Diagnostic Considerations
Sepsis is often associated with or preceded by other conditions (see Table 2 below). [39, 40, 41] Noninfectious conditions that present in a manner similar to that of sepsis must also be considered, as should the host's immunocompetence. Early diagnosis with rapid initiation of appropriate therapy is the cornerstone of reducing mortality and morbidity associated with sepsis. Diagnostic studies should be sent within the first 3 hours of suspected sepsis, and antibiotics should be initiated within the first 45 minutes after appropriate cultures are collected. If the blood pressure remains less than 65 mm Hg despite initial fluid resuscitation of 30 mL/kg or if the initial lactate level is 4 mmol/L (36 mg/dl) or higher within 6 hours, further hemodynamic assessments should be performed to ensure adequate organ perfusion. It is essential to reach a preliminary diagnosis within the first 12 hours of presentation to decrease the likelihood of adverse clinical outcomes.
Table 2. Clinical Conditions Associated With Sepsis (Open Table in a new window)
| System | Associated With Sepsis |
Not Typically Associated With Sepsis |
| GI tract | Liver Gallbladder Colon Abscess Intestinal obstruction Instrumentation |
Esophagitis Gastritis Pancreatitis (may have multiorgan dysfunction but not infectious in origin) Small bowel disorders GI bleeding |
| GU tract | Pyelonephritis Intra- or perinephric abscess Renal calculi Urinary tract obstruction Acute prostatitis/abscess Renal insufficiency Instrumentation in patients with bacteriuria |
Urethritis Cystitis Cervicitis Vaginitis Catheter-associated bacteriuria (in otherwise healthy hosts without genitourinary tract disease) |
| Pelvis | Peritonitis Abscess |
|
| Upper respiratory tract | Deep neck space infection Abscess |
Pharyngitis Sinusitis Bronchitis Otitis |
| Lower respiratory tract | Community-acquired pneumonia (with asplenia) Empyema Lung abscess |
Community-acquired pneumonia (in otherwise healthy host)
|
| Intravascular | IV line sepsis Infected prosthetic device Acute bacterial endocarditis |
|
| Cardiovascular | Acute bacterial endocarditis Myocardial/perivalvular ring abscess |
Subacute bacterial endocarditis
|
| CNS | Bacterial meningitis |
Aseptic meningitis |
Skin/soft-tissue
|
Necrotizing fasciitis
|
Osteomyelitis Uncomplicated wound infections |
CNS = central nervous system; GI = gastrointestinal; GU = genitourinary; IV = intravenous. Adapted from: Cunha BA, Shea KW. Fever in the intensive care unit. Infect Dis Clin North Am. Mar 1996;10(1):185-209. [39] |
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Pseudosepsis
A common medicolegal error is failure to consider pseudosepsis as a cause of the presenting syndrome. Most causes of pseudosepsis are readily treatable if recognized and managed early.
Thus, before embarking on a workup for sepsis or beginning empiric antibiotic therapy, it is vital to rule out the treatable causes of pseudosepsis early in the disease process. Consider other causes or conditions that mimic the clinical and hemodynamic parameters of sepsis and differentiate between the distributive presentation versus septic shock (see Table 3 below). The causes of pseudosepsis must be identified because they require supportive, rather than antimicrobial, therapy.
Table 3. Noninfectious Conditions Mimicking Clinical and Hemodynamic Parameters of Sepsis (Open Table in a new window)
Clinical Presentations Mimicking Sepsis |
Hemodynamic Parameters Mimicking Sepsis |
Myocardial infarction |
Spinal cord injury |
Pancreatitis |
Adrenal insufficiency |
Diabetic ketoacidosis |
Acute pancreatitis |
Systemic lupus erythematosus flare with abdominal crisis |
Hemorrhage |
Ventricular pseudoaneurysm |
Pulmonary embolism |
Massive aspiration/atelectasis |
Anaphylaxis |
Systemic vasculitis |
|
Hypovolemia (eg, due to diuretics, dehydration) |
|
Pseudosepsis is a common cause of misdiagnosis in hospitalized patients, particularly in the emergency department (ED) and ICU. The most common causes of pseudosepsis include gastrointestinal (GI) hemorrhage, pulmonary embolism, acute myocardial infarction (MI), acute pancreatitis (edematous or hemorrhagic), diuretic-induced hypovolemia, and relative adrenal insufficiency.
