Cardiorespiratory Fitness, Health Outcomes, and Health Care Costs: The Case f...
Ron LM recovered file 2015
1. Clinical meaningful
outcomes after pARDS
Francois Aspesberro, MD
Pediatric Critical Care Medicine
Seattle Children’s Hospital
University of Washington School of Medicine
Seattle, WA
2. Critical care begins and ends outside the
walls of the PICU
Angus DC et al. Intensive Care Med 2003;29:368-377
3. Historical Decline of PICU
Mortality
Aspesberro F, Mangione-Smith R, Zimmerman JJ. Intensive Care Med 2015 July;41(7):1235-1246
4. Pediatric critical care has exchanged
mortality for morbidity
Mortality
Morbidity
Simon DW et al. Pediatr Crit Care Med 2014;15(3):264-266
5. Post Intensive Care Syndrome
PICS
Needham DM, Davidson J, Cohen H, et al:. Crit Care Med 2012;40:502-509
7. pARDS mortality rates 1993 -
2013
Quasney MW, Lopez-Fernandez YM, Santschi M, Watson RS. Peds Crit Care Med 2015;16(5Supl1):S23-40
8. Risk Factors for ARDS
Mortality
Immunodeficiencies
Hematologic malignancies
HSCT
DIC
MODS
Sepsis (indirect lung injury)
History of lung disease
Preexisting chronic organ dysfunction
Degree of hypoxemia
Quasney MW, Lopez-Fernandez YM, Santschi M, Watson RS. Peds Crit Care Med 2015;16(5Supl1):S23-40
Erickson S, Schibler A, Numa A, Nuthall G et al. Peds Crit Care 2007;8:317-323
9. pARDS Mortality and MODS
Lopez-Fernandez Y, Martinez-de Azagra A, de la Oliva P et al. Crit Care Med 2012;40:3238-3245
12. “ Despite resounding evidence that there are
significant long-term consequences in adult
ARDS survivors, the long-term consequences
of pARDS remain largely unknown.”
Quasney MW, Lopez-Fernandez YM, Santschi M, Watson RS. Peds Crit Care Med 2015;16(5Supl1):S23-40
16. Toronto ARDS Study
“… relatively young (median age, 45 years) previously working patients
with few comorbidities and without documented preexisting lung
disease, regain normal or near-normal function …”
Herridge MS, Tansey CM, Matte A, et al. Functional disability 5 years after ARDS. NEJM 2011;364:1293-1304
17.
18. Toronto ARDS Study
N=25 patients Chest CT
Between 2-year and 5-year follow-up
Most common minor findings: non-dependent pulmonary
fibrotic changes (VILI)
(1/3) bronchiectasis, new pulmonary fibrosis, bullae,
pleural thickening
Herridge MS, Tansey CM, Matte A, et al. Functional disability 5 years after ARDS. NEJM 2011;364:1293-1304
19. Changes in Lung Parenchyma
after ARDS
Nöbauer-Huhmann et al. 2001
First one to perform HR-CT
N=15
6-10 months after ARDS
Nöbauer-Huhmann IM, Eibenberger K, Schaefer-Prokop C et al. Eur Radiol 2001;11:2436-2443
23. Rapid disuse atrophy of diaphragm fibers
in mechanically ventilated humans
Intraoperative biopsy specimens from the diaphragms
N=14 brain dead organ donors (18 - 69h diaphragm
inactivity and mechanical ventilation)
N=8 control subjects undergoing surgery
Levine S, Nguyen T, Taylor N, et al. NEJM 2008;358:1327-1335
24.
25. Risk Factors for Critical Illness
Myopathy
1. MODS/severity of illness
2. Muscle inactivity
3. Hyperglycemia
4. Corticosteroids
5. Neuromuscular blockers
de Jonghe B, Lacherade JC, Sharshar T, Outin H. Crit Care Med 2009;37:S309-S315
26. Qualitative ultrasound in acute
critical illness muscle wasting
US echogenicity assessment of Rectus Femoris
Muscle bx of Vastus Lateralis
N=15
Significant correlation between US echogenicity and
myofiber necrosis
Early and rapid loss of skeletal muscle mass
Skeletal muscle function depends on its quantity and
quality
Puthucheary ZA, Phadke R, Rawal J et al. Crit Care Med 2015
28. Acute Muscle Wasting in
Critical Illness
N=63, mean age 55, APACHE II 23.5
>48 h MV, projected ICU LOS > 7 days, survive ICU d/c
US cross-sectional area CSA of the Rectus Femoris
Muscle protein synthesis and breakdown rates
Muscle wasting occurred early and rapidly during 1st week
More severe with MOF
Balance of protein synthesis/breakdown: catabolic state
Puthucheary ZA, Rawal J, McPhail M, et al. JAMA 2013;310(15):1591-1600
29.
30.
