Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Resuscitation 2015-the new guidelines

Sudden cardiac arrest is amongst the major causes of death in industrialized countries. The patient's prognosis however is still very serious. Because diagnosis and therapy in medicine constantly undergo further development, guidelines on cardiopulmonary resuscitation are updated und published frequently, to ensure that every patient receives the best state of the art medical therapy and consequently has the best chances to survive. On October 15, 2015, the new guidelines on cardiopulmonary resuscitation were published. This article gives a short summary of the most important changes

Therapeutic hypothermia in 2015. Influence of the TTM study on the intensive care procedure after cardiac arrest

In the 1960s, Peter Safar et al. postulated the benefit of postcardiac arrest hypothermia after successful cardiopulmonary resuscitation (CPR). However, therapeutic hypothermia postCPR did not become a standard procedure until the first few years of the new millennium. Various noninvasive and invasive cooling methods are available. Generally, more invasive cooling methods are more effective-but also tend to involve more complications. Furthermore, invasive measures need more time and thus may be instituted late in the postCPR process, delaying the cooling efforts in the initial phase. There is ongoing controversy about when best to commence cooling. Recent studies of initial out-of-hospital cooling did not show any benefit for the patients compared to starting cooling in the hospital. The exact target temperature is the subject of multiple ongoing discussions. A recent study showed no disadvantage of cooling to 36 aintegral compared to 33 aintegral, which is in the widely accepted standard target temperature range of 32-34 aintegral. Nevertheless, cooling to 32-34 aintegral according to the 2010 guidelines is still the accepted standard procedure unless and until new studies generate more evidence. The European Resuscitation Council has given advance notice of a statement on the optimal target temperature in the near future. Finally, large registry studies have demonstrated the benefit of combining postCPR hypothermia with early percutaneous cardiac interventions (PCI) in acute coronary syndromes, which are often a cause of cardiac arrest. Transport of patients after CPR to specialized postcardiac arrest centres with the possibility of acute PCI and cooling, comparable to the transfer of multiple trauma patients to trauma centres, may be beneficial