Sepsis is the result of systemicinflammatory response to infection, and theincidence is on the rise. Severe sepsis—sepsiswith one or more signs of organ failure—isfast moving, difficult to treat, and oftendeadly, as inflammatory events adversely alterendothelial-cell function and tissue perfusion.Find out what you need to know to take onsevere sepsis.RUTH M. KLEINPELL, RN-CS, ACNP, CCRN, PhDAssociate Professor • Rush University College of NursingNurse Practitioner • Our Lady of the Resurrection Medical Center •Chicago, Ill.

The author has disclosed that she has no significant relationships with or financial interest in any com-mercial companies that pertain to this educational activity.

Adapted from Kleinpell, R.: “Working Out the Complexities of Severe Sepsis,” Nursing Management.35(5):48A-B, 48D, 48F, 48H.

PATIENTS LIKE ROSE MCKENNA are areal clinical challenge. This petite, 64-year-old mother of three and grandmother ofseven doesn’t just have sepsis; she has se-vere sepsis, defined as sepsis with acutefailure of one or more organ systems.

Severe sepsis is devastating and becomingmore common: Each year, an estimated750,000 cases develop in the United States,leading to 215,000 deaths and annual costs ofover $17 billion. According to the Society ofCritical Care Medicine, sepsis is the leadingcause of death in noncoronary intensive careunits in the United States; reported mortalityrates for severe sepsis range from 28% to50% in adults, making it the 10th leadingcause of death in the United States.

Why has sepsis taken off like this? For onething, more patients with chronic diseasesthat increase their risk for sepsis are surviv-ing longer; Mrs. McKenna, for example, has

26 Nursing made Incredibly Easy! November/December 2004

1.5 ANCC/AACN CONTACT HOURS

C E

had type 2 diabetes for 20 years. For another,more widespread use of invasive devices formonitoring and treating critically ill patientsis literally opening a portal for infections,which increases incidence rates. And finally,health care providers are ordering moretreatments that improve survival rates forunderlying diseases, but also cause immuno-suppression.

Spiraling out of controlSepsis stems from an overwhelming bacte-rial bloodstream infection. This infectiontriggers a series of systemic inflammatoryand cellular events that lead to altered cir-culation and coagulation, endothelial dys-function, and impaired tissue perfusion.The pathophysiology is a complex seriesof interactions between the bacteria andthe body’s immune system.

Here’s what happens. Bacteria invade thebody and are recognized by white blood

November/December 2004 Nursing made Incredibly Easy! 27

Winning the battle against severesepsis

Clinical signs of sepsisSystemic inflammatory response syndrome (SIRS)Two or more of the following conditions can indicate sepsis:♦ temperature >38° C (100.4° F) or <36° C (96.8° F)♦ heart rate >90 beats/minute♦ respiratory rate >20 breaths/minute or PaCO2 <32 mm Hg (<4.3 kPa)♦ white blood cell count >12,000 cells/mm3, <4,000 cells/mm3, or >10%immature (band) forms.Additional signs and symptomsBesides two or more of the criteria for SIRS, watch for the appearance ofany one or more of the following:♦ chills♦ hypotension♦ decreased skin perfusion♦ decreased urine output♦ significant edema or positive fluid balance (>20 ml/kg over 24 hours)♦ decreased capillary refill or mottling♦ hyperglycemia (plasma glucose >120 mg/dl) in the absence of diabetes♦ unexplained change in mental status.

Source: Levy, M., et al.: “2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis DefinitionsConference,” Critical Care Medicine. 31:1250-1256, April 2003.

cells (monocytes and neutrophils). Themonocytes release substances responsible forinflammation (cytokines and prostaglandin)to fight the infection. Tissue factor, alsoreleased by the monocytes, initiates the clot-ting cascade, resulting in blood clots. Bloodclots form as the body attempts to seal bacte-ria into specific areas so that the bacteria canbe targeted and destroyed more effectively.But there’s a problem: Because bacteria arefound throughout the body in sepsis, smallclots begin to form in all the tiny blood ves-sels, leading to impaired blood circulation

and tissue perfusion. To make mattersworse, the normal mechanism to breakdown blood clots is impaired, so clots thatform remain in the vessels.

