Delirium, ICU survivors, Intensive care unit, Posttraumatic stress disorder, Sleep disturbances



  1. Pinkas, Jamie MSN, AGACNP-BC, CCRN
  2. Horowitz, Abigail MSN, AGACNP-BC, CCRN


When patients are in the intensive care unit (ICU), they are in their most vulnerable and fragile state. These critically ill patients are often unable to make their needs known, which can produce an overwhelming feeling of helplessness and fear. The environment can seem threatening and foreign, and patients are often subjected to a multitude of disturbances that can be detrimental to their physical and psychological recovery. Loud noises, diagnostic tests performed at all hours, and poor natural lighting contribute to debilitating delirium and disturbed diurnal rhythms. Loss of privacy and basic human dignity, as well as painful procedures, has been associated with traumatic memories and distress in the post-ICU survivor population. All of these factors have contributed to patients developing ICU-related posttraumatic stress disorder after they leave the hospital. Recently, there has been an increase in awareness regarding this phenomenon within the medical community, which has generated more literature on the topic. Evidence suggests that ICU-related posttraumatic stress disorder can be mitigated. This article proposes the implementation of interventions by critical care health care providers that focus on reducing sleep disturbances, delirium, and benzodiazepine use in ICU patients, thereby improving patient comfort and reducing the severity of posttraumatic stress disorder in ICU survivors.


Article Content

Posttraumatic Stress Disorder Defined

Posttraumatic stress disorder (PTSD) is defined as a psychiatric condition that develops in individuals who have experienced a shocking, scary, or dangerous event.1 The disorder is characterized by intrusion or the individual re-experiencing the traumatic event via flashbacks, persistent memories, or nightmares. Avoidance is another characteristic, where the individual may try to avoid reminders of the event and exhibit emotional "numbness." These occurrences stimulate the autonomic nervous system, causing hyperarousal that can manifest as difficulty sleeping, irritability, and exaggerated startle response. Posttraumatic stress disorder is diagnosed if the symptoms persist longer than 4 weeks, cause great distress, or interfere with work or home life.2 Posttraumatic stress disorder has traditionally been associated with specific populations, such as those who have experienced combat, violent personal assaults, or survivors of natural or human-caused disasters. The recognition of PTSD in survivors of critical illness has only recently come to the forefront.


PTSD in Intensive Care Unit Survivors

Millions of people require intensive care unit (ICU) treatment annually, and with the ever-evolving advancement of health care technology, more patients are surviving ICU admissions. This increase of survival has prompted research on long-term outcomes of ICU survivors, with an emphasis on mental health. In a 2015 meta-analysis, the total prevalence of PTSD symptoms after ICU discharge was 24% for the first 1 to 6 months and 22% in the subsequent 7 to 12 months.3 Alarmingly, prevalence of PTSD in the ICU survivor population rivals the prevalence rates of PTSD associated with sexual-relationship violence, such as rape, which has been reported to occur in 33% of that population (Table).4

TABLE Posttraumatic ... - Click to enlarge in new windowTABLE Posttraumatic Stress Disorder (PTSD) Prevalence Across Different Populations

The same 2015 meta-analysis also found that clinically important PTSD symptoms occur in 1 of 5 patients in the first 12 months after an ICU admission and are associated with poor health-related quality of life.3 These data were later supported in a 2019 systematic review and meta-analysis of 48 studies, which also found 1 in every 5 adult survivors of critical care (19.83%) develops PTSD symptoms in the year following ICU discharge.5 In the United States, 5.7 million patients are admitted annually to ICUs, with an average mortality rate ranging from 10% to 29%. Using these data, one can estimate that approximately 1 million patients develop PTSD after ICU admission annually.5


The stressful experience of a life-threatening illness places ICU patients at a higher risk for PTSD compared with other patients, due in large part to the interventions received in the ICU. They may also have a more complicated recovery because PTSD is associated with increased rates of coronary artery disease, chronic pain, gastrointestinal disorders, arthritis, and decreased quality of life.2 The nature of PTSD symptoms in former ICU patients seems to be largely characterized by intrusive thoughts and stress.3,4,6,7


Predictors of PTSD in ICU survivors have been explored in various studies and include younger age, being female, benzodiazepine and vasopressor administration, and severe sepsis. Additionally, studies have reported that post-ICU memories of frightening experiences, memory of pain, uninterrupted use of sedatives, sleep disturbances, mechanical ventilation, agitation, comorbid psychopathology, and delirium are all positive predictors of PTSD in ICU survivors.8


Although some of these predictors are not modifiable, most of them are iatrogenic and can be reduced by the practice of preventive trauma-informed care. Disseminating awareness to critical care health care providers on the prevalence of ICU PTSD could prompt the implementation of simple, preventive measures to be carried out in the ICU.


