September 14, 2020

Background: Though it’s been stated numerous times on this blog, it bears repeating: the pillars of sepsis care remain early identification of sepsis, early appropriate empiric antibiotics, source control, and supportive care. The focus should be on getting the basics right but, it is important to evaluate whether other adjunctive therapies can help decrease mortality in a common and frequently fatal condition. Ascorbic acid and thiamine deficiency have been described in patients with sepsis and are thought to be due to reduced intake and increased metabolic demands.  Corticosteroids have had mixed results but seem to improve shock reversal in patients with septic shock based on best available evidence (Link is HERE). There have been a slew of RCTs evaluating this metabolic cocktail (vitamin C, thiamine, & corticosteroids) in recent months. Though biologically plausible, this treatment approach has not been shown to improve patient-oriented outcomes.

August 24, 2020

Background Information:

It is well documented throughout the literature that critically ill patients admitted to the intensive care unit (ICU) with acute kidney injury have a higher morbidity and mortality.1–4 Acute kidney injury may be complicated by acidosis, hyperkalemia and other major metabolic disorders and thus the initiation of renal replacement therapy (RRT) is generally considered beneficial in these patients.5 In patients without these complications, the timing of when to initiate RRT remains unclear and is frequently debated. There are three trials to know before getting to this one: ELAIN, IDEAL and AKIKI. The ELAIN trial was the only one of the three to show reduced 90-day mortality with early vs delayed initiation of RRT and was the smallest in sample size.6 The IDEAL trial concluded that early planned initiation of dialysis in stage V chronic kidney disease was not associated with improvement in survival or clinical outcomes.7 Lastly, the AKIKI trial found no significant difference with regard to mortality between an early and delayed strategy of RRT and actually saw an appreciable number of patients avert the need for RRT in a delayed strategy.8 The authors of the following study sought to investigate whether an accelerated strategy for RRT would result in lower risk of death from any cause at 90 days when compared to a standard strategy of RRT initiation.

August 3, 2020

 Background Information:

The care and management of patients with acute respiratory distress syndrome (ARDS) is complex and follows an inciting injury to the lungs. This constellation of symptoms is characterized by hypoxemia, diffuse lung inflammation, decreased lung compliance and noncardiogenic pulmonary edema typically seen as bilateral opacities on radiographical imaging.1  Slow progress has been made in developing effective ARDS treatments, among them are low tidal volumes which have been shown to improve mortality.2 Over time the development of guidelines such as the ARDSnet protocol have also helped provide a stepwise framework to treatment. However, there are a subset of patients who continue to remain hypoxic and refractory hypoxemia accounts for 10-15% of deaths in ARDS patients.3   The therapies typically implemented to correct refractory hypoxia include proning, inhaled pulmonary vasodilators, extracorporeal membranous oxygenation (ECMO), paralysis, recruitment maneuvers, unconventional ventilator modes and more.4–8 The following post and included infographics focus on the following therapies: Proning, Paralytics and (lung) Protection. It is important to note that regardless of the therapy, specializing care on an individual basis with a risk-benefit analysis is required to give patients the best possible chance at survival.

July 30, 2020

What is it HLH? Hemophagocytic Lymphohistiocytosis (HLH) is a rare and often fatal syndrome of uncontrolled and ineffective inflammatory response to a certain trigger. It is characterized by excessive proliferation of lymphocytes and macrophages (histiocytes), hence the name “lymphohistiocytosis”. This results in the overproduction of cytokines, responsible for many of the clinical features present in this syndrome. Familial, or genetic, HLH occurs as a result of a genetic mutation leading to impaired cytotoxic function. There have been several genetic mutations indicated in the development of HLH, including an association with congenital immunodeficiency syndromes, such as Chediak-Higashi, Griscelli and X-Linked Lymphoproliferative Syndromes. This form most often occurs within the first year of life (median age 8 months), with the majority of pediatric cases occurring <2 years of age, but can range from infancy to adulthood. Acquired HLH occurs in the setting of an underlying condition, such as immunodeficiency, malignancy, or autoimmune disease. When HLH is secondary to a predisposing autoimmune disease, it is referred to as macrophage activating syndrome (MAS).  Acquired HLH is the most common cause of this syndrome in adults, but this form can be seen in all ages. Overall, the syndrome is most often triggered by an infectious agent in an otherwise healthy person.

July 16, 2020

Background: The cornerstones of sepsis management continues to include early identification, early appropriate empiric antibiotics, definitive source control, and vasopressors to support end organ perfusion. There have been multiple studies looking at the co-administration of hydrocortisone, ascorbic acid, and thiamine (known as HAT therapy or the metabolic cocktail) to help reduce mortality and reverse shock. Despite the original Marik study showing an association between HAT therapy and a 31.9% overall decrease in mortality and a 3-fold decrease in time to vasopressor discontinuation in patients presenting with severe sepsis and septic shock, the mortality benefit has not been reproduced in subsequent randomized clinical trials.  Studies focused specifically on the use of corticosteroids have demonstrated reduced time on vasopressors in patients in septic shock.  The bigger question is does vitamin C and thiamine add anything additional to help improve mortality (The ORANGES Trial)?