Ketamine

Indications/Exposures

Anesthesia Where Skeletal Muscle Relxation is Not Required

  • Especially suited for short procedures (although additional doses can be used for longer procedures)

Bipolar Disorder (see Bipolar Disorder, [[Bipolar Disorder]])

  • xxx

Complex Regional Pain Syndrome

  • xxxx

Depression (see Depression, [[Depression]])

  • xxx

Drug of Abuse

  • xxxx

Intensive Care Unit Sedation (see Sedation, [[Sedation]])

  • xxxx

Neuropathic Pain (see xxxx, [[xxxx]])

  • xxxx

Post-Operative Analgesia

  • xxxx

Procedural Sedation (see Sedation, [[Sedation]])

  • Bone Marrow Biopsy (see Bone Marrow Biopsy, [[Bone Marrow Biopsy]])
  • Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])
  • Endoscopy
  • Endotracheal Intubation
  • Fine Needle Aspiration (FNA) of Mass/Lesion
  • Foreign Body Extraction: particularly in pediatric populations
  • Surgery

Refractory Bronchospasm Due to Status Asthmaticus (see Asthma, [[Asthma]])

  • Clinical Efficacy
    • xxxx

Sedation in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury, [[Traumatic Brain Injury]])

  • Clinical Efficacy
    • Systematic Review of Sedation in TBI (Crit Care Med, 2011) [MEDLINE]
      • No Evidence that One Sedative is Superior to the Others in Terms of Improvement in Patient-Centered Outcomes, Intracranial Pressure, or Cerebral Perfusion Pressure in TBI
      • High Bolus Doses of Opiates, Have Potentially Deleterious Adverse Effects on Intracranial Pressure and Cerebral Perfusion Pressure
    • Systematic Review of Ketamine in Traumatic Brain Injury (Neurocrit Care, 2014) [MEDLINE]
      • Ketamine Does Not Increase ICP in TBI and May Decrease it in Selected Cases (Oxford Level 2b, GRADE C Evidence)

Contraindications


Pharmacology

Non-Barbiturate Dissociative Anesthetic

  • Analgesia: this is unique among the major intravenous sedatives
  • Bronchodilation: likely due to a vagolytic effect
  • Cardiovascular Stimulation
  • Increased Cerebral Perfusion: via sympathetic stimulation
  • Normal Pharyngeal-Laryngeal Reflexes: results in normal airway patency
  • Normal-Slightly Enhanced Skeletal Muscle Tone
  • Respiratory Stimulation
    • However, it May Occasionally Induce Transient, Minimal Respiratory Depression
    • Rapid Administration or Overdosage Can Result in Respiratory Depression

Pharmacokinetics (Intravenous)

  • Onset: 30 sec
  • Initial Slope (Alpha Phase): corresponds clinically to the anesthetic effect of the drug
    • Half-Life: 10-15 min
    • Duration: 45 min
    • Alpha phase is terminated by redistribution of drug from central nervous system to peripheral tissues and by hepatic biotransformation to metabolite I (this metabolite is 1/3 as active as ketamine)
  • Beta Phase
    • Half-Life: 2.5 hrs

Metabolism

  • Hepatic N-Demethylation
    • Norketamine Active Metabolite

Administration

  • IM (General Anesthesia Induction): 9-13 mg/kg
    • Onset of Anesthesia: within 3-4 min
    • Duration of Anesthetic Effect: 12-25 min
  • IV (General Anesthesia Induction): 1-2 mg/kg (usual adult dose: 100 mg) slow push over 1-2 min
    • Onset of Anesthesia (for 2 mg/kg dose): within 30 sec
    • Duration of Anesthetic Effect (for 2 mg/kg dose): 5-10 min
    • Give with Adjuvants
      • Anti-Sialagogue: decreases salivation
      • Benzodiazepine (Midazolam, etc) decreases risk of emergence reaction
  • IV Loading Dose (ICU Sedation): 0.1-0.5 mg/kg
  • IV Infusion (ICU Sedation): 0.05-0.4 mg/kg/hr (Crit Care Med, 2013) [MEDLINE]
    • Alaris Pump Units (ICU): mg/kg/hr (max: 2 mg/kg/hr)
    • Alaris Pump Units (Anesthesia): mg/kg/min

Dose Adjustment

  • Hepatic: undefined (use with caution in liver disease)
  • Renal: none

Use in Pregnancy (see Pregnancy, [[Pregnancy]])

