is optimized. if the scvo2 is less than 70%, blood may be given to reach a hemoglobin of 10 g/dl and then inotropes are added until the scvo2 is optimized. in those with acute respiratory distress syndrome (ards) and sufficient tissue blood fluid, more fluids should be given carefully. crystalloid solution is recommended as the fluid of choice for resuscitation. albumin can be used if a large amount of crystalloid is required for resuscitation. crystalloid solutions shows little difference with hydroxyethyl starch in terms of risk of death. starches also carry an increased risk of acute kidney injury, and need for blood transfusion. various colloid solutions (such as modified gelatin) carry no advantage over crystalloid. albumin also appears to be of no benefit over crystalloids. blood products the surviving sepsis campaign recommended packed red blood cells transfusion for hemoglobin levels below 70 g/l if there is no myocardial ischemia, hypoxemia, or acute bleeding. in a 2014 trial, blood transfusions to keep target hemoglobin above 70 or 90 g/l did not make any difference to survival rates; meanwhile, those with a lower threshold of transfusion received fewer transfusions in total. erythropoietin is not recommended in the treatment of anemia with septic shock because it may precipitate blood clotting events. fresh frozen plasma transfusion usually does not correct the underlying clotting abnormalities before a planned surgical procedure. however, platelet transfusion is suggested for platelet counts below (10 × 109/l) without any risk of bleeding, or (20 × 109/l) with high risk of bleeding, or (50 × 109/l) with active bleeding, before a planned surgery or an invasive procedure. iv immunoglobulin is not recommended because its beneficial effects are uncertain. monoclonal and polyclonal preparations of intravenous immunoglobulin (ivig) do not lower the rate of death in newborns and adults with sepsis. evidence for the use of igm-enriched polyclonal preparations of ivig is inconsistent. on the other hand, the use of antithrombin to treat disseminated intravascular coagulation is also not useful. meanwhile, the blood purification technique (such as hemoperfusion, plasma filtration, and coupled plasma filtration adsorption) to remove inflammatory mediators and bacterial toxins from the blood also does not demonstrate any survival benefit for septic shock. vasopressors if the person has been sufficiently fluid resuscitated but the mean arterial pressure is not greater than 65 mmhg, vasopressors are recommended. norepinephrine (noradrenaline) is recommended as the initial choice. delaying initiation of vasopressor therapy during septic shock is associated with increased mortality. norepinephrine is often used as a first-line treatment for hypotensive septic shock because evidence shows that there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. norepinephrine raises blood pressure through a vasoconstriction effect, with little effect on stroke volume and heart rate. in some people, the required dose of vasopressor needed to increase the mean arterial pressure can become exceedingly high that it becomes toxic. in order to reduce the required dose of vasopressor, epinephrine may be added. epinephrine is not often used as a first-line treatment for hypotensive shock because it reduces blood flow to the abdominal organs and increases lactate levels. vasopressin can be used in septic shock because studies have shown that there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. however, vasopressin reduces blood flow to the heart, finger/toes, and abdominal organs, resulting in a lack of oxygen supply to these tissues. dopamine is typically not recommended. although dopamine is useful to increase the stroke volume of the heart, it causes more abnormal heart rhythms than norepinephrine and also has an immunosuppressive effect. dopamine is not proven to have protective properties on the kidneys. dobutamine can also be used in hypotensive septic shock to increase cardiac output and correct blood flow to the tissues. dobutamine is not used as often as epinephrine due to its associated side effects, which include reducing blood flow to the gut. additionally, dobutamine increases the cardiac output by abnormally increasing the heart rate. steroids the use of steroids in sepsis is controversial. studies do not give a clear picture as to whether and when glucocorticoids should be used. the 2016 surviving sepsis campaign recommends low dose hydrocortisone only if both intravenous fluids and vasopressors are not able to adequately treat septic shock. the 2021 surviving sepsis campaign recommends iv corticosteroids for adults with septic shock who have an ongoing requirement for vasopressor therapy. a 2019 cochrane review found low-quality evidence of benefit, as did two 2019 reviews. during critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. this has been termed critical illness–related corticosteroid insufficiency. treatment with corticosteroids might be most beneficial in those with septic shock and early severe ards, whereas its role in others such as those with pancreatitis or severe pneumonia is unclear. however, the exact way of determining corticosteroid insufficiency remains problematic. it should be suspected in those poorly responding to resuscitation with fluids and vasopressors. neither acth stimulation testing nor random cortisol levels are recommended to confirm the diagnosis. the method of stopping glucocorticoid drugs is variable, and it is unclear whether they should be slowly decreased or simply abruptly stopped. however, the 2016 surviving sepsis campaign recommended to taper steroids when vasopressors are no longer needed. anesthesia a target tidal volume of 6 ml/kg of predicted body weight (pbw) and a plateau pressure less than 30 cm h2o is recommended for those who require ventilation due to sepsis-induced severe ards. high positive end expiratory pressure (peep) is recommended for moderate to severe ards in sepsis as it opens more lung units for oxygen exchange. predicted body weight is calculated based on sex and height, and tools for this are available. recruitment maneuvers may be necessary for severe ards by briefly raising the transpulmonary pressure. it is recommended that the head of the bed be raised if possible to improve ventilation. however, β2 adrenergic receptor agonists are not recommended to treat ards because it may reduce survival rates and precipitate abnormal heart rhythms. a spontaneous breathing trial using continuous positive airway pressure (cpap), t piece, or inspiratory