Paracetamol as a basic component of a modern approach to adequate perioperative analgesia
The problem of adequate perioperative anesthesia is one of the most pressing in the current health care system, given its medical, humanistic and socio-economic aspects. Currently, the standard of postoperative analgesia is multimodal analgesia (MMA). One of the major and required components of MMA is paracetamol, which has antipyretic and analgesic effects with limited peripheral anti-inflammatory activity. Most authors consider intravenous paracetamol as a base drug in a multimodal analgesia strategy for a variety of surgical interventions, which reduces the need for opioids and reduces the side effects of the latter, which in turn significantly affects the results of treatment and the length of hospital stay.
Numerous studies in many countries have created a broad evidence base for the clinical use of this drug. Due to its pharmacokinetic and pharmacodynamic properties, it has been shown that intravenous paracetamol has several advantages over oral and rectal forms: early and more effective onset of analgesia and stable maintenance of the therapeutic dose of paracetamol are explained by the formation of a faster and higher peak in the concentration of the drug. The side effects of using paracetamol can be compared with placebo. The mechanism of action of the drug is different from the mechanism of action of NSAIDs, however, is still not fully understood. It may possibly involve inhibition of cyclooxygenase, cannabinoid, or nitric oxide pathways in the central nervous system. Intravenous paracetamol is a safe and effective first-line drug for the treatment of moderate pain in the perioperative period.
Brennan F, Carr DB, Cousins M. Pain management: a fundamental human right. Anesthesia & Analgesia. 2007 Jul 1;105(1):205-21.
Apfelbaum JL, Chen C, Mehta SS, Gan and TJ. Postoperative Pain Experience: Results from a National Survey Suggest Postoperative Pain Continues to Be Undermanaged. Anesthesia & Analgesia [Internet]. Ovid Technologies (Wolters Kluwer Health); 2003 Aug;97(2):534–40. Available from: https://doi.org/10.1213/01.ane.0000068822.10113.9e
Wu CL, Raja SN. Treatment of acute postoperative pain. The Lancet [Internet]. Elsevier BV; 2011 Jun;377(9784):2215–25. Available from: https://doi.org/10.1016/s0140-6736(11)60245-6
Reddi D, Curran N. Chronic pain after surgery: pathophysiology, risk factors and prevention. Postgraduate Medical Journal [Internet]. BMJ; 2014 Feb 26;90(1062):222–7. Available from: https://doi.org/10.1136/postgradmedj-2013-132215
Dubrov SA, Kuchin YuL Basic principles of accelerated recovery of patients after surgical interventions [Osnovnyye printsipy uskorennogo vosstanovleniya patsiyentov posle khirurgicheskikh vmeshatel'stv]. Zdorov'ya Ukrayiny. 2016;1(23):3. [In Russian]
Kehlet H, Dahl JB. The Value of ”Multimodal” or ”Balanced Analgesia” in Postoperative Pain Treatment. Anesthesia & Analgesia [Internet]. Ovid Technologies (Wolters Kluwer Health); 1993 Nov;77(5):1048-1056. Available from: https://doi.org/10.1213/00000539-199311000-00030
Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. The American journal of surgery. 2002 Jun 1;183(6):630-41.
Buvanendran A, Kroin JS, Tuman KJ, Lubenow TR, Elmofty D, Moric M, et al. Effects of Perioperative Administration of a Selective Cyclooxygenase 2 Inhibitor on Pain Management and Recovery of Function After Knee Replacement. JAMA [Internet]. American Medical Association (AMA); 2003 Nov 12;290(18):2411. Available from: ttps://doi.org/10.1001/jama.290.18.2411
Perkins FM, Kehlet H. Chronic Pain as an Outcome of Surgery. Anesthesiology [Internet]. Ovid Technologies (Wolters Kluwer Health); 2000 Oct;93(4):1123–33. Available from: https://doi.org/10.1097/00000542-200010000-00038
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Barden J, Edwards J, Moore A, McQuay H. Single dose oral paracetamol (acetaminophen) for postoperative pain. Barden J, editor. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2004 Jan 26; Available from: https://doi.org/10.1002/14651858.cd004602
Weil K, Hooper L, Afzal Z, Esposito M, Worthington HV, van Wijk A, et al. Paracetamol for pain relief after surgical removal of lower wisdom teeth. Cochrane Database of Systematic Reviews [Internet]. Wiley; 2007 Jul 18; Available from: https://doi.org/10.1002/14651858.cd004487.pub2
Duggan ST, Scott LJ. Intravenous Paracetamol (Acetaminophen). Drugs [Internet]. Springer Science and Business Media LLC; 2009;69(1):101–13. Available from: https://doi.org/10.2165/00003495-200969010-00007
Most Common Inpacient Procedures. Avaliable from: https: //www.beckershospitalreview.com.quality/14-most-common-inpacient-surgical-procedures.html
Chiam E, Weinberg L, Bellomo R. Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration. Heart, lung and vessels. 2015;7(2):121-132.
