You Na P. Kheir, MD

is Assistant Professor of Clinical Psychiatry, Indiana University School of Medicine, IU Health Neuroscience Center, Indianapolis, IN;

s a Resident, Department of Psychiatry, Indiana University School of Medicine, IU Health Neuroscience Center;

is Resident, Department of Internal Medicine, Indiana University School of Medicine;

is Associate Professor of Medicine, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Internal Medicine, Indiana University School of Medicine.

Post-intensive care syndrome (PICS) is a rapidly growing phenomenon in older adults. As survival rates from ICU hospitalizations have increased over the past few decades, the long-term cognitive, psychological, and physical sequelae of the illness have become a major challenge in critical care medicine. More than half of all ICU survivors suffer from at least one PICS-related impairment, and these effects can persist as long as 5 or more years.

PICS has become an increasingly important phenomenon in older adults for several reasons. First, the number of older adults with critical illness is rapidly increasing as the population ages and now accounts for about 50% of ICU admissions.

 Second, more than 70% of older adults hospitalized in the ICU develop delirium, which is a major risk factor for ICU-acquired cognitive impairments.

 Third, cognitive and functional impairment before an ICU hospitalization increases the likelihood of cognitive and functional decline afterward.

Paul, a 76-year-old widower, was found lying on the floor of his home. When the emergency medical technicians arrived, he was having trouble breathing and was not oriented to place or time. In the emergency department, the diagnosis was sepsis secondary to pneumonia. He was intubated and placed on mechanical ventilation. In the ICU he was treated with intravenous fluids, vasopressors, and antibiotics for overwhelming infection and septic shock. After 1 week, he was extubated and transferred to the regular floor. For the first few days on the regular floor, he remained confused and only sometimes recognized his surroundings. Eventually, he improved physically and was fully oriented to person, place, and time upon discharge.

Two months later, Paul’s neighbor brought him to his primary care physician. Paul was having difficulties paying his bills and keeping track of his medication regimen. He was still able to drive a few blocks to the grocery store but became tired if he drove more than 30 minutes. He was also less willing to drive to unfamiliar places because he had difficulty following the GPS. The neighbor noted that Paul was frequently repeating himself and misplacing items. Paul seemed withdrawn and depressed.

ICU-acquired long-term cognitive impairments (LTCIs) affect 30% to 80% of survivors. LTCIs appear to affect multiple domains, including executive functioning, memory, and attention. For many, LTCIs improve within the first year, although they can persist for many years in some people. Risk factors for LTCIs in older adults include neurological dysfunction, infection or severe sepsis, and acute dialysis. Duration of delirium is also a risk factor for LTCIs.

Current theories suggest that LTCIs from delirium may be distinct from Alzheimer disease (AD). While beta-amyloid deposition appears to be a key factor in the development of AD, long-term cognitive impairment from delirium appears to be caused by hypoxia and pro-inflammatory cytokines.

 This theory is consistent with the observation that the onset of LTCIs from delirium may depend on the duration of exposure to the pathophysiologic processes of delirium.

Evidence also suggests that LTCIs from delirium appear to differ from AD in several important ways. First, many patients’ LTCIs improve after the acute hospitalization. This trajectory is quite different from the progressive nature of AD. Second, executive functioning in LTCIs is associated with more severe depression and subsequently worse mental health quality of life.

 Finally, LTCIs may be associated with white matter damage and smaller superior frontal lobes, thalamus, and cerebellar volumes, whereas AD is classically associated with predominant hippocampal atrophy. However, it is interesting to note that smaller hippocampal volumes are also associated with longer duration of delirium.

Depression, anxiety, and PTSD are the best-characterized mental health impairments in PICS. Among adult ICU survivors, the prevalence of depression is 19% to 37%

; the prevalence of anxiety is 32% to 40%

; and the prevalence of PTSD is 19% to 22%.

 Psychiatric comorbidity in ICU survivors is 4 to 6 times more common than in the general population (25% to 33% of ICU survivors versus 6% for the general population).

 Moreover, patients in whom critical illness develops may be more likely to have premorbid psychiatric illness compared with those hospitalized in general wards and the general population.

Paul was referred to an interdisciplinary ICU survivor clinic for further workup and management. He completed the Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS), a 30-minute cognitive screen. His test results showed that he had mild cognitive impairment, multidomain amnestic type, and comorbid moderate depression. The consulting psychiatrist recommended starting venlafaxine to help with his depression and neuropathic pain. He was also referred for additional outpatient physical therapy and to a psychologist for cognitive behavioral therapy for his depression.

There are no multisite randomized, double-blind, placebo-controlled studies that show the efficacy of medications to ameliorate long-term cognitive impairment or mental health symptoms of PICS. Studies are underway to test the efficacy of treatments for PICS. The mobile Critical Care Recovery Program is an ongoing clinical trial studying the efficacy of a home-based multidisciplinary intervention for PICS. The IMPROVE trial is another ongoing clinical trial to test whether combined physical and cognitive training can improve outcomes of long-term cognitive impairment.

