KETAMINE HCL
Chemistry - A congener of phencyclidine, ketamine HCl occurs as white, crystalline powder. It hasa melting point of 258-261°C, a characteristic odor, and will precipitate as the free base at high pH.
One gram is soluble in 5 ml of water, and 14 ml of alcohol. The pH of the commercially availableinjections are between 3.5-5.5.
Do not mix ketamine with barbiturates or diazepam in the same syringe or IV bag as precipitationmay occur.
Effects on muscle tone are described as being variable, but ketamine generally either causes nochanges in muscle tone or increased tone. Ketamine does not abrogate the pinnal and pedal reflexes, nor the photic, corneal, laryngeal or pharyngeal reflexes.
Ketamine's effects on the cardiovascular system include increased cardiac output, heart rate, meanaortic pressure, pulmonary artery pressure, and central venous pressure. Its effects on totalperipheral resistance are described as being variable. Cardiovascular effects are secondary to increased sympathetic tone; ketamine has negative inotropic effects if the sympathetic system isblocked.
Ketamine does not cause significant respiratory depression at usual doses, but at higher doses itcan cause respiratory rates to decrease. In humans with asthma, ketamine causes decreased airwayresistance.
Uses, Indications - Ketamine has been approved for use in humans, sub-human primates and cats, although it has been used in many other species (see dosage section). The approved indications forcats include, "for restraint, or as the sole anesthetic agent for diagnostic, or minor, brief, surgicalprocedures that do not require skeletal muscle relaxation.... and in subhuman primates forrestraint." (Package Insert; Ketaset® - Bristol).
Ketamine is distributed into all body tissues rapidly, with highest levels found in the brain, liver, lung, and fat. Plasma protein binding is approximately 50% in the horse, 53% in the dogs, and 37-53% in the cat.
The drug is metabolized in the liver principally by demethylation and hydroxylation and thesemetabolites along with unchanged ketamine are eliminated in the urine. Ketamine will inducehepatic microsomal enzymes, but there appears to be little clinical significance associated with thiseffect. The elimination half-life in the cat, calf, and horse is approximately 1 hour, in humans it is 2-3 hours. Like the thiobarbiturates, the redistribution of ketamine out of the CNS is more of a factorin determining duration of anesthesia than is the elimination half-life.
By increasing the dose, the duration of anesthesia will increase, but not the intensity.
Contraindications/Precautions - Ketamine is contraindicated in patients who have exhibitedprior hypersensitivity reactions to it and in animals to be used for human consumption. Its use inpatients with significant hypertension, heart failure, and arterial aneurysms could be hazardous. Themanufacturer warns against its use in hepatic or renal insufficiency, but in humans with renalinsufficiency the duration of action has been demonstrated not to be prolonged. Because ketaminedoes not give 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 elevatedpressures or when head trauma has occurred. Because of its supposed epileptogenic potential, itshould 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 undergoingthis procedure.
Ketamine is considered to be relatively contraindicated when increased intra-ocular pressure oropen globe injuries exist, and for procedures involving the pharynx, larynx, or trachea. Animals whohave 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 animalssusceptible to this is controversial. Hyperthyroid human patients (and those receiving exogenousthyroid replacement) may be susceptible to developing severe hypertension and tachycardia whengiven ketamine. The veterinary significance of this potential problem is unknown.
Cat's eyes remain open after receiving ketamine, and should be protected from injury plus anophthalmic lubricant (e.g., Lacrilube®) should be applied to prevent excessive drying of the cornea.
To minimize the incidences of emergence reactions, it is recommended to minimize exposure tohandling or loud noises during the recovery period. The monitoring of vital signs should still beperformed during the recovery phase, however.
Because ketamine can increase blood pressure, careful control of hemorrhaging post-surgery (e.g., declawing) should be accomplished. 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.
Seizures have been reported to occur in up to 20% of cats that receive ketamine at therapeuticdosages. Diazepam is suggested to be been used for treatment if necessary.
Pain after IM injection may occur.
To reduce the incidence of hypersalivation and other autonomic signs, atropine or glycopyrrolateis often administered.
Overdosage - Ketamine is considered to have a wide therapeutic index (approximately 5 timesgreater when compared to pentobarbital). When given in excessive doses or too rapidly, significantrespiratory depression may occur. Treatment using mechanically assisted respiratory support isrecommended versus the use of analeptic agents. In cats, yohimbine with 4-aminopyridine has beensuggested to be used as a partial antagonist.
Thyroid hormones when given concomitantly with ketamine have induced hypertension andtachycardia in humans. Beta-blockers (e.g., propranolol) may be of benefit in treating these effects.
Neuromuscular blockers (e.g., succinylcholine and tubocurarine) may cause enhanced orprolonged respiratory depression.
One gram is soluble in 5 ml of water, and 14 ml of alcohol. The pH of the commercially availableinjections are between 3.5-5.5.
Storage, Stability, Compatibility
Ketamine may be mixed with sterile water for injection, D5W, and normal saline for diluent purposes. Ketamine is compatible with xylazine in the same syringe.Do not mix ketamine with barbiturates or diazepam in the same syringe or IV bag as precipitationmay occur.
Pharmacology - KETAMINE HCL
Ketamine is a rapid acting general anesthetic that also has significant analgesicactivity and a lack of cardiopulmonary depressant effects. It is thought to induce both anesthesiaand amnesia by functionally disrupting the CNS through over stimulating the CNS or inducing acataleptic state. Ketamine inhibits GABA, and also may block serotonin, norepinephrine, anddopamine in the CNS. The thalamoneocortical system is depressed while the limbic system isactivated. It induces anesthetic stages I & II, but not stage III. In cats, it causes a slight hypothermiceffect as body temperatures decrease on average by 1.6°C after therapeutic doses.Effects on muscle tone are described as being variable, but ketamine generally either causes nochanges in muscle tone or increased tone. Ketamine does not abrogate the pinnal and pedal reflexes, nor the photic, corneal, laryngeal or pharyngeal reflexes.
