Neuropsychological Effects of ARDS Persist 2 Years Later

Abstract & Commentary

Saadia R. Akhtar, MD, MSc, Pulmonary and Critical Care Medicine, Yale University School of Medicine, is Associate Editor for Criticall Care Alert.

Synopsis: This single center observational cohort study reveals that ARDS survivors have persistent neurocognitive, psychiatric and quality of life impairments at 2 years.

Source: Hopkins RO, et al. Am J Respir Crit Care Med. 2005;171(4):340-347.

The study objective was to assess neurocognitive and emotional function and quality of life in survivors of the acute respiratory distress syndrome (ARDS) 2 years after hospital discharge. The primary outcome was the overall impairment score (defined below). Surviving patients at least 16 years of age with ARDS (defined by usual criteria) who were prospectively enrolled from 1994-1999 in a randomized trial of mechanical ventilation were invited to participate in long-term follow-up. Traumatic brain injury or prior neurocognitive deficits were among the exclusion criteria for the initial study. One-year follow-up was reported in a prior publication.1

Nine standardized neuropsychological tests were performed at 2-year follow-up. Neurocognitive sequela was defined as 2 or more tests with scores at least 1.5 standard deviation (SD), or 1 test more than 2 SD, below normative population means. An overall impairment score was calculated for each subject by summing the total number of SD below the normative means for all tests. Quality of life was measured by the Medical Outcome Study 36-Item Short Form Survey (SF-36).

Seventy-four subjects were enrolled in the initial study, of whom 66 (93%) were available for 1-year follow-up. From 1-2 years, there were 2 deaths and 2 patients declined further follow-up. Thus 62 (90%) were available for evaluation at 2 years. At that time, 34% of them were full-time students or working, 34% had been on disability since hospital discharge, and 32% were retired or unemployed. Intelligence quotients were in the normal range at 2 years. Although paired comparisons revealed that individual neurocognitive test scores and overall impairment scores improved from hospital discharge to 1 year, there were no significant changes between 1 and 2 years.

Neurocognitive sequelae were present in 47% of the patients. Moderate-to-severe symptoms of depression and anxiety were found in 23%; these did not correlate with neurocognitive test results, suggesting that neurocognitive impairment was independent of depression or anxiety. No correlation was found between neurocognitive scores at 2 years and duration of hypoxemia, intubation or sedation, mean blood pressure less than 60 mm Hg, ICU length of stay, or severity of illness scores. SF-36 scores in all domains were below normal at 2 years. Physical, role emotional, pain and general health scores were stable from 1 to 2 years but mental health domain scores declined.


This report by Hopkins and colleagues is one of the longest follow-up studies with certainly the most comprehensive neuropsychological assessment at follow-up of survivors of ARDS published to date. Their follow-up rate is excellent at 90%. Their findings are striking and important; although survivors of ARDS may have improvement in neurocognitive function and quality of life from hospital discharge to 1 year later, there is no further improvement or normalization over the following year.

Almost half the patients in this cohort had persistent neurocognitive sequelae and about a quarter had depression or anxiety at 2 years. (In contrast, at hospital discharge and during rehabilitation, only 12% of patients in this cohort were identified as having cognitive deficits and needing cognitive rehabilitation.) These results are similar to those in other reports that have revealed persistent reductions in quality of life and neuropsychiatric functioning, among other problems, as much as 8 years (median follow-up) after hospital discharge from ARDS.2,3

It is less clear from this and prior studies whether the degree of impairment noted is more severe for survivors of ARDS compared to survivors of other critical illnesses. This is the primary limitation of this work—the absence of a control group of age, severity-of-illness, and date-of-admission matched critically ill patients without ARDS. One prior study evaluated quality of life after ARDS using a matched parallel cohort of critically ill patients and found more severe reductions in quality of life for survivors of ARDS.4 Further similar analyses are needed to confirm these findings.

Other limitations of Hopkins et al’s study include lack of information on subjects’ baseline neuropsychological status and quality of life (something that may be near-impossible to attain) and limited generalizability of results. These patients were not all-comers with ARDS; they were already enrolled in another study and were recruited from a single center in Utah, an area not clearly representative of other US urban regions.

Nevertheless, this report is an important reminder that critical illness and ARDS may adversely affect long-term outcomes other than survival and physical health. As acute care of patients with ARDS continues to improve and survival continues to increase, greater attention must be given to maximizing long-term quality of life and neuropsychological functioning.


1. Orme J, et al. Am J Respir Crit Care Med. 2003;167(5): 690-694.

2. Kapfhammer HP, et al. Am J Psychiatry. 2004;161(1): 45-52.

3. Herridge MS, et al. N Engl J Med. 2003;348(8): 683-693.

4. Davidson TA, et al. JAMA. 1999;281(4):354-360.