Jennifer Cole is a Critical Care and Internal Medicine Pharmacy Specialist at the Veterans Health Care System of the Ozarks in Fayetteville, Arkansas. Correspondence: Jennifer Cole (jennifer.cole@va.gov)
Author disclosures The author reports no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the author and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Objective: Insomnia and delirium have gained much attention since the publication of recent guidelines for the management in critically ill adults. Neurologic effects such as sleep disturbance, psychosis, and delirium are commonly cited adverse effects (AEs) of corticosteroids. Steroid use is considered a modifiable risk factor in intensive care unit patients; however, reported mechanisms are often lacking. This focused review will specifically evaluate the effects of steroids on sleep deprivation, psychosis, delirium, and what is known about these effects in a critically ill population.
Observations: The medical literature proposes 3 pathways primarily responsible for neurocognitive AEs of steroids: behavior changes through modification of the hypothalamic-pituitary-adrenal axis, changes in natural sleep-wake cycles, and hyperarousal caused by modification in neuroinhibitory pathways. Initial search fields produced 285 articles. Case reports, reviews, letters, and articles pertaining to primary care or palliative populations were excluded, leaving 8 relevant articles for inclusion.
Conclusions: Although steroid therapy often cannot be altered in the critically ill population, research showed that steroid overuse is common in intensive care units. Minimizing dosage and duration are important ways clinicians can mitigate AEs.
Sleep disturbance in the critically ill has received much attention over recent years as this is a common result of intensive care unit (ICU) admission. Disruptions in sleep not only can, at a minimum, cause distress and lower patient satisfaction, but also inhibit recovery from illness and increase morbidity.1,2 Several studies have been conducted highlighting the altered sleep patterns of critically ill patients; although total sleep time may seem normal (7-9 hours), patients can experience multiple awakenings per hour, more time in light sleep (stages 1 and 2), and less time in restorative sleep (stages 3 and 4, [REM]rapid eye movement).2-5
There are several hypothesized physiologic detriments that contribute to slower ICU recovery with sleep deprivation. Research in noncritically ill subjects suggests that sleep deprivation contributes to hypoventilation and potentially prolonged time on the ventilator.6-9 Cardiovascular morbidity may be adversely affected by inflammatory cytokine release seen in sleep disruption.10,11 Studies of noncritically ill patients also suggest that immune response is impaired, potentially protracting infection recovery.12,13 Finally, although not directly investigated, sleep deprivation may contribute to ICU delirium, an independent adverse effect (AE) associated with increased mortality and worse long-term outcomes.14-16
The Society of Critical Care Medicine (SCCM) recently updated its consensus guidelines for the management of pain, agitation/sedation, delirium, immobility, and sleep disruption (PADIS) in adult patients.17 These guidelines offer limited interventions to promote sleep in ICU patients based on available evidence and steer the clinician toward minimizing exacerbating factors. Although factors that affect sleep patterns are multifactorial, such as noise levels, pain, mechanical ventilation, and inflammatory mediators, medication therapy is a known modifiable risk factor for sleep disturbance in critically ill patients.2 This focused review will specifically evaluate the effects of steroids on sleep deprivation, psychosis, delirium, and what is known about these effects in a critically ill population.
To include articles relevant to a critically ill population, a systematic search of MEDLINE and PubMed from 1966 to 2019 was performed using the following Medical Subject Headings (MeSH) terms: delirium/etiology, psychoses, substance-induced/etiology, sleep-wake disorders/chemically induced, neurocognitive disorders/chemically induced, dyssomnias/drug effects plus glucocorticoids/adverse effects, adrenal cortex hormones/adverse effects, prednisone/adverse effects, methylprednisolone/adverse effects, and hydrocortisone/adverse effects. The initial search produced 285 articles. Case reports, reviews, letters, and articles pertaining to primary care or palliative populations were excluded, leaving 8 relevant articles for inclusion (Table 1).18-25
