Survival is Just the Beginning: The Post-Intensive Care Syndrome

by Marilyn Michelow, MD 
UCSF School of Medicine, Department of Anesthesia and Perioperative Care
&
Kevin Thornton, MD
UCSF School of Medicine, Department of Anesthesia and Perioperative Care

Volume 28 | Issue 1 | Winter 2017

A considerable body of evidence published over the past decade has deepened our understanding of the immense challenges faced by survivors of critical illness as they leave the hospital and begin the recovery process.  It is essential to our mission as intensivists to understand the long-term physical, cognitive, and emotional sequelae of critical illness, as well as to incorporate into our practice evidence-based interventions that can not only reduce mortality, but also improve quality of life for our surviving patients and their families.  

Taken together, the evidence suggests that at least half of patients who survive critical illness and leave the ICU will experience new, long lasting (6 months to a year or greater) health related quality of life impairments in multiple domains including physical function, cognitive ability, and emotional wellness. ^1,2  A framework to capture these multidimensional morbidities, developed at a stakeholder conference of the Society of Critical Care Medicine in 2010, was termed the “post-intensive care syndrome”, or PICS. ³  

This article is intended to briefly summarize the evidence surrounding PICS and highlight possible interventions to reduce morbidity in some domains.  For the interested clinician, several reviews of the post-intensive care syndrome have recently been published, including an excellent article by Herridge et. al. in Intensive Care Medicine in 2016, ¹ which can serve as a more detailed resource.

The post-intensive care syndrome can be divided into physical challenges, pain, cognitive impairments, and psychological challenges.  These cumulatively impact health related quality of life in dimensions such as the ability to complete activities of daily living, ongoing needs for caregiver assistance, and the ability to return to employment following a life-threatening illness.  For an overview, one recent meta-analysis by Yende et al. of nearly 2000 patients who lived independently prior to an episode of sepsis found that at six months, approximately ⅓ of the cohort had died, and ⅓ of the survivors had not yet returned to independent living.  Of survivors at six months, nearly 40% had problems with completing usual daily activities, and in these survivors, half had died or had persistent difficulties with mobility at one year. ² 

Physical challenges faced by those who survive critical illness include persistent weakness and pulmonary deconditioning.  Muscle mass decreases by approximately 2% per day with acute disease in the ICU. ⁴  ICU-acquired weakness, encompassing critical illness myopathy and polyneuropathy, is a bilateral and symmetric weakness following critical illness, not related to another specific etiology. ⁵ The estimated incidence from one review of ICU-acquired weakness was 25-30% in medical ICUs and 55-75% in surgical ICUs. ⁵ Persistent weakness even at 5 years after hospitalization has been described. ⁶  A recent quantitative study of weakness in 56 survivors of critical illness by Solverson et al. found that at 6 months, over 50% of their cohort did not achieve 80% of their age- and gender-expected muscle strength, as measured by hand-held dynametry. ⁷ Another recent study measuring exercise capacity, muscle strength, and self-reported physical functioning in 193 survivors of acute respiratory distress syndrome found physical declines in 86% of their cohort at six months. ⁸

Chronic pain is closely related to ongoing muscle weakness and difficulty with physical mobility.  A recent review of chronic pain after critical illness suggested that there is a 12-44% prevalence of ongoing pain 6 months after hospital discharge. ⁹  Much of this pain was of moderate to severe intensity.  It is unclear at this time how much of this pain is related to chronic injury, and what role opiate use, withdrawal, and sensitization may be playing.

Cognitive function is significantly impacted by critical illness. Research has demonstrated that survivors of intensive care may suffer from memory impairment, difficulty concentrating, decreased attention, and impaired language function. ^1,6  For example, one prospective cohort study of 821 survivors of critical illness found that 40% of the cohort had global cognition scores 1.5 standard deviations below the population mean at six months.  The study authors describe this degree of cognitive impairment as analogous to sustaining a moderate traumatic brain injury. ¹⁰ These deficits largely persisted at 12 months after hospital discharge.

The post-intensive care syndrome also encompasses the significant anxiety, depression, post-traumatic stress disorder, and sleep disturbances that can shadow survival of a critical illness.  Estimates of the prevalence of these psychological challenges vary.  One recent review of the post-intensive care syndrome suggested a prevalence of 19-33% for post-traumatic stress disorder, 23-48% for anxiety symptoms, and 17-43% for depression following an intensive care stay. ¹¹  By contrast, the relative prevalences of depression and post-traumatic stress disorder in the general population are <10% and  <5%, respectively. ⁶  It is increasingly recognized that the psychological effects of critical illness extend beyond the patient to affect family members as well. In one study of critically ill patients and their family members, both patients and their relatives demonstrated similar rates of post-traumatic stress disorder, and had poorer health related quality of life than a normative sample population. ¹²  Another recent study reported a nearly 70% rate of depression in caregivers of critically ill patients, with the rate of depression remaining 43% at one year. ¹³ 

The summative consequences of the post-intensive care syndrome include an ongoing need for caregiver support for a prolonged period after hospitalization with an inability to compete basic activities of daily living, a decreased likelihood to return to work if previously employed, and an overall decrease in quality of life compared with the general population.  Financial impacts of ongoing needs following critical care can be substantial for both patients and their families.  A 2013 study of 293 patients who spent greater than 48 hours in an ICU found that 22% of the cohort was in need of assistance for basic care at one year. ¹⁴  In the study there was also a 50% decrease in the number of patients who reported employment to be their principle source of income at one year. ¹⁴  Others have noted that while mortality after one year may normalize with the general population, ⁶ patients who survive critical illness in general have a lower overall quality of life than age or gender matched controls at one year after ICU discharge. ¹⁵

