sepsis 2016

Sepsis- overview and management 2016

DR SUBHANKAR CHATTERJEE

MortalitySepsis: 30% - 50%

Septic Shock: 50% - 60%

Why we are spending time on sepsis?

Why we are spending time on sepsis?

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The third International Consensus 2016 Definition for Sepsis ( Sepsis 3)

SEPSIS IS A LIFE THREATENING ORGAN DYSFUNCTION CAUSED BY A DYSREGULATED HOST

RESPONSE TO INFECTION

Epidemiology

Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003). The epidemiology of sepsis in the United States from 1979 through 2000. New England Journal of Medicine, 348(16), 1546–1554.

Harrison, D. A., Welch, C. A., & Eddleston, J. M. (2006). The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Critical Care, 10(2), R42.

Brun-Buisson, C., Meshaka, P., Pinton, P., Vallet, B., EPISEPSIS Study Group. (2004). EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Medicine, 30(4), 580–588.

[1993 - 2001]...a 17% reduction in mortality.

[1993-2001]...a 75% increase in... severe sepsis...

Incidenceof Sepsis

Mortalityof Sepsis

Why the burden of sepsis increasing?

Increased geriatric population Increasing number of immunocompromised host Increasing drug resistant organism Increasing metabolic disorder

eitherBacteraemia (or viraemia/fungaemia/protozoan)is the presence of bacteria within the bloodstream

Septic focus (abscess / cavity / tissue mass)

Infection

Sepsis is not merely an infection

THE CULPRIT HERE IS OVER REACTION OF OUR DEFENCE MECHANISM – NOT THE INVADER ALONE.

Dysregulated host response leads to..

Immune system Vs. mortality

How to suspect sepsis?

Suspect sepsis…

Altered mental status

Edema or increased fluid balance

Hyperglycemia (absent diabetes)Hypoglyemia

Increased CRP or procalcitonin

Hypotension

Increased SvO2

CI > 3.5 L/min/m2

Arterial hypoxemia (PaO2/FiO2 < 300)

Acute oliguria (> 2 hours)

Increased serum Cr (> 0.5 mg/dL)

Coagulopathy (INR > 1.5)

Ileus (absent bowel sounds)

Thrombocytopenia (< 100,000/uL)

Hyperbilirubinemia (> 40 mg/dL or 70 mmol/L)

Hyperlactatemia (> 1 mmol/L)

Decreased capillary refill or mottling

Levy MM, et al. Crit Care Med. 2003.

How to recognize organ dysfunction?

Change in international guideline

Sepsis 2 Sepsis = SIRS + Infection Infection sepsis severe

sepsis septic shock MODS

Sepsis 3 Sepsis= infection + >2 SOFA

score from baseline NO Severe sepsis

SIRS to SOFA

Organ failure in sepsis

Vincent, J.-L., Sakr, Y., Sprung, C. L., Ranieri, V. M., Reinhart, K., Gerlach, H., Moreno, R., et al. (2006). Sepsis in European intensive care units: results of the SOAP study. Critical Care Medicine, 34(2), 344–353.

P/FPlateletsBiliBPGCSCr/UOP

SOFA SCORE VARIABLES

Sequential Organ Failure Assessment (SOFA)

► Previously known as Sepsis-related Organ Failure Assessment because it was initially developed in 1994 to describe the degree of organ dysfunction associated with sepsis in a mixed, medical-surgical ICU patients.

► Nowadays, it has since been validated to describe the degree of organ dysfunction in various ICU patient groups with organ dysfunctions not due to sepsis.

► The SOFA score involves six organ systems (respiratory, cardiovascular, renal, hepatic, central nervous, coagulation), and the function of each is scored from 0 (normal function) to 4 (most abnormal), giving a possible score of 0 to 24.


► Mortality rate increases as number of organs with dysfunction increases.

► Unlike other scores, the worst value on each day is recorded. ► A key difference is in the cardiovascular component; instead of the

composite variable, the SOFA score uses a treatment-related variable (dose of vasopressor agents).


► Maximal (highest total) SOFA score: is the sum of highest scores per individual during the entire ICU stay. A score of >15 predicted mortality of 90%.

► Mean SOFA score (ΔSOFA): is the average of all total SOFA scores in the entire ICU stay. ΔSOFA for 1st 10 days is significantly higher in non-survivors.

