Ketamine Hydrochloride

Dose and dosage

Dog

As an adjunct to anesthesia:
a) For use in combination with an opioid and ketamine (so-called “doggie magic”) to provide anesthesia and pain management (Note: reference has dosing tables for conversion of patient weight to various micrograms/m2 doses of dexmedetomidine; opioid concentrations used in the reference are: Butorphanol 10 mg/mL, Hydromorphone 2 mg/mL, Morphine 15 mg/mL, & Buprenorphine 0.3 mg/mL. Ketamine concentration is 100 mg/mL. As these drugs may be available in other concentrations, only use those products with the above concentrations if using this protocol.):
For geriatric dogs, dogs with renal or liver dysfunction as a premed prior to propofol or face mask induction, followed by maintenance on isoflurane or sevoflurane: dexmedetomidine at 62.5 micrograms/m2. Combine with equal volumes of one of the opioids noted above and ketamine. May administer IM or IV.
For slightly heavier sedation in ASA class II or II dogs requiring sedation for radiographic procedures: Dexmedetomidine at 125 micrograms/m2. Combine with equal volumes of one of the opioids noted above and ketamine. May administer IM or IV.


For dogs undergoing minor surgery, Penn hip or OFA-types of radiographic procedures that require significant muscle relaxation:
Dexmedetomidine at 250 micrograms/m2. Combine with equal volumes of one of the opioids noted above and ketamine. May administer IM or IV.
To induce a surgical plane of anesthesia for OHE, castration, or other abdominal surgery: Dexmedetomidine at 375 micrograms/m2.
Combine with equal volumes of one of the opioids noted above and ketamine. May administer IM or IV. Provides rapid immobilization; lateral recumbency in 5-8 minutes. Dogs can be intubated and maintained on oxygen. Supplemental low doses of isoflurane (0.5%) or sevoflurane (1%) can be used.


For immobilizing extremely fractious dogs and wolf-hybrid dogs:
Dexmedetomidine at 500 micrograms/m2. Combine with equal volumes of one of the opioids noted above and ketamine. Administer IM. This dose is rarely required.
To reverse above, atipamezole IM at the same volume as the dexmedetomidine. (Ko 2009)
As an NMDA antagonist for adjunctive pain control:
a) 0.1–1 mg/kg PO, IM or SC q4–6h for mild to moderate pain in conjunction with opioids. (Nieves 2002)
b) For intraoperative use: If anesthesia was induced with a drug other than ketamine, give a loading dose of 0.5 mg/kg IV, then an infusion of 10– 20 micrograms/kg/minute. A CRI of 2–10 micrograms/kg/minute can be used post-op. (Hellyer 2006)
c) In combination with opioids or lidocaine: 0.5 mg/kg IV loading bolus followed by 10 micrograms/kg/min CRI during surgery and 2 micrograms/kg/min for 24 hrs following surgery. (Shaffran 2009)

