EARLIER TODAY, Irene Smith, 75, was admitted for I.V. antibiotics to treat a complicated urinary tract infection. Her medical history includes hypothyroidism, mild-to-moderate aortic stenosis, Parkinson disease, osteoporosis, and osteoarthritis. When you enter her room at the beginning of your shift, you find that she's dusky, lethargic, and tachypneic. You check her vital signs: heart rate, 125 beats/min; BP, 87/52 mm Hg; respirations, 38; and temperature, 38.6° C (101.5° F). You call for the rapid response team (RRT).
Ms. Smith is at risk for severe sepsis, which kills about 215,000 people in the United States each year, out of the more than 750,000 people who develop the condition. Deaths from sepsis outnumber those from breast, colorectal, pancreatic, and prostate cancer combined.1
Early recognition of sepsis and early goal-directed therapy can sometimes halt the progression of sepsis to severe sepsis and septic shock. This article will follow Ms. Smith's case, which shows how rapid response and aggressive care can improve patient outcome in a critical situation.
Sepsis starts with a systemic inflammatory response syndrome (SIRS) that alters capillary endothelium, increasing nitric oxide production and impairing vasoregulation.2 The interplay of inflammatory cells and mediators leads to a cascade of endothelial injury, global tissue hypoxia, microthrombi formation (due to decreased levels of activated protein C, which promotes fibrinolysis), and abnormal oxygen use. Without treatment, this cascade can lead to organ dysfunction and failure and death.
SIRS is a clinical response to an infectious or noninfectious insult. A patient with SIRS will have at least two of these signs:
- Core temperature below 96.8° F (36° C) or above 100.4° F (38° C).
- Heart rate greater than 90 beats/min.
- Respiratory rate greater than 20 or Paco2 less than 32 mm Hg (normal range, 35 to 45 mm Hg).
- White blood cell (WBC) count less than 4,000 cells/mm3 or greater than 12,000 cells/mm3 (normal range, 4,500 to 10,500 cells/mm3) or greater than 10% immature neutrophils (normal range, 0% to 3%).1
Sepsis is the presence of SIRS accompanying an infection. Severe sepsis is sepsis plus evidence of end-organ dysfunction as a result of hypoperfusion.3 (Indications of organ dysfunction include lactic acidosis, oliguria, and acute change in mental status.) Septic shock is severe sepsis with persistent hypotension despite fluid resuscitation and acute circulatory failure resulting in tissue hypoperfusion. (See Defining sepsis for clinical criteria.4)
Patients who have a greater risk of developing sepsis are those age 65 or older and those under age 1; patients with chronic illness; those who take immunosuppressant agents; or those with infection due to surgery or an invasive procedure. Patients over age 65 have a higher infection risk due to impaired immunity, decreased mobility, skin breakdown, dementia, decreased gag and cough reflex, and poor bladder emptying.1
The national estimated mortality for sepsis is 30% to 50% for severe sepsis and 50% to 60% for septic shock, higher if the patient develops acute respiratory distress syndrome and respiratory failure.1,5 Common complications of septic shock include myocardial dysfunction, acute renal failure and chronic renal dysfunction, disseminated intravascular coagulation (DIC), and liver failure. Prolonged tissue hypoperfusion can cause long-term neurological complications.
Taking a proactive approach
In 2008, the international Surviving Sepsis Campaign updated its guidelines for managing severe sepsis and septic shock.4 Key objectives of this endeavor were to build awareness of sepsis, improve early detection, educate healthcare professionals caring for patients with sepsis, and increase the use of appropriate interventions.6 Treating patients with severe sepsis costs hospitals nearly $17 billion per year, a significant burden on the healthcare system.7 In one study, median total hospital costs per patient dropped from $21,985 to $16,103 after a sepsis protocol was implemented.8
The practice guidelines recommended by the Surviving Sepsis Campaign call for a group, or "bundle" of related interventions that, when executed together, result in better outcomes than when implemented individually.1,4 By being vigilant for the signs of early sepsis and acting quickly to halt its progression, patient mortality from sepsis can be reduced by as much as 16%.1
The mainstays of this early goal-directed therapy, which we'll describe in detail later, include:
- treatment of the infection with appropriate antimicrobial therapy
- resuscitation and hemodynamic support with I.V. fluids and vasopressors
- full organ support (such as renal replacement therapy or mechanical ventilation)
- modulation of the inflammatory response with recombinant human activated protein C
- sedation and analgesia as needed
- optimal nutrition.6
Recognizing sepsis isn't always easy. Many patients can have vital signs that fit the SIRS criteria. For example, patients with influenza, a gastrointestinal virus, or a urinary tract infection may have fever, tachypnea, and leukocytosis, but generally these patients improve with the first steps of the early goal-directed therapy for sepsis (fluid and antimicrobial administration). Remember that a patient who meets the criteria for SIRS isn't always septic, and that patients can develop sepsis late in the course of a hospital stay. Be vigilant at all times for early signs of sepsis.
