Neuropsychiatric Assessment of the ICU Survivor

By Erin A. Dean, MD; Michelle Biehl, MD; Kathryn Bash, APRN, CNP; Jeremy Weleff, DO; and Leopoldo Pozuelo, MD

This is part one of a two-part article reprinted (without references) from the Cleveland Clinic Journal of Medicine (2021;88[12]:669-679). The open-access and fully referenced original article is available at ccjm.org/content/88/12/669.

Millions of patients are admitted to the intensive care unit (ICU) annually in the United States. Considering the increased rates of ICU survival (currently 71% to 90%) and the growing elderly population, more people are likely to use ICU resources.

Any survivor of a critical illness and ICU stay is susceptible to health problems that continue to persist after discharge and may lead to post-intensive care syndrome (PICS). PICS was designated as a syndrome by the Society of Critical Care Medicine in 2010, occurs in 50% to 70% of ICU survivors, and is defined as new or worsening dysfunction in one or more of the following domains:

• Physical impairment
• Cognitive impairment
• Emotional impairment

As a result, critical care practitioners have broadened their focus on outcomes and care of ICU survivors to include the acute post-ICU survival period (30 days after ICU discharge) as well as the months and even years after ICU discharge. Post-ICU recovery care is even more necessary during the COVID-19 pandemic, as early studies noted ICU admission rates of approximately one-third of all COVID-19 patients, increasing the number of ICU survivors in need of care.

This review focuses on neuropsychiatric aspects of the care of ICU survivors, particularly regarding symptoms associated with PICS including neuropsychiatric diagnostic, screening and treatment recommendations, as well as the value of post-ICU recovery clinics. This part of the review covers diagnostic and screening aspects.

Physical impairment in PICS

ICU-acquired weakness can be categorized as critical illness polyneuropathy, critical illness myopathy, and critical illness neuropathy and myopathy. It may affect up to half of ICU survivors admitted for one week or more. Specifically, about two-thirds of mechanically ventilated patients, 60% of patients with adult respiratory distress syndrome and half of patients with sepsis will experience some degree of ICU-acquired weakness.

Several aspects of critical illness contribute to ICU-acquired weakness, from the cellular level (mitochondrial dysfunction, release of inflammatory cytokines) to systemic concerns such as inactivity and malnutrition. Patients with ICU-acquired weakness who have comorbid cognitive or emotional dysfunction may be less able to participate in physical rehabilitation and other therapies to improve weakness, thus placing them at further risk of prolonged physical weakness and highlighting the importance of targeted prevention and intervention for overall mental and physical recovery.

Other important aspects of physical morbidity are exercise limitation, fatigue, joint immobility, impairment of activities of daily living, shortness of breath, hair loss, voice changes, dysphagia and sexual dysfunction. All of these impairments may affect quality of life and can subsequently interfere with the mental health of ICU survivors.

Cognitive impairment in PICS

ICU survivors are at risk of acute and chronic cognitive dysfunction. From 20% to 40% of ICU survivors experience persistent cognitive impairment, an undeniable major complication of critical illness that most commonly affects cognitive areas of executive function, attention and memory. Cognitive dysfunction in ICU survivors has been associated with decreased quality of life, even in patients who recover physically. Some patients with persistent cognitive impairment are no longer able to work.

Depending on the severity of the cognitive impairment, patients’ family members are sometimes obligated to forfeit their social and occupational roles and adopt a new role of caregiver; this can be a significant financial burden for patients and families and also has societal impact in view of the substantial productivity loss.

Delirium. Delirium is a well-known cognitive complication of ICU admission, affecting up to 75% of ICU patients with an increased incidence in mechanically ventilated patients. One study noted a longer duration of delirium to be associated with worse global cognition and executive function at three and 12 months and with worsening depressive symptoms and quality of life one year after ICU discharge.

Pathophysiologic causes of delirium include acute inflammatory responses, metabolic derangements (particularly hyperglycemia and hormonal disturbances) and toxic or medication-induced delirium from exposure to benzodiazepines, opiates, sedatives, hypnotics, steroids and anticholinergic medications.

