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Home > Library > From inflammation to MODS: Stopping sepsis in its tracks |
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Abstract
Severe sepsis is the leading causeof noncardiac critical care deathsin the United States. You may be the first to see changes in your patient's condition that might lead to multiple organ dysfunction syndrome. Find out what you need to know for early intervention.  Figure. No caption available. SEPSIS IS SERIOUS BUSINESS: In 2003, septicemia—a type of sepsis—ranked as the 10th leading cause of death in the United States. About 750,000 patients are diagnosed with sepsis each year, and it's the leading cause of noncardiac deaths in intensive care units. Despite intensive research efforts to develop effective treatments, the sepsis mortality rate hasn't declined: 28% to 50% of patients who develop sepsis die. The death rate is even higher among those with more severe cases. Not only is the condition physically devastating for patients, but it also places an enormous strain on the health care system. The annual cost for treating sepsis is a staggering $16 billion to $17 billion—approximately $22,000 per sepsis patient. In this article, I'll give you some insights into what sepsis is, who's at risk, and how you can intervene.  Figure. No caption available. A continuum of severity
Sepsis can be described as a step along a continuum that begins with a generalized inflammatory response to a trigger. The progression from infection to sepsis to septic shock to multiple organ dysfunction syndrome (MODS) is known as systemic inflammatory response syndrome (SIRS). The trigger is often a general or localized infection, but SIRS can also result from a noninfectious injury, such as a trauma or burn, or a serious illness, such as pancreatitis. SIRS is a condition of progressive severity rather than a specific disease entity. Let's take a closer look at the four stages, from low to high severity: * Infection can be caused by Gram-negative microorganisms, Gram-positive microorganisms, fungi, viruses, or parasites. Until 1988, Gram-negative microorganisms were the most frequent cause of sepsis-related infections. Since then, Gram-positive microorganisms have been the biggest culprits. The number of cases of sepsis caused by fungal infections has also risen dramatically since 1979.
* Sepsis involves organ dysfunction, as the pathogens or toxins from pathogens travel through the blood and into tissues. Any organ system can be affected, but the cardiovascular and pulmonary systems are often the first to become involved.
* Septic shock is the next stage in the continuum. It presents differently in adults than in children. The hallmark of septic shock in adults is persistent unexplained hypotension despite adequate fluid volume resuscitation. In children, the earliest sign of septic shock is usually tachycardia, with signs of decreased tissue perfusion.
* MODS , also referred to as multisystem organ failure, is the end stage—and the most severe stage—of SIRS, and it frequently ends in death. Some researchers speculate that MODS may actually represent the body's last-ditch attempt to ensure cell survival in the face of overwhelming systemic infection and inflammation. They believe that MODS may be an endocrine-mediated metabolic response to a massive attack on the body.
Organ dysfunction in MODS can be primary or secondary. In primary organ dysfunction, the organs have received a direct insult from disease, infection, or trauma that's causing the dysfunction. In secondary organ dysfunction, unchecked inflammation causes the dysfunction. In either type, the risk of death increases as more of the body's organs become dysfunctional. Complex pathophysiology
The pathophysiology of SIRS is complex. We don't completely understand it, and it hasn't yet been well defined in medical literature. According to one source, four elements may be involved in its development: * Individual host response . A patient's physiologic response (host response) to the insult or infection primarily determines whether the person will recover. Because this host response differs from one patient to another, treatment that works for one patient may not work for the next. So, it's important for the treatment regimen to be individualized.
* Endothelial cell and monocyte response . Endothelial cells and monocytes (large white blood cells involved in the first line of immune defense and in the inflammatory process) are both central to beginning and continuing the host response. They've been described as the cornerstones of immune response because they recognize invading pathogens and initiate the host response to invasion.
* Simultaneous inflammation and coagulation . SIRS involves the simultaneous activation of the body's inflammatory and coagulation cascades. In the inflammatory cascade, anti-inflammatory mediators are released. In the coagulation cascade, the body attempts to isolate the infection and protect itself. This results in widespread microvascular clotting.
* Host response to inflammation . The patient's response to inflammation may cause collateral damage of normal tissues. This damage is usually localized, so dysfunction will develop in a limited number of organs. The endothelium is believed to determine the sites of the localized response. In general, the host response to infection is believed to be more important than the type of infectious organism involved.
Early recognition is key
Effective treatment requires early recognition of SIRS—and the best way to catch the syndrome in its early stages is to identify patients who are most at risk for developing it. They include: * very young and very old patients
* malnourished or immunocompromised patients
* patients who have invasive catheters
* patients with preexisting chronic disease
* critically ill or critically injured patients
* patients on long-term steroid medications or antibiotics
* patients who are comatose when admitted.
