SGEM#457: Inhale – Nebulized or IV Ketamine for Acute Pain?

Date: October 7, 2024 Reference: Nguyen et al. Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial. Annals of EM 2024. Guest Skeptic: Dr. Brendan Freeman is an emergency medicine physician, assistant professor of emergency medicine, and medical education fellow at Staten Island University Hospital. He completed his residency training at New York Presbyterian Brooklyn Methodist after graduating from medical school at Touro University College of Osteopathic Medicine in California. Case: You’re working your usual day shift in the emergency department (ED) from 9 am to 5 pm on a Tuesday. The next patient you pick up is a 38-year-old male with a history of kidney stones, presenting with severe flank pain radiating to the groin. He has a history of difficult intravenous (IV) access, is hemodynamically stable, and has no signs of infection. His allergies to acetaminophen, non-steroidal anti-inflammatories (NSAIDs), and opioids limit your pain management options. A bedside sonogram shows no significant hydronephrosis. You’re considering ketamine for pain relief but wonder if you should choose IV sub-dissociative ketamine or nebulized ketamine? Background: Ketamine has long been recognized as a versatile drug in emergency medicine, particularly for its role in analgesia and procedural sedation. Initially developed as an anesthetic in the 1960s, ketamine’s unique pharmacological profile makes it particularly suitable for acute care settings. It is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, which induces dissociative anesthesia, meaning patients experience analgesia and amnesia without the loss of consciousness typically associated with other anesthetics​​. In recent years, ketamine has gained popularity in the ED, particularly for treating acute pain. It is used at lower doses than those required for anesthesia (0.1–0.3 mg/kg IV) and is called “low-dose” or sub-dissociative ketamine (SDK). These lower doses of ketamine effectively manage pain without producing full dissociation, reducing the likelihood of severe adverse effects​​. This ability to provide analgesia with minimal respiratory depression and hypotension makes ketamine an attractive alternative to opioids, particularly in patients for whom opioid use is problematic​​. Ketamine’s administration is flexible, with several routes available including IV, intranasal (IN), and more recently, nebulized forms. Each method has its advantages, and ongoing research continues to refine the efficacy and safety of these delivery methods in acute pain management in the ED​​. Prior research by this same group has shown ketamine breath-actuated nebulizer (K-BAN) has effective analgesic properties at three different doses 0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg up to 120 minutes. However, no one has compared K-BAN analgesic efficacy to IV-SDK though. Clinical Question: Which ketamine regimen is superior for treating moderate to severe acute pain in the emergency department, 0.75 mg/kg nebulized or 0.3 mg/kg intravenously? Reference: Nguyen et al. Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial. Annals of EM 2024. Population: Adults aged 18 and older presenting to the ED with acute pain numerical rating scale (NRS) pain score of ≥5​ Exclusions: Patients with altered mental status, respiratory distress, hypotension, or known allergy to ketamine​. Intervention: Nebulized ketamine at 0.75 mg/kg via breath-actuated nebulizer (K-BAN) plus IV saline infusion Comparison: IV sub-dissociative dose ketamine (IV-SDK) at 0.3 mg/kg plus nebulized saline Outcome: Primary Outcome: Reduction in pain scores on ...