Management of Severe Sepsis & Septic Shock

Prof.Dr.K.S.CHENTHIL IMCU

Dr.Rakesh Pinninti

• Understanding the concept of ‘BUNDLES’• Severe Sepsis Bundles• Diagnosing Sepsis• Individual components of each Bundles• Scientific proof & Basis for inclusion of Bundle

component.• Measuring and Documenting the Bundles• Conclusions & Take Home Msgs.

Understanding the Bundle Concept

A "bundle" is a group of therapies for a given disease that, when implemented together, may result in better outcomes than if implemented individually.

In a bundle, the individual elements included are built around

“best evidence-based practices“

The science supporting the individual treatment strategies in a bundle is sufficiently mature such that implementation of the approach should be considered either best practice or a reasonable and generally accepted practice.

Understanding the Bundle Concept

• Making the Severe Sepsis Bundles standard practice will eliminate the piecemeal or chaotic application of standards for sepsis care that characterize many clinical environments today.

• The Severe Sepsis Bundles have been designed, to achieve a 25 percent reduction in mortality due to severe sepsis or septic shock.

Severe Sepsis Bundles• There are two Severe Sepsis Bundles. • Each bundle articulates objectives to be accomplished

within specific timeframes.

• The bundles have been developed based upon the ...."2008 Surviving Sepsis Campaign Guidelines “ for the Management of Severe Sepsis and Septic Shock.

A)Sepsis Resuscitation BundleB) Sepsis Management Bundle

Sepsis Resuscitation Bundle

• The Sepsis Resuscitation Bundle describes seven tasks that should begin immediately, but must be accomplished within the first 6 hours of presentation for patients with severe sepsis or septic shock.

• The goal is to perform all indicated tasks 100 percent of the time within the first 6 hours of identification of severe sepsis.

Sepsis Management Bundle

• Evidence-based goals that must be completed within 24 hours for patients with severe sepsis, septic shock and/or lactate > 4 mmol/L (36 mg/dL).

• For patients with severe sepsis, as many as four bundle elements must be accomplished within the first 24 hours of presentation

• The goal is to perform all indicated tasks 100 percent of the time within the first 24 hours of presentation:

Infection documented or suspected & followinga)General variablesb)Inflammatory variablesc)Hemodynamic variablesd)Organ dysfunction variablese)Tissue perfusion variables

Severe Sepsis

Serum lactate measured• Hyperlactatemia is typically present in patients with

severe sepsis or septic shock and may be secondary to anaerobic metabolism due to hypoperfusion.

• The prognostic value of raised blood lactate levels has been well established in septic shock patients particularly if the high levels persist.

• In addition, blood lactate levels have been shown to have greater prognostic value than oxygen-derived variables.

• Obtaining a lactate level is essential to identifying tissue hypoperfusion in patients who are not yet hypotensive but who are at risk for septic shock.

ImplicationsGiven the high risk for septic shock, all patients with elevated lactate >4

mmol/L (36 mg/dL) enter the early goal-directed therapy portion of the Severe Sepsis Resuscitation Bundle, regardless of blood pressure. This approach is consistent with the trial that established the value of early

goal-directed therapies, Rivers et al. Turnaround TimeSerum lactate must be available in ny institution with rapid turnaround time (within minutes) to effectively treat severely septic patients. An arterial blood gas analyzer located in the clinical laboratories usually accomplishes this. . It is essential for hospitals to invest in adequate equipment in order to meet present standards of care for septic patients. The technique of obtaining serum lactate by venipuncture typically carries a 24- to 48-hour turnaround time and will not be suitable to care for septic patients.

BLOOD CULTURES OBTAINED PRIOR TO ANTIBIOTIC ADMINISTRATION

• Thirty percent to 50 percent of patients presenting with a clinical syndrome of severe sepsis or shock have positive blood cultures. Therefore, blood should be obtained for culture in any critically ill septic patient.

• Collecting blood cultures prior to antibiotic administration offers the best hope of identifying the organism that caused severe sepsis in an individual patient. .

Collection Strategy

Two or more blood cultures are recommended. (1) In patients with suspected catheter-related infection, a pair of blood cultures obtained through the catheter hub and a peripheral site should be obtained simultaneously. 2) Volume of blood may also be important

IndicationsFever, Chills,Hypothermia, Leukocytosis, Left shift of neutrophils, Neutropenia, and Development of otherwise unexplained organ dysfunction, e.g., renal failure/AKI

Blood cultures should be taken as soon as possible after the onset of fever or chills.

IMPROVE TIME TO BROAD-SPECTRUM ANTIBIOTICS

• Recent evidence supports that for patients with septic shock, the duration of hypotension prior the administration of antibiotics is a critical determinant in the survival of septic shock.

• The balance of evidence unwaveringly suggests that early administration of appropriate antibiotics reduces mortality in patients with Gram-positive and Gram-negative bacteremias.

The major sources of infection in severe sepsis or shock are pneumonia and intra-abdominal infections ***and other sources generally account for < 5 percent of cases. Choice of AntibioticsThe choice of antibiotics should be guided by the susceptibility of likely pathogens in the community and the hospitalThe regimen should cover all likely pathogens since there is little margin for error in critically ill patients.48- to 72-Hour Re-evaluationThe antimicrobial regimen should always be reassessed after 48–72 hours 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. The duration of therapy should typically be 7–10 days and guided by clinical response.

*** run-Buisson C, Doyon F, Carlet J. Bacteremia and severe sepsis in adults: A multicenter prospective survey in ICUs and wards of 24 hospitals. Am J Respir Crit Care Med. 1996;154:617–624. 6. Opal SM, Garber GE, LaRosa SP, et al. Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated). Clin Infect Dis. 2003;37:50–58

*****************• Establish a standardized clinical protocol that

includes the empiric administration of antibiotics in severe sepsis within 3 hours of presentation for ED admissions and 1 hour for ICU admissions.

