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Introduction

  1. Pharmacology. Ketamine, an arylcylohexylamine dissociative anesthetic agent similar to phencyclidine (PCP), is widely used as an induction agent for rapid sequence intubation (RSI) and in pediatric procedural sedation. It is a racemic mixture, and the S isomer is more potent with a shorter duration of action. The analgesic and dissociative effects are mediated through N-methyl-d-aspartate (NMDA) receptor antagonism. Sympathomimetic effects are mediated through inhibition of reuptake of dopamine, norepinephrine, and serotonin in the brain; these effects may contribute to its cardiovascular side effects as well as potential therapeutic benefit for patients with depression. Additionally, ketamine binds to mu-, delta-, sigma-, and kappa-opioid receptors contributing to its analgesic effects. Other pharmacologic effects mediated via epigenetic modulation and expression of microRNA, inflammatory mediators, and nitric oxide synthase may mediate its sustained therapeutic effects for the management of psychiatric and mood disorders, anti-inflammatory actions, and treatment of status asthmaticus. Ketamine is well absorbed via the intramuscular route and is metabolized in the liver to an active metabolite norketamine. It has poor oral (16%) and variable intranasal (25-50%) bioavailability. The relatively high lipid solubility and low protein binding facilitate rapid uptake into the brain with a rapid onset of action, which may occur 30 seconds after intravenous administration and 3 minutes after intramuscular administration and lasting up to 10 and 25 minutes, respectively. The serum half-life is 2-3 hours.
  2. Indications
    1. Induction agent for rapid sequence intubation (RSI). Ketamine may be used to facilitate sedation for endotracheal intubation, especially in trauma patients and hypotensive patients.
    2. Procedural sedation. Ketamine can produce sedation and amnesia with minimal respiratory depression.
    3. Analgesia. Low-dose ketamine has been used alone or with opioids for analgesia in emergency department, postoperative, and cancer-associated pain.
    4. Agitation. Ketamine may be used as a sedating agent for agitated delirium, either alone or in combination with midazolam.
    5. Other potential indications include postanesthetic shivering, complex regional pain syndrome, status asthmaticus, depression and mood disorders, suicidal ideation, refractory status epilepticus, and opioid and alcohol withdrawal.
  3. Contraindications
    1. Known hypersensitivity to the drug.
    2. Do not use in infants younger than 3 months due to propensity for airway adverse events.
    3. Use with caution in patients with high blood pressure or when elevation of blood pressure is unwanted.
    4. Use with caution if ketamine-induced increased intraocular pressure could cause acute complications (eg, in a patient with a ruptured orbit).
  4. Adverse effects
    1. Emergence reactions (dreamlike states, vivid imagery, hallucinations) or recovery agitation has been reported with variable incidence, ranging from 0% to 36%. Premedication with intravenous midazolam minimizes this risk.
    2. Laryngotracheal spasm is rare, occurring in 0.3% of children. The effect is temporary and usually responsive to bag-valve-mask ventilation.
    3. Transient apnea or respiratory depression is also rare, occurring in 0.8% of children and less so in adults. It is more common with rapid IV infusions and prevented by slow IV administration over at least 60 seconds.
    4. Hypertension; hypersalivation; emesis (7-26%); muscular hypertonicity; random, purposeless movements; clonus; and hiccupping may occur.
    5. Ketamine is a potential drug of abuse. Long-term users may develop cystitis or bladder problems and a decline in mental health (cognitive impairments, psychotomimetic effects).
    6. Use in pregnancy. This drug has not been categorized by the FDA. Therefore, safe use in pregnancy has not been established.
  5. Drug or laboratory interactions
    1. Ketamine will potentiate the CNS-depressant effects of opioids, ethanol, benzodiazepines, sedative-hypnotics, and other sedating drugs.
    2. Although structurally similar to phencyclidine (PCP), it does not cross-react with any of the commercially available urine drug-testing assays.
  6. Dosage and method of administration
    1. Induction agent for RSI. Give 2 mg/kg IV or 4-5 mg/kg IM along with a neuromuscular blocking agent. The IV route is preferable in patients requiring RSI.
    2. Procedural sedation. Give 4-5 mg/kg IM or 1.5-2 mg/kg IV in children. Give 4 mg/kg IM or 1-2 mg/kg IV in adults. Administer intravenous doses over 30-60 seconds since more rapid administration may result in respiratory depression or apnea. A single loading dose is preferred to initiating the sedation with titration. If sedation is inadequate after 5-10 minutes, additional half to full doses may be given. Intravenous midazolam (0.03 mg/kg) may minimize the risk of emergence reactions in adults.
    3. Analgesia. Give 0.1-0.6 mg/kg IV alone or as an adjunct to opioid analgesia.
    4. Agitation. Give 4 mg/kg IM or 1-2 mg/kg IV to agitated, combative adults. Initiate cardiopulmonary monitoring after ketamine administration. If sedation is inadequate after 5-10 minutes, additional half doses may be given.