31. Herridge MS, Cheung AM, Tansey CM, et al. NEJM 2003;348(8):683-93
Acute Muscle Wasting in
Critical Illness
33. Neuromuscular Dysfunction
Confusing terminology
Critical illness neuropathy or polyneuropathy
Critical illness myopathy
ICU-acquired paresis
ICU-acquired weakness
Critical Illness Neuro-Muscular Abnormalities CINMA
Muscle and nerve lesions often coexist
34. Critical Illness Polyneuropathy
Systematic review by Stevens et al.
N=1400 critically ill patients
CINMA incidence of 50%
Common: SIRS. SEPSIS, ARDS
Diagnostic tests: nerve conduction, velocities, needle
electromyography, direct muscle stimulation,
histopathology of muscle or nerve tissue
Stevens RD, Dowdy DW, Michaels RK, et al. Int Creae Med 2007;33:1876-1891
35. Critical Illness Polyneuropathy
Difficult to identify weakness in unresponsive or minimally
interactive critically ill patients
EMG:
1. Primary axonal degeneration of the motorneurons
2. Followed by sensory neural fibers
36. Additional Physical Morbidities
Entrapment neuropathy
- prevalence 6% at 1-year follow-up (Toronto study)
- peroneal and ulnar nerve palsies
- preclude return to work
- resolved by 5 years
Heterotopic ossification
- deposition of para-articular ectopic bone
- associated with polytrauma, burns, pancreatitis and ARDS
Cosmetic
- scars: laparotomy, chest tube, AL, CVL, tracheostomy, burns, striae
from
fluid overload, facial scars from NIMV
37. Additional Physical Morbidities
Tracheal stenosis/malacia
Tracheal resection
Tracheostomy
Contractures
Frozen shoulders
Hoarseness
Voice changes
Tooth loss
Sensorineural hearing loss
Tinnitus
Emotional outcomes
Social isolation
Sexual dysfunction
38. Hopkins RO, Weaver LK, Pope D, et al. Am J Respir Crit Care Med 1999;160:50-56
N=55 ARDS survivors at 1-year ICU discharge
Hospital d/c: 100% cognitive impairments (memory,
attention, or concentration)
1-year f/u: 78% impairment at least one cognitive function
48% decreased speed of mental processing
Neurocognitive dysfunction impacts HRQOL
41. Schelling, Gustav; Stoll, Christian; Haller, Mathias; et al. Crit Care Med 1998 26(4):651-659
Cohort of 80 ARDS patients (2 control groups)
4 years following discharge
PTSS-10 Post Traumatic Stress Syndrome 10-Questions Inventory
1/3 ARDS survivors reported compromised memory, disturbing dreams,
anxiety, and sleeping difficulties
42. Risk Factors for PTSD,
Depression and Anxiety
Delusional memories
Memory for nightmares
Complete absence of any ICU memory
Hx of psychopathology
Psychotic experiences
Greater ICU Benzodiazepine exposure
43. ICU diaries that contained information and photographs
from the ICU stay
N=352 were randomized at 1 month following ICU
discharge
Final PTSD assessment at 3 months
44.
45. Caregiver and Family Burden
60% survivors who received long-term MV still required
assistance of a family caregiver 1 year after discharge
Experience burden from patient’s physical and psychological
dysfunction
Lifestyle disruption
PTSD
Emotional distress
Depression
Anxiety Chelluri L, Im KA, Belle SH, et al. Crit Care Med 2004;32(1):61-9
Cameron JI, Herridge MS, Tansey CM, et al. Crit Care Med 2006;34(1):81-6
Foster M, Chaboyer W. Scand J Caring Sci 2003;17(3):205-14
Douglas SL, Daly BJ, Kelley CG, et al. Chest 2005;128(6):3925-36
Pochard F, Darmon M, Fassier T, et al. J Crit Care 2005;20(1):90-6
46. Caregiver and Family Burden
Pochard F, Azoulay E, Chevret S, Lemaire F, Hubert P, Canoui P, et al. Crit Care Med 2001, 29(10):1893-1897
48. HRQOL after ARDS
Lower HRQOL scores in ARDS survivors
Largest decrement:
- Role-physical
- Physical functioning
- Social functioning
Important patient-centered metric of recovery
Schelling, Gustav; Stoll, Christian; Haller, Mathias; et al. Crit Care Med 1998 26(4):651-659
Davidson TA, Caldwell ES, Curtis JR, et al. JAMA 1999;281(4):354-360
Angus DC, Musthafa AA, Clermont G, et al. Am J Resoir Crit Care Med 2001;163(6):1389-94
Dowdy DW, Eid MP, Dennison CR, et al. Intensve Care Med 2006;32(8):1115-24
Orme J, Romney JS, Hopkins RO, et al. Am J Respir Crit Care Med 2003;167(5):690-4
49. HRQOL after ARDS
Adversely influenced by physical and neuropsychological
morbidities
An episode of severe lung injury changes the trajectory of
functional outcome
May necessitate a change in employment
Raise awareness among the critical care community
regarding long-term morbidity
50. Conclusions
Development of specialized pediatric intensive care has
contributed to substantially reduced mortality for children with
pARDS over the past few decades.
