Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More recently, vitamin C has emerged as a potential therapeutic agent to treat sepsis. Vitamin C has been shown to be deficient in septic patients and the administration of high dose intravenous as opposed to oral vitamin C leads to markedly improved and elevated serum levels. Its physiologic role in sepsis includes attenuating oxidative stress and inflammation, improving vasopressor synthesis, enhancing immune cell function, improving endovascular function, and epigenetic immunologic modifications. Multiple clinical trials have demonstrated the safety of vitamin C and two recent studies have shown promising data on mortality improvement. Currently, larger randomized controlled studies are underway to validate these findings. With further study, vitamin C may become standard of care for the treatment of sepsis, but given its safety profile, current treatment can be justified with compassionate use.
Objectives:
To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU.
Data Sources:
Source data were obtained from a PubMed literature review.
Study Selection:
English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies.
Data Extraction:
Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice.
Data Synthesis:
Approximately 30–50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion.
Conclusions:
The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients.
Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a five-year period with serial neurological exams, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first two years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease.
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