Post-intensive care syndrome (PICS)

INTRODUCTION — Advances in critical care medicine have resulted in a growing population of survivors of critical illness. Many survivors experience impairment in cognition, mental health, and physical function, known as post-intensive care syndrome (PICS). The mental health of family members may also be adversely affected, which is termed PICS-family (PICS-F). The coronavirus disease 2019 (COVID-19) pandemic has increased awareness of PICS and the long-term impairments that survivors of critical illness often experience.

In this topic, we review the definition, epidemiology, clinical manifestations, evaluation, treatment, and outcome of PICS and PICS-F. The management and prognosis of patients following a cardiac arrest, of patients requiring prolonged mechanical ventilation, and following COVID-19 are discussed separately. (See "Prognosis and outcomes following sudden cardiac arrest in adults" and "Management and prognosis of patients requiring prolonged mechanical ventilation" and "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")".)

DEFINITION — Although there is no official definition for post-intensive care syndrome (PICS), most clinicians agree that PICS constitutes new or worsening function in one or more of the following domains after critical illness (figure 1) [1]:

●Cognitive function

●Psychiatric function

●Physical function

This definition is inclusive of adult patients who reside in long-term acute care rehabilitation units, skilled nursing facilities, and at home. In addition, PICS, in general, excludes patients admitted with traumatic brain injury and stroke. PICS is usually identified in the immediate period following a critical illness. However, because symptoms are long-lasting and the condition is underrecognized, there is no set duration of time after a critical illness where PICS can or cannot occur. (See "Overview of ischemic stroke prognosis in adults".)

The term post-intensive care syndrome-family (PICS-F) has been coined to encompass the effects of critical illness on acute and chronic psychological morbidity among patients' family members [1]. It is considered the family response to the stress of critical illness in a loved one. It includes the symptoms that are experienced by family members during the critical illness as well as those that occur following death or discharge of a loved one from the intensive care unit. (See 'Post-intensive care syndrome-family' below.)

EPIDEMIOLOGY — In the United States, among the 5.7 million annual admissions to the intensive care unit (ICU), approximately 4.8 million will survive the ICU stay [2-8]. Although the exact prevalence of PICS among survivors is unknown, one-half or more will suffer from some component of PICS (cognitive, psychiatric, physical dysfunction) [6-11]. In an observational cohort study of survivors of critical illness who received life support in the ICU, a significant proportion of survivors had newly acquired cognitive impairment, depression, and/or disability in activities of daily living at three months (64 percent) and 12 months (56 percent) [10]. At six months, new disability is found in approximately one out of three survivors and the incidence and severity of disability is similar for survivors of COVID-19-related critical illness [12].

The discussion in this section is limited to survivors of critical illness in general. The incidence of sequelae following acute respiratory distress syndrome (ARDS) is discussed in detail separately. (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Morbidity among survivors'.)

Several studies have reported the incidence of cognitive, psychiatric, and physical dysfunction following critical illness:

●Cognitive – Cognitive impairment after critical illness has been reported to occur on average in 25 percent of survivors with some studies reporting an incidence as high as 78 percent [7,13-23]. The incidence of cognitive impairment was best illustrated by a prospective study of 821 patients that examined the long-term cognitive effects of critical illness in patients admitted to medical or surgical ICUs with shock and/or respiratory failure requiring mechanical ventilation (the BRAIN-ICU Study) [8]. While at baseline, 6 percent had cognitive impairment, at three months post-discharge 40 percent had deficits that were similar to patients with moderate traumatic brain injury, and 26 percent had deficits that were similar to mild dementia. At 12 months post-discharge, the deficits persisted for most patients.

●Psychiatric – Psychiatric illnesses also appear to be common among survivors of critical illness, with depression, anxiety, and posttraumatic stress disorder (PTSD) as the most common disorders reported [17,24-28]. The absolute risk varies between studies and ranges from 1 to 62 percent with high rates frequently reported in ARDS survivors. One national database registry of over 24,000 survivors of mechanical ventilation reported that 1 percent of patients had a new psychiatrist-diagnosed psychologic disorder (mostly anxiety and depression) while 19 percent received one or more prescriptions for psychoactive medications [24]. Systematic reviews of observational cohorts reported higher rates with the incidence of depressive and PTSD symptoms in critical illness survivors as 28 and 22 percent, respectively [28-30]. In survivors from the BRAIN-ICU study, 37 percent of patients experienced symptoms of depression, the rate appeared to be modified by pre-existing psychiatric disease, and the symptoms were largely the result of somatic symptoms [8]. An observational study reported an incidence of PTSD of 10 percent in ICU survivors at both 3 and 12 months post-hospitalization [28].

●Physical – ICU-acquired weakness is the most common form of physical impairment occurring in 25 percent or more of ICU survivors [8,9,31-33]. One multicenter study reported that 64 percent of ICU survivors had problems with mobility at six months [6]. In addition, 73 percent reported moderate or severe pain. One-quarter of patients reported themselves in need of care for more than 50 hours per week, the majority of which was provided by family members (80 percent). Consistent with these needs, 32 percent of patients from the BRAIN-ICU study were disabled in their activities of daily living at three months, 26 percent were disabled in instrumental activities of daily living, disability was prominent in those with and without pre-existing functional disability, and these disabilities persisted in most patients at 12 months.

The clinical presentation, risk factors, and outcomes of neuromuscular weakness related to critical illness are discussed in detail separately. (See "Neuromuscular weakness related to critical illness".)

The public health burden of PICS is substantial due to the presence of neuropsychological and functional disability that occurs in association with this syndrome [6,13,34]. In a study of 293 patients that survived ICU admission, 44 percent required visitation by their community nurse [6]. A negative impact on family income was reported by one-third to one-half of patients and families of survivors.

RISK FACTORS — Risk factors for the development of post-intensive care syndrome (PICS) vary depending on the component of PICS that is studied (table 1 and table 2) [35]. Risk factors can be broadly categorized into the following:

●Pre-existing factors (eg, neuromuscular disorders, cognitive impairment, psychiatric illness, comorbid conditions, functional decline, frailty [11,36])

●Intensive care unit (ICU)-specific factors (eg, mechanical ventilation, acute delirium, sepsis, acute respiratory distress syndrome)

Whether ICU-related factors unmask pre-existing illness and to what degree critical illness accelerates pre-existing neuropsychological or functional decline is unclear, although some of this morbidity is likely also entirely new [37]. The relative contributions of specific critical illnesses (eg, sepsis, acute respiratory distress syndrome, stroke, trauma), as opposed to general critical care (eg, frequent bedrest, excessive sedation, inadequate treatment of delirium or hospitalization), have not been addressed. In addition, it has been speculated that recurrent medicine disruptions play a role in the high rates of 90-day recurrent hospitalizations following discharge from the ICU [38-40].

Factors associated with socioeconomic disadvantage may also contribute to the development of PICS, particularly in older adults (>65 years). After adjusting for confounding variables, one study of over 500 ICU hospitalizations in older adults reported that socioeconomic disadvantage (as defined by dual eligibility for Medicare-Medicaid) was associated with a 28 percent increase in disability and a tenfold increase in the risk of transitioning to dementia compared with older adults who were less disadvantaged [41]. There did not appear to be an increased risk for depression or anxiety. Potentially related to socioeconomic disadvantage and/or pre-existing functional decline, social isolation was associated with greater disability and increased one-year mortality after an ICU hospitalization [42]. Additional factors that may contribute to this disparity are unclear and need further study.

Risk factors for the three domains of PICS are discussed below. We use the term risk factor in the prognostic sense (that patients who experience the risk factor are more likely to experience PICS), even though the evidence for causal relationships is unclear in some cases.

