All Pharmacy Pearls

Introduction

    visit the emergency department (ED)

  • 2. It is estimated that at least 30,000 people die in the

    • United States as a direct result of the use of opioids

    each year

  • 3. Although it seems that no specific specialty has been

    • primarily responsible for the opioid epidemic, clinicians

    in the ED are uniquely positioned on the front lines to

    be able to combat the ongoing crisis

  • 4. An expanding body of research is beginning to

    • emerge that suggests that nonopioid medications such

    as acetaminophen or nonsteroidal anti-inflammatories

Pharmacology

AgentDoseOnsetDurationIndication
Acetaminophen325–1000 mg PO/Rectal/IVPO 10–30 min; IV ~5 minPO ~4.5 hr; IV ~3 hrMild to moderate pain
Ibuprofen400–800 mg PO15–30 min~6 hrsMild to moderate pain
Ketorolac10–30 mg PO/IV/IM~30 min4–6 hoursAcute flank, abdominal, MSK, headache, fractures
Ketamine0.15–0.30 mg/kg ± 0.15–0.25 mg/kg/hr infusion IV/IM/IN10–30 min30–60 minModerate to severe MSK pain, flank pain
Lidocaine1.5 mg/kg IV; 5% Patch 12 hr out of 24 hr (IV/transdermal)IV 1–5 min; Patch ~4 hrIV 0.5–1 hr; Patch ~12 hrRenal colic, mild MSK pain
Metoclopramide/prochlorperazine + diphenhydramine10 mg + 25–50 mg diphenhydramine IV/PO5–10 min3–5 hrMigraine

Evidence

Author, YearDesign / Sample Size / Type of PainNonopioid InterventionComparatorOutcome
Chang, 2017RCT; n=411; moderate to severe acute extremity painIbuprofen 400 mg + APAP 1000 mgOxycodone/APAP 5/325 mg; Hydrocodone/APAP 5/325; Codeine/APAP 30/300 mgReduction in pain score 2 hours after single dose: Ibuprofen 400 mg + APAP 1000 mg = 4.3; Oxycodone/APAP 5/325 mg = 4.4; Hydrocodone/APAP 5/325 = 3.5; Codeine/APAP 30/300 mg = 3.9. “…no statistically significant or clinically important differences in pain reduction.”
Rainer, 2000RCT; N=148; painful isolated limb injuriesIV Ketorolac 10 mg x 1 + PRN IV ketorolac 5 mg q5m (max 30 mg)Morphine 5 mg x 1 + PRN morphine 2.5 mg q5m (max 15 mg)No difference in median time to pain relief. Patients’ satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). Median reduction in pain score was 1.09/hr vs 0.87/hr in the ketorolac and morphine group respectively (P=0.003).
Motov, 2018RCT; n=30; severe acute abdominal, flank, MSK, or malignant painIV Ketamine 0.3 mg/kg over 15 minMorphine 0.1 mg/kg over 15 minPrimary change in mean pain scores was not significantly different. Higher rates of psychoperceptual adverse effects with ketamine. No statistically significant differences with respect to changes in vital signs and need for rescue medication.
Soleimanpour, 2012RCT; n=240; renal colicIV lidocaine (1.5 mg/kg)IV morphine (0.1 mg/kg)Pain score at 5 min lidocaine 3.18 vs morphine 4.45 (p=0.001). Pain score at 30 min lidocaine 1.13 vs morphine 2.23 (p=0.001). Lidocaine 90% vs 70% morphine responded appropriately (score < 3) at end of treatment (p=0.0001).
Kostic, 2010RCT; n=66; acute migraineIV prochlorperazine 10 mg + IV diphenhydramine 12.5 mgSubQ sumatriptan 6 mg + placeboBaseline pain scores were similar for the groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm vs 50 mm. Sedation, nausea, and headache recurrence rates were similar.

Conclusions

  • Because opioids carry substantial harm and emergency clinicians are well positioned to curb the opioid crisis, nonopioid agents such as acetaminophen and NSAIDs should be considered first-line for mild-to-moderate pain in the ED.
  • A combination of ibuprofen 400 mg plus acetaminophen 1000 mg provided pain relief comparable to oral opioid/acetaminophen combinations for acute extremity pain (Chang 2017), with no clinically important difference in pain reduction at 2 hours.
  • IV ketorolac performed at least as well as morphine for limb injury (Rainer 2000), and IV ketamine matched morphine for acute pain though with more psychoperceptual adverse effects (Motov 2018) — supporting NSAIDs and ketamine as opioid-sparing options.
  • Agent selection can be tailored to the pain syndrome: IV lidocaine outperformed morphine in renal colic (Soleimanpour 2012), and IV prochlorperazine plus diphenhydramine was an effective nonopioid regimen for acute migraine (Kostic 2010).

References

1.
Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from
http://www.micromedexsolutions.com/
2.
Motov S. The Treatment of Acute Pain in the Emergency Department: A White Paper Position Statement Prepared for the American
Academy of Emergency Medicine. J Emerg Med. 2018 May;54(5):731-736.
3.
Chang AK. 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
4.
Rainer TH. Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind
randomised controlled trial. BMJ. 2000 Nov 18;321(7271):1247-51.
5.
Motov S. Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A
randomized controlled trial. Am J Emerg Med. 2018 May 16. pii: S0735-6757(18)30407-8.
6.
Soleimanpour H. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency
department. BMC Urol. 2012 May 4;12:13. doi: 10.1186/1471-2490-12-13.
7.
Kostic MA. A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine
therapy in the emergency department. Ann Emerg Med. 2010 Jul;56(1):1-6.
Tags: acetaminophen ibuprofen NSAIDs opioids

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