◆ Sepsis is the presence of a known or suspected infection and a systemic inflammatory response.
◆ Severe sepsis is sepsis with acute organ dysfunction. Septic shock is a subset of severe sepsis characterized by systemic arterial hypotension or occult hypoperfusion.
◆ Severe sepsis is common, affecting more than 750 000 individuals in the United States each year with a hospital mortality of about 30%.
◆ Severe sepsis is a medical emergency that requires early identification, prompt evaluation, and treatment.
◆ The signs and symptoms of sepsis are influenced by the virulence of the pathogen, the portal of entry, the degree of organ dysfunction as well as the susceptibility and response of the host.
Sepsis is a clinical syndrome resulting from the presence of both an infection and a systemic inflammatory response. It can be complicated by organ dysfunction (severe sepsis) and shock (septic shock) [1,2]. Although the consensus definition for septic shock requires frank hypotension however, some have argued that evidence of hypoperfusion such as an elevated blood lactate ≥4 mmol/L should also be regarded as shock .
In the United States, more than 750 000 individuals develop severe sepsis each year with a hospital mortality of about 30% . Typically, about two cases per 100 hospital admissions develop severe sepsis, and about 10% of all ICU patients have severe sepsis on admission or during their ICU stay [5,6].
The Sepsis Occurrence in Acutely Ill Patients (SOAP) study across Europe reported that more than 35% of ICU patients had sepsis at some point during their ICU stay, with a mortality rate of 27% .
Nearly all microbes can cause sepsis. In immuno-competent hosts, typical causes are Gram-positive and Gram-negative bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Escherichia coli and Pseudomonas species . In immunocompromised hosts, in addition to the usual pathogens, sepsis can also develop secondary to opportunistic organisms. The most frequent type of infection that leads to severe sepsis is pneumonia (44%), followed by primary bacteraemia (17%), genitourinary infection (9%), abdominal infection (9%), and, less commonly, wound and soft tissue infections (7%) . Approximately one-third of septic patients are culture-negative . Bacteria is the predominant cause of severe sepsis, with Gram-positive bacteria accounting for about 52% of cases, Gram-negative bacteria (38%), polymicrobial infections (5%), anaerobes (1%), and fungi (5%) .
When to suspect sepsis
Obvious sepsis cases with fever, leukocytosis, hypotension, and known infection require little skill to detect. The astute clinician recognizes that the initial presentation of sepsis can be subtle and non-specific, such as unexplained tachypnoea, altered mental status, hyperglycaemia, and diaphoresis. It is also important to recognize that elderly and immuno-suppressed patients with sepsis often do not have fever or leukocytosis. In such patients, hypothermia should specifically be sought for, and if found, treated seriously. Other physical and laboratory findings that prompt an experienced clinician to conclude that an infected patient ‘looks septic’ are outlined in Box 295.1. This list is by no means specific, but should help the clinician in identifying a septic patient and guide the early institution of adequate therapy including empiric antimicrobial therapy.
Reproduced from Levy MM, '2001 SCCM/ESICM/ ACCP/ATS/SIS International Sepsis Definitions Conference', Critical Care Medicine, 31(4), pp. 1250–6, copyright 2003, with permission from Wolters Kluwer Health and Society of Critical Care Medicine.
How to work up sepsis
History and physical
Determining the nature of the underlying infection and presence of organ dysfunction is critical. Presence of predisposing conditions such as advanced age, history of organ transplantation, immunosuppression, diabetes mellitus, trauma, and surgery should be quickly ascertained. Travel and pet exposure as well as history of intravenous drug and alcohol use should be obtained.
Vital signs need to be closely monitored. Although many patients with sepsis will be febrile, up to half of septic patients can be hypothermic or normothermic . Tachycardia is a common sign as is tachypnoea and respiratory status needs to be closely monitored for evidence of respiratory failure. Blood pressure particularly diastolic pressure is usually lower than normal, with severe sepsis being the most common cause of vasodilatory shock .
A detailed examination could give you direct clues on the likely source of infection as well as the general clinical state of the patient. There may be evidence of depleted intravascular volume with dry mucous membranes and low jugular venous pressure as well as signs of impaired cutaneous perfusion with livedo reticularis and poor capillary refill. Altered mental status is often an important early indicator of sepsis with abnormalities in attention and cognition present especially in elderly patients. Careful attention should be paid to abnormalities in lung and abdominal examination such as asymmetric air entry and abdominal tenderness. Indwelling devices and surgical incisions should be closely examined for areas of tenderness, swelling, or erythema. Patients with diabetes mellitus are at risk for invasive polymicrobial infections such as necrotizing fasciitis and careful attention should be paid to the skin and soft tissues in such patients.