• Combination therapies should last 3–5 days and be de-escalated following determination of microbial susceptibilities

TREAT HYPOTENSION AND/OR ELEVATED LACTATE WITH FLUIDS

• The Surviving Sepsis Campaign recommends A) fluid resuscitation with either natural/artificial colloids or crystalloids.

There is no evidence-based support for one type of fluid over anotherB) fluid resuscitation initially target a CVP of at least 8 mm Hg (12 mm Hg in

mechanically ventilated patients). Further fluid therapy is often requiredC) fluid challenge technique be applied, wherein fluid administration is

continued as long as the hemodynamic improvement (e.g., arterial pressure, heart rate, urine output) continues.

D) fluid challenge in patients with suspected hypovolemia be started with at least 1000 mL of crystalloids or 300-500 mL of colloids over 30 min. More rapid administration and greater amounts of fluid may be needed in patients with sepsis-induced tissue hypoperfusion

E) the rate of fluid administration be reduced substantially when cardiac filling pressures (CVP or pulmonary artery balloon-occluded pressure) increase without concurrent hemodynamic improvement

APPLY VASOPRESSORS FOR ONGOING HYPOTENSION

• The Surviving Sepsis Campaign recommends a) Mean arterial pressure (MAP) be maintained ≥ 65 mm Hgb) Either norepinephrine or dopamine as the first choice vasopressor

agent to correct hypotension in septic shock (administered through a central catheter as soon as one is available)

c) Epinephrine, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock

d) Do not wait to start vasopressors until a fluid challenge or bolus of intravenous fluid is completed before using vasopressor agents if severe hypotension is present.****

**** Adequate fluid resuscitation is a fundamental aspect of the hemodynamic management of patients with septic shock, and should ideally be achieved before vasopressors and inotropes are used, but using vasopressors early as an emergency measure in patients with severe shock is frequently necessary. When that occurs, great effort should be directed to weaning vasopressors with continuing fluid resuscitation.

******** The Surviving Sepsis Campaign suggests that during the first 6 hours of resuscitation of severe sepsis or septic shock, if ScvO2 or 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 μg·kg-1·min-1) be utilized to achieve this goal

ADMINISTER LOW-DOSE STEROIDS BY A STANDARD POLICY

• Intravenous corticosteroids (hydrocortisone 200–300 mg/day, for 7 days in three or four divided doses or by continuous infusion) are suggested in for adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy.

• Earlier Shock Reversal:Low-dose corticosteroids promote more rapid shock reversal than when they are not administered to patients with septic shock.

• Choice of Steroid: Hydrocortisone is preferred to other glucocorticoids in patients with septic shock in most clinical trials.

• However, a recent large, European multicenter trial (CORTICUS) failed to show a mortality benefit with steroid therapy of septic shock

• CORTICUS did show a faster resolution of septic shock in patients who received steroids.

• The Surviving Sepsis Campaign recommends that corticosteroids not be administered for the treatment of sepsis in the absence of shock.

ADMINISTER RECOMBINANT HUMAN ACTIVATED PROTEIN C (RHAPC)

BY A STANDARD POLICY

• The Surviving Sepsis Campaign suggests that adult patients with sepsis-induced organ dysfunction associated with a clinical assessment of high risk of death, most of whom will have APACHE II ≥25 or multiple organ failure, receive drotrecogin alfa (activated), a.k.a, recombinant activated protein C (rhAPC), if there are no contraindications. (24 μg•kg•hr during 96 hrs)

Following populations are excluded in trails evaluating efficacy of rhAPC

• morbidly obese patients,• Pregnant females• patients admitted to an intensive care unit in moribund state with an almost

certain likelihood to die• Children • acute pancreatitis • anticoagulation & hematologic diseases that could interfere with the anticoagulant

effects of rhAPC ContraindicationsBleeding is the most frequent and serious adverse event that may be

induced by rhAPC treatment, and patients at high risk of serious bleeding events should not be treated with rhAPC

Intracranial bleeding is the most severe bleeding event observed in clinical studies or rhAPC.

The main risk factors for intracranial bleeding were severe thrombocytopenia and meningeal infection.

Patients with a baseline platelet count of < 30,000/mm3 should not receive rhAPC; previous platelet transfusion should likely not be used to allow rhAPC treatment;

MAINTAIN ADEQUATE GLYCEMIC CONTROL

• Effective glucose control in the intensive care unit (ICU) has been shown to decrease morbidity across a large range of conditions and also to decrease mortality.

• An initial investigation by Van den Berghe and colleagues suggested that controlling blood glucose levels by intensive insulin therapy decreased mortality and morbidity in surgical critically ill patients.

• Intensive insulin therapy halved the prevalence of:

• Bloodstream infections • Prolonged inflammation • ARF requiring dialysis or hemofiltration • Critical illness polyneuropathy • Transfusion requirements Patients receiving intensive insulin therapy were also less likely to require prolonged mechanical ventilation and intensive care.

• Evidence based on surgical patients

• The NICE-SUGAR investigators concluded that that intensive glucose control increased mortality among adults in the ICU and that a blood glucose target of < 180 mg/dL resulted in lower mortality than did a target of 81 to 108 mg/dL.

• VISEP investigators found that the rate of severe hypoglycemia was higher in the intensive-therapy group than in the conventional-therapy group as was the rate of serious adverse events

Additional factors

• Mechanical ventilation & related events & guidelines

• Sedation, analgesia, neuromuscular blockade• Renal replacement therapy• Bicarbonate therapy• DVT prophylaxis• Stress ulcer prophylaxis

THANK YOU