EBM: Sub-dissociative dose of Ketamine for Pain Control in the Emergency Department

Pain and fear are the two most common reasons why patients come to the Emergency Room on any given day. Medication options when controlling acute pain are varied and nuanced with many multimodal options of analgesics. Consider if sub-dissociative doses of ketamine may be right for the patient in front of you on your next shift.

Background

70-80% of patient presentations to the ED involve acute pain. While there are many analgesic medications available, there are known side effects from our commonly used medications such as opiates or NSAIDs. Studies have consistently shown equal efficacy with opiates and ketamine for pain control.

Ketamine was first synthesized in the early 1960s as an alternative to PCP and was used less commonly for sedation with the advent of propofol in the late 1980s. Initial concerns with using ketamine included potential for abuse, common with most analgesics, and, now disproven, perpetuated concern for increased intracranial pressure (ICP) which led to its decreased use.

 

Pharmacokinetics

Ketamine works as an antagonist of the NMDA receptor by blocking glutamate. It can produce analgesia and modulates central sensitization, hyperalgesia and opiate tolerance. It has first pass hepatic metabolism and is ultimately excreted via urine.

 

Dosing

Ketamine dosing is variable based on route and goal of effect. Ketamine can be given intravenous, intramuscular, intranasal, and orally. Studies reviewed for the purpose of this literature review primarily focused on sub-dissociative dose ketamine delivered via intravenous route.

 Dosing appropriate for SDK analgesia has been studied between 0.1-0.3mg/kg. It is notable, however, that most studies did not include patients with a BMI > 40 or weight > 115kg, limiting the appropriate data behind using ketamine as analgesia for patients who weight greater than these cut offs.

This also begs the question if this “weight-based dosing” is based on ideal body weight, actual body weight or adjusted body weight. Sedative doses of ketamine have been recommended to be given as 1-2mg/kg of ideal body weight due to the lipophilicity of ketamine and the clearance of ketamine, however no consensus is present for sub-dissociate ketamine. In the setting of this and until further studies are completed using patient populations with morbid obesity and dose adjustments, it is best to consider using the lower end of your dosing range using actual body weight and dosing this at 0.1mg/kg, to minimize risk of unwanted side effects such as perception of unreality.

Administration

Intravenous administration of sub-dissociative ketamine can be done one of two ways: via rapid push versus short infusion (commonly referred to as “piggyback”) over 15 minutes. In 2017, a study by Motov et al was conducted as a prospective, double blinded RCT comparing 0.3mg/kg intravenous push dose versus 0.3mg/kg piggyback over 15 minutes for treatment of moderate to severe pain in the ED. Results of this showed no statistical significance in need for rescue medications or change in vital signs. Notably, however, the overall rate of the feeling of unreality was 92% in the patients who received the push versus 54% who received the infusion.

IV piggyback is commonly available from hospital pharmacy and requires a pharmacist to reconstitute this medication which often delays administration relative to more often readily available IV push ketamine. While many considerations are important, most notably time to pain medication for patients with acute pain, this trend seen in Motov et al’s study suggests using the piggyback formulation when appropriate to reduce risk of unwanted side effects.

 

 Proposed Guideline

 AUTHORED BY: SHAGUN BERRY, DO (PGY3)

FACULTY EDITING BY: NIK SEKOULOPOULOS, MD

References

  1. Altirkistani BA, Ashqar AA, Bahathiq DM, et al. The Effectiveness of Ketamine Versus Opioids in Patients With Acute Pain in the Emergency Department: A Systematic Review and Meta-Analysis. Cureus. 2023; 15(3): e36250.

  2. Parvizrad R, Nikfar S. Low‐dose ketamine as an analgesic agent in the emergency department: Efficacy and safety. J Family Med Prim Care. 2022;11:6464‐71.

  3. Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium. Crit Care. 2020; 24: 315.

  4. Drayna PC, Estrada C, Wang W, Saville BR, Arnold DH. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emerg Med. 2012; 30(7): 1215-1218.

  5. American College of Emergency Physicians. Sub-dissociative dose ketamine for analgesia. Policy Statement. Approved October 2017. https://www.acep.org/patient-care/policy-statements/sub-dissociative-dose-ketamine-for-analgesia.

  6. Fjenbo Galili, et al. Subanesthetic single-dose ketamine as an adjunct to opioid analgesics for acute pain management in the Emergency Department: A systemiatic review and meta-analysis. BMJ Open. 2023; 13(3).

  7. Schwenk ES, Viscusi ER, Buvanendran A, et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine. 2018;43:456-466.

  8. Rezaie S. (2019, February 7). Low dose ketamine for acute pain in the ED: IV push vs short infusion?. REBELEM-Emergency Medicine Blog. https://rebelem.com/low-dose-ketamine-for-acute-pain-in-the-ed-iv-push-vs-short-infusion/

  9. Moradi M. et al. Sub dissociative dose of ketamine with haloperidol versus fentanyl on pain reduction n patients with acute pain in the emergency department; a randomized clinical trial. Am J Emerg Med. 2022; 54:165-171.

  10. Alshahrani MS, AlSulaibikh AH, ElTahan MR, et al. Ketamine administration for acute painful sickle cell crisis: A randomized controlled trial. Acad Emerg Med. 2022;29:150–158.

  11. Lovett S, Reed T, Riggs R, et al. A randomized, noninferiority, controlled trial of two doses of intravenous subdissociative ketamine for analgesia in the emergency department. Acad Emerg Med. 2021;28:647–654.

  12. Balzer N, McLeod SL, Walsh C, Grewel K. Low‐dose ketamine for acute pain control in the Emergency Department: A systematic review and meta‐analysis. Acad Emerg Med. 2021;28(4), 444–454.

  13. Esfahani H, Khazaeipour Z, Safaie A, Aghili SM. Ketamine Sub-Dissociative Dose Vs. Morphine Sulfate for Acute Pain Control in Patients with Isolated Limb Injuries in the Emergency Department: A Randomized, Double-blind, Clinical Trial. Bull Emerg Trauma. 2021; 9(2):73-79.

  14. Motov S, Mai M, Pushkar I, et al. 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. Am J Emerg Med. 2017 Aug;35(8):1095-1100.

EBMLauren McCaffertyebm, evidence based, ketamine, pain, subdissociative