Ketalar - Drug Monograph

Introduction

Ketalar (ketamine hydrochloride) is a rapid-acting general anesthetic and dissociative agent that has been in clinical use since its FDA approval in 1970. Originally developed as a safer alternative to phencyclidine (PCP), ketamine has gained renewed interest in recent years for its unique pharmacological properties and expanding clinical applications beyond anesthesia. It remains the only clinically available intravenous anesthetic with analgesic, amnestic, and hypnotic properties that does not typically cause respiratory depression.

Mechanism of Action

Ketamine primarily acts as a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, blocking glutamate-mediated excitatory neurotransmission. This mechanism produces a functional dissociation between the thalamocortical and limbic systems, creating a state called "dissociative anesthesia" where patients appear awake but are unresponsive to painful stimuli. Additionally, ketamine interacts with opioid receptors (primarily μ and κ), monoaminergic receptors, muscarinic receptors, and voltage-sensitive calcium channels. Its antidepressant effects are believed to involve increased glutamate release leading to enhanced synaptic plasticity through AMPA receptor activation.

Indications

• Induction and maintenance of general anesthesia
• Diagnostic and surgical procedures requiring anesthesia
• Supplement to low-potency agents such as nitrous oxide

• Treatment-resistant depression (particularly as esketamine nasal spray)
• Acute and chronic pain management
• Status asthmaticus (as a bronchodilator)
• Sedation in emergency departments
• Rapid-sequence intubation adjunct
• Refractory status epilepticus

Dosage and Administration

• IV: 1-4.5 mg/kg administered over 60 seconds
• IM: 6.5-13 mg/kg

• IV: 0.5-1 mg/kg as needed
• Continuous infusion: 10-45 mcg/kg/min

• IV: 0.2-0.75 mg/kg bolus followed by 0.05-0.2 mg/kg/hr infusion
• Low-dose ketamine: 0.1-0.3 mg/kg IV/IM

• Elderly: Reduce dose by 25-50%
• Hepatic impairment: Consider dose reduction
• Renal impairment: No significant adjustment needed
• Pediatric: Similar mg/kg dosing as adults

Pharmacokinetics

Contraindications

• Known hypersensitivity to ketamine or any component of the formulation
• Patients in whom a significant elevation of blood pressure would constitute a serious hazard
• Schizophrenia or psychotic disorders (relative contraindication)

Warnings and Precautions

• Not recommended in patients with known psychosis; may exacerbate psychiatric conditions

• Emergence reactions: May cause hallucinations, confusion, or delirium during recovery
• Increased intracranial pressure: Use with caution in patients with CNS masses, hydrocephalus, or head trauma
• Hypertension: Can significantly increase blood pressure and heart rate
• Airway protection: Laryngeal reflexes may remain intact but cannot be relied upon for airway protection
• Prolonged recovery: Effects may persist for hours after procedure
• Abuse potential: Schedule III controlled substance with potential for psychological dependence

Drug Interactions

• CNS depressants (benzodiazepines, opioids, alcohol): Enhanced sedative effects
• Theophylline: May lower seizure threshold
• Sympathomimetics: Additive cardiovascular effects
• Thyroid hormones: Increased risk of hypertension and tachycardia
• CYP3A4 inhibitors (azole antifungals, macrolides): May increase ketamine levels
• CYP3A4 inducers (rifampin, carbamazepine): May decrease ketamine levels
• Halogenated anesthetics: Prolonged recovery time

Adverse Effects

• Cardiovascular: Hypertension, tachycardia
• CNS: Dizziness, diplopia, nystagmus
• Psychiatric: Vivid dreams, emergence reactions
• Gastrointestinal: Nausea, vomiting
• Respiratory: Increased secretions

• Respiratory depression or apnea (with rapid administration)
• Laryngospasm
• Severe emergence reactions requiring intervention
• Allergic reactions including anaphylaxis
• Raised intracranial pressure
• Hepatotoxicity with chronic use

Monitoring Parameters

• Vital signs: Blood pressure, heart rate, respiratory rate continuously during administration
• Oxygen saturation: Continuous pulse oximetry
• ECG: In patients with cardiac history
• Mental status: During recovery period
• Emergence reactions: Particularly in first hour post-administration
• Pain scores: When used for analgesia
• Liver function tests: With prolonged use

Patient Education

• You will likely experience unusual dreams or hallucinations during recovery
• You may feel disconnected from your body or environment
• Do not operate machinery or drive for at least 24 hours after administration
• Report any persistent psychological effects to your healthcare provider
• This medication has abuse potential and should only be used as prescribed
• Inform your doctor if you have a history of psychiatric disorders, heart problems, or high blood pressure
• The effects may last longer than you expect; plan accordingly

References

1. FDA. (2020). Ketalar (ketamine hydrochloride) prescribing information. 2. Bokor, G., & Anderson, P. D. (2014). Ketamine: an update on its clinical uses and abuses. Journal of Pharmacy Practice, 27(6), 582-586. 3. Zanos, P., et al. (2018). Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacological Reviews, 70(3), 621-660. 4. Miller, R. D., et al. (2020). Miller's Anesthesia (9th ed.). Elsevier. 5. Sanacora, G., et al. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399-405. 6. Cohen, S. P., et al. (2018). Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine, 43(5), 521-546. 7. Jilani, T. N., et al. (2023). Ketamine. In StatPearls. StatPearls Publishing. 8. World Health Organization. (2021). WHO Model List of Essential Medicines - 22nd List.