended dose of ketamine (intravenous anesthetic) for anesthesia induction, pain management, and treatment-resistant depression?

Ketamine Dosing for Anesthesia Induction, Pain Management, and Treatment-Resistant Depression

For anesthesia induction, administer ketamine 1-2 mg/kg IV over 60 seconds (average 2 mg/kg produces 5-10 minutes of surgical anesthesia), or 9-13 mg/kg IM for procedures requiring deeper sedation; for perioperative pain management as an adjuvant, use 0.5 mg/kg IV bolus followed by optional infusion of 0.1-0.2 mg/kg/h (maximum 0.4 mg/kg/h); for treatment-resistant depression, the standard dose is 0.5 mg/kg IV infused over 40 minutes. 1, 2, 3

Anesthesia Induction Dosing

Intravenous Route

• Initial dose: 1-4.5 mg/kg IV, with 2 mg/kg being the average dose that produces 5-10 minutes of surgical anesthesia within 30 seconds 1
• Administer slowly over 60 seconds to avoid respiratory depression and enhanced vasopressor response 1
• For rapid sequence induction in hemodynamically unstable patients (e.g., trauma, brain injury), use 1-2 mg/kg IV 2
• The 100 mg/mL concentration must be diluted 1:1 with sterile water, normal saline, or 5% dextrose before IV administration 1

Intramuscular Route

• Initial dose: 6.5-13 mg/kg IM, with 9-13 mg/kg producing surgical anesthesia within 3-4 minutes and lasting 12-25 minutes 1
• For pediatric procedural sedation (laceration repair, fracture reduction): 2.5-4 mg/kg IM 2
• IM ketamine at 4 mg/kg demonstrates superior onset (3 minutes) compared to alternative sedation regimens 2

Pediatric Considerations

• For orthopedic procedures: 2 mg/kg IV or 4 mg/kg IM produces adequate sedation with average onset of 96 seconds (IV) or 4 minutes 42 seconds (IM) 2
• For breakthrough pain in PACU: 0.5 mg/kg IV, titrated to effect 2
• Consider reduced dose of 0.25-0.5 mg/kg when using S-ketamine (esketamine) due to its fourfold greater NMDA receptor affinity 2, 4

Perioperative Pain Management (Adjuvant Dosing)

Intraoperative Use

• Bolus: 0.5 mg/kg IV as adjunct to intraoperative opioids 2
• Continuous infusion: 0.1-0.2 mg/kg/h (maximum 0.4 mg/kg/h) following the initial bolus 2
• Administer after anesthesia induction to prevent psychodysleptic side effects 2
• Stop infusion 30 minutes before end of surgery 2
• This dosing reduces morphine consumption by approximately 15 mg over 24 hours and decreases acute pain intensity 2

Clinical Context for Ketamine Use

The European Society for Paediatric Anaesthesiology recommends ketamine specifically for: 2

• Surgery with high risk of acute or chronic postoperative pain
• Patients with vulnerability to pain (especially those on long-term opioids)
• As part of multimodal analgesia to reduce opioid requirements by 30-50% 5

Maintenance Anesthesia

• Microdrip infusion: 0.1-0.5 mg/minute (or 0.5 mg/kg/min for induction as infusion) maintains general anesthesia in adults 1
• For military/field anesthesia: 2 mg/kg/hour continuous infusion (achieved by mixing ketamine 200 mg + midazolam 5 mg + vecuronium 12 mg in 50 mL normal saline, infused at rate in mL/hour equal to 50% of body weight in kg) 6

Treatment-Resistant Depression

Standard Protocol

• Dose: 0.5 mg/kg IV infused over 40 minutes is the most commonly studied and effective regimen 3, 4
• Some patients respond to doses as low as 0.1 mg/kg, while others may require up to 0.75 mg/kg 3
• Session duration can range from 2-100 minutes, though 40 minutes is conventional 3

Alternative Routes for Depression

• Intranasal esketamine has shown comparable antidepressant effect and received FDA "breakthrough therapy" designation 4
• Other routes (oral, sublingual, transmucosal, intramuscular, subcutaneous) have demonstrated safety and efficacy, though IV remains most common 3

Treatment Course

• Single-dose studies show response rates >60% at 4.5 hours, sustained at 24 hours, and >40% at 7 days 4
• Repeat dosing (2-3 doses per week) sustains response over several weeks 4
• For maintenance, dose "a little before the effect of the previous session is expected to wear off" 3

Critical Safety Considerations and Monitoring

Mandatory Monitoring

• Continuous vital signs including oxygen saturation, heart rate, blood pressure, and respiratory rate 1, 2
• Emergency airway equipment must be immediately available 1
• Administer antisialagogue prior to induction due to increased salivation 1

Common Adverse Effects

• Transient hypertension and tachycardia (heart rate increases ~18%, blood pressure elevation) 2, 1
• Emesis (7-8%), nausea (4-5%), ataxia (7-8%), dysphoria (1%) 2
• Transient dissociative and psychotomimetic effects (mitigated by co-administration of benzodiazepines) 1, 4
• Hypoxemia risk: 6% with ketamine alone vs 24% with fentanyl/midazolam combinations 7

Respiratory Safety

• Maintain oxygen saturation >93% on room air 2
• Transient oxygen desaturation (<85%) may occur but typically resolves with temporary interruption and blow-by oxygen 8
• Laryngospasm incidence is very low (0.9-1.4%) 7

Special Populations and Contraindications

Genitourinary Concerns

• In chronic ketamine users, case reports describe genitourinary pain potentially related to treatment 1
• Consider cessation if genitourinary pain continues with other urinary symptoms 1

Combination Therapy

• With midazolam: Add 0.05 mg/kg to reduce emergence reactions, particularly in older children 7
• With benzodiazepines: Augment with IV benzodiazepine for prevention of neuropsychological manifestations during emergence 1
• Concurrent administration with lidocaine is acceptable for difficult-to-manage pain 2

Recovery Time

• IV ketamine: Average 84 minutes (range 22-215 minutes) 2
• IM ketamine: Average 90 minutes (range 60-130 minutes) 2
• Most patients (>70%) recover within 30 minutes with midazolam/ketamine combinations 8

Common Pitfalls and How to Avoid Them

Rapid IV administration causes respiratory depression and enhanced vasopressor response—always administer over 60 seconds minimum 1

Inadequate initial dosing (1 mg/kg IV) results in 54% of patients requiring additional doses, compared to only 5.5% with 1.5 mg/kg 2—start with adequate dosing rather than titrating up.

Failure to dilute concentrated formulations—never inject 100 mg/mL concentration IV without 1:1 dilution 1

Ignoring nil per os guidelines—ketamine is not recommended in patients who have not fasted, despite some airway protection from active laryngeal reflexes 1

Prolonged postoperative ketamine infusions increase hallucination risk without significantly enhancing analgesia—stop 30 minutes before end of surgery 2