UNDER CONTROL Easy-to-use IV NSAIDs let you get a potent non-opioid analgesic on board before surgery.

Why include intravenous NSAIDs in your multimodal pain protocol? As these reasons show, IV anti-inflammatories are likely to promote better outcomes, faster discharges and better overall recoveries.

• They control dynamic pain. The 3 approved IV agents — Toradol (ketorolac), Caldolor (ibuprofen) and Dyloject (diclofenac) — not only help reduce pain, they're especially effective in combating dynamic pain. That's the pain post-operative patients experience when they try to move. Unlike opioids, which can be very effective for patients who are at rest, NSAIDs can play an important role in recovery, because they improve mobility. They help subdue the spike in pain that patients typically experience when they try to engage in any sort of physical activities.
• They're easy to use and completely under your control. They let you get a potent non-opioid analgesic on board before surgery and/or immediately after, without having to worry about whether a given patient can swallow pills.
• They're fast-acting. They work better than oral agents, delivering a more rapid onset of pain control.
• They offer flexibility. You can administer them at the beginning of the case, or keep them in reserve to use instead of opioids in the recovery room. (Or you can do both.)
• They're safer than opioids. By potentially helping to reduce (or even eliminate) the need for opioids, they're also likely to reduce (or eliminate) common nuisance opioid-related side effects, like nausea and vomiting, as well as more serious side effects, like respiratory depression.

When to use them
When during the perioperative continuum should you administer IV NSAIDs? That's a matter of clinician preference. The labels don't mandate when to use them.

Toradol, the oldest of the three, doesn't have an indication for pre-incision administration, but that's only because the formulators didn't study its pre-operative effectiveness. (Many clinicians administer ketorolac pre-operatively anyway.) Caldolor and Dyloject, on the other hand, were both tested for pre-incision efficacy, so their labels say they can be used both pre- and post-operatively. You can use an IV NSAID as an around-the-clock drug from pre-incision until the time the patient doesn't have IV access. Or you can use one as a PRN — so when a patient has a spike in pain during recovery, you administer it instead of opioids. Again, it's up to the clinician.

Which is best?
There's never been a study comparing the 3 head to head, so no one can point to clear evidence that one is better than another. They're all COX inhibitors, although there are slight differences in the relative balance of COX-1 and COX-2, as well as some other minor differences. Unlike the other two, ibuprofen has to be mixed before it's administered; you can just bolus ketorolac and diclofenac. Ibuprofen also has to be infused over a longer period of time, because it can burn a little if you give it too rapidly. Another small difference: Ketorolac administration is limited to 5 days. The others have no time limitations.

There are also differences in price. Ketorolac is generic, so it's very inexpensive. But the others are reasonably priced, too.

DISHEARTENING?
The Link Between NSAIDs And Cardiovascular Issues

Short-term use of IV NSAIDs appears to be safe and effective in patients who have acceptable risk profiles.

How concerned should we be about the potential for NSAIDs to cause cardiovascular events? As you probably know, the FDA issued a strongly worded letter (osmag.net/9bTEsW) last summer, warning that NSAIDs can cause heart attacks and strokes. But the agency hasn't said whether short-term use of NSAIDs is a significant concern.

The letter does clearly suggest that patients who've had cardiovascular issues — heart attacks or strokes — might face greater risks. But the risk seems to be dose- and duration-dependent. We haven't seen an increased risk with the short-term use of any of these drugs.

If you look closely at the potential side effects of the 3 approved IV NSAIDs — Toradol (ketorolac), Caldolor (ibuprofen) and Dyloject (diclofenac) — all of which have COX-1 and COX-2 inhibiting properties, you'll find that ketorolac, which is more dominantly COX-1, would likely be associated with more standard NSAID risks, like bleeding, GI irritation and kidney effects. Ibuprofen and diclofenac, on the other hand, are more dominantly COX-2 and therefore might be more likely to be associated with cardiovascular issues.

The bottom line is that clinicians should be aware of the potential risks, and should be selective about using all NSAIDs for longer periods of time and in patients who have a history of heart-related issues. But short-term use of IV NSAIDs appears to be safe and effective in patients who have acceptable risk profiles.

— Eugene R. Viscusi, MD

Any downsides?
Last summer, the FDA issued a safety communication, strengthening warnings about the potential role of NSAIDs in cardiovascular events (see "The Link Between NSAIDs and Cardiovascular Issues" above), but it's yet to be determined whether short-term use poses any significant danger, particularly in patients with no significant cardiovascular risks.

Still, there are some potentially significant side effects to consider. The primary contraindication is patients who have renal disease. The IV NSAIDs all affect renal function. And it's important to be aware that hypovolemia worsens the effects. Otherwise-healthy patients who are given NSAIDs may have renal failure if they're hypovolemic.

There's also an anti-platelet effect, so there's some concern about the potential for bleeding. Gastrointestinal erosion is another concern. You don't want to use IV NSAIDs on patients who have a history of GI bleeds or who have had bariatric surgery.

While it's been suggested that bone healing can be impaired by NSAIDs, that concern seems to be falling by the wayside. More and more surgeons are using NSAIDs during spinal fusions and fracture repairs, and they're being widely used for joint replacements, without any evidence of impairment. Their effect on soft tissue healing has also been called into question, but that concern has clearly been shown to be invalid.

FINE FOR SPINE Surgeons are increasingly using IV NSAIDs during spine procedures, as previous concerns about their effects on bone healing are allayed.

Moving forward
If you've already embraced the concept of multimodal analgesia — and thankfully, more and more are embracing it all the time — IV NSAIDs provide a great starting point that's completely under your control and that you can extend from pre-operative to intraoperative to post-operative care.

While IV acetaminophen (Ofirmev) is not in the NSAID class, it, too, can have an additive effect with NSAIDs, further reducing pain and opioid requirements. As an IV agent, it shares the utility of the other intravenously administered drugs.

Concerns about opioids are legitimate and they're growing. Regulators are establishing new guidelines, and the discussion has entered the political arena. By establishing a multimodal perioperative pathway that uses IV NSAIDs to augment combinations of local or regional anesthesia, acetaminophen, and maybe gabapentin or pregabalin, we can stay ahead of the regulators, dramatically reduce opioid use, and often completely eliminate the need for them. Those are goals we should all be striving for. OSM