The systemic inflammatory response alsodamages the endothelial lining of blood ves-sels and cell membranes. This causes fluidto leak from the intravascular and intracel-lular spaces into the interstitial space. Thefluid shift from increased capillary perme-ability results in reduced circulating fluidvolume, which, in turn, causes the bloodpressure to drop. The blood vessels alsodilate, which leads to a further plunge in theblood pressure. Increased clotting, increasedcapillary permeability, and the increasedinflammatory response will eventuallycause impaired tissue perfusion and multi-ple organ failure.

Once organs begin to fail, sepsis is de-fined as severe and can progress to septicshock—that is, sepsis with severe hypoten-sion and perfusion abnormalities. In severesepsis, changes in vital signs and lab test re-sults, along with signs and symptoms of al-tered tissue perfusion, reflect acute organsystem dysfunction. See Signs of Acute Or-gan System Failure for more details.

Irreversible multiple organ system failurecan happen in a matter of hours, and it’s amajor cause of sepsis-related death. Anyorgan system can fail in sepsis, but the respi-ratory and renal systems are most oftenaffected. So early recognition and prompttreatment of severe sepsis are critical to yourpatient’s survival.

A deadly game of hide-and-seekIdentifying severe sepsis can be tough be-cause the clinical presentation can varyfrom patient to patient. Infections that leadto severe sepsis can arise anywhere in thebody, but most commonly appear first inthe kidneys, lungs, skin, bowel, and liveror gall bladder. Mrs. McKenna, for exam-ple, has an infected foot ulcer that is sus-pected of triggering sepsis.

28 Nursing made Incredibly Easy! November/December 2004

Wow! Sepsisdestroys

pretty mucheverythingin sight!

Signs of acute organsystem failureCardiovascular• Tachycardia• Arrhythmias• Hypotension• Elevated central venous and pulmonary

artery pressuresRespiratory• Tachypnea• HypoxemiaRenal• Oliguria• Anuria• Elevated creatinineHematologic• Jaundice• Elevated liver enzymes• Decreased albumin• Coagulopathy Gastrointestinal• Ileus (absent bowel sounds)Hepatic• Thrombocytopenia• Coagulopathy• Decreased protein C levels• Increased D-dimer levelsNeurologic• Altered consciousness• Confusion• Psychosis

Adapted from Balk, R.: “Pathogenesis and Management ofMultiple Organ Dysfunction or Failure in Severe Sepsis andSeptic Shock,” Critical Care Clinician. 16:337-352, vii, April 2000.

A closer look

Patients may present with unexplainedchanges in mental status, exhibiting confu-sion or delirium. Other clinical features mayinclude hyperglycemia, hyperventilation,hypothermia or fever with chills and shiver-ing, and tachycardia.

Besides the systemic inflammatoryresponse syndrome (SIRS) criteria discussedin Clinical Signs of Sepsis, signs and symp-toms of severe sepsis include clinical indica-tors of altered tissue perfusion, like hypo-tension, oliguria (decreased urine output),and decreased skin perfusion (such asdecreased capillary refill, mottled skin, andrashlike appearance). What you need toremember is that a patient who exhibits twoor more SIRS criteria and has symptoms of a

known or suspected infection is waving abig red flag at you; he needs to be evaluatedfor sepsis.

The health care provider will order at leasttwo blood cultures to help identify theorganism at the root of sepsis and to guideantimicrobial therapy. If the patient has avascular access device, you can draw onesample from it and the other percutaneously.Depending on the specifics of the case, thehealth care provider might also want to cul-ture the patient’s urine, cerebrospinal fluid,wound fluid, respiratory secretions, or otherbody fluids. Although lab tests can confirmthe presence of infection, a definitive sourceof infection isn’t identified in 20% to 30% ofpatients with sepsis.

November/December 2004 Nursing made Incredibly Easy! 29

Treatment strategies

Adapted from Dellinger, R., et al.: “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” Critical Care Medicine. 32:858-872, March2004.

