Analgesics for Acute Pain in Adults

Acute pain can result from acute illness (e.g., renal colic, sickle cell crisis), injury, or surgery.7,86 As opposed to chronic pain, its etiology and location is usually clear.4 Acute pain is self-limited, improving over hours to weeks as the injury heals.4 Treatment minimizes detrimental physiologic responses (e.g., tachycardia, shallow breathing, immobility, muscle spasms, ileus, impaired immune response), adverse psychological effects (e.g., anxiety, fear), and progression to chronic pain.87, However, use of opioids for acute pain should be with the lowest necessary dose for the shortest duration possible to prevent help transition of acute use to chronic use.88 Set realistic goals for pain relief and function (e.g., 33% to 50% decrease in pain).59 Some hospitals are developing ALternatives To Opioid (ALTO)74 or Enhanced Recovery After Surgery (ERAS) protocols. Perioperatively, different medications and routes are combined (i.e., a multimodal or balanced approach) to increase efficacy and decrease side effects.56,59 The charts below review various analgesics to treat different types and severities of acute pain in adults. The first chart reviews preferred or first-line analgesics for acute pain. The second chart reviews other analgesic options that can be considered for use in patients with acute pain.

Preferred Analgesics for Acute Pain in Adults

Drug or Drug Class

Consider for…

Comments

NSAID

(e.g., ibuprofen 400 mg every four to six hours)
  • osteoarthritis58
  • dental pain (including surgery)6,86
  • renal colic89
  • low back pain83
  • fractures82
  • musculoskeletal pain75
  • tension headache81
  • migraine headache10,78
  • biliary colic14
  • abdominal surgery86
  • orthopedic surgery86
  • episiotomy85
  • opioid-sparing effect.56
    • Use WITH acetaminophen for better efficacy (e.g., [adults] acetaminophen 500 to 1,000 mg WITH ibuprofen 200 to 400 mg every six hours as needed).17
  • One in two to three patients with moderate to severe pain has a 50% reduction in pain over four to six hours.1
  • Oral ibuprofen at doses of 400, 600, and 800 mg provide similar pain relief.76
  • Ibuprofen 400 mg plus acetaminophen 1,000 mg reduces moderate-to-severe musculoskeletal pain as well as many opioid and acetaminophen combinations.75
  • Oral ketorolac has similar efficacy to other NSAIDs, but the risks associated with its use outweigh the possible benefits.57,58
  • Topical NSAIDs may work as well as oral NSAIDs for acute musculoskeletal pain (e.g., sprain).16
  • Available injectable NSAIDs and cost per dosea: ibuprofen (Caldolor [US: ~$23]), ketorolac (Toradol [Canada], generics [US: ~$10, Canada: ~$1.50]), meloxicam (Anjeso [US: ~$93]).
  • Injectable ketorolac and ibuprofen have not been proven more effective than oral ibuprofen.8,12,40 Consider an injection for renal colic, and for patients unable to take oral NSAIDs.5,12
  • Injectable meloxicam may not be appropriate for acute pain due to slow onset (~2 to 3 hours vs ~1 hour with other IV NSAIDs).42 There is no good evidence that it is safer than other injectable NSAIDs, despite being more COX-2 selective.
  • Limit use to <15 days/months to reduce the risk of medication overuse headache.72
  • In the US, NSAIDs are contraindicated for perioperative pain due to CABG.
  • For information on the use of NSAIDs in patients with kidney or cardiovascular disease, and mitigation of gastrointestinal risk, see our FAQ, Managing NSAID Risks.

Acetaminophen
  • osteoarthritis58,*
  • dental pain (including surgery)86,*
  • renal colic5,*
  • fractures9
  • musculoskeletal pain86
  • tension headache11
  • migraine headache10
  • abdominal surgery86
  • orthopedic surgery86
  • episiotomy85,*
  • opioid-sparing effect56

*NSAID may be more effective

  • Use WITH an NSAID for better efficacy (e.g., acetaminophen 500 to 1,000 mg WITH ibuprofen 200 to 400 mg every six hours as needed in adults).17
  • One in three to four patients with moderate to severe pain has a 50% reduction in pain over four to six hours with acetaminophen 1,000 mg.1
  • Acetaminophen 1,000 mg may not relieve pain much better than 500 mg.1,84
  • Ibuprofen 400 mg plus acetaminophen 1,000 mg reduces moderate-to-severe acute extremity pain as well as many opioid and acetaminophen combinations.75
  • In chronic liver impairment, limit the total daily dose to 2 to 3 grams (instead of the usual 4 gram max adult daily dose).13
  • May post a higher risk of medication overuse headache than NSAIDs.73 Limit use to <15 days/month to reduce the risk.72