Cat

Most clinicians recommend giving atropine or glycopyrrolate before use to decrease hypersalivation.
a) 11 mg/kg IM for restraint; 22–33 mg/kg for diagnostic or minor surgical procedures not requiring skeletal muscle relaxation (Package
Insert; Ketaset®—Bristol)
b) For use in combination with an opioid and ketamine (so-called “kitty magic”, “DKT” or “Triple Combination”) to provide sedation and analgesia (Note: Opioid concentrations used in the reference are: Butorphanol 10 mg/mL, Hydromorphone 2 mg/mL, Morphine 15 mg/mL, & Buprenorphine 0.3 mg/mL. Ketamine concentration is 100 mg/mL. Dexmedetomidine concentration is 0.5 mg/mL. As these drugs may be available in other concentrations, only use those products with the above
concentrations if using this protocol.):
c) In combination as an immobilizing agent: For cats requiring more sedation when insufficient sedation from opioid, higher doses of medetomidine, and midazolam: butorphanol 0.2 mg/kg; medetomidine 0.015–0.02 mg/kg; midazolam 0.05–0.2 mg/kg; ketamine 1–5 mg/kg; all are given IM. For painful procedures consider adding buprenorphine at 0.02–0.04 mg/kg or substituting butorphanol or buprenorphine with either morphine 0.5 mg/kg or hydromorphone 0.1 mg/kg.
For highly aggressive cats, 1 mL of ketamine can be sprayed into the open mouth or directed into the cat’s mouth using a feline urethral catheter through the cage bars. The drug should be sprayed quickly so the cat does not chew and swallow the catheter. (Moffat 2008)
As an NMDA antagonist for adjunctive pain control:
a) 0.1–1 mg/kg IM or SC q4–6h for mild to moderate pain in conjunction with opioids. (Nieves 2002)
b) For intraoperative use: If anesthesia was induced with a drug other than ketamine, give a loading dose of 0.5 mg/kg IV, then an infusion of 10– 20 micro grams/kg/minute. A CRI of 2–10 micrograms/kg/minute can be used post-op. (Hellyer 2006)
c) In combination with opioids or lidocaine: 0.5 mg/kg IV loading bolus followed by 10 micrograms/kg/min CRI during surgery and 2 micrograms/kg/min for 24 hrs following surgery.
Using the MLK (morphine/lidocaine/ketamine) mixture: To a 500 mL bag of LRS add 10 mg morphine sulfate, 120 mg lidocaine, and 100 mg ketamine. Infuse at a rate of 10 mL/kg/hr (will provide morphine at 0.2 mg/kg/hr, lidocaine 40 micrograms/kg/minute, and ketamine 2 mg/kg/hr). Can add dexmedetomidine if needed. (Shaffran 2009)

Small mammals

For chemical restraint:
a) Mice: Alone: 50 –100 mg/kg IM or IP, 50 mg/kg IV; In combination with diazepam: Ketamine 200 mg/kg with Diazepam 5 mg/kg IM or IP;
In combination with xylazine: Ketamine 100 mg/kg with Xylazine 5–15 mg/kg IM or IP (Burke 1999)
b) Rats: Alone: 50 –100 mg/kg IM or IP, 40–50 mg/kg IV; In combination with diazepam: Ketamine 40–60 mg/kg with Diazepam 5– 10 mg/kg IP;
In combination with xylazine: Ketamine 40–75 mg/kg with Xylazine 5–12 mg/kg IM or IP (Burke 1999)
c) Hamsters/Gerbils: 100 mg/kg IM; In combination with diazepam: Ketamine 50 mg/kg with Diazepam 5 mg/kg IM; In combination with xylazine: Not recommended (Burke 1999)
d) Guinea pig: Alone: 10–30 mg/kg IM; In combination with diazepam: Ketamine 60–100 mg/kg with Diazepam 5–8 mg/kg IM; In combination with xylazine: Ketamine 85 mg/kg with Xylazine 12–13 mg/kg IM (Burke 1999)
e) Rabbits: Alone: 20–60 mg/kg IM or IV; In combination with diazepam: Ketamine 60–80 mg/kg with Diazepam 5– 10 mg/kg IM;
In combination with xylazine: Ketamine 10 mg/kg with Xylazine 3 mg/kg IV (Burke 1999)
f) Rabbits: Alone: 20–50 mg/kg IM or 15–20 mg/kg IV In combination with diazepam for induction: Diazepam 5–10 mg/kg IM give ketamine 30 minutes after diazepam at 20–40 mg/kg IM or Diazepam 0.2–0.5 mg/kg and Ketamine 10–15 mg/kg (to effect) IV;
In combination with diazepam for anesthesia without inhalants: Diazepam 5–10 mg/kg IM plus ketamine 60–80 mg/kg IM 30 minutes later; In combination with xylazine: Not recommended for pet rabbits (Ivey & Morrisey 2000)
g) Injectable anesthesia: 

Rodents: midazolam (5 mg/kg) + ketamine (100 mg/kg) + buprenorphine (0.05 mg/kg) IP.
Rabbits: Midazolam (0.05 mg/kg) + buprenorphine (0.03 mg/kg) + ketamine (10 mg/kg) IM. (Bennett 2009)

Ferrets

a) For injectable anesthesia: Butorphanol 0.1 mg/kg, Ketamine 5 mg/kg, medetomidine 80 micrograms/kg. Combine in one syringe and give IM. May need to supplement with isoflurane (0.5–1.5%) for abdominal surgery. (Finkler 1999)

