Factors which influence intensive care outcome

Question 8 from the second paper of 2007  discussed the influence of old age on ICU outcomes, and Question 23 from the second paper of 2007 brought up the issue of genetic susceptibility to various ICU-related illnesses. Other issues associated with actually measuring  the outcomes are the topic for Question 25 from the first paper of 2013, but this got pushed into the Adminstration section.

In brief, it would be fair to say that old age makes everything worse for the ICU patient, and this is reflected in mortality data and functional outcomes following discharge. As for genetics... That question was done very poorly by the candidates, and since its appearance in 2007 the college have not revisited this area.

Age-related influences on intensive care outcome

This was the subject of Question 8 from the second paper of 2007. The college answer to this question was slightly weird- they went on and on about various physiological changes associated with age (to be fair, most of these are adverse influences on outcome). Fortunately, there is an excellent article (de Rooij et al, 2005) which seems almost tailor-made to answer this question. Salient points from this article are summarised below:

Influence of age on intensive care outcome

  • Relative to patients younger than 35 years, the adjusted odds of death in patients aged 80–84 years and ≥90 years were 3.9 and 4.7, respectively.
  • In-hospital mortality in mechanically ventilated  octogenarians was 70%, as compared with 32% in patients aged 29 years or younger.
  • If the reason for ventilation was pneumonia, in-hospital mortality for the over-65s was 62%
  • In patients aged 80–84 years hospital mortality was 85% for those with infection as their reason for admission
  • For brain injury, risk of death or disability is doubled in the elderly
  • Mortality was 30% in patients who had an Activities of Daily Living score of 1–6 (dependent), as compared with 7.8% in patients with a score of 0 (independent).
  • Likewise, mortality was 55.9% in patients with severe cognitive impairment versus 8.2% in those without cognitive impairment.
  • Delirium (to which they are prone) is an independent predictor of reintubation, prolonged hospital stay and mortality.
  • Low BMI increases mortality in the elderly.
  • Only 14% of patients aged 85 years or older went home without home health care.
  • After discharge, mortality occurred predominantly during the first 3 months. If you survive ninety days, you're probably going to be ok.
  • Many elderly patients do not want intensive care. "In a population of patients with limited life expectancy and aged 60 years or older, 74% stated that they would not choose treatment if the burden of treatment were high and the anticipated outcome survival with severe functional impairment".

Caveats in measuring the influence of age on ICU outcome

  • Limitations on therapy may be applied to patients with severe chronic disease, and this group is under-represented in the studies (i.e. they never even make it into the ICU, because futility, etc)
  • If you don't ever admit these people, focusing only on the "good octogenarians", you may develop statistics which are excessively optimistic about the outcome of elderly people in the ICU.
  • On the other hand, many of these patients may also have life-sustaining treatment (appropriately) withdrawn, and that would skew the statistics in the direction of increased mortality.

Genetic influences on intensive care outcome

The SAQ on this topic (Question 23 from the second paper of 2007) was passed by only 13% of the candidates, reflecting the fact that we are generally umprepared to discuss such trivial gibberish. Does one's lack of awareness within this topic diminish one's effectiveness as an ICU specialist? Perhaps. Tellingly, this question has never been repeated again, nor has it ever surfaced as a viva station. The time-poor exam candidate may safely abandon all reading on this topic.

In brief, the following specific associations between genotype and response to critical illness have been found:

  • Risk of developing MODS from acute pancreatitis is influenced by TNF-α gene variants (Bishehsari et al, 2012)
  • Risks of developing ARDS in community acquired pneumonia is related to genes encoding proteins A and D of pulmonary surfactant (García-Laorden et al, 2011)
  • Susceptibility to sepsis (and to death from sepsis) seems to be related to a whole host of genetic variations, specifically in the genes encoding interleukin (IL)-1 receptor antagonist gene, the heat shock protein gene, the IL-6 gene, the IL-10 gene, the CD-14 gene, the Toll-like receptor (TLR)-4 gene, and the TLR-2 gene (Holmes et al, 2003)
  • Delirium in critical illness is associated with a apolipoprotein E4 polymorphism (Ely et al, 2007)
  • Outcome in brain injury seems to be worse for people featuring the apolipoprotein E-ε4 genotype (Friedman et al, 1999)

In addition, the following comorbidities feature significantly in ICU outcomes, and have a known genetic basis:

  • IHD
  • Emphysema (α-1 antitrypsin deficiency)
  • Cerebrovascular disease
  • Various genetic disorders and sporadic mutations / chromosomal abnormalities; of which some notable examples are Down syndrome, which results in congenital cardiac defects, and Prader-Willi, which is associated with OSA and obesity hypoventilation syndrome.


de Rooij, Sophia E., et al. "Factors that predict outcome of intensive care treatment in very elderly patients: a review." Critical Care 9.4 (2005): R307.

Chung, T. Philip, et al. "Functional genomics of critical illness and injury." Critical care medicine 30.1 (2002): S51-S57.

Villar, Jesús, et al. "Bench-to-bedside review: understanding genetic predisposition to sepsis." Critical Care 8.3 (2004): 180.

Ely, E. Wesley, et al. "Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*." Critical care medicine 35.1 (2007): 112-117.

Bion, J. F. "Susceptibility to critical illness: reserve, response and therapy."Intensive care medicine 26.1 (2000): S057-S063.

Bishehsari, Faraz, et al. "TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis." Pancreatology 12.2 (2012): 113-118.

García-Laorden, M. Isabel, et al. "Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study." Crit Care 15.1 (2011): R57.

Holmes, Cheryl L., James A. Russell, and Keith R. Walley. "Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy." CHEST Journal 124.3 (2003): 1103-1115.

Ely, E. Wesley, et al. "Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*." Critical care medicine 35.1 (2007): 112-117.

Friedman, G., et al. "Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury." Neurology 52.2 (1999): 244-244.