Strong oral opioids

(e.g., hydrocodone, oxycodone)
  • Pain not relieved by nonopioids, assuming patient can take oral medications.7,56
  • Pain not expected to be relieved by non-opioids (e.g., invasive surgery [open abdominal surgery], major trauma [crush injuries, burns], assuming patient can take oral medications.4,7,56
  • Not proven more effective than ibuprofen 400 mg at achieving 50% reduction in moderate to severe pain.1
  • Do not use extended-release opioids for acute pain.7
  • May be as effective as IV opioids, even after significant surgeries (e.g., cardiac surgery).43
  • Consider combining with nonopioids to provide better analgesia and minimize side effects (e.g., opioid-sparing effect).56,59
  • Advise patients to taper off the opioid as their pain resolves, being mindful of the total daily dose of acetaminophen if weaning from an opioid/acetaminophen combo to acetaminophen.7
  • For more safety considerations, see our toolbox, Appropriate Opioid Use.

Parenteral opioids

(IV, epidural, or spinal [intrathecal])
  • Pain not expected to be relieved by non-opioids (e.g., invasive surgery [open abdominal surgery], major trauma [e.g., crush injuries, burns]) in patients who cannot take oral medications.4,7,56
  • Moderate to severe pain in patients with suspected malabsorption.56
  • Moderate to severe pain requiring immediate relief or rapid dose titration.56
  • Painful procedures.59
  • Pain due to MI despite nitroglycerin and beta-blocker (IV morphine).35
  • IV opioids have a quicker onset of action than oral opioids, allowing for faster titrations, but have more risks (e.g., adverse effects, ), and shorter duration of action.56
  • Consider combining with nonopioids to provide better analgesia and minimize side effects (e.g., opioid-sparing effect).56,59
  • PCAs may be preferred over intermittent dosing or continuous infusion due to improved pain control (despite lower doses), improved tolerability, and patient satisfaction (e.g., post-op patients).4
  • Use our chart, Equianalgesic Dosing of Opioids for Pain Management, for help with initial IV dosing, converting between opioids, or converting from IV to oral opioids once pain is controlled and oral intake is tolerated.
  • Follow policies to get pain service approval before adding a systemic opioid to a regional (e.g., epidural, spinal) opioid.

Fentanyl:

  • Consider fentanyl for patients with true allergy to morphine or hydromorphone.18
  • Consider when a fast onset but short duration of action is needed (e.g., procedures). IV: peaks in four to six minutes, and a single dose lasts 30 to 60 minutes.4,42 Epidural: a single dose lasts two to three hours.42
  • Accumulates in fat with repeat dosing; may not be a good choice in obesity.4
  • A preferred opioid in kidney disease.15 Dose cautiously.42

Hydromorphone

  • A preferred opioid in kidney impairment.15 However, use lower starting doses for CrCl <60 mL/min.15

Morphine:

  • Use IV morphine with caution in acute MI patients with bradycardia, right ventricular infarct, or hypotension.4
  • Not recommended in kidney impairment.4
  • Intrathecal or epidural morphine can last up to 24 hours.4,19

Local Anesthetics

(e.g., bupivacaine, ropivacaine, lidocaine, mepivacaine)