●Cognitive – Risk factors for cognitive impairment are better studied than the psychiatric or physical components of PICS. Major risk factors include the following:

•Delirium – In the largest study of cognitive sequelae following critical illness, the duration of delirium, but not sedating medications, was an independent risk factor for cognitive impairment at 6 and 12 months [8]. (See "Diagnosis of delirium and confusional states".)

•Prior cognitive deficit – Poor cognitive reserve prior to the critical illness has also been associated with the development of cognitive impairment, which in turn can be affected by older age, pre-existing cognitive deficits, premorbid health conditions, and ApoE genotype [13,43,44]. Conversely, attaining a higher level of education (ie, cognitive reserve) has been associated with a greater likelihood of being PICS-free at 3 and 12 months [11]. (See "Evaluation of cognitive impairment and dementia".)

•Sepsis – In an eight-year prospective cohort study of 1194 older patients (mean age, 80 years), compared with survivors of non-sepsis hospitalizations, severe sepsis survivors were three times more likely to develop moderate to severe cognitive impairment (odds ratio 3.3, 95% CI 1.5-7.3) [18]. After adjusting for premorbid cognitive status, sepsis survivors had a higher prevalence of cognitive dysfunction (16 versus 6 percent). Similar findings were seen in the Cardiovascular Health Study [45]. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

•Acute respiratory distress syndrome (ARDS) – Several observational studies of ARDS survivors report that up to 73 percent experience moderate to severe cognitive impairment upon discharge from the ICU with persistent dysfunction at one year (46 to 55 percent) and two years (47 percent) [17,46,47]. The relative contribution of ARDS, the complications of ARDS (eg, hypoxemia), and mechanical ventilation per se is unknown. (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Morbidity among survivors'.)

•Other – Additional cited risk factors include acute brain dysfunction (eg, alcoholism, stroke), hypoxemia (eg, acute respiratory distress syndrome, cardiac arrest), hypotension (eg, sepsis, trauma), glucose dysregulation, respiratory failure (eg, prolonged mechanical ventilation, chronic obstructive pulmonary disease), congestive heart failure, cardiac surgery, obstructive sleep apnea, acute in hospital stress/inflammation, blood transfusions, sedative medications, delirium, and use of renal replacement therapy [8,14-18,45,48-58].

The pathogenesis of cognitive impairment after critical illness is likely complex and multifactorial. Possible mechanisms include ischemia, neuroinflammation, disruption of the blood-brain barrier and white matter integrity in areas involved in executive function and memory [17,59-63].

●Psychiatric – Risk factors for psychiatric disease (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) are similar to those for cognitive impairment following critical illness. They include, severe sepsis and ARDS as well as respiratory failure, trauma, hypoglycemia, and hypoxemia [17,46,47,51,52,55,56,64-69]. Pre-existing anxiety, depression, and PTSD increase the risk of ICU-related psychiatric symptoms, as well as female sex, tall stature in males, age <50 years, lower education level, pre-existing disability/unemployment, premorbid alcohol abuse, ICU sedative and analgesia use, recollection of frightening experiences in the ICU, and early symptoms of mental health impairments after critical illness [17,24,25,27,28,70-79].

Glucocorticoids are associated with a reduced risk for PTSD [77,80,81]. Reduced levels of cortisol are thought to play a role in the development of PTSD and it has been hypothesized that the administration of glucocorticoids during a critical illness may replenish cortisol levels thereby reducing the risk of developing PTSD. (See "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Risk factors' and "Unipolar minor depression in adults: Epidemiology, clinical presentation, and diagnosis" and "Posttraumatic stress disorder in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

●Physical – Conditions strongly associated with the development of ICU-acquired weakness include pre-existing functional disability, frailty, pre-existing cognitive impairment. Other factors associated with ICU-acquired weakness include prolonged mechanical ventilation (more than seven days), sepsis, multisystem organ failure, and as well as prolonged duration of bedrest [31,32,82-85]. Multiple observational studies also report related risk factors associated with ICU-acquired weakness such as ARDS, systemic inflammatory response syndrome, glucose dysregulation, older age, hyperoxia, and use of vasoactive agents and corticosteroids [18,27,86-93]. The association between neuromuscular blocking agents and neuromuscular weakness has not been reproduced consistently, although one systematic review suggests the relationship may exist among patients with sepsis [1,32,82,94]. (See "Neuromuscular weakness related to critical illness".)

CLINICAL MANIFESTATIONS — The clinical presentation of post-intensive care syndrome (PICS) includes a constellation of cognitive, psychiatric, and physical signs and symptoms with the hallmark feature that they are newly recognized or worsened after a critical illness. Common symptoms include weakness, poor mobility, poor concentration, fatigue, anxiety, and depressed mood, which are corroborated by examination and formal testing. Although recovery is possible, many of the signs and symptoms of PICS last for months to years [1,32,95].

A complex relationship exists between all three components of PICS (cognitive, psychiatric, physical), with impairment in one domain frequently being associated with new or worsening function in a separate domain [10,17,27,65,96-99]. Conversely, physical rehabilitation appears to decrease cognitive impairment and psychiatric morbidity, as well as improve physical function [97-100]. The clinical manifestations of the three domains of PICS are described in the sections below.

Cognitive impairment — The severity of cognitive impairment varies from mild to severe – from subtle difficulties in accomplishing complex executive tasks to a profound inability to conduct one's activities of daily living. In the largest study of cognitive sequelae following critical illness, at three months 40 percent had deficits that were similar to patients with moderate traumatic brain injury, and 26 percent had deficits that were similar to mild dementia [8].

The areas of cognition that are commonly affected in PICS include the following:

●Attention/concentration

●Memory

●Mental processing speed

●Executive function

Memory and executive function are the most commonly affected domains that frequently prohibit individuals from engaging in purposeful, goal-directed behaviors necessary for effective daily functioning and complex cognition [23]. For example, these functions are critical to effectively carry out a discharge plan (eg, medication adherence, dietary restrictions, scheduling and maintaining appointments), further impairing recovery.

Impaired cognition may also contribute to communication difficulties frequently observed in patients admitted to rehabilitation following a critical illness. Cognitive impairment is frequently unrecognized due to the inability of patients to communicate and because neither screening nor formal testing are routinely used in clinical practice [21,22]. (See 'Diagnostic evaluation' below.)

Psychiatric impairment — Psychiatric morbidity after critical illness is often disabling, and is associated with reduced quality of life for both the patient and their family [17,24,25,28-30,65,66,70]. The mood disorders most commonly encountered in patients with PICS include anxiety, depression and posttraumatic stress disorder (PTSD).

The most common symptoms of anxiety include excessive worry, irritability, restlessness, and fatigue. Patients with symptoms of depression may complain of fatigue, loss of interest, poor appetite, sense of hopelessness, and insomnia. Symptoms suggestive of PTSD include affective and behavioral responses to stimuli that provoke flashbacks, hyperarousal, and severe anxiety, as well as intrusive recollection and avoidance of experiences that evoke symptoms. (See "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis", section on 'Clinical manifestations'.)

Sexual dysfunction is common particularly in those with symptoms of PTSD. One prospective observational study of 127 patients who spent more than three days in an intensive care unit (ICU), reported sexual dysfunction in 44 percent of patients [101]. There was a strong association between sexual dysfunction and symptoms of PTSD but no association with age, sex, length of stay, use of mechanical ventilation, or tracheostomy. (See "Sexual dysfunction in older adults".)

Survivors of critical illness may have increased risk of suicide and self-harm. Among over 420,000 consecutive ICU survivors, one retrospective study reported that survivors of critical illness had a higher risk of suicide and self-harm compared with non-ICU hospital survivors (hazard ratio [HR] 1.22, 95% CI 1.11-1.33; HR 1.15, 95% CI 1.12-1.19, respectively) [102]. Factors associated with suicide or self-harm included previous depression or anxiety, previous PTSD, invasive mechanical ventilation, and renal replacement therapy.