It should be noted that very little research has been devoted to the subset of ICU survivors who can be described as chronically critically ill, requiring prolonged mechanical ventilation and care in a long term facility.  One small study of this population, by Lamas et al., found, unsurprisingly, even lower overall quality of life compared with the general population of ICU survivors.  In their study of 50 chronically critically ill patients and their surrogates, nearly 70% of the group described the patient’s current quality of life as poor, with persistent problems with hunger, thirst, difficulty communicating, boredom, and impaired mobility. ¹⁶

There are considerable ongoing efforts to understand the factors related to hospitalization that may cause PICS, however there is little concrete evidence at this stage to guide the design of interventions that diminish the incidence or prevalence of PICS.  Duration of mechanical ventilation and duration of bed rest have both been linked to chronic ICU acquired weakness. ^1,8  However, despite considerable study there has been no clear demonstrated link between the use of neuromuscular blocking agents in the ICU and prolonged weakness.  The use of high dose steroids has also not conclusively been demonstrated to cause long term weakness. ⁷  Hypoxia, prolonged hypotension, hyperglycemia, and blood glucose variability have been implicated in post-ICU cognitive impairment, though data is limited. ¹ There is some suggestion that a conservative fluid management strategy may be associated with long-term cognitive impairment. ¹⁷  Data are conflicting but largely do not show a link yet between sedation levels in the ICU or the incidence of delirium to the risk of developing PTSD, anxiety, or depression in the months following hospital discharge. ^1,18  There is some suggestion that post-traumatic stress disorder is related to high circulating levels of norepinephrine, and there is active study of the use of beta-blockers (possibly helpful) or statins (trials did not show benefit yet) for this purpose. ¹ Research is ongoing to clarify the role that nutrition and glycemic control during critical illness may play in PICS. 

One major initiative designed to mitigate some of the risk factors for the development of the PICS is the Society of Critical Care Medicine’s ICU Liberation Campaign ABCDEF bundle.  Through its focus on reducing delirium, improving pain management, and mitigating ICU acquired weakness, it is hoped that this bundle may also impact long term survivor quality of life in multidimensional ways. ¹  The ABCDEF bundle stands for A- assess, prevent and manage pain, B- both spontaneous awakening trials and spontaneous breathing trials, C- choice of analgesia and sedation, D- delirium assessment, prevention, and management, E- early mobility and exercise, and F- family engagement and empowerment.  Those seeking more information on the ABCDEF bundle are directed to http://www.iculiberation.org/Bundles/Pages/default.aspx. 

Others have suggested that closer attention to pain control and judicious use of opiates, ⁹ early treatment of sepsis, and close attention to nutrition status may impact the development of PICS. ⁷  ICU diaries, kept by patients or their relatives and caregivers, have also been evaluated as a method to reduce the incidence of post-traumatic stress disorder after critical illness.  Although some small studies have shown that ICU diaries have a benefit both for patients and their family members, a recent Cochrane review of the use of ICU diaries to reduce post-traumatic stress disorder did not show clear harm or benefit for this intervention. ¹⁹ 

After the episode of intensive care, several groups have evaluated the effect of post-discharge interventions such as psychotherapy, physical therapy, and physician visits targeted to review the episode of critical illness.  A systematic review of post-ICU follow up consultations completed in 2015 did not show a benefit for these clinic visits in improving quality of life, diminishing anxiety or depression, improving physical or cognitive function, or in helping patients return to work.  Post-ICU consultation did lead to a modest reduction in levels of post-traumatic stress disorder. ¹¹  However, active research continues on post-ICU clinics, and at the  least as a tool for detecting the symptoms of PICS and referring patients for appropriate treatment, clinics or standard post-operative screening tools may show value.  There are some recent documents to guide teams developing physical rehabilitation programs after ICU discharge, despite the lack of benefit shown to date from post-ICU rehabilitation programs in a Cochrane review of randomized controlled trials. ^20,21 

Moving forward, the development of interventions that can mitigate PICS will be essential.  One major limitation in this field is the lack of studies that consider quality of life measures as major endpoints in trials evaluating potential therapies and interventions in the critically ill.  Whether an intervention shows a mortality benefit or reduces ICU length of stay may or may not have any relation to the potential impact on the long-term symptoms of post-intensive care syndrome.  Incorporating quality of life measures as core outcomes of future critical care studies could have an enormous impact in the field of ICU medicine.  The long-term human and financial costs of post-intensive care syndrome are too great not to make these outcomes a major focus of our future studies.

For those seeking further resources on PICS, the Society for Critical Care Medicine offers grants and opportunities for collaboration through their THRIVE program, as well as patient resources including a video explaining PICS for patients and families http://www.sccm.org/Research/Quality/thrive/Pages/default.aspx.  The OACIS (Outcomes After Critical Illness and Surgery) group, centered at Johns Hopkins, also provides a rich array of resources and information related to the study of the post-intensive care syndrome http://www.hopkinsmedicine.org/pulmonary/research/outcomes_after_critical_illness_surgery/ .

Resources 

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