Studies of ARDS survivors suggest that a combination of acute hypoxia, hypoperfusion, and hyperglycemia plays an important role in the long-term cognitive sequelae of critical illness [3, 58, 59] . However, it has been difficult to demonstrate a clear relationship, given the lengthy interval between stimulus and effect and the great number of additional contributing variables that can obscure downstream effects. Among ARDS survivors, Hopkins and colleagues showed that the degree of CD at 1 year is significantly correlated with the durations of hypoxia [58] and mean arterial blood pressure less than 50 mmHg during the ICU stay [3] . In animals, hyperglycemia markedly enhances hypoxic-ischemic brain damage due to increased brain edema and disrupted cerebral metabolism [60] . In ARDS survivors, the duration of blood glucose greater than 180 mg/dl has been shown to correlate with worse visual spatial abilities, visual memory, processing speed, and executive function at 1 year [59] . Given the recent interest in maintaining tight glucose control during critical illness as a means of reducing mortality, it will be interesting to see whether patients managed using this technique have better cognitive outcomes. Clearly, such an approach will need to balance the benefits of tight glucose control with the known risks that hypoglycemia poses to the CNS.