While there are numerous factors involved in the development of ICU PTSD, this article focuses on 3 modifiable predictors of ICU PTSD: sleep disturbances, delirium, and the administration of benzodiazepines. These 3 predictors precipitate a host of negative sequelae that contribute to ICU PTSD. The authors propose certain interventions be implemented by ICU registered nurses and critical care health care providers with the goal of reducing the aforementioned modifiable, trauma-inducing events in the ICU and thus reducing the severity of post-ICU PTSD.


Sleep Disturbances

The biological requirement for sleep varies individually and can depend on age, gender, and genetics. However, the recommended average duration of sleep in adults is about 7 to 8 hours each night.9 The circadian rhythm, the body's intrinsic clock, is responsible for normalizing nocturnal rest and is mainly influenced by light. Light stimuli that fall on the retina influence functioning of the anterior subthalamus that is responsible for regulating the circadian systems and telling the body it is time for rest.9 Sleep has a restorative function and promotes health, giving the body a chance to recuperate. While a person is ill, his/her body is in a state of constant stress. Sleep is essential in combating that chronic stress state and stimulating the healing process.9


Sleep disturbances in the ICU settings have been studied for over 30 years. Assessing the quality of sleep is subjective in nature, and communication with ICU patients is often limited because of a variety of factors such as mechanical ventilation or use of sedation. Therefore, sleep is an issue commonly forgotten and frequently ignored by medical personnel. Studies have long discovered that, in a healthy population, sleep deprivation has significant pathologic consequences including weakening of the immune system leading to increased risk of infections, reduced respiratory drive, decreased pain and glucose tolerance, increased corticosteroid and catecholamine levels, and decreased healing ability.9


Sleep quality of ICU patients is poor and intermittent in nature due in large part to an increased number of awakenings throughout the night. Studies have shown that environmental noise, bright lights, staff interventions, medications, pain, stress, anxiety, delirium, and depression are contributing factors to poor quality sleep in the critical care setting. All of these factors that hinder sleep lead to acute confusion and ultimately increased length of hospital stay or increased risk of hospital-acquired complications, such as pneumonia, pressure ulcers, impaired mobility, or delirium.10 It can be argued that the consequences of sleep deprivation in the ICU population, in comparison to a healthy population, are compounded and significantly more pronounced. This can be detrimental to the healing process because it adds more stress to an individual who is already combating critical illness.


Noise is a predominating factor in sleep disturbance for ICU patients. A study done in 1999 investigated the impact noise had on total sleep time in ICU patients and found environmental noise was responsible for 11.5% to 17% of awakenings and increased sleep fragmentation.11 In 1999, the World Health Organization recommended noise levels remain less than 35 dB in patient rooms.12 However, one study found that noise in ICU patient rooms exceeded 35 dB 70% to 90% of the time. Other studies showed that patients could remember frequent sleep interruptions that induced pain, fear, and anxiety and reduced their ability to sleep. One study revealed that 14% of their sample cohort reported nightmares negatively influencing their quality of life even 6 months after their ICU stay, and 51% of them experienced dreams and nightmares.9 Through these studies, it is apparent that lack of quality sleep in the ICU setting is traumatogenic and is a driving factor in influencing ICU PTSD. It is also evident that the vast majority of factors influencing sleep in the ICU are caused by health care providers and therefore has the potential to be greatly reduced.