(For more on lidocaine patches and other topical pain relievers, see our chart, Topicals for Pain Relief.)
  • Opioid-sparing effect for patients at high risk from opioids (e.g., patients with lung disease, obstructive sleep apnea, morbid obesity, opioid tolerance, opioid misuse).20,21
  • Intrathoracic, abdominal, or spinal surgery (e.g., epidural anesthesia)22
  • Upper extremity/hand surgery (e.g., peripheral nerve block).24
  • Lower extremity surgery (e.g., total hip/knee arthroplasty (e.g., spinal or epidural anesthesia, peripheral nerve block)24
  • Carotid endarterectomy (e.g., peripheral nerve block)33
  • Deep laceration repair (e.g., local infiltration, peripheral nerve block)37
  • Post-op pain (e.g., surgical site pain [e.g., local anesthetics], intravenous lidocaine)32,38
  • For epidural administration, local anesthetics are often combined with an opioid to reduce the amount of local anesthetic needed.4
  • Ensure safe antithrombotic management in patients receiving regional anesthesia.
  • Elastomeric pumps (e.g., On-Q) can provide continuous infusion of local anesthetics to the surgical site for up to five days.31
  • Liposomal bupivacaine(Exparel [US]) is indicated for single-dose infiltration at the surgical site and as an interscalene brachial plexus nerve block to produce postsurgical local (infiltration) or regional (peripheral nerve block) analgesia.36 The bupivacaine implant (Xaracoll [US]) is indicated for placement into the surgical site to produce postsurgical analgesia for up to 24 hours after open inguinal hernia repair.39 Bupivacaine/meloxicam extended-release (Zynrelef [US]) is applied to the surgical site prior to suturing after foot and ankle, small-to-medium open abdominal, and lower extremity joint arthroplasty surgical procedures.41 Posimir (US) is a bupivacaine solution approved for administration into the subacromial space at the end of arthroscopic shoulder surgery.90
    • Data do not demonstrate consistent or substantial clinical advantages with use of liposomal bupivacaine over other local anesthetics.30
    • Compared to standard bupivacaine, bupivacaine/meloxicam extended-release reduces opioid use by ~5 to 10 mg of morphine in the first 24 hours, and pain score differences don’t seem clinically significant after about 24 hours.41
    • Avoid repeat bupivacaine doses, or other local anesthetics, for at least 96 hours after administration of Exparel, Xaracoll, or Zynrelef, and at least 168 hours after Posimir, due to persistence of bupivacaine in the systemic circulation and potential for overdose.36,39,41,90
    • Expensive; ~$365 for Exparel (266 mg), ~$250 for Xaracoll (300 mg), or ~$280 for Zynrelef (400 mg/12 mg), Posimir ($319) vs a few dollars for regular bupivacaine.a
  • Continuous IV lidocaine infusion may be an option when local or regional anesthesia is not possible.61 IV lidocaine may be most beneficial for patients undergoing abdominal surgeries in reducing early post-op pain and opioid use.53
  • Use our clinical resource, Safe Use of Local Anesthetics, for tips to minimize risks associated with local anesthetics.

Ketamine
  • Surgery in which severe post-op pain is expected (e.g., abdominal, thoracic, orthopedic)(best evidence).27
  • Surgical patients who are opioid-tolerant.27
  • Surgical patients at high risk of respiratory depression caused by opioids (e.g., patients with sleep apnea).27
  • As an opioid adjunct for sickle cell crisis.27
  • Acute pain in patients presenting to the ED in whom an opioid is undesirable (e.g., opioid-tolerant, history of opioid misuse, opioid-naïve, elderly, taking medication-assisted treatment for opioid use disorder).60
  • Low-dose IV ketamine (<0.5 mg/kg) may provide similar pain relief compared to opioids in the ED for pain from a variety of causes.60
  • Ketamine at doses ≥0.3 mg/kg may be associated with more neuropsychiatric side effects compared to standard care (e.g., dizziness, drowsiness, emergence phenomena, dissociation, dysphoria, hallucinations, nightmares).60,47
  • Consider doses of ≤0.35 mg/kg (bolus), or an infusion of 0.1 to 0.5 mg/kg/hour (max 1 mg/kg/hour).27
    • Many studies and protocols use bolus doses of 0.1 to 0.3 mg/kg given over 15 minutes.62 Dose can be repeated once after 30 minutes if needed.55
      • Infusion over 15 minutes instead of 5 minutes helps minimize neuropsychiatric side effects.64
    • There is less evidence for nasal administration. Consider a dose of 0.7 to 1 mg/kg, with a maximum of 1 mL per nostril.62
    • Some ED protocols set a maximum cumulative dose of 0.3 mg/kg, up to 50 mg.54
    • Examples of monitoring in the ED include continuous pulse oximetry, telemetry (or vitals every 10 minutes), and immediate availability of the ED physician for at least 30 min post-dose.54,55
  • Perioperative ketamine does not seem to benefit patients undergoing surgery not associated with moderate to severe pain.27
  • A meta-analysis of ketamine administered preoperatively, intraoperatively, or postoperatively, mostly at doses of 0.25 to 1 mg/kg as boluses or an infusion at 0.12 to 0.3 mcg/kg/hour seems to reduce postoperative opioid use and pain scores.20,46 However, other studies have not shown benefit of pre-op boluses.20,47
  • Avoid ketamine in patients with psychosis, uncontrolled cardiovascular disease or hypertension, pregnancy, moderate to severe liver impairment, or increased intraocular or intracranial pressure.27
  • For information on use of ketamine in the ICU, see our chart Meds for ICU Analgesia and Sedation.
  1. Wholesale acquisition cost (WAC). US pricing by Elsevier, accessed October 2023.

