Post-ICU Syndrome and the Post-ICU Clinic

FIGURE 12.1 Onychomadesis after critical illness.

Cognitive problems in ICU survivors occur in areas of memory, attention, and executive functioning, all domains that have clear implications for daily functioning (32–36). The risk factors potentially associated with cognitive impairment after critical illness are many and include delirium, hypoxia, glucose and metabolic dysregulation, inflammation, and the effects of medications (e.g., sedatives and narcotics) (31). The extent to which each of these possible contributors affects cognitive outcomes is unclear; each is closely associated with the others and with ICU hospitalization more generally.

Much of the research pertaining to cognitive outcomes after critical illness has focused on delirium. Delirium is common during critical illness, though its prevalence has decreased in recent years (37–45). Contributors to the development of delirium are the subjects of intensive investigation and include genetic (e.g., APOE-4 allele), pathophysiologic (e.g., infection), medical (e.g., sedating medications), and environmental factors (e.g., chaotic ICU environment, dysregulation of sleep/wake cycle) (46–48). Cognitive vulnerability may also play a role (31). The exact mechanisms by which delirium confers a higher likelihood of cognitive dysfunction following critical illness have yet to be elucidated, though inflammation and neuronal death are each associated with delirium and may lead to untoward brain-related developments including brain atrophy (49).

A variety of mechanisms are believed to foster the development of cognitive impairment. A profound systemic inflammatory response is a common feature of critical illness (e.g., sepsis). The inflammatory response is characterized by production of proinflammatory cytokines (e.g., interleukin-6 [IL-6], IL-1, and tumor necrosis factor alpha [TNF-α] (50,51), which have been associated with Alzheimer’s and vascular dementia, as well as cardiovascular disease (52,53). Inflammation may lead to a permanent shift in brain chemistry and likely is a major contributor to chronic brain dysfunction. Recent investigation using a mouse model of sepsis has revealed long-term neuroinflammation resulting in cognitive changes months after recovery from the acute illness (54).

Also common in critical illness is hypoxia, especially among patients with ARDS (55); hypoxia has been associated with significant memory decrements (56–58). Patients admitted to the ICU for critical illnesses are often geriatric; old age is a risk factor for pro-inflammatory responses, delirium, and cognitive decline (59–61). Pre-existing cognitive impairment, whether mild or severe, also appears to be a risk factor for cognitive impairment and accelerated decline following ICU hospitalization and critical illness (62). But younger patients are not spared, and the impact of cognitive impairment after critical illness is marked by profound decrements in functional status, independence, and employment in this population (63).

Psychiatric Domain

Critical illness is known to have significant impact on psychological outcomes of patients (64,65) and their families (66). Investigating psychological issues has been identified as a critical research priority by the Multisociety Strategic Planning Task Force for Critical Care Research (1). Psychological areas most frequently impacted include depression and posttraumatic stress disorder (PTSD).

Depression

Depression and depressive symptoms are common in the setting of critical illness and occur in nearly 30% of individuals (in contrast to 10% for any mood disorder in the general population) (67). Clinically significant depressive symptoms in patients after critical illness have been reported in over 30 studies (68). A recent analysis of ICU survivors showed that the risk of receiving a new prescription for a psychoactive medication in the 6 months after hospital discharge was 21 times greater than in the general population (69). Depression manifests in cognitive–affective symptoms but may result in somatic symptoms in ICU survivors in particular. These include fatigue and exhaustion, sleep disturbance, problems initiating physical activity, and preoccupation with health concerns (70). Depressive symptoms may increase the probability of developing recurrent critical illness, as individuals suffering from depression may make unwise and potentially harmful choices and engage in maladaptive health-related behaviors, such as smoking, sedentary lifestyle, alcohol consumption, malnutrition, and noncompliance with recommended preventive or treatment regimens. People with major depression die almost a decade earlier than their nondepressed counterparts from health conditions such as cardiovascular diseases, diabetes, and chronic obstructive pulmonary disease (COPD), likely due to early onset of maladaptive health behaviors (71,72). Health behavior change is a difficult process for many individuals, especially if those behaviors serve to momentarily enhance mood or reduce tension or fatigue (73). Conversely, a positive adaptive response to critical illness may be a renewed motivation to improve health behaviors. A subset of survivors of critical illness finds that their experiences, difficult as they may be, are the gateway to significant growth and to a fundamental reordering of priorities. This “posttraumatic growth” occurs in up to a third of survivors of trauma and frequently results in increased gratitude, greater life satisfaction, and increased optimism and resilience (74,75).