According to criteria developed by the International Sepsis Definitions Conference, sepsis is diagnosed in adults by determining the presence or suspicion of infection, as well as the presence of additional symptoms divided into general, inflammatory, hemodynamic, organ dysfunction, and tissue perfusion categories. In children, the diagnostic criteria for sepsis include signs and symptoms of inflammation and infection with increased or decreased temperature, and signs of organ dysfunction. Two or more of the following SIRS conditions can indicate sepsis: * temperature more than 38°C (100.4°F) or less than 36°C (96.8°F)
* heart rate more than 90 beats per minute
* respiratory rate more than 20 breaths per minute or Paco 2 less than 32 mm Hg (less than 4.3 kPa)
* white blood cell count more than 12,000 cells/mm 3 , less than 4,000 cells/mm 3 , or more than 10% immature (band) forms.
Other signs and symptoms of sepsis include: * chills
* hypotension
* decreased skin perfusion
* decreased urine output
* significant edema or positive fluid balance (more than 20 ml/kg over 24 hours)
* decreased capillary refill or mottling
* hyperglycemia (plasma glucose more than 120 mg/dl) in the absence of diabetes
* unexplained change in mental status.
The earlier you help identify possible infection or sepsis, the earlier the treatment can begin—and the sooner treatment is started, the better chance your patient has of surviving. Treating SIRS
The first step in caring for a patient with SIRS is to identify and treat the underlying cause. If infection is present, the patient's health care provider will institute appropriate antibiotic therapy. See New treatment strategies for severe sepsis for more information. In general, treatment is individualized to fit the patient's physiologic response to SIRS. For example: * mechanical ventilation for a SIRS patient with inadequate oxygenation and ventilation
* intravenous (I.V.) fluids and vasopressors for a patient whose blood pressure isn't stable
* hemodialysis or kidney replacement therapy for a patient with decreased or absent urine output
* I.V. insulin for all patients with a serum glucose level consistently higher than 110 mg/dl
* blood and blood products for a patient who develops anemia.
Only one drug has been approved by the Food and Drug Administration for treating severe sepsis in adults: recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated; Xigris). See A novel way to fight severe sepsis for more information on this drug. What's your role?
Nurses play a critical role in the early identification of sepsis. As one of the health care professionals closest to the patient, you're in a good position to identify changes in the patient's condition that can herald sepsis. Additionally, as health care professionals become increasingly aware of the need to diagnose and treat sepsis quickly, some facilities have instituted “sepsis codes” and have organized rapid-response teams that assist nurses at the first sign of a possible sepsis case. If your facility has either or both of these programs, you're a step ahead of the game. Even if it doesn't, however, the best you can do for your patients is to know the risk factors for sepsis, thoroughly assess each patient, and be prepared to identify any patient in your care who appears to be at risk. Vigilant assessment will help you spot changes that could indicate sepsis early in the process, when the patient has a better chance of surviving. If you suspect a patient may be developing SIRS, keep a close eye on his vital signs. As you know, fever is a common sign of infection. However, immunocompromised patients can't mount a “defense” against infection, so you may see a lower-than-normal body temperature. As I mentioned earlier, organ dysfunction from SIRS occurs most frequently in the cardiovascular and pulmonary systems, so monitor your patient closely for changes in pulse, blood pressure, and respiratory rate. In adults, you'll notice increased pulse and respiration rates before you see a drop in blood pressure. In children who may be developing SIRS, increased pulse and respiratory rate are also the main indicators of possible organ dysfunction. If you anticipate problems, report your concerns and monitor vital signs more frequently. Some signs and symptoms of organ failure are specific to the organ system that's affected. Kidney dysfunction , for example, may result in decreased urine output and/or a high serum creatinine level. Keep accurate intake and output records. A patient with liver dysfunction may have yellowish (jaundiced) skin, and he may have dark urine and light stools. If the patient has hematologic dysfunction , he may show signs of bleeding such as petechiae, tarry stools, or significant bruising, or he may exhibit frank bleeding. With gastrointestinal dysfunction , the patient may experience nausea, vomiting, or diarrhea; have hyperactive, hypoactive, or absent bowel sounds; or have large tube feeding residuals. The patient with neurologic dysfunction may exhibit altered states of consciousness ranging from new onset confusion to coma. Expect to administer broad-spectrum antibiotics; change I.V. lines, dressings, and catheters aseptically (according to your institution's policies); keep accurate intake and output records; and check vital signs frequently. Wash your hands often to protect your patients from nosocomial infections. If your patient continues to deteriorate, notify his health care provider immediately. Better odds
As the number of older patients in the United States increases, the incidence of sepsis is expected to grow by 1.5% annually. You can help improve your patient's chance of surviving by recognizing early changes, keeping close tabs on vital signs, and being vigilant with treatment. Signs of acute organ system failure
Cardiovascular * Tachycardia
* Arrhythmias
* Hypotension
* Elevated central venous and pulmonary artery pressures
Respiratory * Rapid breathing
* Low blood oxygen level
Renal * Scant or absent urine production
* Elevated creatinine
Hematologic * Jaundice
* Elevated liver enzymes
* Decreased albumin
* Insufficient clotting
Gastrointestinal * Ileus (absent bowel sounds)
Hepatic * Low platelet count
* Insufficient clotting
* Decreased protein C levels
* Increased D-dimer levels
Neurologic * Altered consciousness
* Confusion
* Psychosis
New treatment strategies for severe sepsis
1. Initiate resuscitation for sepsis-induced hypoperfusion .
* Fluid resuscitation to a central venous pressure of 8 to 12 mm Hg
* Transfusion of packed red blood cells to achieve a hematocrit of 30% or higher
* Administration of inotropic infusion (such as dobutamine)
2. Obtain appropriate diagnostics .
* Obtain at least two blood cultures, with one drawn percutaneously and one drawn through each vascular access device; obtain cultures of other sites, such as urine, wounds, and respiratory secretions before initiating antibiotic therapy.
