|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
Ketalar® may be confused with Kenalog®, ketorolac
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(KEET a meen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Induction and maintenance of general anesthesia
Use: Unlabeled/Investigational
Analgesia, sedation
Restrictions
C-III
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 dependant 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 on an outpatient basis, 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 >65 years of age 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, apnea, and enhanced pressor response. 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 is 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, hyper-/hypotension, pulse rate increased
Central nervous system: CSF pressure increased
Dermatologic: Erythema (transient), morbilliform rash (transient)
Gastrointestinal: Anorexia, nausea, 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, respiratory depression or stimulation, 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 (major) of CYP2B6, 2C9, 3A4
Drug Interactions
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 (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). 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
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). 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 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: Propofol.
Compatibility in syringe: Compatible: Bupivacaine with fentanyl, clonidine with tetracaine, lidocaine with morphine, meperidine, morphine. Incompatible: Amobarbital, diazepam, doxapram, methohexital, pentobarbital, phenobarbital, secobarbital, thiopental.
Compatibility when admixed: Compatible: 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. Releases endogenous catecholamines (epinephrine, norepinephrine) which maintain blood pressure and heart rate. 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
Metabolism: Hepatic via hydroxylation and N-demethylation; the metabolite norketamine is 33% as potent as parent compound
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.
Oral: Sedation (unlabeled use/route): 6-10 mg/kg for 1 dose (mixed in 0.2-0.3 mL/kg of cola or other beverage) given 30 minutes before the procedure
I.M.: Sedation/analgesia (unlabeled use): 4-5 mg/kg/dose; doses up to 13 mg/kg have been reported
I.V.: Sedation/analgesia (unlabeled use): 1-2 mg/kg/dose; titrate repeat doses for desired effect
Continuous I.V. infusion: Sedation (unlabeled use): 5-20 mcg/kg/minute; titrate to reach desired level of sedation
Children ?16 years and Adults:
Induction of anesthesia:
I.M.: 6.5-13 mg/kg; usual dose to produce 12-25 minutes of anesthesia: 10 mg/kg
I.V.: 1-4.5 mg/kg; usual dose to produce 5-10 minutes of anesthesia: 2 mg/kg
I.V. infusion: 1-2 mg/kg infuse over 0.5 mg/kg/minute; may administer with diazepam to prevent emergence reactions
Maintenance of anesthesia: Supplemental doses of 1/2 to the full induction dose; may also be maintained with a continuous infusion of 0.1-5 mg/minute
Administration: Oral
Use 100 mg/mL I.V. solution and mix the appropriate dose in 0.2-0.3 mL/kg of cola or other beverage.
Administration: I.V.
Do not exceed 0.5 mg/kg/minute or administer faster than 60 seconds. Solutions for infusion should not exceed final concentration of 2 mg/mL.
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
Additional Information
Produces 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 commonly seen.
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 neuronal 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 commonly seen.
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 myocardial oxygen demand secondary to catecholamine release. 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).
Cardiovascular Considerations
Ketamine increases myocardial demand secondary 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
Assess other medications patient may be taking for effectiveness and interactions. Assess results of laboratory tests, therapeutic effect, and adverse/toxic effects. Keep patient under observation. Monitor cardio/respiratory status and institute patient safety precautions. Monitor effectiveness of therapy and adverse reactions. Monitor respiratory status (for conscious sedation, includes pulse oximetry), cardiovascular status, CNS status (when used for procedures monitor sedation score); cardiac monitor and blood pressure monitor required.
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)
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): $16.99
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 Krauss B, “Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation in Children,” Ann Emerg Med, 2004, 44(5):460-71.
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 121: 433-443.
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.
Marx GF, Hwang HS, and Chandra P, “Postpartum Uterine Pressures With Different Doses of Ketamine,” Anesthesiology, 1979, 50(2):163-6.
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.
Moro-Sutherland DM and Shook JE, “Ketamine Use in a Pediatric Emergency Room,” Acad Emerg Med, 1995, 2:428-9.
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, 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.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
| 
