Sepsis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

The therapy of sepsis rests on antibiotics, surgical drainage of infected fluid collections, fluid replacement and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition, if necessary by parenteral nutrition, is important during prolonged illness.

A problem in the adequate management of septic patients has been the delay in administering therapy after sepsis has been recognized. Published studies have demonstrated that for every hour delay in the administration of appropriate antibiotic therapy there is an associated 7% rise in mortality. A large international collaboration was established to educate people about sepsis and to improve patient outcomes with sepsis, entitled the "Surviving Sepsis Campaign." The Campaign has published an evidence-based review of management strategies for severe sepsis, with the aim to publish a complete set of guidelines in subsequent years.

Early Goal Directed Therapy (EGDT), developed at Henry Ford Hospital by E. Rivers, MD, is a systematic approach to resuscitation that has been validated in the treatment of severe sepsis and septic shock. It is meant to be started in the Emergency Department. The theory is that one should use a step-wise approach, having the patient meet physiologic goals, to optimize cardiac preload, afterload, and contractility, thus optimizing oxygen delivery to the tissues. More recently, the GENESIS Project has validated this approach.

In EGDT:

• fluids are administered until the central venous pressure (CVP), as measured by a central venous catheter reaches 8-12 cm of water (or 10-15 cm of water in mechanically ventilated patients).
• If the mean arterial pressure is less than 65 mmHg or greater than 90 mmHg, vasopressors or vasodilators are given as needed to reach the goal. Then,
• The central venous saturation (ScvO2), i.e. the oxygen saturation of venous blood as it returns to the heart as measured at the superior vena cava, is optimized. If the ScvO2 is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the ScvO2 is optimized. Elective intubation may be performed to reduce oxygen demand if the ScvO2 remains low despite optimization of hemodynamics.

Urine output is also monitored, with a goal of 0.5 ml/kg/h. In the original trial, mortality was cut from 46.5% in the control group to 30.5% in the intervention group. The Surviving Sepsis Campaign guidelines recommends EGDT for the initial resuscitation of the septic patient with a level B strength of evidence (single randomized control trial).

The protocol per the GENESIS Project is:the GENESIS Project has validated this approach.

• Measure serum lactate
• Obtain blood cultures and administer broad-spectrum antibiotic within 3 hours of emergency department admission
• If hypotensive or serum lactate 4 mmol/L
  • 20 mL/kg of crystalloid
  • If needed, add vasopressors to keep mean arterial pressure >65 mm Hg
  • If needed, aim for central venous pressure 8 mm Hg
  • If needed, aim for central venous oxygen saturation 70%

Most therapies aimed at the inflammatory process itself have failed to improve outcome, however drotrecogin alfa (activated protein C, one of the coagulation factors) has been shown to decrease mortality from about 31% to about 25% in severe sepsis. To qualify for drotrecogin alfa, a patient must have severe sepsis or septic shock with an APACHE II score of 25 or greater and a low risk of bleeding. Low dose hydrocortisone treatment has shown promise for septic shock patients with relative adrenal insufficiency as defined by ACTH stimulation testing.

Standard treatment of infants with suspected sepsis consists of supportive care, maintaining fluid status with intravenous fluids, and the combination of a beta-lactam antibiotic (such as ampicillin) with an aminoglycoside such as gentamicin.

Surviving sepsis campaign: international guidelines for initial resuscitation of severe sepsis and septic shock: 2008 (DONOT EDIT)

“

Management of Severe Sepsis Initial Resuscitation The guideline committee recommends the protocolized resuscitation of a patient with sepsis-induced shock, defined as tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate concentration equal to or greater than 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending intensive care unit (ICU) admission. During the first 6 hours 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 (CVP): 8–12 mm Hg Mean arterial pressure (MAP) >65 mm Hg Urine output >0.5 mL/kg/hour Central venous (superior vena cava) or mixed venous oxygen saturation >70% or >65%, respectively (Grade 1C) The guideline committee suggests that during the first 6 hours of resuscitation of severe sepsis or septic shock, if central venous oxygen saturation (SCVO2) or mixed venous saturation (SvO2) of 70% or 65% respectively is not achieved with fluid resuscitation to the CVP target, then transfusion of packed red blood cells to achieve a hematocrit of >30% and/or administration of a dobutamine infusion (up to a maximum of 20 micrograms/kg/min) be utilized to achieve this goal. (Grade 2C)

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For Level of evidence and classes click here.

