[Music] the definition of sepsis is a life-threatening organ dysfunction caused by a disregulated host response to an infection in sepsis the body's response to the infection ends up causing damage to the organs eventually leading to failure of the organs and death it's important to know that not all patients with infections have sepsis but any infection has the potential to lead to sepsis in general the organ dysfunction from sepsis results from increased metabolic demands combined with insufficient circulation this means increased demand and a reduction in Supply it's normal for an inflammatory response to be generated towards an infection but this tends to be localized it includes the innate response release of cyto mines and recruitment of inflammatory cells like neutrophils and macras in sepsis however this response is disregulated which doesn't necessarily mean excessive but it is enough to impair normal functioning of the body we said that circulation is compromised in sepsis and this is where knowing some of the physiology makes sepsis much easier to understand the components that affect effect blood circulation are the cardiac output given by the stroke volume multiplied by heart rate and the systemic vascular resistance which is the resistance blood Encounters in the blood vessels also known as afterload when these two are multiplied together they roughly provide the mean arterial pressure which is a major determinant of perfusion and therefore delivery of blood to tissues one of the main featur features of the disregulated immune response is release of nitric oxide which is a vasod dilator producing systemic vasod dilation involving both arteries and veins the problem with this is less Venus return of blood known as preload and so A reduced stroke volume and therefore cardiac output in an effort to maintain the cardiac output the heart must therefore beat faster and in the early stages Tech to accomplish this however left untreated it will eventually fail the Vaso dilation also affects the arteries reducing systemic vascular resistance put together this means that the mean arterial pressure is reduced and this lower blood pressure can therefore result in reduced perfusion to organs and when hypotension is severe enough it is defined as septic shock which is a form of distributive shock shock on top of this nitric oxide can also reduce myocard oy contractility directly thereby reducing the ability of the heart to pump blood effectively and sepsis features increased vessel permeability so fluid can extravasate and further reduce the circulating volume there is also an increase in procoagulant factors and a reduction in anti-coagulants which generates a coagulopathy ultimately this results in formation of thrombi particularly in the smaller vessels further impairing blood flow through the capillaries to the tissues red blood cells can even become less flexible and so cannot as easily deliver oxygen to the tissues so this can mean even if an organ is perused delivery of nutrients and oxygen can still be impaired in most cases a bacterial infection is the source with stail coccus orus ponus and eoli being isolated in over 50% of cases but it can be due to viruses fungi and parasites as well lower respiratory tract infections like pneumonia are the most common primary source of infection followed by the abdomen and urinary tract but can be from any source and in the elderly the urinary tract is the most common source sepsis is sometimes referred to as septicemia which means poisoning of the blood but the blood does not necessarily need to be contaminated to cause sepsis but is infected in around 15% of cases in up to 1/3 of cases no source of infection is found certain factors increase the likelihood that an infection will lead to sepsis for example older age above 65 years or those who are very young or an immuno compromised State like the presence of malignancy anti-cancer medication or steroid use others include recent surgery or invasive procedures indwelling catheters and lines diabetes meletus or hemodialysis alcohol or drug use and even pregnancy sepsis has an extremely varied presentation usually featuring some source of infection with its own features for example a cough in pneumonia a fever is usually present but it does not have to be for example in the elderly this may be absent and remember that hypothermia may also be a manifestation of sepsis other possible features include Tachi cardia tpia altered mental status or slurred speech and a reduction in urine output overall it is a clinical diagnosis based on the presence of an infection and organ dysfunction the S criteria or systemic inflammatory response syndrome criteria were previously used which included two or more of the S criteria examples of which include a temperature above 38.3 de or below 36 tachicardia tpia hypoglycemia without diabetes altered mental status or a high or low white blood cell count however more recently there has been a shift away from using these criteria and instead using the sofa score which stands for sequential organ failure assessment this was devised for use in the Intensive Care Unit to determine the extent of organ failure in sepsis patients It generally requires a score of two or more or a change of two to indicate organ dysfunction and therefore Define sepsis this score is based on six parameters reflecting the cardiovascular resp spiratory renal and liver function the conscious level and coagulation initial scores of 10 or higher indicate a 50% mortality while scores of 14 or above are associated with a 95% mortality a condensed version of the score called quick suur or Q suur including teyia altered mental status or reduced conscious level and systolic blood pressure below 100 mm of mercury with two out of three of these indicating the need for further investigation as it highlights potential sepsis patients with a greater risk of adverse outcomes for septic shock the definition is sepsis with coexisting persistent hypotension requiring vasor presses to maintain a mean arterial pressure above 65 and a serum lactate above two there is a low threshold to begin treating for sepsis the initial management of suspected sepsis is based on six steps known as the sepsis six these are divided into three things to give and three things to take the three to take are blood cultures which ideally are before antibiotics are given but should not delay delivery of antibiotics Bloods including a lactate level and the urine output needs to be measured most reliably through insertion of a urinary catheter generally empirical intravenous antibiotics are given as well as intravenous fluid the fluids are crucial in counteracting the physiological effect of sepsis because it helps to restore the preload and ultimately the circulation oxygen is also generally given additional measures can include vasor presses followed by ionotropes in patients not maintaining adequate blood pressure with IV fluid resuscitation