By Richard Kallet, MS, RRT, FAARC, FCCM

Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital

Mr. Kallet reports no financial relationships relevant to this field of study.

SYNOPSIS: Both ARDS and mechanical ventilation (MV) are independently associated with delirium, and the presence of delirium in patients with ARDS strongly influences mortality.

SOURCE: Hsieh SJ, et al. The association between acute respiratory distress syndrome, delirium, and in-hospital mortality in intensive care unit patients. Am J Respir Crit Care Med 2015;191:71-78.

This prospective, observational study of 564 adult, medical-surgical intensive care unit (ICU) patients at two urban academic hospitals investigated: 1) whether acute respiratory distress syndrome (ARDS) is associated with a higher prevalence of delirium compared to non-ARDS respiratory failure; and 2) the effect of delirium on the relationship between ARDS and hospital mortality. The study sample was divided into three cohorts: ICU patients who never required mechanical ventilation (MV) (n = 198), those who needed MV but never developed ARDS (n = 318), and those requiring MV for ARDS (n = 48). Delirium developed in 43% of patients and was associated with older age, increased number of comorbidities, severe sepsis, higher illness severity scores, as well as a history of dementia, alcohol, and drug abuse. As anticipated, delirium was also linked to usage of opiates, benzodiazepines, and steroids in the ICU.

A significantly higher incidence of delirium and persistent coma was found in the ARDS cohort (73% and 19%, respectively) compared to the intubated, non-ARDS cohort (52% and 7%) and ICU patients who never required MV (21% and 0.5%) (P < 0.001). After adjusting for multiple covariates including age, dementia, alcohol abuse, comorbidities, severe sepsis, steroid and sedative use, the presence of ARDS carried a seven-fold higher risk for delirium compared to a two-fold higher risk in those on MV without ARDS. Most importantly, adjusting for the presence of delirium and persistent coma in the ARDS cohort reduced the odds ratio for hospital mortality from 10.44 (95% CI, 3.16-34.50, P < 0.001) to 5.63 (95% CI, 1.55-20.45, P = 0.009).


This study suggests that prospective studies will be required to assess whether reducing delirium in ARDS improves mortality. ICU delirium occurs in 60-80% of patients requiring MV with an estimated mortality risk of 10% per day of delirium.1 However, a recent meta-analysis of randomized clinical trials did not find an association between reduced delirium duration and mortality.2 Therefore, we should be cautious when modifying therapies proven to reduce mortality in ARDS in order to reduce the perceived mortality risk associated with delirium.

Most importantly, interventions that reduce ICU delirium (e.g., targeted light sedation, daily sedation interruptions, spontaneous breathing trials) may not be appropriate in severe ARDS. Under these circumstances, strict lung protective ventilation (LPV) is imperative as low tidal volumes (VT) and higher positive end-expiratory pressures (PEEP) reduce lung stress and strain, repetitive shear injury, and oxygen toxicity that intensify the inflammatory response to severe infection or injury.

The authors justifiably stress that reducing “modifiable” risk factors for delirium in ARDS necessitates further prospective research. However, what, how, and in whom those factors are tested presents a nettlesome problem.

LPV often requires a set VT below that targeted by patients in severe distress because of numerous stimuli including hypoxemia, acidosis, irritant receptor firing, and the effects of loaded breathing. Exaggerated breathing efforts stymy effective ARDS management by increasing alveolar edema formation (from vigorous negative intrathoracic pressures), countering the effectiveness of PEEP (from intense, expiratory muscle recruitment), and magnifying intrapulmonary shunt (from the effects of increased oxygen consumption). The importance of controlling these factors are implied both by evidence that mortality in ARDS is dependent on the ability to clear alveolar edema and meta-analyses showing that lower VT, higher PEEP, paralytics, and prone positioning reduce mortality in severe ARDS.

However, liberalizing LPV targets may be appropriate for some patients with mild or moderate ARDS. In relatively severe ARDS, the incidence of stretch-related injury increases substantially above 8-9 mL/kg.1 On the other hand, stable ICU patients on MV appear to tolerate increased breathing exertion of at least twice normal. Therefore, clinically stable patients with ARDS may tolerate some combination of increased breathing exertion and judiciously increased VT that might reduce the apparent mortality risk associated with delirium. To further improve outcomes in ARDS, we need well-designed clinical trials that enlighten us as to the risks of favoring one paradigm over another, in clearly defined clinical situations. Hsieh and colleagues are to be commended for bringing this important issue to light.


1. Hsieh SJ, et al. Can intensive care unit delirium be prevented and reduced? Ann ATS 2013;10:648-656.

2. Al-Qadheeb NS, et al. Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short term mortality: a systematic review and meta-analysisCrit Care Med 2014;42:

3. Roupie E, et al. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. Am J Respir Crit Care Med 1995;152:121-128.