Surviving sepsis campaign: international guidelines for antibiotic therapy of severe sepsis and septic shock: 2008 (DONOT EDIT)

“

Antibiotic therapy 1. The guideline committee recommends that intravenous antibiotic therapy be started as early as possible and within the first hour of recognition of septic shock (Grade 1B) and severe sepsis without septic shock (Grade 1D). Appropriate cultures should be obtained before initiating antibiotic therapy, but should not prevent prompt administration of antimicrobial therapy. (Grade 1D) 2a. The guideline committee recommends that initial empirical anti-infective therapy include one or more drugs that have activity against all likely pathogens (bacterial and/or fungal) and that penetrate in adequate concentrations into the presumed source of sepsis. (Grade 1B) 2b. The guideline committee recommends that the antimicrobial regimen be reassessed daily to optimize activity, to prevent the development of resistance, to reduce toxicity, and to reduce costs. (Grade 1C) 2c. The guideline committee suggests combination therapy for patients with known or suspected Pseudomonas infections as a cause of severe sepsis. (Grade 2D) 2d. The guideline committee suggests combination empiric therapy for neutropenic patients with severe sepsis. (Grade 2D) 2e. When used empirically in patients with severe sepsis, the guideline committee suggests that combination therapy should not be administered for more than 3 to 5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known. (Grade 2D) 3. The guideline committee recommends that the duration of therapy typically be 7 to 10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, or who have immunologic deficiencies including neutropenia. (Grade 1D) 4. If the presenting clinical syndrome is determined to be due to a noninfectious cause, the guideline committee recommends antimicrobial therapy be stopped promptly to minimize the likelihood that the patient will become infected with an antibiotic resistant pathogen or will develop a drug related adverse effect. (Grade 1D)

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For Level of evidence and classes click here.

Surviving sepsis campaign: international guidelines for source control of severe sepsis and septic shock: 2008 (DONOT EDIT)

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Source control 1a. The guideline committee recommends that a specific anatomic diagnosis of infection requiring consideration for emergent source control- for example necrotizing fasciitis, diffuse peritonitis, cholangitis, intestinal infarction – be sought and diagnosed or excluded as rapidly as possible (Grade 1C) and within the first 6 hours following presentation (Grade 1D). 1b. The guideline committee further recommends that all patients presenting with severe sepsis be evaluated for the presence of a focus of infection amenable to source control measures, specifically the drainage of an abscess or local focus of 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 (Grade 1C) 2. The guideline committee suggests that when infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and non-viable tissues has occurred. (Grade 2B) 3. The guideline committee recommends that when source control is required, the effective intervention associated with the least physiologic insult be employed, for example, percutaneous rather than surgical drainage of an abscess. (Grade 1D) 4. The guideline committee recommends that when intravascular access devices are a possible source of severe sepsis or septic shock, they be promptly removed after establishing other vascular access. (Grade 1C)

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For Level of evidence and classes click here.

Surviving sepsis campaign: international guidelines for fluid therapy of severe sepsis and septic shock: 2008 (DONOT EDIT)

“

Fluid Therapy 1. The guideline committee recommends fluid resuscitation with either natural/artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another. (Grade 1B) 2. The guideline committee recommends fluid resuscitation initially target a CVP of at least 8 mm Hg (12 mm Hg in mechanically ventilated patients). Further fluid therapy is often required. (Grade 1C) 3a. The guideline committee recommends that a fluid challenge technique be applied, wherein fluid administration is continued as long as the hemodynamic improvement (for example, arterial pressure, heart rate, urine output) continues. (Grade 1D) 3b. The guideline committee recommends fluid challenge in patients with suspected hypovolemia be started with at least 1000 mL of crystalloids or 300 to 500 mL of colloids over 30 minutes. More rapid administration and greater amounts of fluid may be needed in patients with sepsis induced tissue hypoperfusion (see initial resuscitation recommendations). (Grade 1D) 3c. The guideline committee recommends the rate of fluid administration be reduced substantially when cardiac filling pressures (CVP or pulmonary artery balloon-occluded pressure) increase without concurrent hemodynamic improvement. (Grade 1D)

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For Level of evidence and classes click here.

References

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