AFFECTING MILLIONS OF people worldwide, sepsis is a systemic response to an overwhelming inflammatory process caused by an infection. Approximately one in four people who develop sepsis will die.1 In January 2013, the international Surviving Sepsis Campaign Guidelines Committee published its 2012 surviving sepsis guidelines (SSG), an update to the 2008 guidelines for early identification and management of sepsis in adults.1 The guidelines highlight the importance of screening every potentially infected patient for sepsis and providing best-practice interventions for managing sepsis, severe sepsis, and septic shock. This article provides an overview of care for the adult patient with sepsis, focusing on sepsis identification and the first 6 hours of goal-directed treatment according to current guidelines.
Sepsis is the presence of infection along with systemic manifestations of infection. If sepsis isn't recognized and treated early, it progresses rapidly to severe sepsis, defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion. Sepsis-induced tissue hypoperfusion is defined as infection-induced hypotension, elevated lactate level, or oliguria.1
Patients with severe sepsis may have low systolic or mean arterial pressure (MAP), a lactate level above 2 mmol/L, or a urine output of less than 0.5 mL/kg/hr for at least 2 hours despite adequate fluid resuscitation.1 Recognizing that a patient has sepsis before it progresses to severe sepsis is essential for early intervention to prevent further progression to septic shock.
Septic shock is sepsis-induced hypotension that persists despite adequate fluid resuscitation. Sepsis-induced hypotension is defined as systolic BP (SBP) less than 90 mm Hg, MAP less than 70 mm Hg, or a decrease in SBP greater than 40 mm Hg or less than two standard deviations below normal for age in the absence of other causes of hypotension.1
Screening patients for sepsis includes monitoring for signs and symptoms of infection and identifying subtle changes in vital signs, mental status, urine output, lab values, and/or markers of tissue perfusion. (See Screening patients for sepsis, severe sepsis, or septic shock.) Identifying sepsis quickly allows for early goal-directed therapy, potentially reducing the patient's mortality risk. To illustrate, let's look at a case study.
Ms. C, 45, embedded a fishhook in her right foot 3 days ago on a fishing excursion with friends. She removed it and didn't seek emergency care for the injury. Because she's been feeling “off” for the last 2 days and her right foot is tender and swollen, a friend brought her to the ED. The friend reports that Ms. C's been acting odd and saying “crazy things.”
Assessment reveals a cool, edematous right foot with patches of erythema on the foot and ankle; oral temperature 101° F (38.3° C); heart rate 102; respirations 24; and BP 88/42 (MAP 57). She's alert and oriented to person, time, and place but can't describe her current situation of needing to seek medical attention for her infected foot. She doesn't remember when she last urinated. Her friend reports she had a tetanus shot last year. An infection in her right foot is suspected and she has signs and symptoms of systemic inflammation (tachycardia, fever, tachypnea, mottling, altered mental status, hypotension, and probable oliguria). Ms. C is identified as having sepsis.
She may have severe sepsis, so the healthcare provider initiates early goal-directed therapy. It's been 10 minutes since Ms. C was first suspected of having sepsis.
Initiating goal-directed therapy
The SSG recommend early goal-directed therapy for patients suspected of having severe sepsis or septic shock and provide targeted time frames and goals for these interventions. Early sepsis management is considered to be similar to management of polytrauma, acute myocardial infarction, or stroke, where the speed and appropriateness of therapy administered in the initial hours are likely to influence the patient's outcome.1 (See Targeted time frames and goals of initial therapy.)
Upon recognizing severe sepsis or septic shock:
* obtain at least two sets of blood cultures using aerobic and anaerobic bottles before starting I.V. antibiotics.
* determine the serum lactate level.
* administer broad-spectrum antibiotics within 1 hour of recognition of severe sepsis or septic shock; antibiotic administration shouldn't be delayed more than 45 minutes to obtain the blood cultures.
* initiate isotonic crystalloid fluid resuscitation at 30 mL/kg to treat hypotension or a lactate level of 4 mmol/L or greater.1
Initiating therapy for Ms. C
Within 1 hour after clinicians recognize severe sepsis in Ms. C, peripheral venous access is obtained and specimens are drawn for blood cultures, serum lactate level, basic metabolic panel, complete blood cell count and differential, prothrombin time/international normalized ratio (PT/INR), and an activated partial thromboplastin time (aPTT). An I.V. broad-spectrum antibiotic is administered for the suspected foot infection. An infusion of 0.9% sodium chloride solution is initiated at a rate of 1,000 mL every 30 to 60 minutes to a total of 3 L (3,000 mL) in 3 hours (Ms. C weighs 220 lb [100 kg] so she receives 30 mL/kg). Her BP is assessed frequently, focusing on achieving a MAP of 65 mm Hg or greater. Because Ms. C couldn't recall her last void and she's hemodynamically unstable, an indwelling urinary catheter is inserted to closely monitor her urine output. Initial resuscitation goals for Ms. C include a urine output of 0.5 mL/kg/hr or more and a MAP of 65 mm Hg or greater.
