Persistent and Chronic Critical Illness

Revised and reviewed 11 December 2016


Advances in intensive care have led to a growing cohort of patients of patients, who would have otherwise succumbed to acute illness, survive in a state dependent on prolonged intensive care therapies including mechanical ventilation

  • heavy burden of costs to the individual, family and society
  • requires extreme use of resources
  • cause of considerable distress to patient and family

Following an acute critical illness there are 3 outcomes:

  • recovery (complete or incomplete)
  • death during the acute illness
  • progression to persistent or chronic critical illness

Between 5 and 10% of patients who require mechanical ventilation for acute conditions develop chronic critical illness


Suggested definitions of chronic critical illness (CCI) are problematic; they include (but are not limited to):

  • a syndrome of ongoing “ventilator dependence, brain dysfunction, neuromuscular weakness, endocrinopathy, malnutrition, anasarca, skin breakdown and symptom distress” that occurs when patients with limited physiological reserve (due, often, to older age and chronic comorbidities) (Nelson, 2010; Iwashyna et al, 2015)
  • “one of 5 eligible clinical conditions plus at least 8 days in an ICU during an acute care hospitalization” (Research Triangle Initiative definition)
    • the 5 eligibility “conditions” were (1)prolonged acute mechanical ventilation (i.e., mechanical ventilation for at least 96 hr in a single episode); (2) tracheotomy; (3)sepsis and other severe infections; (4) severe wounds; and (5) multiple organ failure, ischemic stroke, intercerebral hemorrhage, or traumatic brain injury
    • primarily used for determining payments to LTAC (longterm acute care) facilities in the USA
  • “need for placement of a tracheostomy after >10 days of mechanical ventilation”
  • “need for prolonged mechanical ventilation (>21 days)”

CCI may be better viewed as a syndrome, with 5 categories (Iwashyna et al, 2015):

  • persistent critical illness (see below)
  • medically complex patients
    • e.g. the RTI definition of CCI
  • diseases with long intrinsic recovery times
    • e.g. Guillain-Barre Syndrome or advanced chronic disease that limits recovery
  • prolonged ventilator weaning
    • traditionally defined as “patients who were eligible for a spontaneous breathing trial (SBT), but for whom the SBT failed at least three times over the course of 7 or more days”
  • prolonged ICU length of stay (LOS)
    • a purely quantitative definition

The pragmatic concept of Persistent Critical Illness (PCI) proposed by Iwashyna et al (2015):

  • PCI refers to those patients whose reason for being in the ICU was now more related to their ongoing critical illness than their original reason for admission to the ICU
  • the disease for which the patient was admitted has been treated and is no longer active
  • failure to wean from mechanical ventilation is not the only, or necessarily the primary, problem
  • at a population level, this appears to occur after about 10 days in ICU
  • the concept requires further validation


Chronic critical illness (CCI) syndrome is characterized by (Nelson, 2010):

  • Preceding acute critical illness, usually with at least one episode of sepsis
  • Prolonged mechanical ventilation
  • ICU-acquired weakness
  • Neuroendocrine dysfunction (e.g. loss of pulsatile secretion if pituitary hormones)
  • Anasarca
  • Malnutrition
  • Vulnerability to infection (including MDROs)
  • Skin breakdown (e.g. nutritional deficiencies, edema, incontinence, and prolonged immobility)
  • Symptom distress (e.g. pain, thirst, dyspnea, depression, anxiety, and inability to communicate)

Some of these features (e.g. brain dysfunction) may be present during the initiating acute illness, others (e.g. malnutrition)


CCI is associated with high mortality and survivors have high rates of institutionalisation and functional dependence. A minority are able to return home.

Prolonged mechanical ventilation (Damuth et al, 2015)

  • 59% mortality at 1 year
  • 50% were successfully liberated from mechanical ventilation at 1 year
  • 19% were discharged to home at 1 year

Persistent critical illness (Iwashyna et al, 2015)

  • 24.5% in-hospital mortality
  • 46.5% discharged home

Clinicians in Australasia report concerns that treatment of patients with PCI (Iwashyna et al ,2015):

  • is often “less than excellent”
  • may lack cost-effectiveness
  • is stressful for staff


Many patients and their families choose to continue life-sustaining therapies when critical illness enters a chronic phase

  • this may in part be due to a lack of information provided to them by treating staff (Nelson et al, 2007)

SUPPORT study (Teno et al, 2000)

  • <40% of patients treated in ICUs for >2/52 reported having a discussion with their physician about prognosis or preferences for life-sustaining treatment
  • ~ 50% of those who preferred care focused solely on their comfort even at the expense of shorter life thought that the treatment they received was contrary to their preference
  • ~ 25% did not know the clinical team’s approach to their care
  • Almost 20% of 70 surrogate decision makers for patients expected to stay more than 3 days in medical or surgical ICUs at 2 medical centers reported receiving no prognostic information
  • In ICU family conferences, physicians commonly missed opportunities to explore comments about patient treatment preferences, as would be required for appropriate clinical decision making


CCI should not be treated without a thorough discussion with the patient and family regarding:

  • benefits and burdens of therapy
  • exploration of the needs, values, preferences and goals of the patient and family
  • education of the patient and family regarding CCI

