By Conrad Stallings, Kevin Crocker, Michael Wells, Nick Smith and Casey Patrick
Case study: EMS respond to a 911 call for an elderly woman in respiratory distress. She is a 71-year-old female with a past medical history significant for chronic obstructive pulmonary disease (COPD), chronic kidney disease and hypercholesterolemia.
The family notes that she was discharged from the hospital 1 week ago, after being treated for pneumonia and COPD exacerbation. They state that she has been acting confused and is not following commands appropriately. Her breathing has become labored over the past day, and she complains of diffuse body aches.
Initial vital signs reveal a blood pressure of 101/72 mmHg, a heart rate of 105 beats per minute, a temperature of 100.9℉, a respiratory rate of 26 breaths per minute and an oxygen saturation of 88% on room air.
Paramedics provided supplemental oxygen and transported her to the hospital emergency department (ED), where she was recently discharged. En route, an IV was established, a fluid bolus was initiated, and an analgesic was considered.
Which analgesic is most appropriate for this patient?
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Pain management: Undertreated?
Pain is one manifestation of a harmful change to the body’s homeostasis and comes in many different forms and intensities, occurring in almost any part of the human body.
Many patients call EMS for pain relief, unaware of the underlying cause. At least 20% of patients transported by EMS report moderate-to-severe pain [1,2].
While transporting patients to the hospital for a thorough diagnostic evaluation is critical, the initial symptomatic treatment of a patient’s illness is also essential. Pain management is recognized as a priority by the National Association of EMS Physicians [3,4]. Unfortunately, pain is often undertreated.
All healthcare and emergency providers must have a basic understanding of pain management and analgesic options. Whether the patient presents with general discomfort or acute, chronic, traumatic, colicky, referred, mild or severe pain, there is usually some relief available that can and should be administered by EMS personnel.
What pain management options are available?
Opioids such as fentanyl and morphine have long been the initial drugs of choice when treating acute pain in the prehospital setting. They are generally very effective at easing pain and have a quick onset. However, the side effects are often significant and must be considered.
Respiratory depression and hypotension are two of the most impactful opioid side effects seen in EMS. Additionally, considering the opioid epidemic, providers are more aggressively reaching for alternatives to opioids to treat patients complaining of pain.
Acetaminophen and ketorolac are two non-opioid options commonly used for analgesia in the ED and hospital settings. Still, no study has compared these to each other in the prehospital environment.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been utilized for decades and can be found on almost all pharmacy, convenience store and grocery store shelves. NSAIDs, such as ketorolac, act on cyclooxygenase (COX) enzymatic activity to inhibit prostaglandin and thromboxane production. The analgesic effects of ketorolac last about 6 hours, with patients noticing some degree of pain relief within 30 minutes of administration. Many contraindications of NSAID use need to be considered in all patients (see below).The most important are related to reversible platelet inhibition and a detrimental impact on kidney function.
Acetaminophen is another well-known analgesic with an established safety and efficacy profile. Though the mechanism of action of acetaminophen is complex and still not clearly described, it is thought to also inhibit the synthesis of prostaglandins along with multiple other potential sites of action.
It is worth noting that acetaminophen is not considered an anti-inflammatory medication and does not inhibit platelet activity. The peak onset of pain relief from intravenous acetaminophen is approximately 10 minutes and lasts 4-6 hours.
Careful consideration should be made before administering acetaminophen, as many over-the-counter and prescription drugs contain acetaminophen. A thorough medication history should be taken to ensure that a patient does not exceed the daily recommended dose.
Pain management contraindications
IV acetaminophen vs. IV/IM ketorolac
MCHD conducted a retrospective cross-sectional evaluation of patients who received IV acetaminophen or IV or IM ketorolac and compared the effectiveness of each [5]. This is the first known case comparing IV acetaminophen and parenteral ketorolac use for analgesia in the prehospital setting. Cases were selected based on the administration of one of these medications to patients with two or more documented pain scores. Patients were excluded if they received both medications and if the indication for medication was fever.
