People in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and people perceive the quality of their sleep to be poor whilst in the ICU. Propofol is an anaesthetic agent which can be used in the ICU to maintain patient sedation and some studies suggest it may be a suitable agent to replicate normal sleep.
To assess whether the quantity and quality of sleep may be improved by administration of propofol to adults in the ICU and to assess whether propofol given for sleep promotion improves both physical and psychological patient outcomes.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 10), MEDLINE (1946 to October 2017), Embase (1974 to October 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to October 2017) and PsycINFO (1806 to October 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles.
We included randomized and quasi-randomized controlled trials with adults, over the age of 16 years, admitted to the ICU with any diagnoses, given propofol versus a comparator to promote overnight sleep. We included participants who were and were not mechanically ventilated. We included studies that compared the use of propofol, given at an appropriate clinical dose with the intention of promoting night-time sleep, against: no agent; propofol at a different rate or dose; or another agent, administered specifically to promote sleep. We included only studies in which propofol was given during ‘normal’ sleeping hours (i.e. between 10 pm and 7 am) to promote a sleep-like state with a diurnal rhythm.
Data collection and analysis
Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings.
We included four studies with 149 randomized participants. We identified two studies awaiting classification for which we were unable to assess eligibility and one ongoing study.
Participants differed in severity of illness as assessed by APACHE II scores in three studies and further differences existed between comparisons and methods. One study compared propofol versus no agent, one study compared different doses of propofol and two studies compared propofol versus a benzodiazepine (flunitrazepam, one study; midazolam, one study). All studies reported randomization and allocation concealment inadequately. We judged all studies to have high risk of performance bias from personnel who were unblinded. We noted that some study authors had blinded study outcome assessors and participants for relevant outcomes.
It was not appropriate to combine data owing to high levels of methodological heterogeneity.
One study comparing propofol with no agent (13 participants) measured quantity and quality of sleep using polysomnography; study authors reported no evidence of a difference in duration of sleep or sleep efficiency, and reported disruption to usual REM (rapid eye movement sleep) with propofol.
One study comparing different doses of propofol (30 participants) measured quantity and quality of sleep by personnel using the Ramsay Sedation Scale; study authors reported that more participants who were given a higher dose of propofol had a successful diurnal rhythm, and achieved a greater sedation rhythmicity.
Two studies comparing propofol with a different agent (106 participants) measured quantity and quality of sleep using the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale; one study reported fewer awakenings of reduced duration with propofol, and similar total sleep time between groups, and one study reported no evidence of a difference in sleep quality. One study comparing propofol with another agent (66 participants) measured quantity and quality of sleep with the Bispectral Index and reported longer time in deep sleep, with fewer arousals. One study comparing propofol with another agent (40 participants) reported higher levels of anxiety and depression in both groups, and no evidence of a difference when participants were given propofol.
No studies reported adverse events.
We used the GRADE approach to downgrade the certainty of the evidence for each outcome to very low. We identified sparse data with few participants, and methodological differences in study designs and comparative agents introduced inconsistency, and we noted that measurement tools were imprecise or not valid for purpose.
We found insufficient evidence to determine whether administration of propofol would improve the quality and quantity of sleep in adults in the ICU. We noted differences in study designs, methodology, comparative agents and illness severity amongst study participants. We did not pool data and we used the GRADE approach to downgrade the certainty of our evidence to very low.
Plain language summary
Propofol at night to improve sleep in the intensive care unit
Lack of sleep affects a person’s physical and mental health and, for people who are critically ill, sleep is thought to improve healing and survival. People in the intensive care unit (ICU) experience poor sleep. Many factors contribute to poor sleep including high noise levels, 24-hour lighting and intrusive patient care activities. Propofol is an anaesthetic agent given by infusion into a vein that is sometimes used to sedate people who are in the ICU. In this review, we looked at studies in which propofol was given to adults at night-time to improve the quality and quantity of sleep.
The evidence is current to October 2017. We included four randomized controlled studies (clinical studies where people are randomly put into one of two or more treatment groups) with 149 participants in the review. Two studies are awaiting classification (because we could not assess their eligibility) and one study is ongoing. All participants were critically ill and were in the ICU.
We did not combine the results from the studies because of differences in comparison (called control) treatments and study design. One study compared propofol with no agent. This study used polysomnography (which records brain waves, oxygen level in blood, heart rate, breathing, and eye and leg movements) to measure sleep quality and quantity. It reported no improvement in duration of sleep with propofol but participants woke up less often and for shorter lengths of time and described their sleep quality as being improved with propofol. One study compared a higher dose of propofol at night described as additional night sedation, with a constant day-time and night-time dose. This study used the Ramsay Sedation Scale (which is normally used by anaesthetists to assess how easily a person is roused) and reported that participants appeared to have an improved sleep rhythm. Two studies compared propofol with benzodiazepines (a tranquilizing medicine; flunitrazepam in one study and midazolam in one study). These studies used the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale to measure quantity and quality of sleep. The study with flunitrazepam reported fewer awakenings of reduced duration with propofol but similar total sleep time in each group and the study with midazolam reported no difference in sleep quality. The study with flunitrazepam also measured sleep with Bispectral Index (used by anaesthetists to assess depth of anaesthesia) and reported longer time in deep sleep, with fewer awakenings. The study with midazolam reported higher levels of anxiety and depression in both groups, and no difference when participants were given propofol. No study reported on side effects.
Quality of evidence
We judged the evidence to be very low quality. We found only four small randomized controlled studies and the results of the studies were not consistent. We noted differences in illness severity of participants and the medicines that were compared with propofol in the included studies. Measuring quality of sleep using diaries, questionnaires and scoring systems is based on, or is influenced by, personal feelings or opinions, and we were concerned that staff and participants were aware which medicine they had been given; we believed that this could have influenced the results. Only one study used polysomnography, which is the most appropriate unbiased measurement tool for sleep.
We were unable to collect sufficient evidence to determine whether propofol given at night to adults in the ICU improves quality and quantity of their sleep, as a way of helping recovery.