Physical impairment — Patients with PICS may exhibit the signs and symptoms of ICU-acquired weakness that ranges from generalized poor mobility and multiple falls to quadriparesis and tetraparesis [6,7,31,32,103]. These signs and symptoms frequently lead to persistent disabilities in activities of daily living and instrumental activities of daily living (eg, ability to take medications, perform housework) [9]. Additional morbidities, which may collectively contribute to physical dysfunction include contractures, poor lung function, and malnutrition.

ICU-acquired weakness — This group of disorders encompasses patients with ill-defined generalized muscle weakness and poor mobility as well as patients with well-defined signs and symptoms of critical illness myopathy (CIM; flaccid quadriparesis), critical illness polyneuropathy (CIP; limb muscle weakness and atrophy), combined CIM/CIP, and prolonged neuromuscular blockade (tetraparesis). Additional conditions that may also contribute to physical impairment in ICU survivors include malnutrition and sensory disorders (hearing and vision impairment) [104]. The clinical manifestations of ICU-acquired neuromuscular weakness are discussed in detail separately. (See "Neuromuscular weakness related to critical illness".)

OTHER — Other manifestations that may contribute to impaired neurocognitive and physical dysfunction in PICS include the following:

●Contractures and limb function – Joint contractures develop as a complication of prolonged immobility. In a study of patients admitted for 14 days or more in the intensive care unit (ICU), 34 percent of patients had a functionally significant contracture at ICU discharge, a limitation which persisted in the majority of these patients throughout the hospitalization [105]. The most commonly affected joints were the elbow and ankle, followed by the hip and knee. The use of glucocorticoids was found to be a protective factor in this study. Upper limb disability, related to shoulder impairment, is also common after critical illness. In a study of patients receiving ICU care for three or more days, 47 percent of patients experienced upper limb dysfunction at six months [106].

●Reduced lung function – The effect of mechanical ventilation on lung function is best studied in patients who survive acute respiratory distress syndrome (ARDS). Lung function following ARDS is commonly compromised for as long as five years [87,88,107]. The most common deficit is a reduction in diffusing capacity for carbon monoxide, followed by reductions in lung volumes and spirometry. In most patients, lung volumes and spirometry will normalize by six months and diffusion capacity should normalize by five years [87,88,107]. Supplemental oxygen is rarely required. (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Morbidity among survivors'.)

●Malnutrition – Weight loss is common during critical illness. This is especially true in patients receiving mechanical ventilation, who often receive less than 60 percent of their daily prescribed energy requirements as a result of feeding intolerance, delays, or interruptions [108]. In one study of 109 ARDS survivors, patients lost 18 percent of their baseline body weight with weight gain to near normal levels by 12 months [87]. Although the relationship is unproven, malnutrition likely contributes to the subjective weakness reported by patients, as well as to the reduction in exercise capacity. In addition, patients who are extubated after prolonged mechanical ventilation have swallowing dysfunction further impairing their ability to eat, thereby committing the patient to enteral or parenteral nutrition. (See "Nutrition support in critically ill patients: An overview" and "Management and prognosis of patients requiring prolonged mechanical ventilation", section on 'Nutrition'.)

●Poor sleep – Sleep disturbance is common following critical illness. One review of 22 studies reported that roughly 50 to 66 percent of patients experience sleep disturbance at one month after hospital discharge for a critical illness that improves over time [109].

DIAGNOSTIC EVALUATION — A high index of suspicion is critical for the identification of post-intensive care unit syndrome (PICS). PICS is frequently unrecognized because neither screening nor formal testing have traditionally been used in this population [21,22]. In our practice, we follow the Society of Critical Care Medicine (SCCM) consensus statement regarding the detection of PICS [35]. We and the SCCM advocate for early and serial assessment, beginning at intensive care unit (ICU) admission, as part of the ICU to floor handoff, a predischarge functional assessment prior to hospital discharge, and then post-discharge (ie, within two to four weeks of hospital discharge and continued throughout recovery) (figure 2). We evaluate every survivor of critical illness for the cognitive, psychiatric, and physical signs and symptoms of PICS. However, those considered at the highest risk of PICS should be prioritized for evaluation (table 1). This includes a thorough history and examination as well as confirmatory testing (eg, pulmonary function, neuroelectrophysiologic testing) and appropriate consultation (eg, occupational and physical therapists, neuropsychologists, psychiatrists), which are discussed in detail in the sections below.

Evaluating PICS criteria — The evaluation of the three domains of PICS (cognitive, psychiatric, physical) is described in the sections below. Consistent with the SCCM consensus statement, we encourage a systematic screening approach to identify potential long-term impairments, beginning within two to four weeks of hospital discharge (table 1) [35].

Cognition — Every patient with suspected PICS should undergo a clinical assessment and/or formal testing for cognitive deficits, when feasible. Although of unproven benefit for patients with PICS, the rationale for this approach is based upon the benefits of cognitive rehabilitation in those with traumatic brain injury and stroke and the potential to improve executive dysfunction in survivors of critical illness [110-112]. (See "Evaluation of cognitive impairment and dementia".)

Validated cognitive impairment screening tests usually performed at the time of hospital discharge or in the post-acute care setting that can be used for patients with suspected PICS include (see "Mental status scales to evaluate cognition"):

●Montreal Cognitive Assessment (MoCA)

●Modified Mini-Mental State examination (MMSE)

●Mini-Cog

Although MMSE and Mini-Cog are the most widely known cognitive screening tests and are the best studied in the general population [113,114] in ICU survivors, neither the MMSE nor the Mini-Cog predicted cognitive impairment at six months [115]. We agree with the SCCM and prefer the MoCA for the evaluation of patients with suspected cognitive dysfunction following a critical illness. This preference is based upon the observation that the MoCA, which incorporates an assessment of executive function abilities, is a more sensitive test for mild impairment [116]. Executive dysfunction is common amongst ICU survivors, and it is also potentially responsive to rehabilitation and compensation strategies. A MoCA score <26 indicates mild cognitive impairment and a score <18 indicates moderate to severe cognitive impairment consistent with dementia. Whether cognitive impairment identified using the MoCA at hospital discharge or shortly thereafter predicts long-term impairment is unknown. The evaluation of patients for cognitive impairment is discussed separately. (See "Evaluation of cognitive impairment and dementia".)

Mental health — Every patient with suspected PICS should undergo a clinical assessment and/or formal mental health screening, when feasible. A number of validated screening tests can be used to identify symptoms consistent with depression, anxiety, or posttraumatic stress disorder (PTSD); although none have been validated for use in PICS the Medical outcomes Study Short Form (SF)-26 has been studied as a possible indicator of general mental health in survivors of acute respiratory failure [9,117-125]. A number of tools, validated in other populations, have been used in studies of critical illness survivors and no dominant questionnaire exists. Familiarity, efficiency, and item content can be used to guide the questionnaire selected. Based upon our clinical experience and supported by the SCCM, our preferred mental health screening scales are the following:

●Hospital Anxiety and Depression Scale (HADS) is recommended as a single instrument to assess for symptoms of depression and anxiety [35,122]. As an alternative, the Beck Depression Inventory and Beck Anxiety Inventory may also be used.

●Impact of Events Scale-Revised (IES-R) and the six-item Impact of Event Scale-6 (IES-6) are reliable screening tools for PTSD symptoms [35,126,127]. Alternatively, posttraumatic stress syndrome 10-questions inventory (PTSS-10) may be used.