Two of the earliest signs of sepsis are a narrow pulse pressure and tachycardia. Tachycardia and hypotension are almost universal findings in patients with sepsis. Early on, in patients who've received partial or full fluid resuscitation, tachycardia and hypotension are associated with high cardiac output (CO) and low peripheral vascular resistance. Patients will have warm extremities and bounding pulses. In contrast, patients who haven't been significantly resuscitated, or who didn't seek medical care until late in the course of illness, will have a low CO and high systemic vascular resistance. These patients will have cold extremities, diaphoresis, and weak, thready pulses, and will need urgent resuscitation.9
Tachypnea is common in patients with sepsis, but its significance may not be clearly understood. As tissue hypoperfusion progresses, the patient's respiratory rate increases in an effort to compensate for metabolic acidosis. The patient may report shortness of breath or appear slightly anxious. Subtle changes in the patient's vital signs or level of consciousness may be the only warning that the patient is in trouble. An older adult may demonstrate mild disorientation or agitation that may progress to obtundation or coma.
Assessing your patient
Baseline vital signs and a complete history of current symptoms are the starting point for evaluating a patient for sepsis. Are vital signs within normal range? What symptoms precipitated hospitalization? Did signs and symptoms include nausea, vomiting and diarrhea, fever, chills, or cough? What type of medical problems has the patient had in the past? This information will help caregivers assess the patient's current signs and symptoms and may pinpoint a potential source of infection.
During the physical assessment, begin by evaluating the patient's general condition. Assess the airway, breathing, circulation, and mental status. Pay particular attention to the patient's skin color and temperature. Check for pallor, mottling, and other signs of poor tissue perfusion, such as delayed capillary bed refill. A patient's skin is often warm to the touch in early sepsis, due to increased CO and peripheral vasodilation; this is referred to as warm shock. As septic shock progresses, the patient's skin will become cooler due to the depletion of intravascular volume and decreasing CO. The patient's extremities will feel cool and clammy and you'll notice decreased capillary refill; this is referred to as cold shock. Petechiae or purpura, which can be associated with DIC, are ominous signs.
Helping Ms. Smith
The RRT arrives and starts administering a bolus of 0.9% sodium chloride solution via Ms. Smith's existing peripheral I.V. site. They establish a second peripheral I.V. line and obtain blood specimens for a complete blood cell (CBC) count, comprehensive metabolic panel, and lactate level. Blood cultures, a DIC screen, and a type and screen may be obtained later, pending further assessment and lab results.
After receiving 2 L of I.V. 0.9% sodium chloride solution, Ms Smith's clinical status remains unchanged. Her urinary tract infection, fever, tachycardia, tachypnea, leukocytosis, hyperlactatemia, and limited response to the fluid bolus lead the healthcare provider to diagnose her with sepsis. A central venous access device (CVAD) is placed for administering vasopressors and additional fluids and medications, as well as for providing central venous pressure (CVP) monitoring.
Treatment for a patient suspected of having sepsis should be started as quickly as possible, ideally within the first hour of presentation. Much like the golden hour for trauma patients, the first hour of caring for a patient with sepsis is critical.
Obtaining lab results is a priority. A CBC count will demonstrate leukocytosis indicating an acute inflammatory process and possible infection, as well as a low hemoglobin level. Hemoglobin is the main component of red blood cells (RBCs) that transports oxygen. Decreased hemoglobin levels can indicate anemia. The comprehensive metabolic panel, which includes blood urea nitrogen, creatinine, and liver enzymes, can indicate renal or hepatic dysfunction, which can indicate severe sepsis. If infection is suspected (or documented, as in our case study) and the patient meets two or more SIRS criteria, a serum lactate level also needs to be obtained.
An elevated serum lactate level can indicate tissue hypoperfusion. Serum lactate is a marker of anaerobic metabolism, which occurs when tissue oxygenation demands exceed supply. Elevated lactate levels (over 2.5 mmol/L) indicate widespread tissue hypoperfusion and are associated with increasing risk of death.10,11
Next, start an I.V. fluid bolus of 0.9% sodium chloride solution, as prescribed. If the CBC count shows a value that meets the SIRS criteria (a WBC count greater than 12,000 cells/mm3 or less than 4,000 cells/mm3 or greater than 10% immature neutrophils), establish an additional venous access and obtain blood specimens for additional lab tests, including two or more blood cultures, type and screen, and a DIC panel. Insert an indwelling urinary catheter and obtain a urine specimen for a urinalysis and culture. Also obtain samples for sputum cultures.
If the patient remains hypotensive despite fluid boluses, prepare for CVAD insertion.
