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Paracetamol (Acetaminophen) for management of postoperative pain

Mechanism of action and positioning in postoperative analgesia

Paracetamol is a non-opioid analgesic and antipyretic. Its mechanism of action is unclear. There is evidence of a central anti-nociceptive effect, possibly involving direct and indirect inhibition of central cyclo-oxygenases, possibly also activation of the endo-cannabinoid system and spinal serotonergic pathways. As a sole agent, it is used to treat weak-moderate postoperative pain, but it can also be used within a multimodal regimen, e.g. as an adjunct to opioid analgesia. It can be administered by oral, rectal and intraveneous routes. It is the first choice non-opioid analgesic for women during pregnancy and lactationANZCA, section 4.2.1. pages 71-72.

Treatment specific perioperative issues

Recommendations specific to the treatment

  • As bioavailability and tolerability of oral administration are good, use of the IV form of paracetamol should be restricted to clinical circumstances where enteral administration is not appropriate ANZCA, section 6.2.3., p 156, FRENCH , 6.2.2., p 406.
  • Avoid rectal administration because absorption is slower and less predictable compared to oral administration FRENCH , 6.2.2., p 406.
  • There is probably no need to reduce the dose given to older people, as there is no consistent evidence that aging has an effect on clearance ANZCA section 11.2.4 . p 403
  • Recommended adult single doses are: oral 500-1000mg; intravenous 1000mg, to a maximum of 4000 mg / day. German Guidelines Table 6.1.2.

Circumstances when the treatment if not recommended

It is common to recommend use with caution or in reduced doses in patients with active liver or renal disease German Guidelines, section, page 13, history of heavy alcohol intake and glucose-6-phosphase dehydrogenase deficiency. Others report that it is safe to use with patients with liver disease and safer compared to NSAIDs, in therapeutic doses, over a short term, and unlikely to cause heptotoxicity in patients who ingest moderate to large amounts of alcohol. ANZCA, section 4.2.1 see Adverse effects, p 72.

Treatment specific issues related to nursing / monitoring patients

Adverse effects of paracetamol are fewer compared to NSAIDs and can be used when the latter are contraindicated (e.g. in patients with a history of asthma or pepetic ulcers). ANZCA, section 4.2.1 see Adverse effects, p 72.

There is no evidence that patients with depleted glutathione stores (e.g. malnourished, have cirrhosis, hepatitis C or HIV) are at increased risk of liver dysfunction when exposed to therapeutic doses of paracetamol. Paracetamol interacts with warfarin to increase the INR ratio. ANZCA section 4.2.1 see Adverse effects, p 72


Paracetamol is a widely used non-opioid medication with analgesic and anti-pyretic properties and can be administered by a variety of routes. After surgery, combined administration of paracetamol with a non-selective NSAID or a COX-2 inhibitor are recommended formoderatetolowpain intensity. For severe pain, it should be combined with an opioid or some other potent analgesic.

Supplementary reading

  1. McNicol ED, Tzortzopoulou A, Cepeda MS, Francia MB, Farhat T, Schumann R. Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis. Br J Anaesth. 2011 Jun;106(6):764-75.