Additional tools that have been validated in other populations include the Zung depression and anxiety scales, the patient health questionnaire-2 and -9 forms (table 3 and table 4), the Posttraumatic Stress Disorder checklist-Event Specific Version (PCL-S), item mapping according to the Diagnostic and Statistical Manual of Mental Disorders-IV and the civilian and military PTSD questionnaire (table 5) [8,117-121,128]. The details of anxiety, depression, and PTSD assessment tools are discussed separately. (See "Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis" and "Screening for depression in adults" and "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis".)

Physical impairment — Patients should be formally assessed by a medical professional trained in the identification of ICU-acquired weakness (usually a physical therapist and an occupational therapist) [85]. This evaluation should begin in the ICU to identify those with weakness who might begin therapy early in their course. Subsequently, patients should be reassessed in the rehabilitation setting or at home to determine functional disabilities that affect activities of daily living (eg, bathing and dressing) and eating (eg, swallowing function), and disabilities that require medical or social support [129,130]. (See "Office-based assessment of the older adult" and "Comprehensive geriatric assessment".)

For those in whom the diagnosis of ICU-acquired weakness is suspected, formal electromyography and nerve conduction studies can confirm the diagnosis but are often not necessary, because management is frequently unaltered by the diagnosis. Although not validated, handgrip dynamometry is a simple tool that can indicate reduced global strength in ICU patients and may be useful to identify those at risk of ICU-acquired weakness [131]. (See "Neuromuscular weakness related to critical illness".)

Formal assessment of lung function with a full set of pulmonary function tests (spirometry, lung volumes, and diffusing capacity) should be performed in select patients as an outpatient, particularly those who are extubated following mechanical ventilation for acute respiratory distress syndrome, or those with known underlying chronic lung disease. All mobile patients reporting symptoms should also undergo exercise tolerance with a six-minute walk test. Full cardiopulmonary exercise testing is not typically performed. (See "Overview of pulmonary function testing in adults".)

Nutrition assessment should occur during and following ICU discharge as well as during the course of recovery to identify altering nutrition needs over time. (See "Dietary assessment in adults" and "Nutrition support in critically ill patients: An overview".)

Ruling out other causes — Important conditions to distinguish from PICS include:

●Pre-existing illnesses – The presence and severity of prior existing cognitive, mental, or physical impairments needs to be evaluated to identify unchanged, as well as, new or worsening symptoms following a critical illness, all of which can impede a meaningful and sustained recovery. Compared with new or worsening symptoms, unchanged symptoms do not support a diagnosis of PICS. Examples of pre-existing illnesses include prior cognitive deficits from developmental defects, dementia or traumatic brain injury, anxiety or panic disorder, depression or schizoaffective disorder, substance abuse, failure to thrive, and neuromuscular disorders such as multiple sclerosis and amyotrophic lateral sclerosis.

Identifying the presence and severity of pre-existing illnesses is sometimes obvious when a prior diagnosis is known. However, it can be challenging in the ICU survivor in whom a prior existing illness is not known (eg, cognitive deficit from chronic substance abuse or mild dementia) or in those who may not have the cognitive capacity to compare their current status with symptoms prior to their admission. Engaging family members, when available, in a collateral history may provide clues to the presence and nature of pre-existing disease. (See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Differential diagnosis' and "Unipolar depression in adults: Assessment and diagnosis", section on 'Differential diagnosis'.)

●Organic causes of symptoms that mimic PICS – Conditions, including stroke, hypothyroidism, hyperthyroidism, vitamin B12 deficiency, anemia, cancer, and obstructive sleep apnea occasionally mimic the cognitive, psychologic, and neuromuscular weakness manifestations of PICS. Some of these organic causes may be obvious on routine laboratory testing or imaging obtained during the ICU stay. Alternatively, others are more subtle (eg, sleep apnea). Testing for organic pathology should be directed by the clinical history and examination or prompted in those who respond atypically to rehabilitation. Laboratory and imaging studies that are routinely obtained following a critical illness include a complete blood count and differential, chemistries, iron and vitamin B12 levels, thyroid stimulating hormone, liver function tests, and chest radiography. Additional testing can be directed by clinical suspicion and may include, computed tomography or magnetic resonance imaging of the brain, or a sleep study. (See "Treatment of vitamin B12 and folate deficiencies" and "Overview of the evaluation of stroke", section on 'Determining a presumptive diagnosis of stroke subtype' and "Clinical manifestations of hypothyroidism" and "Overview of the clinical manifestations of hyperthyroidism in adults" and "Overview of paraneoplastic syndromes of the nervous system" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)

●Muscle weakness disorders other than ICU-acquired weakness – Conditions including rhabdomyolysis, cachectic myopathy, and Guillain-Barré syndrome may be confused with ICU-acquired weakness. However, they are usually obvious on admission or identified as the initiating reason for ICU admission and therefore, do not qualify as PICS. The spectrum of ICU-acquired weakness disorders includes critical illness myopathy (CIM), critical illness polyneuropathy (CIP), combined CIM/CIP, prolonged neuromuscular blockade. Although not frequently performed, neuromuscular disorders are usually distinguished from one another by laboratory and electrodiagnostic findings and occasionally by muscle biopsy. The indication for testing is usually dependent upon the identification of a disorder where management other than physical rehabilitation will affect the outcome (eg, glucocorticoids for polymyositis). (See "Neuromuscular weakness related to critical illness".)

●Post-hospital syndrome – PICS appears to be distinct from hospitalization-associated disability (also known as "post-hospital syndrome"). Hospitalization, particularly in older patients, can be associated with a number of functional disabilities which are often transient (days to weeks) [132-134]. In contrast, the manifestations of PICS are wide-ranging and are typically enduring rather than transient [132].

PREVENTION AND TREATMENT — In our experience, the most effective strategy to prevent post-intensive care syndrome (PICS) is to prevent critical illness. For example, public health measures (eg, masking) and vaccination reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thereby reduce the risk of hospitalization or death related to COVID-19. In patients with moderate to severe acute hypoxemic respiratory failure, the use of high-flow oxygen therapy, compared with standard oxygen therapy, reduces the need for invasive mechanical ventilation and the inherent harms associated with its use. (See "Evaluation and management of the nonventilated, hospitalized adult patient with acute hypoxemia", section on 'Patients with requirements for advanced respiratory support' and "Evaluation and management of the nonventilated, hospitalized adult patient with acute hypoxemia", section on 'Humidified, high-flow oxygen delivered via nasal cannulae (HFNC)'.)

Once critical illness has developed, the most effective strategy to prevent PICS is one that minimizes sedation and prioritizes early physical rehabilitation during the intensive care unit (ICU) stay and continuing through the recovery process. While cognitive rehabilitation may prove to be of benefit in conjunction with physical therapy, further study is required to examine the efficacy of this approach [9]. The management of PICS focuses on treating the individual impairments (cognitive, psychiatric, physical) with additional referral to appropriate health care personnel, when necessary. A multidisciplinary team approach with a clinician responsible for coordinating care is critical to the successful management of PICS (eg, primary care clinician, physical rehabilitation clinician).

