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Sepsis

**Sepsis**
*Classification & external resources*
ICD-10	A40. - A41.0
ICD-9	995.91
DiseasesDB	11960
MeSH	D018805

Sepsis is a serious medical condition characterized by a whole-body inflammatory state caused by infection.

Traditionally the term sepsis has been used interchangeably with septicaemia/septicemia ("blood poisoning").^[1] However, these terms are no longer considered synonymous as they are considered a subset of sepsis.^[2]

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Signs and symptoms

Symptoms of sepsis are often related to the underlying infectious process. When the infection crosses into sepsis, the resulting symptoms are that of systemic inflammatory response syndrome (SIRS): general inflammation, fever, elevated white blood cell count (leukocytosis), and raised heart rate (tachycardia) and breathing rate (tachypnea). Secondary to the above, symptoms also include flu like chill.

The immunological response that causes sepsis is a systemic inflammatory response causing widespread activation of inflammation and coagulation pathways. This may progress to dysfunction of the circulatory system and, even under optimal treatment, may result in the multiple organ dysfunction syndrome and eventually death.

Epidemiology

In the United States, sepsis is the leading cause of death in non-coronary ICU patients, and the tenth most common cause of death overall according to data from the Centers for Disease Control and Prevention.^[3] Sepsis is common and also more dangerous in elderly, immunocompromised, and critically ill patients. It occurs in 1%-2% of all hospitalizations and accounts for as much as 25% of intensive care unit (ICU) bed utilization. It is a major cause of death in intensive care units worldwide, with mortality rates that range from 20% for sepsis to 40% for severe sepsis to >60% for septic shock.

Definition of sepsis

Sepsis is considered present if infection is highly suspected or proven and two or more of the following systemic inflammatory response syndrome (SIRS) criteria are met:^[4]

Heart rate > 90 beats per minute
Body temperature < 36 (96.8 °F) or > 38 °C (100.4 °F)
Hyperventilation (high respiratory rate) > 20 breaths per minute or, on blood gas, a P_aCO₂ less than 32 mm Hg
White blood cell count < 4000 cells/mm³ or > 12000 cells/mm³ (< 4 x 10⁹ or > 12 x 10⁹ cells/L), or greater than 10% band forms (immature white blood cells).

Consensus definitions however continue to evolve with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.^[5]

The more critical subsets of sepsis are severe sepsis (sepsis with acute organ dysfunction) and septic shock (sepsis with refractory arterial hypotension). Alternatively, when two or more of the systemic inflammatory response syndrome criteria are met without evidence of infection, patients may be diagnosed simply with "SIRS." Patients with SIRS and acute organ dysfunction may be termed "severe SIRS."

Patients are defined as having "severe sepsis" if they have sepsis plus signs of systemic hypoperfusion; either end organ dysfunction or a serum lactate greater than 4 mmol/dL. Patients are defined as having septic shock if they have sepsis plus hypotension after an appropriate fluid bolus (typically 20 ml/kg of crystaloid).

The criteria for diagnosing an adult with sepsis do not apply to infants under one month of age. In infants, only the presence of infection plus a "constellation" of signs and symptoms consistent with the systemic response to infection are required for diagnosis (Oski's Pediatrics, 2006).

Treatment

The therapy of sepsis rests on antibiotics, surgical drainage of infected fluid collections, fluid replacement and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition, if necessary by parenteral nutrition, is important during prolonged illness.

A problem in the adequate management of septic patients has been the delay in administering therapy after sepsis has been recognized. Published studies have demonstrated that for every hour delay in the administration of appropriate antibiotic therapy there is an associated 7% rise in mortality. A large international collaboration was established to educate people about sepsis and to improve patient outcomes with sepsis, entitled the "Surviving Sepsis Campaign." The Campaign has published an evidence-based review of management strategies for severe sepsis,^[6] with the aim to publish a complete set of guidelines in subsequent years.

