Approach Considerations
Multiple clinical, laboratory, radiologic, and microbiologic data are required for the diagnosis of sepsis and septic shock. Sepsis should never be diagnosed based on a single abnormality. However, the diagnosis is often made empirically at the bedside upon presentation or retrospectively when follow-up data return (eg, positive blood culture result) or a response to antibiotics is evident. Importantly, the identification of a pathogenic organism, although preferred, is not always feasible since the responsible organism may be unidentified in many patients.
In general, the workup for sepsis may include the following:
-
Blood culture and urine analysis and culture
-
Chemistry studies that can suggest organ dysfunction, such as liver or kidney function tests
-
Serum lactate levels obtained urgently and serially.
-
Chest radiology
-
Diagnostic imaging of the chest and abdomen/pelvis
-
Cardiac studies such as ECG and troponins, as indicated
-
Interventions such as paracentesis, thoracentesis, lumbar puncture, or aspiration of an abscess, as clinically indicated
-
Measurement of biomarkers of sepsis such as procalcitonin levels
Laboratory Studies
Complete blood cell count
A complete blood cell (CBC) count is usually not specific. Leukocytosis with a left shift is also a nonspecific diagnostic finding and can be seen in noninfectious conditions. Leukopenia, anemia, and thrombocytopenia may be observed in sepsis.
Complete metabolic profile
A complete metabolic profile identifies changes in organ function, especially the liver and kidneys.
Bacterial cultures
Obtain blood cultures in all patients upon admission. Negative blood culture results are also necessary to include pseudosepsis in the differential diagnosis. [44] Blood culture isolates might suggest the underlying disease process. Bacteroides fragilis suggests a colonic or pelvic source, whereas Klebsiella species or enterococci suggest a gallbladder or urinary tract source.
If central intravenous (IV) line sepsis is suspected, remove the line and send the tip for semiquantitative bacterial culture. If culture of the catheter tip yields positive results and demonstrates 15 or more colonies and if the isolate from the tip matches the isolate from the blood culture, an infection associated with the central IV line is diagnosed.
ICU patients are at a greater risk for colonization by MRSA, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Enterobacteriaceae (CRE). It is critical to deescalate or change the empiric antibiotic regimen once the organism susceptibilities are available.
Gram staining
Buffy coat analysis of CBC may be useful in identifying certain infectious agents, although the yield is low. [45]
Urinalysis with reflex to culture
If urosepsis is suspected, obtain a urine Gram stain, urinalysis, and urine culture. A systematic review found that in adult ICU patients, catheter-associated urinary tract infection was associated with significantly higher mortality and a longer stay. [46]
Microbiology
Organism identification via culture in a patient who fulfills the definition of sepsis is highly supportive of a sepsis diagnosis but is unnecessary. The rationale behind its lack of inclusion in the diagnostic criteria for sepsis is that a culprit organism goes unidentified in up to half of patients who present with sepsis, and a positive culture result is not required to make a decision regarding treatment with empiric antibiotics.
Unique laboratory findings
Laboratory and clinical features that may suggest an underlying etiology of sepsis are as follows:
-
Leukocytosis (WBC count >12,000/µL) or leukopenia (WBC count < 4000/µL)
-
Normal WBC count with greater than 10% immature forms (left shift with bandemia)
-
Hyperglycemia (plasma glucose level >140 mg/dL or 7.7 mmol/L) in the absence of diabetes [25]
-
Plasma C-reactive protein level of more than 2 standard deviations above the reference value
-
Arterial hypoxemia (PaO 2/FiO 2 ratio < 300 mm Hg)
-
Acute oliguria (urine output < 0.5 mL/kg/hour for at least 2 hours despite adequate fluid resuscitation)
-
Creatinine increase >0.5 mg/dL or 44.2 mmol/L
-
Coagulation abnormalities (INR >1.5 or PTT >60 seconds)
-
Thrombocytopenia (platelet count < 100,000/µL) [24]
-
Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L)
-
Adrenal insufficiency (eg, hyponatremia, hyperkalemia) and euthyroid sick syndrome can also be found in sepsis.