At the 2-hour mark after severe sepsis was recognized, Ms. C's BP is 92/36 (MAP 55), she's receiving the third liter of 0.9% sodium chloride solution, her urine output is 0.3 mL/kg/hr, and her initial lactate level is 4.5 mmol/L (normal, 0.5 to 1.5 mmol/L). Lactic acidosis is generally defined as a plasma lactate concentration greater than 4 mmol/L, even without overt acidemia.2 Because she isn't responding to fluid resuscitation and her MAP and urine output remain low, the healthcare provider prescribes I.V. vasopressor therapy using a norepinephrine infusion to achieve a MAP of 65 mm Hg. Meanwhile, the initial fluid resuscitation continues at 30 mL/kg. Once this is complete, the healthcare provider prescribes another infusion of 0.9% sodium chloride solution at 100 mL/hr. Because Ms. C's been started on vasopressors, the ICU is notified of a probable admission and possible central venous catheter (CVC) placement.
Ms. C's vital signs are reviewed, particularly her BP of 92/36 (MAP 55). The abnormally low diastolic pressure creates a wide pulse pressure (the difference between the systolic and diastolic BP, normally one-third the systolic). Ms. C's pulse pressure is 56 mm Hg (92-36). Her pulse pressure should normally be one-third the systolic BP, or 30 (92 ÷ 3).3
In sepsis as well as other systemic inflammatory syndromes, the arterioles and capillary beds vasodilate, resulting in a widened pulse pressure and at times a low diastolic pressure. As the capillary beds dilate, fluid leaks into the interstitial spaces, resulting in an intravascular volume deficit. The dilated capillary beds and resulting dehydration impair oxygen delivery to the tissues and promote intravascular thrombosis.3 Early goal-directed therapy focusing on fluid resuscitation at 30 mL/kg restores circulating blood volume, increases tissue perfusion, and lessens the chance of thrombus formation. If fluid fails to restore an adequate BP (MAP of 65 mm Hg or more), I.V. vasopressors such as norepinephrine are added to constrict the arteriole beds and restore homeostasis.
Ms. C is transferred to the ICU, a triple-lumen CVC is placed in her right subclavian vein, and a central venous pressure (CVP) reading of 6 mm Hg is obtained. The SSG recommend a target CVP reading of 8-12 mm Hg to indicate adequate circulating volume.1
Fluid continues to leak into the interstitial spaces, requiring Ms. C to continue receiving fluid replacement and I.V. norepinephrine to restore hemodynamic stability. As Ms. C is receiving substantial amounts of crystalloids to restore circulating volume, a colloid such as albumin may be added. Hydroxyethyl starches should be avoided.
When fluids fail
Norepinephrine is recommended as the first-line vasopressor if fluid fails to restore an adequate BP.1 Norepinephrine is a strong alpha-adrenergic receptor agonist that causes peripheral arteriolar vasoconstriction.4 This action slows the leakage of fluid into the interstitial spaces and helps maintain circulating blood volume. Norepinephrine also acts on the beta1 receptors in the heart, increasing myocardial contractility and heart rate.4 This may increase oxygen consumption by the tissues, so the patient's oxygen saturation and response to therapy must be closely monitored.
To gauge the patient's oxygen consumption, the healthcare provider may want to measure central venous oxygen saturation (ScvO2) using blood obtained from the CVC distal port. ScvO2 is an indicator of tissue perfusion and reflects the percentage of oxygen being returned to the right side of the heart after tissue consumption.5 The target ScvO2 for Ms. C is 70%. An abnormally low or high ScvO2 or mixed venous oxygen saturation (SvO2) should be evaluated for cause. (See Sorting out causes of altered ScvO2 or SvO2.)
One hour after starting the norepinephrine infusion (4 hours since severe sepsis was identified), a venous blood gas sample and a lactate level are obtained from the distal port of Ms. C's CVC. Her ScvO2 is 68% and her lactate level has dropped to 2.8 mmol/L; both values indicate improving tissue perfusion. Her skin is warm and moist, her urine output is 0.8 mL/kg/hr, and she's asking the staff why she's in the hospital, indicating improving mental status. Over the next few days, Ms. C is continually monitored for signs and symptoms of improvement in clinical status and deterioration into septic shock.
Early identification and rapid goal-directed therapy to treat severe sepsis in the first 6 hours from identification are essential to reducing mortality. Ms. C's severe sepsis was identified early, her altered tissue perfusion corrected with rapid administration of I.V. antibiotics, I.V. fluids, and the addition of an I.V. vasopressor when fluid failed to maintain the targeted MAP of 65 mm Hg and CVP of 8-12 mm Hg.