pressure augmentation can be helpful in reducing the duration of ventilation. minimizing intermittent or continuous sedation is helpful in reducing the duration of mechanical ventilation. general anesthesia is recommended for people with sepsis who require surgical procedures to remove the infective source. usually, inhalational and intravenous anesthetics are used. requirements for anesthetics may be reduced in sepsis. inhalational anesthetics can reduce the level of proinflammatory cytokines, altering leukocyte adhesion and proliferation, inducing apoptosis (cell death) of the lymphocytes, possibly with a toxic effect on mitochondrial function. although etomidate has a minimal effect on the cardiovascular system, it is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. the small amount of evidence there is, however, has not found a change in the risk of death with etomidate. paralytic agents are not suggested for use in sepsis cases in the absence of ards, as a growing body of evidence points to reduced durations of mechanical ventilation, icu and hospital stays. however, paralytic use in ards cases remains controversial. when appropriately used, paralytics may aid successful mechanical ventilation, however, evidence has also suggested that mechanical ventilation in severe sepsis does not improve oxygen consumption and delivery. source control source control refers to physical interventions to control a focus of infection and reduce conditions favorable to microorganism growth or host defense impairment, such as drainage of pus from an abscess. it is one of the oldest procedures for control of infections, giving rise to the latin phrase ubi pus, ibi evacua, and remains important despite the emergence of more modern treatments. early goal directed therapy early goal directed therapy (egdt) is an approach to the management of severe sepsis during the initial 6 hours after diagnosis. it is a step-wise approach, with the physiologic goal of optimizing cardiac preload, afterload, and contractility. it includes giving early antibiotics. egdt also involves monitoring of hemodynamic parameters and specific interventions to achieve key resuscitation targets which include maintaining a central venous pressure between 8–12 mmhg, a mean arterial pressure of between 65 and 90 mmhg, a central venous oxygen saturation (scvo2) greater than 70% and a urine output of greater than 0.5 ml/kg/hour. the goal is to optimize oxygen delivery to tissues and achieve a balance between systemic oxygen delivery and demand. an appropriate decrease in serum lactate may be equivalent to scvo2 and easier to obtain. in the original trial, early goal-directed therapy was found to reduce mortality from 46.5% to 30.5% in those with sepsis, and the surviving sepsis campaign has been recommending its use. however, three more recent large randomized control trials (process, arise, and promise), did not demonstrate a 90-day mortality benefit of early goal-directed therapy when compared to standard therapy in severe sepsis. it is likely that some parts of egdt are more important than others. following these trials the use of egdt is still considered reasonable. newborns neonatal sepsis can be difficult to diagnose as newborns may be asymptomatic. if a newborn shows signs and symptoms suggestive of sepsis, antibiotics are immediately started and are either changed to target a specific organism identified by diagnostic testing or discontinued after an infectious cause for the symptoms has been ruled out. despite early intervention, death occurs in 13% of children who develop septic shock, with the risk partly based on other health problems. those without multiple organ system failures or who require only one inotropic agent mortality is low. other treating fever in sepsis, including people in septic shock, has not been associated with any improvement in mortality over a period of 28 days. treatment of fever still occurs for other reasons. a 2012 cochrane review concluded that n-acetylcysteine does not reduce mortality in those with sirs or sepsis and may even be harmful. recombinant activated protein c (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high apache ii score), where it was thought to confer a survival benefit. however, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality. it was removed from sale in 2011. another medication known as eritoran also has not shown benefit. in those with high blood sugar levels, insulin to bring it down to 7.8–10 mmol/l (140–180 mg/dl) is recommended with lower levels potentially worsening outcomes. glucose levels taken from capillary blood should be interpreted with care because such measurements may not be accurate. if a person has an arterial catheter, arterial blood is recommended for blood glucose testing. intermittent or continuous renal replacement therapy may be used if indicated. however, sodium bicarbonate is not recommended for a person with lactic acidosis secondary to hypoperfusion. low-molecular-weight heparin (lmwh), unfractionated heparin (ufh), and mechanical prophylaxis with intermittent pneumatic compression devices are recommended for any person with sepsis at moderate to high risk of venous thromboembolism. stress ulcer prevention with proton-pump inhibitor (ppi) and h2 antagonist are useful in a person with risk factors of developing upper gastrointestinal bleeding (ugib) such as on mechanical ventilation for more than 48 hours, coagulation disorders, liver disease, and renal replacement therapy. achieving partial or full enteral feeding (delivery of nutrients through a feeding tube) is chosen as the best approach to provide nutrition for a person who is contraindicated for oral intake or unable to tolerate orally in the first seven days of sepsis when compared to intravenous nutrition. however, omega-3 fatty acids are not recommended as immune supplements for a person with sepsis or septic shock. the usage of prokinetic agents such as metoclopramide, domperidone, and erythromycin are recommended for those who are septic and unable to tolerate enteral feeding. however, these agents may precipitate prolongation of the qt interval and consequently provoke a ventricular arrhythmia such as torsades de pointes. the usage of prokinetic agents should be reassessed daily and stopped if no longer indicated. prognosis sepsis will prove fatal in approximately 24.4% of people, and septic shock will prove fatal in 34.7% of people within 30 days (32.2% and 38.5% after 90 days). lactate is a useful method of determining prognosis, with those who have a level greater than 4 mmol/l having a