Not Preferred for Acute Pain

Drug or Drug Class

Comments

Buprenorphine

(partial agonist [mu]/

antagonist [kappa])
  • Buprenorphine is a mixed opiate with partial agonist and antagonist activity.42
  • See our chart, FAQs About Buprenorphine for Chronic Pain, for more on buprenorphine, including why sublingual, buccal, and transdermal buprenorphine products should NOT be used for acute pain, and drawbacks of parenteral buprenorphine.

Codeine
  • Codeine is metabolized to morphine via CYP2D6.2
    • Genetic polymorphisms may result in poor response to codeine (poor metabolizers) or toxicity (ultrarapid metabolizers).2,23
    • Efficacy of codeine is reduced by strong CYP2D6 inhibitors (e.g., bupropion, fluoxetine).23
  • Avoid codeine in children and breastfeeding women.23,28

Fentanyl

(non-injectable formulations [e.g., patches, transmucosal lozenge, buccal tablet])
  • Reserve the non-injectable fentanyl products for patients with chronic pain who are opioid-tolerant (e.g., have been taking the equivalent of at least 60 mg of morphine equivalent daily for at least one week) due to risk of toxicity, including respiratory depression.34,50

Gabapentinoids (gabapentin or pregabalin)
  • Mounting evidence suggests any benefit of pre-op gabapentin or pregabalin are marginal and likely don’t outweigh risks, such as delirium, dizziness, respiratory depression, or visual disturbances.3,44
  • Avoid gabapentinoids in the elderly, patients with kidney impairment, and patients with sleep apnea.3,45
  • See our chart, Enhanced Recovery After Surgery: Developing an ERAS Protocol for dosing.

Meperidine
  • Meperidine has a neurotoxic metabolite, normeperidine, that can cause anxiety, tremors, myoclonus, hallucinations, and seizures.29 Normeperidine can accumulate with repeated meperidine dosing, especially in patients with kidney or liver impairment and in the elderly.29,42,48
  • Meperidine poses a higher risk of postoperative delirium than other opioids.42
  • Other side effects include confusion and dysphoria.42
  • Meperidine is poorly effective orally.48
  • Naloxone is not effective for treating normeperidine toxicity, and in fact may worsen it.77
  • Meperidine’s vagolytic activity can cause increased ventricular response in patients with supraventricular tachyarrhythmias.42
  • Poses risk of serotonin syndrome with other serotonergic medications.42

Oliceridine (Olinvyk)
  • There is a ceiling dose of 27 mg/day due to risk of QT prolongation. Once a cumulative daily dose of 27 mg is met, a different analgesic will be needed until the next day.80
  • There is limited safety data beyond 48 hours.80
  • Patients taking a moderate to strong CYP2D6 or CYP3A4 inhibitor may need less frequent dosing; monitor response CYP3A4 inducers may reduce efficacy.80
  • Poses risk of serotonin syndrome with other serotonergic medications.80

Other mixed agonist/antagonists

(e.g., butorphanol, nalbuphine)
  • Analgesic effects of partial agonists (kappa)/antagonists (mu) are limited by a dose ceiling.51
  • Avoid in opioid-tolerant patients, as use may lead to withdrawal symptoms.42
  • Butorphanol use is often reserved for pain when other options are not effective, tolerated, or inadequate.63
    • Use may also be limited by adverse effects (e.g., psychotomimetic effects) and prolonged respiratory depression at higher doses.63
  • Nalbuphine efficacy and safety data compared with morphine are inconsistent.52
    • Avoid doses greater than 20 mg/dose, especially in opiate-naive patients.42
    • Nalbuphine may be associated with less itching and less respiratory depression compared to morphine.52
  • See our chart, Equianalgesic Dosing of Opioids for Pain Management, for equivalent doses, other considerations, and potential side effects.