Cattle

a) Premedicate with atropine and xylazine, then ketamine 2 mg/kg IV bolus (Thurmon & Benson 1986)
b) After sedation, 2.2 mg/kg IV (Mandsager 1988)
c) As a CRI for adjunctive analgesia: 0.4–1.2 mg/kg/hr. (Miesner 2009)

Horse

a) For field anesthesia: Sedate with xylazine (1 mg/kg IV; 2 mg/kg IM) given 5–10 minutes (longer for IM route) before induction of anesthesia with ketamine (2 mg/kg IV). Horse must be adequately sedated (head to the knees) before giving the ketamine (ketamine can cause muscle rigidity and seizures). If adequate sedation does not occur, either: 1) Redose xylazine: up to half the original dose, or 2) Add butorphanol (0.02–0.04 mg/kg IV). Butorphanol can be given with the original xylazine if you suspect that the horse will be difficult to tranquilize (e.g., high-strung Thoroughbreds) or added before the ketamine. This combination will improve induction, increase analgesia and increase recumbency time by about 5–10 minutes, or 3) Diazepam (0.03 mg/kg IV). Mix the diazepam with the ketamine. This combination will improve induction when sedation is marginal, improve muscle relaxation during anesthesia and prolong anesthesia by about 5–10 minutes, or 4) Guaifenesin (5% solution administered IV to effect) can also be used to increase sedation and muscle relaxation. (Mathews 1999)
b) Initially give xylazine 1.1 mg/kg IV and wait for full sedative effect (4– 8 minutes); then give ketamine 2.2–2.75 mg/kg IV only (the higher dose may be necessary for ponies, young “high-strung” Arabians, Hackneys, and Thoroughbreds) as a bolus. Do not administer to an “excited” horse. If surgery time requires additional anesthesia, ⅓–½ of the original xylazine/ketamine doses may be given IV. For procedures where better muscle relaxation is required, use guaifenesin-thiobarbiturate. Do not disturb horse until fully recovered. (Thurmon & Benson 1987)
c) For foals and ponies: Add 500 mg ketamine and 250 mg xylazine to 500 mL of 5% guaifenesin solution. For induction, give 1.1 mL/kg IV rapidly. Anesthesia may be maintained by constant IV infusion of 2–3 mL/kg/hr. Lower doses for foals, higher doses for ponies. (Thurmon & Benson 1987)
d) For induction of surgical colic patients: Use guaifenesin to effect, than 1.6–2.2 mg/kg ketamine (Mandsager 1988)
e) 200 mg bolus (in a 454 kg horse) intra-operatively to reduce movement with light general anesthesia (Mandsager 1988)

Swine

a) Give atropine, then ketamine at 11 mg/kg IM. To prolong anesthesia and increase analgesia give additional ketamine 2–4 mg/kg IV. Local anesthetics injected at the surgical site (e.g., 2% lidocaine) may enhance analgesia. (Thurmon & Benson 1986)
b) Ketamine (22 mg/kg) combined with acepromazine (1.1 mg/kg) IM (Swindle 1985)
c) 4.4 mg/kg IM or IV after sedation (Mandsager 1988)

Sheep

a) Premedicate with atropine (0.22 mg/kg) and acepromazine (0.55 mg/kg; then ketamine 22 mg/kg IM. To extend anesthetic time, may give ketamine intermittently IV at 2–4 mg/kg. (Thurmon & Benson 1986)
b) 2 mg/kg IV for induction, then 4 mL/minute constant infusion of ketamine in a concentration of 2 mg/mL in D5W (Thurmon & Benson 1986)

Goat

a) Give atropine 0.4 mg/kg, followed by xylazine 0.22 mg/kg IM 20–25 minutes later. Approximately 10 minutes after xylazine give ketamine 11 mg/kg IM. To extend anesthesia give ketamine 2–4 mg/kg IV (shorter extension) or 6 mg/kg (longer extension). (Thurmon & Benson 1986)

Reptiles (Large)

a) Medium to small land Tortoises: Medetomidine 100–150 micrograms/kg with ketamine 5–10 mg/kg IV or IM; 

Freshwater Turtles: Medetomidine 150–300 micrograms/kg with ketamine 10–20 mg/kg IV or IM;

