This survey demonstrates that current UK analgo-sedation practice continues to involve morphine and midazolam in the majority of cases; delirium screening at the time of this survey was infrequent, and that trials of sedative agents would be acceptable to the majority of clinicians.
The strength of the study is that it is the first description of UK PICU analgo-sedation practice in over 15 years, and it includes responses from HCPs working in 100% of the 29 UK PICUs. This enables us to describe practice both according to unit of response, as well as to gauge the opinion of a wide range of professionals. A further strength is the multidisciplinary nature of the sample.
This study is different from Jenkins et al (2007) which was an observational study involving 360 patients. They found almost all mechanically ventilated children received intravenous (IV) morphine, and 70% received midazolam. Six percent received adjunctive enteral clonidine (4% received IV clonidine) (5). The recent SCCM-PANDEM guidelines suggest that alpha agonists should be the primary sedative class for PICU sedation, with dexmedetomidine for cardiac surgical patients expected to extubate early (2). However, a recent Europe-wide study found that alpha agonists made up part of the first choice sedative regimen in 18% of PICUs surveyed, although this only included 3 responses from the United Kingdom (10). Between 10 and 17% of respondents in our survey (dependent on patient category) reported using clonidine in > 75% of patients which appears to be consistent with the findings of the European survey (10). The most recent North American- focussed study was in 2014, and showed a continuing predominance of opiate/benzodiazepine combination for first choice analgo-sedation, alpha agonists being first choice in 8% of units surveyed, although this may have changed in the subsequent years (11).
Figure 1 demonstrates the reported patterns of analgesic and sedative use reported by respondents. Whilst clonidine use appears to have increased somewhat from the 6% found in 2007, midazolam is clearly still the predominant sedative agent in the UK and dexmedetomidine is not used frequently.
It is of interest that, despite recent safety concerns regarding the use of chloral hydrate for sedation, only 12–26% of respondents reported never using chloral hydrate and 13–27% of respondents reported using it in almost all patients. In the recent European survey Chloral hydrate was only used as first choice in 1% of units, used for difficult sedation in 16% (10). There are no Food and Drug Administration (FDA) approved products containing chloral hydrate available for use in North America and its use there is highly restricted (12).
Our data suggest that overall, the UK was not currently meeting the SCCM-PANDEM recommendations for screening for delirium, and screen for delirium less frequently than North American PICUs. (13) However, this has changed within the last 6 months with a national drive to implement delirium scoring across PICUs. This is important as the frequency of delirium was a prioritised by respondents as an outcome measure for future trials. The majority of respondents reported using midazolam ‘very often’ or ‘always’ in the paediatric age group, suggesting that, although it is recommended that benzodiazepine use is minimised to reduce incidence of delirium, use remains widespread. We are closer to meeting the recommendations regarding screening for IWS, with over 70% of units having screening in place (2).
There has been increasing research interest in the use of alpha-agonists as alternative or adjunct to benzodiazepines for ICU sedation, with five RCTs, and one pilot RCT in children (4, 14–18). A total of 110 children from 3 studies were randomised to either dexmedetomidine or midazolam (14, 15, 16) with results demonstrating reductions in pain, frequency of IWS and opiate use; 129 children to clonidine or midazolam which found reduced frequency of IWS but increased use of vasoactive medications with clonidine (4); and 96 children randomised to clonidine as an adjunct compared to placebo showing a reduction in benzodiazepine use in the clonidine group (17). Many of these studies were, however, underpowered making interpretation difficult.
Adult evidence has involved much larger trials (19–22). However, the largest, SPICE-III trial (Sedation Practice in Intensive Care Evaluation), failed to show difference in outcomes with dexmedetomidine compared to usual care, a finding replicated by the MENDS-2 group in patients with sepsis (23, 24). A pilot ‘BABY-SPICE’ trial assessed the feasibility of a larger paediatric trial using dexmedetomidine as the primary sedative in PICU and found it to be safe and feasible (18).
Research in the critically ill paediatric population is challenging, with a small, heterogeneous population and concerns regarding long term neurodevelopmental side effects of sedative/analgesic agents (25). However, since the closure of the CLOnidine compared with midazolam for SEDation of paediatric patients (CLOSED) and Safety profile, and the Efficacy and Equivalence in Paediatric Intensive Care Sedation (SLEEPS) trials (3, 4), the adoption of research without prior consent has greatly enhanced feasibility of recruitment to trials in the UK (26, 27). We have demonstrated that generally HCPs find trials comparing sedative agents acceptable, and recruitment would be optimised by excluding children under 3 months of age, especially those with cardiac conditions, from future work. Patient and parent involvement (PPI) may increase willingness to recruit if acceptability to parents was demonstrated.
This study is limited because it is a self-reported survey of practice and, as such, the accuracy of responses as a representation of clinical practice cannot be verified. It is further limited by some incompletely answered questions, although representation was available for all questions from 100% of units. Lastly, the respondents to the survey are all HCPs, and parents’ views were not sought.