Effects of epidural volume extension by saline injection on the efficacy and safety of intrathecal local anaesthetics: systematic review with meta-analysis, meta-regression and trial sequential analysis.

Epidural volume extension, a modification of combined spinal-epidural anaesthesia, involves the epidural injection of saline in order to increase the spread of drugs given intrathecally. Results from individual studies have so far been contradictory and we aimed to gather the available evidence for this technique. We performed a systematic literature search for randomised, controlled trials comparing epidural volume extension after spinal injection with a control group without epidural injection in patients undergoing surgery. Conventional meta-analyses, trial sequential analyses and meta-regression were performed, with the Grading of Recommendations on Assessment, Development and Evaluation (GRADE) approach used to express reliability of outcome estimates. We included 15 studies with 1177 participants. Meta-analyses for the primary outcomes, such as maximum sensory height (6 studies, 274 participants, mean difference (MD) (95%CI) -0.59 (-1.24 to 0.07) dermatomes, low-quality evidence) and hypotension (10 studies, 683 participants, risk ratio (95%CI) 0.84 (0.66-1.07), low-quality evidence), did not differ significantly between the two treatment arms, but trial sequential analysis suggested insufficient evidence to be certain of these findings. Meta-regression suggested a volume-dependent effect, with higher volumes causing a higher spread of intrathecal drugs and a higher incidence of hypotension. A sub-group analysis indicated a pronounced effect on motor block recovery time when a lower anaesthetic dose plus epidural volume extension was compared with a higher anaesthetic dose without epidural volume extension, the MD (95%CI) being -66.75 (-76.0 to -57.5) min, with trial sequential analysis suggesting the evidence was sufficient to draw this conclusion. In trials using the same anaesthetic mixture in the epidural volume extension and the control groups, motor block recovery time did not differ between groups, with a MD (95%CI) of -1.06 (-5.48 to 3.36) min, although trial sequential analysis suggested insufficient evidence. In summary, there is not enough evidence to draw definite conclusions on the effect of epidural volume extension. The quality of the current evidence is low for both efficacy (maximum sensory height) and safety (hypotension). However, there may be a significantly shorter motor block recovery time when different anaesthetic mixtures are used in epidural volume extension and control groups; this warrants further investigation.