Francesca Rubulotta

Predisposition, insult/infection, response, and organ dysfunction: A new model for staging severe sepsis.

Objective: To generate and validate an initial version of the predisposition, insult/infection, response, and organ dysfunction (PIRO) staging model for risk stratification in severe sepsis. The goal was to create distinct levels of mortality risk within each of the four categories (P, I, R, and O), and that these risk levels would be meaningful in terms of prediction independent of the other categories. Design: Retrospective analysis using a statistical model utilizing two large, global databases of patients with severe sepsis. Setting and Patients: Database #1: Placebo-treated patients from a phase III clinical trial of patients with severe sepsis (PROtein C Worldwide Evaluation in Severe Sepsis [PROWESS], 840 patients). Database #2: Global severe sepsis registry performed in 276 intensive care units in 37 countries (PROmoting Global Research Excellence in Severe Sepsis [PROGRESS], 10,610 patients). Interventions: None. Methods: Classification and regression trees were used to classify patients and derive a scoring system from the PROWESS and PROGRESS databases with internal validation. Regression tree parameters included Chi-square tests and a minimum of five patients per node. The risk levels were done in a stepwise manner, adjusting for the previous categories. Initially, the predisposition scoring was developed, and subsequently, the infection scoring was then developed after adjusting for the predisposition levels, and so on. Logistic regression analyses, odds ratios, and area under the receiver operator characteristic curve were used to evaluate the scoring systems. Measurements and Main Results: Each of the four PIRO components had similar odds ratios in multivariable logistic regressions. In PROWESS, the correlation of the PIRO total score and in-hospital mortality rates was 0.974 (p < 0.0001), and in PROGRESS, the correlation of the PIRO total score and hospital mortality rates was 0.998 (p < 0.0001). Conclusions: PIRO can develop into an effective model for staging severe sepsis, seems to be predictive of mortality, and may be useful in future sepsis research.

An international survey: Public awareness and perception of sepsis

Background:Sepsis is a common cause of death throughout the world. Early treatment improves outcome; however, treatment may be delayed if the patient does not present himself/herself for medical care until late in the disease process. Lack of knowledge about the syndrome may contribute to delay in presenting for medical care. However, we need to acknowledge the complexity of sepsis. General awareness of sepsis by the public may increase political pressure for research funding. Increased public awareness of acute myocardial infarction has contributed to reduced mortality over the last 50 yrs. This example provides a rationale for future efforts to increase the public awareness of sepsis. Objective:The survey was designed to gain insight into public perceptions and attitudes regarding sepsis. Design:Prospective, international survey performed using structured telephone interviews. Subjects:A total of 6021 interviewees, 5021 in Europe and 1000 in the United States. Measurements and Main Results:In Italy, Spain, the United Kingdom, France and the United States, a mean of 88% of interviewees had never heard of the term “sepsis”. In Germany 53% of people knew the word sepsis. In Italy, Spain, United Kingdom, France, and United States, of people who recognized the term sepsis, 58% did not recognize that sepsis is a leading cause of death. Conclusions:There is poor public awareness about the existence of a syndrome known as sepsis. Results of this questionnaire underscore the challenges in early management and treatment of infected patients at risk for developing sepsis syndrome.

Recommendations for ulcer prophylaxis in the treatment of patients with severe sepsis and septic shock: a dog chasing its tail?

The guidelines for the treatment of patients with severe sepsis and septic shock, presented in 2004, take into consideration the problem of gastro-protective treatments [1]. The indications provided by this document prompt the use of agents for stress ulcer prophylaxis in all patients with severe sepsis and septic shock [1, 2], and mark this recommendation as gradeA, according to the methodology suggested by Sackett et al. [3]. Treatment with histamine2 (H2) inhibitors, aimed at avoiding gastrointestinal bleeding, is considered “more efficacious than sucralfate”, and a direct comparative study between H2 inhibitors and proton pump inhibitors has never been carried out [1, 2]. Although the authors admit that specific studies on septic patients have never been performed, the literature [4, 5, 6, 7] demonstrates the benefit of prophylaxis on a vast population of critically ill patients, including a number of septic patients [1]. Critical appraisal of all references that represent the evidence for the recommendation made for stress ulcer prophylaxis in patients with severe sepsis and septic shock [1] shows that [4, 5, 6, 7]:

Second International Conference on Rapid Response System and Medical Emergency Team, 28–30 June 2006, Pittsburgh, PA, USA

The 2nd International Conference on Rapid Response System (RRS) & Medical Emergency Team (MET) took place at the Pittsburgh Convention Center in June 2006. The conference was attended by 450 people coming from seven different countries. The majority of the participants were Americans. However, US attendees came from 32 different States. The Michael DeVita, MD from the University of Pittsburgh was the Program Chairman with Drs. Rinaldo Bellomo from Melbourne and Ken Hillman, from Sydney, as course co-Directors. The program included numerous oral presentations, workshops, pro-con debates, tutorials, panel discussion and posters presentations. In attendance were patient safety officers, hospitalists and hospital based physicians, critical care medicine physicians, hospital administrators, nursing directors, critical care nurses, general ward nursing staff, respiratory care directors, and therapists, and finally resuscitation and clinical outcomes researchers from around the country.

