Page 142 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

108 PART 1: An Overview of the Approach to and Organization of Critical Care

1- and 2- year cognitive outcomes
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Hospital DC
80 1 Year
Percent with deficits 60
2 Years

40

20

0
Processing Memory Executive Attention IQ
speed
FIGURE 15-2. Cognitive outcomes after ARDS. (Data from Hopkins RO, Weaver LK, Pope D et al: Neuropsychological sequelae and impaired health status in survivors of severe acute respira-
tory distress syndrome, Am J Respir Crit Care Med. 1999 Jul;160(1):50-56 and Weaver LK, Collingridge D: Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress
syndrome. Am J Respir Crit Care Med. 2005 Feb 15;171(4):340-347.)

and muscles of the axial skeleton appears to be an early and ubiquitous genes that are dysregulated in older muscle, and specifically, appear to
finding. In their landmark work, Levine and colleagues noted that be upregulated by inflammatory factors. 80
33
patients from very diverse clinical groupings (stroke, motor vehicle Recently, the importance of TNF-α has been highlighted in this
accident, drug overdose, gunshot wound) had similar muscle injury literature. Higher levels of TNF-α and IL-6 have been associated
attributed to increased activity of the ubiquitin-proteosome pathway. with increased mortality in the community-dwelling elderly, a lower
Follow-up observations from these same investigators showed marked observed quadriceps strength in older men and women and stimulation
decreases in myosin heavy chains and atrophic AKT-FOXO signaling of apoptotic signaling pathways. There appears to be a very complex
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play important roles in eliciting the myofiber atrophy and decreases interplay between these mediators and there may be some valuable, and
in diaphragm force generation associated with prolonged human dia- potentially clinically applicable, insights as well. For example, IL-6 is
phragm disuse. Other recent work cites induction of autophagy and released from skeletal muscle during exercise and this increase can result
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mitochondrial dysfunction in human muscle —observations not linked in an inhibition of TNF-α. It is possible that the benefits of early mobil-
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to a specific disease etiology. A recent comprehensive review on the ity programs, currently under study in many ICUs, not only address
molecular mechanisms of muscle and nerve injury in critical illness has disuse atrophy but may also have important immunomodulatory effects
outlined these mechanisms in more detail (Fig. 15-2). These important on recovering skeletal muscle after critical illness. 83-85
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observations were not linked to a specific inciting disease and support The collapse of these different risk strata into a single population
the hypothesis that muscle injury is not specifically linked to underlying or cohort for evaluation may account for the observed heterogene-
disease or etiology. ity in functional outcomes currently reported in the literature and
may obscure the ability to identify distinct clinical phenotypes. Risk
DIFFERENTIAL REPAIR modification is also an important consideration and deserves mention.
Modifiers may include mood disorders, cognitive dysfunction, 87,88
9,86
Muscle injury may be inevitable but repair across patient groupings financial and family caregiver resources.
appears to be variable. Most muscle repair and functional recovery ICU survivors with ICUAW rely on family caregivers for support
occurs early and stabilizes by 6 months to 1 year after critical illness. as they transition to home and reintegrate into the community.
2
This variability in outcome supports the notion of a spectrum of dis- Approximately 57% of ICU survivors who received long-term mechani-
ability related to age, comorbid disease, and ICU length of stay. Current cal ventilation still required the assistance of a family caregiver 1 year
evidence supports these are key determinants of functional outcome after their critical illness. Current literature suggests this may have
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and compromised HRQoL. 4,5,71-75 Patient demographic and clinical char- a negative impact on caregivers, including poor HRQoL compared
acteristics may serve as proxy measures for nerve and muscle reserve with age- and sex-matched persons, posttraumatic stress disorder,
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and/or comorbid organ dysfunction that existed prior to the episode of emotional distress, 91-93 burden, depression, and anxiety. Previous
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critical illness. work from our group found ARDS survivors’ depression and provision
of high levels of care to be important contributors to caregiver depres-
SARCOPENIA OF AGING sion. Others recently report caregivers experience more depression and
8
difficulty maintaining participation in valued activities when caring for
Sarcopenia is defined as a decline in skeletal muscle mass, strength, male ICU survivors with poorer functional ability. 91,95,96 Determining the
power, and physical functioning in association with aging. Sarcopenia impact of ICUAW specifically on family caregiver health and well-being
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contributes significantly to physical inactivity, functional disability, is necessary to understand the interplay between the survivor and the
increased health care utilization, costs, and mortality in older patients. caregiver and the impact on recovery.
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The muscle wasting and weakness observed in survivors of critical ill-
ness may have a similarly significant impact on functional outcomes and ADDITIONAL PHYSICAL MORBIDITIES
health care utilization. The parallels are striking.
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There is considerable evidence that increased cytokine levels, in com- As discussed previously, the main morbidities of critical illness include
bination with reduced growth factor levels, contribute to sarcopenia and ICUAW and neuropsychological dysfunction. However, several other
age-related decline. Early work showed an association between elevated physical sequelae also influence physical HRQoL and subsequent health
IL-6 levels and advancing age where the highest levels were associated care utilization. Again, these have been studied most extensively in
with the greatest degree of physical debility and significant mortality. survivors of ARDS. These include pulmonary dysfunction, entrapment
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Giresi and others use microarray gene expression profiling to identify neuropathy, late tracheal stenosis, heterotopic ossification, and a variety
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