Sandbox Sepsis medical therapy: Difference between revisions

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===Transfusion===
===Transfusion===
In septic shock, leukoreduced erythrocyte transfusion is associated with similar clinical outcomes (90 day [[mortality]] and [[ischemic]] events) among patients who are administered [[erythrocyte]] transfusion at a [[hemoglobin]] threshold of 7 g/dL compared to those who receive it at a higher threshold of 9 g/dL.<ref name="pmid25270275">{{cite journal| author=Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S et al.| title=Lower versus higher hemoglobin threshold for transfusion in septic shock. | journal=N Engl J Med | year= 2014 | volume= 371 | issue= 15 | pages= 1381-91 | pmid=25270275 | doi=10.1056/NEJMoa1406617 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25270275  }} </ref>
In septic shock, leukoreduced erythrocyte transfusion is associated with similar clinical outcomes (90 day [[mortality]] and [[ischemic]] events) among patients who are administered [[erythrocyte]] transfusion at a [[hemoglobin]] threshold of 7 g/dL compared to those who receive it at a higher threshold of 9 g/dL.<ref name="pmid25270275">{{cite journal| author=Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S et al.| title=Lower versus higher hemoglobin threshold for transfusion in septic shock. | journal=N Engl J Med | year= 2014 | volume= 371 | issue= 15 | pages= 1381-91 | pmid=25270275 | doi=10.1056/NEJMoa1406617 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25270275  }} </ref>
==Contraindicated Medications==
{{MedCondContrAbs
|MedCond =Sepsis|Etanercept|Sitagliptin And Metformin Hydrochloride}}
==2012 Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock (DO NOT EDIT)<ref>{{Cite journal| doi = 10.1097/CCM.0b013e31827e83af| issn = 1530-0293| volume = 41| issue = 2| pages = 580–637| last1 = Dellinger| first1 = R. Phillip| last2 = Levy| first2 = Mitchell M.| last3 = Rhodes| first3 = Andrew| last4 = Annane| first4 = Djillali| last5 = Gerlach| first5 = Herwig| last6 = Opal| first6 = Steven M.| last7 = Sevransky| first7 = Jonathan E.| last8 = Sprung| first8 = Charles L.| last9 = Douglas| first9 = Ivor S.| last10 = Jaeschke| first10 = Roman| last11 = Osborn| first11 = Tiffany M.| last12 = Nunnally| first12 = Mark E.| last13 = Townsend| first13 = Sean R.| last14 = Reinhart| first14 = Konrad| last15 = Kleinpell| first15 = Ruth M.| last16 = Angus| first16 = Derek C.| last17 = Deutschman| first17 = Clifford S.| last18 = Machado| first18 = Flavia R.| last19 = Rubenfeld| first19 = Gordon D.| last20 = Webb| first20 = Steven A.| last21 = Beale| first21 = Richard J.| last22 = Vincent| first22 = Jean-Louis| last23 = Moreno| first23 = Rui| last24 = Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup| title = Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012| journal = Critical Care Medicine| date = 2013-02| pmid = 23353941}}</ref>==
===Initial Resuscitation and Infection Issues===
====Initial Resuscitation====
{{cquote|
1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L). Goals during the first 6 hrs of resuscitation:
* Central venous pressure 8–12 mm Hg
* Mean arterial pressure (MAP) ≥ 65 mm Hg
* Urine output ≥ 0.5 mL/kg/hr
* Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively. {{GRADE1|C}}
2. In patients with elevated lactate levels targeting resuscitation to normalize lactate. {{GRADE2|C}}
}}
====Screening for Sepsis and Performance Improvement====
{{cquote|
1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy. {{GRADE1|C}}
2. Hospital–based performance improvement efforts in severe sepsis.
}}
====Diagnosis====
{{cquote|
1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s). {{GRADE1|C}} At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. {{GRADE1|C}}
2. Use of the 1,3 beta-D-glucan assay {{GRADE2|B}}, mannan and anti-mannan antibody assays {{GRADE2|C}}, if available and invasive candidiasis is in differential diagnosis of cause of infection.
3. Imaging studies performed promptly to confirm a potential source of infection.
}}
====Antimicrobial Therapy====
{{cquote|
1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock {{GRADE1|B}} and severe sepsis without septic shock {{GRADE1|C}} as the goal of therapy.
2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis. {{GRADE1|B}}
2b. Antimicrobial regimen should be reassessed daily for potential deescalation. {{GRADE1|B}}
3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection. {{GRADE2|C}}
4a. Combination empirical therapy for neutropenic patients with severe sepsis {{GRADE2|B}} and for patients with difficult-to-treat, multidrug- resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. {{GRADE2|B}} For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for ''P. aeruginosa'' bacteremia. {{GRADE2|B}} A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections. {{GRADE2|B}}
4b. Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known. {{GRADE2|B}}
5. Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia. {{GRADE2|C}}
6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin. {{GRADE2|C}}
7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause.
}}
====Source Control====
{{cquote|
1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible. {{GRADE1|C}}
2. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred. {{GRADE2|B}}
3. When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess).
