Anesthesia Where Skeletal Muscle Relxation is Not Required

• Ketamine is Especially Well-Suited for Short Procedures (Although Additional Doses Can Be Used for Longer Procedures)

Bipolar Disorder (see Bipolar Disorder)

Clinical Efficacy

• xxxx

Complex Regional Pain Syndrome

Clinical Efficacy

• xxxx

Depression (see Depression)

Clinical Efficacy

• xxxx

Drug of Abuse

• xxxx

Induction for Rapid Sequence Endotracheal Intubation (see Airway Management)

Clinical Efficacy

• In the KETASED Multicenter, Randomized Trial of Etomidate vs Ketamine for Intubation of Acutely Ill Patients, Ketamine was a Safe Alternative to Etomidate for Endotracheal Intubation (Although the Percentage of Patients with Adrenal Insufficiency was Significantly Higher in the Etomidate Group) (Lancet, 2009) [MEDLINE]
• In a Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients, Patient-Centered Outcomes were Comparable for Either Agent (Ann Emerg Med, 2017) [MEDLINE]

Neuropathic Pain (see xxxx)

Clinical Efficacy

• xxxx

Postoperative Analgesia

Clinical Efficacy

• xxxx

Procedural Sedation (see Sedation)

• Bone Marrow Biopsy (see Bone Marrow Biopsy)
• Bronchoscopy (see Bronchoscopy)
• Endoscopy
  • Colonoscopy (see Colonoscopy)
  • Esophagogastroduodenoscopy (EGD) (see Esophagogastroduodenoscopy)
• 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)

Clinical Efficacy

• Cochrane Database Systematic Review of Ketamine in Childhood Asthma (Chest, 2022) [MEDLINE]
  • The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showing benefits of ketamine in both non-ventilated and ventilated children
  • There were no significant side effects of ketamine
  • We could not find any trials on ventilated children
  • To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance
• In a Review of Ketamine, it Has Been Suggested that Ketamine May Be Useful in Status Asthmaticus, Due to its Bronchodilating Properties (Chest, 2022) [MEDLINE]
• Systematic Review of Ketamine in the Treatment of Refractory Asthma Exacerbation (Eur J Clin Pharmacol, 2022) [MEDLINE]
  • Systematic Review Does Not Support the Use of Ketamine in Refractory Severe Asthma Exacerbation
  • A Limited Number of Prospective Studies with Large Heterogeneity was Found
  • Future Well-Designed Multicenter Randomized Controlled Trials are Required

Sedation in the Intensive Care Unit (ICU) (see Sedation)

Clinical Efficacy

• Study of Predictors of Patient Undergoing Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial from National Quality Improvement Data (Chest, 2022) [MEDLINE]
  • Population Included Patients from 68 Intensive Care Units
    • Spontaneous Awakening Trial: n = 4,847
    • Spontaneous Breathing Trial: n = 4,936
  • Factors Associated with Higher Odds of a Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial
    • Documented Target Sedation Level (Adjusted Odds Ratio: 1.68; 95% CI: 1.41-2.01; Adjusted Odds Ratio: 1.46; 95% CI: 1.24-1.72)
    • Dexmedetomidine Administration (Adjusted Odds Ratio: 1.23; 95% CI: 1.05-1.45; Adjusted Odds Ratio: 1.52; 95% CI: 1.27-1.80)
    • More Frequent Level of Arousal Assessments (Adjusted Odds Ratio: 1.22; 95% CI: 1.03-1.43; Adjusted Odds Ratio: .32; 95% CI: 1.13-1.54)
    • Physical Restraint Use (Adjusted Odds Ratio: 1.63; 95% CI: 1.42-1.87; Adjusted Odds Ratio: 1.83; 95% CI,: 1.60-2.09)
  • Factors Associated with Lower Odds of a Next-Day Spontaneous Awakening Trial/Spontaneous Breathing Trial
    • Benzodiazepine Administration (Adjusted Odds Ratio: 0.83; 95% CI: 0.72-0.95; Adjusted Odds Ratio: 0.67; 95% CI: 0.59-0.77)
    • Deep Sedation/Coma (Adjusted Odds Ratio: 0.69; 95% CI: 0.60-0.80; Adjusted Odds Ratio: 0.33; 95% CI: 0.28-0.37)
    • Ketamine Administration (Adjusted Odds Ratio: 0.34; 95% CI: 0.16-0.71; Adjusted Odds Ratio: 0.40; 95% CI: 0.18-0.88)
• Academic Tertiary Hospital Retrospective Cohort Study of Ketamine Use for Adult Medical/Cardiac Intensive Care Unit Patients Who Required Mechanical Ventilation (PLoS One. 2022) [MEDLINE]: n = 564
  • Median Continuous Infusion Dose was 0.11 (0.06-0.23) mcg/kg/h
  • Of All Patients, 83.2% Received Continuous Ketamine Infusion Concomitant with Analgosedation
  • Blood Pressure and Vasopressor Inotropic Scores Did Not Change After Continuous Ketamine Infusion
  • Heart Rate Decreased Significantly from 106.9 bpm (91.4-120.9) at 8 hrs Before Ketamine Initiation to 99.8 bpm (83.9-114.4) at 24 hrs After Ketamine Initiation
  • Respiratory Rate Decreased from 21.7 breaths/min (18.6-25.4) at 8 hrs Before Ketamine Initiation to 20.1 breaths/min (17.0-23.0) at 24 hrs After Ketamine Initiation
  • Overall Opiate Usage was Significantly Decreased from 3.0 (0.0-6.0) mcg/kg/h as Fentanyl Equivalent Dose at 8 hrs Before Ketamine Initiation to 1.0 (0.0-4.1) mcg/kg/h as Fentanyl Equivalent Dose at 24 hrs After Ketamine Initiation
  • However, the Use of Sedatives and Antipsychotic Medications Did Not Decrease with Ketamine Administration
  • Ketamine Did Not Increase the Incidence of Delirium within 24 hrs After Ketamine Infusion

