Sepsis is defined as a systemic inflammatory response associated with bacterial infection that encompasses a series of clinical events, which play a vital role in the progression of sepsis to severe septic shock and influence the development of multiple organ dysfunction syndrome, including respiratory distress, hypotension, cardiac arrhythmias, bleeding complications, and low or absent urine output. As each successive organ fails, mortality dramatically increases.

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In 2012, there were over 1,665,000 patients diagnosed with sepsis in the United States. Mortality continues to be as high as 50%, directly linked to delayed diagnosis and initiation of treatment. In fact, sepsis is the number one cause of death in the ICU and the 11th-leading cause of death in the United States, accounting for 2% of hospital admissions but 17% of in-hospital deaths. American hospitals spend approximately $20 billion each year combating sepsis.

For many years, there have been variations in how sepsis is treated worldwide. In an effort to decrease the mortality associated with sepsis, 68 medical experts, representing 30 different international organizations, met to draft new sepsis guidelines. The goal was to develop universal recommendations that direct global medical teams to utilize evidence-based practice (EBP) interventions to reduce sepsis-related mortality.

The international experts evaluated current and proposed interventions, reviewed 25,000 patient records from 186 hospitals, and made recommendations based on the quality of evidence that clearly showed improvement in the clinical outcomes of patients with sepsis. The recommendations were rated on the Grading of Recommendations Assessment, Development, and Evaluation system-known as the GRADE system-to guide the assessment of EBP research from high to very low and determine the strength of recommendations as strong or weak. Recommendations were classified into three groups: 1. those directly targeting severe sepsis, 2. those targeting the general care of the critically ill patient and considered high priority in severe sepsis, and 3. pediatric considerations.

Figure. Continuous monitoring is essential; even with aggressive therapy, patients may progress to organ failure.

The international guidelines for the management of severe sepsis and septic shock provide healthcare teams with clear, time-sensitive, EBP interventions to diagnose and treat the patient with confirmed sepsis or septic shock. In this article, we'll break down these interventions into care bundles.

Diagnosis care bundle

NEW focus: Utilize serum procalcitonin (PCT) levels for early diagnosis of sepsis leading to early administration of antibiotics within 1 hour for patients suspected of sepsis and aggressive administration of antibiotics for patients with suspected septic shock.

When providing care for a patient exhibiting symptoms of sepsis, obtain all serum, sputum, urine, and wound cultures immediately to help identify the source of the infection before initiating antibiotic therapy. Ensure that the cultures are collected using appropriate sterile technique to prevent contamination of the sample and an inaccurate result. Obtaining these cultures shouldn't delay the administration of antibiotic agents longer than 45 minutes.

A new recommendation is that a minimum of two sets of blood cultures (anaerobic and aerobic) should be obtained to provide accurate identification of the specific bacterial organism causing the infection before administering antibiotic medication. At least one of the blood culture samples should be obtained percutaneously and one sample should be obtained through each vascular access device, unless the vascular device was inserted less than 48 hours earlier. If more than one culture result reveals the presence of the same organism, the likelihood that the organism is causing the sepsis is confirmed. Two blood cultures obtained from different locations are necessary to maximize the chances of obtaining a positive culture result.

It's imperative that the source of the infection be identified quickly to allow the healthcare team to customize the antibiotic treatment regimen and reduce complications and mortality. If the source of the infection is identified as an abscess, the healthcare team should select the most effective intervention that's associated with the least amount of physiologic risk. For example, if the source of the infection is an infected wound, the healthcare team may elect to perform a percutaneous needle aspiration rather than surgical drainage of an abscess. If intravascular or medical devices are suspected as the potential source of the sepsis, they should be removed immediately and replaced under sterile conditions.

The guidelines now recommend utilizing a serum PCT level if the patient exhibits clinical symptoms of sepsis. (See "The Predictive Value of Procalcitonin in Sepsis" on page 52 for more information.) PCT is a serum lab test utilized to evaluate if a patient has developed a systemic bacterial infection causing sepsis or septic shock, diagnose bacterial sepsis in the very early stages, and differentiate a bacterial infection from a viral or parasitic infection.

