Multimodal Analgesia & IV Acetaminophen

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In 1989 Torodol (ketorolac) became available in the USA and, in my mind, multi-modal postoperative analgesia was born. Since then we've made a lot of progress in multimodal analgesia. We still have a long way to go when it comes to putting multimodal analgesia into practice. Opioids remain heavily used by many anesthesia providers during general anesthesia, despite strong evidence that doing so results in acute opioid tolerance and poorer postoperative pain relief.

Acetaminophen IV (Ofirmev) is often a reasonable choice for part of a good multimodal analgesia plan. There are studies that show it is more effective than I ever would have thought, despite acetaminophen's reputation as a very mild analgesic. This is pretty much the same process we went through when ketorolac came out, and ketorolac is now firmly estabilshed in postoperative analgesia. But let's make sure we don't have to relearn the lesson of acetaminophen overdose and liver damage as we integrate Ofirmev into our anesthetic plan. So many medications have acetaminophen in them that it is way too easy to overdose on acetaminophen if one doesn't pay very close attention. Not only do many over-the-counter medications contain acetaminophen, but many drugs used for postoperative analgesia do as well: Lortab, Endocet, and Tylenol with codine to name just a few.

Acetaminophen has been a leading cause of acute liver failure in the United States.

Acetaminophen has been a leading cause of acute liver failure in the United States. As a result, the FDA initiated a program to reduce the likelihood that patients would unknowingly overdose on acetaminophen. If we use the 1,000 mg adult dose of IV acetaminophen every 6 hours, the patient will have received the maximum dose of acetaminophen for 24 hours and any additional acetaminophen in any other analgesic (e.g. a dose of Lortab) would result in an overdose. If we give IV acetaminophen at the beginning of a long case and again 6 hours later before the patient leaves the PACU (2,000 mg) and the patient takes only 2 Lortab, they will have reached the recommended limit for acetaminophen as a single drug for 24 hours (3,000 mg). (Interestingly, the maximum 24-hour dose limit is higher for the IV form than for the oral form of acetaminophen.)

I'm not arguing that we do not use IV acetaminophen as part of a multimodal analgesia technique. But over the now nearly 30 years I've practiced anesthesia, I've seen some really unfortunate near misses and deaths associated with new drugs and the learning curve for health care providers of all stripes. The potency of both midazolam and sufentanil, for example, were underestimated. The result was patient deaths and many, many patients on ventilators in the PACU for a very, very long time. We can avoid relearning the lesson of acetaminophen overdose if we think ahead to what the surgeon is planning on prescribing for pain and what the patient is likely to take on their own once they are home. IV acetaminophen is an effective part of multimodal pain relief only if it first does no harm.

Michael A. Fiedler, PhD, CRNA

For more information on Ofirmev see the following issues on

June 2013 - Effect of preemptive and preventive acetaminophen on postoperative pain score: a randomized, double-blind trial of patients undergoing lower extremity surgery J Clin Anesth. 2013;25:188-92

February 2011 - The effects of preoperative intravenous acetaminophen in patients undergoing abdominal hysterectomy Arch Gynecol Obstet, Published online: 23 Feb 2011