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Pronunciation
(KEET a meen)
Generic Available (U.S.)
Yes
Index Terms
Controlled Substance
C-III
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Induction and maintenance of general anesthesia
Use: Unlabeled
Analgesia, sedation
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies. Ketamine crosses the placenta and can be detected in fetal tissue. Ketamine produces dose dependent increases in uterine contractions; effects may vary by trimester. The plasma clearance of ketamine is reduced during pregnancy. Dose related neonatal depression and decreased APGAR scores have been reported with large doses administered at delivery.
Contraindications
Hypersensitivity to ketamine or any component of the formulation; conditions in which an increase in blood pressure would be hazardous
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). When used for outpatient surgery, the patient should be accompanied by a responsible adult.
• Dependence: May cause dependence (withdrawal symptoms on discontinuation) and tolerance with prolonged use.
• Emergence reactions: Postanesthetic emergence reactions which can manifest as vivid dreams, hallucinations, and/or frank delirium occur; these reactions are less common in patients <15 years of age and >65 years and when given intramuscularly. Emergence reactions, confusion, or irrational behavior may occur up to 24 hours postoperatively and may be reduced by pretreatment with a benzodiazepine and the use of ketamine at the lower end of the dosing range.
• Respiratory depression: Rapid I.V. administration or overdose may cause respiratory depression or apnea. Resuscitative equipment should be available during use.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with coronary artery disease, catecholamine depletion, hypertension, and tachycardia. Cardiac function should be continuously monitored in patients with increased blood pressure or cardiac decompensation.
• Cerebrospinal fluid (CSF) pressure elevation: Use with caution in patients with CSF pressure elevation; an increase in CSF pressure may be associated with use.
• Ethanol use: Use with caution in the chronic alcoholic or acutely alcohol-intoxicated.
Other warnings/precautions:
• Experienced physician: Should be administered under the supervision of a physician experienced in administering general anesthetics.
Adverse Reactions
Frequency not always defined.
Cardiovascular: Arrhythmia, bradycardia/tachycardia, hyper-/hypotension
Central nervous system: Intracranial pressure increased
Dermatologic: Erythema (transient), morbilliform rash (transient)
Gastrointestinal: Anorexia, nausea, salivation increased, vomiting
Local: Pain at the injection site, exanthema at the injection site
Neuromuscular & skeletal: Skeletal muscle tone enhanced (tonic-clonic movements)
Ocular: Diplopia, intraocular pressure increased, nystagmus
Respiratory: Airway obstruction, apnea, bronchial secretions increased, respiratory depression, laryngospasm
Miscellaneous: Anaphylaxis, dependence with prolonged use, emergence reactions (~12%; includes confusion, delirium, dreamlike state, excitement, hallucinations, irrational behavior, vivid imagery)
Metabolism/Transport Effects
Substrate of CYP2B6 (major), CYP2C9 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP2B6 Inhibitors (Moderate): May decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2B6 Inhibitors (Strong): May decrease the metabolism of CYP2B6 Substrates. Risk D: Consider therapy modification
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates. Risk C: Monitor therapy
Quazepam: May increase the serum concentration of CYP2B6 Substrates. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Storage
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Reconstitution
The 50 mg/mL and 100 mg/mL vials may be further diluted in D5W or NS to prepare a maintenance infusion with a final concentration of 1 mg/mL (or 2 mg/mL in patients with fluid restrictions). The 10 mg/mL vials are not recommended to be further diluted. Do not mix with barbiturates or diazepam (precipitation may occur).
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Cefepime, ceftazidime, propofol.
Compatibility in syringe: Compatible: Bupivacaine, bupivacaine with fentanyl, clonidine, clonidine with tetracaine, dexamethasone sodium phosphate, fentanyl, lidocaine, lidocaine with morphine, meperidine, midazolam. Incompatible: Diazepam, doxapram. Variable (consult detailed reference): Morphine.
Mechanism of Action
Produces a cataleptic-like state in which the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. Ketamine is a noncompetitive NMDA receptor antagonist that blocks glutamate. Low (subanesthetic) doses produce analgesia, and modulate central sensitization, hyperalgesia and opioid tolerance. Reduces polysynaptic spinal reflexes.