Normal serum PCT levels for healthy individuals are less than 0.05 ng/mL. A serum PCT level of 0.05 to 1.9 ng/mL is indicative of a localized infection. As the number trends higher, the patient is trending toward sepsis and septic shock. A serum PCT level of greater than 2 ng/dL is indicative of sepsis; greater than 10 ng/dL is indicative of septic shock.

Figure. No caption available.

Table Common lab findings in sepsis.

The international experts found that PCT monitoring can prevent the healthcare team from administering antibiotics for what's later determined to be a viral; parasitic; or mild, localized bacterial infection, which can predispose the patient to methicillin-resistant Staphylococcus aureus infection.

Initial care bundle

Focus: When evaluating a patient with suspected sepsis, begin with the ABCs-airway, breathing, and circulation.

You may identify a patient with sepsis by his or her clinical presentation or symptoms such as fever, tachycardia, localized erythema, low urine output (less than 0.5 mL/kg/hr for at least 2 hours despite adequate fluid resuscitation), hypotension, or shortness of breath. Assess for impaired oxygenation and hemodynamic instability.

Clinical signs of impaired oxygenation are low oxygen saturation levels, an SvO₂ level below 70%, a PaO₂ level below 60 mm Hg, a serum lactate level above 1, lethargy, confusion, poor concentration, agitation, and unresponsiveness.

Clinical signs of hemodynamic instability are a systolic BP below 90 mm Hg, a mean arterial pressure (MAP) below 65 mm Hg, a heart rate below 50 or above 120, or the presence of dysrhythmias on the ECG monitor.

The guidelines recommend that healthcare teams monitor SvO₂ because it's the most accurate way to assess for adequate oxygenation. The SvO₂ level should be maintained above 70% to ensure that the patient is adequately oxygenating.

Fluid management bundle

NEW focus: Administer fluid to achieve a central venous pressure (CVP) between 8 and 12 mm Hg.

Patients with sepsis may become hypotensive as a result of systemic circulatory vasodilation and fluid shifting out of the blood vessels. If the patient is hypotensive, assess the CVP and begin fluid resuscitation; vasopressor therapy may be started if the hypotension doesn't resolve.

The goal is a CVP of 8 to 12 mm Hg. If the CVP is less than 8 mm Hg, the new guidelines recommend that an I.V. fluid challenge of 20 mL/kg crystalloid solution should be administered over a 5- to 10-minute period. If the patient exhibits clinical signs of impaired perfusion to tissues, the crystalloid I.V. fluid can be increased to more than 30 mL/kg. Auscultate lung sounds to assess for increasing fluid or severe crackles in the lung fields that occur simultaneously with lowered oxygen levels. If the lung sounds are stable, the bolus is repeated every 20 to 30 minutes until the CVP reaches 8 mm Hg.

When the CVP is below 8 mm Hg, the new guidelines strongly discourage the administration of colloid I.V. fluids, such as hydroxyethyl starch, because research studies have directly shown an increase in mortality with fluid resuscitation with hydroxyethyl starch versus crystalloid solution for patients experiencing septic shock.

Instead, albumin is recommended to treat severe hypotension in patients with severe sepsis and septic shock for whom large amounts of crystalloid fluids are required. The goal of fluid administration in septic shock is to replace the fluid that has shifted out of the vessel and restore BP in the presence of the profound vasodilation that accompanies most shock states.

Unresponsive septic shock is defined as hypotension that persists despite fluid resuscitation and vasopressors for more than 60 minutes. The new guidelines recommend that corticosteroid therapy should only be used if the patient is in unresponsive septic shock or for children with adrenal insufficiency. In those circumstances, an I.V. corticosteroid dose of 200 mg/day is recommended.

The guidelines recommend conservative fluid administration for patients with established acute respiratory distress syndrome (ARDS) who don't have evidence of tissue hypoperfusion (systolic BP less than 90 mm Hg, MAP less than 60 mm Hg, mental status changes, cyanotic distal extremities, urine output less than 30 mL/hr, and rising serum creatinine).

Remember that patients may have underlying cardiac disease before admission that may predispose them to pulmonary hypertension, cardiac arrhythmias, or myocardial infarction if excess fluid volume is added to their circulatory system.