Physical and occupational therapy should be utilized to ameliorate functional difficulties. Home health services can be invaluable for the patient who remains in the home independently, while reducing caregiver burden. Added medications during the hospitalizations can result in polypharmacy, which psychiatrists can help reduce.

ICU patients are often discharged on inappropriate medications, and they continue to take these medications for a significant duration. These medications include anticholinergics, opioids, nonbenzodiazepine hypnotics and benzodiazepines, and atypical antipsychotics. Despite the recommendation to minimize use of antipsychotics, close to one-quarter of patients who were given a new antipsychotic during their hospitalization were discharged on an antipsychotic. If clinicians decide to continue psychotropics upon discharge from the ICU, they should carefully weigh the benefits versus risks, such as the FDA black box warning for antipsychotics.

Evidence for the efficacy of psychotropics specific for ICU survivors is limited. It makes sense, however, to deliver evidence-based mental health treatment and for primary care physicians to screen for depression and anxiety using self-report questionnaires such as the Patient Health Questionnaire-9 (PHQ-9) for depression and Generalized Anxiety Disorder-7 (GAD-7) for anxiety. ICU survivors with depression and anxiety should be aggressively treated with antidepressants and depression-focused psychotherapies. Those who have a history of treatment with mental health specialists, have been hospitalized on psychiatric wards, received ECT, or are not responding to first-line treatments should be referred for subspecialty mental health treatment.

Dedicated post-ICU survivor clinics are another important resource. In 2016, the Society of Critical Care Medicine (SCCM) sponsored the creation of a national collaborative network of ICU survivor clinics, known as the Thrive Post-ICU Clinic Peer Collaborative. A small longitudinal study of the Critical Care Recovery Center in Indianapolis found beneficial effects on patients’ cognitive and functional symptoms.

 Future studies will need to further examine the effectiveness of ICU survivor clinic across the US.

There are a number of special challenges with older adults. Although age is not a risk factor for long-term cognitive impairment, older adults are more likely to develop delirium compared with their younger counterparts. Older adults are also more likely to develop functional difficulties post-ICU, since they may already have functional disability before hospitalization.

Studies have found mixed results on whether age increases the risk of mental health symptoms. Nevertheless, older adults frequently encounter additional barriers as they seek mental health treatment. For example, older adults who need psychotropics may be at increased risk for adverse effects of medications and may have to overcome more physical challenges to attend psychotherapy sessions.

Post-intensive care syndrome-family (PICS-F) describes the psychological impact of ICU hospitalization and post-ICU recovery on family members and other caregivers. PICS-F symptoms can start in the ICU and often persist in the post-ICU phase. Interventions for PICS-F include keeping diaries and using educational materials. Diaries are written by the ICU staff and family, and include photos of patients and family members during the ICU stay. Educational materials include pamphlets or brochures about PICS and informational videos available on the hospital TV and social media.

The rapid growth in numbers of older ICU survivors presents the field of medicine and surgery with an unprecedented clinical challenge to care for this population. Psychiatric morbidity in ICU survivors is associated with adverse effects on patients’ quality of life and increased acute care service utilization after discharge from the ICU. However, the role of mental health professionals in these ICU survivorship models has not been well-defined.

Psychiatrists can play a key role in building and leading new health delivery models for PICS. Because clinical practice guidelines for the neuropsychiatric sequelae in ICU survivors do not exist, psychiatrists provide invaluable input on the diagnosis and management of post-ICU cognitive and mental health impairments. Next, psychiatrists need to collaborate with the leadership in the hospital to build system-wide interventions for ICU survivors. These interventions should focus on a proactive assessment of psychiatric comorbidity for both patients and caregivers upon admission. These interventions should create a plan for ongoing management throughout patients’ entire hospitalization and in the outpatient setting. A recovery care coordinator needs to be identified during the ICU hospitalization. This ensures that care coordination starts with patients and caregivers during the ICU hospitalization. The recovery care coordinator can collaborate with the psychiatrist to implement the individual care plans and ensure continuity of care in outpatient settings. Most importantly, the recovery care coordinator continues to work with the patient and family in the outpatient setting until the care plan goals are achieved.

All psychiatrists, including geriatric psychiatrists, can be part of interdisciplinary teams by providing clinical services and leading clinical practice and research innovations. They can provide diagnostic and treatment recommendations via traditional face-to-face visits, electronic/telephone consultation, or videoconferencing. Psychiatrists can also increase their impact by educating trainees in the fields of mental health and medical and surgical subspecialties. Proactive collaboration between psychiatry and medical and surgical fields will raise awareness of cognitive and mental health impairments and decrease the stigma of mental health treatment.

Dr. Wang reports that she received book royalties from American Psychiatric Publishing Inc. Drs. Kheir, Allen, and Khan report no conflicts of interest concerning the subject matter of this article.

-Dr. Wang is supported by NIA 2P30AG010133, NCATS UL1TR001108 (Project Development Team), and DOD AZ160032. Dr. Khan is supported by NIA K23-AG043476, NHLBI R01HL131730, and NIA R01AG055391.

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