sepsis n : the presence of pus-forming bacteria or their toxins in the blood or tissues
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. While the term sepsis is frequently used to refer to septicemia (blood poisoning), septicemia is but one type of sepsis. Bacteremia specifically refers to the presence of bacteria in the bloodstream (viremia and fungemia are analogous terms for viruses and fungi).
Signs and symptomsIn 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.
EpidemiologyIn 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. 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 sepsisSepsis 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:
- Heart rate > 90 beats per minute (tachycardia)
- Body temperature 38 °C (100.4 °F) (hypothermia or fever)
- Respiratory rate > 20 breaths per minute or, on blood gas, a PaCO2 less than 32 mm Hg (4.3 kPa) (tachypnea or hypocapnia due to hyperventilation)
- White blood cell count 12000 cells/mm³ (9 or > 12 x 109 cells/L), or greater than 10% band forms (immature white blood cells). (leukopenia, leukocytosis, or bandemia)
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 fashion:
- Heart rate > 2 standard deviations above normal for age in the absence of stimuli such as pain and drug administration, OR unexplained persistent elevation for greater than 30 minutes to 4 hours. In infants, also includes Heart rate < 10th percentile for age in the absence of vagal stimuli, beta-blockers, or congenital heart disease OR unexplained persistent depression for greater than 30 minutes.
- Body temperature obtained orally, rectally, from Foley catheter probe, or from central venous catheter probe > 38.5°C or < 36°C. Temperature must be abnormal to qualify as SIRS in pediatric patients.
- Respiratory rate > 2 standard deviations above normal for age OR the requirement for mechanical ventilation not related to neuromuscular disease or the administration of anesthesia.
- White blood cell count elevated or depressed for age not related to chemotherapy, or greater than 10% bands + other immature forms.
Note that SIRS criteria are very non-specific, 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.
- acute lung injury(ALI) (PaO2/FiO2 2/FiO2 < 200)
- multifocal necrotizing leukoencephalopathy
More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.:
- generally well appearing
- previously healthy
- full term (at ≥37 weeks gestation)
- no antibiotics perinatally
- no unexplained hyperbilirubinemia that required treatment
- no antibiotics since discharge
- no hospitalizations
- no chronic illness
- discharged at the same time or before the mother
- no evidence of skin, soft tissue, bone, joint, or ear infection
- WBC count 5,000-15,000/mm3
- absolute band count ≤ 1,500/mm3
- urine WBC count ≤ 10 per high power field (hpf)
- stool WBC count ≤ 5 per high power field (hpf) only in infants with diarrhea
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.
Sepsis in Adults and ChildrenThe 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, 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.
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 oxygen 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. Low dose hydrocortisone treatment has shown promise for septic shock patients with relative adrenal insufficiency as defined by ACTH stimulation testing.
Rule Out Sepsis and Suspected Sepsis in NeonatesNote that in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, 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.
PrognosisPrognosis can be estimated with the MEDS score.
- 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.
- Fungemia is the presence of fungi in the blood.
- Septic arthritis is an infection of a joint: it may be due to hematogenous spread of infection resulting in bacteremia, or the direct effect of penetrating 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) and/or direct damage due to the inflammatory agents unleashed by the host's immune response.
- Arrhythmia is an abnormal heart rhythm. In the setting of sepsis, this can arise because of the activation of various neuroendocrine counter-regulatory mechanisms, because of direct effects of cytokines and other inflammatory agents on the myocardium, or because of coronary hypoperfusion due to heart failure related to sepsis.
- Ileus or ischemic colitis can be the result (hypoperfusion) of or cause of sepsis. (Injury to the bowel can result in increased permeability of the bowel wall, allowing pathogens and toxins to freely enter the blood.)
- 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 cause of sepsis.
- Osteomyelitis is an infection of the bone; it can be the cause of sepsis.
- Endocarditis, infection of the inner surface of heart which is in contact with blood, can also be a cause of sepsis.
- Pneumonia is an infection of the lungs.
- Pyelonephritis is infection of the kidney.
- Pyaemia — causes abscesses.
- Septicemia in the Medical Encyclopedia, Medline Plus ("A service of the United States National Library of Medicine [NLM] and the National Institutes of Health [NIH]"). Updated October 27, 2005. Accessed August 31, 2007.
- Surviving Sepsis Campaign
- International Sepsis Forum
- Advances in Sepsis journal
- Medscape Sepsis Resource Center
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