Muscle Relaxants
  • Adverse effects (e.g., sedation, dizziness, etc) are common with all muscle relaxants.79 The CNS depression commonly seen with muscle relaxants is additive with other CNS depressants (e.g., opioids, alcohol, benzodiazepines) and has led to respiratory depression and death.79 Muscle relaxants should be used cautiously in the elderly as most are listed on the Beers Criteria as potentially inappropriate for use in older adults due to their sedative effects, increased risk of falls, etc.79
  • Muscle relaxants may be used for acute pain that is not relieved with NSAIDs and acetaminophen.79 They should not be used longer than two to three weeks, and many recommend limiting their duration to no more than seven days.79
  • The old product Orphengesic Forte (orphenadrine 50 mg, aspirin 770 mg, caffeine 60 mg) was reintroduced in 2020 for mild to moderately painful musculoskeletal conditions.65 It is important to note the aspirin content of this product; the maximum dose provides a total daily aspirin dose of 3,080 mg.
  • For more information on orphenadrine and other muscle relaxants for pain, see our chart, Muscle Relaxants.

Tramadol
  • One in eight patients with moderate to severe pain has a 50% pain reduction over four to six hours with tramadol (i.e., less effective than NSAIDs or acetaminophen).1
  • Tramadol’s abuse potential may be similar to that of strong opioids.67
  • In addition to the usual opioid toxicities such as respiratory depression, tramadol can cause serotonergic effects such as nausea, vomiting, and perhaps seizures, hyponatremia, and hypoglycemia even at therapeutic doses.48,66-70
  • Hallucinations are reported in <1% of patients taking tramadol; however there may be an increasing number of cases. A Health Canada review established a link between normal doses and visual and auditory hallucinations in patients ≥65 years of age.71
  • Efficacy of tramadol is reduced in poor CYP2D6 metabolizers and by strong CYP2D6 inhibitors.23 Conversely, effects are increased in ultrarapid CYP2D6 metabolizers due to increased levels of tramadol’s active metabolite.23
  • Tramadol also interacts with CYP3A4 inhibitors and inducers, and serotonergic drugs.67
  • Withdrawal from tramadol usually presents as a typical opioid withdrawal syndrome, but 10% of cases are characterized by confusion, hallucinations, paranoia, extreme anxiety and panic, and numbness and tingling in the extremities.70
  • Maximum adult daily dose 300 mg or 400 mg, depending on product.25,26 See product labeling for dosing in elderly patients, or in patients with renal or hepatic dysfunction.
    • In elderly patients with CrCl <30 mL/min., avoid extended-release tramadol products due to central nervous system adverse effects.48
  • Although tramadol overdose can be treated with naloxone, seizures have been reported in some instances.42
  • Avoid tramadol in children and breastfeeding women.23.28,49

Abbreviations: CABG = coronary artery bypass graft; ED = emergency department; IV = intravenous; MI = myocardial infarction; NSAID = nonsteroidal anti-inflammatory drug; PCA = patient-controlled analgesia