-
Hyperlactatemia (serum lactate >2 mmol/L) can result from organ hypoperfusion in the presence or absence of hypotension and indicates a poor prognosis. A serum lactate level of 4 mmol/L or more (especially arterial lactate) indicates septic shock.
Procalcitonin levels
Procalcitonin (PCT) is an acute-phase reactant that is elevated in severe bacterial infections. In most clinical assays, the reference range of PCT is below detectable. Measurement of PCT and C-reactive protein (CRP) at onset and on the fourth day of treatment can predict survival of patients with ventilator-associated pneumonia. A decrease in either one of these marker values predicts survival. [9]
A study from van Nieuwkoop et al examined the use of PCT levels in predicting bacteremia in a group of 581 patients, 136 of whom had bacteremia; PCT levels successfully identified 94-99% of the patients with bacteremia. [7]
Heyland et al, in a systematic review of the economic value of PCT-guided reduction in antibiotic use in intensive care, found that with hospital mortality and length of stay unchanged, PCT testing to reduce antibiotic treatment broke even when daily antibiotics cost about $150 in Canadian dollars. [8]
Chest Radiology and Chest CT Scan
Chest Radiography
No radiologic signs are specific to the identification of sepsis, but chest radiography can aid in identifying a specific infection site. Chest radiography is important to rule out pneumonia and diagnose other causes of pulmonary infiltrates, such as the following:
-
Pulmonary drug reactions
-
Pulmonary embolism
-
Pulmonary hemorrhage
-
Primary or metastatic pulmonary neoplasms
-
Lymphangitic spread of malignancies
-
Large pleural effusions
-
Pneumothorax
-
Hydrothorax
-
Fluid overload
-
Congestive heart failure (CHF)
-
Acute myocardial infarction (MI)
-
Acute respiratory distress syndrome
Chest CT Scanning
Chest CT scanning is a very sensitive modality for diagnosing the lung pathology listed above.
Abdominal Ultrasonography, CT Scanning, and MRI
Perform abdominal ultrasonography if biliary tract obstruction is suspected based on the clinical presentation. However, abdominal ultrasonography is suboptimal for the detection of abscesses or perforated hollow organs. Ultrasonograms in patients with cholecystitis may show a thickened gallbladder wall or biliary calculi but no dilatation of the common bile duct (CBD). Stones in the biliary tract may or may not be visible in patients with cholangitis, but the CBD typically is dilated. [47]
Use computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen if a nonbiliary intra-abdominal source of infection is suspected on the basis of the history or physical examination findings. Abdominal CT or MRI is also helpful in delineating intrarenal and extrarenal pathology. Gallium or indium scanning has no place in the initial workup of sepsis; patients with sepsis are acutely ill by definition, and rapid diagnostic tests (eg, CT or MRI of the abdomen and ultrasonography of the right upper quadrant) are time-critical, life-saving tools. However, MRI is more time consuming than CT scanning, and the latter is preferred in emergent situations. [47]
Cardiac Studies
If acute MI is likely, perform electrocardiography (ECG) and obtain cardiac enzyme levels. Remember that certain patients may present with a silent, asymptomatic MI, which should be included in the differential diagnosis of otherwise unexplained fever, leukocytosis, and hypotension. Silent MIs are common in elderly patients and in those who have recently undergone abdominal or pelvic surgical procedures. They are also common in individuals with alcoholism, diabetes, and uremic conditions.
The following cardiac studies may be useful if cardiac involvement or disease is suspected as a cause or complication of infection:
-
Electrocardiography (ECG) to evaluate for conduction abnormalities or delays or arrhythmias
-
Cardiac enzyme levels
-
Echocardiography to evaluate for structural heart disease
Invasive Interventions
Invasive diagnostic procedures that may be considered are discussed below.
Thoracentesis/paracentesis
Perform thoracentesis for diagnostic purposes in patients with substantial pleural effusion. Perform paracentesis in patients with gross ascites.
Surgical incision and drainage
Drainage of fluid collections/abscesses is crucial in establishing good source control and in facilitating a good clinical response to subsequent antibiotic therapy.