Sedation in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)

Clinical Efficacy

• Systematic Review of Sedation in Traumatic Brain Injury (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 Traumatic Brain Injury (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 (TBI) (Neurocrit Care, 2014) [MEDLINE]
  • Ketamine Did Not Increase Intracranial Pressure in Traumatic Brain Injury (TBI) and May Decrease it in Selected Cases (Oxford Level 2b, Grade C Evidence)

Ketamine is a Non-Barbiturate Dissociative Anesthetic

• Analgesia: this property is unique among the major intravenous sedatives
• Bronchodilation: likely due to a vagolytic effect (Chest, 2022) [MEDLINE]
• 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

Intravenous (IV) Use for Intensive Care Unit (ICU) Sedation

• Dose (Loading Dose for ICU Sedation): 0.1-0.5 mg/kg
• Dose (Intravenous Infusion for 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

Intravenous (IV) Use for General Anesthesia Induction

• Dose (General Anesthesia Induction): 0.5-2 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
    • Antisialagogue: decreases salivation
      • Glycopyrrolate (Robinul) (see Glycopyrrolate)
    • Benzodiazepine (Midazolam, etc) (see xxxx): decreases risk of emergence reaction

Intramuscular (IM) Use for General Anesthesia Induction

• Dose (General Anesthesia Induction): 9-13 mg/kg
  • Onset of Anesthesia: within 3-4 min
  • Duration of Anesthetic Effect: 12-25 min

Dose Adjustment

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

Use in Pregnancy (see Pregnancy)

• xxXXXXXxx

Use During Breast Feeding

• 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

Allergic Adverse Effects

Anaphylaxis (see Anaphylaxis)

• Epidemiology
  • Anaphylaxis Has Been Reported with Ketamine Use

Cardiovascular Adverse Effects

Arrhythmias

• Epidemiology
  • Arrhythmias May Occur in Some Cases

Enhanced Pressor Response

• Clinical
  • Enhanced Pressor Response May Occur with Rapid Ketamine Administration

Hypertension (see Hypertension)

• Clinical
  • Hypertension Occurs Shortly After Ketamine Injection
  • Blood Pressure Generally Returns to Normal within 15 min After Ketamine Injection

Hypotension (see Hypotension)

• Epidemiology
  • Hypotension May Occur in Some Cases

Sinus Bradycardia (see Sinus Bradycardia)

• Epidemiology
  • Sinus Bradycardia May Occur in Some Cases

Gastrointestinal Adverse Effetcs

Anorexia (see Anorexia)

• Epidemiology
  • XXXXXXX
• Clinical
  • Anorexia is Usually Not Severe or Prolonged

Nausea/Vomiting (see Nausea and Vomiting)

• Epidemiology
  • XXXXXXX
• Clinical
  • Nausea/Vomiting is Usually Not Severe or Prolonged

Sialorrhea (Hypersalivation) (see Sialorrhea)

• Epidemiology
  • Common
• Management
  • Glycopyrrolate (Robinul) (see Glycopyrrolate): may be used to decrease secretions

Neurologic Adverse Effects

Diplopia (see Diplopia)

• Epidemiology
  • Diplopia May Occur

Emergence Reaction

• Epidemiology
  • Incidence
    • Emergence Reaction Occurs in 12% of Cases
    • Emergence Reaction is Less Common in Elderly (>65 y/o)
    • Emergence Reaction is Less Common with Intramuscular Administration
  • Duration: few hrs
    • Although Cases Have Been Reported with Recurrence Up to 24 hrs Later Postoperatively
• Clinical
  • Agitation (see Agitation)
  • Delirium/Confusion (see Delirium)
  • Dream-Like State
  • Hallucination (see 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)

Fasciculations

• Epidemiology
  • Fasciculations May Occur

Hyporeflexia (see Hyporeflexia)

• Epidemiology
  • Hyporeflexia May Occur

Increased Cerebrospinal Fluid (CSF) Pressure

• Clinical
  • Use Ketamine with Caution in Setting of Increased Cerebrospinal Fluid Pressure

Increased Intraocular Pressure

• Epidemiology
  • Increased Intraocular Pressure May Occur

Nystagmus (see Nystagmus)

• Epidemiology
  • Nystagmus May Occur

Tonic-Clonic Movements (Seizure-Like Movements)

• Epidemiology
  • Tonic-Clonic Movements May Occur
• Physiology
  • Due to Enhanced Muscle Tone

Pulmonary Adverse Effects

Respiratory Depression/Respiratory Failure (see Respiratory Failure)

• Epidemiology
  • Respiratory Depression/Respiratory Failure May Occur with Rapid Ketamine Administration or Overdosage

Laryngospasm (see Laryngospasm)

• Epidemiology
  • Laryngospasm May Occur

Renal Adverse Effects

Irritative/Inflammatory Urinary Tract and Bladder Symptoms

• Epidemiology
  • Irritative/Inflammatory Urinary Tract and Bladder Symptoms May Occur with Chronic Ketamine Abuse
• Clinical
  • Cystitis

Other Adverse Effects

Local Pain and Exanthema at Injection Site

• Epidemiology
  • Local Pain and Exanthema at Injection Site Has Been Reported

Transient Erythema/Morbilliform Rash

• Epidemiology
  • Transient Erythema/Morbilliform Rash Has Been Reported