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Acute Pain | Chronic Pain | General

Analgesic efficacy of NSAIDs: comparison of different routes in acute pain

Clinical bottom line:

In renal colic NSAIDs act faster when given intravenously compared with intramuscular or rectal routes. This may be clinically relevant. In all other pain conditions there is no evidence that injected NSAIDs were better than oral. There is, however, increased reporting of adverse effects with intravenous and rectal administration. Where possible, patients should be given NSAIDs orally. Better trials are needed to provide a definitive answer to the question of which routes are the most effective.

Different routes of NSAID administration

NSAIDs are an important component of simple "low-technology" pharmacological control of acute and chronic pain, and, given orally, are surprisingly effective in patients with moderate to severe postoperative pain. Invasive procedures such as continuous extradural opiate infusion, or patient-controlled analgesia, carry recognised risks. Rectal and injectable formulations are currently fashionable, despite unclear evidence for any advantage over oral routes (for patients who are conscious, can swallow, have no nausea or ileus).

Systematic review

Tramèr M, Williams J, Carroll D, Wiffen PJ, McQuay HJ, Moore RA. Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes for acute and chronic pain. Acta Anaesth Scand 1998; 42:71-9.

Inclusion criteria were full journal publication of randomised controlled trials of direct comparisons of NSAIDs given by different routes; acute and chronic pain; pain outcomes; group size at least 10; design with internal sensitivity (i.e. at least two dose comparison or placebo control). Topical and intra-articular applications were excluded.

Statistically significant findings were extracted from the original reports, and then qualitatively summarised. Compared routes were intravenous, intramuscular, rectal and oral.


Postoperative pain

There were five comparisons across different routes (with ketorolac and diclofenac). Only one of three trials showed improved pain intensity scores with intravenous compared with intramuscular administration. One trial compared intramuscular and intravenous NSAID at induction with one hour pre-operative oral administration, and demonstrated significantly lower pain scores and less rescue analgesics with both routes compared with oral administration. One of two trials repeated this finding with intramuscular versus oral administration. Design flaws in trials make it difficult to provide a definitive answer.

Renal colic

One trial looked at intramuscular vs. intravenous dipyrone and diclofenac. Onset of analgesic action was faster with the intramuscular route. In two of two trials intravenous indomethacin vs. rectal indomethacin was associated with better pain relief and less rescue analgesics (even, with one trial, at lower doses). However, all positive trials reported improvements at 10 to 20 minutes after drug administration, which is likely to be of clinical relevance in this setting.

Adverse effects

Typical NSAID adverse effects were reported in trials. Those related to route of administration were most often reported for intramuscular and rectal regimens. The main adverse effects were discomfort at site of injection (intramuscular), diarrhoea, rectal irritation and non-retention of suppositories (rectal).

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