The Surviving Sepsis Campaign's resuscitation bundle of interventions calls for administering broad-spectrum antibiotics within 3 hours of ED admission and 1 hour of non-ED admission.1 Because you'll likely administer several antibiotics in rapid succession, administer the antibiotics with the shortest infusion times first.
The goals of fluid resuscitation in the first 6 hours include a CVP of 8 to 12 mm Hg, a mean arterial pressure (MAP) of 65 mm Hg or greater, a urine output of 0.5 mL/kg/hour or greater, and a central venous oxygen saturation of 70% or greater or mixed venous oxygen saturation (SVO2) of 65% or greater.4 In mechanically ventilated patients, a higher targeted CVP of 12 to 15 mm Hg is recommended, to account for positive-end expiratory pressure and increases in intrathoracic pressure.1 If the patient can't maintain a systolic BP greater than 90 mm Hg or a MAP of 65 mm Hg or greater after fluid resuscitation, start an infusion of norepinephrine or dopamine (the initial vasopressors of choice) as prescribed via the CVAD and titrate it to meet a target MAP of 65 mm Hg or greater.
For the patient who remains hypotensive despite fluid resuscitation and norepinephrine administration of more than 5 to 10 mcg/min, the next step is to administer vasopressin.1 Obtain an SVO2 sample from the CVAD to check for hypoperfusion and impaired oxygenation. Check the patient's hematocrit level if the SVO2 value isn't over 65% despite other parameters having responded to fluid resuscitation (that is, CVP is 8 mm Hg or greater, urine output is greater than 0.5 mL/kg/hour, and MAP is 65 mm Hg or greater). If the patient's SVO2 can't be brought up to target by these interventions, the healthcare provider will consider further fluid resuscitation and packed RBCs if needed to bring the hematocrit to at least 30%. A dobutamine infusion may also be prescribed.4
Obtain a repeat SVO2 reading 30 minutes after initiating the dobutamine infusion. Reevaluate the patient if the value is still less than 65%.
Treating Ms. Smith
Here's how the interventions described above would proceed with Ms. Smith. As prescribed, you start an infusion of cefepime, a broad-spectrum, cephalosporin antibiotic. The RRT nurse stays with Ms. Smith until she's transferred to an ICU bed for aggressive care and treatment with a sequence of multiple antibiotics.
Over the next 72 hours, her blood work results show improvement: immature neutrophils decrease from 30% to 1%, lactate level decreases from 8.1 to 2.5 mg/dL, and WBC count decreases from 35,200 to 13,500 cells/mm3. Ms. Smith's clinical status continues to improve. She's moved to a step-down unit and then back to a general medical unit. Upon discharge, she's transferred to a rehabilitation care facility. After 2 weeks, she returns home and resumes her usual activity.
Caring for a patient with sepsis is challenging and often requires multiple resources, such as emergency or critical care physicians and nurses, pharmacists, and respiratory therapists. The first line of treatment is to identify and eliminate the underlying infection. If your facility has an RRT, contact the team early in the process. Transfer your patients to an ICU as soon as possible.
By recognizing sepsis early and treating it promptly, you may be able to prevent the patient from progressing to septic shock.
An adult patient with sepsis has a documented or suspected infection, plus some of the systemic manifestations of infection outlined below:
- Fever (core temperature above 38.3° C)
- Hypothermia (core temperature below 36° C)
- Heart rate greater than 90 beats/min or more than 2 standard deviations above the normal value for age
- Altered mental status
- Significant edema or positive fluid balance (greater than 20 mL/kg over 24 hours)
- Hyperglycemia (plasma glucose of 140 mg/dL or greater) in a patient without diabetes
- Leukocytosis (WBC count over 12,000 cells/mm3)
- Leukopenia (WBC count below 4,000 cells/mm3)
- Normal WBC count with more than 10% immature forms (or "bands")
- Plasma C-reactive protein level more than 2 standard deviations above the normal value
- Plasma procalcitonin level more than 2 standard deviations above the normal value
Arterial hypotension (systolic BP less than 90 mm Hg; MAP less than 70 mm Hg; or a systolic BP decrease of more than 40 mm Hg in adults or less than 2 standard deviations below normal for age)
Organ dysfunction variables
- Arterial hypoxemia (Pao2/Fio2 of 300 or less)
- Acute oliguria (urine output less than 0.5 mL/kg/hour for at least 2 hours, despite adequate fluid resuscitation)
- Creatinine level increase of more than 0.5 mg/dL
- Coagulation abnormalities, such as an International Normalized Ratio greater than 1.5 or activated partial thromboplastin time more than 60 seconds
- Ileus (absent bowel sounds)
- Thrombocytopenia (platelet count less than 100 × 103/mm3)
- Hyperbilirubinemia (plasma total bilirubin greater than 4 mg/dL)
Tissue perfusion variables
- Hyperlactatemia (above the upper limit of lab normal)
- Decreased capillary refill or mottling.