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Acute Pain | Chronic Pain | General

Paracetamol in acute postoperative pain

Clinical bottom line

Paracetamol is an effective analgesic. A single dose of 1000 mg paracetamol had an NNT of 3.8 (3.4-4.4) for at least 50% pain relief over 4-6 hours in patients with moderate or severe pain compared with placebo based on information from 2,759 patients. Paracetamol 600/650 mg had an NNT of 4.6 (3.9-5.5) based on information from 1,886 patients. Paracetamol is not associated with increased adverse effects in single dose administration.


Paracetamol (Acetaminophen) is an important non-opiate analgesic. It accounts for over 5 million prescriptions in England alone (1995), as well as being widely available without prescription.

Systematic reviews

RA Moore, S Collins, D Carroll, HJ McQuay. Paracetamol with and without codeine in acute pain: a quantitative systematic review. Pain 1997 70:193-201.

RA Moore, SL Collins, D Carroll, HJ McQuay, J Edwards. Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. The Cochrane Library, Update Software, Oxford 2000.

J Barden, JE Edwards, RA Moore, SL Collins, HJ McQuay. Single dose paracetamol (acetaminophen) for postoperative pain. The Cochrane Library, Update Software, Oxford 2002.

Inclusion criteria were full journal publication of trials of paracetamol in acute postoperative pain; single oral dose; randomised; placebo-controlled; double-blind; moderate to severe baseline pain; adult populations; group sizes 10; sufficient data to calculate the area under the curve for pain relief (TOTPAR).

For each trial the mean TOTPAR values for paracetamol and placebo groups were converted to the percent of maximum total pain relief based on the categorical pain scales (%maxTOTPAR). These values were then converted to dichotomous information on the proportion, and then the number of patients, who achieved at least 50%maxTOTPAR. A number-needed-to-treat for at least 50% pain relief and the relative benefit of the treatment were then calculated.

Findings

All doses of paracetamol between 325 mg and 1500 mg were statistically superior to placebo (Table 1). Compared with placebo a single dose of 1000 mg paracetamol had an NNT of 3.8 (3.4-4.4) for at least 50% pain relief over 4-6 hours in patients with moderate or severe pain compared with placebo (Figure 1). A 600/650 mg dose had an NNT of 4.6 (3.9-5.5).

Figure 1: Randomised comparisons of paracetamol 1000 mg versus placebo

Table 1: NNTs for at least 50% pain relief over 4-6 hours for paracetamol at different doses compared with placebo

At least 50% pain relief
number/total (%)
Paracetamol dose
(mg)
Number of trials
Paracetamol
Placebo
Relative benefit
(95% CI)
NNT
(95% CI)
325 1 34/49 (69) 22/51 (43) 1.6 (1.1 to 2.3) 3.8 (2.2 to 13.3)
500 6 179/290 (61) 86/271 (32) 1.9 (1.6 to 2.3) 3.5 (2.7 to 4.8)
600/650 19 358/954 (38) 145/932 (16) 2.4 (2.0 to 2.8) 4.6 (3.9 to 5.5)
1000 24 746/1627 (46) 222/1132 (20) 2.1 (1.8 to 2.3) 3.8 (3.4 to 4.4)
1500 1 53/81 (65) 22/57 (39) 1.7 (1.2 to 2.5) 3.7 (2.3 to 9.5)

The dose-response of paracetamol against placebo was rather flat (Figure 2), although there were few patients and trials in the comparisons at extremes of dose. With paracetamol 600/650 mg 38% of patients with initial pain of moderate or severe intensity had at least 50% pain relief over 4-6 hours, as did 46% with paracetamol 1000 mg and 65% with paracetamol 1500 mg.

Figure 2: Response with different doses of paracetamol against placebo

Adverse effects

No study reported a significant difference in number of adverse effects between paracetamol and placebo. Adverse effects in studies of paracetamol against placebo were variable, mild and transient and there were no significant differences between paracetamol and placebo for drowsiness/somnolence/sleepiness, dizziness, headache, nausea or vomiting. There were four withdrawals with paracetamol and one with placebo in these trials.

Comment

Paracetamol is an effective analgesic, but somewhat less effective that others. For Paracetamol 1000 mg (the usual UK and European dose) there was information on over 2,700 patients and for 600/650 mg (the usual US dose) information on nearly 1,900 patients.

Further reading

These are two very good reviews which address similar questions about the effectiveness of paracetamol with and without codeine, but in slightly different ways, and without NNTs:

de Craen AJM, Di Giulio G, Lampe-Schoenmaeckers AJE, Kessels AGH, Kleijnen J. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: A systematic review. British Medical Journal 1996; 313:321-325.

Zhang WY, Li Wan Po A. Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain - A meta-analysis. Journal of Clinical Pharmacy and Therapeutics 1996; 21:261-282.

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