AnaConDa-S for sedation with volatile anaesthetics in intensive care

AnaConDa-S is an efficient delivery system for using inhaled sedation in an intensive care setting without needing a scavenging system

4.1 Experts explained that AnaConDa-S is the only device that allows delivery of inhaled sedation in an intensive care setting without the need for a gas scavenging system. The alternative would be to use an anaesthetic trolley or machine used for general anaesthesia with a gas scavenger, but the clinical experts said that intensive care units are not routinely equipped with scavenging systems. The experts also said that before AnaConDa-S was implemented, patients needing inhaled sedation with vaporisers had to be transferred to operating theatres where scavenging systems for volatile anaesthetics are built into the hospital system (that is, the exhaust port of the anaesthetic circuit or ventilators are connected to the operating theatre scavenging system). The committee concluded that AnaConDa-S is an efficient delivery system for inhaled sedation in an intensive care setting not equipped with scavenging systems.

No published clinical evidence is available on using AnaConDa-S in children

4.2 Although no clinical evidence in children was presented to the committee, a clinical expert said that AnaConDa-S has been used for 15 years in their paediatric intensive care and it is an effective way of delivering inhaled sedation. No major contraindications exist for using inhaled sedation in children, apart from malignant hyperthermia susceptibility. The EAC extrapolation of the efficacy of inhaled sedation from adults to children considered it reasonable to assume that children respond similarly to the intervention to adults. The committee accepted the assumption and concluded that AnaConDa-S is a useful option for allowing delivery of volatile sedation in children.

Evidence shows that inhaled sedation using AnaConDa-S is consistently associated with faster wake up time

4.3 Six clinical studies (5 randomised controlled trials [RCTs] and 1 comparative non-RCT) reported statistically significant differences in wake up between the intravenous sedation and the inhaled sedation using AnaConDa-S. The EAC reported that the extubation time is likely dependent on the type of sedative agent used rather than using the AnaConDa-S device itself. Nevertheless, the clinical experts agreed that using inhaled sedation delivered with AnaConDa-S leads to more predictable wake up time in people having sedation for long time and this is useful when patients need to be woken quickly to make clinical assessments.

The evidence for replacing intravenous sedation with inhaled sedation delivered by AnaConDa-S is uncertain because of heterogeneity

4.4 The 21 studies had heterogenous patient populations that included people after cardiac surgery (9 studies), people after cardiac arrest having therapeutic temperature management (3 studies), people with acute respiratory distress syndrome (2 studies), patients with various surgical indications (2 studies), people having head and neck surgery who need a tracheostomy (1 study), people with pulmonary disorders (1 study) and people with over 12 hour (1 study) and 24 hour sedation needs (2 studies). The committee concluded that there was uncertainty about which specific patient population would benefits more from using inhaled sedation. But, based on expert advice, it agreed that AnaConDa-S should be an available option for delivering inhaled sedation in intensive care settings when considered clinically appropriate.

Length of stay in intensive care and the time on mechanical ventilation depend on the underlying condition

4.5 Clinical experts said that the length of stay in intensive care and the time on mechanical ventilation are outcomes that depend on a patient's underlying condition. The committee understood that this means it is particularly challenging to show evidence of benefit for length of stay in the context of a clinical study. However, clinical experts explained that using inhaled sedation can reduce the time on mechanical ventilation and shorten the time the patient stays in intensive care after extubation by some hours. The committee concluded that type of sedation used was likely to only have a small effect on the length of stay in intensive care or time on mechanical ventilation.

AnaConDa-S delivered inhaled sedation is useful for sparing intravenous agents during emergency situations

4.6 Clinical experts reported that during the SARS-COV-2 pandemic, inhaled sedation using AnaConDa-S has been used to preserve intravenous sedative agents that could potentially be in limited supply. The committee concluded that AnaConDa-S is a useful option to spare intravenous sedative agents during unexpected emergency situations when large number of people need mechanical ventilation such as in the recent SARS-COV-2 pandemic.