TABLE 12.1 Patient Perspectives on Post-ICU Recovery: Clinical Vignettes

Acute and Posttraumatic Stress

Acute distress symptoms are common during critical illness and are frequently followed by posttraumatic stress in the ICU recovery period (76,77). As many as one in two ICU survivors experience clinically significant symptoms of PTSD during the first year after ICU discharge, though recent investigations have suggested that the true prevalence of PTSD is between 10% and 20%. Still, this is nearly fourfold higher than the lifetime prevalence of posttraumatic stress symptoms in the general US population (76,78). PTSD may be driven by exposure to a variety of traumatic experiences, including the critical illness itself, the ICU environment, and delusional memories or delirious states (76,79). PTSD symptoms after critical illness often manifest in symptoms of avoidance, apprehension about discussing any signs or symptoms of a possible medical condition with providers, and reluctance to seek help. Patients may almost phobically avoid medical appointments, which can increase the likelihood of worsening symptoms (Table 12.1).

MANAGEMENT OF PICS AND THE POST-ICU CLINIC

Just as with ICU “bundles” or protocols for sepsis, ARDS, or diabetic ketoacidosis, protocols for ICU survivorship will be required in the future, and organizational change is key. The specific components of ICU follow-up have not been established, but stakeholders have created an agenda for what should be included for advancing research and practice in this realm (80). First, and critically important, is recognizing, preventing, and treating signs and symptoms of PICS. Second, we must identify and address needs and build institutional capacity to support survivors and families. Third, we must study and develop an understanding of barriers and facilitators to patient care across the spectrum of care environments.

Much of the work on long-term functional outcomes after critical illness has been epidemiologic and descriptive: what proportion of patients are discharged to home, what is their level of function, their perceived quality of life, how frequently are they readmitted, and how long do they survive? Important gaps remain in our knowledge about effective interventions to improve these outcomes through changes in practice as well as the optimal time points for intervention (i.e., during the episode of critical illness or later during the recovery period). Understanding such “phenotypes” of ICU survivors is a crucial next step (81).

Intensivists may be in the best position to understand the potential sequelae of the ICU experience, and should themselves be the ones caring for patients during the post-ICU recovery period. Doing so requires intensivists to have more knowledge, understanding, awareness, skills, and availability beyond the acute ICU stay. By some estimates, issues related to ICU survivorship are discussed during the index ICU episode only very rarely, and only 20% of hospitals have formal ways of communicating discharge follow-up planning to primary care providers (82). Even if intensivists are knowledgeable about survivorship, less than 5% of hospitals report having support groups for ICU survivors. Support groups could serve to identify the optimal time points for intervention while also providing needed care and support to patients, many of whom fall through the proverbial cracks following hospital discharge. And, while they are not yet widely recognized as valuable or effective, largely due to limited rigorous study to date, ICU follow-up clinics may be one important way to address the growing number of patients with PICS.

ICU follow-up clinics are not a new concept, but they have had some difficulty gaining traction in general practice. In the UK, about 30% of ICUs had a follow-up clinic program in 2006. Over half of those clinics were led by nurses, only 59% were funded by their affiliated hospital, and almost 90% of ICUs studied reported financial constraints (83). Another study of ICU follow-up clinics in the UK was unable to show a benefit in health-related quality of life (HRQoL) at 1 year among almost 300 patients participating in an ICU follow-up program (84). The lack of observed benefit may have been related to the fact that ICU follow-up clinics up to that time in the UK had developed in an ad hoc manner, were providing inconsistent service and staffing models, and were not uniformly available in hospitals across the country. All patients who required intensive care were eligible, raising the possibility that only a subset of patients would benefit from an after-care program. The intervention consisted of a self-directed, manual-based recovery plan, introduced by a study nurse and formally reviewed in the clinic at 3 and 9 months. Although there was no difference in HRQoL or mortality between the groups, a third required medical specialist referral and another third needed referral for psychological services. The authors called for more work on the roles of early physical rehabilitation, delirium, cognitive dysfunction, and relatives in the ICU recovery process. An interdisciplinary team approach may improve outcomes through better coordination of care, but the optimal structure of such a team in a chaotic ICU environment with a variety of medical diagnoses and severity of illnesses is not yet clear (85).

