Abstract

Background: Intensive care patients often suffer from short, fragmented and low-quality sleep. Poor sleep can cause prolonged mechanical ventilation, delirium and deranged metabolic function. Sound scientific evidence for sleeppromoting treatments is lacking. Benzodiazepines, which are frequently used to treat sleep disturbances, may themselves have a disruptive effect on sleep. This survey describes the current practice of treating sleep disturbances in Dutch intensive care units (ICUs).

Methods: For this retrospective cross-sectional survey, we visited Dutch ICUs and used a structured case report form. The primary outcome was the frequency of use of sleeppromoting medication. Secondary outcomes were: type of sleep medication, non-pharmacological treatments, exposure to environmental factors and the presence of protocols on the promotion of sleep.

Results: 279 patients from 21 ICUs where included. Of 225 patients who did not receive continuous deep sedation at night, 76 (33.8%) received sleep-promoting medication. Benzodiazepines and zopiclone were most commonly used (60/225, 26.7%). Men received more sleep medication than women. Exposure to mechanical ventilation, noise, patient age and access to an entertainment system did not influence the likelihood of receiving sleep medication. Of the 21 ICUs, 16 had a protocol on sleep disturbances of which 13 advised benzodiazepines.

Conclusion: 33.8% of the patients in our survey received at least one sleep-promoting drug, most commonly a benzodiazepine. Nearly all evaluated ICU protocols on sleep promotion advised the use of benzodiazepines. More research on optimal sleep-promoting therapies is needed.

Introduction

Patients admitted to the intensive care unit (ICU) often suffer from sleep disturbances.[1-4] Patients typically suffer from shorter, more fragmented sleep and sleep quality is often poor.[5-9] In the existing literature, the term sleep quality is often used to describe both sleep architecture and subjective sleep quality reports from patients. Sleep architecture describes the time spent in the different sleep stages. The sleep stages can be divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep can be further divided into three stages: N1, N2 and N3 (also called slow-wave) sleep.[10] The REM and slow-wave stages are thought to be the most important contributors to the restorative function of sleep.[3,7,8] Hence, sleep quality may largely be determined by the time spent in these stages. Sleep in ICU patients is affected by a variety of environmental, disease-related and psychological factors. Environmental factors include those inherent to intensive care such as alarms, noisy equipment, mechanical ventilation, permanent light and nightly examinations or interventions.[1,3,7,8] Disease-related aspects include organ dysfunction, pain and adrenergic stress,[7,8] as well as certain frequently prescribed medication such as opioids, catecholamines and steroids.[1,3,9,11] And finally, psychological factors such as stress, anxiety and fear may also induce sleep disturbances.[8]

Sleep disturbances cause emotional and psychological distress for patients[3] and may lead to prolonged mechanical ventilation,[1,9,11,12] deranged immune function,[1,3,9,11] catabolism and reduced glucose tolerance,[1,9] and cognitive impairment. [3,7,11]

The current literature describes many tactics to improve sleep in ICU patients, both non-pharmacological and pharmacological. However, most of these interventions lack the sound scientific evidence required to support their effectiveness. This makes an evidence-based approach to improve sleep on the ICU difficult. In daily practice, sleep disturbances in ICU patients are often treated with benzodiazepines. Although they provide effective treatment of stress and anxiety, they have a disruptive effect on the architecture of sleep. Benzodiazepines, in particular, reduce the time spent in the restorative phases of slow-wave and REM sleep and in addition to that may induce or prolong delirium in ICU patients.[1,3,9,13,14]

In 2018, the Society of Critical Care Medicine (SCCM) published the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (the PADIS guideline).[8] The guideline gives several recommendations on how to treat or prevent sleep disruption. Non-pharmacological recommendations are selecting a certain ventilator mode (assist control instead of pressure support), reducing the amount of noise and light, and using a dedicated sleep promotion protocol. However, the position of pharmacological options in this guideline remains uncertain. A recommendation on use of benzodiazepines is absent, although it does state that they may increase disturbance of sleep. The guideline does advise against the use of propofol to treat sleep disturbances because of REM sleep suppression. The effect of melatonin and dexmedetomidine remains uncertain due to a lack of underpinning scientific evidence. In other studies, however, dexmedetomidine is shown to promote a more natural sleep architecture and hence appears to be a promising alternative for sleep-promoting treatment. [1,2]

To investigate the current approach to the treatment of sleep disturbances in the Dutch ICU, we conducted a nationwide survey. The objective was to describe the current practice of prevention and treatment of sleep disturbances. We aimed to describe the type and frequency of sleep-promoting medication use, as well as application of non-pharmacological interventions and the presence of specific protocols for the prevention and treatment of sleep disturbances.

Methods

This was a retrospective, cross-sectional study of the current practices of sedation, use of sleep-promoting medication and environmental factors in Dutch ICUs and it was carried out between May 2019 and July 2020. To achieve a representative sample of Dutch intensive care practices, tertiary academic ICUs, major non-academic hospitals and smaller local hospitals were approached. The study was coordinated by the Haga Teaching Hospital in The Hague, the Netherlands. Because of the retrospective and anonymous cross-sectional database study approach, the regional ethical review board (METC Leiden, The Hague and Delft) waived the requirement for an individually informed consent procedure for the study.

Participating hospitals were visited by single investigators. Using a pre-defined, structured case-record form, we extracted data about the use of sedatives, opioids, sleep medication, environmental information and anonymous demographic data from the previous 24 hours of patients' digital records. Patients were eligible for inclusion when they had been treated for at least one full night in the ICU. If a participating ICU facilitated medium or high care beds under the medical supervision of the intensivist, these patients were also included. Coronary care unit patients admitted to combined units were not included. Patients admitted after 18:00 hours in the evening before data collection or were discharged or had died before 06:00 in the morning of data collection were excluded. There were no other exclusion criteria. If patients were deeply sedated during the night of data collection, they were considered not to be ‘at risk’ of receiving sleep medication. A patient was considered to be deeply sedated with a Richmond Agitation and Sedation Scale (RASS) of -3 or lower and the presence of continuous sedation. We recorded information on the presence of noise-generating medical devices, such as mechanical ventilation, without discriminating whether it had or had not been present during the entire 24- hour observation period.

The primary outcome of this study was the frequency of administration of sleep-promoting medication during the night section of the 24-hour observation period (22:00-06:00 hours). For all sedative drugs administered during the night, we reviewed the nurses’ and doctors’ notes for information about the indication of the prescription. Medication that was considered likely to be prescribed primarily for anxiety, such as a three-times daily oxazepam prescription, was not counted as sleep-promoting medication, even if the evening dose was administered during the night section of the observation period. Secondary outcomes were type of sleep medication, daytime use of sedatives, non-pharmacological treatments, exposure to environmental factors and the presence of ICU protocols on sleep-promoting treatments. We also intended to study the effect of demographic and environmental predictors on the likelihood of receiving sleep medication during the observation period. Predictors were selected based on the available literature, the feasibility of assessing them during a visit and the probability they were documented by the participating ICUs.

Statistical analyses
SPSS Statistics v 26 was used for all analyses. A p-value of environmental and demographic factors and the use of sleep medication. Univariable logistic regression was used to identify potential factors associated with a higher likelihood of receiving sleep medication. Factors with a univariable p-value of 0.10 or below were selected for stepwise backward modelling strategy.

Table 1. Population characteristics (n=279)