Bronchoscopy
Bronchoscopy with washing, lavage, or other invasive sampling is performed in patients with suspected pneumonia and in patients with suspected invasive fungal infections of the lung.
Swan-Ganz catheterization
In highly selected cases, a Swan-Ganz catheter may be useful in managing the fluid status of the patient and in assessing left ventricular dysfunction; however, routine use is not recommended.
Imaging Studies
Site-specific soft tissue imaging includes ultrasonography, CT scanning, or MRI to assess for possible abscess, fluid collection, or necrotizing skin infection. These are essential for diagnostic purposes and for monitoring the response to therapy.
Contrast-enhanced CT scanning or MRI of the brain/neck is performed to assess for possible masses, abscess, fluid collection, or necrotizing infection.
-
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
- Table 1. Infectious and Noninfectious Causes of Fever [14]
- Table 2. Clinical Conditions Associated With Sepsis
- Table 3. Noninfectious Conditions Mimicking Clinical and Hemodynamic Parameters of Sepsis
- Table 4. Characteristics of Pseudosepsis and Sepsis
- Table 1. Table of Current Recommendations and Changes From Previous 2016 Recommendations [1]
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. [41] |
||
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. |
||
| Recommendations 2021 | Recommendation Strength and Quality of Evidence | Changes From 2016 Recommendations |
|---|---|---|
| 1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. | Strong; moderate-quality evidence (for screening) | Changed from Best practice statement |
| “We recommend that hospitals and hospital systems have a performance improvement program for sepsis including sepsis screening for acutely ill, high-risk patients.” | ||
| Strong; very low-quality evidence (for standard operating procedures) | ||
| 2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single-screening tool for sepsis or septic shock. | Strong; moderate-quality evidence | NEW |
| 3. For adults suspected of having sepsis, we suggest measuring blood lactate. | Weak; low quality of evidence | |
| INITIAL RESUSCITATION | ||
| 4. Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately. | Best practice statement | |
| 5. For patients with sepsis induced hypoperfusion or septic shock we suggest that at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hr of resuscitation. | Weak; low quality of evidence | DOWNGRADE from Strong; low quality of evidence |
| “We recommend that in the initial resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hr” | ||
| 6. For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation, over physical examination or static parameters alone. | Weak; very low quality of evidence | |
| 7. For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. | Weak; low quality of evidence | |
| 8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. | Weak; low quality of evidence | NEW |
| MEAN ARTERIAL PRESSURE | ||
| 9. For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets. | Strong; moderate-quality evidence | |
| ADMISSION TO INTENSIVE CARE | ||
| 10. For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 hr. | Weak; low quality of evidence | |
| INFECTION | ||
| 11. For adults with suspected sepsis or septic shock but unconfirmed infection, we recommend continuously re-evaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials if an alternative cause of illness is demonstrated or strongly suspected. | Best practice statement | |
| 12. For adults with possible septic shock or a high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 hr of recognition. | Strong; low quality of evidence (Septic shock) | CHANGED from previous: “We recommend that administration of intravenous antimicrobials should be initiated as soon as possible after recognition and within one hour for both a) septic shock and b) sepsis without shock” |
| Strong; very low quality of evidence (Sepsis without shock) | ||
| Strong recommendation; moderate quality of evidence | ||
| 13. For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus noninfectious causes of acute illness. | Best practice statement | |
| 14. For adults with possible sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for infection persists, the administration of antimicrobials within 3 hr from the time when sepsis was first recognized. | Weak; very low quality of evidence | NEW from previous: |
| “We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock” | ||
| Strong recommendation; moderate quality of evidence | ||
| 15. For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobials while continuing to closely monitor the patient. | Weak; very low quality of evidence | NEW from previous: |
| “We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock“ | ||
| Strong recommendation; moderate quality of evidence | ||
| 16. For adults with suspected sepsis or septic shock, we suggest against using procalcitonin plus clinical evaluation to decide when to start antimicrobials, as compared with clinical evaluation alone. | Weak; very low quality of evidence | |
