Abstract: We included three new RCTs in this update, which now comprises 10 studies with a total of 614 participants. We judged most trials as having uncertain risk of bias regarding randomization. Other than this, the overall risk of bias was low. Most included trials had small sample sizes. All of the trials assessed the primary outcome of conversion to general anaesthesia. Ten trials comparing anaesthesia performed with hyperbaric and isobaric bupivacaine failed to show any difference in need for conversion to general anaesthesia (RR 0.33, 95% CI 0.09 to 1.17, 614 participants, very low quality of evidence). Nine trials also failed to show a difference in the need for supplemental analgesics (RR 0.61, 95% CI 0.26 to 1.41, 554 participants, very low quality of evidence). Four trials comparing requirement for ephedrine did not show any difference (RR 0.89, 95% CI 0.57 to 1.38, 256 participants, very low quality of evidence). Seven trials did not provide convincing evidence of difference in nausea and vomiting (RR 0.99, 95% CI 0.57 to 1.72, 433 participants, low quality of evidence). Three trials failed to show a difference in headache (OR 1.82, 95% CI 0.47 to 6.99, 234 participants, low quality of evidence). Two trials showed that the time until sensory block to the thoracic 4th (T4) spinal level was shorter with hyperbaric bupivacaine (MD -1.06 minutes, 95% CI -1.80 to -0.31, 128 participants, moderate quality of evidence). Six trials showed no difference in the amount of ephedrine used (RR 0.23, 95% CI -1.65 to 2.12, 386 participants, moderate quality of evidence). Three trials failed to show any difference in high block (RR 0.88, 95% CI 0.16 to 4.90, 205 participants). Data are limited for some of the outcomes. Reporting of the included trials is less than optimal. For these reasons the overall quality of evidence is low or very low for most of the outcomes, based on the GRADE method of assessment. This review found that intrathecal hyperbaric bupivacaine had a more rapid onset of sensory blockade at the 4th thoracic vertebra (T4) level than isobaric bupivacaine. Hower, despite incorporating more data in the analysis, we found little evidence that the need for conversion to general anaesthesia and supplemental analgesia differed between the hyperbaric or isobaric bupivacaine groups. This is mainly due to the rarity of these outcomes, variability in the dose, use of adjuvant drugs and differences in the technique used for regional anaesthesia. There were no differences in the adverse effects studied. Any possible advantage of hyperbaric bupivacaine needs to be confirmed in larger randomized trials. In future research, criteria for conversion to general anaesthesia need to be defined objectively and applied uniformly.

Plain-language summary: The evidence is current to March 2016. We found 10 clinical trials evaluating these two types of bupivacaine, involving 614 women. The studies assessed the following effects of the two types of medicine: women needing to switch to general anaesthesia, additional drugs for pain relief or low blood pressure, experiencing nausea and vomiting, headache and excessive numbness. We found that all the studies had been done properly. None of them reported their source of funding. We await responses from the authors of two more studies, and will cover these when we next update the review. We found that there is insufficient evidence to establish whether denser or normal bupivacaine is the more effective in reducing the need for: a) switching to general anaesthesia; b) additional pain relief medication. Denser bupivacaine had a more rapid onset of pain relief. Due to the differences among the included studies in doses given, variety of additional drugs used for pain relief, variation in regional anaesthesia techniques and the small numbers of participants, we rated the overall quality of evidence for different outcomes from very low to moderate, as very few women experienced untoward events in all trials. We conclude that the denser form provides faster pain relief than the normal one. More research is required to be certain about the effectiveness of the denser form for other outcomes.