Approach Considerations
Early aggressive medical therapy is indicated in patients with suspected sepsis. [30, 31, 48, 49, 50, 51, 52, 53, 54, 55]
Sepsis Treatment
Patients with sepsis are generally ill and require inpatient hospitalization or admission to the intensive care unit (ICU) for monitoring and treatment. Admission to an ICU depends on the severity of the septic process and the degree of organ dysfunction. In July 2018, the US Centers for Medicare and Medicaid Services (CMS) began public reporting of a national sepsis bundle quality measure, commonly referred to as SEP-1. Early data demonstrated that only half of sepsis patients nationally received the full CMS-recommended bundle for emergency and hospital care. The treatment guidelines have been revised by IDSA/ Emergency Medicine Collaborative Task Force [56] and Surviving Sepsis Campaign Guidelines 2021. [1]
Determine the likely source of the infection, and administer intravenous (IV) empiric antimicrobial agents until culture results become available, at which point more narrow-spectrum agents can be used (see below). In addition, offer supportive therapy aimed at maintaining organ perfusion, and provide respiratory support when necessary. [50, 57, 58]
A recent prospective study of 5787 adult patients with severe sepsis revealed the importance of goal-directed treatment. Patients triaged and managed according to 4 clinical goals (blood cultures before antibiotics, lactate before 90 minutes, IV antibiotics before 180 minutes, and 30 mL/kg of IV fluids before 180 minutes) were significantly less likely to die in the hospital than were those for whom all 4 of these goals were not met (22.6% vs 26.5%, respectively). [59]
In a multivariate regression analysis adjusted for age, admission to the intensive care unit (ICU), vasopressor initiation, central venous catheter insertion, and monitoring of central venous pressure and central venous oxygen saturation, complete compliance with the clinical goals was associated with a survival odds ratio of 1.194 (1.04-1.37). [59]
Surgical Intervention
Early evaluation in patients with presumed intra-abdominal or pelvic sepsis is essential, and surgical consultation should be obtained in appropriate patients.
Consultations
Obtain a consultation with a surgeon for patients with presumed intra-abdominal or pelvic sepsis. Obtain a consultation with an infectious disease specialist, as indicated, in patients with presumed or proven sepsis. [30]
Antimicrobial Therapy
Appropriate antimicrobial therapy depends on adequate coverage of the bacteria associated with the specific organ or organ system associated with the infection. [30, 31, 32, 48, 49] Agents suitable for empiric monotherapy regimens (depending on the source and underlying microbiology of the sepsis because the agent must be able to cover all of the likely pathogens) may include the following:
-
Imipenem
-
Meropenem
-
Tigecycline
-
Piperacillin-tazobactam
-
Ampicillin-sulbactam
-
Moxifloxacin
Combination therapeutic regimens include metronidazole plus either levofloxacin, aztreonam, a third- or fourth-generation cephalosporin, or an aminoglycoside.
Many advocate also using antistaphylococcal coverage (eg, vancomycin) empirically.
Although no drug regimen may be superior to another, time to first dose administration is very important. Mortality data suggest that early administration of appropriate antibiotics is correlated with better survival. Alternative agents may be used alone or in combination, with a good adverse-effect profile. [30, 31, 48, 49]
Antibiotics are normally continued until the septic process and surgical interventions have controlled the source of infection. Ordinarily, patients are treated for approximately 2 weeks, although duration may vary according to the source, site, and severity of the infection. As soon as patients are able to tolerate medications orally, they may be switched to an equivalent oral antibiotic regimen in an IV-to-oral conversion program.
Empiric therapy for IV line infections
A detailed discussion of catheter-associated infections is available in the IDSA catheter-associated line-related infections (CRBSI) guidelines. [60] IV line infections most often are due to Staphylococcus aureus (methicillin-sensitive S aureus [MSSA] or methicillin-resistant S aureus [MRSA]), but gram-negative bacilli can be involved. The preferred empiric therapy for these infections is meropenem or cefepime (for Pseudomonas) plus additional coverage for staphylococci. [37, 38] If MRSA is prevalent in the institution, add linezolid, vancomycin, or daptomycin. Otherwise, nafcillin, oxacillin, or cefazolin provide adequate coverage for MSSA.