TABLE 12.2 Wide-Ranging Implications of Postintensive Care Syndrome

The wide array of affected functional domains has led to an emerging team-based approach to diagnosing and treating PICS. However, while awareness of post-ICU problems is becoming broader, evidence is lacking to guide diagnostic criteria and treatment options, and the absence of a defined team model has resulted in a patchwork of efforts around the United States and the world. Bookending the physical, cognitive, and psychiatric components of the syndrome are the wide-reaching systemic effects of this public health problem. These include, on the systems side, effects on health care utilization, and on the individual and family side, socioeconomic and quality-of-life factors (Table 12.2).

Clearly, this is a monumental collection of problems to be addressed in any one setting. And yet, by tailoring the post-ICU recovery approach to the individual patient, the intensivist may arrive at a high-yield, relatively low-resource intervention to minimize further morbidity and mortality.

Goals of an ICU Recovery Program

Screen for Known Complications

Although the long-term effects of critical illness are still being described, a number of common complications are known. Among the best studied of these is polypharmacy, most commonly, the unintentional and inappropriate continuation of medications started in the ICU setting (86). Common classes of inappropriately continued medications include antipsychotics, gastric acid suppressants, benzodiazepines, and inhaled bronchodilators and steroids. Without early intervention, inappropriate medication continuation often persists up to 1 year after hospital discharge, at the cost of millions of dollars and countless adverse drug events.

Conversely, previously appropriate medications may be stopped during critical illness and not restarted at hospital discharge (87). Due to rapidly changing clinical status, renal function, and hospital location or team, appropriate medications may be underdosed, overdosed, or lacking monitoring following hospital discharge. Careful medication reconciliation, pharmacy counseling, review of barriers to adherence, and implementation of medication compliance strategies are just a few ways a pharmacist can contribute to post-ICU recovery.

Pain is a common complaint after critical illness; unrelieved pain in the ICU increases the risk of chronic pain in the post-ICU period (88). Maladaptive hyperalgesia, whether induced by damage to peripheral or central nerve fibers, opioid administration or interruption, or inflammation, is further exacerbated in the post-ICU period by altered emotional and cognitive processing (89). Paresthesias are common; while therapeutic studies are lacking, neuropathic pain medications including gabapentin, capsaicin cream, SSRIs, and venlafaxine have been used (21).

Serious airway complications of prolonged MV, such as tracheal stenosis, are relatively rare, but can have potentially devastating effects. Thus, timely identification and subspecialty referral are key. Vocal cord dysfunction is more common, and often self-limiting. However, persistently symptomatic vocal cord pathology is best referred to otolaryngology, as targeted interventions and speech therapy can result in significant improvement.

Other subspecialty referrals common to the post-ICU period are wound care, plastic surgery, infectious diseases, and community mental health.

Above all, the systematic coordination of post-ICU care presents a unique opportunity for improvements in patient safety, recovery, and quality of life. Among the benefits of such coordinated (and potentially interdisciplinary) follow-up is the prevention of preventable readmissions, morbidity, and mortality.

Educate Patients and Families

In most cases, survivors of critical illness are unaware of the many difficulties they will potentially face as a consequence of their critical illness. Few lay people and relatively few professionals are familiar with literature that supports an association between sepsis, for example, and prolonged cognitive deficits, or with the voluminous evidence that links critical illness to the development of PTSD. Consequently, when new cognitive and mental health difficulties emerge or when old ones worsen, they have no particular context by which to understand them. In the absence of any understanding of the natural history or the “normal” clinical course of these conditions, patients often develop intense anxiety and are reluctant to talk about their fears with health care professionals. For these and many other reasons, proper education that both explains to patients what is happening, that is, describes what PICS is and normalizes it, helps set appropriate expectations, such as “these symptoms will probably persist for a time but will likely be better in 6 months to a year,” and provides treatment recommendations—“consider focused cognitive rehabilitation with an occupational therapist or a rehabilitation psychologist for the treatment of attention deficits”—is a crucial part of post-ICU care.