Pharmacodynamics/Kinetics
Onset of action:
I.V.: Anesthetic effect: 30 seconds
I.M.: Anesthetic effect: 3-4 minutes
Duration: Anesthetic effect: I.V.: 5-10 minutes; I.M.: 12-25 minutes
Distribution: Vd: 3 L/kg
Metabolism: Hepatic via hydroxylation and N-demethylation; the metabolite norketamine is 33% as potent as parent compound; greater conversion to norketamine occurs after oral administration as compared to parenteral administration
Bioavailability: Oral: 16%; Intranasal: 50%
Half-life elimination: Alpha: 10-15 minutes; Beta: 2.5 hours
Excretion: Primarily urine
Dosage
May be used in combination with anticholinergic agents to decrease hypersalivation.
Children: Note: Titrate dose for desired effect.
Sedation (unlabeled use): Oral (unlabeled route): 5-8 mg/kg for 1 dose (mixed in 0.2-0.3 mL/kg of cola or other beverage) given 30 minutes before the procedure (Sacchetti, 1994; Rosenberg, 1991)
Sedation/analgesia (unlabeled use):
I.M.: 2-5 mg/kg/dose (Green, 2011; Krause, 2000; McGlone, 2004; White, 1982)
I.V.: 0.5-1 mg/kg/dose (Sacchetti, 1994; Tobias, 1990)
Continuous I.V. infusion: 5-20 mcg/kg/minute (White, 1982; Tobias, 1990)
Children ≥16 years and Adults: Note: Titrate dose for desired effect.
Sedation/analgesia (unlabeled use):
I.M.: 2-4 mg/kg (White, 1982)
I.V.: 0.2-0.75 mg/kg (White, 1982)
Continuous I.V. infusion: 2-7 mcg/kg/minute (Hocking, 2003; Remérand, 2009; Zakine, 2008)
Induction of anesthesia (unlabeled dosing):
I.M.: 4-10 mg/kg (Green, 1990; Miller, 2010; White, 1982)
I.V.: 0.5-2 mg/kg (Miller, 2010; White, 1982)
Maintenance of anesthesia: May administer supplemental doses of one-half to the full induction dose or a continuous infusion of 0.1-0.5 mg/minute (per manufacturer). Note: To maintain an adequate concentration of ketamine for maintenance of anesthesia, 1-2 mg/minute has been recommended (White, 1982); doses in the range of 15-90 mcg/kg/minute (~1-6 mg/minute in a 70-kg patient) have also been suggested (Miller, 2010). Concurrent use of nitric oxide reduces ketamine requirements.
Administration: Oral
Mix the appropriate dose (using the 100 mg/mL injectable solution) in cola or other beverage; drink immediately after preparation.
Administration: I.V.
Administer bolus doses over 1 minute; more rapid administration may result in respiratory depression and enhanced pressor response. Note: The 100 mg/mL concentration should not be administered I.V. unless properly diluted with an equal volume of either SWFI, NS, or D5W.
Monitoring Parameters
Heart rate, blood pressure, respiratory rate, transcutaneous O2 saturation, emergence reactions; cardiac function should be continuously monitored in patients with increased blood pressure or cardiac decompensation
Test Interactions
May interfere with urine detection of PCP (false-positive).
Additional Information
May produce emergence psychosis including auditory and visual hallucinations, restlessness, disorientation, vivid dreams, and irrational behavior in ~12% of patients; pretreatment with a benzodiazepine reduces incidence of psychosis by >50%. Spontaneous involuntary movements, nystagmus, hypertonus, and vocalizations are also common.
The analgesia outlasts the general anesthetic component. Bronchodilation is beneficial in asthmatic or COPD patients. Laryngeal reflexes may remain intact or may be obtunded. The direct myocardial depressant action of ketamine can be seen in stressed, catecholamine-deficient patients. Ketamine increases cerebral metabolism and cerebral blood flow while producing a noncompetitive block of the glutaminergic postsynaptic NMDA receptor. It lowers seizure threshold and stimulates salivary secretions (atropine/scopolamine treatment is recommended).
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Can produce emergence psychosis, including auditory and visual hallucinations, restlessness, disorientation, vivid dreams, and irrational behavior in 5% to 30% of patients; risk factors include age >15 years, female gender, dose >2 mg/kg I.V., and a history of personality problems/frequent dreams (White, 1982). Pretreatment with a benzodiazepine reduces incidence of psychosis by >50%. Spontaneous involuntary movements, nystagmus, hypertonus, and vocalizations are also common.