► Delta SOFA score: maximum SOFA – admission SOFA

Crit Care Med 1998;26:1793-1800

Sequential Organ Failure Assessment

qSOFA for Non ICU patients with Infection – early recognition of severity

SEPTIC SHOCK

Septic shock is a subset of sepsis in which profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone

CLINICAL CRITERIA FOR SEPTIC SHOCK 2016

DESPITE ADEQUATE FLUID RESUSCITATION

VASOPRESSOR NEEDED TO MAINTAIN MAP >_65mm Of Hg AND

LACTATE >2 MMOL/LIT

Basal lactate production

Muscle

Brain RBC WBC Platel

etsRenal medu

lla

Gut muco

saSkin

0.13 mmol/kg/hr

0.14 mmol/kg/hr

0.18 mmol/kg/hr

0.11 mmol/kg/hr0.11

mmol/kg/hr

Total = 1290 mmol / 24 hours for 70 kg

Hyperlactataemia (> 2mmol/L)

How is lactate produced?

If pyruvate production > oxidation in CAC then lactate formation increases

PDH

Hypoxia blocks oxidative phosphorylation prevents NADH re-oxidation to NAD increases the NADH/NAD ratio increases the lactate/pyruvate ratio Normal ratio around 10:1

Cardiogenic shock

L/P ratio 40:1Consistent with hypoxia

Resuscitated septic shock

L/P ratio 14:1Not consistent with hypoxia

When lactate hypoperfusion

Cardiogenic shockHemorrhagic shockSeptic shock if

Catecholamine resistant + depressed Cardiac Index

Unresuscitated (see Rivers)

Prognostic value Source doesn’t matter High lactate still a marker of severe

physiological stress and risk of death

High lactate often not hypoxia related but represents metabolic changes of severe stress

Management of SEPSIS FLUIDS ANTIBIOTICS SOURCE IDENTIFICATION AND CONTROL VASOACTIVE DRUGS TO MAINTAIN MAP EARLY ORGAN SUPPORT LUNG PROTECTIVE VENTILATION AND MANY MORE…

BUT THE MOST IMPORTANT IS A SYSTEMATIC APPROACH

System-based Approaches to sepsis

Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368–1377.


Early-Goal Directed TherapyINCLUSION = SEPSIS AND [BP < 90 after fluid OR Lactate > 4]

CVP 8-12 Fluids CVP 8-12

MAP > 65 Vasopressors MAP > 65

TransfusionsDobutamine ScvO2 > 70%

49% mortality 33% mortality


Control Intervention EGDT



Used to promote:1. CVP > 8 as an initial target2. Use of Svo2 monitoring and use of blood/dobutamine

A Multidisciplinary Community Hospital Program for Early and Rapid Resuscitation of Shock in Non-trauma Patients

Sebat, F., Johnson, D., Musthafa, A. A., Watnik, M., Moore, S., Henry, K., & Saari, M. (2005). A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest, 127(5), 1729–1743.

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Control EGDTRelative Risk

(95% Confidence Interval)

P

In-Hospital 46.5 30.5 0.58 (0.38-0.87) 0.009

28-day Mortality 49.2 33.3 0.58 (0.39 – 0.87) 0.01

60-day Mortality 56.9 44.3 0.67 (0.46-0.96) 0.03

Rivers E. N Engl J Med. 2001;345: 1368-1377.Slide 39

Copyright 2014 SCCM/ESICM

Surviving Sepsis Campaign Suggests bundled initiative for hospitals to reduce sepsis

related mortality.

00.10.20.30.40.50.60.70.80.9

1

Resuscitation Bundle Management Bundle

CompliantNon-Compliant

TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION*: 1. Measure lactate level

2. Obtain blood cultures prior to administration of antibiotics

3. Administer broad spectrum antibiotics4. Administer 30ml/kg crystalloid for hypotension or lactate

≥4mmol/L * “Time of presentation” is defined as the time of triage in the emergency department or, if presenting from another care venue, from the earliest chart annotation consistent with all elements of severe sepsis or septic shock ascertained through chart review.

TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION: 5. Apply vasopressors (for hypotension that does

not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg

6. In the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, re-assess volume status and tissue perfusion and document findings according to Table 1

7. Re-measure lactate if initial lactate elevated

DOCUMENT REASSESSMENT OF VOLUME STATUS AND TISSUE PERFUSION WITH

EITHER • Repeat focused exam (after initial fluid resuscitation) by licensed independent practitioner including vital signs, cardiopulmonary, capillary refill, pulse, and skin findings.

