Sakusic, Amra

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. Design: An observational case-control study. Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. Conclusions: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

Purpose of review There is an increasing realization in the critical care community that persistent cognitive impairment is a common and disabling complication after ICU care. In this review, we discuss the best available information on the magnitude of the problem, its possible mechanisms, risk factors, management strategies and prognosis. Recent findings Estimates of the incidence of persistent cognitive impairment after critical illness vary widely across studies but the most solid prospective information indicates that it may occur in 20–40% of patients discharged from the ICU. From the available evidence, it is difficult to discriminate between de novo cognitive impairment and exacerbation of preexistent cognitive decline. The pathogenesis is multifactorial but inflammatory mechanisms causing derangements of endothelial function and blood–brain barrier integrity might play an important role. Brain atrophy and white matter tract disruption can be structural correlates of the cognitive decline. Prolonged delirium in the ICU is the strongest risk factor for the development of subsequent persistent cognitive impairment. Management strategies are currently limited to those designed to prevent and improve delirium. Cognitive trajectories may vary but a substantial proportion of patients with cognitive impairment 3 months after ICU discharge are still cognitively impaired at 12 months. Summary Persistent cognitive impairment is a major complication of critical illness. Our knowledge of this problem remains incomplete. Collaborative research is indispensable to improve our understanding of this disabling sequel and to identify ways to prevent it.

Objectives: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. Design: Retrospective case series. Setting: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. Patients: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. Interventions: None. Measurements and Main Results: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50–74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58–87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p < 0.01), malignancy (p < 0.01), and solid organ transplantation (p = 0.04), whereas seizure disorder was more common in survivors (p = 0.02). After adjustment, serum ammonia level was not associated with increased mortality. Conclusions: Hyperammonemia occurs in a substantial minority of critically ill patients without liver failure. These patients have a poor prognosis, although ammonia level per se is not independently associated with mortality. Serum ammonia should be measured when risk factors are present, such as nutritional deficiencies and protein refeeding, treatment with valproic acid, high tumour burden, and known or suspected urea cycle abnormalities.