Prevention — To minimize the likelihood of developing PICS in critically-ill patients, particularly in those receiving mechanical ventilation, we prefer the ABCDEF bundle approach that promotes the following strategies [135-139]:

●Awakening and Breathing Coordination with daily sedative interruption and ventilator liberation practices [140]

●Delirium monitoring and management [141,142]

●Early ambulation in the ICU, when feasible [97,143-145]

●Family empowerment and engagement

In addition, the clinician should provide care known to optimize neurologic outcomes including light sedation practice, and avoiding hypoglycemia and hypoxemia, when feasible. The best level of evidence to support this practice is derived from a prospective cohort study of over 15,000 ICU adults, which reported that use of the ABCDEF bundle was associated with a lower likelihood of death within seven days (hazard ratio 0.32, 95% CI 0.17-0.62), mechanical ventilation (odds ratio [OR] 0.28 95% CI 0.22-0.36), and coma (OR 0.35, 95% CI 0.22-0.56), as well as delirium, physical restraint use, and ICU readmission [146]. There was a dose-response relationship between the components of bundle use and these outcomes. In another randomized trial, a tailored multicomponent program decreased self-perceived discomfort in adult critically ill patients compared with standard care [147]. In an extension of this study, the same program reduced the prevalence of posttraumatic stress disorder symptoms at one year [148]. (See "Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal", section on 'Avoid excess sedation' and "Initial weaning strategy in mechanically ventilated adults".)

The following interventions have been studied to determine their efficacy in preventing the cognitive, psychiatric and physical deficits in ICU survivors with mixed results:

●ICU diaries – Diaries can foster the formation of factual memories, lost by the patient during their ICU stay. However, while small prospective or randomized studies have shown that the use of an ICU diary maintained prospectively during the patient's ICU stay by family members, health care providers, or both decreases symptoms of posttraumatic stress disorder (PTSD) [149-152], a large randomized trial failed to confirm this benefit [153]. In a trial of 657 patients who received mechanical ventilation for at least two days in the ICU, the prevalence of significant PTSD symptoms at three months after ICU discharge were reported to be similar in the group who received ICU diary intervention compared with those who did not (in 30 and 34 percent). Similarly, no difference in PTSD, anxiety, or depression symptoms in family members was reported. In contrast with prior nonrandomized studies, debrief, post-discharge, was not included as part of the intervention in the trial.

In one study of 352 patients who were randomized to receive an ICU diary or no diary at one month following discharge, the use of a diary reduced the incidence of PTSD (5 versus 13 percent) at three months [149]. In another study of 378 ICU patients, ICU diaries reduced PTSD symptom scores in surviving ICU patients (21 versus 34) at 12 months [150]. One systematic review of five randomized trials examined the impact of ICU diaries, four studies showed positive effects of diaries on reducing the incidence of PTSD at three months (5 versus 13 percent) [151].

Diary implementation can be challenging, with administrative, informational, and operational difficulties. An article summarized the practical experience of two different hospitals who successfully navigated these challenges [154].

●Early ambulation/physical therapy – In general, our approach is to minimize sedation and mobilize ICU patients as soon as is feasible, ideally on the first ICU day, provided that the patient is stable from a cardiovascular, respiratory, and neurologic standpoint (stable or weaning doses of vasopressors and mechanical ventilation should not be barriers to mobilization). Although evidence is conflicting, this approach is supported by the American Thoracic Society, American College of Chest Physicians, and Society of Critical Care Medicine [137,138,155], as well as one well-conducted randomized trial in surgical ICU patients [145].

Several studies report that early physical therapy/ambulation within the first 72 hours may improve physical function [97,98,143,156-159]. As examples:

•One international multicenter randomized trial of 200 surgical ICU patients who had been mechanically ventilated for <48 hours and expected to require ventilation for ≥24 hours, compared a daily goal-directed early mobilization strategy (interprofessional closed-loop communication and mobilization algorithm) with usual care [145]. Early mobilization resulted in improved mobilization scores (surgical ICU optimum mobilization score 2.2 versus 1.8), decreased ICU length of stay (7 versus 10 days), and improved functional mobility at hospital discharge (mini-modified functional independence score 8 versus 5). In a post-hoc analysis, a nonsignificant improvement in hospital mortality was also reported in those receiving early mobilization. The major difference between this trial and others that reported no improvement with early mobilization [160] is that a facilitator ensured that patients actually received the daily intervention. However, 70 percent of patients screened did not meet inclusion criteria suggesting limited applicability.

•Small randomized studies that compared early ambulation to usual care have demonstrated that early intervention is safe and results in reduced duration of delirium (two versus four days), more ventilator-free days (21 versus 24 days), as well as increased likelihood of return to independent functional status at hospital discharge (59 versus 35 percent) [97,143].

•One systematic review of 14 randomized trials examined the efficacy of a variety of interventions designed to improve physical function in ICU survivors (eg, physical therapy, parenteral nutrition) [161]. Only physical therapy-based interventions (early and following ICU stay) consistently (five of seven trials) reported benefits on physical function in ICU survivors. Another meta-analysis of four trials reported that compared with usual care, interventions targeted at early mobilization were associated with a shorter duration of mechanical ventilation (mean difference 2.7 fewer days) and increased ambulation at discharge (64 versus 41 percent) [137].

In contrast, other trials report minimal of no benefits associated with early and/or aggressive physical therapy (PT) interventions in the ICU or hospital stay [160,162-164]. As examples:

•In a randomized trial of 750 patients undergoing mechanical ventilation in 49 hospitals across three continents, increased early mobilization (sedation minimization and daily physiotherapy) did not impact the number of days alive outside of the hospital or three-month mortality, when compared with usual care (the level of mobilization that was normally provided in the ICU) [165]. In addition, among survivors, there was no difference in cognitive and psychological function, quality of life, and disability at 180 days. This lack of difference was notable despite a significant increase in the duration of active mobilization (21 versus 9 minutes per day). Approximately three-quarters of patients in both groups were also able to stand within three to five days. Increased mobilization was associated with increased adverse events (9 versus 4 percent, mostly, arrhythmia, oxygen desaturation, and altered blood pressure). However, in contrast to earlier studies, which typically begin with range of motion and escalate depending upon patient tolerance and stability, the intervention in this trial was comparatively aggressive. In addition, since 40 percent of patients in the usual care group were able to walk with assistance, this may have minimized the difference between the groups and suggests the absence of a difference may reflect both the usual care and the intervention group being above a critical threshold of mobilization to improve outcomes.

•Two randomized, multicenter trials testing early aggressive PT during the post-ICU hospital stay or later in the ICU stay (240 patients and 120 patients respectively) reported no improvement in physical recovery, mental health, or health-related quality of life, although these studies had limited power to rule out a smaller but clinically meaningful effect [162,163].

•A single-center randomized trial of 300 critically ill patients ventilated for acute respiratory failure compared usual care requested as needed by the health care team with intensive daily physical rehabilitation delivered in the ICU until hospital discharge [160]. At six months following admission, there was no difference in the length of stay, duration of mechanical ventilation, handgrip strength, or physical and mental health scores. However, the intensive daily PT regimen was associated with improved physical performance, as measured by a four-meter walk, sit-to-stand exercise, and test of balance, findings that warrant further investigation. In addition, unlike other randomized trials that have shown benefit [145], the administration of daily PT in this study was not facilitated by a dedicated coordinator and considerable time was spent preparing the patient for PT rather than delivering therapy.

•Adding early in-bed cycling and electrical muscle stimulation of the quadriceps muscle to an early rehabilitation program did not improve global muscle strength at ICU discharge in one randomized trial of 314 critically ill patients [166]. However, it should be noted that the study's control group received daily weekday assessment and intervention by physical therapists which may have biased the outcome.

Importantly, despite the potential benefits, early or aggressive PT strategies should not prevent the institution of other life-sustaining therapies of benefit in certain subsets of patients (eg, neuromuscular blockade and prone positioning in severe acute respiratory distress syndrome) [167,168]. (See "Prone ventilation for adult patients with acute respiratory distress syndrome" and "Acute respiratory distress syndrome: Supportive care and oxygenation in adults".)

