Abstract link:https://doi.org/10.1111/acem.13502
Full citation: Karlow N, Schlaepfer CH, Stoll CR, Doering M, Carpenter CR, Colditz GA, Motov S, Miller J, Schwarz ES. A systematic review and meta-analysis of ketamine as an alternative to opioids for acute pain in the emergency department. Acad Emerg Med 2018;25(10):1087–97.
Article type: Systematic Review and Meta-analysis
Ratings: Methods – 4/5 Usefulness – 3/5
INTRODUCTION
Background
Opioids have an established efficacy and safety profile for treating acute pain in the emergency department (ED). Low-dose ketamine may be a preferred analgesic option in opioid dependent or tolerant patient populations, or patients at high risk of opioid related respiratory depression. To consider alternative treatments, such as ketamine, similar efficacy and safety to opioids should be established.
Objectives
(1) Compare the short-term efficacy of ketamine administered as a single-agent intravenous (IV) bolus versus opioid analgesia for the treatment of acute pain in the ED. (2) Quantify risk of adverse events from using ketamine as opioid alternative.
METHODS
Design
Systematic review of randomized controlled trials (RCTs) comparing IV opioids with IV ketamine for pain control.
Eligibility criteria
RCTs published in English. No placebo comparison groups. No coadministration of another pharmacologically active substance less than 20 minutes after IV ketamine/opioid treatment.
Subjects
Adults (>18) presenting to ED with acute pain beginning within the past 7 days.
Intervention
IV ketamine (<0.5 mg/kg) for acute pain compared with IV opioids.
Outcomes
(1) Change in either visual analog scale or numeric rating scale (NRS) from baseline to a second pain score, at time point reported closest to 10 minutes after receiving medication. (2) Rates of reported adverse effects.
RESULTS
Three studies were found to meet eligibility criteria. Ketamine (0.3 or 0.5mg/kg) was found to be noninferior to morphine (0.1mg/kg) in reducing NRS pain scores (relative reduction = 0.42, 95% confidence interval, -0.70 to 1.54). The authors conclude that no severe adverse events occurred in any study; however, increased rates of nonsevere adverse events in ketamine groups were observed. Adverse events, such as disorientation, dizziness, dysphoria, were more common in the ketamine treatment groups.
APPRAISAL
Strengths
• Clear, focused, and relevant question
• Adherence to PRISMA reporting guidelines and checklist
• Sensible eligibility criteria
• Comprehensive literature search
• Primary studies were generally low risk of bias
• No other psychoactive medications were coprescribed that may have affected analgesia efficacy or adverse effects experienced
Limitations
• Small number of patients (261 overall)
• Small number of primary studies (only three studies met inclusion criteria)
• Various adverse event categories reported by study precluded meta-analysis
• Variable timing for second pain scores documented by each study
• One study only included patients with acute pain from long-bone fractures
• The age range of patients (18–59 years) does not include pediatric/elderly populations
CONTEXT
The American College of Emergency Physicians include the use of ketamine in their policy on treating acute pain in the ED, stating that it may be used alone, or as part of multimodal therapy, to treat traumatic and nontraumatic pain.1 Consensus guidelines from American Anesthesia and Pain Medicine groups suggest ketamine may be beneficial in patients with acute pain who are opioid tolerant, dependent, or at high risk for opioid-related respiratory depression (e.g., obstructive sleep apnea).Reference Schwenk, Viscusi and Buvanendran2 Giving ketamine by short infusion (15–20 minutes) by hanging a bag, or by infusion pump, may be more practical than remaining at bedside to give a push dose over 3–5 minutes and is associated with fewer neuropsychiatric side effects.Reference Motov, Mai and Pushkar3
BOTTOM LINE
This high-quality systematic review, with low rates of bias but only a total sample size of 261 patients, found low-dose ketamine (0.3 or 0.5 mg/kg) to be clinically noninferior to morphine (0.1 mg/kg) for treating acute pain in the ED. Ketamine was associated with higher rates of nonsevere adverse events, particularly neuropsychiatric symptoms, such as disorientation, dysphoria, and emergence reaction. Based on this study, and its support in clinical guidelines and policy, low-dose ketamine may be considered as an alternative to opioids for treatment of acute pain in the ED. Given its association with increased nonsevere adverse events, use of ketamine should be limited to when it may offer potential benefit over opioids, such as in patients with known opioid tolerance, dependence, or high risk of opioid related respiratory depression.