References

  1. Bandolier. The Oxford League table of analgesic efficacy. http://www.bandolier.org.uk/booth/painpag/Acutrev/Analgesics/lftab.html. (Accessed October 28, 2023).
  2. FDA drug safety communication: safety review update of codeine use in children; new boxed warning and contraindication on use after tonsillectomy and/or adenoidectomy. February 20, 2013. https://www.fda.gov/media/85072/download. (Accessed October 31, 2023).
  3. Park CM, Inouye SK, Marcantonio ER, et al. Perioperative Gabapentin Use and In-Hospital Adverse Clinical Events Among Older Adults After Major Surgery. JAMA Intern Med. 2022 Nov 1;182(11):1117-1127.
  4. Kral LA, Ghafoor VL. Pain and its management. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Wolters Kluwer Health, 2018:1170-204.
  5. Gu HY, Luo J, Wu JY, et al. Increasing Nonsteroidal Anti-inflammatory Drugs and Reducing Opioids or Paracetamol in the Management of Acute Renal Colic: Based on Three-Stage Study Design of Network Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2019 Feb 22;10:96.
  6. Moore RA, Derry S, Aldington D, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015 Sep 28;2015(9):CD008659.
  7. Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022 Nov 4;71(3):1-95.
  8. Bookstaver PB, Miller AD, Rudisill CN, Norris LB. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever. J Pain Res. 2010 May 25;3:67-79.
  9. Paoloni JA, Milne C, Orchard J, Hamilton B. Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use. Br J Sports Med. 2009 Oct;43(11):863-5.
  10. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021 Jul;61(7):1021-1039.
  11. Stephens G, Derry S, Moore RA. Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults. Cochrane Database Syst Rev. 2016 Jun 16;2016(6):CD011889.
  12. Zhou P, Chen L, Wang E, et al. Intravenous ibuprofen in postoperative pain and fever management in adults: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res Perspect. 2023 Aug;11(4):e01123.
  13. Imani F, Motavaf M, Safari S, Alavian SM. The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations. Hepat Mon. 2014 Oct 11;14(10):e23539. doi: 10.5812/hepatmon.23539. PMID: 25477978; PMCID: PMC4250965.
  14. Long B, April MD. Are Nonsteroidal Anti-inflammatory Drugs Efficacious in Relieving Biliary Colic Pain? Ann Emerg Med. 2017 Dec;70(6):822-824.
  15. Roy PJ, Weltman M, Dember LM, et al. Pain management in patients with chronic kidney disease and end-stage kidney disease. Curr Opin Nephrol Hypertens. 2020 Nov;29(6):671-680.
  16. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017 May 12;5(5):CD008609.
  17. Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database Syst Rev. 2013 Jun 24;2013(6):CD010210.
  18. Miller B, Vahle R, Ferguson MC. What is a true opioid allergy? Pract Pain Manag 2021;21(1):
  19. Martinez-Velez A, Singh P. Epidural Morphine. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541073/. (Accessed October 30, 2023).
  20. Siu EY, Moon TS. Opioid-free and opioid-sparing anesthesia. Int Anesthesiol Clin. 2020 Spring;58(2):34-41.
  21. Gupta L, Agarwal J, Saxena KN. Opioid-free anaesthesia: The conundrum and the solutions. Indian J Anaesth. 2022 Mar;66(Suppl 2):S91-S94.
  22. Novak-Jankovič V, Markovič-Božič J. REGIONAL ANAESTHESIA IN THORACIC AND ABDOMINAL SURGERY. Acta Clin Croat. 2019 Jun;58(Suppl 1):96-100.
  23. Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021 Oct;110(4):888-896.
  24. Kamel I, Ahmed MF, Sethi A. Regional anesthesia for orthopedic procedures: What orthopedic surgeons need to know. World J Orthop. 2022 Jan 18;13(1):11-35.
  25. Gibson TP. Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Am J Med. 1996 Jul 31;101(1A):47S-53S.
  26. Kizilbash A, Ngô-Minh CT. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations. J Pain Res. 2014 Mar 24;7:149-61.
  27. Schwenk ES, Viscusi ER, Buvanendran A, et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466.
  28. Food and Drug Administration. FDA drug safety communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. April 20, 2017. https://www.fda.gov/media/104268/download. (Accessed November 1, 2023).
  29. Buck ML. Is Meperidine the Drug That Just Won't Die? J Pediatr Pharmacol Ther. 2011 Jul;16(3):167-9.
  30. Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021 Feb 1;134(2):283-344.
  31. Avanos. On-Q pain relief system. https://avanospainmanagement.com/solutions/acute-pain/on-q-pain-relief-system/. (Accessed October 30, 2023).
  32. Stamenkovic DM, Bezmarevic M, Bojic S, et al. Updates on Wound Infiltration Use for Postoperative Pain Management: A Narrative Review. J Clin Med. 2021 Oct 11;10(20):4659. doi: 10.3390/jcm10204659. PMID: 34682777; PMCID: PMC8537195.