The choice to continue treatment may be reasonable, though it should involve these additional considerations:

  • consideration of a time-limited therapeutic trial
  • periodic reevaluation of progress
  • concomitantly address the palliative needs of the patient and family

Multi-disciplinary approach, including effective communication, potentially involving:

  • nursing, including relevant specialists (e.g. wound care)
  • physiotherapists
  • dieticians
  • occupational therapists
  • orthoticists
  • speech and language therapists
  • pharmacists
  • social workers
  • psychologists

Specific therapeutic considerations include:

  • management of delirium
  • physiotherapy
  • nutritional support
  • wound care and pressure injuries
  • psychosocial support for the patient and family

Disposition — care of persistent critical illness may occur in different venues, including:

  • ICU
  • Long-term acute care (LTAC) hospitals (in the USA)
  • Hospital wards
  • Hospice and palliative care facilities
  • Nursing homes
  • Home


Iwashyna et al, 2016

  • retrospective, population-based, observational study using data from the ANZICS Adult Patient Database
  • 1,028,235 critically ill patients from 182 ICUs across Australia and New Zealand (Jan 2000 to Dec 2014)
  • Inclusion: patients >16 years of age admitted to ICU
  • Exclusions: patients transferred from another hospital; patients admitted to an ICU for palliative care or awaiting organ donation
  • Primary outcome: in-hospital mortality
  • Findings:
    • “admission diagnosis and physiological derangements, which accurately predicted outcome on admission (AUROC 0·898 in the validation cohort), progressively lost their predictive ability and no longer predicted outcome more accurately than did simple antecedent patient characteristics (eg, age, sex, or chronic health status) after 10 days in the ICU
    • 5·0% of ICU patients had persistent critical illness, but accounted for 32·8% of ICU bed-days and 14.7 hospital bed-days
    • 24.5% in-hospital mortality
    • 46.5% discharged home
  • Conclusion
    • Onset of persistent critical illness (10 days in ICU) can be empirically measured at a population level
    • This condition requires extensive resources and has a poorer prognosis (not necessarily in keeping with initial illness severity scores) characterised by high mortality and decreased likelihood of discharge to home

References and Links


Journal articles

  • Cox CE. Persistent systemic inflammation in chronic critical illness. Respiratory care. 57(6):859-64; discussion 864-6. 2012. [pubmed] [free full text]
  • Damuth E, Mitchell JA, Bartock JL, Roberts BW, Trzeciak S. Long-term survival of critically ill patients treated with prolonged mechanical ventilation: a systematic review and meta-analysis. The Lancet. Respiratory medicine. 3(7):544-53. 2015. [pubmed]
  • Girard TD. Brain dysfunction in patients with chronic critical illness. Respiratory care. 57(6):947-55; discussion 955-7. 2012. [pubmed]
  • Iwashyna TJ, Hodgson CL, Pilcher D. Towards defining persistent critical illness and other varieties of chronic critical illness. Critical Care and Resuscitation. 17(3):215-8. 2015. [pubmed]
  • Iwashyna TJ, Hodgson CL, Pilcher D, Bailey M, Bellomo R. Persistent critical illness characterised by Australian and New Zealand ICU clinicians. Critical care and resuscitation. 17(3):153-8. 2015. [pubmed]
  • Iwashyna, Theodore J et al. Timing of onset and burden of persistent critical illness in Australia and New Zealand: a retrospective, population-based, observational study. Lancet Respiratory Medicine [website] [podcast]
  • Lamas D. Chronic critical illness. The New England journal of medicine. 370(2):175-7. 2014. [pubmed]
  • Macintyre NR. Chronic critical illness: the growing challenge to health care. Respiratory care. 57(6):1021-7. 2012. [pubmed] [free full text]
  • MacIntyre NR, Epstein SK, Carson S. Management of patients requiring prolonged mechanical ventilation: report of a NAMDRC consensus conference. Chest. 128(6):3937-54. 2005. [PMID 16354866]
  • Maguire JM, Carson SS. Strategies to combat chronic critical illness. Current opinion in critical care. 19(5):480-7. 2013. [pubmed]
  • Nelson JE, Cox CE, Hope AA, Carson SS. Chronic critical illness. American journal of respiratory and critical care medicine. 182(4):446-54. 2010. [pubmed] [free full text]
  • Nelson JE, Mercado AF, Camhi SL. Communication about chronic critical illness. Archives of internal medicine. 167(22):2509-15. 2007. [pubmed]
  • Nelson JE, Kinjo K, Meier DE, Ahmad K, Morrison RS. When critical illness becomes chronic: informational needs of patients and families. Journal of critical care. 20(1):79-89. 2005. [pubmed]
  • Schulman RC, Mechanick JI. Metabolic and nutrition support in the chronic critical illness syndrome. Respiratory care. 57(6):958-77; discussion 977-8. 2012. [pubmed] [free full text]
  • Teno JM, Fisher E, Hamel MB. Decision-making and outcomes of prolonged ICU stays in seriously ill patients. Journal of the American Geriatrics Society. 48(5 Suppl):S70-4. 2000. [pubmed]

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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