Bronchodilation is beneficial in asthmatic or COPD patients. Laryngeal reflexes may remain intact or may be obtunded. The direct myocardial depressant action of ketamine can be seen in stressed, catecholamine-deficient patients. Ketamine releases endogenous catecholamines (epinephrine, norepinephrine) which maintain blood pressure and heart rate, and increase myocardial oxygen demand. Ketamine increases cerebral metabolism and cerebral blood flow while producing a noncompetitive block of the neuronal postsynaptic NMDA receptor. It lowers seizure threshold and stimulates salivary secretions. Recent laboratory/clinical studies support the use of low-dose ketamine to improve postoperative analgesia/outcome (Adam, 2005; Menigaux, 2000).
Ketamine, because of its effects on cardiovascular sympathetic tone, is the anesthetic drug of choice for patients with cardiac tamponade and restrictive pericarditis. Relative contraindications include patients with increased ICP (spontaneously breathing), increased intraocular pressure/open globe, and patients with schizophrenia or psychosis. (S)-ketamine (ie, esketamine) is available in a preservative-free solution in Europe for intrathecal/epidural use; however, it currently is not approved by the FDA.
Laboratory animal data has shown that ketamine accentuates apoptosis in newborn rat brains after cerebral ischemia/reperfusion (Mellon, 2007). Conversely, in adult animals, ketamine-induced neuroprotection may involve antiapoptotic and antinecrotic cell death. (Reeker, 2000). These data do not currently support a change in clinical practice.
Cardiovascular Considerations
Ketamine, secondary to catecholamine release, increases blood pressure, heart rate, and cardiac output thereby increasing myocardial oxygen demand. The mechanism by which ketamine stimulates the cardiovascular system has yet to be elucidated. The use of concurrent benzodiazepine, inhaled anesthetics, and propofol or administration of ketamine as a continuous infusion may reduce these cardiovascular effects. Ketamine is a bronchial smooth muscle relaxant probably due to catecholamine release.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Increased salivation.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Vivid dreams and hallucinations common
Mental Health: Effects on Psychiatric Treatment
Contraindicated in patients with psychotic disorders; barbiturates and hydroxyzine may increase the effects of ketamine; avoid combination
Nursing: Physical Assessment/Monitoring
Monitor cardio/respiratory status and CNS status (when used for procedures monitor sedation score); cardiac monitor and blood pressure monitor required. Monitor for emergence reactions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 10 mg/mL (20 mL); 50 mg/mL (10 mL); 100 mg/mL (5 mL, 10 mL)
Ketalar®: 10 mg/mL (20 mL); 50 mg/mL (10 mL); 100 mg/mL (5 mL)
Pricing: U.S. (www.drugstore.com)
Solution (Ketamine HCl)
50 mg/mL (10): $17.70
References
Adam F, Chauvin M, Du Manoir B, et al, "Small-Dose Ketamine Infusion Improves Postoperative Analgesia and Rehabilitation After Total Knee Arthroplasty," Anesth Analg, 2005, 100(2):475-80.
Clements JA and Nimmo WS, "Pharmacokinetics and Analgesic Effect of Ketamine in Man," Br J Anaesth, 1981, 53(1):27-30.
Cote CJ, "Sedation for the Pediatric Patient: A Review," Pediatr Clin North Am, 1994, 41(1):31-58.
Felser JM and Orban DJ, "Dystonic Reaction After Ketamine Abuse," Ann Emerg Med, 1982, 11(12):673-5.
Ghoneim MM and Korttila K, "Pharmacokinetics of Intravenous Anaesthetics: Implications for Clinical Use," Clin Pharmacokinet, 1977, 2(5):344-72.
Glickman A, "Ketamine: The Dissociative Anesthetic and the Development of a Policy for Its Safe Administration in the Pediatric Emergency Department," J Emerg Nurs, 1995, 21(2):116-24.
Green SM and Johnson NE, "Ketamine Sedation for Pediatric Procedures: Part 2, Review and Implications," Ann Emerg Med, 1990, 19(9):1033-46.
Green SM, Roback MG, Kennedy RM, et al, "Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update," Ann Emerg Med, 2011, 57(5):449-61.
Gutstein HB, Johnson KL, Heard MN, et al, "Oral Ketamine Premedication in Children," Anesthesiology, 1992, 76(1):28-33.
Hartvig P, Larsson E, and Joachimsson PO, "Postoperative Analgesia and Sedation Following Pediatric Cardiac Surgery Using a Constant Infusion of Ketamine," J Cardiothorac Vasc Anesth, 1993, 7(2):148-53.
Hartvig P, Valtysson J, Lindner KJ, et al, "Central Nervous System Effects of Subdissociative Doses of (S)-Ketamine Are Related to Plasma and Brain Concentrations Measured With Positron Emission Tomography in Healthy Volunteers," Clin Pharmacol Ther, 1995, 58(2):165-73.
