Table 5.

Initial pharmacologic management of pain in seriously ill or end-of-life emergency department patients

Medication	Details
First-line agents to consider
Acetaminophen/Tylenol	Excellent, often underutilized and underdosed agent, especially in combination with an NSAID. Consider 650–975 mg PO or IV every 6–8 h. Daily max ranges from 4 g (young and healthy) to 2 g (elderly with underlying liver disease).
Motrin/Advin/ibuprofen, Aleeve/naproxen, Toradol/ketorolac, etc.	Particularly helpful for inflammatory pain. Available in IV/IM/PO forms. Generally, well tolerated at evidence-based doses (example of Ibuprofen 400–600 mg every 6 h, rather than 800 mg as it is not any more effective but has more side effects). Must weigh risk/benefit in each patient (advanced age, systemic anticoagulation, renal disease, etc.), though one-time dosing in ED is generally lower risk than chronic use.
Topical Voltaren/diclofenac (NSAID) gel, lidocaine patches/cream, and other topical agents	Generally, well tolerated and easy to use. Topical NSAID gel can be very helpful for inflammatory pain (musculoskeletal, superficial tumor like posterior spinal metastases, etc.) and systemic absorption is minimal.
Local injections and nerve blocks	Increasingly used in ED patients for a variety of indications with great effect. When done properly, generally very safe and well tolerated. Some examples include trigger point injections for muscle spasm, local injection for dental pain, fascia iliaca blocks for hip fracture, intercostal nerve blocks for rib fracture, etc.
Opioids
Short-acting	Numerous PO/IV/SQ agents including morphine, hydromorphone, oxycodone, hydrocodone, oxycodone, fentanyl, etc. Can convert between them using an opiate equianalgesic dosing chart or calculator. Typically start with the patient’s home dose (or equivalent), or in opioid naive patients a dose based on their age/weight/hepato-renal function. Oral medications’ peak effect is ~ 45 min, IV morphine and hydromorphone have peaks ~ 20 min, and IV fentanyl is ~ 2 min. If effective relief of pain can continue current dose every 2–3 h, adjust as needed. If partial response, repeat initial dose. If no response to initial dose, increase by 50%–100% and give immediately (eg, morphine 4 mg IV → 6 or 8 mg).
Long-acting	Numerous PO and SQ options including long-acting morphine, hydromorphone, oxycodone, fentanyl, methadone, suboxone, etc. An IV opioid infusion (“drip”) is another form of “long-acting” or “basal” analgesia. ED clinicians should not start these agents without guidance from a subspecialist (palliative care, etc.) but for patients already on one of them it is important to continue basal opioid analgesia while they are in the ED (either their home agent and dose or something equivalent) in addition to using short-acting medications. Of note, it can be helpful to think of opioid-dependent patients like patients who are insulin-dependent. In both cases, the long-acting agent (opioid or insulin) can be reduced if indicated (hypoglycemia or delirium respectively, for example) but generally should NOT be stopped entirely. Involve subspecialty consultants early-on in both cases if concerned.
Opioid infusions (“drips”)	Historically usually initiated in the ED for patients at the end of life. However, in many cases an opioid infusion is not necessary and intermittent boluses of short-acting opioids can adequately manage the patient’s symptoms. In patients no longer able to take their PO long-acting opioids, an equivalently dosed opioid infusion can be started in their place. For patients nearing or at the end of life who require frequent boluses of short-acting opioids over a span of several hours, adding on an opioid infusion can be helpful. Atypical starting dose would be the total bolus/PRN needs, divided by the number of hours gone by, multiplied by ½ (eg, if morphine 16 mg IV (4 mg x 4) was needed in PRNs over 4 h, start the infusion at 16 mg/4 h x ½ = 2 mg/h). Worsening pain should be treated with boluses of short-acting opioids (not reflexively increasing the infusion), and the infusion rate adjusted every few hours based on the patient’s needs. (Any changes to the infusion rate require several half-lives to take effect.)
Other adjuvants
Ketamine	Typical ED starting dose for pain is 0.1–0.3 mg/kg IV. Infusing over 10–15 min instead of rapid push can reduce side effects. Continuous infusions of 0.15–0.2 mg/kg/h can also be used for analgesia, though this is less common in the ED. Ketamine be used independently or as an opioid adjuvant.
Other neuropathic agents	Gabapentin, pregabalin, SSRIs, SNRIs, etc. Not started in the ED but, if able, important to continue in patients already on them.
Medications to avoid
Codeine and Tramadol	Older opioids, previously marketed as “gentle opioids” or [falsely] as “opioid alternatives”. They both have variable and unpredictable metabolism as well as high risk of side effects and potentially life-threatening complications. Tramadol in particular has been linked to increased risk of delirium, seizures, refractory hypoglycemia, and death.
Combination drugs (such as Percocet or Vicodin)	Typically, an opioid combined with low (below recommended) dose acetaminophen. However, patients can combine this with OTC acetaminophen and inadvertently overdose. Better to prescribe optimally dose acetaminophen and (if needed) also an opioid.

Abbreviations: ED, emergency department; IM, intramuscular; IV, intravenous; NSAID, nonsteroidal anti-inflammatory drugs; PO, per oral; PRN, pro re nata; SNRIs, serotonin and norepinephrine reuptake inhibitors; SQ, subcutaneous; SSRIs, selective serotonin reuptake inhibitors.

Data from Jason Bowman, MD.