Recent publications suggest that pediatric critical care may have
“exchanged” decreased mortality for increased long-term
morbidity.
The ‘Post Intensive Care Syndrome’, first described in adults,
may also occur in this vulnerable population of children.
51. Conclusions
Recent research has identified physical, cognitive, and
mental health domains as the major areas of impairment
in survivors of critical illness.
There is an urgent need for additional clinical research to
better characterize PICS and its risk factors towards a
goal of minimizing adverse sequelae associated with
critical illness.
52. Future
Identify PICU survivors most at risk.
Characterize long-term outcomes.
Generate recovery curves for various illnesses.
Identify factors associated with long-term morbidity and
recovery.
Define potential targets for intervention.
53. Words of Wisdom
“ Ultimately, maximizing long-term FS and
HRQOL should be the most important goals
of critical care medicine. “
Dr. J
Zimmerman
Editor's Notes
Recently, there has been greater recognition that critical care begins and ends outside the walls of the intensive care unit.
Historically, the management of pediatric critical illness has focused on survival as the primary goal.
It is still the most commonly used determinant in outcome studies after intensive care.
Variable mortality rates (15-50%) reflect populations of children with differing etiologies of ARDS, some associated with higher mortalities, comorbid conditions that influence the severity of ARDS, perhaps, as well, changing ventilatory strategies and other general care in the PICU. This compares with mortality rates of 35-45% in adults!
1 year prospective multicenter observational study in Spain
21 PICUs, 146 children, aged 1 mo to 15 years, 1994 AECC criteria
Prospective observational single-center study from CHOP
283 children
Initial P/F and OI values were not helpful for prognostication
After 24 hours after meeting pARDS criteria (AECC and Berlin) they accurately stratified outcomes
Increased prevalence of high-risk populations
McHugh,1994; evaluated pulmonary function in 37 ARDS survivors at 3, 6, and 12 months
Pulmonary function improved substantially by 6 months, but little thereafter.
FVC Functional Vital Capacity
TLC Total Lung Capacity
DLCO Diffusing Capacity
Toronto ARDS cohort study by Margaret Herridge NEJM 2011
Most patients had recovery to normal or near normal spirometry within 6- 12 months after ICU discharge
Pulmonary function remained stable through the 5-year follow-up
21-year-old man, 9 moinths after ARDS, HRCT
a.
23-year-old woman, 8 months ARDS
Carried out histologic, biochemical, and gene-expression studies
Slow-twitch and fast-twitch fibers in the case specimens are smaller than those on the control diaphragm
Neither inflammatory infiltrate nor necrosis was present in case and control specimens
The proportions of slow- and fast-twitch fibers did not differ
At the time of discharge ARDS survivors had lost 18% of base line body weight
71% of the patients returned to their base line weight by 1 year
Top panel: Survival rates; Kaplan-Meier curve to 5 years (dashed line 95% CI)
Middle panel: 6- Minute walk distance (meters solid line and percent predicted in dashed line)
Bottom panel: HRQOL; SF-36 subscale scores for physical component and mental component score
Relatively young previously working patients with few comorbidities may not regain their pre-critical illness functional status nor HRQOL by 5 years after ICU discharge.
Complicating the ability to understand discrete risk factors or natural history
Critical Illness Neuro-Muscular abnormalities
Landmark paper in 1999 by Hopkins
Wechsler Adult Intelligence Scale-Revised
Figure 4 . Comparison of scores of the German version of the Post Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10) between patients with the acute respiratory distress syndrome (ARDS) and control groups 2 and 3. Hatched boxes indicate patients after the acute respiratory distress syndrome and open boxes indicate surgical patients and United Nations soldiers. The "whiskers" at the top and bottom of each box indicate the minimal and maximal values of the distribution, respectively. The top and bottom of each box indicate the 75th and 25th percentiles; the line through the box indicates the median (the 50th percentile). The dashed line indicates the PTSS-10 threshold for diagnosis of posttraumatic stress disorder (36 points). 0 indicates outliers. *Significant difference of PTSS-10 scores in ARDS patients compared with all other groups (p < .001, Kruskal-Wallis test); UN, United Nations.
The provision of an ICU diary was effective in aiding psychological recovery and reducing the incidence of new PTSD
More than 2/3 of family members visiting patients in the ICU suffer from symptoms of anxiety or depression.
Psychological morbidity
including critical decision-making
Toronto ARDS cohort 5-year follow-up
Improvement of physical component score of the SF-36 at 2 years after ICU d/c
With a plateau below normal predicted values to 5 years
With maturation of the field of pediatric critical care medicine, critical care practitioners now have the opportunity as well as the obligation to look beyond PICU discharge with a goal of minimizing not only mortality but also the burden of long term morbidity in accordance with patients’ and families’ expectations.
