Morbidity In Critical Illness Research Articles

Oxidative stress in critically ill ventilated adults: effects of vitamin D3 and associations with alveolar macrophage function.

BackgroundDisruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: 1) characterize the plasma and alveolar thiol/disulfide redox pools, 2) examine their associations with alveolar macrophage phagocytosis, and 3) determine the effect of high dose vitamin D3 on plasma thiol/disulfide redox.MethodsSubjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D3 or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14.ResultsBaseline plasma Cys was inversely associated with alveolar PI (ρ = −0.69, P=0.003), and EhCySS was positively associated with PI (ρ = 0.61, P=0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P<0.01 for both), with no difference by treatment group. Vitamin D3 decreased oxidized plasma GSSG to a more normal state (P for group × time=0.009).ConclusionsOxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D3 decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.

HIGHER BALANCED SOLUTION USE IS ASSOCIATED WITH LESS SEVERE KIDNEY INJURY AND MORTALITY: A MIMIC 2 ANALYSIS

Balanced solutions may be associated with lower morbidity in critical illness in comparison with chloride-rich solutions, including acute kidney injury (AKI). Lactated ringer (LR) is one of most widely used balanced solutions. Nevertheless, it is unclear if fluid mix during the first days of ICU admission influences the development of AKI after controlling for other relevant confounders such as fluid balance, illness severity and comorbidities.

Hypovitaminosis D and morbidity in critical illness: is there proof beyond reasonable doubt?

Vitamin D is recognized to have important actions outside its well-recognized role in musculoskeletal health. These include antimicrobial action, anti-inflammatory, and cardio-protective properties. A high prevalence of vitamin D deficiency and its association with adverse clinical outcomes have now been widely documented in observational studies in the critically ill. These studies of association, however, do not necessarily imply causation, as vitamin D deficiency may be merely a marker of higher illness severity and consequently poorer outcomes. This issue can be clarified only by undertaking high-quality randomized controlled trials of vitamin D supplementation in this vulnerable population.

Glutamine: role in critical illness and ongoing clinical trials

This review will assess recent clinical and mechanistic data examining glutamine's ability to reduce morbidity and mortality in critical illness. Updated metaanalysis data reveal a significant benefit of glutamine supplementation on mortality, length of stay, and infectious morbidity in critical illness. Recent data support glutamine's use in critically ill patients requiring parenteral nutrition and new data reveal safety and efficacy in head-injured patients. Further, new findings on glutamine's beneficial effect on insulin resistance in critical illness will be reviewed. Recent laboratory data have clarified a number of key mechanistic pathways by which glutamine may improve outcome in critical illness. Severe glutamine deficiencies occur rapidly in critical illness. The magnitude of glutamine deficiency is correlated with ICU mortality. Further, metaanalysis reveals glutamine reduces morbidity and mortality in critical illness. It is likely that our new understanding of the molecular pathways by which glutamine acts will lead to insight on how best to utilize glutamine as a nutritional therapy. Presently, randomized, multicenter clinical trials utilizing glutamine as both nutritional replacement and pharmacologic intervention, independent of nutritional needs, are ongoing.

Mechanisms of kidney protection by intensive insulin therapy during critical illness

Strict blood glucose control with intensive insulin therapy reduces mortality and morbidity of critical illness, including newly acquired kidney injury [1-3].

Tight Blood Glucose Control With Insulin in the ICU: Facts and Controversies

Recently, the concept that stress hyperglycemia in critically ill patients is an adaptive, beneficial response has been challenged. Two large randomized studies demonstrated that maintenance of normoglycemia with intensive insulin therapy substantially prevents morbidity and reduces mortality in these patients. Since then, questions have been raised about the efficacy in general and in specific subgroups, and about the safety of this therapy with regard to potential harm of brief hypoglycemic episodes and of high-dose insulin administration. These issues are systematically addressed in relation to the available evidence. Intensive insulin therapy during intensive care is effective in reducing the mortality and morbidity of critical illness. The available randomized studies show that an absolute reduction in risk of hospital death of 3 to 4% is to be expected from this therapy in an intention-to-treat analysis. In order to confirm this survival benefit and assign it as statistically significant, future studies should be adequately powered, and hence sample size should be at least 5,000. The absolute reduction in the risk of death increases to approximately 8% when patients are treated with intensive insulin for at least 3 days. Data available thus far indicate that blood glucose control to strict normoglycemia is required to obtain the most clinical benefit. The risk of hypoglycemia increases with this therapy, but it remains unclear whether this is truly harmful in the setting of critical care.