Pain occurs in more than half of ED patient. Analgesia is often sub-optimally addressed or reassessed in a significant number of patients. A combination of non-pharmacologic and pharmacologic (opioid and non-opioid) analgesics modalities can enhance the quality of pain management.

1. Pharmacologic Treatment of Acute Pain in Emergency Department
Reza Aminnejad, MD.
Anesthesiologist, pain specialist
Dr. Reza Aminnejad

2. Introduction
❑ Pain occurs in more than half of ED patient.
❑ Analgesia is often sub-optimally addressed or reassessed in a significant number of
patients.
❑ A combination of non-pharmacologic and pharmacologic (opioid and non-opioid)
analgesics modalities can enhance the quality of pain management.
❑ Opioids are effective analgesics that are commonly used for acute pain management in
the ED (with desirable effects such as analgesia, anti-inflammatory properties, and
euphoria).
Dr. Reza Aminnejad

3. Why not opioids?
❑ Respiratory and central nervous system depression
❑ Nausea
❑ Vomiting
❑ Dizziness
❑ Constipation
❑ Tolerance
❑ Dependence
❑ Misuse
Dr. Reza Aminnejad

4. Dr. Reza Aminnejad
Patients given opioids for abdominal pain in the ED had 57% increased odds of a return ED visit within
30 days compared with those given only acetaminophen or NSAIDs.

5. Opioid Use Disorder (OUD)
❑ A substantial proportion of OUD patients were first exposed to prescription opioids.
❑ Some individuals who developed OUD by misusing prescription opioids will progress to
more dangerous substances like heroin and fentanyl.
❑ EM providers are on the front lines of the opioid epidemic.
❑ Studies estimate 12–21% of opioid-naive ED patients prescribed opioids for acute pain
at discharge filled additional opioid prescriptions at up to one year after visit.
Dr. Reza Aminnejad

6. Dr. Reza Aminnejad

7. Multimodal Pain Control
Multimodal pain control involves simultaneously using multiple agents from different
classes acting on different target sites for the treatment of pain, in order to work
synergistically to improve analgesic efficacy and reduce the dose of any individual agent.
Dr. Reza Aminnejad

8. CERTA
Channels-Enzymes-Receptors Targeted Analgesia, also known as “CERTA”, is a multimodal
analgesic strategy that promotes a mechanistic view of pain signaling transmission in order
to target the physiologic pathway that is the stimulus for pain.
Dr. Reza Aminnejad

9. Dr. Reza Aminnejad

10. Non-pharmacologic treatment
A MAINSTAY OF EM PAIN MANAGEMENT
Dr. Reza Aminnejad

11. Goals
❑ Reduction in inflammatory mediators that cause pain
❑ Distraction of the nervous system to decrease the painful experience
❑ Promotion of healing that leads to improved function
Dr. Reza Aminnejad

12. MODALITIES
❑ Cryotherapy (ice and cold pack): ankle sprains, orthopedic post-surgical populations &
LBP
❑ Heat therapy: acute back pain & neck pain
❑ Physical manipulation (osteopathic manipulation techniques (OMT), physical therapy,
and early mobilization): acute LBP & ankle sprain
❑ Electrical stimulation (TENS)
❑ Acupuncture: headaches, migraine, neck pain, back pain, and osteoarthritis
❑ Music therapy
Dr. Reza Aminnejad

13. Pharmacological treatment
❑ Acetaminophen
❑ NSAIDs
❑ Lidocaine
❑ Ketamine
❑ Dopamine receptor antagonists
❑ Calcium channel blocking anticonvulsants: “Gabapentinoids”
Dr. Reza Aminnejad

14. Dr. Reza Aminnejad

15. Acetaminophen
❑ The combination of NSAIDs and acetaminophen together has may have additive efficacy
in treating some painful conditions.
❑ Current evidence does not support IV acetaminophen as a primary analgesic in the ED.
❑ Use it in patients with acute pain unable to take oral acetaminophen (rectal
administration of acetaminophen may also be indicated).
Dr. Reza Aminnejad

16. Non-steroidal anti-inflammatory drugs
❑ NSAIDS are indicated for a variety of conditions, ranging from musculoskeletal pain,
headache, inflammatory abdominal pain, renal colic, gout flairs and pain related to other
inflammatory conditions.
❑ Adverse effects include gastrointestinal (GI) bleeding, renal dysfunction, abnormal platelet
aggregation, and cardiovascular sequelae. These effects are typically seen with long-term use,
though caution should be used in patients with renal insufficiency or at high risk of bleeding.
❑ Regarding selective inhibitors like celecoxib, significant GI side effects remain when
compared to placebo.
❑ With a comparable efficacy, naproxen may have less cardiovascular side effects than
ibuprofen.
Dr. Reza Aminnejad

