Ketamine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	5-10 mg/kg	Single dose for induction; may be repeated as needed	Duration: Anesthesia lasts 10-15 minutes Notes: Often combined with diazepam (0.25-0.5 mg/kg IV) or medetomidine (0.01-0.04 mg/kg IM) for better muscle relaxation.
Dog	IM	10-20 mg/kg	Single dose	Duration: Anesthesia lasts 20-30 minutes Notes: May be combined with acepromazine (0.05-0.1 mg/kg) or medetomidine.
Cat	IV	5-10 mg/kg	Single dose for induction	Duration: Anesthesia lasts 10-15 minutes Notes: Often combined with diazepam or midazolam.
Cat	IM	10-20 mg/kg	Single dose	Duration: Anesthesia lasts 20-30 minutes Notes: Commonly combined with acepromazine (0.05-0.1 mg/kg) or medetomidine (0.01-0.08 mg/kg).
Horse	IV	2-2.5 mg/kg	Single dose for induction	Duration: Anesthesia lasts 10-20 minutes Notes: Usually preceded by xylazine (1.1 mg/kg IV) or detomidine (0.02-0.04 mg/kg IV).
Horse	IV (infusion)	0.04-0.08 mg/kg/min	Continuous rate infusion (CRI) for maintenance	Duration: As needed Notes: Often combined with other anesthetics (e.g., guaifenesin, propofol).
Cattle	IV	2-5 mg/kg	Single dose	Duration: Anesthesia lasts 10-20 minutes Notes: Often combined with xylazine (0.05-0.1 mg/kg IV).
Cattle	IM	5-10 mg/kg	Single dose	Duration: Anesthesia lasts 20-30 minutes Notes: May be combined with xylazine.
Sheep/Goat	IV	2-5 mg/kg	Single dose	Duration: Anesthesia lasts 10-20 minutes Notes: Often combined with xylazine or diazepam.
Sheep/Goat	IM	5-10 mg/kg	Single dose	Duration: Anesthesia lasts 20-30 minutes Notes: Commonly combined with xylazine (0.05-0.1 mg/kg).
Rabbit	IM	25-50 mg/kg	Single dose	Duration: Anesthesia lasts 30-40 minutes Notes: Often combined with xylazine (5-10 mg/kg) or medetomidine (0.2-0.5 mg/kg).
Bird (e.g., psittacines)	IM	10-30 mg/kg	Single dose	Duration: Anesthesia lasts 10-20 minutes Notes: Often combined with midazolam or xylazine.
Reptiles	IM	20-50 mg/kg	Single dose	Duration: Anesthesia lasts 30-60 minutes Notes: May be combined with medetomidine or butorphanol.

Clinical Indications & Species Uses

General Indications

Dissociative anesthesia
Analgesia
Chemical restraint

Dog (Canine)

Induction and maintenance of anesthesia
Chemical restraint for diagnostic or minor procedures
Analgesia (subanesthetic doses)
Adjunct to other anesthetics (e.g., with diazepam or medetomidine)

Cat (Feline)

Induction and maintenance of anesthesia
Chemical restraint
Analgesia (subanesthetic doses)
Adjunct to other anesthetics (e.g., with acepromazine or medetomidine)

Horse (Equine)

Induction of anesthesia (usually with alpha-2 agonists)
Maintenance of anesthesia (as part of balanced anesthesia)
Analgesia (subanesthetic doses)

Cattle (Bovine)

Chemical restraint
Induction of anesthesia (often with xylazine)
Analgesia (subanesthetic doses)

Small Ruminants (Sheep / Goat)

Chemical restraint
Induction of anesthesia (often with xylazine or diazepam)
Analgesia (subanesthetic doses)

Rabbit & Small Mammals

Chemical restraint
Induction and maintenance of anesthesia (often combined with xylazine or medetomidine)

Avian & Poultry

Chemical restraint
Anesthesia (often combined with other agents)

Exotic & Other Species

Chemical restraint and anesthesia in various exotic species (e.g., reptiles, small mammals)

Pharmacology & Mechanism of Action

Drug Class: Dissociative Anesthetic | Pharmacological Group: NMDA Receptor Antagonist

Mechanism of Action: Ketamine is a non-competitive antagonist at the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor. By blocking NMDA receptor-mediated calcium influx, it disrupts excitatory neurotransmission in the central nervous system, leading to dissociative anesthesia, analgesia, and amnesia. It also interacts with opioid receptors, monoaminergic receptors, and voltage-gated sodium channels, contributing to its analgesic and anesthetic effects.

Pharmacodynamics: Ketamine produces a cataleptic state characterized by profound analgesia, amnesia, and immobility, while maintaining protective laryngeal and pharyngeal reflexes (though not always reliable). It increases heart rate, cardiac output, and blood pressure due to central sympathetic stimulation, and causes bronchodilation. It also increases cerebral blood flow and intracranial pressure. At subanesthetic doses, it provides analgesia and may have neuroprotective and anti-inflammatory effects.

⚡ Pharmacokinetics Summary

Absorption: Ketamine is well absorbed after intramuscular (IM) and subcutaneous (SC) administration, with peak plasma concentrations occurring within 5-15 minutes. Oral bioavailability is low (17-20%) due to extensive first-pass metabolism, but it is used orally in some species for analgesia. Rectal and intranasal routes have variable absorption.

Distribution: Ketamine is highly lipid-soluble, leading to rapid distribution into well-perfused tissues including the brain, heart, and lungs. It crosses the blood-brain barrier and placenta readily. The volume of distribution is large (2-4 L/kg in dogs).

