CME Information : A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department

BACKGROUND Opioids are commonly prescribed in the emergency department (ED) for the treatment of acute pain. Analgesic alternatives are being explored in response to an epidemic of opioid misuse. Low-dose ketamine (LDK) is one opioid alternative for the treatment of acute pain in the ED. OBJECTIVES This systematic review and meta-analysis sought to quantify whether LDK is an effective and safe opioid alternative for acute pain reduction in adults in the ED setting. (PROSPERO Registration Number CRD42017065303). METHODS This was a systematic review of randomized controlled trials comparing intravenous opioids to LDK for relief of acute pain in the ED. Studies where the control group initially received opioids prior to ketamine were excluded. A research librarian designed the electronic search strategy. Changes in visual analog scale or numeric rating scale pain scales were analyzed to determine the relative effects of LDK and opioids in the treatment of acute pain. RESULTS Three studies met the criteria for inclusion in this meta-analysis. Compared to pain scale reduction with morphine, ketamine was not inferior (relative reduction = 0.42, 95% confidence interval = -0.70 to 1.54). No severe adverse events were reported in any study, but higher rates of nonsevere adverse events were observed with ketamine. CONCLUSIONS Ketamine is noninferior to morphine for the control of acute pain, indicating that ketamine can be considered as an alternative to opioids for ED short-term pain control.

[1]  Lynsey J. Martin,et al.  The impact of social media promotion with infographics and podcasts on research dissemination and readership. , 2018, CJEM.

[2]  P. Bijur,et al.  Comparative Effectiveness of Patient‐Controlled Analgesia for Treating Acute Pain in the Emergency Department , 2017, Annals of emergency medicine.

[3]  A. Dahan,et al.  An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers , 2017, British journal of anaesthesia.

[4]  P. Homel,et al.  A prospective randomized, double‐dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED , 2017, The American journal of emergency medicine.

[5]  Michael Lawrence Barnett,et al.  Opioid‐Prescribing Patterns of Emergency Physicians and Risk of Long‐Term Use , 2017, The New England journal of medicine.

[6]  E. Kharasch,et al.  Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance , 2016, Anesthesiology.

[7]  Eun Nam Lee,et al.  The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis , 2016, PloS one.

[8]  Wenhua Zhou,et al.  Ketamine abuse potential and use disorder , 2016, Brain Research Bulletin.

[9]  M. Lyons,et al.  Emergency Department Prescription Opioids as an Initial Exposure Preceding Addiction. , 2016, Annals of emergency medicine.

[10]  K. Olkkola,et al.  Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy , 2016, Clinical Pharmacokinetics.

[11]  C. Johnston,et al.  Analgesia, nil or placebo to babies, in trials that test new analgesic treatments for procedural pain , 2016, Acta paediatrica.

[12]  V. Martinez,et al.  Ketamine for pain management in France, an observational survey. , 2015, Anaesthesia, critical care & pain medicine.

[13]  A. Likourezos,et al.  Development of an opioid reduction protocol in an emergency department. , 2015, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[14]  P. Homel,et al.  Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. , 2015, Annals of Emergency Medicine.

[15]  Y. Eyi,et al.  Low-Dose Ketamine Infusion for Managing Acute Pain. , 2015, The American journal of emergency medicine.

[16]  B. Frazee,et al.  Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain. , 2015, Pain medicine.

[17]  P. Dalawari,et al.  Oligoanalgesia in blunt geriatric trauma. , 2015, The Journal of emergency medicine.

[18]  S. Motov,et al.  The use of subdissociative-dose ketamine for acute pain in the emergency department. , 2015, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[19]  V. Bebarta,et al.  Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. , 2015, The American journal of emergency medicine.

[20]  P. Shekelle,et al.  Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement , 2015, Systematic Reviews.

[21]  M. Bezzi,et al.  Are benzodiazepines and opioids really safe in patients with severe COPD? , 2014, Minerva medica.

[22]  R. Merchant,et al.  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. , 2014, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[23]  A. Graudins,et al.  Sub‐dissociative‐dose intranasal ketamine for moderate to severe pain in adult emergency department patients , 2014, Emergency medicine Australasia : EMA.

[24]  Mehrdad Esmailian,et al.  Comparison of Intravenous Ketamine with Morphine in Pain Relief of Long Bones Fractures: a Double Blind Randomized Clinical Trial , 2014, Emergency.

[25]  P. Anderson,et al.  Ketamine: an update on its abuse. , 2014, Journal of pharmacy practice.