The study included 2,178 patients from Jan. 1, 2019, to Nov. 30, 2021. A total of 856 patients received IV acetaminophen, and 1,322 received parenteral ketorolac. Protocols allowed for 1,000 mg IV acetaminophen, 15 mg IV ketorolac, or 30 mg IM ketorolac for analgesia if a patient self-reported pain greater than 3/10 in severity.
Adjusting for confounders and selection bias, the analysis — which utilized inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to address for potential confounding from the paramedics choosing the analgesic — concluded that there was no statistically significant difference in pain relief between the two groups with a treatment effect by IPTW of 0.11(95% Cl -0.16, 0.37) and by PSM of 0.15 (95% Cl -0.13, 0.43).
Both analgesics provided a clinically meaningful change in pain scores for all patients and a subgroup of traumatic pain patients. Also, while hypotension has been reported with IV acetaminophen use, no significant blood pressure changes were noted after either medication [6].
The bottom line: IV acetaminophen and IV/IM ketorolac worked similarly when used by EMS to treat moderate to severe prehospital pain.
| More: Why haven’t you brought IV Tylenol into your service?
If that doesn’t work, it’s embedded in this article: https://www.ems1.com/pain-management/articles/why-havent-you-brought-iv-tylenol-into-your-service-XyYsdrOJ6g1o6XkG/
Back to our patient
In the ambulance, paramedics elected to administer IV acetaminophen to our 71-year-old patient for her diffuse body aches. Her reported pain score improved by three points before arrival at the hospital. The patient clearly benefited from the timely analgesia. IV acetaminophen was felt to be a more advantageous medication to administer in her unique circumstance for multiple reasons:
- Oral medications were not ideal as she presented in an altered mental state, which placed her at a higher risk of aspiration.
- NSAIDs were contraindicated due to her advanced age, higher risk of bleeding and history of kidney disease.
- Fentanyl (and other opioids) could have decreased her respiratory drive, thereby exacerbating any potential underlying pulmonary or metabolic disease processes, as her history was concerning for sepsis/recurrent pneumonia.
Another factor that EMS agencies and hospitals must consider is medication cost. At the time of our analysis, IV acetaminophen cost approximately $9 per dose, while parenteral ketorolac was slightly more than $1 per dose. Though ketorolac is currently cheaper than IV acetaminophen, the considerably greater side-effect risk profile may negate this price advantage. The final medication choice will be service- and budget-specific, and depend on local and state protocol availability.
Ketorolac’s use remains advantageous in certain situations. Currently, there is no acetaminophen in IM form. Therefore, patients with difficult IV access would still benefit from ketorolac use, assuming PO or rectal options were unavailable, and no contraindications were present.
In closing, equal attention should be given to both ketorolac and acetaminophen as potential prehospital analgesics. There was no significant difference in pain relief between the two medications, and IV acetaminophen cost continues to decline in the US. Contraindications, cost, convenience and local/state protocols should drive the decision of which medication to stock and administer.
REFERENCES
- Cordell WH, Keene KK, Giles BK, Jones JB, et al. The high prevalence of pain in emergency medical care. “Am J Emerg Med”. 2002;20(3):165-169.
- McLean SA, Maio RF, Domeier RM. The epidemiology of pain in the prehospital setting. “Prehosp Emerg Care”. 2002;6: 402–5. PMID: 12385606.
- Alonso-Serra HM, Wesley K, National Association of EMS Physicians Standards and Clinical Practices Committee. Prehospital pain management. “Prehosp Emerg Care”. 2003;7(4):482-488.
- Sobieraj DM, Martinez BK, Miao B, et al. Comparative effectiveness of analgesics to reduce acute pain in the prehospital setting. “Prehosp Emerg Care”. 2020;24(2):163-174.
- McArthur R, Cash, RE, Rafique Z, Dickson R, et al. (2024). Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review. “The Journal of Emergency Medicine”. 67(3), e259–e267.
- Maxwell EN, Johnson B, Cammilleri J, Ferreira JA. (2019). Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. “The Annals of pharmacotherapy”. 53(10), 1033–1041.