Delirium is not always associated with persistent cognitive impairment, as many patients recover cognitive function with treatment of their underlying medical conditions. However, Gunther and colleagues linked delirium duration to brain changes in patients admitted to the ICU with respiratory failure or shock. Longer delirium duration was independently associated with smaller overall brain volumes on MRI as well as smaller superior frontal lobe volumes at hospital discharge and three-month follow-up. Significantly smaller hippocampal volumes were noted at discharge in patients with increased delirium duration; these differences were statistically significant, but there was not a statistically significant difference at three-month follow-up. Serial MRI studies have shown decreased thalamic and cerebellar volumes at three-month follow-up in patients with longer periods of hospital delirium that were associated with worse executive functioning and visual attention impairment at 12 months post-ICU.

Delirium in COVID-19 patients. Delirium has been identified in 10% to 30% of hospitalized COVID-19 patients. Delirium can present in COVID-19 patients in the ICU even in the absence of respiratory symptoms; while the incidence is not precisely known, estimates range from 50% to 80%. Management of delirium associated with COVID-19 involves a step-based pharmacologic intervention protocol established by Massachusetts General Hospital with a graduated progression from melatonin to alpha-2 agonists to low-potency antipsychotics and then to valproic acid and dopamine agonists.

Delirium risk factors. There are several nonmodifiable pre-ICU risk factors for delirium, including older age, lower level of education, pre-existing cognitive impairment, acute severity of illness, and presence of the apolipoprotein E epsilon 4 allele or major genetic risk factor for Alzheimer’s disease (even in the absence of major neurocognitive disorder). Thus, practitioners need to identify and implement prevention strategies for potentially modifiable risk factors for delirium, including sleep hygiene, frequent reorientation, assurance that sensory augmentation devices are provided (eyeglasses, hearing aids), avoidance of deliriogenic medications (narcotics, hypnotics, anticholinergics), metabolic and hemodynamic stability, and appropriate sedation weaning.

Emotional impairment in PICS

Up to one-third of ICU survivors may experience a range of psychiatric dysfunctions after discharge. Patients with emotional impairment related to PICS are more likely to experience decreased quality of life. For the purpose of this article, emotional impairment encompasses psychiatric, psychological and mental health symptoms.

Depression. Post-ICU depression affects about 30% of ICU survivors and is associated with increased medical admissions and emergency department visits. Of note, patients with post-ICU depression more often report somatic symptoms (fatigue, decreased physical energy, psychomotor slowing) rather than cognitive-affective symptoms. These symptoms can be difficult to differentiate from physical symptoms of critical illness. Somatic symptoms of depression are less likely to respond to antidepressant medications and may require more comprehensive treatment strategies. The BRAIN-ICU study reported that severe depressive symptoms in the early post-ICU period (first three months) were likely to persist, as 33% of the study population experienced at least mild depressive symptoms at three-month follow-up that continued at 12-month follow-up.

Anxiety. The prevalence of anxiety in ICU survivors is estimated to be about 70%. Patients with post-ICU anxiety often have comorbid post-ICU depression or post-traumatic stress disorder (PTSD). As previously noted, patients who report anxiety after ICU admission also report decreased quality of life. Many patients with post-ICU anxiety have anxiety symptoms that persist 12 months after discharge.

Post-traumatic stress disorder. PTSD prevalence after ICU care ranges from 10% to 50%. Davydow and colleagues reported that 40% of ICU survivors developed clinically significant symptoms of avoidance and hyperarousal, occurring twice as frequently as intrusion symptoms (nightmares and flashbacks); this is crucial for accurate assessment of post-ICU trauma symptoms. It is important to ask patients if they are avoiding medical appointments, taking alternate routes to avoid driving by hospitals or their doctor’s office, or feeling constantly “on guard” since hospitalization. These post-ICU PTSD symptoms also lower health-related quality of life.

Predictors of post-ICU PTSD include psychopathology (particularly PTSD or depression) prior to hospitalization and greater ICU benzodiazepine use. Interestingly, there is a greater risk of PTSD symptoms with higher total benzodiazepine dose rather than prolonged benzodiazepine duration. Finally, post-ICU memories of frightening or psychotic ICU experiences are risk factors. Examination of post-ICU PTSD has shown mechanical ventilation use or duration of use, ICU length of stay and ICU admission diagnosis not to be significant risk factors. There is mixed evidence on whether delirium is a risk factor for post-ICU PTSD.

