Journal Club Podcast #28: April 2016
A brief discussion in the use of ketamine for pain control in the ED, weighing both the evidence and the anecdote...
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Article 1: Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. Answer Key.
Article 2: Galinski M, Dolveck F, Combes X, Limoges V, Smaïl N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. Answer Key.
Article 3: Majidinejad S, Esmailian M, Emadi M. Comparison of Intravenous Ketamine with Morphine in Pain Relief of Long Bones Fractures: a Double Blind Randomized Clinical Trial. Emerg (Tehran). 2014 Spring;2(2):77-80. Answer Key.
Article 4: Motov S, Rockoff B, Cohen V, et al. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2015 Sep;66(3):222-229.e1. Answer Key.
It's two o'clock in the afternoon during a typical weekend TCC shift, when you get a page that a triage patient is coming to room 4. You look at the chart and see that it's a 45-year-old man who was riding his horse and got bucked off, landing on his left arm in an awkward position. The triage nurse has noted a deformity to the upper arm with intact pulses and sensation distally. You notice that the triage doctor has ordered IV lidocaine for the man, which you find most confusing.
Your evaluation of the patient confirms much of the triage note. He has swelling and bruising to the left upper arm, concerning for a mid-shaft humerus fracture. He is neurovascularly intact and has stable vital signs. He denies any past medical history and has no allergies.
You decide to ask your attending about the IV lidocaine, which the patient says hasn't really helped his pain, but Dr. Cohn just shakes his head and sighs. You then ask about giving the patient low-dose ketamine for his pain, having recently listened to a podcast on the subject (SGEM#130: Low Dose Ketamine for Acute Pain Control in the Emergency Department). Dr. Cohn laughs in your face and turns his back on you. Later, he comes back and explains that while he admittedly hasn't read the literature on the subject, he isn't a big fan of replacing one addictive substance with another, especially one that's less familiar to him.
Curious about what the evidence actually shows, and wanting to be prepared to look smart in front of your pompous attending, you decide to search the literature and see what the evidence actually shows...
Population: Adult patients in the ED with acute pain
Intervention: IV ketamine
Comparison: Usual care with IV opiate analgesia
Outcome: Pain control, adverse events (hypoxia, respiratory depression, dysphoria, etc.), patient satisfaction, ED length of stay
PubMed was searched using the terms “ketamine AND analgesia AND emergency”, resulting in 169 articles (http://tinyurl.com/znjvzc4). The titles of these were searched, and the four most relevant articles chosen.
Ketamine has been used as a dissociative agent in the emergency department for procedural sedation for years, going so far as to warrant its own clinical practice guideline from ACEP. With known analgesic properties, ketamine has well-demonstrated utility in the management of perioperative pain, which has led some to suggest a potential use for pain management in the ED.
The literature on this topic is still somewhat limited, primarily comprising small studies that compare morphine to ketamine alone, or to combination therapy with morphine and ketamine. One of the earliest of these studies (Galinski 2007) enrolled patients with “severe acute pain” following trauma, being transported by mobile intensive care units staffed by physicians. Patients received either morphine and ketamine, or morphine alone. They demonstrated similar reductions in pain scores at 30 minutes with higher morphine consumption (0.2 mg/kg vs. 0.15 mg/kg) among those not receiving ketamine. Notably, the incidence of neuropsychological adverse effects was much higher among those receiving ketamine (36% vs. 3%).
A study out of the Rhode Island Hospital ED (Beaudoin 2014) compared the use of morphine alone to the use of morphine with two different doses of ketamine (0.15 mg/kg and 0.3 mg/kg) among patients with moderate to severe acute pain. Twenty patients were enrolled in each group, and they found that pain reduction was better among those receiving ketamine, with no difference in pain reduction between the two ketamine groups. Oddly, the amount of rescue analgesia provided was not different among the three groups, suggesting that perhaps those patients receiving only morphine were inadequately treated, which may account for the differences observed in the primary outcome, rather than a benefit due to ketamine. Length of stay was over half an hour longer in the two ketamine groups than it was among those receiving morphine only.
A third study, conducted in Isfahan, Iran (Majidinejad 2014), enrolled 126 patients with long bone fractures, randomizing them to receive either morphine or ketamine (here at a rather high dose of 0.5 mg/kg). They looked at pain control just 10 minutes after drug injection, and found similar rates of pain control, with a successful decrease in pain severity seen in nearly all patients in both groups at 10 minutes (93.7% of patients in the ketamine group and 96.8% in the morphine group). Almost 10% of patients receiving ketamine developed emergence phenomena, while no adverse effects were seen in those receiving morphine. This study did a poor job reporting data according to Consort guidelines, making interpretation of the results difficult.
The finally study out of Maimonides Medical Center in Brooklyn, NY (Motov 2015) enrolled 90 patients with acute abdominal, flank, back, or musculoskeletal pain, and randomized them to receive either morphine or ketamine (0.3 mg/kg). They found no difference in the primary outcome, reduction in pain at 30 minutes, but did demonstrate a significantly higher need for rescue analgesia with IV fentanyl at 120 minutes.
While these studies certainly confirm the analgesic effects of IV ketamine in patients with acute pain, they do not necessarily demonstrate a benefit over typical IV opiate administration. Instead, there seems to be a higher incidence of adverse effects (primarily dysphoria), increased ED length of stay, and a potentially greater need for rescue analgesia, likely owing to the relatively short duration of action of ketamine. Unfortunately, patients for whom we would typically consider ketamine as an alternative to opiates due to concerns regarding respiratory or cardiac depressive effects (i.e. the elderly, those with pulmonary compromise, or those with unstable vital signs) were understandably excluded from all of these studies. While it seems biologically plausible that ketamine would provide adequate analgesia in such patients with a reduction in the risk of major adverse events, there is currently no data in the literature to directly support this (external validity).