17. ❑ Dual therapy with concomitant use of NSAIDs and ACEinhs or ARBs may result in acute renal
failure.
❑In extremity pain there is no difference in pain scores between NSAIDs combined with
acetaminophen compared to three different opioid regimens combined with acetaminophen.
❑ Choosing the lowest effective dose for the shortest duration to adequately manage pain is
important to mitigate adverse effects (ketorolac has an analgesic ceiling at 10 mg and
ibuprofen at 400mg)
❑ When prescribing NSAIDs for acute pain, patients should be instructed to take the lowest
effective dose for a three to five day period should be warned of the side effects of long-term
use.
❑ Topical NSAIDs are also an effective treatment for acute and chronic musculoskeletal pain
that spare adverse effects from systemic exposure and can be used longer term.
Dr. Reza Aminnejad

18. In patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief
compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of
rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable
alternative. Dr. Reza Aminnejad

19. Parenteral ketorolac doses of 15 mg IV or 30 mg IM did not demonstrate a greater need for rescue analgesia compared to
doses of 30 mg IV or 60 mg IM. Dr. Reza Aminnejad

20. Lidocaine
❑ Lidocaine has analgesic, anti-inflammatory, and opioid-sparing properties.
❑ IV lidocaine has superior efficacy to morphine for renal colic and limb ischemia, equivalent
efficacy to ketorolac for acute radicular lower back pain, and is more efficacious than
dihydroergotamine for acute migraine, but less efficacious than IV chlorpromazine.
❑ The FDA has approved 5% lidocaine patches for the treatment of post-herpetic neuralgia; other
indications including diabetic neuropathy, osteoarthritis, and lower back pain.
❑ IV lidocaine can be a good choice in pain management in biliary colic and can reduce pain in less
time than morphine sulfate (in 10 min) without adding significant side effects (1).
1- Akhgar A, Pouryousefi T, Nejati A, Rafiemanesh H, Hossein-Nejad H. The efficacy of intravenous lidocaine and its side effects in comparison with intravenous morphine sulfate in
patients admitted to the ED with right upper abdominal pain suspected of biliary colic. Am J Emerg Med. 2021 Jun;44:300-305. doi: 10.1016/j.ajem.2020.04.010. Epub 2020 Apr 9.
PMID: 32595055.
Dr. Reza Aminnejad

21. Dr. Reza Aminnejad

22. Ketamine
❑ Ketamine is a phencyclidine derivative and a NMDA blocker.
❑ Depression, acute agitation, post-operative pain, chronic pain, and, most notably, acute pain in
the ED are it’s recent indications.
❑ Ketamine in sub-dissociative doses directly act on the mu opioid receptor, enhancing opioid-
induced analgesia while preventing hyperalgesia.
❑ At doses ranging from 0.1 mg/kg to 0.3 mg/kg, the most common side effects of IV ketamine
(particularly IV piggyback over 15 min) are nausea, vomiting, dizziness, and ‘feeling of unreality’,
which are all typically mild to moderate and resolve without intervention even in geriatric patients.
❑ Ketamine (1.5mg/kg) may be a reasonable IN alternative to fentanyl, though more data are
needed in adult patients as dosing is limited by volume.
Dr. Reza Aminnejad

23. The favorable safety and efficacy profile of ketamine has led the American College
of Emergency Physicians (ACEP) to recommend it as a first line analgesic, specifically
in patients whom opioids and/or other non-opioid analgesics are absolutely or
relatively contraindicated.
Dr. Reza Aminnejad

24. Dopamine receptor antagonists
❑ Prochlorperazine and chlorpromazine are phenothiazine class anti-dopaminergic agents that act
predominantly on D2-dopamine receptors, producing primarily an anti-emetic effect, with minimal anti-
muscarinic (M1) and anti-histamine (H1) effect. prochlorperazine is frequently used for treatment of
headaches [in migraine HA it is better than metoclopramide, and more effective than magnesium, ketorolac,
sumatriptan, octreotide, ketamine and hydromorophone (safer in infusion over 15 min)].
❑ Haloperidol and droperidol are butyrophenones, with more sedative effects as well as anti-emetic efficacy.
Recently, haloperidol has gained attention for the treatment of gastroparesis, cyclic vomiting, and
cannabinoid hyperemesis syndrome. The most common side effect of droperidol, consistent with other
studies, was akathisia (2.9%).
❑ Metoclopramide blocks both central and peripheral dopamine D2 receptors in low doses, with some anti-
serotonin effects at higher doses. It also stimulates cholinergic receptors on gastric smooth muscle cells, and
thus useful as a pro-motility agent. Ten mg IV infusion of plasil over 10-15 min is safe and efficacious as a first
line treatment in migraine HA. Dr. Reza Aminnejad

25. Use of dopamine antagonists and NSAIDs are associated with a reduced need for second round medications in ED
primary headache patients. Conversely, non-dopamine antagonist antiemetic medications and intravenous fluids are
associated with a significantly increased need for second round medications.
Dr. Reza Aminnejad