Vasopressor therapy bundle

Focus: If needed, administer vasopressor therapy to maintain a MAP of at least 65 mm Hg.

The new guidelines recommend norepinephrine alone as the first-line vasopressor to maintain a MAP above 65 mm Hg for patients with sepsis. It's usually delivered via I.V. drip titrated to maintain a MAP greater than 65 mm Hg or a cerebral perfusion pressure greater than 60 mm Hg. All patients requiring vasopressors should have an arterial catheter placed as soon as possible to allow for accurate invasive MAP monitoring.

When hypotension persists after norepinephrine has been administered, an additional vasopressor is often needed to maintain the BP and MAP at the desired goal. In this case, the new guidelines recommend epinephrine via I.V. drip titrated to maintain the targeted BP and a MAP goal of greater than 65 mm Hg.

A vasopressin infusion of 0.3 units/min can be added to norepinephrine if the goal is to raise the MAP above 65 mm Hg or lower the norepinephrine dosage. Vasopressin should never be used alone because it can cause profound vasoconstriction and impair blood flow to vital tissue and organs. Vasopressin doses exceeding 0.3 units/min are reserved only for salvage therapy-medical treatments that are used when all other treatment protocols have failed.

Dopamine is no longer recommended as the primary vasopressor because it can cause profound vasoconstriction and tachycardia. It's contraindicated in patients with septic shock unless the patient has bradycardia and is at low risk for tachyarrhythmia. Low-dose dopamine shouldn't be used for renal protection.

Phenylephrine is no longer recommended to treat septic shock unless the patient is experiencing arrhythmias associated directly with norepinephrine or has a high cardiac output with low BP. It can be used as a salvage therapy when combined with other vasopressors.

The new guidelines recommend that dobutamine infusions of up to 20 mcg/kg/min can be administered or added to other vasopressors only when myocardial dysfunction is present or when symptoms of tissue hypoperfusion continue despite achieving an adequate MAP. Myocardial dysfunction is suspected when the CVP is elevated and low cardiac output continues.

Blood bundle

NEW focus: Less use of blood products in patients with sepsis because few benefits have been observed in severe sepsis or septic shock, and the risk of transfusion-related complications should be avoided.

The new recommendations advise multidisciplinary teams to:

* transfuse red blood cells only for patients with a hemoglobin level less than 7 g/dL to target a hemoglobin concentration of 7 to 9 g/dL in adults

* no longer use erythropoietin to reverse sepsis-associated anemia

* no longer use fresh frozen plasma (FFP) to correct lab clotting abnormalities unless active bleeding or a surgical intervention is planned

* administer FFP for patients with a platelet count of 10,000/mm³ or less (indicating severe sepsis) in the absence of active bleeding or when platelet counts are 20,000/mm³ or less if the patient has a high risk of bleeding

* use higher platelet counts (50,000/mm³ or greater) for active bleeding, surgery, or invasive procedures to minimize the risk of hemorrhage.

Daily care bundle

NEW focus: The multidisciplinary team should evaluate the effectiveness of the medication and treatment regimens each day.

Monitor SvO₂ and serum sodium levels; white blood cell (WBC) counts; hemoglobin; lactic acid; and blood, sputum, and urine culture sensitivity results to ensure that the bacteria is sensitive to the current antibiotic therapy. The guidelines advocate the use of blood lactate levels as a marker of tissue hypoperfusion, targeting the return of lactate levels to normal as rapidly as possible. Sodium bicarbonate shouldn't be used to improve hemodynamics, reduce the amount of vasopressors being utilized to maintain the MAP at goal, or resolve hypoperfusion-induced lactic acidemia with a low pH.

Despite aggressive therapy, the patient may experience persistent hypoperfusion and progressive organ failure. The multidisciplinary team should promptly reassess the antibiotic regimen and blood culture results, and for the possibility that unexpected complications have occurred such as a pneumothorax following central venous catheter (CVC) insertion.

If the patient has responded to interventions with restored perfusion and an SvO₂ greater than 70%, clinical symptoms and lab parameters should continue to be followed closely. Monitor the following:

* capillary refill time

* BP

* MAP

* peripheral and central pulses

* arterial lactate

* urine output

* creatinine

* platelet count

* Glasgow Coma Scale score

* serum bilirubin

* liver enzymes

* gastrointestinal (GI) function.