Substance abuse. Post-ICU substance abuse has not been well studied. It is known that alcohol use disorders are independent risk factors for the development of critical illness and are associated with an increased risk of mortality in critically ill patients. However, there are minimal data outlining alcohol use disorders before and after ICU admission. In examining alcohol use in patients at the time of critical illness and up to 12 months after ICU discharge, Davydow and colleagues found a significant decrease in alcohol use from the period just before critical illness to three months after ICU discharge. This is not atypical as patients tend to make healthier lifestyle choices and avoid harmful behaviors after critical illness. However, alcohol use significantly increased from 3.8% of the study population at three months to 7.5% at 12 months after ICU discharge. Many patients with post-ICU alcohol abuse also had unhealthy alcohol use in the year before ICU admission: 80% and 67% of patients with unhealthy alcohol use at three- and 12-month follow-up, respectively, exhibited unhealthy alcohol use in the year prior to ICU admission.

Assessment and screening

Several screening tools are used to identify the different aspects of PICS, thereby complicating result comparisons. Turnbull et al. examined 425 studies and found 250 instruments used for different measures of ICU survivorship, including physical limitations, cognitive limitations, mental health limitations, participation restrictions and quality of life. Needham and colleagues aimed to minimize heterogeneity through the Core Outcome Measurement Set with the objective of developing a core set of measurement tools for use in all clinical research of acute respiratory failure survivors after hospital discharge (including acute respiratory distress syndrome). Although identification of these measurement tools is a significant advance in consistency in clinical research of symptoms of critically ill patients who have been discharged, caution should be used when implementing these tools in the general ICU survivor population, as the study focused only on patients with acute respiratory failure.

Screening tools. The screening tools most commonly used for cognitive impairment in PICS patients include the Montreal Cognitive Assessment (MoCA), MoCA-Blind (MoCA without visual elements) and the Mini-Mental State Examination (MMSE).

Needham and colleagues noted that for the “cognitive” outcome group in acute respiratory failure survivors, no instrument reached a priori for consensus; however, the highest rated tool was MoCA, used to screen patients for neurocognitive symptoms in the post-ICU period. It has been shown to be a reliable screening tool independent of being used for patients who were hospitalized or in the ICU. MoCA uses a cutoff score of 26 to differentiate between normal cognitive function and cognitive impairment; these cutoffs have been found to differ based on patient race and ethnicity. It has been recommended to use MoCA-Blind, excluding the areas with visual elements (visuospatial, executive functioning and naming portions), to facilitate administering the instrument by phone if needed. The MMSE has been shown to be a poor measure of cognitive deficits in survivors of acute respiratory failure and may underestimate the degree of cognitive impairment compared with other assessment tools that focus on specific cognitive domains.

Commonly used tools for measuring post-ICU emotional dysfunction include the Hospital Anxiety and Depression Scale (HADS) for detection of anxiety and depression symptoms and the Impact Event Scale-Revised (IES-R) for assessment of PTSD symptoms. Both the HADS and IESR have been recommended as core outcome measurement sets by Needham et al. From a psychiatric perspective, the Patient Health Questionnaire-9 (PHQ-9) is used to screen for depression while the Generalized Anxiety Disorder-7 (GAD-7) is used to screen for anxiety, and the IES-R is used to screen for PTSD.

This is part one of a two-part article reprinted from the Cleveland Clinic Journal of Medicine (2021;88[12]:669-679). The open-access and fully referenced original article is available at ccjm.org/content/88/12/669.

Dr. Dean is a staff physician, Dr. Weleff is a PGY4 resident, and Dr. Pozuelo is Department Chair, all in Cleveland Clinic’s Department of Psychiatry and Psychology. Dr. Biehl is Director of the Post-ICU Recovery Clinic and Ms. Bash is a certified nurse practitioner, both in Cleveland Clinic’s Department of Pulmonary and Critical Care Medicine.