| 17. For adults with sepsis or septic shock at high risk for MRSA, we recommend using empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage. | Best practice statement | NEW from previous: |
| “We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
| Strong recommendation; moderate quality of evidence | ||
| 18. For adults with sepsis or septic shock at low risk for MRSA, we suggest against using empiric antimicrobials with MRSA coverage, as compared with using antimicrobials without MRSA coverage. | Weak; low quality of evidence | NEW from previous: |
| “We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
| Strong recommendation; moderate quality of evidence | ||
| 19. For adults with sepsis or septic shock and high risk for multidrug resistant (MDR) organisms, we suggest using two antimicrobials with gram-negative coverage for empiric treatment over one gram-negative agent. | Weak; very low quality of evidence | |
| 20. For adults with sepsis or septic shock and low risk for multidrug resistant (MDR) organisms, we suggest against using two gram-negative agents for empiric treatment, as compared to one gram-negative agent. | Weak; very low quality of evidence | |
| 21. For adults with sepsis or septic shock, we suggest against using double gram-negative coverage once the causative pathogen and the susceptibilities are known. | Weak; very low quality of evidence | |
| 22. For adults with sepsis or septic shock at high risk for fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy. | Weak; low quality of evidence | NEW from previous: |
| “We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
| Strong recommendation; moderate quality of evidence | ||
| 23. For adults with sepsis or septic shock at low risk of fungal infection, we suggest against empiric use of antifungal therapy | Weak; low quality of evidence | NEW from previous: |
| “We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.“ | ||
| Strong recommendation; moderate quality of evidence | ||
| 24. We make no recommendation on the use of antiviral agents. | No recommendation | |
| 25. For adults with sepsis or septic shock, we suggest using prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion. | Weak; moderate-quality evidence | |
| 26. For adults with sepsis or septic shock, we recommend optimising dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic (PK/PD) principles and specific drug properties. | Best practice statement | |
| 27. For adults with sepsis or septic shock, we recommend rapidly identifying or excluding a specific anatomical diagnosis of infection that requires emergent source control and implementing any required source control intervention as soon as medically and logistically practical. | Best practice statement | |
| 28. For adults with sepsis or septic shock, we recommend prompt removal of intravascular access devices that are a possible source of sepsis or septic shock after other vascular access has been established. | Best practice statement | |
| 29. For adults with sepsis or septic shock, we suggest daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment for de-escalation. | Weak; very low quality of evidence | |
| 30. For adults with an initial diagnosis of sepsis or septic shock and adequate source control, we suggest using shorter over longer duration of antimicrobial therapy. | Weak; very low quality of evidence | |
| 31. For adults with an initial diagnosis of sepsis or septic shock and adequate source control where optimal duration of therapy is unclear, we suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobials over clinical evaluation alone. | Weak; low quality of evidence | |
| HEMODYNAMIC MANAGEMENT | ||
| 32. For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation. | Strong; moderate-quality evidence | |
| 33. For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation. | Weak; low quality of evidence | CHANGED from weak recommendation; low quality of evidence. |
| “We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock” | ||
| 34. For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids. | Weak; moderate-quality evidence | |
| 35. For adults with sepsis or septic shock, we recommend against using starches for resuscitation. | Strong; high-quality evidence | |
| 36. For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation. | Weak; moderate-quality evidence | UPGRADE from weak recommendation; low quality of evidence |
| “We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock.” | ||
| 37. For adults with septic shock, we recommend using norepinephrine as the first-line agent over other vasopressors. | Strong | |
| Dopamine. High-quality evidence | ||
| Vasopressin. Moderate-quality evidence | ||
| Epinephrine. Low quality of evidence | ||
| Selepressin. Low quality of evidence | ||
| Angiotensin II. Very low-quality evidence | ||
| 38. For adults with septic shock on norepinephrine with inadequate mean arterial pressure levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine. | Weak; moderate quality evidence | |
| 39. For adults with septic shock and inadequate mean arterial pressure levels despite norepinephrine and vasopressin, we suggest adding epinephrine. | Weak; low quality of evidence | |