Patients with evidence of sepsis should have blood drawn for basic laboratory data including a complete blood count, complete metabolic panel as well as coagulation parameters. Leukocytosis, leucopenia, metabolic acidosis, renal or hepatic dysfunction should be sought. Abnormal liver function may also be a clue to the presence of acalculous cholecystitis, hepatic abscess, or biliary sepsis and further imaging may thus be useful. In addition, a blood lactate level should be obtained in the septic patient with an elevated level reflecting evidence of sepsis-related organ hypo perfusion. It is important to remember that except for immediate post-ictal patients and patients on an epinephrine infusion, an elevated lactate level, while not necessarily indicating sepsis, is always abnormal. Compensated cirrhotic have normal lactate levels. Only when they become ill do their lactate levels rise. Whenever possible, especially in the septic patient with tachypnoea or change in mental status, a blood gas should be obtained, as it provides a wealth of data in one simple test. If your facility’s blood gas analyser allows it, always check a lactate level with the gas, as well as other useful basic laboratory indices such as haemoglobin, ionized calcium, and potassium. Early on in the septic process, an acute respiratory alkalosis will be apparent reflecting a state of increased minute ventilation. Metabolic acidosis occurs later in the septic process and thus if present, indicates greater severity. In patients who already have a central venous catheter, a venous blood gas sample is just as useful as an arterial gas, especially when combined with a working pulse oximetry value. Only if PaO2 is a specific concern is an arterial gas needed. The arterial pH as well as PCO2 can easily be inferred by adding ~0.05 to the venous pH and subtracting ~5 from the venous PCO2 levels . In addition, a central venous blood gas can provide you central venous oxygen saturation, while an arterial gas cannot. Central venous lactate and arterial lactate are essentially equivalent.
In a patient with sepsis, all likely foci of infection should be cultured. Blood cultures should be routinely sent; however, 70% of patients with sepsis will not have organisms recovered from blood . The Surviving Sepsis Campaign recommends obtaining appropriate cultures prior to antimicrobial therapy provided that such cultures do not cause a significant delay in antibiotic administration . At least two sets of blood cultures should be obtained and if a vascular device is present, at least one is drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. If the same organism is recovered from both cultures, the likelihood that the organism is causing the severe sepsis is enhanced. In addition, if the culture drawn through the vascular access device is positive much earlier than the peripheral blood culture (i.e. >2 hrs earlier), the vascular access device is the likely source of infection . If the likelihood that a vascular device is infected is felt to be high, it should be removed even before culture results are available. The search for the culprit pathogen should not be limited to blood alone, but depending on the clinical scenario could include examination and culture of materials from the lower respiratory tract, urine, cerebrospinal fluid, wounds, or other body fluids that may be the source of infection.
Imaging studies should be geared towards localizing the source of infection and the pros and cons of various imaging modalities. Chest radiographs are routinely obtained, but are limited in critically ill patients with pneumonia. A portable supine chest film has a sensitivity of 0.60 and specificity of only 0.29 for the prediction of pneumonia in the critically ill patient with pneumonia . Patients who are volume depleted or neutropenic may initially not have any detectable infiltrate on a chest radiograph. Generally, this becomes more obvious after hydration.
Ultrasounds are valuable particularly as they can be done at the bedside in unstable patients. It is commonly used to visualize the biliary tree and liver parenchyma in patients with unexplained abnormal liver function tests. It is also useful in viewing the renal parenchyma and the collecting system in the septic patient with suspected perinephric abscess and to exclude an obstructive uropathy. Importantly, bedside ultrasound may be of value for other diagnostic purposes such as estimating a patient’s intravascular volume status. Both plain films and ultrasound have limited utility in establishing diagnosis of disease states like sinusitis, occult abscesses or fluid collections, ischaemic bowel or a perforated viscus. For such conditions, a computed tomographic (CT) scan is more useful.
Many biomarkers have been evaluated for use in sepsis. Most have been evaluated as prognostic markers in sepsis; others for diagnosis. Thus far, none have been found to have sufficient specificity or sensitivity to be routinely employed. Procalcitonin has been the most widely studied, but has known false positives (e.g. massive trauma, burns, and severe shock) and false negatives (early infection, localized abscesses). As a prognostic marker, procalcitonin levels have been shown to correlate with mortality and some authors have proposed using procalcitonin levels to help decide on length of antibiotic treatment especially in culture negative sepsis . The true clinical role of biomarkers remains to be determined.
The extent of infection and the severity of organ failure have a significant impact on the prognosis of patients with sepsis. The site of infection also has a prognostic value. In the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) trial, patients with urinary tract infections as their source of severe sepsis had a 28 day mortality of 21% compared with patients with a pulmonary source who had a mortality rate of 34% (p < 0.01) . Additionally, the response to infection varies among patients, reflecting the enormous heterogeneity in the patient population suffering from severe sepsis. While some patients have a marked systemic response, such as in patients with meningococcal sepsis, others often die of overwhelming infection with an inadequate host response for example neutropenic cancer patients with septic shock.
The PIRO model has recently been proposed as a way of stratifying septic patients according to their Predisposing condition, the severity of Infection, the host Response to infection, and the degree of Organ dysfunction . PIRO is a staging score similar to the tumour nodes metastases (TNM) staging system in clinical oncology. The PIRO staging system could be used to assess risk and predict outcome in septic patients since the classification represents the different factors that contribute to the development of and outcome from sepsis. It could also help in early identification of those patients that need immediate ICU admission.
The degree of organ dysfunction can be assessed with various scoring systems, one of the most common being the Sequential Organ Failure Assessment (SOFA) score-a simple, but effective method to describe organ dysfunction or failure in critically ill patients . Another prognostic scoring system, the Acute Physiology and Chronic Health Evaluation II (APACHE II), evaluates the risk of mortality, but however do not individualize the various degrees of organ dysfunction .
Severe sepsis is a medical emergency that is frequently fatal. It requires early identification, prompt evaluation, and treatment. The signs and symptoms of sepsis are influenced by the virulence of the pathogen, the portal of entry, as well as the susceptibility and response of the host. A quick and thorough history and examination with relevant ancillary studies are needed in evaluating a patient with sepsis. No biomarker has yet been found to have sufficient specificity or sensitivity to be routinely employed in the management of a septic patient.
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