Ketamine is a well-established drug in anesthesia literature as it has been available for over 50 years. Ketamine is a NMDA and glutamate receptor antagonist that has multiple pharmacologic mechanisms and characteristics making it an ideal agent for a growing number of indications.1 Common uses include treatment of acute and/or chronic pain, rapid sequence intubation, procedural sedation, and acute agitation. Ketamine exhibits different properties when varying weight-based doses are administered. Doses range from 0.1 to 4.5 mg/kg depending on the indication and can be administered intravenously, intranasally, or intramuscularly.
Ketamine possesses analgesic, amnesic and anesthetic properties.2-3 Low dose ketamine has been shown to be a safe and effective option for acute and chronic pain.4 Administered at low, or subdissociative doses (0.1-0.3 mg/kg IV push or IVPB), it retains potent analgesic and some amnesic properties without inducing full dissociation. These patients may become partially dissociated, while experiencing some awareness, but still not fully connected with the outside world. Studies have shown a connection with ketamine-induced side effects, such as dizziness and the feeling of unreality, with rapid rates of administration. Motov et al. compared adverse effects and efficacy of low dose ketamine (0.3 mg/kg) administered either IV push (over 5 min) or short infusion (over 15 min) for acute pain in the ED. They showed ketamine given as a short infusion may produce less unwanted neurological side effects.5 Since publication of this study we have conducted an internal MUE demonstrating no difference in clinically relevant neurological adverse effects when administered IV push (over < 10 mg/min) in the emergency department. Ketamine comes in a 50mg/5mL syringe that can be used for patients receiving the medication IV push. Ketamine may be administered intranasal at 0.5-1 mg/kg and intramuscularly at 0.2-0.6 mg/kg for acute pain as well. For intranasal (IN) or intramuscular (IM) administration the most concentrated formulation available (500mg/5mL) should be utilized to ensure optimal absorption.
Ketamine is a useful agent for procedural sedation due to its analgesic and anesthetic effects while maintaining hemodynamic and respiratory status. The adult dose is 0.5 – 1.0 mg/kg IV push and may be repeated based on patient response and/or duration of the procedure. The dose for pediatrics is 1.0 – 2.0 mg/kg IV or 4 mg/kg IM. In pediatrics, ondansetron may be given at 0.15 mg/kg IV or PO to prevent nausea or vomiting.
When used for rapid sequence intubation ketamine produces a unique dissociative state where the patient appears awake, but unconscious and detached from their current surroundings. Ketamine can be used either alone, or in conjunction with other sedative agents. When used alone the dose is 1 to 4.5 mg/kg IV. In conjunction with other sedatives, such as midazolam, a lower dose of 0.5-2 mg/kg IV can be used. If ketamine was to be continued for continuous sedation, the starting rate is 0.5 to 1mg/kg/hr with titration by 0.5 mg/kg/hr every 10 minutes until at goal RASS with a maximum recommended dose of 6 mg/kg/hr.
Ketamine is also effective in managing the acutely agitated and violent patient due to its dissociative properties and relatively safe side effect profile. 6 For acute agitation the dose is 1 mg/kg IV or 4 mg/kg IM. For IM administration it is important to use the 500 mg/5 mL to limit administration volume. Ketamine dosing for acute agitation resembles dosing for conscious sedation. Like other sedatives, ketamine may induce apnea or respiratory depression requiring intubation. Physicians should be present during and after administration at these doses to monitor and manage the airway if needed.