Closely related to patient and family education is the education of outpatient medical providers, whether they are subspecialists, general practitioners, or mental health professionals (psychiatrists, psychologists, social workers). The disconnect between inpatient critical care providers and their outpatient counterparts has been well described; only infrequently do inpatient and outpatient physicians engage in professional “crosstalk.” Accordingly, providers not involved in ICU care are rarely apprised of and sometimes not sensitive to the often profound debilities from which their patients now suffer. Primary care providers are extremely receptive to such information but without education, they are often as perplexed as survivors at the unusual constellation of symptoms they are seeing. Attempts to develop a primary care–based program to treat the sequelae of critical illness are underway, but have yet to be shown effective in improving outcomes (90). Post-ICU clinic personnel can play an invaluable role by bridging the gap between inpatient and outpatient providers. Outlining a summary of the ICU stay and current problems along with specific resources for the cognitive, mental health, and physical/functional decrements specific to PICS (sometimes referred to as a “health passport”) may be a useful adjunct for patients, families, and medical teams.

Solidify Positive Change

Another issue central to ICU follow-up care involves solidifying changes that have already been made during critical illness. Whether active or passive, these changes can represent unique opportunities to improve health. For example, many patients arrive in the ICU with long histories of alcohol and nicotine use, patterns that predispose them to the development of critical illness (91,92). For such patients, a prolonged ICU hospitalization may represent the longest period of time they have been free of such substances in a lifetime. Similarly, many morbidly obese patients lose significant weight over the course of a critical illness—weight loss greater than 100 pounds is not unheard of—although this usually involves the loss of muscle as well as fat. In these instances, longstanding habits will rapidly re-emerge after patients return home unless active efforts are made to help make their new behaviors (e.g., smoking cessation) or conditions (e.g., decreased BMI) more permanent. ICU follow-up care providers can engage patients in smoking cessation programs, weight loss and nutrition programs, or alcohol treatment programs at the critical “teachable moment” between an ICU stay and the return to baseline function. These programs can be embedded in follow-up clinics—for example, smoking cessation programs can be delivered at little cost and require relatively little specialized expertise—or patients can be referred to appropriate specialists either at the hospital or in the community. An interdisciplinary team approach is especially well-suited to this type of health behavioral modification (Tables 12.3 and 12.4). While many of the impairments observed in the post-ICU period will improve over time, documenting them and explaining them to patients can serve as a powerful motivator in the pursuit of “best recovery.”

Necessary and Desired Elements of an ICU Recovery Program

Little if any systematic study has been done of the crucial elements comprising ICU follow-up care. One of these is a dedicated ICU recovery center or clinic (Fig. 12.2), yet this is not the only method or model. Promising approaches that have a lower barrier to entry involve the use of telephone- or telehealth-related modalities to facilitate traditional interactions between patients and providers (93). Other potential models involve the use of peer guides or mentors or support groups. While peers have rarely been employed in post-ICU settings, they have proven to be highly effective in the management of patients with other chronic conditions such as diabetes, rheumatoid arthritis, and HIV/AIDS. These carefully selected individuals are matched by demographic and illness-related variables. As successful “navigators” of life after critical illness, they often have knowledge and insights about recovery that medical providers lack and can be particularly valuable in promoting effective recovery. Like peer mentoring programs, support groups have a long history of effectiveness with other groups but are in their infancy as applied to ICU survivors (94). They represent a relatively simple and cost-effective way to engage the needs of individuals after critical illness by using the considerable strengths and motivations of patients who are frequently highly motivated to help one another. Even more independent of the medical system are self-directed or manual-based recovery programs, such as those developed in the United Kingdom (95). Several European studies have evaluated the potential benefits of keeping an intensive care diary, with promising effects on post-ICU anxiety, depression, quality of life, and PTSD in patients and families (96–102).

TABLE 12.3 Clinical Scenarios Highlighting Interdisciplinary Assessment and Intervention in an ICU Recovery Program