Stundner O, Poeran J, Ladenhauf HN, Berger MM, Levy SB, Zubizarreta N, et al. Effectiveness of intravenous acetaminophen for postoperative pain management in hip and knee arthroplasties: a population-based study. Regional Anesthesia & Pain Medicine [Internet]. BMJ; 2019 Mar 13;44(5):565–72. Available from: https://doi.org/10.1136/rapm-2018-100145
Mannila A, Kumpulainen E, Lehtonen M, Heikkinen M, Laisalmi M, Salo T, et al. Plasma and Cerebrospinal Fluid Concentrations of Indomethacin in Children After Intravenous Administration. The Journal of Clinical Pharmacology [Internet]. Wiley; 2007 Jan;47(1):94–100. Available from: https://doi.org/10.1177/0091270006295202
Bujalska M. Effect of nitric oxide synthase inhibition on antinociceptive action of different doses of acetaminophen. Pharmacological Reports. 2004 Sep 1;56(5):605-10.
Oscier CD, Milner QJ. Peri‐operative use of paracetamol. Anaesthesia. 2009 Jan;64(1):65-72.
Niemi TT, Backman JT, Syrjälä MT, Viinikka LU, Rosenberg PH. Platelet dysfunction after intravenous ketorolac or propacetamol. Acta Anaesthesiologica Scandinavica [Internet]. Wiley; 2000 Jan;44(1):69–74. Available from: https://doi.org/10.1034/j.1399-6576.2000.440113.x
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase‐2 inhibitor in man. The FASEB Journal [Internet]. Wiley; 2007 Sep 20;22(2):383–90. Available from: https://doi.org/10.1096/fj.07-8506com
Pickering G, Estève V, Loriot M-A, Eschalier A, Dubray C. Acetaminophen Reinforces Descending Inhibitory Pain Pathways. Clinical Pharmacology & Therapeutics [Internet]. Springer Science and Business Media LLC; 2007 Oct 24;84(1):47–51. Available from: https://doi.org/10.1038/sj.clpt.6100403
Flower RJ, Vane JR. Inhibition of Prostaglandin Synthetase in Brain explains the Anti-pyretic Activity of Paracetamol (4-Acetamidophenol). Nature [Internet]. Springer Science and Business Media LLC; 1972 Dec;240(5381):410–1. Available from: https://doi.org/10.1038/240410a0
Skjelbred P, Løkken P, Skoglund LA. Postoperative administration of acetaminophen to reduce swelling and other inflammatory events. Current therapeutic research. 1984;35(3):377-85.
