GUIDELINE TITLE guidelines for management of severe sepsis and septic shock

 

MAJOR RECOMMENDATIONS

The grades of recommendations (A-E) and grades of evidence (I-V) are defined at the end of the "Major Recommendations" field.

Initial Resuscitation

 

1. The resuscitation of a patient in severe sepsis or sepsis-induced tissue hypoperfusion (hypotension or lactic acidosis) should begin as soon as the syndrome is recognized and should not be delayed pending intensive care unit (ICU) admission. An elevated serum lactate concentration identifies tissue hypoperfusion in patients at risk who are not hypotensive. During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as one part of a treatment protocol:
   • Central venous pressure: 8–12 mm Hg
   • Mean arterial pressure >65 mm Hg
   • Urine output >0.5 mL/kg/hr
   • Central venous (superior vena cava) or mixed venous oxygen saturation >70%

   Grade of Recommendation B

 

1. During the first 6 hrs of resuscitation of severe sepsis or septic shock, if central venous oxygen saturation or mixed venous oxygen saturation of 70% is not achieved with fluid resuscitation to a central venous pressure of 8–12 mm Hg, then transfuse packed red blood cells to achieve a hematocrit of >30% and/or administer a dobutamine infusion (up to a maximum of 20 micrograms/kg/min) to achieve this goal.

   Grade of Recommendation: B

 

1. Diagnosis
2. Appropriate cultures should always be obtained before antimicrobial therapy is initiated. To optimize identification of causative organisms, at least two blood cultures should be obtained with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. Cultures of other sites such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids should be obtained before antibiotic therapy is initiated as the clinical situation dictates.

   Grade of Recommendation: D

3. Diagnostic studies should be performed promptly to determine the source of the infection and the causative organism. Imaging studies and sampling of likely sources of infection should be performed; however, some patients may be too unstable to warrant certain invasive procedures or transport outside of the ICU. Bedside studies, such as ultrasound, may be useful in these circumstances.

   Grade of Recommendation: E

Antibiotic Therapy

1. Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained.

   Grade of Recommendation: E

2. Initial empirical anti-infective therapy should include one or more drugs that have activity against the likely pathogens (bacterial or fungal) and that penetrate into the presumed source of sepsis. The choice of drugs should be guided by the susceptibility patterns of microorganisms in the community and in the hospital.

   Grade of Recommendation: D

3. The antimicrobial regimen should always be reassessed after 48–72 hrs on the basis of microbiological and clinical data with the aim of using a narrow-spectrum antibiotic to prevent the development of resistance, to reduce toxicity, and to reduce costs. Once a causative pathogen is identified, there is no evidence that combination therapy is more effective than monotherapy. The duration of therapy should typically be 7–10 days and guided by clinical response.

   Grade of Recommendation: E

   1. Some experts prefer combination therapy for patients with Pseudomonas infections.

      Grade of Recommendation: E

   2. Most experts would use combination therapy for neutropenic patients with severe sepsis or septic shock. For neutropenic patients, broad-spectrum therapy usually must be continued for the duration of the neutropenia.

      Grade of Recommendation: E

1. If the presenting clinical syndrome is determined to be due to a noninfectious cause, antimicrobial therapy should be stopped promptly to minimize the development of resistant pathogens and superinfection with other pathogenic organisms.

   Grade of Recommendation: E

 

Source Control

1. Every patient presenting with severe sepsis should be evaluated for the presence of a focus on infection amenable to source control measures, specifically the drainage of an abscess or local focus on infection, the debridement of infected necrotic tissue, the removal of a potentially infected device, or the definitive control of a source of ongoing microbial contamination. (See Appendix A in the original guideline document for examples of potential sites needing source control.)

   Grade of Recommendation: E

2. The selection of optimal source control methods must weigh benefits and risks of the specific intervention. Source control interventions may cause further complications such as bleeding, fistulas, or inadvertent organ injury; in general, the intervention that accomplishes the source control objective with the least physiologic upset should be employed, for example, consideration of percutaneous rather than surgical drainage of an abscess.

   Grade of Recommendation: E

3. When a focus of infection amenable to source control measures, such as an intra-abdominal abscess, a gastrointestinal perforation, cholangitis, or intestinal ischemia, has been identified as the cause of severe sepsis or septic shock, source control measures should be instituted as soon as possible following initial resuscitation.

   Grade of Recommendation: E

4. If intravascular access devices are potentially the source of severe sepsis or septic shock, they should be promptly removed after establishing other vascular access.

   Grade of Recommendation: E

 

Fluid Therapy

1. See initial resuscitation recommendations (A1–2) for timing of resuscitation.
2. Fluid resuscitation may consist of natural or artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another.

   Grade of Recommendation: C

3. Fluid challenge in patients with suspected hypovolemia (suspected inadequate arterial circulation) may be given at a rate of 500–1,000 mL of crystalloids or 300–500 mL of colloids over 30 mins and repeated based on response (increase in blood pressure and urine output) and tolerance (evidence of intravascular volume overload).