  33. Rerkasem A, Orrapin S, Howard DP, et al. Local versus general anaesthesia for carotid endarterectomy. Cochrane Database Syst Rev. 2021 Oct 13;10(10):CD000126.
  34. Institute for Safe Medication Practices. Acute care. ISMP Medication Safety Alert! Ongoing, preventable fatal events with fentanyl transdermal patches are alarming! June 28, 2007. https://www.ismp.org/resources/ongoing-preventable-fatal-events-fentanyl-transdermal-patches-are-alarming. (Accessed October 31, 2023).
  35. Dunn BL, Page RL. Acute coronary syndrome. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Wolters Kluwer Health, 2018:231-60.
  36. Product information for Exparel. Pacira Pharmaceuticals. San Diego, CA 92121. March 2022.
  37. deLemos DM. Skin laceration repair with sutures. (Last updated April 12, 2022). In UpToDate, Post TW (ed), UpToDate, Waltham, MA 02013.
  38. Foo I, Macfarlane AJR, Srivastava D, et al. The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety. Anaesthesia. 2021 Feb;76(2):238-250.
  39. Product information for Xaracoll. Innocoll Pharmaceuticals Limited. Athlone, Ireland N37 VW42. September 2020.
  40. Neighbor ML, Puntillo KA. Intramuscular ketorolac vs oral ibuprofen in emergency department patients with acute pain. Acad Emerg Med. 1998 Feb;5(2):118-22.
  41. Product information for Zynrelef. Heron Therapeutics. San 92121. Diego, CA December 2022.
  42. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2023. http://www.clinicalkey.com. (Accessed October 29, 2023).
  43. Ruetzler K, Blome CJ, Nabecker S, et al. A randomised trial of oral versus intravenous opioids for treatment of pain after cardiac surgery. J Anesth. 2014 Aug;28(4):580-6.
  44. Kharasch ED, Clark JD, Kheterpal S. Perioperative Gabapentinoids: Deflating the Bubble. Anesthesiology. 2020 Aug;133(2):251-254.
  45. Deljou A, Hedrick SJ, Portner ER, et al. Pattern of perioperative gabapentinoid use and risk for postoperative naloxone administration. Br J Anaesth. 2018 Apr;120(4):798-806.
  46. Brinck EC, Tiippana E, Heesen M, et al. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018 Dec 20;12(12):CD012033.
  47. Avidan MS, Maybrier HR, Abdallah AB, et al. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. Erratum in: Lancet. 2017 Jul 15;390(10091):230.
  48. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 Jul;71(7):2052-2081.
  49. Government of Canada. Summary safety review – tramadol-containing products – assessing the potential risks of serious breathing problems (respiratory depression) in children and adolescents. February 22, 2017. https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-tramadol-potential-risk-serious-breathing-problems-children-adolescents.html.(Accessed November 1, 2023).
  50. FDA. Risk Evaluation and Mitigation Strategy (REMS) document. Transmucosal immediate release fentanyl (TIRF) shared system REMS progam. November 2019. https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2022_12_08_REMS_Full.pdf. (Accessed October 31, 2023).
  51. Helm S, Trescot AM, Colson J, et al. Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35.
  52. Zeng Z, Lu J, Shu C, et al. A comparison of nalbuphine with morphine for analgesic effects and safety : meta-analysis of randomized controlled trials. Sci Rep. 2015 Jun 3;5:10927.
  53. Weibel S, Jokinen J, Pace NL, et al. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth. 2016 Jun;116(6):770-83.
  54. UNC Healthcare guideline. Low-dose ketamine for analgesia in the ED. Last updated June 2015. https://www.med.unc.edu/emergmed/wp-content/uploads/sites/649/2018/04/low-dose-ketamine-for-analgesia-in-the-ed.pdf. (Accessed October 31, 2023).
  55. Mo H, Campbell MJ, Fertel BS, et al. Ketamine Safety and Use in the Emergency Department for Pain and Agitation/Delirium: A Health System Experience. West J Emerg Med. 2020 Jan 27;21(2):272-281.
  56. Herzig SJ, Mosher HJ, Calcaterra SL, et al. Improving the Safety of Opioid Use for Acute Noncancer Pain in Hospitalized Adults: A Consensus Statement From the Society of Hospital Medicine. J Hosp Med. 2018 Apr;13(4):263-271.
  57. Irizarry E, Restivo A, Salama M, et al. A randomized controlled trial of ibuprofen versus ketorolac versus diclofenac for acute, nonradicular low back pain. Acad Emerg Med. 2021 Nov;28(11):1228-1235.
  58. Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Oct. Report No.: 11(12)-EHC076-EF.
  59. Anderson WG, Liao S. Improving pain management for hospitalized medical patients: a Society of Hospital Medicine implementation guide. https://www.hospitalmedicine.org/globalassets/clinical-topics/clinical-pdf/shm_painmanagement_guide.pdf. (Accessed October 29, 2023).
