Acute pain is the most common presentation in the emergency department (ED), accounting for approximately 78% of visits and highlighting the need for rapid and effective pain management. Ketamine is a well-established analgesic that can serve as an alternative when opioids are contraindicated. Recently, low-dose ketamine (LDK), also known as sub-dissociative or subanesthetic ketamine, has emerged as a potential option for acute pain control in ED settings; however, evidence regarding its efficacy and safety remains inconsistent. This systematic review aimed to evaluate the effectiveness and safety of LDK for acute pain management in the emergency department. A comprehensive search of SCOPUS, PubMed, and Web of Science was conducted using predefined keywords related to ketamine, acute pain, and emergency care. Peer-reviewed randomized controlled trials (RCTs) published in English between 2015 and 2025 involving adults aged ≥ 18 years were included, and the risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB-2) tool. Sixteen RCTs including 1908 adult patients met the inclusion criteria. The findings were heterogeneous: several studies demonstrated that LDK provided effective pain reduction within 30 min compared with commonly used analgesics such as morphine, ketorolac, and fentanyl, whereas others found no significant superiority, including one placebo-controlled trial. The analgesic effect appeared dose- and administration-dependent, with short intravenous infusions showing better tolerability than bolus dosing. Transient neuropsychiatric adverse effects were reported, but no serious adverse events were identified. Larger multicenter studies are needed to further clarify optimal dosing strategies and confirm the safety profile of LDK in ED pain management.
AlMulhim et al. (2026) studied this question.