   Grade of Recommendation: E

 

Vasopressors

1. When an appropriate fluid challenge fails to restore adequate blood pressure and organ perfusion, therapy with vasopressor agents should be started. Vasopressor therapy may also be required transiently to sustain life and maintain perfusion in the face of life-threatening hypotension, even when a fluid challenge is in progress and hypovolemia has not yet been corrected.

   Grade of Recommendation: E

2. Either norepinephrine or dopamine (through a central catheter as soon as available) is the first-choice vasopressor agent to correct hypotension in septic shock

   Grade of Recommendation: D

3. Low-dose dopamine should not be used for renal protection as part of the treatment of severe sepsis.

   Grade of Recommendation: B

4. All patients requiring vasopressors should have an arterial catheter placed as soon as practical if resources are available.

   Grade of Recommendation: E

5. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose conventional vasopressors. Pending the outcome of ongoing trials, it is not recommended as a replacement for norepinephrine or dopamine as a first-line agent. If used in adults, it should be administered at infusion rates of 0.01– 0.04 units/min. It may decrease stroke volume.

   Grade of Recommendation: E

Inotropic Therapy

1. In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output. If used in the presence of low blood pressure, it should be combined with vasopressor therapy.

   Grade of Recommendation: E

2. A strategy of increasing cardiac index to achieve an arbitrarily predefined elevated level is not recommended.

   Grade of Recommendation: A

Steroids

1. Intravenous corticosteroids (hydrocortisone 200–300 mg/day, for 7 days in three or four divided doses or by continuous infusion) are recommended in patients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood pressure.

   Grade of Recommendation: C

   1. Some experts would use a 250-microgram adrenocorticotropic hormone (ACTH) stimulation test to identify responders (>9 micrograms/dL increase in cortisol 30–60 mins post-ACTH administration) and discontinue therapy in these patients. Clinicians should not wait for ACTH stimulation results to administer corticosteroids.

      Grade of Recommendation: E

   2. Some experts would decrease dosage of steroids after resolution of septic shock.

      Grade of Recommendation: E

   3. Some experts would consider tapering the dose of corticosteroids at the end of therapy.

      Grade of Recommendation: E

   4. Some experts would add fludrocortisone (50 micrograms orally four times per day) to this regimen.

      Grade of Recommendation: E

1. Doses of corticosteroids >300 mg hydrocortisone daily should not be used in severe sepsis or septic shock for the purpose of treating septic shock.

   Grade of Recommendation: A

2. In the absence of shock, corticosteroids should not be administered for the treatment of sepsis. There is, however, no contraindication to continuing maintenance steroid therapy or to using stress dose steroids if the patient’s history of corticosteroid administration or the patient’s endocrine history warrants.

   Grade of Recommendation: E

Recombinant Human Activated Protein C (rhAPC)

1. rhAPC is recommended in patients at high risk of death (Acute Physiology and Chronic Health Evaluation II >25, sepsis-induced multiple organ failure, septic shock, or sepsis-induced acute respiratory distress syndrome [ARDS]) and with no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit of rhAPC. (See Appendix B in original guideline document for absolute contraindications and prescription information for warnings.)

   Grade of Recommendation: B

 

Blood Product Administration

1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as significant coronary artery disease, acute hemorrhage, or lactic acidosis (see recommendations for initial resuscitation), red blood cell transfusion should occur only when hemoglobin decreases to <7.0 g/dL (<70 g/L) to target a hemoglobin of 7.0–9.0 g/dL.

   Grade of Recommendation: B

2. Erythropoietin is not recommended as a specific treatment of anemia associated with severe sepsis but may be used when septic patients have other accepted reasons for administration of erythropoietin such as renal failure induced compromise of red blood cell production.

   Grade of Recommendation: B

3. Routine use of fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures is not recommended.

   Grade of Recommendation: E

4. Antithrombin administration is not recommended for the treatment of severe sepsis and septic shock.

   Grade of Recommendation: B

5. In patients with severe sepsis, platelets should be administered when counts are <5,000/mm³ (5 x 10⁹/L) regardless of apparent bleeding. Platelet transfusion may be considered when counts are 5,000–30,000/mm³ (5–30 x 10⁹/L) and there is a significant risk of bleeding. Higher platelet counts (>50,000/mm³ [50 x 10⁹/L]) are typically required for surgery or invasive procedures.

   Grade of Recommendation: E

Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/ARDS

1. High tidal volumes that are coupled with high plateau pressures should be avoided in ALI/ARDS. Clinicians should use as a starting point a reduction in tidal volumes over 1–2 hrs to a "low" tidal volume (6 mL per kilogram of predicted body weight) as a goal in conjunction with the goal of maintaining end-inspiratory plateau pressures <30 cm H₂O. (See Appendix C in the original guideline document for a formula to calculate predicted body weight.)

