Sepsis Case Study

The guidelines’ first focus is the definition of sepsis, which makes sense, because there is no way to effectively treat sepsis without an accurate and categorical definition of the term. The guidelines define sepsis as “the presence (probable or documented) of infection together with systemic manifestations of infection”. Such systemic manifestations can include fever, tachypnea, AMS, WBC >12k, among others; these manifestations are listed in full in Table 1 of the guidelines. The definition for severe sepsis builds on to the definition of sepsis, bringing organ dysfunction and tissue hypoperfusion (oliguria, hypotension, elevated lactate) into the picture; full diagnostic criteria is listed in Table 2. The guidelines recommend that all

severely ill patients or those with potential infection be regularly screened for severe sepsis. This is to facilitate early identification of sepsis, leading to prompt, early therapy, resulting in improved patient outcomes. Septic shock is defined to be hypotension due to sepsis (SBP 40 mmHg or less than two standard deviations below the mean for patient age in the absence of other hypotension causes) that persists despite adequate fluid resuscitation.
To treat severe sepsis, the authors recommend the implementation of a treatment protocol with quantitative goals in mind for effective treatment. The goals for the first 6 hours of resuscitation are as follows: CVP 8-12 mmHg, MAP ≥ 65 mmHg, urine output ≥ 0.5 mL/kg/hr, SCVO2 of 70% or SVO2 of 65%. The authors also make a slightly weaker recommendation to normalize lactate in those patients in whom elevated lactate was used as a marker for tissue hypoperfusion. Cultures should also be taken prior to the administration of antibiotics to help pinpoint the cause of infection, unless these cultures delay antibiotic administration by more than 45 minutes. At least two sets of blood cultures (aerobic & anaerobic bottles) are to be obtained, and at least one should be drawn percutaneously and one drawn through each access device, unless that device was placed within 48 hours of the draw. If candidiasis is a possible infection source, a 1,3 beta-D-glucan assay, mannan, and anti-mannan immunoassays should be performed, if available. Imaging studies are also an option to help identify the source of infection. The 2012 guidelines contain a bundle with completion goals at 3 and 6 hours, it is as follows:

To be completed within 3 hrs: To be completed within 6 hrs:
Assess lactate level If hypotensive despite initial fluid resuscitation:
Administer vasopressors
Goal MAP: ≥ 65 mmHg
Blood cultures before antibiotics If in septic shock or initial lactate ≥ 4 mmol/L:
Measure CVP (goal: ≥ 8 mmHg)
Measure SCVO2 (goal ≥ 70%)
Administer broad spec.

antibiotics Reassess lactate level if initial was elevated (goal: WNL)

If hypotensive or lactate ≥ 4 mmol/L:

Administer 30 mL/kg crystalloid

Antimicrobial therapy is the cornerstone sepsis treatment, and the therapeutic goal should be centered around administration of effective IV antibiotics within 60 minutes of septic shock or severe sepsis (without shock) recognition. The initial antimicrobial therapy should be empiric and focused on having activity against all expected pathogens (bacterial, fungal, viral), based on each individual patient situation. Daily reassessment of antimicrobial therapy should be performed, with de escalation in mind; procalcitonin levels can be of use to direct discontinuation in patients with no evidence of infection following initial septic

presentation.
In patients with severe sepsis that are neutropenic, or in those with MDR bacterial pathogens (ex. Acinetobacter, Pseudomonas), combination empirical therapy should be utilized. For severe infections that are associated with respiratory failure and septic shock, a combination of extended-spectrum B-lactam and aminoglycoside or FQ is recommended. A beta-lactam and macrolide combination is recommended for treatment of septic shock due to bacteremic S. pneumoniae infections. The empiric therapy selected should not exceed a duration of 3-5 days; as soon as susceptibility data is available, the patient should be de-escalated to single therapy. Total duration of therapy is usually 7-10 days, with longer durations necessary in certain cases such as: neutropenia and other immunodeficiencies, undrainable infectious foci, S. aureus bacteremia, slow clinical response. If viral cause is implicated in the cause of severe sepsis or septic shock, antivirals should be initiated as soon as possible.
Anatomical diagnosis of infection should be performed as soon as possible to determine need for source control. Source control of the infection should be performed within 12 hours of diagnosis, if possible; if required in a severely septic patient, this should be least invasive in nature. If infected peripancreatic necrosis is present, intervention should be delayed until viable and non viable tissues have been demarcated to an acceptable degree. Intravascular access devices are implicated as possible infection sources, they should be removed after other routes of vascular access have been established. Oral and digestive decontamination should be performed to reduce risk of VAP; oral chlorhexidine gluconate should be used for oropharyngeal decontamination.
The preferred initial fluids in fluid resuscitation of severely septic patients or those in septic shock are crystalloids; hydroxyethyl starches should not be used, and albumin should be added in when substantial amounts of crystalloids are used. 30 mL/kg of crystalloids (with or without albumin equivalent) is to be the minimum for initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspected hypovolemia, although higher rates and amounts may be required in some scenarios.
Vasopressors should be used with a target MAP of 65 mmHg, with norepinephrine as first line therapy.

Epinephrine can be added to NE if needed to maintain acceptable BP, or substituted if necessary. Vasopressin (0.03 units/min) can be used as an adjunct to increase MAP,or to lower NE dose; it should not be used as a single agent. Dopamine can be used as an alternative to NE, but only in patients meeting criteria due to risk of arrhythmias; low dose dopamine not to be used for renal protection. Phenylephrine not recommended in most cases; can be utilized if NE leads to serious arrhythmias, CO is known to be high yet BP continues to be low, or as salvage therapy when MAP target is not achieved by other means. An arterial cath should be placed ASAP in patients who require vasopressors. Inotropes can be added to vasopressors or used alone, with a doubatmine trial of up to 20 mcg/kg/min as an option if myocardial dysfunction is suspected by elevated cardiac filling pressures and low CO, or if hypoperfusion is still evident although intravascular volume and MAP are at goal. Bicarbonate should not be used in patients with pH greater than or equal to

7.15.
If vasopressors and fluids cannot restore hemodynamic stability, IV hydrocortisone can be used in adults at a dose of 200 mg/day, but only in the presence of shock in addition to sepsis. A continuous infusion should be used, and the dosage should be tapered based on clinical response.
Upon hypoperfusion resolution, and absence of MI, severe hypoxemia, acute hemorrhage, or IHD, RBC transfusion should be performed when hemoglobin decreases to below 7.0 g/dL; target 7-9 g/dL. Erythropoietin and antithrombin should not be used. FFP should not be used to correct coagulopathies in the absence of bleeding or planned invasive procedures. In severe sepsis patients, platelet prophylaxis should be performed in the following scenarios: 180 mg/dL
● BG to be monitored every 1-2 hrs until insulin infusion rates and BG values are stable
○ Every 4 hours afterwards
● Caution with use of POC glucose testing

DVT Prophylaxis Stress Ulcers Prophylaxis
● Severe sepsis → SubQ LMWH daily
● Pharmacotherapy + pneumatic compression if possible
● If CI to heparin → mechanical compression ● H2RA or PPI in severe sepsis or septic shock patients with bleeding risk factors
● PPIs preferred over H2RAs (outdated?)
● No ppx for patients without risk factors