●Cognitive therapy – One pilot study that randomized 87 patients from medical and surgical ICUs reported that, compared with usual care or physical therapy alone, there was no benefit to the addition of twice daily cognitive therapy delivered during the ICU stay [169]. A separate, small pilot randomized trial incorporated goal-management training to mitigate executive dysfunction into a physical therapy program post-discharge and found that executive function was significantly improved in the intervention group [112]. Further study will be needed to determine if there is efficacy associated with early cognitive therapy in critically ill patients for the prevention of PICS. (See "Overview of psychotherapies", section on 'Cognitive and behavioral therapies'.)

●Other – The use of an insulin protocol, titrated to normoglycemia, has been shown to reduce the rate of ICU-acquired weakness [90,144]. However, this potential benefit must be weighed against the long-term neuropsychological harm associated with hypoglycemia in the critically ill. Similarly, although the administration of glucocorticoids has been reported to reduce the risk of PTSD, they should not be administered solely for this indication. (See "Glycemic control in critically ill adult and pediatric patients".)

Treatment — For ICU survivors with the signs and symptoms of PICS, the clinician should treat each component accordingly and seek appropriate post-ICU discharge services (eg, cognitive, mental health, physical therapy, occupational rehabilitation, social support). Physical rehabilitation initiated early in critical illness may decrease cognitive impairment and psychiatric morbidity, as well as improve physical function [97,98,100,163]. In addition, many benefits of specific cognitive treatments are unproven in PICS but are typically used based upon data extrapolated from populations with similar deficits (eg, dementia, stroke, motor vehicle accidents, developmental delay). The general management and follow-up of cognitive, mental and physical deficits in PICS are discussed in the following sections:

●Cognitive deficits can be treated with a combination of nonpharmacologic and pharmacologic interventions (see "Mild cognitive impairment: Prognosis and treatment")

●Anxiety can be treated with pharmacotherapy, psychotherapy, and nonpharmacologic therapy (see "Generalized anxiety disorder in adults: Management" and "Generalized anxiety disorder in adults: Cognitive-behavioral therapy and other psychotherapies" and "Complementary and alternative treatments for anxiety symptoms and disorders: Herbs and medications")

●Depression is usually treated with a combination of pharmacotherapy and nonpharmacologic therapy (see "Unipolar major depression in adults: Choosing initial treatment" and "Bipolar major depression in adults: Efficacy and adverse effects of antidepressants")

●PTSD is usually treated with a combination of pharmacotherapy and nonpharmacologic therapy (see "Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults")

●Physical dysfunction is usually treated with a multidisciplinary program that includes exercise endurance and symptom management as well as the provision of mobility aids and environmental adjustments (see "Geriatric rehabilitation interventions" and "Cardiac rehabilitation in patients with heart failure" and "Pulmonary rehabilitation" and "Physical rehabilitation for cancer survivors")

●Sexual dysfunction is typically addressed by treating the underlying illness (often posttraumatic stress disorder), related mental health conditions, and pharmacologic therapies (see "Treatment of male sexual dysfunction" and "Overview of sexual dysfunction in females: Management")

●Malnutrition is usually treated by the provision of calories preferably by mouth, but, occasionally, tube feeding or intravenous nutrition is required (see "Geriatric nutrition: Nutritional issues in older adults", section on 'Treatment of weight loss' and "Dietary assessment in adults")

Follow-up — The optimal follow-up is unknown, but most patients will need follow-up for years at appropriate intervals (initially every two to three months) that are individualized to the unique needs of each patient. The care of this population is best done with a multidisciplinary team approach that includes internists, specialist providers, social services, and occupational and physical therapists. The natural history is unknown, but most patients will need care for months and even years as the signs and symptoms of PICS often persist. Future research is necessary to identify the natural history of PICS, the effect of novel treatment strategies, and appropriate follow-up.

Communication between in-hospital providers and outpatient or rehabilitation facility providers should be optimized, including functional reconciliation that accounts for a patient's pre-ICU functional abilities and documents their abilities and an explicit expectation that patients be evaluated for all three domains of PICS upon discharge from the ICU, rehabilitation facility, or home. Patients should be evaluated within two to four weeks of hospital discharge [35] and re-evaluated should they move from one facility to another (eg, rehabilitation facility to home).

Peer support groups are a novel strategy being attempted across three continents to mitigate PICS [170,171]. When used after cardiac surgery, heart attack, trauma, and pediatric critical care, peer support appears to reduce psychological distress and increase social support [172]. Additional benefits that may result from establishing a peer support community include the provision of empathy and practical advice to facilitate recovery. could also serve to augment our understanding of the survivor experience and their recovery, including providing system-specific feedback on current gaps in handoffs and transitions of information, thereby supporting quality improvement programs and improving customer experience.

PICS clinics — PICS clinics have been introduced in both the United States and the United Kingdom in recognition of the need for the care of patients and families with medical, mental health, social support, and counseling requirements after critical illness [170,173-177]. A growing body of literature exists that provides practical advice for establishing ICU recovery programs [178-181], and evidence is emerging that describes the benefits of these programs.

●One systematic review of eight randomized trials of several interventions for PICS identified that aftercare by ICU follow-up clinic, reduced the Impact of Event Scale (an indicator of posttraumatic stress disorder) for women [151].

●A multicenter randomized trial of 291 survivors of sepsis and septic shock reported that a primary care clinician-based team intervention that included clinician contact, education, subspecialist referral, medications, administered by trained personnel did not improve mental health-related quality of life (measured by mental health summary scores) six months after ICU discharge [182]. However, the baseline mental health scores were close to population norms and patients with significant cognitive dysfunction were excluded from the trial, which may have limited the detection of a potential benefit from the treatment strategy.

●In a series of studies describing Scotland's Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) program, investigators found that a five-week, complex multidisciplinary rehabilitation program initiated 12 weeks after hospital discharge was feasible and was associated with improved health-related quality of life, improved self-efficacy scores, and fewer symptoms of depression, outcomes that were sustained to one year postintervention [183-185].

●Survivors who attended ICU recovery programs, compared with survivors who did not attend such a program, described five benefits of recovery programs: care continuity, symptom assessment/management, normalization and expectation management, validation of progress through recovery, and mitigating feelings of guilt and helplessness [186].

Anecdotal evidence from providers at such clinics has emphasized their role as diagnosticians and triagers, as well as the perception that post-ICU care activities can lead to improvements in ICU care [187]. However, focused research is needed to examine whether clinic interventions such as these improve definitive outcomes in PICS survivors or their family.

Useful links — Additional details on the rehabilitation of patients following critical illness can be found from guidelines issued by the National Institute for Health and Care Excellence. Support for patients and family member following critical illness can also be found at the ARDS Foundation, the ARDS Foundation Canada, Healthtalk, and The Society of Critical Care Medicine's Thrive initiative. Systematically collected, curated, and analyzed patient stories of their ICU experience the United Kingdom are available from healthtalk.org.

OUTCOME

Overview — The signs and symptoms of post-intensive care syndrome (PICS) improve modestly over the first 6 to 12 months following discharge from the intensive care unit (ICU). However, in many patients, deficits persist for years. PICS is frequently associated with the inability to return to work and decreased quality of life as well as an increased risk of death over the subsequent few years [188]. The effect of preventative or therapeutic interventions on outcome is unknown. In addition, whether patients with a prior history of PICS are at increased risk for subsequent hospitalizations, critical illness, or recurrent PICS in particular, is also unknown. (See "Acute respiratory distress syndrome: Prognosis and outcomes in adults", section on 'Morbidity among survivors' and "Management and prognosis of patients requiring prolonged mechanical ventilation", section on 'Outcomes'.)

Reported outcomes among the individual components of PICS include the following:

●Cognitive impairments – Although cognitive function may improve over the first 6 to 12 months, in the vast majority the improvements are small and the impairment persists for years [8,18,20,50,65,189]. This was best illustrated in the largest study of ICU survivors, up to 40 percent of whom had cognitive impairment, that reported minimal improvements in cognition between 3 and 12 months (40 and 34 percent, respectively) [8]. In addition, impaired cognition is particularly associated with psychiatric impairment, the inability to return to work, and decreased quality of life [18,20,50,65,189].

