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

Project Summary Title and Description

Title
Comparative Effectiveness of Analgesics to Reduce Acute Pain in the Prehospital Setting
Description
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% absolute risk difference for any adverse event, and 5% 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 (ED) 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 (IN). 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, strength of evidence is generally low, and future research in the prehospital setting is needed.
Attribution
N/A
Authors of Report
N/A
Methodology description
N/A
PROSPERO
CRD42018114959
DOI
10.26300/mm39-2c80
Notes
At this time, the project has not yet been published (July 2019). The data of this project was entered retrospectively by uploading data to the project from other software and file format such as Excel or Word.
Funding Source
AHRQ

Key Questions

1. Key Question (KQ) 1. What is the comparative effectiveness of the initial analgesic agent treatment for achieving reduction in moderate-to-severe acute-onset pain level when administered by EMS personnel in the prehospital setting? KQ 1a. How does effectiveness vary by patient characteristics? KQ 1b. How does effectiveness vary by routes of administration, dosing, and timing?
2. KQ 2. What are the comparative harms of analgesic agents when administered by EMS personnel to control moderate-to-severe pain in the prehospital setting? KQ 2a. How do harms vary by patient characteristics? KQ 2b. How do harms vary by routes of administration, dosing, and timing? KQ 2c. What are the comparative harms to EMS personnel who administer analgesics to patients for the control moderate-to-severe pain in the prehospital setting?
3. KQ 3. In patients whose moderate-to-severe acute-onset pain level is not controlled following initial analgesic treatment, what is the comparative effectiveness of switching the analgesic regimen compared to repeating the initial treatment? KQ 3a. How does effectiveness vary by patient characteristics? KQ 3b. How does effectiveness vary by timing of the second treatment administration?
4. KQ 4. In patients whose moderate-to-severe acute-onset pain level is not controlled following initial analgesic treatment, what are the comparative harms of switching to another analgesic agent? KQ 4a. How do harms vary by patient characteristics? KQ 4b. How do harms vary by routes of administration, dosing, and timing?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.
Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial.
Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial.
Management of severe acute pain in emergency settings: ketamine reduces morphine consumption.
Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.
Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial.
Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial.2009
Management of severe acute pain in emergency settings: ketamine reduces morphine consumption.2007
A comparison of ketamine and morphine analgesia in prehospital trauma care: a cluster randomized clinical trial in rural Quang Tri province, Vietnam.-- Not Found --
Analgesic Efficacy of Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe Pain in Children: A Prospective, Randomized, Double-Blind Study.2018
Project for the introduction of prehospital analgesia with fentanyl and morphine administered by specially trained paramedics in a rural service area in Germany.
Impact of age, sex and route of administration on adverse events after opioid treatment in the emergency department: a retrospective study.-- Not Found --
Expedited Delivery of Pain Medication for Long-Bone Fractures Using an Intranasal Fentanyl Clinical Pathway.2015
Morphine versus fentanyl for pain due to traumatic injury in the emergency department.-- Not Found --
Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients.-- Not Found --
Analysis of the paramedic administration of fentanyl.
Effectiveness and safety of fentanyl compared with morphine for out-of-hospital analgesia.
Intravenous paracetamol vs ibuprofen in renal colic: a randomised, double-blind, controlled clinical trial.2018
Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.2019
Comparison of Fentanyl and Morphine in the Prehospital Treatment of Ischemic Type Chest Pain.2016
The effectiveness and adverse events of morphine versus fentanyl on a physician-staffed helicopter.2012
A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting.2007
A randomized, double-blind study comparing morphine with fentanyl in prehospital analgesia.2005
Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial.2014
A randomized clinical trial of oral transmucosal fentanyl citrate versus intravenous morphine sulfate for initial control of pain in children with extremity injuries.2007
A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department.2007
Comparison of clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic: a randomized, double-blind, controlled trial.2014
Effect of Intravenous Morphine and Ketorolac on Pain Control in Long Bones Fractures.2017
Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic.2006
Oral Analgesics Utilization for Children With Musculoskeletal Injury (OUCH Trial): An RCT.2017
Comparison of paracetamol (apotel®) and morphine in reducing post pure head trauma headache.2014
Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.
Low-dose intravenous ketamine versus intravenous ketorolac in pain control in patients with acute renal colic in an emergency setting: a double-blind randomized clinical trial.2019
Comparison of Intravenous Morphine Versus Paracetamol in Sciatica: A Randomized Placebo Controlled Trial.2016
Intravenous paracetamol versus dexketoprofen versus morphine in acute mechanical low back pain in the emergency department: a randomised double-blind controlled trial.2014
Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial.2012
Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department.2012
Comparison of IV dexketoprofen trometamol, fentanyl, and paracetamol in the treatment of renal colic in the ED: A randomized controlled trial.2018
Comparison of intranasal ketamine versus IV morphine in reducing pain in patients with renal colic.2017
Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial.2019
Acute Pain Management in Emergency Department, Low Dose Ketamine Versus Morphine, A Randomized Clinical Trial.2017
Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial.2015
Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial.2015
Comparison of Intravenous Ketamine with Morphine in Pain Relief of Long Bones Fractures: a Double Blind Randomized Clinical Trial.2014
Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial.2018
Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis.2018
Multicenter, Prospective Study of Prehospital Administration of Analgesia in the U.S. Combat Theater of Afghanistan.-- Not Found --
Prehospital pain medication use by U.S. Forces in Afghanistan.2015
Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial.2012
The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting.2009
A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma.2007
Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter Emergency Medical Service.2017
Comparing the analgesic efficacy of morphine plus ketamine versus morphine plus placebo in patients with acute renal colic: A double-blinded randomized controlled trial.2019
The Use of Ketamine for Acute Treatment of Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.2017
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
Can low-dose of ketamine reduce the need for morphine in renal colic? A double-blind randomized clinical trial.2018
Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The PRIME Randomized Clinical Trial.2019
Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.2017
The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries.2015
Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safety.2016
Intranasal ketamine administration for narcotic dose decrement in patients suffering from acute limb trauma in emergency department: a double-blind randomized placebo-controlled trial2018
Comparing the effect of intravenous acetaminophen (Apotel®) and intravenous morphine in controlling the pain of forearm and leg fractures in adults2016
A prospective randomized pilot comparison of intranasal fentanyl and intramuscular morphine for analgesia in children presenting to the emergency department with clinical fractures1999
Sub-dissociative ketamine for the management of acute pediatric pain.
Efficacy of intravenous paracetamol versus intravenous morphine in acute limb trauma2016
Efficacy of nebulized fentanyl and low dose ketamine for pain control of patients with long bone fractures: a randomized, double-blind, clinical trial2019

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