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For the genus of flies of this name, see Sepsidae.
| 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.
Sepsis is broadly defined as the presence of various pus-forming and other pathogenic organisms, or their toxins, in the blood or tissues.Stedman\'s Medical Dictionary. URL: http://www.emedicine.com/asp/dictionary.asp?keyword=sepsis. Accessed on: February 22, 2008. While the term sepsis is frequently used to refer to septicemia (blood poisoning), septicemia is but one type of sepsis.Stedman\'s Medical Dictionary. URL: http://www.emedicine.com/asp/dictionary.asp?keyword=septicemia. Accessed on: June 30, 2007. Bacteremia specifically refers to the presence of bacteria in the bloodstream (viremia and fungemia are analogous terms for viruses and fungi). Septicemia is a term that is deprecated in clinical use.[citation needed]
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In addition to symptoms related to the provoking infection, sepsis is characterized by evidence of acute inflammation present throughout the entire body, and is therefore frequently associated with fever and elevated white blood cell count (leukocytosis). The modern concept of sepsis is that the host\'s immune response to the infection causes most of the symptoms of sepsis, resulting in hemodynamic consequences and damage to organs. This host response has been termed systemic inflammatory response syndrome (SIRS) and is characterized by hemodynamic compromise and resultant metabolic derangement.
This immunological response causes widespread activation of acute phase proteins, affecting the complement system and the coagulation pathways, which then cause damage to the vasculature as well as to the organs. Various neuroendocrine counter-regulatory systems are then activated as well, often compounding the problem. Even with immediate and aggressive treatment, this may progress to multiple organ dysfunction syndrome and eventually death.
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.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. 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.
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: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.
Fever and leukocytosis are features of the acute phase reaction, while tachycardia is often the initial sign of hemodynamic compromise. Tachypnea may be related to the increased metabolic stress due to infection and inflammation, but may also be an ominous sign of inadequate perfusion resulting in the onset of anaerobic cellular metabolism.
In children, the SIRS criteria are modified in the following fashionGoldstein B, Giroir B, Randolph A (2005). "International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics". Pediatr Crit Care Med 6 (1): 2–8. doi:10.1097/01.PCC.0000149131.72248.E6. PMID 15636651. :
Note that SIRS criteria are very non-specificLevy 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., and must be interpreted carefully within the clinical context. These criteria exist primarily for the purpose of more objectively classifying critically-ill patients so that future clinical studies may be more rigorous and more easily reproducible.
Consensus definitions however continue to evolve with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.
To qualify as sepsis, there must be an infection suspected or proven (by culture, stain, or polymerase chain reaction(PCR)), or a clinical syndrome pathognomonic for infection. Specific evidence for infection includes WBCs in normally sterile fluid (such as urine or cerebrospinal fluid(CSF), evidence of a perforated viscus (free air on abdominal x-ray or CT scan, signs of acute peritonitis), abnormal chest x-ray (CXR) consistent with pneumonia (with focal opacification), or petechiae, purpura, or purpura fulminans
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. Other signs include oliguria and altered mental status. Patients are defined as having septic shock if they have sepsis plus hypotension after aggressive fluid resuscitation (typically upwards of 6 liters or 40 ml/kg of crystalloid).
Examples of end-organ dysfunction include the followingAbraham E, Singer M (2007). "Mechanisms of sepsis-induced organ dysfunction". Crit. Care Med. 35 (10): 2408–16. PMID 17948334. :
More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.
In common clinical usage, sepsis specifically refers to the presence of a serious bacterial infection(SBI) (such as meningitis, pneumonia, pyelonephritis, or gastroenteritis) in the setting of fever. Criteria with regards to hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not arise in neonates until death is imminent and unpreventable.
It is difficult to clinically exclude sepsis in newborns less than 90 days old who have fever (defined as a temperature > 38° C (100.4° F). Except in the case of obvious acute viral bronchiolitis, the current practice in newborns less than 30 days old is to perform a complete workup including complete blood count with differential, blood culture, urinalysis, urine culture, and cerebrospinal fluid(CSF) studies and CSF culture, admit the newborn to the hospital, and treat empirically for serious bacterial infection for at least 48 hours until cultures are demonstrated to show no growth. Attempts have been made to see if it is possible to risk stratify newborns in order to decide if a newborn can be safely monitored at home without treatment despite having a fever. One such attempt is the Rochester criteria.
A study performed at Strong Memorial Hospital in Rochester, New York, showed that infants ≤ 60 days old meeting the following criteria were at low-risk for having a serious bacterial illnessDagan R, Powell KR, Hall CB, Menegus MA (1985). "Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis". J. Pediatr. 107 (6): 855–60. PMID 4067741. :
Those meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up.
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—preferrably by enteral feeding, but 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,Dellinger RP, Levy MM, Carlet JM, et.al. International Surviving Sepsis Campaign Guidelines Committee. "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008." Crit Care Med. 2008;36(1):296-327. PMID 18158437 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.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.
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). This may require around 6 liters of isotonic crystalloid solution, rapidly administered. 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 mixed venous oxygen saturation (SvO2), i.e. the oxgyen saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the SvO2 is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the SvO2 is optimized. Elective intubation may be performed to reduce oxygen demand if the SvO2 remains low despite optimization of hemodynamics. Urine output is also monitored, with a minimum 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. 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).
Most therapies aimed at the inflammation 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.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. Low dose hydrocortisone treatment has shown promise for septic shock patients with relative adrenal insufficiency as defined by ACTH stimulation testing.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.
Note that in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is eminent, so if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of causing biliary stasis.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, Escherichia coli, and Listeria monocytogenes (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as Streptococcus pneumoniae and Neisseria meningitidis. Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.
Prognosis can be estimated with the MEDS score.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.
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