The Role of Intravenous Acetaminophen in Multimodal Pain Protocols for Perioperative Orthopedic Patients
Abstract
Multimodal pain management should be considered for all perioperative orthopedic patients. The goal of reducing the amount of perioperative opioid medication given may be achieved by using nonopioid medications, including intravenous acetaminophen. The site of action of acetaminophen is a variety of receptors in the central nervous system. When given intravenously, acetaminophen produces a much higher plasma concentration, which then leads to higher levels in the cerebrospinal fluid. The safety profile and relative lack of systemic adverse reactions make this an attractive analgesic for a wide variety of orthopedic surgical patients. Clinical studies have demonstrated the efficacy and safety of intravenous acetaminophen in elective total hip and knee arthroplasty, knee arthroscopy, lumbar spine surgery, and for acute traumatic limb pain.
- 1.Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003; 97:534–540.
10.1213/01.ANE.0000068822.10113.9E Crossref Medline, Google Scholar - 2.Morrison RS, Magaziner J, McLaughlin MA, The impact of post-operative pain on outcomes following hip fracture. Pain. 2003; 103:303–311.
10.1016/S0304-3959(02)00458-X Crossref Medline, Google Scholar - 3.Pizzi LT, Toner R, Foley K, Relationship between potential opioid-related adverse effects and hospital length of stay in patients receiving opioids after orthopedic surgery. Pharmacotherapy. 2012; 32(6):502–514.
10.1002/j.1875-9114.2012.01101.x Crossref Medline, Google Scholar - 4.Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North Am. 2005; 23:21–36.
10.1016/j.atc.2004.11.013 Crossref Medline, Google Scholar - 5.Perkins FM, Kehlet H. Chronic pain as an outcome of surgery: a review of predictive factors. Anesthesiology. 2000; 93:1123–1133.
10.1097/00000542-200010000-00038 Crossref Medline, Google Scholar - 6.Oderda GM, Said Q, Evans RS, Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay. Ann Pharmacother. 2007; 41:400–406.
10.1345/aph.1H386 Crossref Medline, Google Scholar - 7.American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2004; 100:1573–1581. Crossref Medline, Google Scholar
- 8.Elvir-Lazo OL, White PF.Postoperativepain management after ambulatory surgery: role of multimodal analgesia. Anesthesiol Clin. 2010; 28:217–224.
10.1016/j.anclin.2010.02.011 Crossref Medline, Google Scholar - 9.Buvanendran A, Kroin JS. Multimodal analgesia for controlling acute postoperative pain. Curr Opin Anaesthesiol. 2009; 22:588–593.
10.1097/ACO.0b013e328330373a Crossref Medline, Google Scholar - 10.Duellman TJ, Gaffigan C, Milbrandt JC, Allan DG. Multi-modal, pre-emptive analgesia decreases the length of stay following total joint arthroplasty. Orthopedics. 2009; 32:167.
10.3928/01477447-20090301-08 Link, Google Scholar - 11.American Society of Anesthesiologists. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012; 116:248–273. Crossref Medline, Google Scholar
- 12.Mattia A, Coluzzi F. What anaesthesiologists should know about paracetamol (acetaminophen). Minerva Anestesiol. 2009; 75:644–653. Medline, Google Scholar
- 13.Mallet C, Barrière DA, Ermund A, TRPV-1 in brain is involved in acetaminophen-induced antinociception. PLoS ONE. 2010; 5:e12748.
10.1371/journal.pone.0012748 Crossref Medline, Google Scholar - 14.Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther. 2005; 12:46–55.
10.1097/00045391-200501000-00008 Crossref Medline, Google Scholar - 15.Schutz RA, Fong L, Chang Y, Royal MA. Open-label, 4-period, randomized crossover study to determine the comparative pharmacokinetics of oral and intravenous acetaminophen administration in healthy male volunteers.
Poster presented at: 32nd Annual Meeting and Workshops American Society of Regional Anesthesia and Pain ;April 19–22, 2007 ;Vancouver, British Columbia, Canada . Google Scholar - 16.Singla NK, Parulan C, Samson R, Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral or rectal acetaminophen. Pain Pract. 2012; 12:523–532.
10.1111/j.1533-2500.2012.00556.x Crossref Medline, Google Scholar - 17.Jahr JS, Lee VK. Intravenous acetaminophen. Anesthesiol Clin. 2010; 28:619–645.
10.1016/j.anclin.2010.08.006 Crossref Medline, Google Scholar - 18.Jensen LL, Handberg G, Brosen K, Schmedes A, Ording H. Paracetamol concentrations in plasma and cerebrospinal fluid. Eur J Aneaesth. 2004; 21(suppl 32):193. Abstract A-785.
10.1097/00003643-200406002-00700 Crossref, Google Scholar - 19.Bannwarth B, Netter P, Lapicque F, Plasma and cerebrospinal fluid concentrations of paracetamol after a single dose of propacetamol. Br J Clin Pharmacol. 1992; 34:79–81.
10.1111/j.1365-2125.1992.tb04112.x Crossref Medline, Google Scholar - 20.Van der Westhuizen , Kuo PY, Reed W, Holder K. Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia. Anaesth Intensive Care. 2011; 39:242–246. Crossref Medline, Google Scholar
- 21.Pan CP, Brietmeyer JB, Royal MA. IV acetaminophen PK/PD correlation following total hip arthroplasty. Nature. 2010; 87(suppl 1):S63. Abstract PIII-75. Google Scholar
- 22.Royal MA, Gosselin NH, Pan CP, Mouksassi MS, Brietmeyer JB. Route of administration significantly impacts hepatic acetaminophen exposure. Nature. 2010; 87(suppl 1):S62. Abstract POO-73. Google Scholar
- 23.Tzortzopoulou A, McNicol ED, Cepeda MS, Single dose intravenous paracetamol or intravenous paracetamol for postoperative pain. Cochrane Database Syst Rev. 2011; (10):CD007126. Medline, Google Scholar
- 24.Sinatra RS, Jahr JS, Reynolds L, Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection for pain management after major orthopedic surgery. Anesthesiology. 2005; 102:822–831.
10.1097/00000542-200504000-00019 Crossref Medline, Google Scholar - 25.Craig M, Jeavons R, Probert J, Benger J. Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department. Emerg Med J. 2012; 29(1):37–39.
10.1136/emj.2010.104687 Crossref Medline, Google Scholar - 26.Cakan T, Inan N, Culhaoglu S, Bakkal K, Basar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol. 2008; 20:169–173.
10.1097/ANA.0b013e3181705cfb Crossref Medline, Google Scholar - 27.Khan ZU, Iqbal J, Saleh H, El Deek AM. Intravenous paracetamol is as effective as morphine in knee arthroscopic day surgery procedures. Pak J Med Sci. 2007; 23:851–853. Google Scholar
- 28.Dobie I, Bennett D, Spence DJ, Murray JM, Beverland DE. Periarticular local anesthesia does not improve pain or mobility after THA. Clin Orthop Relat Res. 2012; 470:1958–1965.
10.1007/s11999-012-2241-7 Crossref Medline, Google Scholar

