What are the recommended ketamine dosing regimens, contraindications, and monitoring requirements for induction and maintenance of anesthesia in adults and children?

Ketamine Drug Information for Anesthesiologists

Mechanism of Action

Ketamine functions as a non-competitive NMDA receptor antagonist, producing dissociative anesthesia by selectively depressing the cortex and thalamus while stimulating limbic structures. 1 This unique mechanism provides simultaneous sedation, analgesia, and amnesia while preserving protective airway reflexes and maintaining cardiovascular and respiratory stability. 1, 2

• The drug also blocks opioid receptors in the brain and spinal cord, contributing to its analgesic properties. 1
• At subanesthetic doses, ketamine modulates central sensitization, prevents hyperalgesia, and blocks opioid tolerance development. 1

Dosing Regimens

Induction of Anesthesia

For IV induction, administer 1-2 mg/kg over 60 seconds; for IM administration, use 4 mg/kg (or 9-13 mg/kg for surgical anesthesia). 1, 3

Intravenous Route:

• Standard induction dose: 2 mg/kg IV produces 5-10 minutes of surgical anesthesia within 30 seconds. 3
• Dosing range: 1-4.5 mg/kg depending on clinical requirements. 3
• Administer slowly over 60 seconds to avoid respiratory depression and enhanced vasopressor response. 3
• Alternative: continuous infusion at 0.5 mg/kg/min for induction. 3
• The 100 mg/mL concentration must be diluted 1:1 with sterile water, normal saline, or D5W before IV administration. 3

Intramuscular Route:

• Dose of 4 mg/kg IM provides onset within 3-5 minutes (average 4 minutes 42 seconds). 1
• For surgical anesthesia: 9-13 mg/kg IM produces effect within 3-4 minutes, lasting 12-25 minutes. 3
• IM ketamine combined with atropine 0.01 mg/kg results in faster onset (3 minutes vs 18 minutes) compared to other sedatives. 4

Maintenance of Anesthesia

Administer repeat increments of one-half to full induction dose as needed, or use continuous infusion at 0.1-0.5 mg/minute. 3

• For microdrip infusion: prepare 1 mg/mL solution by adding 10 mL of 50 mg/mL vial (or 5 mL of 100 mg/mL vial) to 500 mL of D5W or normal saline. 3
• When using 1.5-2 mg/kg initial dose, only 5.5% of patients require supplemental dosing compared to 54% with 1 mg/kg. 4
• For 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). 1

Pediatric Considerations

For pediatric procedural sedation, use 1.5-2 mg/kg IV or 4 mg/kg IM, with repeat IM doses of 2-4 mg/kg allowed after 5-10 minutes if needed. 4, 5

• Ketamine 4 mg/kg IM with atropine 0.01 mg/kg provides superior sedation for lumbar puncture with faster onset and shorter discharge time. 4
• Combination with midazolam 0.05 mg/kg reduces emergence reactions, particularly in children over 10 years (reducing agitation from 35.7% to 5.7%). 4

Timing and Duration

IV ketamine has onset within 30-96 seconds; IM onset occurs in 3-5 minutes. 1, 4

• Duration of anesthetic effect: 15-30 minutes after IV administration. 1
• Average total recovery time: 84 minutes IV (range 22-215 minutes), 90 minutes IM. 4
• Analgesic effects may persist longer than anesthetic effects. 1
• Elimination half-life: approximately 2-3 hours. 1

Contraindications

Ketamine is contraindicated in patients where significant blood pressure elevation would constitute serious hazard, and in those with known hypersensitivity. 3

Absolute Contraindications:

• Uncontrolled cardiovascular disease or hypertension. 1, 4
• Active psychosis. 1, 4
• Severe hepatic dysfunction. 1, 4
• Elevated intracranial or intraocular pressure. 1, 4

Relative Contraindications:

• Ischemic heart disease (use lower doses: 1 mg/kg in multiply injured patients). 4
• Cerebrovascular disease. 4

Monitoring Requirements

Continuous monitoring of vital signs including oxygen saturation, heart rate, blood pressure, and capnography is mandatory throughout ketamine administration. 4, 3

• Emergency airway equipment must be immediately available. 3
• Document vital signs at least every 5 minutes during deep sedation. 4
• Maintain oxygen saturation >93% on room air during procedures. 4
• Monitor for respiratory depression, though serious events are rare (hypoxemia occurs in 1.6-7.3% of patients, typically transient and responsive to supplemental oxygen). 4

Cardiovascular Effects

Ketamine produces dose-dependent increases in heart rate, blood pressure, and cardiac output through sympathetic nervous system stimulation. 1, 4

• This makes ketamine ideal for hemodynamically unstable patients, trauma victims, and those with hypovolemic or septic shock. 6, 7
• In coronary artery bypass grafting, ketamine 2 mg/kg provides better hemodynamic stability during induction compared to propofol. 8
• Brain levels reach 10-40 times blood levels due to high lipid solubility. 1

Respiratory Effects

Ketamine does not cause respiratory depression and maintains hypercapnic reflex and functional residual capacity with moderate bronchodilation. 2, 9

• Ketamine is the anesthetic of choice for patients with bronchospasm due to bronchodilatory and anti-inflammatory properties. 6
• Protective airway reflexes are relatively preserved, though vomiting and aspiration can still occur. 3
• Bag-valve-mask ventilation required in approximately 2% of cases. 4

Adjunctive Medications

Administer an antisialagogue (atropine 0.02-0.05 mg/kg or 0.01 mg/kg IM) prior to induction to prevent excessive salivation. 10, 4

Benzodiazepine Combination:

• Consider midazolam 0.05-0.1 mg/kg IV to reduce emergence reactions (occurring in 10-30% of adults). 1, 4
• Midazolam significantly reduces recovery agitation in patients over 10 years old. 4
• Warning: Combination with midazolam increases risk of respiratory depression requiring enhanced monitoring. 1

Common Adverse Effects

Emergence reactions (floating sensations, vivid dreams, hallucinations, delirium) occur in 10-30% of adults. 1

• Mild recovery agitation: 17.6% of patients; moderate-to-severe agitation: 1.6%. 4
• Emesis without aspiration: 6.7% of cases (associated with increasing age). 10, 4
• Nausea: 4-5% of patients. 5
• Ataxia: 7-8% of patients. 5
• Dysphoria: 1% of patients. 5

Critical Safety Considerations

Ketamine should only be administered by or under the direction of physicians experienced in general anesthesia, airway management, and ventilation. 3

• Not recommended for patients who have not followed nil per os (NPO) guidelines due to aspiration risk. 3
• In chronic ketamine users, monitor for genitourinary pain; consider cessation if pain continues with other genitourinary symptoms. 3
• Purposeless and tonic-clonic movements of extremities may occur during anesthesia; these do not indicate inadequate anesthesia or need for additional doses. 3
• Use immediately after dilution; discard if discolored or contains particulate matter. 3

Special Clinical Scenarios

For hemodynamically unstable trauma patients, ketamine 1-2 mg/kg remains appropriate as it maintains blood pressure through central NMDA blockade and preserved adrenal function. 4

• Suitable for prehospital induction of anesthesia. 2
• Safe in patients with traumatic brain injuries (does not increase intracranial pressure). 2
• For orthopedic procedures in children, ketamine/midazolam combination demonstrates superior safety (6% hypoxia) compared to fentanyl/midazolam (20% hypoxia). 10, 5