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severe sepsis and septic shock
The grades of recommendations (A-E) and
grades of evidence (I-V) are defined at the end of the "Major
Recommendations" field.
Initial Resuscitation
-
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
- 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
ความเห็น
- Diagnosis
- 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
- 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
- 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
- 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
- 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
- Some experts prefer combination therapy for patients with
Pseudomonas infections.
Grade of Recommendation: E
- 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
- 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
- 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
- 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
- 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
- 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
- See initial resuscitation recommendations (A1–2) for timing of
resuscitation.
- 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
- 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
- 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
- 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
- Low-dose dopamine should not be used for renal protection as
part of the treatment of severe sepsis.
Grade of Recommendation: B
- All patients requiring vasopressors should have an arterial
catheter placed as soon as practical if resources are available.
Grade of Recommendation: E
- 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
- 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
- A strategy of increasing cardiac index to achieve an
arbitrarily predefined elevated level is not recommended.
Grade of Recommendation: A
Steroids
- 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
- 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
- Some experts would decrease dosage of steroids after resolution
of septic shock.
Grade of Recommendation: E
- Some experts would consider tapering the dose of
corticosteroids at the end of therapy.
Grade of Recommendation: E
- Some experts would add fludrocortisone (50 micrograms orally
four times per day) to this regimen.
Grade of Recommendation: E
- 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
- 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)
- 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
- 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
- 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
- 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
- Antithrombin administration is not recommended for the
treatment of severe sepsis and septic shock.
Grade of Recommendation: B
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