Honoré P, Buritova J, Besson J-M. Aspirin and acetaminophen reduced both Fos expression in rat lumbar spinal cord and inflammatory signs produced by carrageenin inflammation. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 1995 Dec;63(3):365–75. Available from: https://doi.org/10.1016/0304-3959(95)00065-8
Delbos A, Boccard E. The morphine-sparing effect of propacetamol in orthopedic postoperative pain. Journal of Pain and Symptom Management [Internet]. Elsevier BV; 1995 May;10(4):279–86. Available from: https://doi.org/10.1016/0885-3924(95)00004-i
Peduto VA, Ballabio M, Stefanini S. Efficacy of propacetamol in the treatment of postoperative pain Morphine-sparing effect in orthopedic surgery. Acta Anaesthesiologica Scandinavica [Internet]. Wiley; 1998 Mar;42(3):293–8. Available from: https://doi.org/10.1111/j.1399-6576.1998.tb04919.x
Moller PL, Juhl GI, Payen-Champenois C, Skoglund LA. Intravenous Acetaminophen (Paracetamol): Comparable Analgesic Efficacy, but Better Local Safety than Its Prodrug, Propacetamol, for Postoperative Pain After Third Molar Surgery. Anesthesia & Analgesia [Internet]. Ovid Technologies (Wolters Kluwer Health); 2005 Jul;101(1):90–6. Available from: https://doi.org/10.1213/01.ane.0000155297.47955.d6
Moller PL, Sindet-Pedersen S, Petersen CT, Juhl GI, Dillenschneider A, Skoglund LA. Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery. British Journal of Anaesthesia [Internet]. Elsevier BV; 2005 May;94(5):642–8. Available from: https://doi.org/10.1093/bja/aei109
Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and Safety of Single and Repeated Administration of 1 Gram Intravenous Acetaminophen Injection (Paracetamol) for Pain Management after Major Orthopedic Surgery. Anesthesiology [Internet]. Ovid Technologies (Wolters Kluwer Health); 2005 Apr;102(4):822–31. Available from: https://doi.org/10.1097/00000542-200504000-00019
Perfalgan. Uxbridge. Middlesex, UK: Bristol-Myers Squibb Pharmaceuticals Ltd; 2007.
Gibb IA, Anderson BJ. Paracetamol (acetaminophen) pharmacodynamics: interpreting the plasma concentration. Archives of disease in childhood. 2008 Mar 1;93(3):241-7.
Jarde O, Boccard E. Parenteral versus Oral Route Increases Paracetamol Efficacy. Clinical Drug Investigation [Internet]. Springer Science and Business Media LLC; 1997 Dec;14(6):474–81. Available from: https://doi.org/10.2165/00044011-199714060-00005
Lirk P, Thiry J, Bonnet M-P, Joshi GP, Bonnet F. Pain management after laparoscopic hysterectomy: systematic review of literature and PROSPECT recommendations. Regional Anesthesia & Pain Medicine [Internet]. BMJ; 2019 Feb 3;44(4):425–36. Available from: https://doi.org/10.1136/rapm-2018-100024
Martinez V, Beloeil H, Marret E, Fletcher D, Ravaud P, Trinquart L. Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials. British Journal of Anaesthesia [Internet]. Elsevier BV; 2017 Jan;118(1):22–31. Available from: https://doi.org/10.1093/bja/aew391
Pierce CA, Voss B. Efficacy and Safety of Ibuprofen and Acetaminophen in Children and Adults: A Meta-Analysis and Qualitative Review. Annals of Pharmacotherapy [Internet]. SAGE Publications; 2010 Feb 11;44(3):489–506. Available from: https://doi.org/10.1345/aph.1m332
Lee SY, Lee WH, Lee EH, Han KC, Ko YK. The Effects of Paracetamol, Ketorolac, and Paracetamol Plus Morphine on Pain Control after Thyroidectomy. The Korean Journal of Pain [Internet]. Korean Pain Society; 2010;23(2):124. Available from: https://doi.org/10.3344/kjp.2010.23.2.124
Kampe S, Warm M, Landwehr S, Dagtekin O, Haussmann S, Paul M, et al. Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer. Current Medical Research and Opinion [Internet]. Informa Healthcare; 2006 Aug 31;22(10):1949–54. Available from: https://doi.org/10.1185/030079906x132659
Tiippana E, Bachmann M, Kalso E, Pere P. Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy. Acta Anaesthesiologica Scandinavica [Internet]. Wiley; 2008 Apr 15;52(5):673–80. Available from: https://doi.org/10.1111/j.1399-6576.2008.01650.x
Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. British Journal of Anaesthesia [Internet]. Elsevier BV; 2002 Feb;88(2):199–214. Available from: https://doi.org/10.1093/bja/88.2.199
Ong CKS, Seymour RA, Lirk P, Merry AF. Combining Paracetamol (Acetaminophen) with Nonsteroidal Antiinflammatory Drugs: A Qualitative Systematic Review of Analgesic Efficacy for Acute Postoperative Pain. Anesthesia & Analgesia [Internet]. Ovid Technologies (Wolters Kluwer Health); 2010 Feb;1. Available from: https://doi.org/10.1213/ane.0b013e3181cf9281
Juhl GI, Norholt SE, Tonnesen E, Hiesse-Provost O, Jensen TS. Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery. European Journal of Pain [Internet]. Wiley; 2006 May;10(4):371–371. Available from: https://doi.org/10.1016/j.ejpain.2005.06.004
Palmer GM, Atkins M, Anderson BJ, Smith KR, Culnane TJ, McNally CM, Perkins EJ, Chalkiadis GA, Hunt RW. IV acetaminophen pharmacokinetics in neonates after multiple doses. British journal of anaesthesia. 2008 Oct 1;101(4):523-30.
Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. Journal of toxicology: clinical toxicology. 2002 Jan 1;40(1):3-20.
Anderson BJ. Comparing the efficacy of NSAIDs and paracetamol in children. Pediatric Anesthesia. 2004 Mar;14(3):201-17.
Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al. Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study. Hepatology [Internet]. Wiley; 2005;42(6):1364–72. Available from: https://doi.org/10.1002/hep.20948
Kuffner E, Green J, Bogdan G, Knox P, Palmer R, Heard K, et al. The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study. BMC Medicine [Internet]. Springer Science and Business Media LLC; 2007 May 30;5(1). Available from: https://doi.org/10.1186/1741-7015-5-13
Munsterhjelm E, Munsterhjelm NM, Niemi TT, Ylikorkala O, Neuvonen PJ, Rosenberg PH. Dose-dependent Inhibition of Platelet Function by Acetaminophen in Healthy Volunteers. Anesthesiology [Internet]. Ovid Technologies (Wolters Kluwer Health); 2005 Oct;103(4):712–7. Available from: https://doi.org/10.1097/00000542-200510000-00009
Niemi TT, Taxell C, Rosenberg PH. Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. Acta Anaesthesiologica Scandinavica [Internet]. Wiley; 1997 Nov;41(10):1353–8. Available from: https://doi.org/10.1111/j.1399-6576.1997.tb04657.x
Silvanto M, Munsterhjelm E, Savolainen S, Tiainen P, Niemi T, Ylikorkala O, et al. Effect of 3 g of intravenous paracetamol on post-operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia. Acta Anaesthesiologica Scandinavica [Internet]. Wiley; 2007 Aug 15;51(9):1147–54. Available from: https://doi.org/10.1111/j.1399-6576.2007.01376.x
Schafer AI. Effects of Nonsteroidal Antiinflammatory Drugs on Platelet Function and Systemic Hemostasis. The Journal of Clinical Pharmacology [Internet]. Wiley; 1995 Mar;35(3):209–19. Available from: https://doi.org/10.1002/j.1552-4604.1995.tb04050.x
Gajraj NM. Cyclooxygenase-2 inhibitors. Anesthesia & Analgesia. 2003 Jun 1;96(6):1720-38.
Warltier DC, Marret E, Flahault A, Samama C-M, Bonnet F. Effects of Postoperative, Nonsteroidal, Antiinflammatory Drugs on Bleeding Risk after Tonsillectomy Meta-analysis of Randomized, Controlled Trials. Anesthesiology [Internet]. Ovid Technologies (Wolters Kluwer Health); 2003 Jun;98(6):1497–502. Available from: https://doi.org/10.1097/00000542-200306000-00030
Li M, Fouad A, Emara E, Maher S, Elminshawy A, Kotb H. 360: Effect of cardiopulmonary bypass on the pharmacokinetics of intravenous paracetamol (propacetmol hydrochloride). Regional Anesthesia and Pain Medicine [Internet]. BMJ; 2007 Sep;32(5):183–183. Available from: https://doi.org/10.1016/j.rapm.2007.06.375
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