   Grade of Recommendation: B

2. Hypercapnia (allowing PaCO₂ to increase above normal, so-called permissive hypercapnia) can be tolerated in patients with ALI/ARDS if required to minimize plateau pressures and tidal volumes.

   Grade of Recommendation: C

3. A minimum amount of positive end-expiratory pressure should be set to prevent lung collapse at end-expiration. Setting positive end-expiratory pressure based on severity of oxygenation deficit and guided by the FIO₂ required to maintain adequate oxygenation is one acceptable approach. (See Appendix C in the original guideline document.) Some experts titrate positive end-expiratory pressure according to bedside measurements of thoracopulmonary compliance (to obtain the highest compliance, reflecting lung recruitment).

   Grade of Recommendation: E

4. In facilities with experience, prone positioning should be considered in ARDS patients requiring potentially injurious levels of FIO₂ or plateau pressure who are not at high risk for adverse consequences of positional changes.

   Grade of Recommendation: E

5. Unless contraindicated, mechanically ventilated patients should be maintained semirecumbent, with the head of the bed raised to 45 degrees to prevent the development of ventilator-associated pneumonia.

   Grade of Recommendation: C

6. A weaning protocol should be in place and mechanically ventilated patients should undergo a spontaneous breathing trial to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria: a) arousable; b) hemodynamically stable (without vasopressor agents); c) no new potentially serious conditions; d) low ventilatory and end-expiratory pressure requirements; and e) requiring levels of FIO₂ that could be safely delivered with a face mask or nasal cannula. If the spontaneous breathing trial is successful, consideration should be given for extubation (see Appendix D of the original guideline document). Spontaneous breathing trial options include a low level of pressure support with continuous positive airway pressure 5 cm H₂O or a T-piece.

   Grade of Recommendation: A

Sedation, Analgesia, and Neuromuscular Blockade in Sepsis

1. Protocols should be used when sedation of critically ill mechanically ventilated patients is required. The protocol should include the use of a sedation goal, measured by a standardized subjective sedation scale.

   Grade of Recommendation: B

2. Either intermittent bolus sedation or continuous infusion sedation to predetermined end points (e.g., sedation scales) with daily interruption/lightening of continuous infusion sedation with awakening and retitration, if necessary, are recommended methods for sedation administration.

   Grade of Recommendation: B

3. Neuromuscular blockers should be avoided if at all possible in the septic patient due to the risk of prolonged neuromuscular blockade following discontinuation. If neuromuscular blockers must be used for longer than the first hours of mechanical ventilation, either intermittent bolus as required or continuous infusion with monitoring of depth of block with train of four monitoring should be used.

   Grade of Recommendation: E

Glucose Control

 

1. Following initial stabilization of patients with severe sepsis, maintain blood glucose <150 mg/dL (8.3 mmol/L). Studies supporting the role of glycemic control have used continuous infusion of insulin and glucose. With this protocol, glucose should be monitored frequently after initiation of the protocol (every 30– 60 mins) and on a regular basis (every 4 hrs) once the blood glucose concentration has stabilized.

   Grade of Recommendation: D

2. In patients with severe sepsis, a strategy of glycemic control should include a nutrition protocol with the preferential use of the enteral route.

   Grade of Recommendation: E

 

Renal Replacement

 

1. In acute renal failure, and in the absence of hemodynamic instability, continuous venovenous hemofiltration and intermittent hemodialysis are considered equivalent. Continuous hemofiltration offers easier management of fluid balance in hemodynamically unstable septic patients.

   Grade of Recommendation: B

 

Bicarbonate Therapy

 

1. Bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements is not recommended for treatment of hypoperfusion-induced lactic acidemia with pH >7.15. The effect of bicarbonate administration on hemodynamics and vasopressor requirement at lower pH, as well as the effect on clinical outcome at any pH, has not been studied.

   Grade of Recommendation: C

 

Deep Vein Thrombosis Prophylaxis

 

1. Severe sepsis patients should receive deep vein thrombosis (DVT) prophylaxis with either low-dose unfractionated heparin or low-molecular weight heparin. For septic patients who have a contraindication for heparin use (i.e., thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage), the use of a mechanical prophylactic device (graduated compression stockings or intermittent compression device) is recommended (unless contraindicated by the presence of peripheral vascular disease). In very high-risk patients such as those who have severe sepsis and history of deep vein thrombosis, a combination of pharmacologic and mechanical therapy is recommended.

   Grade of Recommendation: A

 

Stress Ulcer Prophylaxis

 

1. Stress ulcer prophylaxis should be given to all patients with severe sepsis. H₂ receptor inhibitors are more efficacious than sucralfate and are the preferred agents. Proton pump inhibitors have not been assessed in a direct comparison with H₂ receptor antagonists and, therefore, their relative efficacy is unknown. They do demonstrate equivalency in ability to increase gastric pH.

   Grade of Recommendation: A