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 May 9, 2019; 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-percent absolute risk difference for any adverse event; and 5-percent absolute risk difference for hypotension, respiratory depression, and mental status changes.
RESULTS: We included 52 randomized controlled trials and 13 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, we found 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 we found 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 than ketamine (low SOE), primarily administered intranasally. Opioids cause less dizziness than ketamine (low SOE) but may increase the risk of respiratory depression compared with ketamine (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 we found 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, we found that giving IV ketamine may reduce pain more and may be quicker than giving additional IV morphine (low SOE, insufficient evidence to determine comparative harms).
CONCLUSION: As initial analgesia administered primarily IV, opioids are no different than ketamine, APAP, and NSAIDs in reducing acute pain in the prehospital setting. Opioids may 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. Combined administration of an opioid and ketamine may reduce acute pain more than an opioid alone, but comparative harms are uncertain. When initial morphine is inadequate in reducing pain, giving ketamine may provide greater and quicker acute pain relief than giving additional morphine, although comparative harms are uncertain. Due to indirectness, SOE is generally low, and future research in the prehospital setting is needed.
Much needed and comprehensive work. Also, very timely in terms of the opioid epidemic. The topic seems ripe for a clinical practice guideline and integration into prehospital EMS algorithms as findings will likely lead to a major shift in guidance.
These are unexpected results but consistent with some smaller emergency department studies.
Lengthy, high-quality evidence appraising multiple pre-hospital analgesic options compared with opioid therapy for acute pain. In the opioid epidemic era, a thoughtful, evidence-based approach to pain management is essential from the pre-hospital environment, through the emergency department, to the inpatient and outpatient settings. This AHRQ contracted review implies no benefits of morphine over ketamine, APAP, nitrous oxide (generally not available in most US EMS rigs), or NSAIDS, but a possible additive role of opioid + ketamine in some situations. The problem to operationalize this information is that: 1. EDs generally cannot change what EMS already used prior to arrival; and 2. EMS services must keep patients NPO and lack IV alternatives to morphine. Nonetheless, this report is interesting.
An area of significant bias and lack of understanding. Few EDs pay serious attention to analgesia and side effects. A review such as this should be compulsory reading for all in this clinical practice area.
There is no evidence supporting opioid use to improve survival; the value of opioids is symptomatic. The comparisons from this study are very important since most opioid alternatives (e.g. acetaminophen, NSAIDs) have better side effect profiles while providing equivalent relief. Particularly in North America, we need a rethink in our attitude toward narcotics and in our attitude to pain as a symptom.
This study largely extrapolated findings from studies in emergency departments to pre-hospital care because there were too few studies in the pre-hospital setting. So, I don't think it adds any new information.
The article does a good job of summarizing current science around prehospital analgesia. Given the difficulties of prehospital research, there is a relative paucity of evidence in this space. The specific focus of the review was the comparison of opioid to non-opioid analgesics. Pain relief was similar with either an opioid or NSAID, acetaminophen or ketamine; the side effect profiles were different. There is also some discussion of what is known about combination or step therapy. The evidence model was well-constructed around a clinically relevant question and the literature review was exhaustive. Although the results will not surprise experienced clinicians in this space, the review will give credibility and impetus to efforts to reduce opioid use. In summary, this manuscript will be an important reference for all future researchers and writers on the topic of prehospital analgesia.
Pain control is important and adequate control should be provided. Although few studies are available in prehospital settings, this review provides evidence on the effectiveness of opioid analgesic in the prehospital setting. Opioid analgesics may cause more adverse events and more drowsiness. Similarly, combined administration of an opioid and ketamine may be harmful. I am concerned about the risks of sedation and whether adequate monitoring is available in prehospital settings.
This review is too long and detailed for the average primary care physician who needs this information.
This meta-analysis evaluated 52 RCTs and 13 observational studies on use of analgesia in the prehospital setting. Due to a lack of evidence in the prehospital setting, the authors used emergency medicine studies. They found opioids are no different than ketamine, APAP, or NSAIDs in reducing pain in the prehospital setting, and they may cause more side effects than APAP or NSAIDs. Ketamine may assist in providing fast pain relief if initial morphine is inadequate, and use of ketamine plus an opioid is likely to reduce pain better than an opioid alone; however, harms with ketamine are uncertain. The strength of evidence is low based on the current literature. Further study is needed.
Although the source is extensive, this is far too long and too detailed to be relevant as a whole for practicing clinicians. Also, using ketamine and opioids together in combination is likely not a good primary care strategy based on risks. Knowledge of the benefits of NSAIDs and Tylenol have permeated the literature and are becoming more widespread.