Patients with pseudosepsis may have fever, chills, leukocytosis, and a left shift, with or without hypotension. Many causes of pseudosepsis produce pulmonary artery catheter readings that are compatible with sepsis (ie, increased cardiac output and decreased peripheral resistance), which could misdirect the unwary clinician (see Table 4 below).
Table 4. Characteristics of Pseudosepsis and Sepsis (Open Table in a new window)
Parameters |
Pseudosepsis |
Sepsis |
Microbiologic |
No definite source PLUS ≥1 abnormalities Negative blood cultures excluding contaminants |
Proper identification/process/source PLUS ≥1 microbiologic abnormalities Positive buffy coat smear result OR several positive blood culture results with a pathogenic organism |
Hemodynamic |
⇓ PVR ⇑ CO |
⇓ PVR ⇑ CO Left ventricular dilatation |
Laboratory |
⇑ WBC count (with left shift) Normal platelet count ⇑ FSP ⇑ Lactate ⇑ D-dimers ⇑ PT/PTT ⇓ Albumin ⇓ Fibrinogen ⇓ Globulins |
⇑ WBC count (with left shift) ⇓ Platelets ⇑ FSP ⇑ Lactate ⇑ D-dimers ⇑ PT/PTT ⇓ Albumin |
Clinical |
≤102°F ± Tachycardia ± Respiratory alkalosis ± Hypotension |
≥102°F OR Hypothermia ± Mental status changes ± Hypotension |
CO = cardiac output; FSP = fibrin split products; GI = gastrointestinal; GU = genitourinary; PT/PTT = prothrombin time/partial thromboplastin time; PVR = peripheral vascular resistance; WBC = white blood cell. |
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Host immunocompetence
Otherwise healthy hosts with community-acquired pneumonia virtually never present with hypotension or sepsis; however, patients with decreased or absent splenic function may present with overwhelming pneumococcal sepsis. If an otherwise healthy patient with community-acquired pneumonia presents with shock and all of the other causes of pseudosepsis are ruled out, then it must be assumed that the patient is a compromised host with impaired or absent splenic function.
Differential Diagnoses
-
Overzealous diuresis
-
A right lower quadrant abdominal wall abscess and enteric fistula are observed and confirmed by the presence of enteral contrast in the abdominal wall.
Tables
System |
Infectious Causes |
Noninfectious Causes |
|---|---|---|
Central nervous |
Meningitis, encephalitis |
Posterior fossa syndrome, central fever, seizures, cerebral infraction, hemorrhage, cerebrovascular accident |
Cardiovascular |
Central line, infected pacemaker, endocarditis, sternal osteomyelitis, viral pericarditis, myocardial/perivalvular abscess |
Myocardial infarction, balloon pump syndrome, Dressler syndrome |
Pulmonary |
Ventilator-associated pneumonia, mediastinitis, tracheobronchitis, empyema |
Pulmonary emboli, ARDS, atelectasis (without pneumonia), cryptogenic organizing pneumonia, bronchogenic carcinoma without postobstructive pneumonia, systemic lupus erythematosus, pneumonitis, vasculitis |
Gastrointestinal |
Intra-abdominal abscess, cholangitis, cholecystitis, viral hepatitis, peritonitis, diarrhea (Clostridium difficile) |
Pancreatitis, acalculous cholecystitis, ischemia of the bowel/colon, bleeding, cirrhosis, irritable bowel syndrome |
Urinary tract |
Catheter-associated bacteremia, urosepsis, pyelonephritis, cystitis |
Allergic interstitial nephritis |
Skin/soft tissue |
Decubitus ulcers, cellulitis, wound infection |
