Nurse considerations for administering low dose ketamine

If you've followed conference proceedings, research journals, or social media you'll know that the evidence for ketamine as a pain control agent is growing. Given the opioid epidemic, there’s been push in the ED for opioid sparing strategies. The result is nurses are giving ketamine more often, and need to know the pharmacodynamics, safety profile, and dosing considerations for administering low dose (sub-dissociative) ketamine.

Ketamine is well understood to be a N-Methyl-D-aspartate (NMDA) receptor antagonist, this action exhibits pain control at the level of the dorsal ganglion as well as the Central Nervous System. In addition to the direct mediation of pain through NMDA receptors (making it well suited for acute pain control), there is emerging evidence that ketamine may also provide analgesia through indirect mechanisms, also making well suited for chronic pain management. From an ED perspective the multi-modal activity of ketamine make it an attractive opioid sparing alternative for acute pain control (Lacobucci, Visnjevac, Pourafkari & Nader, 2017).

Ketamine has been assessed as an ED pain control agent in a number of studies. A 2018 systematic review of these studies found ketamine no worse (non-inferior) to opioids for pain control (relative reduction = 0.42, 95%,  confidence interval = -0.70 to 1.54), and may offer opioid sparing effects (Karlow et al., 2018). While Ketamine seems to offer similar benefits in the realm of pain control there are some concerns about side effects.Ketamine can be used in a dose dependent manner to illicit effects that range from analgesia to general anesthesia. General anesthetic doses will tend to range from 1-4.5mg/kg IV; with the average required dose being about 2mg/kg (Truven Health Analytics, 2015). By comparison non-dissociative doses have been defined as doses ranging from 0.1-0.3mg/kg (Motov et al., 2015); to as high as 0.5mg/kg (Karlow et al., 2015); approximately 1/10 of the dose required for sedation. My experience however is that doses will be ordered in the range of 0.1-0.3mg/kg. The bulk of the literature has examined low dose ketamine given IV direct over 3-5min, as opposed to IV intermittent, which may explain the side effect profile noted in the literature.

The side effects of Ketamine can range from mild (dizziness/nausea) to moderate (hallucinations/disorientation), to severe (respiratory depression/dysrhythmias). Although it hasn't been well explicated in the literature there is an expected dose dependent relationship on side effects. There is also evidence that rate of administration may influence side effects. A double dummy RCT of direct vs. intermittent IV low dose ketamine suggests that diluting doses in 100ml and slowly infusing over 15 minutes may reduce side effects (Motov et al., 2017).

From a nursing perspective we should appreciate that:

1. Ketamine, as monotherapy or adjunct, is viable for pain control;
2. Patients receiving low dose ketamine have a potential for complications ranging from agitation to respiratory depression and require some form of monitoring (at a minimum intermittent BP plus continuous SpO2);
3. Diluting and slowly administering ketamine (over 15minutes) reduces side effects while maintaining analgesia;
4. Precautions and discharge planning for patients who have received ketamine should be the same as those who have received opioids (no driving, etc).   

References

Karlow, N., Schlaepfer, C. H., Stoll, C. R., Doering, M., Carpenter, C. R., Colditz, G. A., ... & Schwarz, E. S. (2018). A Systematic Review and Meta‐analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department. Academic Emergency Medicine.

Iacobucci, G. J., Visnjevac, O., Pourafkari, L., & Nader, N. D. (2017). Ketamine: An Update on Cellular and Subcellular Mechanisms with Implications for Clinical Practice. Pain physician, 20(2), E285-E301.

Motov, S., Rockoff, B., Cohen, V., Pushkar, I., Likourezos, A., McKay, C., ... & Fromm, C. (2015). Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: a randomized controlled trial. Annals of emergency medicine, 66(3), 222-229.

Motov, S., Mai, M., Pushkar, I., Likourezos, A., Drapkin, J., Yasavolian, M., ... & Fromm, C. (2017). A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED. The American journal of emergency medicine, 35(8), 1095-1100.

Truven Health Analytics. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 907804, Ketamine; [updated 2015 Aug 27, cited 2 Oct 2018]; Retrieved from http://www.dynamed.com.ahs.idm.oclc.org/login.aspx?direct=true&site=DynaMed&id=907804.