The healthcare provider may discontinue antibiotic therapy using procalcitonin levels or similar biomarkers. Procalcitonin levels that drop to 0.5 mcg/L or by more than 80% to 90% from baseline have been used as a marker for timing antibiotic discontinuation.6
The SSG offer supportive therapy recommendations for patients who continue to deteriorate or who don't respond to early goal-directed measures. Other hemodynamic therapies that may be added include additional vasopressors and inotropic agents (see Vasopressors and inotropic choices for managing sepsis).
In the 2008 SSG, dopamine was recommended as a substitute for norepinephrine.7 Dopamine is now recommended only as an alternative to norepinephrine in cases where the risk of tachydysrhythmias is low or the patient is experiencing bradycardia.1 Additional hemodynamic support includes adding I.V. hydrocortisone daily if the patient fails to achieve hemodynamic stability with I.V. fluids and vasopressors.1 Because Ms. C achieved hemodynamic stability with fluids and vasopressors, she didn't need a course of hydrocortisone.
Other recommendations to support the care of the patient with severe sepsis after the first 6 hours are outlined in the guidelines. Recommendations for transfusing packed red blood cells after tissue hypoperfusion has resolved and in the absence of extenuating circumstances (myocardial ischemia, acute hemorrhage, severe hypoxemia, or myocardial infarction) include a hemoglobin level less than 7 g/dL. For patients with severe sepsis, prophylactic platelet transfusions are recommended only if the platelet count is 10,000/mm3 or less in the absence of severe bleeding, or 20,000/mm3 or less for a high risk of bleeding. For patients who are actively bleeding, going to surgery, or having another invasive procedure, the guidelines suggest platelet transfusion for counts of 50,000/mm3 or less.1
In the past, immune-modulating nutritional supplements such as I.V. selenium and the administration of I.V. immunoglobulins have been tried to improve sepsis outcomes. Neither of these interventions is recommended in the 2012 SSG. The administration of recombinant-activated protein C is discussed in the guidelines but isn't available for administration since its withdrawal from the market.1
For severely ill patients with sepsis who may need mechanical ventilator support, the guidelines provide ventilator strategies for reducing mortality from sepsis-induced acute respiratory distress syndrome. The guidelines recommend using the least amount of sedation and avoiding administration of neuromuscular blocker agents to patients with sepsis who are receiving mechanical ventilation.1
For ICU patients with severe sepsis, the guidelines provide recommendations for glucose control. The SSG recommend not treating with insulin infusions until two consecutive glucose readings are above 180 mg/dL. Glucose control is targeted at maintaining the blood glucose level at less than 180 mg/dL and monitoring blood glucose every 1 to 2 hours until glucose values and insulin infusion rates are stable, and then every 4 hours thereafter.1
Other recommendations address managing patients who may need dialysis, bicarbonate administration, stress ulcer prophylaxis, prevention of deep vein thrombosis (DVT), and nutrition.
* In patients who require renal replacement therapy for acute renal failure, continuous renal replacement therapies and intermittent hemodialysis are seen as equivalent.
* The guidelines recommend against treating sepsis-induced lactic acidemia with bicarbonate therapy for pH levels greater than or equal to 7.15.
* The guidelines support preventing DVT by administering prophylactic anticoagulation with subcutaneous low-molecular-weight heparin or unfractionated heparin.
* The guidelines also support the use of intermittent pneumatic compression devices, both for patients receiving prophylactic anticoagulation and for those with contraindications to anticoagulant therapy.
* The guidelines support administration of proton pump inhibitors or H2 blockers to prevent stress ulcers in patients with severe sepsis/septic shock who have risk factors for bleeding.
* Nutritional support (oral or enteral nutrition) should be started within 48 hours of recognizing severe sepsis in combination with low-dose I.V. glucose (up to 500 kcal/day) for the first week. If the patient requires parenteral nutrition, the guidelines recommend combining it with enteral feedings.1
The final supportive recommendation involves guidelines for setting goals of care. As sepsis is associated with high mortality, the guidelines recommend discussing and setting goals of care (including end-of-life care) with the family and patient as soon as possible but no longer than 72 hours after admission.1
Ms. C's tissue perfusion continued to improve and she was weaned off her vasopressor support on day 3 in the ICU. On day 4 she was transferred to the medical-surgical unit and her antibiotic therapy was transitioned to oral preparations. Her central line was discontinued and her urinary catheter was removed. She was discharged home on oral antibiotics on day 6 following admission.
Timing is key
Early identification and initiation of goal-directed therapies for sepsis are essential for reducing mortality. By learning how to identify and screen every potentially infected patient for sepsis, nurses can save lives.