Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Evaluation of 'Dementia Friends' programme for undergraduate nursing students: Innovative practice.

The ‘dementia friends’ programme was launched by the Alzheimer’s Society in the UK two years ago with the purpose of educating members of the public about the things they can do which can enhance the lives of people living with dementia. The aim of this project was to deliver a two-hour ‘Dementia Friendly Community Workshop’ written by the Alzheimer’s Society, to an entire cohort of first-year undergraduate nursing students in one Higher Education Institutions in Northern Ireland. Following delivery of the programme, students were asked to complete a short questionnaire on their knowledge and confidence in relation to dementia care before and after the Dementia Friendly Community programme. A total of 322 undergraduate first-year nursing students took part in the Dementia Friendly Community programme. Of these, 304 returned questionnaires; 31.25% of students stated their perceived improvement in dementia knowledge was ‘good’ while 49.01% stated their perceived improvement in dementia knowledge was ‘very good’ and 13.49% stated their perceived improvement in dementia knowledge was ‘excellent’. In relation to confidence in engaging with people with dementia, 31.91% stated ‘good’ improvement, 40.79% stated ‘very good’ improvement and 11.84% stated ‘excellent’ improvement. The Dementia Friendly Community programme was positively reviewed by the undergraduate students as it enhanced knowledge and confidence in relation to care of someone living with dementia.

Impact of the Roots of Empathy Programme on Social-Emotional Learning: A Randomized Controlled Trial

Roots of Empathy (ROE) is a universal, school-based social and emotional learning programme aimed at increasing prosocial behaviour and reducing difficult behaviour. This paper reports the findings of a cluster randomized controlled trial of the effects of ROE on 8-9 year old children. 74 schools and 1,181 children took part. The findings provide evidence that ROE is effective in increasing prosocial behaviour (g=+.20, p=.043) and some potential evidence that it may reduce difficult behaviour (g=-.15, p=.070). While ROE was found to lead to improvements in positive behaviour, these were not associated with improvements in empathy or other social and emotional learning outcomes.

A Design & Feasibility Study of the Spaced Learning Programme

Objectives There is evidence from neuroscience, cognitive psychology and educational research that the delivery of a stimulus in a spaced format (over time) rather than a massed format (all at once) leads to more effective learning. This project aimed to pilot spaced learning materials using various spacing lengths for GCSE science by exploring the feasibility of introducing spaced leaning into regular classrooms and by evaluating teacher fidelity to the materials. The spaced learning methods will then be compared with traditional science revision techniques and a programme manual will be produced. Design A feasibility study. Methods A pilot study (4 schools) was carried out to examine the feasibility and teacher fidelity to the materials, using pupil workshops and teacher interviews. A subsequent random assignment experimental study (12 schools) will involve pre and post testing of students on a science attainment measure and a post-test implementation questionnaire. Results The literature review found that longer spacing intervals between repetitions of material (>24 hours) may be optimal for long term memory formation than shorter intervals. A logic model was developed to inform the design of various programme variants for the pilot and experimental study. This paper will report qualitative data from the initial pilot study. Conclusions The paper uses this research project as an example to explain the importance of conducting pilot work and small scale experimental studies to explore the feasibility and inform the design of educational interventions, rather than prematurely moving to RCT type studies.