4. If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established.
}}
====Infection Prevention====
{{cquote|
1a. Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; This infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective. {{GRADE2|B}}
1b. Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis. {{GRADE2|B}}
}}
===Hemodynamic Support and Adjunctive Therapy===
====Fluid Therapy of Severe Sepsis====
{{cquote|
1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock. {{GRADE1|B}}
2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock. {{GRADE1|B}}
3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids. {{GRADE2|C}}
4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients. {{GRADE1|C}}
5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables.
}}
====Vasopressors====
{{cquote|
1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg. {{GRADE1|C}}
2. Norepinephrine as the first choice vasopressor. {{GRADE1|B}}
3. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure. {{GRADE2|B}}
4. Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage.
5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents).
6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia). {{GRADE2|C}}
7. Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target. {{GRADE1|C}}
8. Low-dose dopamine should not be used for renal protection. {{GRADE1|A}}
9. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available.
}}
====Inotropic Therapy====
{{cquote|
1. A trial of dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP. {{GRADE1|C}}
2. Not using a strategy to increase cardiac index to predetermined supranormal levels. {{GRADE1|B}}
}}
====Corticosteroids====
{{cquote|
1. Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day. {{GRADE2|C}}
2. Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone. {{GRADE2|B}}
3. In treated patients hydrocortisone tapered when vasopressors are no longer required. {{GRADE2|D}}
4. Corticosteroids not be administered for the treatment of sepsis in the absence of shock. {{GRADE1|D}}
5. When hydrocortisone is given, use continuous flow. {{GRADE2|D}}
}}
===Other Supportive Therapy of Severe Sepsis===
====Blood Product Administration====
{{cquote|
1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0 –9.0 g/dL in adults. {{GRADE1|B}}
2. Not using erythropoietin as a specific treatment of anemia associated with severe sepsis. {{GRADE1|B}}
3. Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures. {{GRADE2|D}}
4. Not using antithrombin for the treatment of severe sepsis and septic shock. {{GRADE1|B}}
5. In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding. We suggest prophylactic platelet transfusion when counts are < 20,000/mm3 (20 x 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 x 109/L]) are advised for active bleeding, surgery, or invasive procedures. {{GRADE2|D}}
}}
====Immunoglobulins====
{{cquote|
1. Not using intravenous immunoglobulins in adult patients with severe sepsis or septic shock. {{GRADE2|B}}
}}
====Selenium====
{{cquote|
1. Not using intravenous selenium for the treatment of severe sepsis. {{GRADE2|C}}
}}
====History of Recommendations Regarding Use of Recombinant Activated Protein C (rhAPC)====
{{cquote|
1. A history of the evolution of SSC recommendations as to rhAPC (no longer available) is provided.
}}
====Mechanical Ventilation of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)====
{{cquote|
1. Target a tidal volume of 6mL/kg predicted body weight in patients with sepsis-induced ARDS ({{GRADE1|A}} vs. 12 mL/kg).
2. Plateau pressures be measured in patients with ARDS and initial upper limit goal for plateau pressures in a passively inflated lung be ≤30 cm H2O. {{GRADE1|B}}
3. Positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at end expiration (atelectotrauma). {{GRADE1|B}}
4. Strategies based on higher rather than lower levels of PEEP be used for patients with sepsis- induced moderate or severe ARDS. {{GRADE2|C}}
5. Recruitment maneuvers be used in sepsis patients with severe refractory hypoxemia. {{GRADE2|C}}
6. Prone positioning be used in sepsis-induced ARDS patients with a Pao2/Fio2 ratio ≤ 100mm Hg in facilities that have experience with such practices. {{GRADE2|B}}
7. That mechanically ventilated sepsis patients be maintained with the head of the bed elevated to 30-45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia. {{GRADE1|B}}
8. That noninvasive mask ventilation (NIV) be used in that minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks. {{GRADE2|B}}
9. That a weaning protocol be in place and that mechanically ventilated patients with severe sepsis undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:
* Arousable
* Hemodynamically stable (without vasopressor agents)
* No new potentially serious conditions
* Low ventilatory and end-expiratory pressure requirements
* Low Fio2 requirements which can be met safely delivered with a face mask or nasal cannula
: If the spontaneous breathing trial is successful, consideration should be given for extubation. {{GRADE1|A}}
10. Against the routine use of the pulmonary artery catheter for patients with sepsis-induced ARDS. {{GRADE1|A}}
11. A conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypo perfusion. {{GRADE1|C}}
12. In the absence of specific indications such as bronchospasm, not using beta 2-agonists for treatment of sepsis-induced ARDS. {{GRADE1|B}}
}}


