Fifteen RCTs (816 patients) were included.
Four different opioids were given to 535 patients in 32 treatment arms and 23 different doses; 281 patients acted as controls. The quality scores ranged from 2 to 5 (median = 3).
Post-operative pain scores (4 RCTs). 1. Morphine (3 RCTs): morphine decreased pain scores for 24 hours post-operatively in 2 RCTs (1 RCT included 2 different doses of morphine), and prolonged pain relief in 1 RCT compared to control.
2. Fentanyl (2 RCTs): no effect for fentanyl was found on pain scores during 24 hours post-operatively.
Time to first administration of supplemental analgesic post- operatively (12 RCTs).
Criteria for the outcome were defined in 10 RCTs.
The median time to first analgesic with local anaesthetic alone was 2 hours (range: 1 - 4 hours) in 10 studies with bupivacaine, and 1 hour and 8 hours in 2 studies with lidocaine and tetracaine, respectively.
1. Morphine (4 RCTs with 6 treatment arms and 3 doses): median time to first analgesic was 27 hours (range: 11 - 29 hours). Morphine at doses of 0.1 and 0.2 mg decreased time to first administration in all 5 comparisons reporting this outcome. A dose of 0.05 mg had no significant effect in 1 comparison.
2. Fentanyl (7 RCTs with 15 treatment arms and 12 doses): reporting of outcomes was limited to one of 7 doses in 1 RCT. Results were inconsistent.
3. Buprenorphine (1 RCT used 2 different doses) and sufentanil (2 RCTs with 5 doses): both drugs increased the time to first administration with all doses.
Consumption of post-operative supplemental analgesics (11 RCTs).
1. Morphine (5 RCTs with 7 treatment arms and 3 doses): morphine at doses of 0.05, 0.1 and 0.2 mg decreased consumption of supplemental analgesic from 0 to 24 hours post-operatively in all comparisons.
2. Fentanyl (6 RCTs with 14 treatment arms and 12 doses): results were inconsistent, with 5 RCTs reporting no effect on consumption with fentanyl compared to control, and 1 RCT reporting decreased consumption.
3. Sufentanil (1 RCT and 2 doses): consumption of supplemental analgesic was reduced from 0 to 6 hours, but not from 6 to 24 hours, post-operatively.
Number of patients not needing supplemental analgesic intra- operatively (13 RCTs, with 739 patients, including 485 receiving opioids and 254 controls): results were inconsistent with 10 of the 28 comparisons showing a significantly-reduced need for intra- operative analgesic, compared to control. The pooled results from all opioids and doses was 96% for patients not requiring supplemental analgesic for opioid treatment, compared to 76% for control. Median NNT was 4.9 (range: 3.9 - 6.9).
Adverse effects (12 RCTs).
Observation periods ranged from 0 to 24 hours in 9 RCTs, and until first narcotic administration, 0 to 12 hours, and 0 to 48 hours post- operatively in 3 RCTs.
1. All opioids.
Nausea (11 RCTs) and vomiting (8 RCTs) were significantly more common with any intrathecal opioid than with control; NNH were 9.7 (95% CI: 6.2, 21.5) and 14.5 (95% CI: 8.1, 70.9), respectively.
Respiratory depression (12 RCTs): pooled NNH for all opioids and all doses was not significantly different for all opioids, compared to control.
Pruritis (11 RCTs): pruritis was significantly more common with opioids treatment. Pooled NNH was 2.3 (95% CI: 1.1, 1.9).
2. Morphine: pruritus (6 RCTs), NNH 2.6 (95% CI: 2.1, 3.3); nausea (5 RCTs), NNH 6.3 (95% CI: 4.2, 12.5); vomiting (6 RCTs), NNH 10.1 (95% CI: 5.7, 41.0).
3. Fentanyl: pruritus (3 RCTs), NNH 2.2 (95% CI: 1.8, 2.7); nausea (4 RCTs), NNH 21.9 (95% CI: 8.0, infinity); vomiting (2 RCTs), NNH 43.3 (95% CI: 11.4, infinity).
4. Data for buprenorphine and sufentanil were based on few studies. Buprenorphine (1 RCT with 45 patients, including 30 receiving opioids and 15 controls): pruritis, NNH 10.0 (95% CI: 4.8, infinity); nausea, NNH 4.3 (95% CI: 2.3, 38.0); vomiting, NNH 6.0 (95% CI: 2.7, infinity).
Sufentanil (2 RCTs with 77 patients, including 67 receiving opioids and 10 controls): pruritis, NNH 1.4 (95% CI: 1.1, 1.9); nausea, NNH 4.3 (95% CI: 2.0, infinity).
Univariate logistic regression showed the relative risk of post- operative pruritus increased with increasing doses of morphine (p<0.00001), fentanyl (p<0.002) and sufentanil (p<0.002). Increasing the dose of morphine also increased the relative risk of post-operative nausea (p<0.0001) and vomiting (p<0.006).