Evidence based medicine can complement other foundation disciplines in intensive care. This is the first article in a series entitled "Evidence Based Critical Care Medicine" which will demonstrate how this approach can be used at the bedside.
Scoring systems to describe organ dysfunction or predict survival are widely used in critically ill patients. Such scores can facilitate description of patient populations, for example for inclusion in clinical trials, and to enable comparison between intensive care units (ICUs) or within the same ICU over time. While early systems focused primarily on survival prediction or the presence or absence of organ failure, recent years have seen the development of newer models able to describe the evolution of individual and multiple organ dysfunction. This review will discuss the development and application of such systems in the ICU.
We developed and validated models to predict 1- and 2-week risk of non-elective hospitalization (NEH) and sepsis hospitalization following outpatient clinic, emergency department treat and release (EDTR), or hospitalization encounters. We employed data from 4,488,579 adults with 1,481,430 hospital, 6,035,296 EDTR, and 86,013,893 clinic encounters. Predictors included administrative, clinical (laboratory tests, vital signs), utilization, and prescription pattern data. We employed 2012-2018 data for development and 2019 data for validation. In validation datasets, discrimination (area under the receiver operator characteristic curve) ranged from 0.687 for NEH within 1 week of hospital discharge to 0.904 for sepsis hospitalization within 2 weeks of clinic visits. At a sensitivity of 40%, numbers needed to evaluate (NNE) ranged from 4.3 for NEH within 2 weeks of hospitalization to 45 for sepsis hospitalization within 1 week of a clinic visit. Our models have potentially clinically actionable NNEs and could support clinical programs for the prevention of short-term hospitalizations and sepsis.
info:eu-repo/semantics/published
Severe sepsis and septic shock are common in the critically ill patient and account for considerable morbidity and mortality not to mention the high associated costs. Advances in our understanding of sepsis pathophysiology and in the important link between the inflammatory response to sepsis and activation of coagulation led to the development and licensing of the first ever, specific, immunomodulatory anti-sepsis drug. Drotrecogin alfa (activated), a recombinant version of activated protein C, was shown in a large randomized controlled clinical trial to reduce mortality rates from 30.8% in the placebo group to 24.7% in the treatment group, which equated to one additional life saved for every 16 patients treated. Vasopressor requirements and duration of mechanical ventilation were also reduced. Apart from an expected increased risk of severe bleeding, mostly associated with interventions, drotrecogin alfa (activated) was not associated with any other adverse reactions. In this article, I will briefly summarize the events leading to the development of drotrecogin alfa (activated) including aspects of sepsis epidemiology and pathophysiology and the results of early animal and clinical studies. The results of the large multicenter phase III PROWESS study will then be reviewed, along with results from subsequent open-label studies. Finally, I will focus on the key side effect issue with drotrecogin alfa (activated), that of increased bleeding, drawing data from the available clinical studies, and highlighting the contraindications and precautions when prescribing this drug.