Reevaluation is indicated if any of these worsen or fail to improve.

Ventilator bundle

Focus: If respiratory failure is imminent, the healthcare team may opt to place an endotracheal (ET) tube and ventilator to support the patient's breathing.

When patients experience severe sepsis or septic shock, they're at high risk for respiratory failure, usually caused by ARDS. The result is atelectasis, hypoxia, pulmonary edema, and continued worsening or degradation of tissue.

The ventilator tidal volume should be set at 6 mL/kg, rather than 12 mL/kg, for patients with sepsis-induced ARDS. The plateau pressures should be maintained at 30 cm H₂O or less, and positive end-expiratory pressure should be added to avoid alveolar collapse at end-expiration (atelectrauma).

The guidelines recommend prone positioning if the patient has ARDS and his or her PaO₂/FiO₂ ratio is 100 mm Hg or less. Prone positioning improves ventilation and oxygenation by changing the distribution of extravascular lung water and lung secretions. It also improves ventilation by changing the lung pleural pressure and lung compression, along with improving the lungs' functional residual capacity.

An aggressive ventilation alveolar recruitment maneuver for patients with severe refractory hypoxemia due to sepsis-induced ARDS is often needed to maintain adequate oxygenation. Aggressive ventilator recruitment methods may include repositioning, increasing positive end-expiratory pressure, or changing the ventilator delivery method to a bilevel setting where the ventilator delivers a breath and holds pressure for an extended period of time to allow the oxygen additional time to absorb through the alveoli.

Common interventions in most ventilator bundles include:

* head of bed elevation of at least 30 to 45 degrees in mechanically ventilated patients unless medically contraindicated to reduce the chances of aspiration, ventilator-associated pneumonia (VAP), and accidental dislodgment of the ET tube and to improve ventilation and alveolar recruitment maneuvers

* frequent cleansing and suctioning of the oropharyngeal airway and secretions; cleansing the oral mucosa with chlorhexidine gluconate is suggested to decrease the risk of VAP in ICU patients with severe sepsis or septic shock

* routine ventilator weaning attempts, referred to as spontaneous breathing trials, at least once a day to evaluate whether the ventilator can be safely discontinued

* minimal use of sedation targeting specific goals (the Richmond Agitation Sedation Scale is often utilized)

* avoiding neuromuscular blockers if possible in patients with sepsis who don't have ARDS; brief infusions or singular doses of neuromuscular blockers shouldn't exceed 48 hours for patients with early ARDS and a PaO₂/FiO₂ ratio less than 150 mm Hg.

Nutrition bundle

Focus: Initiate oral or enteral (if necessary) feedings within the first 48 hours after a diagnosis of severe sepsis or septic shock.

Critically ill patients have complex nutritional needs and require intensive nutritional input. As part of the metabolic response to injury, resting energy expenditure may be raised, leading to extensive catabolism, hyperglycemia, progressive lean body mass loss, changes in serum trace element levels, fluid retention, and reduced synthesis of visceral proteins such as albumin.

Catabolism combined with malnutrition inhibits healing and increases morbidity and mortality. Examples of complications from poor nutritional management include impaired wound healing, impaired immune response, impaired coagulation capacity, impaired gut function, muscle wasting, and reduced respiratory muscle function.

Feeding should be initiated at a low rate, such as 500 calories/day, and advanced as tolerated. I.V. glucose and enteral feeding should be utilized rather than parenteral nutrition, or parenteral nutrition and enteral feeding should be started within the first 7 days after a diagnosis of sepsis or septic shock.

There's ongoing debate regarding preferred routes for administration of nutrition. Many clinicians are proponents of utilizing the gut as soon as possible. However, peripheral nutrition may also be utilized due to lack of gut function. Both methods have potential complications; with either choice, it's imperative that nutrition be combined with careful and tight glycemic control.

Utilize stress ulcer prophylaxis, such as a proton-pump inhibitor or H2 blocker, to prevent upper GI bleeding in patients with bleeding risk factors and reduce stress-related mucosal disease (SRMD). If the patient doesn't have bleeding risk factors or SRMD, he or she shouldn't receive stress ulcer prophylaxis.

