Clinical meaningful outcomes after pARDS

Francois Aspesberro, MDPediatric Critical Care Medicine

Seattle Children’s HospitalUniversity of Washington School of Medicine

Seattle, WA

Critical care begins and ends outside the walls of the PICU

Angus DC et al. Intensive Care Med 2003;29:368-377

Historical Decline of PICU Mortality

Aspesberro F, Mangione-Smith R, Zimmerman JJ. Intensive Care Med 2015 July;41(7):1235-1246

Pediatric critical care has exchanged mortality for morbidity

Mortality

Morbidity

Simon DW et al. Pediatr Crit Care Med 2014;15(3):264-266

Post Intensive Care Syndrome PICS

Needham DM, Davidson J, Cohen H, et al:. Crit Care Med 2012;40:502-509

pARDS mortality rates 1980-2007

Zimmerman JJ, Akhtar Z, Caldwell E, Rubenfeld GD. Pediatrics 2009;124:87-95

pARDS mortality rates 1993 - 2013

Quasney MW, Lopez-Fernandez YM, Santschi M, Watson RS. Peds Crit Care Med 2015;16(5Supl1):S23-40

Risk Factors for ARDS Mortality

ImmunodeficienciesHematologic malignanciesHSCTDICMODSSepsis (indirect lung injury)History of lung diseasePreexisting chronic organ dysfunctionDegree of hypoxemia

Quasney MW, Lopez-Fernandez YM, Santschi M, Watson RS. Peds Crit Care Med 2015;16(5Supl1):S23-40Erickson S, Schibler A, Numa A, Nuthall G et al. Peds Crit Care 2007;8:317-323

pARDS Mortality and MODS

Lopez-Fernandez Y, Martinez-de Azagra A, de la Oliva P et al. Crit Care Med 2012;40:3238-3245

pARDS Mortality and Hypoxemia

Lopez-Fernandez Y, Martinez-de Azagra A, de la Oliva P et al. Crit Crae Med 2012;40:3238-3245

pARDS Mortality and Hypoxemia

Yehya N, Servaes S, Thomas NJ. Crit Care Med 2015;43:937-946

“ 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

Pulmonary Function after ARDS

FEV1FVCTLCDLCOExercise limitation (distance walked in 6 min)

Pulmonary Function in ARDS Survivors

McHugh LG, Milberg JA, Whitcomb ME, et al. Am J Respir Crit Care Med 1994;150(1):90-4

Pulmonary Function in ARDS Survivors

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

Toronto ARDS StudyN=25 patients Chest CT Between 2-year and 5-year follow-upMost 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

Changes in Lung Parenchyma after ARDS

Nöbauer-Huhmann et al. 2001First one to perform HR-CT N=156-10 months after ARDS

Nöbauer-Huhmann IM, Eibenberger K, Schaefer-Prokop C et al. Eur Radiol 2001;11:2436-2443

Hila levelLocalized parenchymal opacification

Traction bronchiectasis Local fibrosis

Upper lobes levelArchitectural distortionHoneycomb pattern

Upper lobes levelGround glass opacitiesThickened IL septa

Functional Disability after ARDS

Rapid disuse atrophy of diaphragm fibers in mechanically ventilated

humans

Intraoperative biopsy specimens from the diaphragmsN=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

Risk Factors for Critical Illness Myopathy

1. MODS/severity of illness2. Muscle inactivity3. Hyperglycemia4. Corticosteroids5. Neuromuscular blockers

de Jonghe B, Lacherade JC, Sharshar T, Outin H. Crit Care Med 2009;37:S309-S315

Qualitative ultrasound in acute critical illness muscle wasting

US echogenicity assessment of Rectus FemorisMuscle bx of Vastus LateralisN=15Significant 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

Day 1 Day 10

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/cUS cross-sectional area CSA of the Rectus FemorisMuscle protein synthesis and breakdown rates

Muscle wasting occurred early and rapidly during 1st weekMore severe with MOFBalance of protein synthesis/breakdown: catabolic state

Puthucheary ZA, Rawal J, McPhail M, et al. JAMA 2013;310(15):1591-1600

Herridge MS, Cheung AM, Tansey CM, et al. NEJM 2003;348(8):683-93

Acute Muscle Wasting in Critical Illness

ICU-acquired weaknes

s

Irreversible

functional disability

Survival rates; Kaplan-Meier curve

6- Minute walk distance

HRQOL; SF-36 subscale scores for physical and mental componentHerridge MS, Tansey CM, Matte A, et al. Functional disability 5 years after ARDS. NEJM 2011;364:1293-1304

Neuromuscular Dysfunction

Confusing terminologyCritical illness neuropathy or polyneuropathyCritical illness myopathyICU-acquired paresis ICU-acquired weaknessCritical Illness Neuro-Muscular Abnormalities CINMA

Muscle and nerve lesions often coexist

Critical Illness Polyneuropathy

Systematic review by Stevens et al. N=1400 critically ill patientsCINMA incidence of 50%Common: SIRS. SEPSIS, ARDSDiagnostic 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

Critical Illness Polyneuropathy

Difficult to identify weakness in unresponsive or minimally interactive critically ill patientsEMG:

1. Primary axonal degeneration of the motorneurons2. Followed by sensory neural fibers

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

Additional Physical Morbidities

Tracheal stenosis/malaciaTracheal resectionTracheostomyContracturesFrozen shouldersHoarsenessVoice changesTooth lossSensorineural hearing lossTinnitusEmotional outcomesSocial isolationSexual dysfunction

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 dischargeHospital 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

Psychiatric MorbidityToronto ARDS study50% patients depression or anxiety between 2-5 years after ICU discharge

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

Risk Factors for PTSD, Depression and Anxiety

Delusional memoriesMemory for nightmaresComplete absence of any ICU memoryHx of psychopathologyPsychotic experiencesGreater ICU Benzodiazepine exposure

ICU diaries that contained information and photographs from the ICU stayN=352 were randomized at 1 month following ICU dischargeFinal PTSD assessment at 3 months

Caregiver and Family Burden

60% survivors who received long-term MV still required assistance of a family caregiver 1 year after dischargeExperience burden from patient’s physical and psychological dysfunctionLifestyle disruptionPTSDEmotional distressDepressionAnxiety 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):81-6Foster M, Chaboyer W. Scand J Caring Sci 2003;17(3):205-14Douglas SL, Daly BJ, Kelley CG, et al. Chest 2005;128(6):3925-36Pochard F, Darmon M, Fassier T, et al. J Crit Care 2005;20(1):90-6

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

HRQOL after ARDS

HRQOL after ARDSLower HRQOL scores in ARDS survivorsLargest 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):651-659Davidson TA, Caldwell ES, Curtis JR, et al. JAMA 1999;281(4):354-360Angus DC, Musthafa AA, Clermont G, et al. Am J Resoir Crit Care Med 2001;163(6):1389-94Dowdy DW, Eid MP, Dennison CR, et al. Intensve Care Med 2006;32(8):1115-24Orme J, Romney JS, Hopkins RO, et al. Am J Respir Crit Care Med 2003;167(5):690-4

HRQOL after ARDSAdversely influenced by physical and neuropsychological morbiditiesAn episode of severe lung injury changes the trajectory of functional outcomeMay necessitate a change in employment

Raise awareness among the critical care community

regarding long-term morbidity

ConclusionsDevelopment 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.

ConclusionsRecent 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.

FutureIdentify 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.

Words of Wisdom

“ Ultimately, maximizing long-term FS and HRQOL should be the most important goals of critical care medicine. “ Dr. J Zimmerman