Saturday, March 24, 2012

IV Acetaminophen - All the Rage?

The Gist:  IVAcetaminophen (APAP) is a safe analgesic and antipyretic useful in the Emergency Department (ED) setting as well as in the management of intra-operative and post-operative pain.  Many studies have demonstrated that IV acetaminophen and its international counterpart, IV paracetamol, reduce narcotic consumption.  In fact, IV morphine and IV acetaminophen may produce comparable analgesia in some clinical situations.  It's also likely that IV acetaminophen in the peri-operative setting may result in decrease morbidity and expedited recovery but there really isn't excellent data to support this idea.  The downside?  IV APAP is expensive and the 4 gram/day limit may be easily reached, especially if opioid/APAP combinations are used in addition.

Background:  IV APAP, now available in the United States, has a decent track record for use on the international scene.  This pharmaceutical is gaining increasing popularity in some peri-operative settings but has not reached widespread use in the either the operating room (OR) or the ED.

What makes IV APAP potentially useful?
*A randomized, double blind small study (n=73) published by Serenken, et al demonstrated that IVparacetamol and IV morphine relieved pain at similar rates in patients with symptomatic nephrolithiasis in the ED (2).  Morphine is a strong, potentially addicting narcotic that may cause respiratory depression, cardiovascular depression, and sedation.  These may delay time to discharge (sedation) or may cause compromise of a patient's airway or mean arterial pressure (MAP).
*Furthermore, studies demonstrate that IV APAP is a great adjunct for post-operative pain control (3,4).  The Sinatra, et al paper demonstrates that acetaminophen has a statistically significant impact on analgesia in the 24 hours following major orthopedic surgery.  In comparing the placebo arm versus the IV acetaminophen arm, the IV acetaminophen group had better pain control (P<0.0001) and a greater time to rescue analgesia medication administration (3).
*A COCHRANE review published in 2011 pooled data from three studies using IV paracetamol demonstrating that a two-fold increase in 50% pain reduction in the four-hour post-operative period (32% vs 16%).  The results were even more favorable if one includes the studies that used IV propacetamol.  The number needed to treat (NNT) to achieve a 50% pain reduction in four hours with IVparacetamol was 3.4 (95% CI 2.8-4.5) (4).  Pretty good.
*Side effects are minimal and comparable to placebo.  IV acetaminophen doesn't carry the adverse effects of respiratory depression, altered cognition, or sedation. This may (operative word may) translate into speedier recovery with reduced number of falls and respiratory sequelae.

Why IV > PO ?
*Quicker onset of action - 15 minutes for analgesia, 30 minutes for antipyretic effects
*Higher, more consistent plasma levels (1, 5).
*Question as to whether mode of delivery affects the patient's perception of analgesia.  Patients may believe that the intravenous meds are "stronger" and acknowledges the significance of their pain although a ketorolac study did this effect.  When patients visit the ED or undergo surgery, they have preconceived ideas of what kind of interventions they will receive.  I don't have evidence to back this up; however, I think most of us have seen this kind power of suggestion in medicine.
*IV acetaminophen is a prescription only medication. This allows tighter control and perhaps more liberal use without suggesting to patients that large doses of acetaminophen are safe.

*IV APAP is only available in the U.S. as Ofirmev which has a wholesale price of over $10/vial (vial = 1gram).  Could the copious quantities of IV APAP flying off of the shelves of the operating room pharmacy be the byproduct of a pharmaceutical campaign that capitalized on repackaging an old product for greater profits?  Perhaps.  Is it worth that kind of money? Probably not.
*Don't use in cases of liver injury/failure and in patients with a creatinine clearance <30 mL/min
*Some of the studies (Sinatra, Serenken, etc) are fairly small.
*Use with combination opioid products could reach the 4g/day limit easily.

*1g IV q6hours for adults (with a daily maximum of all acetaminophen/APAP products of 4 grams) infused over 15 minutes
*Pediatric dosing > 2 years old:  15 mg/kg IV q6 hours with a 24 hour maximum of 75 mg/kg/day

1.  Brett CNBarnett SGPearson J.Brett CNBarnett SGPearson J.  Postoperative plasma paracetamol levels following oral or intravenous paracetamol administration: a double-blind randomised controlled trial. Anaesth Intensive Care. 2012 Jan;40(1):166-71.
2.  Serinken, Eken, Turkcuer, et al.  Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial Emerg Med J doi:10.1136/emermed-2011-200165
3.  Sinatra RSJahr JSReynolds LGroudine SBRoyal MABreitmeyer JBViscusi ER.   Intravenous Acetaminophen for Pain after Major Orthopedic Surgery: An Expanded Analysis. Pain Pract. 2011 Oct 19. doi: 10.1111/j.1533-2500.2011.00514.x 
4.  Tzortzopoulou A. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database Of Systematic Reviews [serial online]. August 4, 2011;(10)Available from: Cochrane Database of Systematic Reviews, Ipswich, MA. Accessed March 24, 2012.
5.  van der Westhuizen JKuo PYReed PWHolder K.  Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.  Anaesth Intensive Care. 2011 Mar;39(2):242-6.


  1. And what about when IV acetaminophen is used concomitantly in patients also prescribed opioid/APAP combination for pain and the daily dose of APAP exceeds 4000 mg/24 hrs because that limit is reached with 1 gm APAP q6hrs?