Although ketamine is known for its safety profile, it does have potential unwanted and serious adverse effects, some of which have been mentioned previously. Potential adverse effects of ketamine include transient laryngospasm, transient apnea or respiratory depression, hypersalivation, emesis and emergence reaction.7-8 Laryngospasm and respiratory depression are more common when administered intravenously, but may still occur with IM administration. When administering ketamine at a dissociative dose, physicians should be present to monitor airway and rapidly manage if needed. If laryngospasm occurs the physician may use the jaw-thrust maneuver to resolve the laryngospasm. When successful this adverse event typically resolves after a few breaths. Although rare, hypersalivation may also occur after administration. Hypersalivation may increase the risk of aspiration in a patient receiving dissociative doses of ketamine. Patients may require elevating the head of bed, suctioning, or pharmacological treatment. Anticholinergic agents such as atropine or glycopyrrolate should not be used for routine prophylaxis, but may be used for clinically relevant hypersalivation.7 If required, atropine 0.5 mg IV or glycopyrrolate 0.5 mcg/kg (max 250 mcg) IV/IM may be administered. Vomiting may occur in 5-15% of adults that receive ketamine.9 Patients may be treated with an antiemetic such as ondansetron. When ketamine is given rapid IV push or at large doses, there is increased risk of neurological adverse effects. The adverse reaction is typically short lived and may be minimized by administering slow IV push (~5 minutes). Risk factors for neurological adverse effects include rapid administration and larger doses of ketamine. Before administering for pain or procedural sedation, physicians and nurses should discuss the potential neurological adverse effects associated with ketamine with the patient. Positive thoughts prior to sedation and maintaining a quiet area during recovery may decrease the incidence of emergence reaction or hallucinations. The patient should be assessed for delirium, excitation and physical combativeness after administering ketamine for any indication. If this occurs, benzodiazepines have been shown to rapidly diminish the excited delirium reaction.6
Due to the varying concentrations of ketamine commercially available; 10mg/mL, 50mg/mL, and 100mg/mL, additional safety measures should be put in place to prevent dosing errors. One option to consider is limiting the number of different concentrations available. Our institution only carries 10mg/mL (20mL vial for intubations and conscious sedation; 5mL prefilled syringe for analgesia) and the concentrated 100mg/mL (5mL vial for IM and IN administration). The 50mg/mL concentration has been eliminated and all instances where this was used and stocked have been converted to the 10mg/mL concentration. Our institution also shrink-wraps the concentrated 500mg/5mL vials with a red high-alert medication label to bring attention to the concentrated product. With proper education and implementation of safety measures, ketamine can be used safely in your emergency department.
One additional consideration is whether or not institutional policies and procedures preclude nurses from administering ketamine. Many institutions have outdated policies, limiting ketamine’s use to providers capable of providing advanced airway support. Policies may not take into consideration the use of low-dose ketamine for pain in which administration would likely fall within a nurses scope of practice. A review of institutional policies, followed by multi-disciplinary education may be necessary to ensure safe and effective use of ketamine for all indications. All members of the interdisciplinary healthcare team should become familiar with ketamine’s dosing and administration and be able to recognize and manage potential side effects as usage continues to increase.
Ketamine’s versatility in treatment and minimal side effect profile make it a suitable choice for the management of multiple indications. It has become the sedative of choice for many painful procedures, allows for avoidance or reduced doses of opioids in the management of acute and chronic pain, and is an effective second line option for agitation and excited delirium. As providers become more familiar with its role, utilization will likely continue to increase.
Michael Thiefault PharmD
- Sleigh, Jamie et al. Ketamine – More mechanisms of action than just NMDA blockade. Trends in Anaesthesia and Critical Care , Volume 4 , Issue 2 , 76 – 81
- Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia, Essays and Researches. 2014;8(3):283-290. doi:10.4103/0259-1162.143110.
- Kolawole IK. Ketamine hydrochloride: A useful but frequently misused drug. Niger J Surg Res. 2001;3:118–25
- Pourmand, A et al. Low dose ketamine use in the emergency department, a new direction in pain management. The American Journal of Emergency Medicine , Volume 35 , Issue 6 , 918 – 921
- Motov S, Mai M, Pushkar I, et al. A prospective randomized, double-dummy trial comparing intravenous push dose of low dose ketamine to short infusion of low dose ketamine for treatment of moderate to severe pain in the emergency department.Am J Emerg Med. 2017 Mar 3. Epub ahead of print. PMID 28283340
- Le Cong M, Gynther B, Hunter E, et al. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012 Apr;29(4):335-7. Epub 2011 May 12
- Green, Steven M. et al. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update Annals of Emergency Medicine , Volume 57 , Issue 5 , 449 – 461
- Niesters, M., Martini, C. and Dahan, A. (2014), Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol, 77: 357–367. doi:10.1111/bcp.12094
- Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008;26: 985-1028.