26. Calcium channel blocking anticonvulsants: “Gabapentinoids”
❑ ED utility for gabapentin and pregabalin is limited.
❑ Both gabapentin and pregabalin are recommended for the treatment of post-herpetic
neuralgia and diabetic neuropathy.
❑ Pregabalin has also demonstrated efficacy in fibromyalgia-related pain.
❑ In a meta-analysis of nine randomized trials, both medications were not effective for low
back pain with or without radiculopathy, and were associated with increased risk for
adverse events.
❑ EM prescribers should be aware of both the danger of respiratory depression, especially
when combining gabapentinoids with opioids, and potential for misuse.
Dr. Reza Aminnejad

27. Skeletal muscle relaxants
❑ Skeletal muscle relaxants are given to 43% of ED patient.
❑ There is no benefit for SMRs in LBP ED patients compared to or in addition to NSAIDs.
❑ Avoidance of the use of skeletal muscle relaxants for treatment of acute pain is
recommended.
Dr. Reza Aminnejad

28. Alternative analgesic strategies
❑ Regional blocks using local anesthetics (e.g. lidocaine, bupivacaine) with or without epinephrine.
❑ Local anesthetics have also been used for trigger points to treat focal, hyper-irritated muscle spasm.
❑ Adverse effects include central nervous system effects like dizziness, drowsiness, and seizures, and
cardiotoxic effects like arrhythmias.
❑ Methoxyflurane and nitrous oxide are both self-administered, self-titrated, rapid-acting, and noninvasive
inhalational agents.
❑ Entonox: nitrous oxide/oxygen
❑ Propofol
❑ Dexmedetomidine is suitable in a patient requires continuous analgosedation and there is concern for
respiratory depression.
❑ Capsaicin (cannabinoid hyperemesis syndrome, postherpetic neuralgia and diabetic neuropathy)
Dr. Reza Aminnejad

29. When opioids are unavoidable
❑ Started at the lowest possible dose
❑ Titrated to reasonable pain management goals
❑ Monitor for adverse effects
❑ In the event that the patient is on chronic opioids, all dosage forms should be converted
into morphine milligram equivalents (MME) in order to inform providers of risk of opioid-
related adverse effects and trend over time. A daily MME of ≤49 mg should be targeted to
avoid opioid-related mortality.
❑ Upon discharge from the ED, providers should prescribe the shortest course of opioids
possible (2-3 days).
Dr. Reza Aminnejad

30. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while
providing effective pain relief. Intravenous is simple to administer, non-invasive, rapid onset, and quick absorption; it
might be a viable choice in a variety of situations to reduce patient suffering or
delays in pain management.
Dr. Reza Aminnejad

31. Dr. Reza Aminnejad
Fentanyl
Ketamine
Dexmedetomidine
Midazolam

32. Intranasal sufentanil versus intravenous morphine
Blancher M, Maignan M, Clapé C, Quesada JL, Collomb-Muret R, Albasini F, Ageron FX, Fey S, Wuyts A, Banihachemi JJ,
Bertrand B, Lehmann A, Bollart C, Debaty G, Briot R, Viglino D. Intranasal sufentanil versus intravenous morphine for
acute severe trauma pain: A double-blind randomized non-inferiority study. PLoS Med. 2019 Jul 16;16(7):e1002849. doi:
10.1371/journal.pmed.1002849. PMID: 31310600; PMCID: PMC6634380.
Dr. Reza Aminnejad

33. Intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to
severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to
fentanyl, but causes more sedation, which should inform the choice of intranasal agent.
Dr. Reza Aminnejad

34. Dr. Reza Aminnejad

35. Tapentadol Versus Tramadol
Roulet L, Rollason V, Desmeules J, Piguet V. Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their
Pharmacological, Efficacy and Safety Profiles in Adult Patients. Drugs. 2021 Jul;81(11):1257-1272. doi: 10.1007/s40265-
021-01515-z. Epub 2021 Jul 1. PMID: 34196947; PMCID: PMC8318929.
Dr. Reza Aminnejad

36. ❑ Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and
monoaminergic properties.
❑ Tapentadol is approximately two to three times more potent than tramadol and two to three times less
potent than morphine.
❑ It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450
enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-
drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes.
❑The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less
exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse
effects (constipation, respiratory depression, abuse) than tramadol.
❑ The trials published to date show overall that tapentadol does not provide a clinically significant analgesic
improvement compared to existing treatments, for which the safety profile is much better known.
Dr. Reza Aminnejad

37. first-line treatment options include pregabalin and duloxetine, with gabapentin seeming a reasonable alternative to
pregabalin treatment. Second- and third-line drugs include opioids and topical analgesics. Indeed, opioids are an effective
alternative in the treatment of neuropathic pain; however adverse reactions and addiction concerns limit their
widespread use. More recently, research has extended beyond symptom alleviation. Pathogenesis-oriented treatments,
including α-lipoic acid and actovegin, appear promising, but results need to be confirmed in more extensive trials.
Dr. Reza Aminnejad

38. Dr. Reza Aminnejad

39. Dr. Reza Aminnejad

40. Dr. Reza Aminnejad