1. Initiate resuscitation for sepsis-induced hypoperfusion.♦ Fluid resuscitation to a central venous pressure of 8 to 12mm Hg♦ Transfusion of packed red blood cells to achieve a hemat-ocrit of >30%♦ Administration of inotropic infusion (such as dobutamine)2. Obtain appropriate diagnostics.♦ Obtain at least two blood cultures, with one drawn percuta-neously and one drawn through each vascular access device;obtain cultures of other sites, such as urine, wounds, and res-piratory secretions before initiating antibiotic therapy.♦ Diagnostic studies (such as ultrasound, imaging studies)3. Initiate antibiotic therapy.♦ Empirical antibiotics4. Control the source of infection.♦ Removal of potentially infected device, drainage of abscess,debridement of infected necrotic tissue5. Enhance perfusion.♦ Fluid therapy♦ Vasopressors♦ Inotropic therapy6. Consider the use of steroids.♦ For patients with relative adrenal insufficiency7. Consider the use of drotrecogin alfa (recombinanthuman activated protein C [Xigris]).♦ For patients with sepsis-induced multiple organ failure with

no absolute contraindication related to bleeding risk8. Administer blood products if hemoglobin is below 7 g/dl.♦ To target hemoglobin of 7 to 9 g/dl9. Initiate mechanical ventilation if needed.♦ Lung-protective ventilation for acute lung injury/acute respi-ratory distress syndrome♦ Use low tidal volumes (6 ml/kg ideal body weight) andplateau pressures at 30 cm H2O or less♦ Keep the head of the bed at 45 degrees or more and providefrequent oral care to prevent ventilator-associated pneumonia10. Provide sedation and analgesia.♦ To provide comfort yet avoid prolonged sedation♦ Consider neuromuscular blockade only as a last resort11. Control the blood glucose level.♦ To maintain blood glucose <150 mg/dl12. Keep the kidneys functioning.♦ Initiate renal replacement therapy in acute renal failure13. Initiate preventive measures.♦ Use subcutaneously administered low-molecular weightheparin or unfractionated heparin if appropriate and mechani-cal compression devices to prevent deep vein thrombosis♦ Use histamine-2 receptor blockers to prevent stress pepticulcer14. Communicate with the patient and family.♦ Family discussion about life-sustaining therapies♦ End-of-life care discussion for critically ill patients

Deliver a knockout punchPatients with severe sepsis need promptand aggressive treatment of the underly-ing infection; fluids, inotropic drugs, andvasopressors to increase tissue perfusion;and targeted organ system support.

Antibiotics are a mainstay of treatment.Fluid therapy, first-line treatment for sepsis,replaces the circulating volume. The recom-mended fluids are 0.9% sodium chlorideand lactated Ringer’s solution because theyclosely match blood plasma. If the patient’shemoglobin level drops below 7 g/dl,packed red blood cells should be given un-til the hemoglobin level is between 7 and 9g/dl. Removing an infected catheter or de-briding an infected wound like the oneMrs. McKenna has, for example, can be asimportant in preventing sepsis from pro-gressing as providing the right antibiotictherapy. If the patient’s blood pressure islow, norepinephrine or dopamine can begiven intravenously (I.V.) to cause vasocon-striction and raise the blood pressure.

Many patients with sepsis need help withbreathing. If the patient is mechanically ven-tilated, keep the tidal volume at 6 ml/kg toprotect the lungs from damage due to high

pressures (barotrauma). Mechanically venti-lated patients are also at risk for ventilator-associated pneumonia (VAP). To reduce thepatient’s risk, keep the head of the bed ele-vated at 45 degrees, provide frequent oralcare, and use aseptic technique when suc-tioning.

Your patient may have kidney damagethat causes acute renal failure. In the past,renal-dose dopamine was used, but ourthinking on this practice has changed. Nowwe know that these patients should undergorenal replacement therapy via hemodialysis,continuous arterial-venous hemofiltration(CAVH) or continuous venous-venoushemofiltration (CVVH). A patient with lowblood pressure who may be unable to with-stand the pull-off of blood with hemodialy-sis may be a good candidate for CAVH orCVVH—at least until his blood pressureimproves—because CAVH and CVVH usethe patient’s blood pressure to drive the rateof dialysis.