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Infectious disease]]
 
[[Category:Intensive care medicine]]
[[Category:Intensive care medicine]]

Latest revision as of 18:42, 18 September 2017

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

Overview

The Surviving Sepsis Campaign was an international effort organized by physicians that developed and promoted widespread adoption of practice improvement programs grounded in evidence-based guidelines. The goal was to improve diagnosis and treatment of sepsis. Included among the guidelines were sepsis screening for high-risk patients; taking bacterial cultures soon after the patient arrived at the hospital; starting patients on broad-spectrum intravenous antibiotic therapy before the results of the cultures are obtained; identifying the source of infection and taking steps to control it (e.g., abscess drainage); administering intravenous fluids to correct a loss or decrease in blood volume; and maintaining glycemic (blood sugar) control. These and similar guidelines have been tested by a number of hospitals and have shown potential for decreasing hospital mortality due to sepsis.[1][2]

Medical Therapy

The delay in administering therapy after sepsis has been recognized, is the main problem in the adequate management of septic patients. 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".

Early Goal Directed Therapy (EGDT)

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.[3] 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.

Although initial studies reported benefit from EGDT,[4][3][5] the more recent ProCESS[6] and ARISE[7] trials failed to demonstrate any benefit. However, the outcomes in the control groups of these trials were much more favorable than in the earlier trials. The extent of protocol-based care in the 'usual care' of the control groups is not known.

In Early Goal Directed Therapy:

  • 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.
  • 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.

GENESIS Project

The protocol per the GENESIS Project is:[5]

  • 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:
    • Administer 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%

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.

Transfusion

In septic shock, leukoreduced erythrocyte transfusion is associated with similar clinical outcomes (90 day mortality and ischemic events) among patients who are administered erythrocyte transfusion at a hemoglobin threshold of 7 g/dL compared to those who receive it at a higher threshold of 9 g/dL.[8]

References

  1. ↑ "Products - Data Briefs - Number 62 - June 2011". Retrieved 2012-09-17.
  2. ↑ Wiedermann CJ, Adamson IY, Pert CB, Bowden DH (1988). "Enhanced secretion of immunoreactive bombesin by alveolar macrophages exposed to silica". Journal of Leukocyte Biology. 43 (2): 99–103. PMID 2826633. Retrieved 2012-09-17. Unknown parameter |month= ignored (help)
  3. ↑ 3.0 3.1 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B; et al. (2001). "Early goal-directed therapy in the treatment of severe sepsis and septic shock". N Engl J Med. 345 (19): 1368–77. PMID 11794169. Review in: ACP J Club. 2002 May-Jun;136(3):90
  4. ↑ Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; et al. (2010). "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial". JAMA. 303 (8): 739–46. doi:10.1001/jama.2010.158. PMID 20179283.
  5. ↑ 5.0 5.1 Cannon CM, Holthaus CV, Zubrow MT, Posa P, Gunaga S, Kella V; et al. (2012). "The GENESIS Project (GENeralized Early Sepsis Intervention Strategies): A Multicenter Quality Improvement Collaborative". J Intensive Care Med. doi:10.1177/0885066612453025. PMID 22902347.
  6. ↑ ProCESS Investigators. Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA; et al. (2014). "A randomized trial of protocol-based care for early septic shock". N Engl J Med. 370 (18): 1683–93. doi:10.1056/NEJMoa1401602. PMC 4101700. PMID 24635773. Review in: Ann Intern Med. 2014 Jun 17;160(12):JC9
  7. ↑ The ARISE Investigators and the ANZICS Clinical Trials Group (2014). "Goal-Directed Resuscitation for Patients with Early Septic Shock". N Engl J Med. doi:10.1056/NEJMoa1404380. PMID 25272316.
  8. ↑ Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S; et al. (2014). "Lower versus higher hemoglobin threshold for transfusion in septic shock". N Engl J Med. 371 (15): 1381–91. doi:10.1056/NEJMoa1406617. PMID 25270275.
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