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Acute Pain | Chronic Pain | General

Pain relief from intra-articular morphine after knee surgery

Clinical bottom line:

Intra-articular morphine may have some effect in reducing postoperative pain intensity and consumption of analgesics. The evidence is more consistent for a prolonged analgesic effect than for short term relief. However, the quality of published trials is poor, and it remains unclear whether any analgesia produced is clinically useful.

The rationale behind the use of intra-articular morphine in postoperative analgesia is based on the assumption that peripheral opioid receptors are activated in inflammation. A number of trials have been carried out to test this assumption, but consensus on the efficacy of this procedure has not been reached.

Systematic review

Kalso E, Tramer M, Carroll D, McQuay H, Moore RA. Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Pain 1997; 71:642-51.

Inclusion criteria were full journal publication, double-blind, randomised, group size 10, and an appropriate comparison group (local anaesthetic agents and pethidine were not considered). The trials also had to demonstrate reliability of internal sensitivity - adoption of a design able to demonstrate sensitivity to intra-articular local anaesthetic or morphine compared with placebo or dose responses.

Effectiveness was defined as a significant difference between:

  1. the active and control groups in pain intensity (either early period 0-6 hours or late period 6-24 hours)
  2. total consumption of rescue analgesics

This was based directly on the data reported in the original trials.


Included trials studied the effects of 0.5 to 5 mg of morphine. Controls were bupivacaine (0.25 to 0.5%) as the only intra-articular local anaesthetic, intra-articular saline or intravenous or intramuscular morphine 1 to 2 mg. Quantitative analysis of pooled data was not carried out because results were presented as means. These are inadequate descriptors of asymmetrically distributed data.

Morphine vs. saline (index of internal sensitivity: bupivacaine vs. intra-articular saline)

Six trials were analysed. In two of six trials there was no internal sensitivity and no difference between intra-articular morphine and saline. Four of six trials demonstrated sensitivity, and three of these also demonstrated significantly lower early pain intensity scores compared with saline. Three of three trials demonstrated significantly lower late period pain intensity scores compared with placebo. Two of two trials demonstrated significantly lower consumption of additional analgesics over 24 hours.

Morphine vs. saline (no active control)

Three trials were analysed. Two of three trials demonstrated significantly lower early period and late period pain intensity. Two of three trials had significantly lower total consumption of analgesics over 24 hours.

Morphine vs. systemic morphine

Three trials were analysed. One of three trials demonstrated significantly lower early period pain intensity, and none of two trials demonstrated a difference in late period pain intensity. One of two showed a decrease in total consumption of analgesics.

Combination of morphine plus bupivacaine versus saline

Four trials were analysed. Only trials which were sensitive to bupivacaine alone and had a positive effect for morphine also showed a significant effect for the combination vs. placebo (early and late periods).

Dose response comparisons

Two trials with no internal sensitivity were analysed. One of two differentiate only between 1 mg intra-articular morphine and control, and the other showed a reverse dose response between 1 and 2 mg. Two internally sensitive trials comparing different doses of morphine in combination with standard dose of bupivacaine were analysed. No dose response was detected between either 1 and 3 mg, or 2 and 5 mg morphine.

In conclusion there is some support for the analgesic efficacy of intra-articular morphine after knee surgery. Convincing evidence for an early effect is lacking. Although there is more evidence for prolonged effect, these measures are weak. Furthermore, it is noted that the evidence rests primarily on four trials fulfilling the sensitivity requirements. These had only 10 patients per group. The additional two trials were methodologically weak.

Adverse effects

No adverse effects that could have been attributed to the intra-articular treatment were reported.

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