RESUMEN
BACKGROUND: Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis. RESEARCH QUESTION: Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis? STUDY DESIGN AND METHODS: We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values. RESULTS: Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics. INTERPRETATION: In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.
RESUMEN
Importance: Agitation is common in mechanically ventilated ICU patients, but little is known about physician attitudes regarding agitation in this setting. Objectives: To characterize physician attitudes regarding agitation in mechanically ventilated ICU patients. Design, Setting, and Participants: We surveyed critical care physicians within a multicenter health system in Western Pennsylvania, assessing attitudes regarding agitation during mechanical ventilation and use of and confidence in agitation management options. We used quantitative clinical vignettes to determine whether agitation influences confidence regarding readiness for extubation. We sent our survey to 332 critical care physicians, of whom 80 (24%) responded and 69 were eligible (had cared for a mechanically ventilated patient in the preceding three months). Main Outcomes and Measures: Respondent confidence in patient readiness for extubation (0-100%, continuous) and frequency of use and confidence in management options (1-5, Likert). Results: Of 69 eligible responders, 61 (88%) agreed agitation is common and 49 (71%) agreed agitation is a barrier to extubation, but only 27 (39%) agreed their approach to agitation is evidence-based. Attitudes regarding agitation did not differ much by practice setting or physician demographics, though respondents working in medical ICUs were more likely (P = .04) and respondents trained in surgery or emergency medicine were less likely (P = .03) than others to indicate that agitation is an extubation barrier. Fifty-three (77%) respondents reported they frequently use non-pharmacologic measures to treat agitation, and 42 (70%) of those who reported they used non-pharmacologic measures during the prior 3 months indicated confidence in their effectiveness. In responses to clinical vignettes, confidence in patient's readiness for extubation was significantly lower if the patient was agitated (P < .001) or tachypneic (P < .001), but the presence of both agitation and tachypnea did not reduce confidence compared with tachypnea alone (P = .24). Conclusions and Relevance: Most critical care physicians consider agitation during mechanical ventilation a common problem and agreed that agitation is a barrier to extubation. Treatment practice varies widely.