Hegenbarth MA and and the Committee on Drugs, "Preparing for Pediatric Emergencies: Drugs to Consider," Pediatrics, 2008, 121:433-43.
Hocking G and Cousins MJ, "Ketamine in Chronic Pain Management: An Evidence-Based Review," Anesth Analg, 2003, 97(6):1730-9.
Kohrs R and Durieux ME, "Ketamine: Teaching an Old Drug New Tricks," Anesth Analg, 1998, 87(5):1186-93.
Little B, Chang T, Chucot L, et al, "Study of Ketamine as an Obstetric Anesthetic Agent," Am J Obstet Gynecol , 1972, 15:113(2):247-60.
Loftus RW, Yeager MP, Clark JA, et al, "Intraoperative Ketamine Reduces Perioperative Opiate Consumption in Opiate-Dependent Patients With Chronic Back Pain Undergoing Back Surgery," Anesthesiology, 2010, 113(3):639-46.
Marx GF, Hwang HS, and Chandra P, "Postpartum Uterine Pressures With Different Doses of Ketamine," Anesthesiology, 1979, 50(2):163-6.
McGlone RG, Howes MC, and Joshi M, "The Lancaster Experience of 2.0 to 2.5 mg/kg Intramuscular Ketamine for Paediatric Sedation: 501 Cases and Analysis," Emerg Med J, 2004, 21(3):290-5.
Mellon RD, Simone AF, and Rappaport BA, "Use of Anesthetic Agents in Neonates and Young Children," Anesth Analg, 2007, 104(3):509-20.
Menigaux C, Fletcher D, Dupont X, et al, "The Benefits of Intraoperative Small-Dose Ketamine on Postoperative Pain After Anterior Cruciate Ligament Repair," Anesth Analg, 2000, 90(1):129-35.
Mercadante S, "Ketamine in Cancer Pain: An Update," Palliat Med, 1996, 10(3):225-30.
Miller RD, Miller's Anesthesia, 7th ed, Philadelphia PA: Churchill Livingstone, 2010.
Moro-Sutherland DM and Shook JE, "Ketamine Use in a Pediatric Emergency Room," Acad Emerg Med, 1995, 2:428-9.
Mortero RF, Clark LD, Tolan MM, et al, "The Effects of Small-Dose Ketamine on Propofol Sedation: Respiration, Postoperative Mood, Perception, Cognition, and Pain," Anesth Analg, 2001, 92(6):1465-9.
Reeker W, Werner C, Mollenberg O, et al, "High-Dose S(+)-ketamine Improves Neurological Outcome Following Incomplete Cerebral Ischemia in Rats," Can J Anesth, 2000, 47(6):572-8.
Remérand F, Le Tendre C, Baud A, et al, "The Early and Delayed Analgesic Effects of Ketamine After Total Hip Arthroplasty: A Prospective, Randomized, Controlled, Double-Blind Study," Anesth Analg, 2009, 109(6):1963-71.
Rosenberg M, "Oral Ketamine for Deep Sedation of Difficult-to-Manage Children Who are Mentally Handicapped: Case Report," Pediatr Dent, 1991, 13(4):221-3.
Sacchetti A, Schafermeyer R, Gerardi M, et al, "Pediatric Analgesia and Sedation," Ann Emerg Med, 1994, 23(2):237-50.
Shannon M, "Recent Ketamine Administration Can Produce a Urine Toxic Screen Which Is Falsely Positive for Phencyclidine," Pediatr Emerg Care, 1998, 14(2):180.
Tobias JD and Rasmussen GE, "Pain Management and Sedation in the Pediatric Intensive Care Unit," Pediatr Clin North Am, 1994, 41(6):1269-92.
Tobias JD, Martin LD, and Wetzel RC, "Ketamine by Continuous Infusion for Sedation in the Pediatric Intensive Care Unit," Crit Care Med, 1990, 18(8):819-21.
Tobias JD, Phipps S, Smith B, et al, "Oral Ketamine Premedication to Alleviate the Distress of Invasive Procedures in Pediatric Oncology Patients," Pediatrics, 1992, 90(4):537-41.
White PF, Way WL, and Trevor AJ, "Ketamine − Its Pharmacology and Therapeutic Uses," Anesthesiology, 1982, 56(2):119-36.
Winters WD, "Epilepsy or Anesthesia With Ketamine," Anesthesiology, 1972, 36(4):309-12.
Zakine J, Samarcq D, Lorne E, et al, "Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study," Anesth Analg, 2008, 106(6):1856-61.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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