●Psychiatric impairments – Psychiatric sequelae of critical illness may also improve but typically persist for years. While most studies report persistent anxiety and depressive symptoms at 12 months, some observational studies report symptoms of posttraumatic stress disorder (PTSD) lasting for up to eight years [17,24,29,30,66,70,190]. A population-based cohort study of over 9000 patients who survived mechanical ventilation reported that between 3 and 12 months following discharge from the ICU, there was a cumulative increase in the incidence of the prescription of psychoactive medications (from 13 to 19 percent) [24]. The two largest observational studies of ICU survivors demonstrate that symptoms of anxiety or depression, when present at three to six months, frequently persist without significant improvement by 12 months [6,8]. Another systematic review of four studies in patients who survived acute lung injury reported that the prevalence of psychiatrist-diagnosed PTSD was 44 percent at hospital discharge, compared with 25 and 24 percent at five and eight years, respectively [66].

●Physical impairments – Compared with the other domains of PICS, physical dysfunction following critical illness is more likely to improve particularly over the first 12 months. One prospective multicenter study of 222 ICU survivors, reported that 36 percent had physical dysfunction on discharge that improved over the first 12 to 24 months (14 and 9 percent, respectively) [32]. This study did not include patients with primary neurologic deficits (eg, stroke, traumatic brain injury), poor prognosis from a pre-existing illness, or prior lung resection in whom physical dysfunction may be more prolonged. The rate of improvement may also be more prolonged in those with physiologically documented polyneuromyopathy, and in those receiving prolonged mechanical ventilation [32,95].

Health-related quality of life — Health-related quality of life (HRQOL) is significantly lower in survivors of critical illness and their family members. In a systematic review that included 53 studies, ICU survivors consistently reported lower quality of life compared with age- and sex-matched controls [191-193]. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)

In general, quality of life, explained in large part by persistently low scores related to physical dysfunction, improves modestly over time but does not return to baseline [191,192]. One prospective multicenter study of 1663 patients who survived ICU admission reported persistently low HRQOL for up to 36 months with only small improvements recorded during that period [8,88].

Most of the poor HRQOL may be due to pre-existing disease with one prospective study suggesting that the majority of the reduction in HRQOL following ICU care was attributable to quality of life-related effects of pre-existing illness (eg, chronic lung disease, malignancy) [192].

Quality of life is worst among those with acute respiratory distress syndrome, prolonged mechanical ventilation, severe sepsis, trauma, and malignancy [53,65,194-199]. Patients at greatest risk of reduced HRQOL are those with cognitive impairments, psychiatric symptoms, poor sleep quality, and pulmonary and sexual dysfunction [17,50,65,80,101,194,199,200].

Reduced quality of life is also found among family members for prolonged periods after ICU discharge or death. One multicenter observational study of 459 relatives of patients who survived or died in the ICU, reported a normal physical component summary score but poor mental component summary scores (eg, emotional score 67, social functioning 70) on the SF-36 assessment scale [201]. Approximately 36 percent were taking anxiolytic or antidepressant drugs, and 8 percent were prescribed psychotropic agents following discharge or death of the patient.

Post-ICU rehospitalization and ongoing medical care — The risk of rehospitalizations is elevated after critical illness and the risk persists for years [202]. As many as one-quarter of these early rehospitalizations included another intensive care unit (ICU) stay. Among sepsis survivors, as many as one-quarter of patients will be readmitted within 30 days, many with another life-threatening infection [40,203-206]. More than 40 percent of these rehospitalizations are for diagnoses that might be preventable with improved access to ambulatory follow-up care [40]; a randomized controlled trial of the efficacy of improved ICU to primary care coordination is underway in Germany [207].

Patients with a higher illness severity, as measured by longer index hospital length of stay, those discharged to a skilled care facility, and those with an oncology diagnosis were at increased risk of early rehospitalization. Compared with non-critically ill hospitalized patients, survivors of critical illness required more frequent rehospitalizations (4.8 versus 3.3 readmissions per person over five years [208] in Scotland; 65.3 percent rehospitalization versus 49.7 percent in Ontario) [209].

Related, in part, to ongoing medical care needs, reduction in employment after critical illness is common. Consequently, many survivors remain unemployed 3 and 12 months after critical illness, leading to financial burden as another patient-important outcome affected by ICU admission [6,210].

Long-term survival — The risk of death remains elevated in patients after critical illness, particularly in the first three to six months after an ICU admission [33,208,211-213]. The reason for poor survival in this population is unknown but is likely multifactorial and related to pre-existing illnesses, new impairments, and/or a decline in pre-existing organ dysfunction and impairments (PICS), that predispose to acute illness.

●One national registry database study that included over 9000 ICU survivors reported that one-, two-, and three- year mortality rates were 13, 19, and 28 percent, respectively [212]. Compared with elective and cardiac surgical patients, medical patients and those with cancer had higher mortality rates (hazard ratio 1.4 and 1.9, respectively).

●Another retrospective cohort study of over 35,000 Medicare beneficiaries reported that, compared with hospital and general population controls (matched for age and sex), ICU survivors had a higher three-year mortality (40 versus 36 and 15 percent, respectively) [213]. Similar mortality findings have been reported in Scotland and Ontario [208,209].

●Another database study reported that ICU survivorship is associated with a higher five-year mortality, when compared with non-ICU patients discharged from hospital (32 versus 22 percent) [208]. Similarly, a study of sepsis survivors also reported increased mortality at one year (hazard ratio 2.18, 95% CI 2.14-2.22) as well as increased rates of major cardiovascular events and stroke when compared with the general population and hospitalized for a nonsepsis diagnosis [214].

The subgroups at greatest risk of death after ICU discharge include [53,131,209,211-213,215]:

●Patients from medical ICUs (as opposed to surgical ICUs)

●Patients with sepsis (see "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Prognosis')

●Patients with malignancy (see "Prognosis of cancer patients in the intensive care unit")

●Patients requiring mechanical ventilation (eg, for acute respiratory distress syndrome) (see "Acute respiratory distress syndrome: Prognosis and outcomes in adults")

●Patients discharged to a skilled nursing or long-term acute care facility (see "Management and prognosis of patients requiring prolonged mechanical ventilation", section on 'Outcomes')

●Patients with neuromuscular weakness (see "Neuromuscular weakness related to critical illness")

●Patients with renal failure (see "Kidney and patient outcomes after acute kidney injury in adults")

Factors that positively influence recovery are poorly studied but may include higher body mass index and functional self-efficacy [104].

POST-INTENSIVE CARE SYNDROME-FAMILY — Family members of critically ill patients can be affected physically and psychologically during the intensive care unit (ICU) stay, with effects persisting after discharge. These long-term effects are termed the post-intensive care syndrome-family (PICS-F) [216]. The most common problems experienced by family members include sleep deprivation, anxiety, depression, complicated grief, and posttraumatic stress disorder (PTSD). Between one-quarter and one-half of ICU survivors may require long-term family care giving support [88,217,218]. In many respects, the psychological and financial impact of caring for ICU survivors resembles that of the caregiving burden of chronic illness [219]. Psychological morbidity may persist for months or even years after their loved one's discharge from the ICU, especially if they do not survive. We advocate for good communication strategies between staff and family members of the critically ill patient.