Metabolism: Ketamine is extensively metabolized in the liver via N-demethylation to norketamine, which is pharmacologically active (about one-third to one-fifth the potency of ketamine). Further metabolism includes hydroxylation and conjugation. In cats, metabolism is slower than in dogs, leading to prolonged effects.

Excretion: Ketamine and its metabolites are primarily excreted in urine (about 90%), with a small amount in feces. Biliary excretion may occur. The elimination half-life varies by species: approximately 1 hour in dogs, 2.5 hours in cats, and 30-60 minutes in horses.

Half-Life: Dogs: ~1 hour; Cats: ~2.5 hours; Horses: ~30-60 minutes; Cattle: ~30 minutes

Bioavailability: IM: ~93% in dogs; Oral: ~17-20% in dogs; IV: 100%

Protein Binding: Approximately 47% in dogs, 50% in cats, and 20-30% in horses.

Available Formulations & Strengths

Injectable Solution 10 mg/mL, 50 mg/mL, 100 mg/mL (IV, IM, SC)

Oral Solution (compounded) Various (e.g., 10 mg/mL) (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to ketamine
Severe cardiovascular disease (e.g., hypertension, congestive heart failure)
Severe hepatic or renal insufficiency
Increased intracranial pressure (e.g., head trauma, brain tumors)
Increased intraocular pressure (e.g., glaucoma)
History of seizures (may lower seizure threshold)
Pregnancy (unless benefits outweigh risks; crosses placenta)

Warnings & Clinical Precautions:

Use with caution in patients with cardiovascular disease, as ketamine can increase heart rate and blood pressure.
May cause respiratory depression, especially at high doses or when combined with other anesthetics.
Protective laryngeal reflexes are not always maintained; risk of aspiration.
In cats, prolonged recovery may occur due to slower metabolism.
Use with caution in patients with hepatic or renal impairment.
May cause emergence reactions (e.g., agitation, hallucinations) in some animals.
In horses, ketamine may cause muscle rigidity and poor muscle relaxation; often used with alpha-2 agonists.
In ruminants, ketamine may cause salivation and bloat; consider premedication with anticholinergics.
In birds, ketamine may cause respiratory depression; monitor closely.
Do not mix with barbiturates in the same syringe (precipitation).

Adverse Effects & Reactions

Common:

Increased heart rate
Increased blood pressure
Salivation
Muscle rigidity
Apnea (at high doses)
Emergence delirium
Hyperthermia (in some species)

Serious / Severe:

Respiratory depression
Cardiac arrhythmias
Seizures
Laryngospasm
Anaphylaxis (rare)
Prolonged recovery

Rare:

Hypersensitivity reactions
Hepatotoxicity (with prolonged use)
Neurotoxicity (with high doses or repeated use)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Alpha-2 agonists (xylazine, medetomidine, detomidine)	Enhanced sedation, muscle relaxation, and analgesia; may cause bradycardia and hypotension.	Moderate
Benzodiazepines (diazepam, midazolam)	Reduced muscle rigidity and seizure risk; may cause respiratory depression.	Moderate
Phenothiazines (acepromazine)	Reduced dose of ketamine needed; may cause hypotension.	Moderate
Opioids (morphine, butorphanol)	Enhanced analgesia; may cause respiratory depression.	Moderate
Halogenated anesthetics (halothane, isoflurane)	Additive cardiorespiratory depression; may cause arrhythmias.	High
Neuromuscular blocking agents	Enhanced neuromuscular blockade.	Moderate
Thyroid hormones	May increase risk of hypertension and tachycardia.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe respiratory depression
Apnea
Seizures
Cardiac arrhythmias
Hypotension
Coma

Emergency Treatment Protocol: Provide supportive care: maintain airway, administer oxygen, and provide mechanical ventilation if needed. Administer IV fluids to support blood pressure. Use anticonvulsants (e.g., diazepam) for seizures. Monitor cardiac function and treat arrhythmias as needed. There is no specific antidote; recovery is usually gradual.

Food Animal Withdrawal Times

🥩 Meat: 3 days🥛 Milk: 3 days

Withdrawal times are species-specific and may vary by country. In the US, ketamine is not approved for food animals; extra-label use requires extended withdrawal periods (e.g., 7 days for meat, 7 days for milk) as per FARAD guidelines. Consult FARAD for specific recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, excursions permitted to 15-30°C).

Handling & Special Conditions: Protect from freezing. Keep in a tightly closed container. Store in a secure, locked area as a controlled substance.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in cats, dogs, and nonhuman primates (as Ketaset®). Not approved for food animals in the US.

Extra-Label (Off-Label) Use: Ketamine is a controlled substance (C-III in the US). Extra-label use in food animals is prohibited or requires extended withdrawal periods under AMDUCA. In the US, ketamine is not approved for use in food animals; use in these species is extra-label and requires a valid veterinary-client-patient relationship and extended withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Ketamine is a versatile anesthetic agent widely used in veterinary medicine for chemical restraint, induction and maintenance of anesthesia, and analgesia. It is particularly valuable in cats and exotic species due to its wide safety margin and minimal cardiovascular depression. However, it produces poor muscle relaxation and may cause emergence reactions; therefore, it is often combined with sedatives or tranquilizers (e.g., alpha-2 agonists, benzodiazepines, acepromazine) to improve anesthesia quality. In dogs and cats, ketamine is commonly used in combination with medetomidine or dexmedetomidine for short procedures. In horses, it is typically used for induction after sedation with alpha-2 agonists. In food animals, its use is extra-label and requires careful consideration of withdrawal times. Ketamine also has analgesic properties at subanesthetic doses and is increasingly used for pain management, particularly in chronic pain conditions. It should be used with caution in patients with cardiovascular disease, increased intracranial pressure, or seizure disorders. Monitoring of respiratory and cardiovascular function is essential during anesthesia.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)