Giant Land Tortoises: 200 kg Aldabra tortoise: Medetomidine 40 micrograms/kg with ketamine 4 mg/kg IV or IM

Smaller Aldabra tortoises: Medetomidine 40–80 micrograms/kg with ketamine 4–8 mg/kg IV or IM. Wait 30–40 minutes for peak effect;
Iguanas: Medetomidine 100–150 micrograms/kg with ketamine 5–10 mg/kg IV or IM;
Reversal of all dosages with atipamezole is 4–5 times the medetomidine dose (Heard 1999)

Birds (Other)

a) Birds weighing:
<100 grams (canaries, finches, budgies): 0.1–0.2 mg/gm IM;
250–500 grams (parrots, pigeons): 0.05–0.1 mg/gm IM;
500 grams–3 kg (chickens, owls, hawks): 0.02–0.1 mg/gm IM;
>3 kg (ducks, geese, swans): 0.02–0.05 mg/gm IM (Booth 1988)
b) In combination with xylazine: Ketamine 10–30 mg/kg IM; Xylazine 2– 6 mg/kg IM; birds less than 250 grams require a higher dosage (per kg) than birds weighing greater than 250 g. Xylazine is not recommended to be used in debilitated birds because of its cardiodepressant effects.
In combination with diazepam: Ketamine 10–50 mg/kg IM; Diazepam 0.5–2 mg/kg IM or IV; doses can be halved for IV use. 

In combination with acepromazine: Ketamine 25–50 mg/kg IM; Acepromazine 0.5–1 mg/kg IM (Wheler 1993)

Zoo, Exotic, Wildlife

For use of ketamine in zoo, exotic and wildlife medicine refer to specific references, including:
a) Zoo Animal and Wildlife Immobilization and Anesthesia. West, G, Heard, D, Caulkett, N. (eds.). Blackwell Publishing, 2007.
b) Handbook of Wildlife Chemical Immobilization, 3rd Ed. Kreeger, T.J. and J.M. Arnemo. 2007.
c) Restraint and Handling of Wild and Domestic Animals. Fowler, M (ed.), Iowa State University Press, 1995
d) Exotic Animal Formulary, 3rd Ed. Carpenter, J.W., Saunders. 2005
e) The 2009 American Association of Zoo Veterinarian Proceedings by D. K. Fontenot also has several dosages listed for restraint, anesthesia, and analgesia for a variety of drugs for carnivores and primates. VIN members can access them at: http://goo.gl/BHRih or http://goo.gl/9UJse


Applications: General Anesthesia
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Ketamine is commonly used for short-term anesthetic procedures in many animal species.

Ketamine is contraindicated in patients who have exhibited prior hypersensitivity reactions to it and animals to be used for human consumption.
Use in patients with significant hypertension, heart failure, and arterial aneurysms could be hazardous. The manufacturer warns against its use in patients with hepatic or renal insufficiency but in humans with renal insufficiency, the duration of action is not prolonged. Because ketamine does not provide good muscle relaxation, it is contraindicated when used alone for major surgery.
Ketamine can cause increases in CSF pressure and it should not be used in cases with elevated pressures or when head trauma has occurred. Because of its supposed epileptogenic potential, it should generally not be used (unless very cautiously) in animals with preexisting seizure disorders. As myelography can induce seizures, ketamine should be used cautiously in animals undergoing this procedure.
Ketamine is considered to be relatively contraindicated when increased intra-ocular pressure or open globe injuries exist, and for procedures involving the pharynx, larynx, or trachea. Animals that have lost significant amounts of blood, may require significantly reduced ketamine dosages.
While ketamine has been used safely in humans with malignant hyperthermia, its use in animals susceptible to this condition is controversial.
Ketamine can increase heart rate, increase blood pressure and myocardial oxygen consumption; its use should be avoided in cats with hypertrophic cardiomyopathy (HCM) or in other patients where an increase in heart rate, blood pressure and myocardial oxygen consumption can be detrimental (e.g., unstable shock or congestive heart failure). Its effects on respiratory function may be enhanced in patients with unstable cardiopulmonary function. Because of ketamine’s tendencies to increase sympathetic tone (increased norepinephrine release), it should be used with caution in animals where increased sympathetic tone concurrently exists (e.g., pheochromocytoma, hyperthyroidism). Hyperthyroid human patients (and those receiving exogenous thyroid replacement) may be susceptible to developing severe hypertension and tachycardia when given ketamine. The veterinary significance of this potential problem is unknown. Cats’ eyes remain open after receiving ketamine, and should be protected from injury plus an ophthalmic lubricant (e.g., Lacri-Lube®) should be applied to prevent excessive drying of the cornea.
Because ketamine is excreted almost exclusively via renal mechanisms, it should be used with caution in cats with reduced renal function. To minimize the incidences of emergence reactions, it is recommended to minimize exposure to handling or loud noises during the recovery period. The monitoring of vital signs should still be performed during the recovery phase, however.
Because ketamine can increase blood pressure, careful control of postsurgical hemorrhage (e.g., declawing) should be managed. It is not essential to withhold food or water prior to surgery, but in elective procedures, it is recommended to withhold food for 6 hours prior to surgery.