Risk factors for PICS-F include poor communication between staff, being in a decision-making role, lower educational level, and having a loved one who died or was close to death [220-224]. Risk factors for persistent depression include younger age, less social support, lower sense of self-mastery, and lower Personal Growth Scale scores [225]. Similarly, in considering post-ICU caregiver trajectory, risk factors for increased depression include female sex, financial difficulty, and being the adult child of the patient [226]. (See "Palliative care: Issues in the intensive care unit in adults", section on 'Communication issues'.)

Clinical manifestations of PICS-F include the following:

●Anxiety – At least one-half of family members suffer symptoms of anxiety at and shortly after discharge [220,227-229]. The proportion of family members suffering these symptoms remains significant at six months [222,227,230].

●Depression – Depressive symptoms are common in family members after discharge and may decrease over time [227,229-231]. Depression occurs among the majority of family members of patients receiving prolonged mechanical ventilation, with 16 percent having persistent and unremitting symptoms one year after discharge [225].

●PTSD – Among family members, PTSD symptoms begin even before discharge. At three and six months after discharge, one-third or more family members will continue to suffer from PTSD [222,227,229,230].

●Financial ramifications – In one United Kingdom study, more than one-half the families of ICU survivors had changes in employment; these included arranged leave, reduced work hours, change in employment, or giving up their jobs [6]. In a United States study, 48.5 percent of family members suffered serious financial stress, which was strongly associated with anxiety and depression [232].

Given that these symptoms begin before discharge, clinicians should also consider an acute Family ICU Syndrome of psychological morbidity among family members of their patients [233]. Additionally, family members of patients who require prolonged mechanical ventilation and require long-term acute care hospitalization suffer psychological and physical morbidity [234,235].

Symptoms of PICS-F appear to last for months to years. Following discharge of the loved one from the ICU, the proportion of family members suffering these symptoms decreases over time but remain present in approximately one-quarter to one-third at six months [220-222,227,230,231,236,237]. Among family members of patients who are discharged with a low quality of life, psychological distress appears to persist for years with one study reporting psychological symptoms present up to four years [238]. An increased cortisol awakening response among family members in the ICU is a risk factor for anxiety at three months after discharge, suggesting the role of physiologic stress in the pathogenesis of PICS-F [239].

The COVID-19 pandemic response resulted in significant limitations on family presence [240]. A study of family members of patients with COVID-19 found that the majority (63.6 percent) suffered symptoms of PTSD [241]. Limiting family presence may have also impacted care [242-244]. Acknowledging that limiting family presence may be an infection prevention measure, it is an ethical imperative that family members support their loved ones, both for the patient's benefit as well as the family's [245]. When presence may be limited (but not eliminated), telephone and teleconferencing families to their loved ones may be of benefit, though outcome data are limited [246].

Across all critically ill populations, clinicians should consider the following preventive measure to reduce potential, future suffering from PICS-F while their patients are still in the ICU:

●Liberalized family presence – A multicenter, randomized trial found that a more flexible family presence policy reduced anxiety and depression scores among family members of critically ill patients, without increasing burnout among the clinical team. However, increased family presence (up to 12 hours daily, compared with 4.5 hours or less daily) did not result in reduced patient delirium, which was the study's primary outcome [247].

●Structured communication approaches – The use of a structured communication strategy reduced anxiety, depression and PTSD among families whose loved ones died in the ICU [224]. The use of conference guided by the mnemonic VALUE (Value family statements, Acknowledge family emotions, Listen to the family emotions, Understand patient as a person, Elicit family questions) resulted in both increased length of family meetings as well as greater family participation in them. Family-centered rounds, in which family members attend and participate in bedside rounding, provides multiple benefits. These include decreasing family stress and anxiety, improving staff-family communication, and increasing family confidence in the care team [248-251]. These do not significantly increase the duration of rounds and may, in fact, reduce total meeting time [249,252-254]. Family-centered rounds meet family's desire for regular and less formal meetings [255]. The use of structured family meetings and family-centered rounds are reflected in the guidelines from the American College of Critical Care Medicine and Society of Critical Care Medicine emphasizing frequent and effective communication with family members, as well as open flexible visitation and family presence on rounds [223,256].

●Increasing access to information – Another prospective study of 551 relatives reported that an information brochure and website designed to meet the family's needs reduced PTSD symptoms [257].

●Family navigator – A multicenter, randomized clinical trial found that the use of a trained nurse or social worker facilitator reduced depressive symptoms among family members at six months. This approach also resulted in decreased ICU costs and substantially reduced length of stay among patients dying in the ICU [258]. Another multicenter randomized clinical trial using trained nurses for family support and communication also found shorter length of stay among decedents, improved clinician-family communication, and family-centeredness, though no effect was found on the rates of family anxiety or depression at six months [259].

●Family participation in bedside care – Family members participating in the bedside care of their adult loved ones through menu of activities have reduced anxiety levels [260]. Families in the neonatal ICU experience reduced stress and anxiety from participating in bedside care, with the additional benefit of additional weight gain for their children [261]. This approach of including families in care to help them cope and adapt is found in the nursing theory of "facilitated sense-making," in which family members participate in the bedside care of their loved ones through activities, such as applying lip balm or massage, and a sense of normalcy is encouraged by reading aloud or talking about daily events [262].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Post-intensive care syndrome (PICS) (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Post-intensive care syndrome (PICS) is defined as new or worsening cognitive, psychiatric, or physical function after a critical illness. PICS-family (PICS-F) is the term used when critical illness of a loved one adversely affects the mental health of family members (figure 1). (See 'Definition' above.)

●Epidemiology – Although the exact prevalence of PICS among critical illness survivors is unknown, it is estimated that one-quarter to one-half or more will suffer from some component of PICS (cognitive, psychiatric, physical). (See 'Epidemiology' above.)

●Risk factors – Commonly cited risk factors for the development of PICS are pre-existing illnesses including neuromuscular disorders, dementia, psychiatric illness, as well as intensive care unit (ICU)-specific factors, in particular, mechanical ventilation, delirium, sepsis, and acute respiratory distress syndrome (table 2). (See 'Risk factors' above.)

●Clinical manifestations – Common presenting features of PICS include muscle weakness, poor mobility, poor concentration, poor memory, fatigue, anxiety, and depressed mood, which are typically corroborated by examination and formal testing. Although recovery is possible, many of the signs and symptoms of PICS last for months to years. Increased health care utilization is very common, particularly in the first 90 days after discharge. (See 'Clinical manifestations' above.)

●Diagnostic evaluation – Every survivor of critical illness should undergo a thorough history and examination for the signs and symptoms of PICS. PICS is identified when new or worsening signs and symptoms are found in any one or more of the three affected domains following a critical illness: cognitive, psychiatric, and physical (figure 2). The identification of each component should rely upon the elucidation of specific findings for each domain with confirmatory testing, when needed. (See 'Diagnostic evaluation' above.)

●Prevention and treatment – In patients who are mechanically ventilated for more than 24 hours, we suggest strategies that promote light sedation and early rehabilitation to prevent PICS rather than usual care. The management of PICS focuses on treating the individual cognitive, psychiatric, and physical impairments with additional referral to appropriate health care personnel, when necessary (table 1). (See 'Prevention and treatment' above.)

●Outcomes – The signs and symptoms of PICS improve over the first 6 to 12 months following discharge from the ICU. However, in many patients, deficits persist for years. PICS is frequently associated with the inability to return to work and decreased quality of life as well as an increased risk of death over the subsequent few years. (See 'Outcome' above.)

●PICS-F – Clinical manifestations of PICS-F include sleep deprivation, anxiety, depression, and posttraumatic stress disorder. The psychological effects may persist for prolonged periods after discharge of the loved one from the ICU. We advocate for good communication strategies between staff and family members of survivors of critical illness (eg, open visitation policies) that facilitate these goals. (See 'Post-intensive care syndrome-family' above.)