Vioxx is out, pulled off the shelves by Merck after a clinical trial revealed that the COX-2 inhibitor increased the risk of heart attacks and strokes in users. Gone, too, is Bextra. Pfizer voluntarily withdrew the drug from the market when further review of data revealed that it, too, can increase the risk of heart attack and stroke. Which leaves Celebrex - slower-acting than Vioxx and Bextra and, for now, with fewer known side effects - as the COX-2 inhibitor used by surgical facilities to tame pain.

Down to just one of the big three, you might want to look at other ways to relieve patients' post-op pain without opioids. Here's a look at your non-steroidal anti-inflammatory drug options and what you need to know about them.

Effectiveness and side-effects
Outside COX-2 inhibitors, not much has changed over the last year. Most are equally efficient. Most have the same side effects. NSAIDs may differ in chemical structure, but they accomplish pretty much the same thing: a reduction in pain. However, because the ability to increase the cardiac and gastrointestinal risks is a potential effect of all NSAIDS - COX-2 inhibitors and prescription and over-the-counter NSAIDs alike - labels of these medications will be revised to assist healthcare providers, patients and consumers use these medications safely.

The most common side effects associated with NSAIDs are GI problems such as nausea, vomiting, heartburn, indigestion, abdominal cramping and bleeding. Other adverse effects include edema, bleeding after surgery, renal dysfunction, exacerbation of hypertension and asthma, drowsiness and skin rash.

However, most of the problems only occur after long-term use and may depend on a patient's tolerance for the specific drug. Still, it's important for surgical facilities to keep more than one NSAID on hand to account for a patient's ability to tolerate a particular medication.

Factors for consideration
Why, then, choose one NSAID over another? It comes down to patient response, tolerance, provider preference and cost of the agent. With each drug having relatively the same effect - depending on a patient's tolerance - hospitals must consider costs in deciding which NSAIDs to employ, especially when it comes to short-term use for acute pain management.

Here is a breakdown, based on chemical structures of the most common NSAIDs indicated for the management of pain (see "Top Choices at a Glance" for more).

• Acetaminophen. The analgesic properties are similar to aspirin (see the section on salicylates). Few side effects occur within the normal dose range.
• COX-2 inhibitors. With Vioxx and Bextra off the market, Celebrex is the most commonly used COX-2 inhibitor. It has relatively few side effects, although it doesn't work as quickly as Vioxx or Bextra. One-time use should pose no problems, although long-time use could be problematic and is a matter that should be discussed between patient and physician. Celebrex doesn't impair the ability of platelets to function; depending on the type of surgery and underlying patient characteristics, this might be a reason to select Celebrex over other NSAIDs for administration before surgery. In addition, the benefits of the drug remain in effect during the post-op period.
• Fenamates. Meclofenamate sodium (Meclomen) starts to take effect in one half-hour. Its analgesic action lasts from four hours to six hours and has a half-life of two hours. Mefenamic acid (Ponstel) starts to act from one-half to one hour, remains active three hours to four hours and has a half-life between two and four hours. GI disturbance, the primary side effect of meclofenamate, is the primary reason it isn't a first-line drug.
• Indoles. Sulindac (Clinoril) begins to act within two hours, continues to act for up to 12 hours and has a half-life of 7.8 hours. Tometin sodium (Tolectin) acts within one hour, is effective from four hours to six hours and has a half-life of one hour to one-and-a-half hours.
• Napthylalkanones. Nabumetone (Relafen) starts to act within three hours and has a half-life of 22.5 hours to 30 hours. It is best known for its COX-2 selectivity and for a non-acidic chemical structure as compared to other NSAIDs.

• Oxicam derivatives. Piroxicam (Feldene) has an extraordinarily long half-life: 30 hours to 86 hours. The drug's long half-life is considered to be a major factor in its low gastrointestinal toxicity profile.
• Phenylacetic acid. Diclofenace sodium (Voltaren) starts to work within one hour to two hours, is effective from six hours to 12 hours and has a half-life of one hour to two hours. It differs from other NSAIDs in that it has a high first-pass effect and a low bioavailability.
• Propionic acid derivatives. The drugs in this class begin to act within a half-hour to one hour, are effective from four hours to seven hours and have a half-life as low as two hours and as high as 50 hours. Ibuprofen is the most commonly used drug in this class. One of the more recent additions is oxaprozin, which has a once-daily dosing.
• Pyranocarboxylic acid. Etodolac (Lodine) begins to act in one-half hour, continues to act from six hours to 12 hours and has half-life of 7.3 hours.
• Pyrazolone derivatives. Phenylbutazone (Azolid, Butazolidin) acts within three hours to four hours, is effective between six and eight hours and has a half-life of one-and-a-half hours to four hours. Phenylbutazone isn't recommended for long-term use because of its association with aplastic anemias.
• Pyrrolpyrrole. Ketorolac, primarily because it's the only injectable NSAID, is commonly used in the perioperative setting and might be the most oft-used drug in this category. Also, unlike other agents, it's indicated for moderately severe acute pain. Several studies have shown it's as effective as morphine for treating post-op pain, with fewer side effects. Unlike the other agents, ketorolac is indicated for moderately severe acute pain.
• Salicylates. The most commonly used and best-studied NSAID is aspirin. Its elimination half-life fluctuates between two-and-a-half hours at low doses and 19 hours at high doses. The stomach rapidly absorbs aspirin, with peak blood levels achieved within one hour of an oral dose. Aspirin has been associated with Reye's Syndrome. Diflunisal, another salicyclate, is tolerated better in the GI system than aspirin. Salsalate and choline magnesium trisalicylate are weak analgesics for acute pain.

Before you reach for the morphine
Anti-inflammatories should be your first choice for post-op pain control in the outpatient setting; because of the minimally invasive nature of many procedures, opioids - which have many problems of their own - are often not needed. Targeting the inflammation and disruption of tissue caused by surgery by using these drugs correctly is often your best course of action.