Ketamine's effects on the cardiovascular system include increased cardiac output, heart rate, meanaortic pressure, pulmonary artery pressure, and central venous pressure. Its effects on totalperipheral resistance are described as being variable. Cardiovascular effects are secondary to increased sympathetic tone; ketamine has negative inotropic effects if the sympathetic system isblocked.
Ketamine does not cause significant respiratory depression at usual doses, but at higher doses itcan cause respiratory rates to decrease. In humans with asthma, ketamine causes decreased airwayresistance.
Uses, Indications - Ketamine has been approved for use in humans, sub-human primates and cats, although it has been used in many other species (see dosage section). The approved indications forcats include, "for restraint, or as the sole anesthetic agent for diagnostic, or minor, brief, surgicalprocedures that do not require skeletal muscle relaxation.... and in subhuman primates forrestraint." (Package Insert; Ketaset® - Bristol).
Pharmacokinetics - KETAMINE HCL
After IM injection in the cat, peak levels occur in approximately 10 minutes.Ketamine is distributed into all body tissues rapidly, with highest levels found in the brain, liver, lung, and fat. Plasma protein binding is approximately 50% in the horse, 53% in the dogs, and 37-53% in the cat.
The drug is metabolized in the liver principally by demethylation and hydroxylation and thesemetabolites along with unchanged ketamine are eliminated in the urine. Ketamine will inducehepatic microsomal enzymes, but there appears to be little clinical significance associated with thiseffect. The elimination half-life in the cat, calf, and horse is approximately 1 hour, in humans it is 2-3 hours. Like the thiobarbiturates, the redistribution of ketamine out of the CNS is more of a factorin determining duration of anesthesia than is the elimination half-life.
By increasing the dose, the duration of anesthesia will increase, but not the intensity.
Contraindications/Precautions - Ketamine is contraindicated in patients who have exhibitedprior hypersensitivity reactions to it and in animals to be used for human consumption. Its use inpatients with significant hypertension, heart failure, and arterial aneurysms could be hazardous. Themanufacturer warns against its use in hepatic or renal insufficiency, but in humans with renalinsufficiency the duration of action has been demonstrated not to be prolonged. Because ketaminedoes not give 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 elevatedpressures or when head trauma has occurred. Because of its supposed epileptogenic potential, itshould 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 undergoingthis procedure.
Ketamine is considered to be relatively contraindicated when increased intra-ocular pressure oropen globe injuries exist, and for procedures involving the pharynx, larynx, or trachea. Animals whohave 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 animalssusceptible to this is controversial. Hyperthyroid human patients (and those receiving exogenousthyroid replacement) may be susceptible to developing severe hypertension and tachycardia whengiven ketamine. The veterinary significance of this potential problem is unknown.
Cat's eyes remain open after receiving ketamine, and should be protected from injury plus anophthalmic lubricant (e.g., Lacrilube®) should be applied to prevent excessive drying of the cornea.
To minimize the incidences of emergence reactions, it is recommended to minimize exposure tohandling or loud noises during the recovery period. The monitoring of vital signs should still beperformed during the recovery phase, however.
Because ketamine can increase blood pressure, careful control of hemorrhaging post-surgery (e.g., declawing) should be accomplished. 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.
Adverse Effects, Warnings
In approved species the following adverse reactions are listed by themanufacturer: "respiratory depression....following high doses, emesis, vocalization, erratic andprolonged recovery, dyspnea, spastic jerking movements, convulsions, muscular tremors, hypertonicity, opisthotonos and cardiac arrest. In the cat, myoclonic jerking and/or tonic/clonicconvulsions can be controlled by ultrashort-acting barbiturates or acepromazine. These latter drugsmust be given intravenously, cautiously, and slowly, to effect (approximately 1/6 to 1/4 the normaldose may be required)." (Package Insert; Ketaset® - Bristol)Seizures have been reported to occur in up to 20% of cats that receive ketamine at therapeuticdosages. Diazepam is suggested to be been used for treatment if necessary.
Pain after IM injection may occur.
To reduce the incidence of hypersalivation and other autonomic signs, atropine or glycopyrrolateis often administered.
Overdosage - Ketamine is considered to have a wide therapeutic index (approximately 5 timesgreater when compared to pentobarbital). When given in excessive doses or too rapidly, significantrespiratory depression may occur. Treatment using mechanically assisted respiratory support isrecommended versus the use of analeptic agents. In cats, yohimbine with 4-aminopyridine has beensuggested to be used as a partial antagonist.
Drug Interactions
Narcotics, barbiturates, or diazepam may prolong the recovery time afterketamine anesthesia. When used with halothane, ketamine recovery rates may be prolonged andthe cardiac stimulatory effects of ketamine may be inhibited. Close monitoring of cardiac status isrecommended when using ketamine with halothane. Chloramphenicol (parenteral) may prolongthe anesthetic actions of ketamine.Thyroid hormones when given concomitantly with ketamine have induced hypertension andtachycardia in humans. Beta-blockers (e.g., propranolol) may be of benefit in treating these effects.
Neuromuscular blockers (e.g., succinylcholine and tubocurarine) may cause enhanced orprolonged respiratory depression.