End-of-life care bundle

Focus: Address the goals of care, including treatment plans, daily progress, and end-of-life planning (if a poor outcome is expected) with the patient and family as early as possible or within 72 hours of ICU admission.

Ensure that end-of-life discussions are held in a quiet, private location. This will allow the healthcare team to discuss palliative and comfort care treatment options with the patient and family in detail. Multidisciplinary team members, such as the physician, nurse, respiratory therapist, chaplain, and social worker, should be available to provide answers to the patient's and family's questions and offer spiritual and social support. Make sure that the patient's religious and spiritual needs are met during this time.

Other updates

* Glycemic control: Blood glucose is now recommended at a target level of less than 180 mg/dL, up from a previous target of less than 150 mg/dL.

The international experts found that when blood glucose levels were targeting at the previous goal of less than 150 mg/dL, many patients experienced hypoglycemia in an effort to maintain such tight control. The guidelines recommend a blood glucose management protocol with insulin dosing starting when two consecutive blood glucose levels are greater than 180 mg/dL, targeting an upper blood glucose level of 180 mg/dL or lower.

Due to the nature of the disease process in the patient with sepsis, serum glucose levels are elevated and tight control is warranted as a part of overall patient management. However, maintaining a glucose level of less than 180 mg/dL is a difficult goal because sepsis causes an overwhelming production of mediators that contribute to many metabolic disturbances such as hyperglycemia that's extremely sensitive to insulin administration. Many clinicians now err on the side of higher glucose levels to avoid the adverse reactions of hypoglycemia.

Blood glucose levels should be obtained every 2 hours until glucose values and the insulin drip infusion rate are stable; blood glucose levels should then be checked every 4 hours. Blood glucose levels obtained from capillary blood may not reflect accurate serum and arterial glucose levels; therefore, blood glucose levels should be obtained with venous or arterial blood samples.

* Continuous venovenous hemofiltration (CVVH): The use of CVVH to remove the active inflammatory mediators associated with the sepsis response may slow the exaggerated inflammatory response and improve the clinical outcome.

CVVH is a form of dialysis that's a crucial adjunct therapy for patients with renal complications due to illness. Research shows that CVVH removes or filters cytokines, which are difficult to remove by other means and greatly affect the inflammatory response. CVVH is also beneficial to safely manage the fluid balance of hemodynamically unstable patients with sepsis.

* Deep vein thrombosis (DVT) prophylaxis: Initiate DVT prophylaxis, such as daily subcutaneous low-molecular weight heparin (LMWH), when the patient is diagnosed with sepsis unless contraindicated to minimize the risk of clot formation associated with reduced mobility.

Common contraindications to enoxaparin and heparin are thrombocytopenia, severe coagulopathy, active bleeding, or recent intracranial hemorrhage. These patients should receive compression stockings or intermittent compression devices. If the patient's creatinine clearance is less than 30 mL/min, dalteparin or another form of LMWH that has reduced renal metabolism should be used.

Early intervention = improved outcomes

The international sepsis guidelines have streamlined the EBP interventions to improve clinical outcomes in patients experiencing sepsis or septic shock. Hospitals that have initiated a strict protocol based on the guidelines have reported a 65% decrease in mortality in their patients with sepsis. Increase your healthcare team's knowledge base by sharing these guidelines, which you can download at http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/IDSA_Practic.

key points

New recommendations

Diagnosis

Figure. No caption available.

* Serum PCT levels are beneficial in diagnosing sepsis and assessing the efficacy of antibiotics.

Fluid management

* Administer crystalloid I.V. fluid if signs of tissue hypoperfusion are present.

* Colloid I.V. fluids, such as hydroxyethyl starch, are no longer recommended.

* Albumin is recommended to treat severe hypotension in patients with severe sepsis.

* Corticosteroid therapy should be used only in unresponsive septic shock or for children with adrenal insufficiency.

Vasopressor therapy

* Administer norepinephrine as the first-line vasopressor to maintain a MAP of greater than 65 mm Hg.

* Epinephrine should be added next to supplement norepinephrine.

* Vasopressin can be added to norepinephrine to raise the MAP above 65 mm Hg or lower the norepinephrine dosage.

