{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:53:36Z","timestamp":1789077216330,"version":"build-2803163510"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims:<\/jats:title>\n                    <jats:p>Acute trauma pain often remains inadequately treated despite opioid therapy. Low-dose ketamine has emerged as a promising adjunct analgesic that may enhance morphine effectiveness while reducing opioid requirements. This systematic review assessed the efficacy and safety of morphine combined with low-dose ketamine versus morphine alone for acute trauma analgesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods:<\/jats:title>\n                    <jats:p>\n                      Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, comprehensive searches were conducted across six databases (2006\u20132024) for studies comparing morphine\u2013ketamine combination versus morphine monotherapy in acute trauma patients. Six eligible randomized controlled trials (RCTs) (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 708) were included. Meta-analysis was performed using RevMan 5.4 software with random-effects modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Six RCTs involving 708 patients from emergency departments and prehospital settings were analyzed. Morphine\u2013ketamine combination demonstrated superior analgesic efficacy with significantly lower final pain scores (mean difference (MD): \u20130.26; 95% confidence interval (CI): \u20130.40 to \u20130.12;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.0003). Subgroup analysis by ketamine dose indicated the most pronounced and statistically significant pain reduction at 0.3 mg\/kg (MD: \u20130.30; 95% CI: \u20130.48 to \u20130.12;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.001), while lower doses showed similar trends. Significant pain reduction occurred at 30 min after sensitivity analysis (MD: \u22120.64,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.00001) and sustained through 60 min (MD: \u22120.32,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001). The combination reduced total morphine consumption by 2.93 mg (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.07). Overall, adverse events increased (odds ratio: 2.37,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.05), but specific events\u2014nausea, vomiting, and hallucinations\u2014showed no significant differences between groups. No serious adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Low-dose ketamine as a morphine adjunct improves acute trauma pain control, shows a trend toward reduced opioid requirements, and maintains an acceptable safety profile, supporting its clinical implementation in emergency settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/joacp.joacp_480_25","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:00:23Z","timestamp":1774440023000},"page":"175-186","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Double relief: A systematic review and meta-analysis of intravenous ketamine and morphine combination for acute trauma analgesia"],"prefix":"10.4103","volume":"42","author":[{"given":"Clara","family":"Alverina","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad F.","family":"Kamaruddin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herdiani S.","family":"Putri","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"R1-20260325","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s40122-017-0090-5","article-title":"A Review of current and emerging approaches to pain management in the emergency department","volume":"6","author":"Todd","year":"2017","journal-title":"Pain Ther"},{"key":"R2-20260325","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.3390\/jcm12093289","article-title":"The pain management of trauma patients in the emergency department","volume":"12","author":"Fabbri","year":"2023","journal-title":"J Clin Med"},{"key":"R3-20260325","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.annemergmed.2005.03.010","article-title":"Intravenous morphine at 0.1 mg\/kg is not effective for controlling severe acute pain in the majority of patients","volume":"46","author":"Bijur","year":"2005","journal-title":"Ann Emerg Med"},{"key":"R5-20260325","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4103\/0259-1162.143110","article-title":"Ketamine:Current applications in anesthesia, pain, and critical care","volume":"8","author":"Kurdi","year":"2014","journal-title":"Anesth Essays Res"},{"key":"R6-20260325","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4274\/eajem.galenos.2020.67689","article-title":"The effect of low dose ketamine on the need for morphine in patients with multiple trauma in emergency department","volume":"19","author":"Heydari","year":"2020","journal-title":"Eurasian J Emerg Med"},{"key":"R8-20260325","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ajem.2023.11.056","article-title":"Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department:A meta-analysis of 15 randomized controlled trials","volume":"76","author":"Guo","year":"2024","journal-title":"Am J Emerg Med"},{"key":"R9-20260325","doi-asserted-by":"crossref","first-page":"e066444","DOI":"10.1136\/bmjopen-2022-066444","article-title":"Subanaesthetic single-dose ketamine as an adjunct to opioid analgesics for acute pain management in the emergency department:A systematic review and meta-analysis","volume":"13","author":"Fjendbo Galili","year":"2023","journal-title":"BMJ Open"},{"key":"R10-20260325","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement:An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"R11-20260325","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2:A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"R12-20260325","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","article-title":"GRADE guidelines:1. 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