According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (2014), delirium is defined as (1) a disturbance in attention and awareness (reduced orientation to the environment); (2) developed over a short period, hours to days, and fluctuating in severity over time; (3) disturbances in cognition (ie, memory deficit, disorientation, language disturbance); (4) development of disturbances in cognition and attention are not caused by a preexisting, established, or evolving dementia; (5) with evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a direct physiologic consequence of a general medical condition, medication intoxication, or medication withdrawal or is multifactorial.12


There are a multitude of factors that have been identified to cause delirium such as advanced age, psychoactive drugs, sleep and light deprivation, mechanical ventilation, prolonged immobilization, low blood pressure, malnutrition, restraints, sepsis, and untreated pain. In the ICU setting, delirium is associated with significant morbidity and mortality.13 The initial mortality rate for a patient suffering from delirium in a critical care setting can be as high as 26%. These patients are twice as likely to die 1 year after experiencing hospital-acquired delirium as similar patients who did not experience delirium. Mortality rates have been reported to be as high as 75% 3 years after an episode of delirium. Delirium is also associated with increased length of mechanical ventilation and hospital length of stay as well as increased cost and prolonged neuropsychological dysfunction.14


The prevalence of delirium is high in the acute care setting, with up to 60% to 80% of mechanically ventilated medical and surgical patients and 50% to 70% of nonventilated medical ICU patients experiencing delirium.15 This is concerning considering the significant increase in mortality and ongoing cognitive deficiencies associated with the disorder. The ability to process the events occurring in the ICU is compromised, and recall of delusional memories is a major risk factor for the development of ICU-related PTSD. Numerous lifesaving interventions are consistently performed in ICUs; however, many of these treatments can be traumatizing, and memories from these experiences may be fragmented. The quality of cognitive processing at the time of the traumatic event might be important to the development of PTSD. Recalling those altered, delusional memories afterward makes it difficult for patients to decipher exactly what occurred to them. This may be a major precipitant of PTSD in the ICU population.14 Like sleep deprivation, much can be done to reduce the pervasiveness of delirium in the ICU because many of the risk factors are modifiable.


Benzodiazepines in the ICU

Benzodiazepines are regularly given in the critical care setting mainly as anxiolytics, to induce sedation and anterograde amnesia during procedures and to alleviate discomfort during mechanical ventilation or other methods of physiologic support. Although the exact mechanism of action is unknown, benzodiazepines are thought to upregulate [gamma]-aminobutyric acid, the neurotransmitter known to counterbalance the action of the excitatory neurotransmitter glutamate, and thereby exert hypnotic and anxiolytic effects.15


Critical care providers should be aware of the many risks associated with benzodiazepine administration. Physiologic and psychological dependence can occur and, as a result, withdrawal symptoms with rapid dose reduction or abrupt discontinuation of the drug. Depression and emotional blunting have been reported as well. Although the mechanism of action is unclear, benzodiazepine-related depression occurs possibly as a result of a reduction in central monoamine activity.16 Paradoxical effects are not uncommon, and patients may exhibit agitation, insomnia, and hallucinations. In addition, tolerance to the anxiolytic effects of benzodiazepines can take effect within a few days, requiring increased doses to maintain adequate sedation levels.17


It is crucial for critical care providers to be cognizant of the effects of benzodiazepines among the elderly, whose presence in ICUs has increased dramatically with the advancement of life-sustaining drugs and treatments. Benzodiazepine use in the elderly is associated with an increased rate of falls and a higher risk of drug interactions due to polypharmacy. Psychomotor slowing and paradoxical disinhibition may be amplified. Cognitive impairment is also common, whereas cognitive deterioration associated with normal aging processes and dementia can be exacerbated by benzodiazepine adverse effects.16


The American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication Use in Older Adults are widely used by clinicians. The AGS Beers Criteria are a clearly defined, evidence-based list of potentially inappropriate medications that are typically best avoided by older adults. Benzodiazepines have been listed as potentially inappropriate medication for older adults since the criteria were created by Mark H. Beers in 1991. Notably, the 2019 update made an addition under "clinically important drug-drug interactions" that stated there is an increased risk of overdose when benzodiazepines are given together with opioids, which is a common occurrence in the critical care setting. However, benzodiazepine use remains common in older adults despite the fact that older adults are highly vulnerable to harms associated with the use of these drugs.18


There is a causal pattern among benzodiazepine use, delirium, and sleep disturbances. Frequently, the goal of benzodiazepine administration is to induce sleep, yet sleep patterns potentiated by benzodiazepines are significantly altered from normal. Benzodiazepines may result in an increased total sleep time; however, their use causes a prolongation in stage sleep and a decrease in slow-wave sleep and rapid eye movement.17 Slow-wave sleep and rapid eye movement are the deep stages of sleep that are thought, by some investigators, to play an important role in cerebral restoration and recovery and to be involved in the maintenance and consolidation of sleep.19