Some patients may need medications toboost the strength of their heart contractions.Dobutamine, given I.V., is recommended inthese situations. As the strength of the heartcontractions increased, the blood pressure

30 Nursing made Incredibly Easy! November/December 2004

did youknow?Responding to thegrim statistics aboutsepsis, a group ofcritical care andinfectious diseaseexperts from 11international organi-zations got togetherand developedmanagement guide-lines for severe sep-sis and septicshock. The guide-lines, released in2003, were pro-duced as part of theSurviving SepsisCampaign, whichwas launched toincrease awarenessand improve out-comes in cases ofsevere sepsis. Formore information,visit http://www.survivingsepsis.org.

A new way to fight severe sepsisDrotrecogin alfa, recombinant human activated protein C (Xigris), was approved in November 2001 bythe Food and Drug Administration for the treatment of severe sepsis in adult patients with a high riskof death. Safety and effectiveness of the treatment for patients under the age of 18 years have notbeen established. Clinical trials were terminated due to significantly lower mortality in patients givendrotrecogin alfa than in patients given placebo.

Drotrecogin alfa is believed to decrease inflammation and coagulation and restore fibrinolysis insevere sepsis. Because of the anticoagulant effects of the treatment, one of the main concerns is thepotential for bleeding. However, because patients who are candidates for drotrecogin alfa have sucha high risk of dying from severe sepsis, the benefit of reduced mortality often outweighs the increasedrisk of bleeding.

Drotrecogin alfa is administered intravenously (I.V.) as a continuous infusion at a rate of 24mcg/kg/hr over 96 hours. Use a dedicated I.V. line or a dedicated lumen of a central venous catheterto infuse the drug. The only other solutions that can be mixed with it are 0.9% sodium chloride, lactat-ed Ringer’s, dextrose, and dextrose and sodium chloride.

Drotrecogin alfa is supplied in 5-mg and 20-mg single-use vials. It should be stored in a refrigeratorbetween 36° F and 46° F (2° C to 8° C).

improves slightly because the heart is work-ing more efficienty.

Several other evidence-based treatmentstrategies show improved outcomes forpatients with severe sepsis (see TreatmentStrategies). Tight glycemic control—that is,maintaining a blood glucose level less than150 mg/dl—is one of them. Mrs. McKennahas been lax in this area the past few years,and her blood glucose level is now over 200mg/dl. Treatment guidelines also include useof steroid therapy for patients with adrenalinsufficiency. Preventive measures for deepvein thrombosis (DVT) and stress pepticulcers should be initiated. Subcutaneouslyadministered low-molecular weight heparin(such as dalteparin [Fragmin], enoxaparin[Lovenox], or tinzaparin [Innohep]) or unfrac-tionated heparin should be used if the patienthas no contraindications for these drugs.Mechanical compression boots can also beused to reduce the risk of DVT. Stress pepticulcers can be prevented with histamine-2receptor blockers (such as cimetidine[Tagamet], famotidine [Pepcid AC], nizati-dine [Axid], and ranitidine [Zantac]). Protonpump inhibitors may also be tried, but furtherresearch is needed for this use.

To combat inflammatory and procoagula-tion responses, drotrecogin alfa (recombinanthuman activated protein C [Xigris]) is indicat-ed for patients with severe sepsis who have atleast two of the SIRS criteria and evidence ofearly organ system failure. Drotrecogin alfa isthe first approved cogin, a class of agents thatinhibit coagulation, decrease the inflammatoryresponse, and promote fibrinolysis in sepsis.Although bleeding is a risk when drotrecoginalfa is given, the health care provider shouldweigh this risk against the potential benefitsfor patients with sepsis-induced organ failure,acute respiratory distress syndrome, and sep-tic shock. See A New Way to Fight Severe Sepsisfor more information on this treatment.

Be on the lookoutThe importance of your role in helping toimprove the outcome for your patients at

risk for or who already havesepsis can’t be overstated.Look for the early warningsigns, such as changes in vi-tal signs, signs of infection,and the presence of SIRScriteria.

While per-forming yourassessment,monitor thepatient forsigns of organsystem dysfunc-tion, such as:■ cardiovascularcompromise with tachycardia and hy-potension■ respiratory compromise requiring me-chanical ventilation■ onset of acute respiratory failure fromacute lung injury or acute respiratory dis-tress syndrome (ARDS)■ acute renal failure with oliguria■ hematologic abnormalities■ skin color changes■ altered mental status.

