The mortality in patients with ARDS has only shown a gradual decline over the last two decades.


(a)       What specific modalities of treatment have contributed to the improvement in mortality?

(b)       Discuss why the observed decline in mortality has not been greater in magnitude?

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College Answer

The mortality in patients with ARDS has only shown a gradual decline over the last two decades.


(a)       What specific modalities of treatment have contributed to the improvement in mortality?

Many promising specific therapies have failed to demonstrate improved mortality when studied in more detail (eg. prone positioning, nitric oxide, exogenous surfactant, liquid ventilation, ECMO, infusion of PGE1, ketoconazole and N-acetylcysteine).   Most of these therapies are not routinely used, and are therefore unlikely to contribute to improved outcomes.

Specific therapies that have recently been demonstrated to potentially improve survival include the use of low tidal volume ventilation (ARDSnet, NEJM), in addition to recruitment and higher levels of PEEP (Amato, NEJM) and the use of steroids in late ARDS (Meduri JAMA).  These techniques are also relatively recent in acceptance/still being evaluated, and are not yet in widespread use.

A combination of factors not individually shown to be beneficial regarding mortality is more likely to have resulted in benefit. Most patients die a non-respiratory death, so general “supportive care” is more likely to have made an impact on survival.  

Specific approaches to be considered include:

  • Prevention: of pulmonary thromboembolism, gastrointestinal bleeding, nosocomial infections (pneumonia, line-related sepsis), complications of sedation and paralysis (better understanding of pharmacology).
  • Early diagnosis and treatment: of nosocomial infections, deficiencies in pituitary-adrenal access.
  • Early nutritional support: especially with regard to early enteral feeding.
  • Additional ventilatory strategies: including better synchrony of patient with ventilator, allowing lower levels of sedation/paralysis; semi-recumbent positioning etc.

(b)       Discuss why the observed decline in mortality has not been greater in magnitude?

A number of factors need to be considered,  in particular the large amount of background  noise making  accurate  assessment  of  improvements  near  impossible.    Indeed,  the  studies  that  have actually shown benefit may not be extrapolatable to the majority of the ARDS population seen in Intensive Care.

The mortality of ARDS is not usually due to respiratory disease per se, but instead to multiple organ dysfunction.    This  in turn  is due  to a multiplicity  of factors  (including  the  underlying  disease process  that  resulted  in  ARDS  [eg.  pancreatitis,  sepsis,  burns],  inflammatory  response  due  to ARDS, nosocomial infections.  No single specific therapy is likely to prevent the cascade of events that result in inflammation.   Insufficient studies have been performed to consistently demonstrate one technique has benefits, let alone which combinations of therapies may be useful.

ARDS  is  also  the  end  result  of  a  large  number  of  predisposing  insults.    The  outcomes  vary dramatically between subgroups (eg. trauma versus pneumonia).  More specific classification or stratification may allow more accurate comparisons.

As a result of better general supportive care, patients that would not previously been considered salvageable  could now be going on to develop  ARDS, and are more likely to have an adverse outcome.   It is probably impossible to accurately compare outcomes now with decades ago, given the inability to control for the many factors that influence outcome.

Discussion

The second part of this question closely resembles Question 28 from the first paper of 2006.

However, the first part is unique, and interesting.

Why indeed have the ARDS outcomes improved?

  • Improvement of old strategies
    • Low tidal volume ventilation
    • Open-lung ventilation
    • improved supportive care and surveillance of complications (eg. early nutrition)
  • Development of new strategies
    • Prone positioning
    • ECMO
    • inhaled pulmonary vasodilators