A 2018 systematic review that aimed to clarify the existing evidence of benzodiazepines administered in the ICU as a possible risk factor for deleterious neuropsychiatric effects found a causal relationship between benzodiazepine administration and delirium. In addition, the review found an association between benzodiazepines and long-term neuropsychiatric outcomes such as PTSD.15 In the aforementioned 2015 meta-analysis, the authors found a greater number of PTSD symptoms were associated with having received any amount of benzodiazepines in 2 of 4 studies evaluated and associated with higher total dose of benzodiazepines in 1 of 2 studies.3 Benzodiazepine use in ICU patients, especially when mechanically ventilated, has also been found to be associated with delirium in several studies.20 Delirium may be the intermediate factor linking benzodiazepines and post-ICU PTSD.21 While it remains unclear to what extent and through what mechanism benzodiazepine use might relate to post-ICU PTSD, benzodiazepine administration likely reflects the management of a patient in an agitated or anxious state, causing a larger likelihood of PTSD due to these symptoms. Therefore, benzodiazepine-related delirium with associated anxiety and agitation may contribute to post-ICU PTSD.6 Studies have shown there is a causal relationship among the risk factors. One risk factor impacts another risk factor, which in turn impacts the first risk factor or another risk factor and ultimately results in trauma and neuropsychiatric complications in the future.



Interventions to decrease sleep disturbances, delirium, and benzodiazepine use in ICU patients may reduce the severity of PTSD in ICU survivors (Figure). Increasing awareness of how these 3 factors can affect ICU-related PTSD within the therapeutic team should be the first intervention and may minimize severity of trauma in ICU survivors. The principal goal should be increasing patient comfort while minimizing the risk of PTSD by addressing the easiest, most modifiable risk factors associated with ICU sleep disturbances, delirium, and benzodiazepine and sedation use. Conveniently, many interventions can positively affect all 3 of these risk factors. It is important to be mindful that patient safety is a priority, and clinicians should use their best judgment for the appropriateness of each intervention as it relates to each individual patient.

Figure. Risk factors... - Click to enlarge in new windowFigure. Risk factors and key interventions to reduce the severity of intensive care unit posttraumatic stress disorder.

In order to decrease sleep disturbances, the ICU staff should reduce light and noise intensity at night and aggregate nursing care to prevent sleep interruptions. Eye masks and ear plugs can help assist patients in blocking out noise and light during the night. Noise reduction can be accomplished by minimizing talking, overhead paging, and other unnecessary noise during established quiet hours; by adjusting monitor, medical device, and ventilator alarms; and by being mindful that patient's room doors are closed.


Light intensity can be reduced by keeping lights dimmed in the patient rooms and outside hallways and providing patients with sleep masks if appropriate. Advanced practice providers and physicians should collaborate with the bedside nurses to plan for the majority of medical interventions, including routine laboratory and diagnostic tests, be performed during designated waking hours.


With these interventions suggested above, it is important to note that, because of the current state of the literature, there is limited evidence regarding the efficacy of these practices, and more research needs to be completed. In a 2015 Cochrane review, the authors searched to assess the efficacy of nonpharmacological interventions for sleep promotion in critically ill adults in the ICU. Thirty trials, with a total of 1569 participants, were included in the review and included several interventions including, but not limited to, relaxation interventions, earplugs or eye masks, and acupressure. The authors concluded that existing evidence relating to the use of these interventions for sleep promotion was low or very low, and further high-quality research is needed to strengthen the evidence base.22


This is further supported in a 2019 systematic review that concluded the authors were unable to recommend specific interventions for hospital sleep promotion related to limited quality studies due to lack of controls, lack of blinding, and lack of self-reported outcomes.23 Both the 2015 Cochrane review and the 2019 systematic review were, however, able to point out specific interventions that had potential to improve sleep and even decrease incidence of delirium in critically ill patients. These interventions included environmental modifications, such as designated quiet times and ear plugs and eye masks.22,23 The Society of Critical Care Medicine's 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS Guidelines), a comprehensive list of evidence-based practice recommendations, state the need for large randomized trials to evaluate strategies focused on improving sleep in the ICU.24


Interventions that can be performed to reduce delirium include daily spontaneous breathing trials for mechanically intubated patients, early mobility, and frequent assessment of delirium through validated and reliable tools. Modifiable and preventable risk factors for delirium should be frequently addressed, and nonpharmacologic interventions should be provided as needed, including reorientation, cognitive stimulation, assessment and treatment of pain, and reduction of sleep interruption.21 Additionally, minimizing restraint use and avoidance or decreased use of benzodiazepines are shown to reduce the occurrence of delirium.