OR TWO OF THE FOLLOWING: • Measure CVP • Measure ScvO2 • Bedside cardiovascular ultrasound • Dynamic assessment of fluid responsiveness with passive leg

raise or fluid challenge Of note, Central Line no harm no gain. Needed for vasoactive

drug therapy. Bedside sonologic assessment of Volume status is prioritized.

fluid in septic shock, How much ?

IVF recommendation Initial fluid challenge ≥ 1000 mL of crystalloids or

minimum of 30 mL/kg of crystalloids in the 1st 4-6 hours (Strong recommendation; Grade 1C).

Crystalloids is the initial fluid for resuscitation (Strong recommendation; Grade 1A).

Adding albumin to the initial fluid resuscitation (Weak recommendation; Grade 2B).

Against hydroxyethyl starches (hetastarches) with MW >200 dalton (Strong recommendation; Grade 1B).

Timing of Antibiotic Administration

Septic Shock: Timing of Antibiotics

Kumar Crit Care Med 2006

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.40

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% Survival% Total receiving antibiotics

0 - .5 .5 – 1.01 - 2 2 - 3 3-4 4 - 5 5 - 6 6 - 9 9 - 1

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424 - 3

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Percent

Time, hrs

14 ICUs; n = 2,731

Only 50% of patients in Septic Shock received antibiotics w/in 6 hrs.

G. Fluid Therapy of Severe Sepsis

H. Vasopressors

I. Inotropic Therapy

J. Corticosteroids

2. Hemodynamic Support and Adjunctive Therapy

Adrenergic Agents

Isoproterenol

Dobutamine

Dopamine

Epinephrine

Norepinephrine

Phenylephrine

Beta

Alpha

Which Inotropes to use? Norepinephrine as the first choice

( Grade 1B) Adding or substituting epinephrine when an additional

drug is needed (Strong recommendation; Grade 1B).

Vasopressin 0.03 units/min may be added (Weak recommendation; Grade 2A)

Dopamine only in highly selected patients at very low risk of arrhythmias or low heart rate (Weak recommendation; Grade 2C).

Dobutamine infusion be started or added with low cardiac output) or ongoing signs of hypoperfusion, even after adequate intravascular volume (Strong recommendation; Grade 1C)

Inotropic Therapy• We recommend that a trial of dobutamine infusion up to 20 μg/kg/min be administered

or added to vasopressor (if in use) in the presence of:• myocardial dysfunction as suggested by elevated cardiac filling pressures and low

cardiac output, or• ongoing signs of hypoperfusion, despite achieving adequate intravascular volume

and adequate mean arterial pressure. (Grade 1C)

• We recommend against the use of a strategy to increase cardiac index to predetermined supranormal levels. (Grade 1B)

Slide 53Copyright 2014 SCCM/ESICM

Diagnosis of Infection Appropriate cultures before antimicrobial therapy as soon as possible (<45

minutes) (Grade 1C).

At least two sets of blood cultures (both aerobic and anaerobic bottles) before antimicrobial therapy, with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hours) inserted. Blood cultures can be drawn at the same time if from a different anatomic site (Grade 1C).


Diagnosis Cultures of other sites (preferably quantitative where

appropriate), such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection, should also be obtained before antimicrobial therapy if doing so does not cause significant delay in antibiotic administration (Grade 1C).

We suggest the use of the 1,3 β-D-glucan assay (Grade 2B), mannan and anti-mannan antibody assays (Grade 2C) when invasive candidiasis is in the differential diagnosis of infection.


Diagnosis

Imaging studies be performed promptly in attempts to confirm a potential source of obscure infection. and aggressive monitoring if the decision is made to transport for a CT-guided needle aspiration) .

Bedside studies, such as ultrasound, may avoid patient transport (Ungraded).


Antimicrobial Therapy The administration of effective intravenous

antimicrobials as soon as possible , but never beyond the first hour of recognition of SEPSIS

Initial empiric anti-infective therapy include one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into the tissues presumed to be the source of sepsis (Grade 1B).

The antimicrobial regimen should be reassessed daily for potential de-escalation to prevent the development of resistance, to reduce toxicity, and to reduce costs (Grade 1B).


Antibiotics

• Abx within 1 hr hypotension: 79.9% survival• Survival decreased 7.6% with each hour of

delay• Mortality increased by 2nd hour post hypotension • Time to initiation of Antibiotics was the single strongest

predictor of outcome

Antimicrobial Therapy …

use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who appeared septic, but have no subsequent evidence of infection

Empiric therapy should attempt to provide antimicrobial activity against the most likely pathogens based upon each patient’s presenting illness and local patterns of infection.