[26]  G. Andolfatto,et al.  Intranasal ketamine for analgesia in the emergency department: a prospective observational series. , 2013, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[27]  J. Mendelson,et al.  Ketamine is associated with lower urinary tract signs and symptoms. , 2013, Drug and alcohol dependence.

[28]  Denise A Esserman,et al.  Side effects from oral opioids in older adults during the first week of treatment for acute musculoskeletal pain. , 2013, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[29]  D. Jolley,et al.  Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial , 2013, Emergency Medicine Journal.

[30]  Fiona Stewart,et al.  The Cochrane collaboration's tool for assessing risk of bias , 2013 .

[31]  M. Stone,et al.  Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. , 2013, The American journal of emergency medicine.

[32]  A. Graudins,et al.  Sub‐dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: A pilot study , 2013, Emergency medicine Australasia : EMA.

[33]  Justin C Roberts,et al.  Ketamine for analgesia. , 2012, British journal of hospital medicine.

[34]  J. Ioannidis,et al.  Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials , 2011, BMJ : British Medical Journal.

[35]  S. Bernard,et al.  Ketamine as an analgesic in the pre‐hospital setting: a systematic review , 2011, Acta anaesthesiologica Scandinavica.

[36]  Kelly A Saran,et al.  Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy. , 2011, Journal of clinical anesthesia.

[37]  Baruch Krauss,et al.  Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. , 2011, Annals of emergency medicine.

[38]  I. Pearce,et al.  Ketamine‐induced vesicopathy: a literature review , 2011, International journal of clinical practice.

[39]  S. Huckson,et al.  Patterns of analgesia for fractured neck of femur in Australian emergency departments , 2010, Emergency medicine Australasia : EMA.

[40]  A. Johansson,et al.  The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting , 2009, Scandinavian journal of trauma, resuscitation and emergency medicine.

[41]  J. V. van Vlymen,et al.  Subdissociative-dose ketamine versus fentanyl for analgesia during propofol procedural sedation: a randomized clinical trial. , 2008, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[42]  W. Baxt,et al.  Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. , 2008, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[43]  Peter Homel,et al.  Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. , 2007, The journal of pain : official journal of the American Pain Society.

[44]  S. Schug,et al.  The role of ketamine in pain management. , 2006, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[45]  M. Biros,et al.  Patient and physician perceptions as risk factors for oligoanalgesia: a prospective observational study of the relief of pain in the emergency department. , 2006, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[46]  E. Seow,et al.  Pain Management in the Emergency Department , 2006, Annals of emergency medicine.

[47]  H. Hense,et al.  Is It Always Unethical to Use a Placebo in a Clinical Trial? , 2005, PLoS medicine.

[48]  F. Miller,et al.  What Makes Placebo-Controlled Trials Unethical? , 2002, The American journal of bioethics : AJOB.

[49]  E. Rome It's a rave new world: rave culture and illicit drug use in the young. , 2001, Cleveland Clinic journal of medicine.

[50]  D. Jaffe,et al.  Comparison of Fentanyl/Midazolam With Ketamine/Midazolam for Pediatric Orthopedic Emergencies , 1998, Pediatrics.

[51]  A. Bhattacharya,et al.  Analgesia for Acute Musculoskeletal Trauma: Low-Dose Subcutaneous Infusion of Ketamine , 1996, Anaesthesia and intensive care.

[52]  A. Daykin,et al.  Respiratory depression after morphine in the elderly , 1986 .

[53]  J. Jones,et al.  Ventilatory response to morphine in young and old subjects , 1983, Anaesthesia.

[54]  Subdissociative-Dose Ketamine for Analgesia. , 2018, Annals of emergency medicine.

[55]  Optimizing the Treatment of Acute Pain in the Emergency Department. , 2017, Annals of emergency medicine.

[56]  Innovative Program Targets Five Common Pain Syndromes With Non-opioid Alternatives. , 2016, ED management : the monthly update on emergency department management.

[57]  A. Shrestha,et al.  Intranasal ketamine for the treatment of patients with acute pain in the emergency department. , 2016, World journal of emergency medicine.

[58]  Mei Gao,et al.  Ketamine use in current clinical practice , 2016, Acta Pharmacologica Sinica.

[59]  Tony Meriano,et al.  Journal Club: Ketamine in the Emergency Department. , 2015, Journal of special operations medicine : a peer reviewed journal for SOF medical professionals.

[60]  C. Bias The Cochrane Collaboration's tool for assessing risk of bias in randomised trials , 2011 .

[61]  A. Daykin,et al.  Respiratory depression after morphine in the elderly. A comparison with younger subjects. , 1986, Anaesthesia.