Ketamine is a widely used anesthetic agent. The precise mechanism of action is not known, but most evidence supports its action as a centrally acting dissociative agent. Ketamine produces mild analgesia and modulates pain via its ability to act as a noncompetitive antagonist for N-methyl D-aspartate (NMDA) receptors.
Ketamine is an equal concentration of two isomers (R-ketamine and S-ketamine). S-ketamine is more active and is eliminated faster. The S-isomer, called esketamine hydrochloride (Spravato), is an intranasal product that has been used in humans for treatment of depression. The mechanism by which it exerts its antidepressant effect is unknown. The major circulating metabolite noresketamine demonstrated activity at the same receptor with less affinity.
Pharmacokinetics: Ketamine is not active orally. It must be injected by IV, IM, or SQ routes. It has a short half-life in most animals (60–90 minutes) and is rapidly metabolized. The metabolite (norketamine) may produce more prolonged NMDA antagonistic effects but with less affinity for the receptor.

The following drug interactions have either been reported or are theoretical in humans or animals receiving ketamine and may be of significance in veterinary patients:
CHLORAMPHENICOL (parenteral): May prolong the anesthetic actions of ketamine
CNS DEPRESSANTS: Narcotics, barbiturates, or diazepam may prolong the recovery time after ketamine anesthesia
HALOTHANE: When used with halothane, ketamine recovery rates may be prolonged and the cardiac stimulatory effects of ketamine may be inhibited; close monitoring of cardiac status is recommended when using ketamine with halothane
IVERMECTIN: It has been recommended not to use ivermectin in reptiles within 10 days of ketamine (Bays 2009)
NEUROMUSCULAR BLOCKERS (e.g., succinylcholine and tubocurarine): May cause enhanced or prolonged respiratory depression
THYROID HORMONES: When given concomitantly with ketamine, thyroid hormones have induced hypertension and tachycardia in humans; betablockers (e.g., propranolol) may be of benefit in treating these effects

Ketamine causes pain with IM injection (pH of solution is 3.5). Tremors, muscle spasticity, and convulsive seizures have been reported. Spontaneous movements, salivation, and increased body temperature are more common in dogs when high doses are used. Ketamine increases sympathetic tone, heart rate, and blood pressure. It produces an increased cardiac output compared with other anesthetic agents. Salivation, mydriasis, and regurgitation are increased in animals that receive ketamine, which may be reduced by premedication within atropine. Apnea may develop in some animals, and oxygen supplementation should be available. Prolonged infusions in horses may delay GI transit times.

Hypertension, hypersalivation, respiratory depression, hyperthermia, emesis, vocalization, erratic & prolonged recovery, dyspnea, spastic jerking movements, seizures, muscular tremors, hypertonicity, opisthotonos, & cardiac arrest; pain after IM injection may occur Cats’ eyes remain open

Ketamine is considered to have a wide therapeutic index (approximately 5 times greater when compared to pentobarbital). When given too rapidly or in excessive doses, significant respiratory depression may occur. Treatment using mechanically assisted respiratory support is recommended versus the use of analeptic agents. In cats, yohimbine with 4-aminopyridine has been suggested for use as a partial antagonist

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously.
Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term.) No specific lactation information was found.