Early Goal Directed Therapy (EGDT), developed at Henry Ford Hospital by E. Rivers, MD, is a systematic approach to resuscitation that has been validated in the treatment of severe sepsis and septic shock. It is meant to be started in the Emergency Department. The theory is that one should use a step-wise approach, having the patient meet physiologic goals, to optimize cardiac preload, afterload, and contractility, thus optimizing oxygen delivery to the tissues.^[7]

In EGDT, fluids are administered until the central venous pressure (CVP), as measured by a central venous catheter, reaches 8-12 cm of water (or 10-15 cm of water in mechanically ventilated patients). If the mean arterial pressure is less than 65 mmHg or greater than 90 mmHg, vasopressors or vasodilators are given as needed to reach the goal. Once these goals are met the central venous saturation (ScvO2), i.e. the oxgyen saturation of venous blood as it returns to the heart as measured at the superior vena cava, is optimized. If the ScvO2 is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the ScvO2 is optimized. Elective intubation may be performed to reduce oxygen demand if the ScvO2 remains low despite optimization of hemodynamics. Urine output is also monitored, with a goal of 0.5 ml/kg/h. In the original trial, mortality was cut from 46.5% in the control group to 30.5% in the intervention group.^[7] The Surviving Sepsis Campaign guidelines recommends EGDT for the initial resuscitation of the septic patient with a level B strength of evidence (single randomized control trial).^[6]

Most therapies aimed at the inflammatory process itself have failed to improve outcome, however drotrecogin alfa (activated protein C, one of the coagulation factors) has been shown to decrease mortality from about 31% to about 25% in severe sepsis. To qualify for drotrecogin alfa, a patient must have severe sepsis or septic shock with an APACHE II score of 25 or greater and a low risk of bleeding.^[8] Low dose hydrocortisone treatment has shown promise for septic shock patients with relative adrenal insufficiency as defined by ACTH stimulation testing.^[9]

Standard treatment of infants with suspected sepsis consists of supportive care, maintaining fluid status with intravenous fluids, and the combination of a beta-lactam antibiotic (such as ampicillin) with an aminoglycoside such as gentamicin.

Prognosis

Prognosis can be estimated with the MEDS score.^[10]

Related conditions/complications

Infection is the invasion of normally sterile host tissues by a microbial pathogen.
Bacteremia is the presence of bacteria in the blood. Bacteremia can occur in sepsis and other serious diseases such as infective endocarditis, bacteremic pyelonephritis or pneumonia and meningitis but it may also be a harmless and transient condition.
Viremia is the presence of viruses in the blood.
Septic joint is an infection of a joint; it is associated with bacteremia and trauma.
Disseminated intravascular coagulation (DIC) can be the result of sepsis
Acute tubular necrosis (ATN) leading to acute renal failure, can be the result of hypoperfusion of the kidneys in sepsis (i.e. not enough blood gets to the kidney and they stop working properly)
Arrhythmia is an abnormal heart rhythm; it can be the result of sepsis.
Ileus or ischemic colitis can be the result (hypoperfusion) or cause of sepsis
Multiple organ dysfunction syndrome can be the result of sepsis
Meningitis, infection of the tissue that covers the brain and spinal cord, can be a complication or cause of sepsis
Osteomyelitis is an infection of the bone; it can be the cause or result of sepsis
Endocarditis, infection of the inner surface of heart which is in contact with blood, can also be a complication or cause of sepsis
Pyaemia — causes abscesses

References

^ Stedman's Medical Dictionary. URL: http://www.emedicine.com/asp/dictionary.asp?keyword=septicemia. Accessed on: June 30, 2007.
^ Stedman's Medical Dictionary. URL: http://www.emedicine.com/asp/dictionary.asp?keyword=sepsis. Accessed on: June 30, 2007.
^ Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. PMID 12700374 Full Text.
^ Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. PMID 1303622.
^ Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.
^ ^a ^b Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73. Erratum in: Crit Care Med. 2004 Jun;32(6):1448. Correction of dosage error in text. Crit Care Med. 2004 Oct;32(10):2169-70. PMID 15090974.
^ ^a ^b Rivers E, Nguyen B, Havstad S, et al (2001). "Early goal-directed therapy in the treatment of severe sepsis and septic shock". N. Engl. J. Med. 345 (19): 1368-77. PMID 11794169.
^ Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. PMID 11236773 Full Text.
^ Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. PMID 12186604.
^ Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW (2003). "Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule". Crit. Care Med. 31 (3): 670-5. doi:10.1097/01.CCM.0000054867.01688.D1. PMID 12626967.