The major concern regarding ketorolac relates to potential renal toxicity, and thus caution should be undertaken in prescribing it to patients with known or suspected renal disease. Although this risk is associated with even a single dose, multiple doses increase the danger and therefore should be avoided.
Ketorolac should also be used with caution in patients with asthma. As a subset of asthma patients will experience severe bronchospasm after NSAID administration, clinicians should always determine whether a patient can tolerate NSAIDs.
Renal Toxicity and GI Effects
Concerns over renal toxicity and potential GI distress are the chief disadvantages of NSAID use. While renal toxicity has been reported in patients without pre-existing kidney dysfunction, it is of much greater concern in patients with pre-existing renal disease or decreased glomerular filtration rate. For this reason, care must be exercised when prescribing NSAIDS to elderly patients, patients with diabetes mellitus, or patients with hypertension (or even worse, a combination of these). Prolonged use of NSAIDs can also cause upper GI bleeding. Nonsteroidal anti-inflammatory drugs are contraindicated in pregnant patients.
Opioid analgesics
Morphine
Morphine is the prototypical compound in the opioid class, and has been utilized for more than two centuries since its isolation in 1804.19 Other opioid compounds include codeine, hydrocodone, oxycodone, morphine, and hydromorphone, which represent different functional groups substituted onto the base morphine molecule. All share similar pharmacology, differing primarily only in potency. The onset of action for codeine, hydrocodone, and oxycodone is 30 to 60 minutes when taken orally, with a peak time of 60 to 90 minutes. Codeine and hydrocodone are at the weak-end of the spectrum (Step 2 medications), while morphine and hydromorphone are more potent (Step 3 medications). The majority of opioids and their metabolites are primarily excreted renally (90%-95%).20 Therefore, care must be exercised regarding dosing and frequency when used in patients with renal insufficiency or disease.
Morphine has several features that make it an attractive analgesic for use in the ED. The ability to administer morphine via IV, IM, subcutaneous, or oral route; its quick onset of action; and safety profile are all advantageous. The onset of action is 5 to 10 minutes when given IV. For oral administration, it is 30 to 60 minutes (similar to the other opioids discussed) and can be given as a tablet or syrup.
Morphine decreases the severity of pain, with an apparent increase in tolerance for any remaining discomfort. The potency and central action of morphine make it ideal for managing moderate and severe pain.
As with other analgesics, morphine and its related compounds have associated drawbacks, of which respiratory depression is the most feared, though this is uncommon at therapeutic doses. The respiratory depressant effect is more pronounced in patients with underlying lung disease, depressed mental status, or concurrent use of sedating medication (eg, benzodiazepines).
Another disadvantage to morphine is that it can cause hypotension, limiting its use in certain clinical situations. Repeated or prolonged use may cause slowing or complete arrest of peristaltic waves in the GI tract, which can lead to significant constipation. Pruritus and nausea are two other frequently reported side effects and may necessitate, respectively, coadministration of diphenhydramine (eg, Benadryl) or an antiemetic (eg, Phenergan or Zofran). As an opioid, morphine is potentially addictive, though it is generally thought to require significant intake over several weeks before such problems arise.
The sedation caused by morphine is also of concern, as patients who are under its influence immediately following discharge cannot safely drive, and may actually not be safe to walk or even utilize public transportation. This concern can be lessened by verifying the patient’s mode of transport prior to administration of the medication, ensuring that patients are not overly sedated at the time of discharge and, as much as possible, accompanied home by an adult relative or friend. In comparison to other frequently used opioids, several features can be considered. The duration of action for codeine, hydromorphone, and morphine is similar at 3 to 5 hours.
Hydromorphone
Hydromorphone (Dilaudid) is approximately seven times more potent than morphine, but otherwise very similar. It is frequently the IV opioid of choice for severe pain and also appears to cause pruritus less frequently than morphine. Hydromorphone has a rapid onset of action (1-5 minutes IV; 15-30 minutes orally) and can be titrated to effect when given via the IV route, making it an ideal agent for the pain associated with long bone or pelvic fractures, vasoocclusive crises in patients with sickle cell disease, and renal colic. The oral formulation of hydromorphone can be utilized for severe pain in the appropriate patient population, usually at a dose of 2 to 4 mg every 4 hours.