* Diagnostic studies (such as ultrasound, imaging studies)
3. Initiate antibiotic therapy .
* Empirical antibiotics
4. Control the source of infection .
* Removal of potentially infected device, drainage of abscess, debridement of infected necrotic tissue
5. Enhance perfusion .
* Fluid therapy
* Vasopressors
* Inotropic therapy
6. Consider the use of steroids .
* For patients with relative adrenal insufficiency
7. Consider the use of drotrecogin alfa (recombinant human activated protein C [Xigris]) .
* For patients with sepsis-induced multiple organ failure with no absolute contraindication related to bleeding risk
8. Administer blood products if hemoglobin is below 7 grams/dl .
* To target hemoglobin of 7 to 9 grams/dl
9. Initiate mechanical ventilation if needed .
* Lung-protective ventilation for acute lung injury/acute respiratory distress syndrome
* Use low tidal volumes (6 ml/kg ideal body weight) and plateau pressures at 30 cm H 2 O or less
* Keep the head of the bed at 45 degrees or more and provide frequent oral care to prevent ventilator-associated pneumonia
10. Provide sedation and analgesia .
* To provide comfort yet avoid prolonged sedation
* Consider neuromuscular blockade only as a last resort
11. Control the blood glucose level .
* To maintain blood glucose at less than 150 mg/dl
12. Keep the kidneys functioning .
* Initiate renal replacement therapy in acute renal failure
13. Initiate preventive measures .
* Use subcutaneously administered low-molecular–weight heparin or unfractionated heparin if appropriate and mechanical compression devices to prevent deep vein thrombosis
* Use histamine- 2 receptor blockers to prevent stress peptic ulcer
14. Communicate with the patient and family .
* Family discussion about life-sustaining therapies
* End-of-life care discussion for critically ill patients
Adapted from Dellinger, R., et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Critical Care Medicine . 32:858–872, March 2004. A novel way to fight severe sepsis
Treating the underlying infection and providing supportive care may not necessarily stop the progression of sepsis. Currently, only one drug is available that can lower the mortality rate for systemic inflammatory response syndrome: recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated). The drug, marketed under the brand name Xigris, was approved in November 2001 by the Food and Drug Administration for the treatment of severe sepsis in adult patients with a high risk of death. Drotrecogin alfa (activated) is administered intravenously (I.V.) as a continuous infusion at a rate of 24 mcg/kg/hr over 96 hours. A dedicated I.V. line or a dedicated lumen of a central venous catheter must be used to infuse the drug. It can only be mixed with 0.9% sodium chloride, lactated Ringer's, dextrose, and dextrose and sodium chloride. The drug works by decreasing inflammation and coagulation and increasing clot breakdown in the body. It's contraindicated, however, in the following patients: * those who are hypersensitive to the drug
* patients with increased risk of hemorrhage
* patients who have an epidural catheter
* patients with an intracranial tumor or a mass lesion
* patients who have cerebral herniation.
Caution is recommended in using drotrecogin alfa (activated) to treat patients who've had a recent bleeding episode, take anticoagulant medications, or have abnormal lab test results for coagulation. In pregnant women, the benefits of use must outweigh the risks. No data exist on whether drotrecogin alfa (activated) is effective for treating children. Widespread use of drotrecogin alfa (activated) for adults has been hampered by the difficulty in identifying patients who can benefit from it, and by the cost of treatment—approximately $6,800 for an average adult. On the Web
Advances in Sepsis: http://www.advancesinsepsis.com , American Sepsis Alliance: http://www.sepsisalliance.org , Sepsis Overview: http://www.sepsis.com , Society of Critical Care Medicine: http://www.sccm.org Selected references
Dellinger RP, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Critical Care Medicine . 32(3):858–73, March 2004. Devlin MM. A new tool for fighting sepsis. Nursing2004 . 34(5):33–35, May 2004. Kleinpell RM. Working out the complexities of severe sepsis. Nursing Management . 30(4):43–4, 46–8, April 2005. Mower-Wade D, Kang TM. Sepsis: When defense turns deadly. Nursing2004 . 34(7):32cc1-32cc4, July 2004. Schuman CS, Hare K. New thoughts on sepsis: The unifier of critical care. Dimensions of Critical Care Nursing . 22(1):20–30. |
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