| 40. For adults with septic shock, we suggest against using terlipressin. | Weak; low quality of evidence | |
| 41. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest either adding dobutamine to norepinephrine or using epinephrine alone. | Weak; low quality of evidence | |
| 42. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest against using levosimendan. | Weak; low quality of evidence | NEW |
| 43. For adults with septic shock, we suggest invasive monitoring of arterial blood pressure over noninvasive monitoring, as soon as practical and if resources are available. | Weak; very low quality of evidence | |
| 44. For adults with septic shock, we suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying initiation until a central venous access is secured. | Weak; very low quality of evidence | NEW |
| 45. There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hr of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after the initial resuscitation. | No recommendation | NEW |
| “We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock” | ||
| Weak recommendation; low quality of evidence | ||
| “We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock.” | ||
| Weak recommendation; low quality of evidence | ||
| VENTILATION | ||
| 46.There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure. | No recommendation | |
| 47. For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over noninvasive ventilation. | Weak; low quality of evidence | NEW |
| 48. There is insufficient evidence to make a recommendation on the use of noninvasive ventilation in comparison to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure. | No recommendation | |
| 49. For adults with sepsis-induced ARDS, we recommend using a low tidal volume ventilation strategy (6 mL/kg), over a high tidal volume strategy (> 10 mL/kg). | Strong; high-quality evidence | |
| 50. For adults with sepsis-induced severe ARDS, we recommend using an upper limit goal for plateau pressures of 30 cm H2O, over higher plateau pressures. | Strong; moderate-quality evidence | |
| 51. For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP. | Weak; moderate-quality evidence | |
| 52. For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared with high tidal volume ventilation. | Weak; low quality of evidence | |
| 53. For adults with sepsis-induced moderate-severe ARDS, we suggest using traditional recruitment maneuvers. | Weak; moderate-quality evidence | |
| 54. When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy. | Strong; moderate-quality evidence | |
| 55. For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for greater than 12 hr daily. | Strong; moderate-quality evidence | |
| 56. For adults with sepsis induced moderate-severe ARDS, we suggest using intermittent NMBA boluses, over NMBA continuous infusion. | Weak; moderate-quality evidence | |
| 57. For adults with sepsis-induced severe ARDS, we suggest using Veno-venous (VV) ECMO when conventional mechanical ventilation fails in experienced centers with the infrastructure in place to support its use. | Weak; low quality of evidence | NEW |
| ADDITIONAL THERAPIES | ||
| 58. For adults with septic shock and an ongoing requirement for vasopressor therapy we suggest using IV corticosteroids. | Weak; moderate-quality evidence | UPGRADE from Weak recommendation , low quality of evidence |
| “We suggest against using IV hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). If this is not achievable, we suggest IV hydrocortisone at a dose of 200 mg/day.” | ||
| 59. For adults with sepsis or septic shock we suggest against using polymyxin B hemoperfusion. | Weak; low quality of evidence | NEW from previous: “We make no recommendation regarding the use of blood purification techniques” |
| 60. There is insufficient evidence to make a recommendation on the use of other blood purification techniques. | No recommendation | |
| 61. For adults with sepsis or septic shock we recommend using a restrictive (over liberal) transfusion strategy. | Strong; moderate-quality evidence | |
| 62. For adults with sepsis or septic shock we suggest against using IV immunoglobulins. | Weak; low quality of evidence | |
| 63. For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding, we suggest using stress ulcer prophylaxis. | Weak; moderate-quality evidence | |
| 64. For adults with sepsis or septic shock, we recommend using pharmacologic venous thromboembolism (VTE) prophylaxis unless a contraindication to such therapy exists. | Strong; moderate-quality evidence | |
| 65. For adults with sepsis or septic shock, we recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis | Strong; moderate-quality evidence | |
| 66. For adults with sepsis or septic shock, we suggest against using mechanical VTE prophylaxis, in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone. | Weak; low quality of evidence | |
| 67. In adults with sepsis or septic shock and AKI, we suggest using either continuous or intermittent renal replacement therapy. | Weak; low quality of evidence | |