  60. Ying M, Zuo Y. Efficacy of Low-dose Ketamine for Control of Acute Pain in the Emergency Setting: A Systematic Review and Meta-analysis of Randomized Controlled Trials. West J Emerg Med. 2023 May 9;24(3):644-653.
  61. McEvoy MD, Raymond BL, Krige A. Opioid-Sparing Perioperative Analgesia Within Enhanced Recovery Programs. Anesthesiol Clin. 2022 Mar;40(1):35-58.
  62. Motov SM, Vlasica K, Middlebrook I, LaPietra A. Pain management in the emergency department: a clinical review. Clin Exp Emerg Med. 2021 Dec;8(4):268-278.
  63. Pharmacy Times. Opioid agonists, partial agonists, antagonists: oh my! January 2018. https://www.pharmacytimes.com/view/opioid-agonists-partial-agonists-antagonists-oh-my. (Accessed November 1, 2023).
  64. Motov S, Drapkin J, Likourezos A, et al. Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department. West J Emerg Med. 2018 May;19(3):559-566.
  65. Product information for Orphengesic Forte. Galt Pharmaceuticals. Atlanta, GA 30339. April 2021.
  66. Fournier JP, Azoulay L, Yin H, et al. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med. 2015 Feb;175(2):186-93.
  67. 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.
  68. de Canecaude C, Rousseau V, Chebane L, et al. Can tramadol really induce hyponatraemia? A pharmacovigilance study. Br J Clin Pharmacol. 2021 Feb;87(2):683-686.
  69. Morrow RL, Dormuth CR, Paterson M, et al.. Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. BMJ Open. 2019 Mar 13;9(3):e026705.
  70. DEA. Tramadol (trade names: Ultram, Ultracet). May 2023. https://www.deadiversion.usdoj.gov/drug_chem_info/tramadol.pdf#search=tramadol. (Accessed November 2, 2023).
  71. Health Canada. Summary safety review-tramadol-containing products-assessing the potential risk of hallucinations. December 28, 2020. https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00253. (Accessed November 2, 2023).
  72. Alstadhaug KB, Ofte HK, Kristoffersen ES. Preventing and treating medication overuse headache. Pain Rep. 2017 Jul 26;2(4):e612.
  73. McNeil M. Headaches in Adults in Primary Care: Evaluation, Diagnosis, and Treatment. Med Clin North Am. 2021 Jan;105(1):39-53.
  74. Floyd SB, NcGarby S, Cordero Romero S, et al. Emergency Department Alternatives to Opioids: Adapting and Implementing Proven Therapies in Practice. Int J Environ Res Public Health. 2023 Jan 10;20(2):1206.
  75. Chang AK, Bijur PE, Esses D, et al. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial. JAMA. 2017 Nov 7;318(17):1661-1667.
  76. Motov S, Masoudi A, Drapkin J, et al. Comparison of Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2019 Oct;74(4):530-537.
  77. Hassan H, Bastani B, Gellens M. Successful treatment of normeperidine neurotoxicity by hemodialysis. Am J Kidney Dis. 2000 Jan;35(1):146-9 [abstract].
  78. Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013 Apr 30;2013(4):CD008039.
  79. Clinical Resource, Muscle Relaxants. Pharmacist’s Letter/Prescriber’s Letter. March 2019.
  80. Product information for Olinvyk. Trevena. Chesterbrook, PA. July 2021.
  81. Derry S, Wiffen PJ, Moore RA, Bendtsen L. Ibuprofen for acute treatment of episodic tension-type headache in adults. Cochrane Database Syst Rev. 2015 Jul 31;2015(7):CD011474.
  82. Murphy PB, Kasotakis G, Haut ER, et al. Efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute pain after orthopedic trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Orthopedic Trauma Association. Trauma Surg Acute Care Open. 2023 Feb 21;8(1):e001056.
  83. Cashin AG, Wand BM, O'Connell NE, et al. Pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2023 Apr 4;4(4):CD013815.
  84. McQuay HJ, Moore RA. Dose-response in direct comparisons of different doses of aspdcirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies. Br J Clin Pharmacol. 2007 Mar;63(3):271-8.
  85. Schachtel BP, Thoden WR, Baybutt RI. Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain. J Clin Pharmacol. 1989 Jun;29(6):550-3.
  86. Chou R, Wagner J, Ahmed AY, et al. Treatments for Acute Pain: A Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Dec. Report No.: 20(21)-EHC006.
  87. Baratta JL, Schwenk ES, Viscusi ER. Clinical consequences of inadequate pain relief: barriers to optimal pain management. Plast Reconstr Surg. 2014 Oct;134(4 Suppl 2):15S-21S.
  88. Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017 Mar 17;66(10):265-269.
  89. Afshar K, Jafari S, Marks AJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev. 2015 Jun 29;(6):CD006027.
  90. Product information for Posimir. Innocoll Pharmaceuticals. Athlone, IE N37 VW42. February 2022.

Cite this document as follows: Clinical Resource, Analgesics for Acute Pain in Adults. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. December 2023. [391224]

Related Articles