* Dopamine isn't recommended as the primary vasopressor in adults.

* Phenylephrine is no longer recommended to treat septic shock except in select circumstances.

* Dobutamine can be administered or added to other vasopressors only when myocardial dysfunction is present.

Blood product administration

* Less use of blood products is recommended for patients with sepsis.

Daily care

* Evaluate the effectiveness of the medication and treatment regimens each day.

Ventilator bundle

* An aggressive alveolar recruitment maneuver for patients with severe refractory hypoxemia on mechanical ventilation may be needed.

* Ventilator weaning attempts should occur at least once daily.

* Avoid neuromuscular blockers unless the PaO₂/FiO₂ ratio is less than 150 mm Hg.

did you know?

Serum lactate levels are helpful in determining if the patient has tissue hypoxia. If tissue hypoxia is present, the serum lactate level will be greater than 1.

Figure. No caption available.

key points

Nursing considerations

* Always monitor the ABCs first! Frequently monitor for compromised airway, breathing, and circulation because patients with sepsis can quickly decline in status. Consider moving a patient with suspected sepsis to an area such as the ICU where he or she can be continuously monitored.

* Establish I.V. access immediately.

* If the patient exhibits respiratory distress or hemodynamic instability, central venous access should be initiated.

* Adults who have hemodynamic instability and require vasopressive or inotropic medications should have an arterial line placed for accurate continuous BP monitoring.

* Draw labs and aerobic and anaerobic blood cultures from two separate sites (CVC line and a peripheral stick) immediately.

* Initiate antibiotic therapy within 1 hour of suspected sepsis.

* Maintain a systolic BP of less than 90 mm Hg or a MAP greater than 65 mm Hg, cerebral perfusion pressure greater than 60 mm Hg, and a heart rate greater than 50 or below 120.

* Maintain a CVP between 8 and 12 mm Hg.

* Monitor for an SvO₂ level below 70% or a serum lactate level greater than 1.

* Initiate oral or enteral feedings within the first 48 hours.

* If the patient is on mechanical ventilation, cleanse the oral mucosa with chlorhexidine gluconate to decrease the risk of VAP. Sedation should be used minimally, targeting specific goals.

* Address the goals of care and daily progress with the patient and family.

* Conduct end-of-life planning (if a poor outcome is expected) as early as possible or within 72 hours of ICU admission.

cheat sheet

Special populations: Pediatrics

* Familiarize yourself with normal and abnormal pediatric vital signs that are specific for each age group.

* For respiratory distress and hypoxemia, start with face mask oxygen or, if needed and available, high flow nasal cannula oxygen or nasopharyngeal continuous positive airway pressure. Consider extracorporeal membrane oxygenation for refractory pediatric septic shock and respiratory failure.

* For improved circulation, peripheral I.V. access or intraosseus access can be used for fluid resuscitation and inotrope infusion when a central line isn't available. Begin peripheral inotropic support until central venous access can be attained in children who aren't responsive to fluid resuscitation. A minimum of two I.V. access sites should be maintained if inotropic therapy is initiated.

* Initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin. If hepatomegaly or crackles exist, then inotropic support should be implemented, not fluid resuscitation. Use diuretics to reverse fluid overload when shock has resolved; if unsuccessful, then CVVH or intermittent dialysis can be used to prevent greater than 10% total body weight fluid overload.

* Vasopressors, such as dopamine or epinephrine, are recommended to achieve a normal MAP and CVP.

* Initiate hydrocortisone therapy only in children with adrenal insufficiency.

* Aerobic and anaerobic blood cultures should be obtained before administering antibiotics when possible but this shouldn't delay administration of antibiotics.

* Begin empiric antibiotics within 1 hour of suspected sepsis.

* To validate that treatment is effective, assess for a capillary refill time of less than or equal to 2 seconds, normal BP for age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output greater than 1 mL/kg/hr, and normal mental status. If treatment isn't effective, consult with the healthcare team immediately.

* Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk for adverse drug-related events.

* Control hyperglycemia using a similar target as in adults (less than 180 mg/dL). Glucose infusion should accompany insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas others are insulin resistant.

* Update the family on the care plan, procedure results, and anticipated care plan at least once a day.

Source: Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.

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