We suggest combination empiric therapy for neutropenic patients with severe sepsis (Grade 2B) and for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp.

Antimicrobial Therapy …

Duration of therapy typically be 7 to 10 days if clinically indicated;

longer courses may be appropriate in patients who have a slow clinical response, Undrainable foci of infection, Bacteremia with Staphylococcus aureus, some fungal and viral Infections, or Immunologic deficiencies, including neutropenia

Source Control

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) (Ungraded).

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 (Ungraded).

Corticosteroids Only when Blood Pessure is not maintained with adquate flid

resuscitation and vasoacive

Intravenous hydrocortisone alone at a dose of 200 mg per day. Continuous Infusion preferred over bolus doses.

Taper steroid when vasopressors are no longer required


Blood product Administration

Transfuse PRBC only when Hb%v<7.0 g/dL to target a hemoglobin concentration of 7.0 to 9.0 g/dL in adults (Grade 1B).

Exceptions are myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic coronary artery disease.

NO Erythropoetin in sepsis No FFP to correct lab abnormality in absence of Bleeding or planned

invasive procedure. Platelet transfusion – <10,000 in absence of bleeding <20000 if bleeding risk high <50,000 if planned procedure, active bleeding or surgery

Glucose Control

• We recommend protocolized approach to blood glucose management, commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL.

• This protocolized approach should target upper blood glucose <180 mg/dL rather than <110 mg/dL (Grade 1A).

• Treatment should avoid hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels Slide 64


Glucose control…

Glucometer measured capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values

Capillary point-of-care testing found to be inaccurate with frequent false glucose elevations over range of glucose levels, but especially in hypoglycemic and hyperglycemic glucose ranges and in hypotensive patients or patients receiving catecholamines..

Bicarbonate Therapy

• No to sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (Grade 2B), in absence of Renal acidosis.


Nutrition

• We suggest administering oral or enteral feedings, as tolerated, rather than complete fasting or provision of only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock (Grade 2C).

• We suggest avoiding mandatory full caloric feeding in the first week, but rather suggest low-dose feeding (e.g., up to 500 kcal per day), advancing only as tolerated


Marik and Zaloga. Crit Care Med. 2001;29:2264–2270 Heyland et al. JPEN J Parenter Enteral Nutr. 2003;27:355-373 Doig et al. Intensive Care Med. 2009;35:2018–2027

• Enteral nurtrition combined with IV Glucose supplementation is preferred than Total parenteral Nutrition

• No evidence for the use of Arginine, Glutamine and Omega 3 fatty acid therapy during acute illness with sepsis

Nutrition…

Renal Replacement Therapy• Continuous renal replacement therapies and intermittent

hemodialysis are equivalent in patients with sepsis and acute renal failure because they achieve similar short-term survival rates (Grade 2B).

• We suggest the use of continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (Grade 2D).


Prophylaxis for VTE

We recommend that patients with severe sepsis receive daily pharmacoprophylaxis against VTE (Grade 1B).

We recommend that septic patients who have a contraindication to heparin not receive pharmacoprophylaxis (Grade 1B).

Rather, we suggest they receive mechanical prophylactic treatment, such as graduated compression stockings or intermittent compression devices, unless contraindicated (Grade 2C).

When the risk decreases, we suggest starting pharmacoprophylaxis (Grade 2C).

Slide 70


Stress Ulcer Prophylaxis

• We recommend that stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with sepsis/septic shock who have bleeding risk factors (Grade 1B).

• We suggest that patients without risk factors should not receive prophylaxis (Grade 2B).


Setting Goals of Care We recommend that goals of care and prognosis be

discussed with patients and families (Grade 1B).

Goals of care be incorporated into treatment and end-of-life care planning, utilizing palliative care principles where appropriate

Goals of care be addressed as early as feasible, but no later than within 72 hours of ICU admission


Take Home message

Take home message… Identify sepsis early More and faster fluid Send cultures early Antibiotic Fast <1 hr, consider early antifungals,

use biomarkers to deescalate or stop Earlier Inotropes, Use norepineprine Chase Lactic acid clearance Sonologic volume assessment is better than CVP Wet first, dry later Higher PEEP

THE END

sepsis 2016

Healthcare