https://journal.chestnet.org/article/S0012-3692(16)38415-X/pdf

Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis

Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

Background Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. Methods We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Results Of the 263 enrolled patients, 130 were ...

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Multiple organ failure (MOF) is a major cause of morbidity and mortali ty in the critically ill patient. Emerging in the 1970s, the concept of MOF was linked to modern developments in intensive care medicine [1]. Although an uncontrolled infection can lead to MOF [2], such a phenomenon is not always found. A number of mediators and the persistence of tissue hypoxia have been incriminated in the development of MOF [3]. The gut has been cited as a possible \"moto r \" of MOF [4]. Nevertheless, our knowledge regarding the pathophysiology of MOF remains limited. Furthermore, the development of new therapeutic interventions aiming at a reduction of the incidence and severity of organ failure calls for a better definition of the severity of organ dysfunction/failure to quantify the severity of illness. Accordingly, it is important to set some simple but objective criteria to define the degree of organ dysfunction/failure. The evolution of our knowledge of organ dysfunction/failure led us to establish several principles: 1. Organ dysfunction/failure is a process rather than an event. Hence, it should be seen as a continuum and should not be described simply as \"present\" or \"absent~' Hence, the assessment should be based on a scale. 2. The time factor is fundamental for several reasons: (a) Development and similarly resolution of organ failure may take some time. Patients dying early may not have time to develop organ dysfunction/failure. (b) The time course of organ dysfunction/failure can be mult imodal during a complex clinical course, what is sometimes referred to as a \"multiple-hit\" scenario. (c) Time evaluation allows a greater understanding of the disease process as a natural process or under the influence of therapeutic interventions. The collection of data on a daily basis seems adequate. 3. The evaluation of organ dysfunction/failure should be based on a limited number of simple but objective variables that are easily and routinely measured in every institution. The collection of this information should not impose any intervention beyond what is routinely performed in every ICU. The variables used should as much as possible be independent of therapy, since therapeutic management may vary from one institution to another and even from one patient to another (Table 1). Until recently, none of the existing systems describing organ failure met these criteria, since they were based on categorial definitions or described organ failure as present or absent [5-7] . The ESICM organized a consensus meeting in Paris in October 1994 to create a so-called sepsis-related organ failure assessment (SOFA) score, to describe quantitatively and as objectively as possible the degree of organ dysfunction/failure over time in groups of patients or even in individual patients (Fig. 1). There are two major applications of such a SOFA score: 1. To improve our Understanding of the natural history of organ dysfunction/failure and the interrelation between the failure of the various organs.

The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.

The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway1–8. The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .

The L-Arginine-Nitric Oxide Pathway

The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide (.N = O) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between .N = O production and the hyperdynamic state. high plasma levels of NO2-/NO3- (the stable end products of .N = O) were observed in septic patients (p less than 0.02). Low SVR and high endotoxin levels were associated with high NO2-/NO3- values (p = 0.029, p = 0.002). Changes in .N = O levels may mediate the vasodilation seen in sepsis. Low NO2-/NO3- levels were observed in trauma patients (p less than 0.001) and remained low even in the presence of sepsis (p = 0.001).

Nitrogen oxide levels in patients after trauma and during sepsis.

OBJECTIVE To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). DESIGN A prospective, randomized, double-blind, multicenter trial. SETTING ICUs in eight different hospitals. PATIENTS Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age ( or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). INTERVENTIONS Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. MEASUREMENTS AND MAIN RESULTS Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. CONCLUSIONS Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections.

Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

Objective. —This review of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) provides an overview of a common but complex problem found in critically ill patients. It emphasizes definitions, common clinical patterns, metabolic responses, and pathophysiological changes. A brief discussion of treatment concepts is also included. Data Sources. —Data for this review were gathered from peer-reviewed journals, review articles by experts in SIRS/MODS, and selections from reference volumes written on SIRS/MODS. Study Selection. —Reference selections were chosen on the basis of quality of research. Peer-reviewed journals were given primary consideration. Those review articles cited were felt to be essential to any discussion of SIRS/MODS. Data Extraction. —Where possible, randomized, controlled, prospective studies were reviewed and conclusions used in this overview of SIRS/MODS. Conclusion. —Our ability to care for critically ill patients has led to a new problem, SIRS and eventually MODS, which may become progressive organ failure and death. Unfortunately, these conditions are extremely frequent and carry high mortality rates. Increased oxygen consumption demands highlight the physiological response. The typical metabolic responses are characterized by hyperglycemia and accelerated protein catabolism. Unrecognized perfusion deficits, an uncontrolled septic focus, a persistent source of inflammation, or injured tissue is commonly present with SIRS/MODS and should be corrected. Restoration of oxygen transport and metabolic support are also important components of treatment. The cause of SIRS/MODS is complex and not fully understood, but multiple mediators and stimulated macrophages likely are important components and areas where treatment may well be focused. (JAMA. 1994;271:226-233)

https://jamanetwork.com/journals/JAMA/articlepdf/362717/jama_271_3_043.pdf

Multiple Organ Failure Syndrome in the 1990s: Systemic Inflammatory Response and Organ Dysfunction

Applied Nutrition in ICU Patients* A Consensus Statement of the American College of Chest Physicians

The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb-salvage arterial surgery was tested Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3) The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 005), less postoperative cardiac morbidity (p less than 005), and less early graft thrombosis (p less than 005) than the control group The overall study mortality rate was 34%, with a mortality rate of 95% in the control group and 15% in the PA catheter groups There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 005) In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome

Frank B. Cerra

Papers

Nitrogen oxide levels in patients after trauma and during sepsis.

Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

Multiple Organ Failure Syndrome in the 1990s: Systemic Inflammatory Response and Organ Dysfunction

Applied Nutrition in ICU Patients* A Consensus Statement of the American College of Chest Physicians

Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial.