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Effective Health Care Program

Comparative Effectiveness of Analgesics to Reduce Acute Pain in the Prehospital Setting

Systematic Review Draft

Open for comment through May 31, 2019

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Purpose of Review

To evaluate effectiveness and harms of opioids compared to nonopioid analgesics as treatment of moderate to severe acute pain in the prehospital setting.

Key Messages

  • Few studies have been conducted in the prehospital setting; we relied on evidence from the emergency department.
  • Analgesics were primarily administered intravenously and for acetaminophen this was the only route studied.
  • As initial therapy and compared with opioids,
    • ketamine may result in a similar reduction of pain but may cause more people to experience a side effect overall or dizziness. Opioids may cause more respiratory depression than ketamine.
    • acetaminophen may result in a similar reduction of pain and may cause fewer people to experience a side effect overall and less dizziness.
    • nonsteroidal anti-inflammatory drugs most likely result in a similar reduction of pain and may cause fewer people to experience a side effect overall and less drowsiness.
    • combining an opioid with ketamine may be more effective in reducing pain.
  • If morphine does not adequately relive pain initially, changing to ketamine may be more effective and more quickly reduce pain than giving additional morphine.

Structured Abstract

Objective. To assess comparative effectiveness and harms of opioid and nonopioid analgesics administered by emergency medical services for treatment of moderate to severe acute pain in the prehospital setting.

Data sources. MEDLINE®, Embase® and Cochrane Central from earliest date through October 16, 2018; hand searches of references of relevant studies and study registries.

Review methods. Two investigators screened abstracts, reviewed full-text files, abstracted data and assessed study level risk of bias. We performed meta-analyses when appropriate and graded the strength of evidence (SOE) upon which conclusions were made for a priori determined comparisons and outcomes. We defined the following as clinically important differences: 2 points on a 0 to 10 pain scale, time to analgesia of 5 minutes, 10% absolute risk difference for any adverse event, and 5% absolute risk difference for hypotension, respiratory depression and mental status changes.

Results. We included 48 randomized controlled trials and 12 observational studies. Due to the absence or insufficiency of prehospital evidence we based conclusions for initial analgesia on indirect evidence from the emergency department setting. As initial analgesics, there is no evidence of a clinically important difference in the change of pain scores with opioids versus ketamine administered primarily intravenously (IV) (low SOE), IV acetaminophen (APAP) (low SOE), or nonsteroidal anti-inflammatory drugs (NSAIDs) administered primarily IV (moderate SOE). The combined use of an opioid and ketamine, administered primarily IV, may reduce pain more than an opioid alone at 15 and 30 minutes (low SOE) but there is no evidence of a clinically important difference at 60 minutes (low SOE). We found no evidence of a clinically important difference in time-to-analgesia with opioids compared with APAP, both administered IV. Opioids may cause fewer adverse events and less dizziness than ketamine (low SOE) but may increase the risk of respiratory depression (low SOE), primarily administered IV. Opioids cause more dizziness (moderate SOE) and may cause more adverse events than APAP (low SOE), both administered IV, but there is no evidence of a clinically important difference in hypotension (low SOE). Opioids may cause more adverse events and more drowsiness than NSAIDs (low SOE), administered primarily IV. Evidence on comparative effects of nitrous oxide and on harms of combined opioid and ketamine is insufficient.

For patients whose pain is not adequately reduced by IV morphine initially, giving IV ketamine may reduce pain more and may be quicker than giving additional IV morphine (low SOE and insufficient evidence to determine comparative harms).

Conclusion. As initial analgesia administered primarily IV, opioids are no different in reducing pain than ketamine, APAP and NSAIDs. Opioids cause fewer total side effects than ketamine, but more than APAP or NSAIDs. Differences in specific side effects vary between analgesics and can further inform treatment decisions. Combining an opioid and ketamine may reduce pain more than an opioid alone but comparative harms are uncertain. When initial morphine is inadequate, giving ketamine may provide greater and quicker pain relief than giving additional morphine, although comparative harms are uncertain. Due to indirectness, strength of evidence is generally low, and future research in the prehospital setting is needed.