Treatment for your patient with sepsisincludes providing circulatory support withfluids, inotropes, and vasopressors; initiatingantibiotic therapy early; giving supportivetreatment with oxygenation and ventilation;and monitoring and reporting the patient’sresponse to treatments. Remember that sep-sis is hard on everyone. Do what you can topromote patient and family comfort: Providethe patient with adequate pain relief andsedation. Educate the patient and family onsepsis.

An important ingredient in sepsis treat-ment is taking steps to prevent it from hap-pening in the first place. You can do yourpart by observing guidelines for handwash-ing; oral care; proper positioning, turning,and skin care; invasive catheter care; andwound care. Identify patients at risk for sep-sis; it’s very likely that these will also be yoursickest patients.

November/December 2004 Nursing made Incredibly Easy! 31

Here’s another reasonfor tight glycemic

control: It can helpimprove outcomes in

severe sepsis.

November/December 2004 Nursing made Incredibly Easy! 33

No guaranteesAlthough the emphasis is often on treat-ment measures for severe sepsis to pro-mote survival, don’t forget the psychoso-cial aspects of care. Help communicatelikely outcomes and realistic treatmentgoals to patients, families, and caregivers,and give them the opportunity to askquestions and express their concerns. Pa-tients with severe sepsis tend to have acomplex medical course and are at risk forextended hospitalization and courses oftreatment, with the end result being ru-inous medical costs and high mortalityrates. Survivors of severe sepsis aren’t outof the woods: According to a recent study,patients have a 26% predicted mortalityrate within 1 year of surviving severe sep-sis. Many die of lung complications.

Severe sepsis is a complex condition witha high mortality rate. It presents a formida-

ble challenge to everyone involved in choos-ing and carrying out the best possible treat-ment strategy. Early detection and prompttreatment will give you an edge in the battleagainst this dangerous foe. ■

Learn more about itAhrens, T., and Vollman, K.: “Severe Sepsis Management:Are We Doing Enough?” Critical Care Nurse. 23(5 Suppl):2-15; quiz 17, October 2003.

Angus, D., et al.: “Epidemiology of Severe Sepsis in theUnited States: Analysis of Incidence, Outcome, and Asso-ciated Costs of Care,” Critical Care Medicine. 29:1303-1310,July 2001.

Benjamin, C., et al.: “The Chronic Consequences of SevereSepsis,” Journal of Leukocyte Biology. 75:408-412, April 2003.

Dellinger, R., et al.: “Surviving Sepsis Campaign Guide-lines for Management of Severe Sepsis and Septic Shock,”Critical Care Medicine. 32:858-872, March 2004.

Kleinpell, R.: “The Role of the Critical Care Nurse in theAssessment and Management of the Patient with SevereSepsis,” Critical Care Nursing Clinics of North America.15:27, March 2003.

Levy, M., et al.: “2001 SCCM/ESICM/ACCP/ATS/SIS In-ternational Sepsis Definitions Conference,” Critical CareMedicine. 31:1250-1256, April 2003.

CE TestWinning the battle against severe sepsis

Instructions• Read the article beginning on page 26.• Take the test, recording your answers in the test answerssection (Section B) of the CE enrollment form on page 35. Eachquestion has only one correct answer.• Complete registration information (Section A) and courseevaluation (Section C).• Mail completed test with registration fee to: Lippincott Williams& Wilkins, CE Group, 333 7th Ave., 19th Floor, New York, N.Y.10001.• Within 3 to 4 weeks after your CE enrollment form is received,you will be notified of your test results.• If you pass, you will receive a certificate of earned contact hoursand an answer key. If you fail, you have the option of taking thetest again at no additional cost.• A passing score for this test is 11 correct answers.• Need CE STAT? Visit http://www.nursingcenter.com for immedi-ate results, other CE activities, and your personalized CE plannertool.• No Internet access? Call 1-800-933-6525, ext. 6617 or ext.6621, for other rush service options.• Questions? Contact Lippincott Williams & Wilkins: 646-674-6617 or 646-674-6621.