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Abstract link:https://doi.org/10.1111/acem.13502
Full citation: Karlow N, Schlaepfer CH, Stoll CR, Doering M, Carpenter CR, Colditz GA, Motov S, Miller J, Schwarz ES. A systematic review and meta-analysis of ketamine as an alternative to opioids for acute pain in the emergency department. Acad Emerg Med 2018;25(10):1087–97.
Article type: Systematic Review and Meta-analysis
Ratings: Methods – 4/5 Usefulness – 3/5
INTRODUCTION
Background
Opioids have an established efficacy and safety profile for treating acute pain in the emergency department (ED). Low-dose ketamine may be a preferred analgesic option in opioid dependent or tolerant patient populations, or patients at high risk of opioid related respiratory depression. To consider alternative treatments, such as ketamine, similar efficacy and safety to opioids should be established.
Objectives
(1) Compare the short-term efficacy of ketamine administered as a single-agent intravenous (IV) bolus versus opioid analgesia for the treatment of acute pain in the ED. (2) Quantify risk of adverse events from using ketamine as opioid alternative.
METHODS
Design
Systematic review of randomized controlled trials (RCTs) comparing IV opioids with IV ketamine for pain control.
Eligibility criteria
RCTs published in English. No placebo comparison groups. No coadministration of another pharmacologically active substance less than 20 minutes after IV ketamine/opioid treatment.
Subjects
Adults (>18) presenting to ED with acute pain beginning within the past 7 days.
Intervention
IV ketamine (<0.5 mg/kg) for acute pain compared with IV opioids.
Outcomes
(1) Change in either visual analog scale or numeric rating scale (NRS) from baseline to a second pain score, at time point reported closest to 10 minutes after receiving medication. (2) Rates of reported adverse effects.
RESULTS
Three studies were found to meet eligibility criteria. Ketamine (0.3 or 0.5mg/kg) was found to be noninferior to morphine (0.1mg/kg) in reducing NRS pain scores (relative reduction = 0.42, 95% confidence interval, -0.70 to 1.54). The authors conclude that no severe adverse events occurred in any study; however, increased rates of nonsevere adverse events in ketamine groups were observed. Adverse events, such as disorientation, dizziness, dysphoria, were more common in the ketamine treatment groups.
APPRAISAL
Strengths
• Clear, focused, and relevant question
• Adherence to PRISMA reporting guidelines and checklist
• Sensible eligibility criteria
• Comprehensive literature search
• Primary studies were generally low risk of bias
• No other psychoactive medications were coprescribed that may have affected analgesia efficacy or adverse effects experienced
Limitations
• Small number of patients (261 overall)
• Small number of primary studies (only three studies met inclusion criteria)
• Various adverse event categories reported by study precluded meta-analysis
• Variable timing for second pain scores documented by each study
• One study only included patients with acute pain from long-bone fractures
• The age range of patients (18–59 years) does not include pediatric/elderly populations
CONTEXT
The American College of Emergency Physicians include the use of ketamine in their policy on treating acute pain in the ED, stating that it may be used alone, or as part of multimodal therapy, to treat traumatic and nontraumatic pain.1 Consensus guidelines from American Anesthesia and Pain Medicine groups suggest ketamine may be beneficial in patients with acute pain who are opioid tolerant, dependent, or at high risk for opioid-related respiratory depression (e.g., obstructive sleep apnea).Reference Schwenk, Viscusi and Buvanendran2 Giving ketamine by short infusion (15–20 minutes) by hanging a bag, or by infusion pump, may be more practical than remaining at bedside to give a push dose over 3–5 minutes and is associated with fewer neuropsychiatric side effects.Reference Motov, Mai and Pushkar3
BOTTOM LINE
This high-quality systematic review, with low rates of bias but only a total sample size of 261 patients, found low-dose ketamine (0.3 or 0.5 mg/kg) to be clinically noninferior to morphine (0.1 mg/kg) for treating acute pain in the ED. Ketamine was associated with higher rates of nonsevere adverse events, particularly neuropsychiatric symptoms, such as disorientation, dysphoria, and emergence reaction. Based on this study, and its support in clinical guidelines and policy, low-dose ketamine may be considered as an alternative to opioids for treatment of acute pain in the ED. Given its association with increased nonsevere adverse events, use of ketamine should be limited to when it may offer potential benefit over opioids, such as in patients with known opioid tolerance, dependence, or high risk of opioid related respiratory depression.
Competing interests
None declared.