| 68. In adults with sepsis or septic shock and AKI, with no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy. | Weak; moderate-quality evidence | |
| 69. For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180mg/dL (10 mmol/L). | Strong; moderate-quality evidence | |
| 70. For adults with sepsis or septic shock we suggest against using IV vitamin C. | Weak; low quality of evidence | NEW |
| 71. For adults with septic shock and hypoperfusion-induced lactic acidemia, we suggest against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements. | Weak; low quality of evidence | |
| 72. For adults with septic shock and severe metabolic acidemia (pH ≤ 7.2) and acute kidney injury (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy | Weak; low quality of evidence | |
| 73. For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 hr) initiation of enteral nutrition. | Weak; very low quality of evidence | |
| LONG-TERM OUTCOMES AND GOALS OF CARE | ||
| 74. For adults with sepsis or septic shock, we recommend discussing goals of care and prognosis with patients and families over no such discussion. | Best practice statement | |
| 75. For adults with sepsis or septic shock, we suggest addressing goals of care early (within 72 hr) over late (72 hr or later). | Weak; low quality of evidence | |
| 76. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on any specific standardized criterion to trigger goals of care discussion. | No recommendation | |
| 77. For adults with sepsis or septic shock, we recommend that the principles of palliative care (which may include palliative care consultation based on clinician judgement) be integrated into the treatment plan, when appropriate, to address patient and family symptoms and suffering. | Best practice statement | |
| 78. For adults with sepsis or septic shock, we suggest against routine formal palliative care consultation for all patients over palliative care consultation based on clinician judgement. | Weak; low quality of evidence | |
| 79. For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral. | Weak; very low quality of evidence | |
| 80. For adults with sepsis or septic shock, we suggest using a handoff process of critically important information at transitions of care over no such handoff process. | Weak; very low quality of evidence | |
| 81. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on the use of any specific structured handoff tool over usual handoff processes. | No recommendation | |
| 82. For adults with sepsis or septic shock and their families, we recommend screening for economic and social support (including housing, nutritional, financial, and spiritual support), and make referrals where available to meet these needs. | Best practice statement | |
| 83. For adults with sepsis or septic shock and their families, we suggest offering written and verbal sepsis education (diagnosis, treatment, and post-ICU/post-sepsis syndrome) prior to hospital discharge and in the follow-up setting. | Weak; very low quality of evidence | |
| 84. For adults with sepsis or septic shock and their families, we recommend the clinical team provide the opportunity to participate in shared decision making in post-ICU and hospital discharge planning to ensure discharge plans are acceptable and feasible. | Best practice statement | |
| 85. For adults with sepsis and septic shock and their families, we suggest using a critical care transition program, compared with usual care, upon transfer to the floor. | Weak; very low quality of evidence | |
| 86. For adults with sepsis and septic shock, we recommend reconciling medications at both ICU and hospital discharge. | Best practice statement | |
| 87. For adult survivors of sepsis and septic shock and their families, we recommend including information about the ICU stay, sepsis and related diagnoses, treatments, and common impairments after sepsis in the written and verbal hospital discharge summary. | Best practice statement | |
| 88. For adults with sepsis or septic shock who developed new impairments, we recommend hospital discharge plans include follow-up with clinicians able to support and manage new and long-term sequelae. | Best practice statement | |
| 89. For adults with sepsis or septic shock and their families, there is insufficient evidence to make a recommendation on early post-hospital discharge follow-up compared with routine post-hospital discharge follow-up. | No recommendation | |
| 90. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation for or against early cognitive therapy. | No recommendation | |
| 91. For adult survivors of sepsis or septic shock, we recommend assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge. | Best practice statement | |
| 92. For adult survivors of sepsis or septic shock, we suggest referral to a post-critical illness follow-up program if available. | Weak; very low quality of evidence | |
| 93. For adult survivors of sepsis or septic shock receiving mechanical ventilation for > 48hr or an ICU stay of > 72 hr, we suggest referral to a post-hospital rehabilitation program. | Weak; very low quality of evidence | |