Vascular ulcers |
Bone/joint |
Chronic osteomyelitis, septic arthritis |
Acute gout |
Other |
Transient bacteremia, sinusitis |
Adrenal insufficiency, phlebitis/thrombophlebitis, neoplastic fever, alcohol/drug withdrawal, delirium tremens, drug fever, fat emboli, deep venous thrombosis, postoperative fever (48 h), fever after transfusion |
| System | Associated With Sepsis |
Not Typically Associated With Sepsis |
| GI tract | Liver Gallbladder Colon Abscess Intestinal obstruction Instrumentation |
Esophagitis Gastritis Pancreatitis (may have multiorgan dysfunction but not infectious in origin) Small bowel disorders GI bleeding |
| GU tract | Pyelonephritis Intra- or perinephric abscess Renal calculi Urinary tract obstruction Acute prostatitis/abscess Renal insufficiency Instrumentation in patients with bacteriuria |
Urethritis Cystitis Cervicitis Vaginitis Catheter-associated bacteriuria (in otherwise healthy hosts without genitourinary tract disease) |
| Pelvis | Peritonitis Abscess |
|
| Upper respiratory tract | Deep neck space infection Abscess |
Pharyngitis Sinusitis Bronchitis Otitis |
| Lower respiratory tract | Community-acquired pneumonia (with asplenia) Empyema Lung abscess |
Community-acquired pneumonia (in otherwise healthy host)
|
| Intravascular | IV line sepsis Infected prosthetic device Acute bacterial endocarditis |
|
| Cardiovascular | Acute bacterial endocarditis Myocardial/perivalvular ring abscess |
Subacute bacterial endocarditis
|
| CNS | Bacterial meningitis |
Aseptic meningitis |
Skin/soft-tissue
|
Necrotizing fasciitis
|
Osteomyelitis Uncomplicated wound infections |
CNS = central nervous system; GI = gastrointestinal; GU = genitourinary; IV = intravenous. Adapted from: Cunha BA, Shea KW. Fever in the intensive care unit. Infect Dis Clin North Am. Mar 1996;10(1):185-209. [39] |
||
Clinical Presentations Mimicking Sepsis |
Hemodynamic Parameters Mimicking Sepsis |
Myocardial infarction |
Spinal cord injury |
Pancreatitis |
Adrenal insufficiency |
Diabetic ketoacidosis |
Acute pancreatitis |
Systemic lupus erythematosus flare with abdominal crisis |
Hemorrhage |
Ventricular pseudoaneurysm |
Pulmonary embolism |
Massive aspiration/atelectasis |
Anaphylaxis |
Systemic vasculitis |
|
Hypovolemia (eg, due to diuretics, dehydration) |
|
Parameters |
Pseudosepsis |
Sepsis |
Microbiologic |
No definite source PLUS ≥1 abnormalities Negative blood cultures excluding contaminants |
Proper identification/process/source PLUS ≥1 microbiologic abnormalities Positive buffy coat smear result OR several positive blood culture results with a pathogenic organism |
Hemodynamic |
⇓ PVR ⇑ CO |
⇓ PVR ⇑ CO Left ventricular dilatation |
Laboratory |
⇑ WBC count (with left shift) Normal platelet count ⇑ FSP ⇑ Lactate ⇑ D-dimers ⇑ PT/PTT ⇓ Albumin ⇓ Fibrinogen ⇓ Globulins |
⇑ WBC count (with left shift) ⇓ Platelets ⇑ FSP ⇑ Lactate ⇑ D-dimers ⇑ PT/PTT ⇓ Albumin |
Clinical |
≤102°F ± Tachycardia ± Respiratory alkalosis ± Hypotension |
≥102°F OR Hypothermia ± Mental status changes ± Hypotension |
CO = cardiac output; FSP = fibrin split products; GI = gastrointestinal; GU = genitourinary; PT/PTT = prothrombin time/partial thromboplastin time; PVR = peripheral vascular resistance; WBC = white blood cell. |
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