Adverse events associated with using AnaConDa-S are uncommon but inhaled sedation is contraindicated in some patients

4.7 The committee heard that were no reported safety concerns around using the AnaConDa-S device. It understood that people in intensive care have highly complex needs and as such most adverse events will be due to the different medications to achieve sedation, rather than using the AnaConDa-S device itself. The only adverse event linked to the device is blockage, which can also happen in heat and moisture exchangers at a similar rate. There are adverse events associated with using volatile anaesthetic drugs. Volatile anaesthetics are contraindicated in patients with malignant hyperthermia susceptibility. Clinical experts said that using volatile anaesthetics in pregnant women, especially in the first trimester, involve clinical judgment in the risk/benefit balance to the unborn foetus and risk to the woman. The committee concluded that using AnaConDa-S is safe.

4.8 There are other adverse events associated with using volatile anaesthetia listed in the British National Formulary.

Some evidence shows inhaled sedation seems to be beneficial to patients

4.9 Clinical experts explained that there are benefits for patients when volatile sedatives are used such as liver, lung and cardiac protection. The EAC reported better awareness quality (1 study) and lower incidence of delirium (1 study) in the AnaConDa-S group compared with the intravenous group.

Clinical experts suggest AnaConDA-S may be more beneficial in some patient subgroups

4.10 The clinical experts agreed that inhaled sedation is likely to be beneficial in the following subgroups:

Children and adults having sedation with inhaled volatiles using AnaConDa-S can be transported for transfer within hospital

4.11 While uncommon, clinical experts said that patients can be transported for additional tests or procedures within hospitals using AnaConDa-S. If transport ventilators do not have scavenging system built in, canisters containing activated carbon, such as FlurAbsorb, can be added to the transport trolley.

Only health care professionals trained in inhaled anaesthetic drugs can use AnaConDa-S

4.12 The clinical experts said that the company offers face-to-face training and an e-learning module for intensive care nurses and intensivists. The clinical experts noted that the company training resources were highly effective.

Economic modelling is limited by the uncertainty in some clinical inputs and its relevance to the NHS clinical pathway

4.14 The committee accepted the EAC's changes to the company model, which showed inhaled sedation delivered with AnaConDa-S was cost saving when compared with intravenous sedation. However, the committee agreed that the modelled clinical scenario comparing intravenous sedation with inhaled sedation using AnaConDa-S does not reflect the average UK duration of time on mechanical ventilation in intensive care so has limited applicability (mean time on mechanical ventilation used in the model was *** days whereas experts reported 5 days to 7 days in the UK). The committee also noted that the clinical evidence used to populate the model had substantial limitations, which affected the robustness of the model and the certainty of the results.

Because of the outcomes measured in the study, the cost savings are not certain

4.15 The committee concluded that the evidence about length of stay in intensive care and the time on mechanical ventilation reported in the post-hoc analysis from Meiser 2021 trial was very weak. Because these inputs were the key drivers that led AnaConDa-S to be cost saving, there was uncertainty if using AnaConDa-S would be cost saving. Despite these uncertainties, the committee noted that AnaConDa-S has a low threshold to be cost saving. The EAC's threshold analysis found that AnaConDa-S was cost saving when duration of non-ventilated days in intensive care was 12 hours shorter than that of intravenous. The committee concluded that AnaConDa-S was likely to be the cost saving.

AnaConDa-S remains cost saving in all analysed scenarios

4.16 The committee noted that AnaConDa-S remained cost saving in all scenario analyses presented. However, the robustness of the estimates of length of stay in intensive care and time on mechanical ventilation were uncertain. The committee concluded that the uncertainty in the clinical inputs could led to inaccuracies in the cost savings calculated.

AnaConDa-S is likely to be cost saving compared with intravenous sedation in both adults and children

4.17 The EAC reported that in modelling, AnaConDa-S is cost saving compared with intravenous sedation by £4,393.20 per adult patient and by £3,396.85 per child. The committee concluded that AnaConDa-S was likely to be cost saving compared with propofol or midazolam but recognised the limitations in the underpinning clinical evidence which made the size of the potential cost savings uncertain.

Further good quality research is needed to address uncertainties about the population for whom AnaConDa-S is most appropriate

4.18 The committee recognised that AnaConDa-S is an efficient and safe way of delivering volatile anaesthetics in intensive care units. The committee concluded that further research is needed to address uncertainties in the appropriate population where AnaConDa-S would be recommended for use compared with standard care. It concluded that, although there is clear evidence that inhaled sedation using AnaConDa-S can lead to faster wake time, the evidence around the decrease in length of stay in intensive care and time on mechanical ventilation are more difficult to because of the complexity of the underlying conditions of people in intensive care unit.