AnaConDa-S for sedation with volatile anaesthetics in intensive care

The main clinical evidence comprises 21 studies

3.1 The EAC assessed 21 full text comparative studies. Thirteen were randomised controlled trials, 5 retrospective studies, 1 prospective study, and 1 study collected data prospectively for the AnaConDa-S arm but utilised retrospective data for the intravenous arm. Fifteen abstracts identified were not included in the evidence review. The EAC focused on primary studies only and did not extract data from 1 meta-analysis to avoid duplication of data. There was no published evidence on using AnaConDa-S in children.

3.2 All included studies were peer-reviewed, and none were done in the UK. The included studies covered 6 population groups:

For full details of the clinical evidence, see section 3 of the assessment report. Find the assessment report in the supporting documentation file in the project documents on the NICE website.

Clinical experts identified 3 particularly important clinical outcomes

3.3 The EAC, after consultation with clinical experts, identified 3 outcomes of particular clinical importance: time on mechanical ventilation, wake up time and sedation efficiency. Other outcomes reported across the 21 included studies were: intensive care and hospital length of stay, cognitive and neurological status, cardiac, renal and hepatic markers and blood gas results.

Evidence shows that inhaled sedation using AnaConDa-S consistently leads to faster wake up time and maintains adequate sedation but time on mechanical ventilation is uncertain

3.4 Wake up time, usually reported as extubation time (the time from stopping the sedative infusion to taking out the endotracheal tube), was measured in 6 studies and found to be significantly shorter in the volatile sedation arms compared with the intravenous arms across all the heterogeneous populations. The EAC concluded that sedation given using AnaConDa-S offers benefit over intravenous sedation in terms of wake up time, but this is likely attributed to using the volatile sedatives that AnaConDa-S allows to be used rather than the device itself.

3.5 Inhaled sedation using isoflurane delivered with AnaConDa-S was non-inferior to propofol in maintaining adequate sedation (time spent at the desired sedation depth) without rescue medications in a large randomised clinical trial (n=301, Meiser 2021).

3.6 Eleven publications reported time on mechanical ventilation. The difference in time on mechanical ventilation between the volatile arms and the intravenous arms was uncertain because only 3 studies reported statistically significant differences (matched analysis of Krannich 2017, Rohm 2008 & 2009) and the rest of the studies found non-significant differences in time on ventilation.

There is uncertainty in the evidence on length of stay for inhaled sedation and intravenous sedation

3.7 All included studies were inconclusive about the measured outcomes for length of stay. The studies looked at different sedative drug combinations and any differences between groups are likely to be because of these drug differences as well as the variables involved in patient treatment and are unlikely to be solely attributed to using the device.

Evidence is inconclusive for other outcomes that benefit patients

3.8 Eight studies reported on cognitive and neurological outcomes, 9 studies reported on cardiac, renal and hepatic biochemical markers and 6 studies reported on patient blood gas results. Most of the studies were not statistically significant in lowering the incidence of delirium, lowering organ-specific biomarkers and improving oxygenation compared with intravenous sedatives.

The company's cost analysis model compares inhaled sedation using the AnaConDa-S device with intravenous sedation

3.9 The company's cost model compared inhaled isoflurane with intravenous propofol. The cost model had a 30-day time horizon and included adult patients needing mechanical ventilation for 24 hours or longer in intensive care. The clinical input parameters included the mean body weight of people having sedation in intensive care, the time on mechanical ventilation (mean in days) and the length of stay in intensive care (mean in days). The company also submitted a scenario analysis that compared inhaled isoflurane with intravenous midazolam. The EAC adapted this analysis to extrapolate the cost analysis in children. The EAC inputted an average body weight of 12 kg for a child but did not change the other clinical paraments. For full details of the cost evidence, see section 4 of the assessment report.

AnaConDa-S device remains cost saving in the EAC's updated model

3.10 The EAC agreed with the company's cost model overall. The EAC noted that the time on mechanical ventilation and the length of stay in intensive care were based on the results of a post-hoc analysis done in a subset of people (******) from the original randomised clinical trial (n=301, Meiser 2021). This subgroup consisted of people that did not have their sedation approach switched after the 48 hour randomisation period. The EAC corrected some costs, added the cost of training for switching from intravenous to inhaled sedation and found that AnaConDa-S remained cost saving by £4,393.20 per adult.

The company cost analysis results are robust but there is uncertainty around the clinical inputs that drive cost savings

3.11 Sensitivity analysis indicated that the cost analysis was robust to changes to drug doses, drug costs and to the addition of training costs with AnaConDa-S. The EAC threshold analysis showed that, if time on mechanical ventilation is the same for both methods of sedation, inhaled sedation using AnaConDa-S was cost saving compared with intravenous propofol when the duration of non-ventilated intensive care days was in the region of 0.5 days to 0.6 days lower. However, the length of stay in intensive care and time on mechanical ventilation, were sourced from the post hoc analysis in a subset of study patients from Meiser 2021. These outcomes were not the primary outcomes of the trial and they were not included in the publication.

Exploratory analysis suggests that inhaled sedation with AnaConDa-S is cost saving in children

3.12 The EAC used the cost analysis model comparing inhaled isoflurane with intravenous midazolam to explore the economic impact of using inhaled sedation in children. Clinical parameters were informed from Krannich 2017. The cost analysis estimated a cost saving of £3,396.85 per child. The clinical experts considered it reasonable to assume that children have a similar response to intervention to adults.