  • xxxx

Use During Lactation

  • xxx

Cautions

  • Use with Caution in the Setting of Chronic Ethanol Abuse or Acute Intoxication
  • Use with Caution in Setting of Increased Cerebrospinal Fluid Pressure

Adverse Effects

Allergic Adverse Effects

Cardiovascular Adverse Effects

  • Arrhythmias
    • Epidemiology: may occur in some cases
  • Enhanced Pressor Response
    • Clinical: may occur with rapid administration
  • Hypertension (see Hypertension, [[Hypertension]])
    • Clinical
      • Occurs shortly after injection
      • Returns to normal within 15 min after injection
  • Hypotension (see Hypotension, [[Hypotension]])
    • Epidemiology: may occur in some cases
  • Sinus Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]])
    • Epidemiology: may occur in some cases

Gastrointestinal Adverse Effetcs

  • Anorexia (see Anorexia, [[Anorexia]]): usually not severe or prolonged
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): usually not severe or prolonged
  • Sialorrhea (Hypersalivation) (see Sialorrhea, [[Sialorrhea]])

Neurologic Adverse Effects

Diplopia (see Diplopia, [[Diplopia]])

  • Epidemiology: may occur

Emergence Reaction

  • Epidemiology
    • Incidence: occurs in 12% of cases
      • Less common in elderly (>65 y/o)
      • Less common with intramuscular administration
    • Duration: few hrs (although cases have been reported with recurrence up to 24 hrs later post-operatively)
  • Clinical
    • Agitation (see Agitation, [[Agitation]])
    • Delirium/Confusion (see Delirium, [[Delirium]])
    • Dream-Like State
    • Hallucination (see Hallucination, [[Hallucination]])
    • Irrational Behavior
    • Vivid Imagery
  • Prevention: measures to decrease the incidence of emergence reactions
    • Minimization of Verbal/Tactile/Visual Stimulation During the Recovery Period
    • Concomitant Intravenous Diazepam During Induction and Maintenance of Anesthesia
    • Lower Ketamine Dose
  • Treatment
    • Small Dose of Short-Acting Barbiturate (see Barbiturates, [[Barbiturates]])

Fasciculations

  • Epidemiology: may occur

Hyporeflexia (see Hyporeflexia, [[Hyporeflexia]])

  • Epidemiology: may occur

Increased Cerebrospinal Fluid (CSF) Pressure

  • Use with Caution in Setting of Increased Cerebrospinal Fluid Pressure

Increased Intraocular Pressure

  • Epidemiology: may occur

Nystagmus (see Nystagmus, [[Nystagmus]])

  • Epidemiology: may occur

Tonic-Clonic Movements (Seizure-Like Movements)

  • Epidemiology: may occur (due to enhanced muscle tone)

Pulmonary Adverse Effects

Respiratory Depression (see Acute Hypoventilation, [[Acute Hypoventilation]])

  • Clinical: may occur with rapid administration or overdosage

Laryngospasm (see Laryngospasm, [[Laryngospasm]])

  • Epidemiology: may occur

Renal Adverse Effects

  • Irritative/Inflammatory Urinary Tract and Bladder Symptoms: may occur with chronic ketamine abuse
    • Cystitis

Other Adverse Effects

  • Local Pain and Exanthema at Injection Site: has been reported
  • Transient Erythema/Morbilliform Rash: has been reported

Ketamine Abuse Syndrome

Clinical Manifestations

Neurologic Manifestations

  • Anxiety (see Anxiety, [[Anxiety]])
  • Disorientation
  • Dysphoria
  • Insomnia (see Insomnia, [[Insomnia]])
  • Flashbacks
  • Hallucinations (see Hallucination, [[Hallucination]])
  • Psychosis (see Psychosis, [[Psychosis]])

Ketamine Withdrawal

Epidemiology

  • Associated with Prolonged Abuse

Clinical Manifestations

Neurologic Manifestations


References

  • Does ketamine have a role in managing severe exacerbation of asthma in adults?  Pharmacotherapy 2001;21(9):1100–1106 [MEDLINE]
  • Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011 Dec;39(12):2743-51. doi: 10.1097/CCM.0b013e318228236f [MEDLINE]
  • Drug absorption, distribution, metabolism and excretion considerations in critically ill adults. Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1067-84. doi: 10.1517/17425255.2013.799137. Epub 2013 May 17 [MEDLINE]

  • Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72 [MEDLINE]

  • The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014 Aug;21(1):163-73. doi: 10.1007/s12028-013-9950-y [MEDLINE]

  • Mechanical ventilation for asthma. Chest 2015;147(6):1671–1680 [MEDLINE]