As the opioid epidemic escalated, emergency departments faced pressure to reduce opioid prescribing for acute pain. Studies showed that up to 50% of ED visits involved pain complaints, and opioids had become first-line therapy for many conditions. Evidence began accumulating that non-opioid alternatives could provide equivalent analgesia for common ED pain presentations.

Proof

Landmark RCTs and pivotal trials that established the evidence base

Motov (2015) demonstrated that subdissociative-dose ketamine (0.3 mg/kg IV) provided analgesia comparable to morphine in 90 ED patients with acute pain. Bijur (2017) showed no difference in pain reduction between three doses of ketorolac (10mg, 15mg, 30mg) in 240 patients, challenging the practice of using higher doses. Chang (2017) conducted a landmark RCT of 416 patients with acute extremity pain showing that oral non-opioid combinations (ibuprofen/acetaminophen) were non-inferior to opioid combinations for pain relief.

Motov 20152015Landmark

Pain reduction comparable between subdissociative ketamine 0.3 mg/kg and morphine 0.1 mg/kg at 30 minutes

Annals of emergency medicineRCTN=90

Bijur 20172017Landmark

No significant difference in pain reduction between 10mg, 15mg, and 30mg ketorolac doses

Annals of emergency medicineRCTN=240

Chang 20172017Landmark

Mean pain reduction: non-opioid combination non-inferior to opioid combinations at 2 hours

JAMARCTN=416

Guidelines

Integration into clinical practice guidelines and recommendations

ACEP guidelines and multimodal analgesia protocols increasingly recommend non-opioid agents as first-line therapy for many acute pain conditions. CDC opioid prescribing guidelines (2022 update) emphasise non-opioid alternatives and limit opioid prescriptions for acute pain to the shortest effective duration.

CDC Clinical Practice Guideline for Prescribing Opioids

Non-opioid therapies preferred for acute pain; limit opioid prescriptions to shortest effective duration

Now

Current standard of care and ongoing research directions

Multimodal, opioid-sparing analgesia is increasingly standard in EDs. Subdissociative ketamine, ketorolac, acetaminophen, regional nerve blocks, and nitrous oxide are all established alternatives. The challenge remains implementing these consistently across diverse ED settings and pain presentations.

Landmark Trials in This Story

Motov 20152015Landmark

Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial

Pain reduction comparable between subdissociative ketamine 0.3 mg/kg and morphine 0.1 mg/kg at 30 minutes

Annals of emergency medicineRCTN=90

Bijur 20172017Landmark

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial

No significant difference in pain reduction between 10mg, 15mg, and 30mg ketorolac doses

Annals of emergency medicineRCTN=240

Chang 20172017Landmark

Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial

Mean pain reduction: non-opioid combination non-inferior to opioid combinations at 2 hours

JAMARCTN=416

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Frequently Asked Questions

Are non-opioid painkillers as effective as opioids in the emergency department?+

For many acute pain conditions, yes. Chang's 2017 JAMA trial of 416 patients with acute extremity pain showed oral ibuprofen/acetaminophen provided equivalent pain relief to opioid combinations. Motov showed subdissociative ketamine matched morphine for acute pain.

What is subdissociative-dose ketamine and how is it used for pain?+

Subdissociative-dose ketamine (0.3 mg/kg IV) provides analgesia without the dissociative effects seen at higher doses. Motov's 2015 RCT showed it provided pain relief comparable to morphine 0.1 mg/kg in ED patients. It is now part of multimodal opioid-sparing protocols in many emergency departments.