Registration Deadline: December 31, 2006

Provider AccreditationThis Continuing Nursing Education (CNE) activity for 1.5 contacthours is provided by Lippincott Williams & Wilkins, which is accred-ited as a provider of continuing education in nursing by theAmerican Nurses Credentialing Center’s Commission onAccreditation and by the American Association of Critical-CareNurses (AACN 00012278, CERP Category A). This activity is alsoprovider approved by the California Board of Registered Nursing,Provider Number CEP 11749 for 1.5 contact hours. LWW is also anapproved provider of CNE in Alabama, Florida, and Iowa and holdsthe following provider numbers: AL #ABNP0114, FL #FBN2454, IA#75. All of its home study activities are classified for Texas nurs-ing continuing education requirements as Type I.

Your certificate is valid in all states. This means that your certifi-cate of earned contact hours is valid no matter where you live.

Payment and Discounts• The registration fee for this test is $12.95.• If you take two or more tests in any nursing journal published byLWW and send in your CE enrollment forms together, you maydeduct $0.75 from the price of each test.• We offer special discounts for as few as six tests and institu-tional bulk discounts for multiple tests. Call 1-800-933-6525,ext. 6617 or ext. 6621, for more information.

34 Nursing made Incredibly Easy! November/December 2004

1. Sepsis and SIRS are associated witha. decreased release of prostaglandins.b. activation of the clotting cascade.c. decreased inflammatory response.

2. Which of these manifestations suggests septic shock?a. bradycardiab. hypoventilationc. hypotension

3. If a patient exhibits unexplained mental statuschanges, which additional observations should you rec-ognize as indicative of sepsis?a. fever, chills, and shiveringb. rales, periorbital edema, and polyuriac. drowsiness and decreased blood glucose

4. Test results you should expect to see in a patient withsepsis includea. decreased red blood cell count.b. decreased hematocrit.c. decreased platelet count.

5. Which class of medication is recommended to in-crease tissue perfusion in a patient with severe sepsis?a. antihypertensivesb. inotropicsc. anticoagulants

6. A patient with a central line catheter for chemotherapyhas symptoms that suggest sepsis. You should obtaintwo blood cultures, one percutaneously and the otherfrom thea. carotid artery.b. femoral artery.c. central line catheter.

7. Adverse effects of drotrecogin alfa (Xigris) includea. bleeding.b. infection.c. dyspnea.

8. The blood glucose level of a patient with severe sepsisshould be maintained at less thana. 50 mg/dl.b. 75 mg/dl.c. 150 mg/dl.

9. Prophylactic treatment for a patient with severe sepsisis aimed at preventing which of these complications?a. deep vein thrombosisb. infected leg ulcerationsc. gangrene of the lower extremities

10. A patient with severe sepsis is a candidate for steroidtherapy if he hasa. recurrent exacerbations of chronic obstructive pulmonary

disease during treatment.b. adrenal insufficiency.c. acute renal failure.

11. The plan of care for a patient with severe sepsisshould includea. applying pressure dressings over infected wounds.b. turning, positioning, and providing skin care.c. limiting oral food and fluid intake.

12. Which of these test results suggests sepsis?a. PaCO2, 36 mm Hgb. white blood cells, 10,000 mm3

c. 15% immature band forms

13. Which central venous pressurereading indicates adequate fluidresuscitation in a patient with se-vere sepsis?a. 4 mm Hgb. 7 mm Hgc. 10 mm Hg

14. Which of these manifestations suggestsorgan failure in a patient with septic shock?a. tachypnea and hypoxemiab. back pain and feverc. sweating and anorexia

15. Which of these testsshould be monitored to de-tect evidence of organ failurein a patient with severe sep-sis?a. liver enzymesb. thyroid studiesc. blood culture and

sensitivity

1.5 ANCC/AACN CONTACT HOURS

C E

Winning the battle against severe sepsisGENERAL PURPOSE: To describe the manifestations, treatment, and nursing management of severe sepsis. LEARNINGOBJECTIVES: After reading the article and taking this test, you’ll be able to: 1. Identify the manifestations and risk factors fordeveloping severe sepsis. 2. Describe recommended treatments for severe sepsis. 3. Explain the nursing management of a pa-tient with severe sepsis.

Are youready to dobattle with

severesepsis?

Turn to page 35 for the CE Enrollment Form.