Letter to Servillo et al.

Dear Sir: With respect to the contribution of Dr. Servillo and Dr. Striano [1], we would like to acknowledge their methodology; nevertheless, we ultimately believe that legal issues have significantly changed medical practice and societal values over the past 30 years all over the world, not just in Italy. Historical cases such as Quinlan (1976), Cruzan (1990), Bland (1993), Gluckesberg (1997), Vacco (1997), Schiavo (2005) and Welby (2007) seem to incorporate the leading principles enforced by laws. Nevertheless, different social and legal impact hides the withholding and withdrawal of mechanical ventilation when compared to nutrition and hydration. Looking at similar landmark cases dealt with in the high courts of various countries, gives insight into differing EOL attitudes. In the US in 1990 the Supreme Court embraced in the Cruzan case the ‘‘liberty interest of refusing lifesustaining treatments’’ proclaiming ‘‘the right to die’’ [2]. Prior to this case, all decisions to terminate life support were considered worldwide as unethical and unlawful. Nowadays, the withholding or withdrawal of life support is legally justified by the principles of informed consent and informed refusal, both of which have strong roots in most countries’ common law [2]. The concept of autonomous choice is usually not directly applicable to ICU patients since fewer than 5% are able to communicate when treatment decisions are being made [3]. As US law is intended to support the principle of autonomous choice under all circumstances, advance health care directives, health care proxies, or the choice of proxy based on a hierarchical list have all received legal recognition [2]. In the UK in 1993 Tony Bland was a 21-year-old boy in a persistent vegetative state since 1989. The dilemma in this scenario involved not only the need for intravenous infusion and nutrition but also the use of antibiotics. This was not deemed to constitute a penal or civil crime [3–6]. Cruzan and Bland are similar cases, although the US and the British Courts had two different attitudes, the first focused on patients’ wishes, the second on the medical judgment. In Italy, on 18 January 2005 Eluana Englaro reached her 13th year in persistent vegetative state. This young woman had a tragic car accident with irreversible cerebral damage. The case is again similar to that of Cruzan and Bland. However, the decision of the Supreme Court in Milan was very different. Italian magistrates did not allow stopping fluids or nutrition to a patient in persistent vegetative state, who is still alive. Nowadays this case is discussed and a definitive legal conclusion has not been declared. These three legal cases are highly representative of divergences between North America, North and South Europe [4–6]. There is a clear dichotomy between the North American approach to EOL decision making and that used in European countries, particularly those in the South [4–6]. The former is seen as favouring patient ‘‘autonomy’’ leading to patient/surrogate-directed decision making and, the latter ‘‘medical judgment’’, allowing physician-directed EOL decision making [4–6]. European physicians perceive a sort of ‘‘Hippocratic commitment’’ to their patient. Similar clinical cases may have different legal interpretations, indicating strong differences between national laws. European and Italian IC physicians have increasingly understood the importance of involving the family in the EOL discussion, and of writing EOL decisions in the patient record as commented by Servillo et al. However, moving suddenly towards a US autonomy model may cause a kind of hidden embarrassment in European physicians, giving the feeling of refusing to accomplish a doctor’s institutional duty, which is caring and therefore deciding for the patient’s best interest.

Outcomes in severe sepsis and patients with septic shock do not matter! PIRO is a score to treat severe septic and septic shock patients not to measure outcomes.

present, whereas 50% of the wholebody selenium is stored in the skeletal muscle (4), i.e., a pool characterized by slow turnover and hence probably requiring a prolonged period of selenium substitution to allow refilling. However, little is known about the distribution, and probably also redistribution, of selenium during systemic inflammation. Furthermore, no data are available about the metabolism and distribution of exogenously administered selenium in critically ill patients. Last, selenium toxicity is linked to the cumulative dose of ingested selenium (5). Therefore, before the widespread adoption of prolonged selenium supplementation in critically ill patients can be advocated, further clinical trials are required that specifically address the safety of high-dose and prolonged selenium supplementation. Dr. Rex received speaking and consulting fees from biosyn Arzneimittel. The Department of Anesthesiology, University Hospital of the RWTH Aachen, has received funding from Biosyn, Germany, as financial support for conducting the clinical trial that is presented in the manuscript. The remaining authors have not disclosed any potential conflicts of interest.