The PADIS Guidelines recommend the use of multicomponent, nonpharmacologic interventions to reduce the incidence of delirium. The recommendations include, but are not limited to, strategies to reduce or shorten delirium, such as the strategies listed above (reorientation and cognitive stimulation), improved wakefulness (reduced sedation), and early mobilization to reduce immobility.24 The multicomponent studies evaluated by the PADIS Guidelines showed improved outcomes in critically ill adult patients, and pilot studies suggested that early combination of cognitive and physical therapy in critical illness is feasible and safe. They also stated that, among the 5 studies evaluated, the use of such strategies reduced delirium significantly.24


A multi-intervention approach called the Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of Analgesia and Sedation; Delirium assess, prevent, and manage; Early Mobility and Exercise; Family engagement/ empowerment bundle (ABCDEF bundle) is another recommended tool by PADIS.24 The ABCDEF bundle approach focuses on symptom assessment, prevention, and management to improve outcomes in critically ill patients.25 One such outcome that has been established is the decreased incidence of delirium. A 2019 multicenter cohort study that included more than 15 000 patients evaluated the relationship between the ABCDEF bundle performance and patient-centered outcomes. The study showed significant and clinically meaningful improvements in outcomes including reduced mortality, mechanical ventilation use, coma and delirium, and restraint-free care.25


Advanced practice providers and physicians are responsible for prescribing and determining, in collaboration with the bedside nurse, when it is appropriate to wean sedation for patients. Minimizing sedation and specifically benzodiazepine use should be a priority and can be done through nonpharmacologic interventions such as reorientation strategies and music therapy and by having familiar items and/or people present in the room. Dexmedetomidine has been studied and shown to be an effective and reliable medication used for sedation in ICU patients.21 Patients should also receive sedation vacations daily and have constant assessments using validated and reliable tools of sedation, such as the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the ICU, to determine the safest score for each patient.


As a clinician, it is important to recognize and remember the pervasive theme of cyclic causality among the risk factors that may be sequential but are most often simultaneous-lack of sound sleep may cause delirium, benzodiazepine use can cause poor sleep quality and delirium, delirium may cause sleep deprivation, and so on. Therefore, interventions would be most effective if implemented in a multimodal fashion by preventing the risk factors concurrently.



The relationship between critical illness and PTSD has been assessed and established by a multitude of studies. Most of the studies done have varied greatly in their methodological rigor but have all increased awareness of how very real of a correlation there is between being in the ICU and the psychological trauma it can cause. Despite growing recognition that PTSD may occur following critical illness, it is difficult to measure the extent of the threat because of the lack of high-quality studies examining this condition and the conflicting results of current research.


Unless researchers continue to investigate the incidence and causes of PTSD in survivors of critical illness, PTSD will continue to develop in ICU survivors. As providers and nursing staff develop strategies to reduce sleep disturbances, delirium, and benzodiazepine use, studies should be conducted to determine their effectiveness and published so others can implement evidence-based practice. Coordinating lighting with the normal day-night cycle, reducing noise, and having informed advanced practice providers who deliberately prescribe interventions to reduce sleep interruptions and minimize the risk for delirium are incredibly simple actions that can be immensely therapeutic and beneficial to patients.


Understanding the nature of the relationship between critical illness and the development of ICU-related PTSD is a challenge that demands attention. Spreading awareness of the psychological trauma caused by an ICU stay among health care professionals and implementing simple therapeutic interventions to reduce its development in the ICU have the potential to increase patient comfort, promote healing, and reduce the severity of ICU-related PTSD.



The authors acknowledge the nursing faculty at the University of Pennsylvania, especially Deborah Becker, for their support and guidance in writing this article.




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