Unless coagulase-negative, methicillin-sensitive staphylococci are recovered from the blood, with high-level bacteremia (3 or 4 positive blood cultures out of 4), avoid vancomycin for empiric therapy if possible; these are low-virulence organisms and may represent contaminants. If treatment is advised, the duration of therapy depends on the severity and site of infection. [60]
Treatment of staphylococcal central line infection and fungal or gram-negative organisms typically requires removal of the line.
Minimize the use of vancomycin in order to prevent the emergence of vancomycin-resistant enterococci (VRE). [37]
Empiric therapy for biliary tract infections
IDSA guidelines for complicated intra-abdominal infections such as biliary tract infections are available. [61] The main biliary tract pathogens include Escherichia coli, Klebsiella species, and Enterococcus faecalis. Coverage for staphylococci is not needed in the biliary tract. Anaerobes can also be important, especially in patients with diabetes or immunosuppression.
Preferred monotherapy regimens for biliary tract infections include imipenem, meropenem, ampicillin-sulbactam, or piperacillin-tazobactam. Cephalosporins or quinolones in combination with metronidazole are alternate first-line agents for the treatment of biliary tract infections.
Empiric therapy for intra-abdominal and pelvic infections
The main pathogens in the lower abdomen and pelvis include aerobic coliform gram-negative bacilli and B fragilis. Enterococci do not require special coverage unless the patient has recurrent infection or enterococci have been specifically and repeatedly isolated. Potent anti–B fragilis and aerobic gram-negative bacillary coverage are essential, in addition to surgical intervention when drainage or repair of intra-abdominal viscera is required.
Preferred monotherapy regimens for intra-abdominal and pelvic infections include imipenem, meropenem, piperacillin-tazobactam, ampicillin-sulbactam, or tigecycline. Alternate combination therapy for intra-abdominal and pelvic infections consists of clindamycin or metronidazole plus a third- or fourth-generation cephalosporin, aztreonam, levofloxacin, or an aminoglycoside. Some authors raise concerns about the use of tigecycline.
Empiric therapy for urosepsis
The primary uropathogens include gram-negative aerobic bacilli, such as coliforms or enterococci. Pseudomonas aeruginosa, Enterobacter species, and Serratia species are rare uropathogens and are associated with urologic instrumentation.
Monotherapy for urosepsis due to aerobic gram-negative bacilli may include aztreonam, levofloxacin, a third- or fourth-generation cephalosporin, or an aminoglycoside. However, preferred monotherapy for enterococcal urosepsis involves ampicillin or vancomycin. For VRE urosepsis, linezolid or daptomycin may be used.
Empiric therapy for community-acquired urosepsis consists of levofloxacin, aztreonam, or an aminoglycoside plus ampicillin. For nosocomial urosepsis, a fourth-generation cephalosporin, piperacillin-tazobactam, imipenem, or meropenem, with or without an aminoglycoside, is preferred.
Empiric therapy for staphylococcal, pneumococcal, and meningococcal sepsis
S aureus sepsis is usually associated with infection caused by devices or bacterial endocarditis. Empiric therapy may be with an anti-staphylococcal penicillin (nafcillin or oxacillin), vancomycin, a cephalosporin, daptomycin, or linezolid, depending on the concern for MRSA.
Pneumococcal or meningococcal sepsis may be treated with penicillin G or a beta-lactam. In patients with associated meningococcal meningitis, the antibiotic selected should penetrate the cerebrospinal fluid (CSF) and should be given in meningeal doses. Consider the regional prevalence of drug-resistant pneumococci when selecting an antibiotic.
Empiric therapy for sepsis of unknown origin
The usual sources of sepsis are the distal gastrointestinal (GI) tract, the pelvis, and the genitourinary (GU) tract. Organisms that should be covered from these areas include aerobic gram-negative bacilli (coliforms) and B fragilis. Enterococci are important pathogens in biliary tract sepsis and urosepsis.
Preferred empiric monotherapy includes meropenem, imipenem, piperacillin-tazobactam, or tigecycline.
Empiric combination therapy includes metronidazole plus levofloxacin, aztreonam, or a third- or fourth-generation cephalosporin.
Outpatient management
If orally administered antibiotics are continued at home, advise the patient about possible adverse effects. If additional antimicrobial therapy is needed outside the hospital setting, it should be given orally, not intravenously. Do not allow the total course of antibiotics to exceed 3 weeks, except for specific clinical scenarios, which may require prolonged courses of oral antibiotics for cure or complete clinical resolution.
-
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 | |
