Sepsis

Wat is sepsis?

• Sepsis is een heftige immuunrespons op bacterien / toxinen in de bloedbaan.

• Gekenmerkt door een systemische inflammatoire respons, SIRS.

• Bij infecties in het bloed, urine, longen, hart, etc.

• SIRS ook bij operatie en trauma

• Continuum van SIRS – septische shock

Wat gebeurt er bij sepsis?

• Sepsis bij circa 2% van de SEH patiënten

• Mortaliteit:

– 33% bij ernstige sepsis

– 59% bij septische shock

Systemic Inflammatory Response Syndrome (SIRS)

Twee of meer criteria:

• Temperatuur >38˚C of <36˚C

• Hartslag >90/min

• Ademhalingsfrequentie > 20/min

• Leuko’s > 12 of < 4

Stadia

Stadia sepsis

Sepsis≥ 2 SIRS-verschijnselen met verdenking op of aanwijzing voor infectie.

Ernstige sepsissepsis met orgaanfalen zoals verwardheid, acute oligurie < 0,5 ml/kg, ARDS

Septische shock

sepsis met hypotensie ondanks adequate volumeresuscitatie (SBP < 90 mmHg of daling > 40 mmHg van baseline)

Types of sepsis

• Sepsis: – Two or more SIRS criteria, known or suspected infection

• Severe sepsis:– Sepsis as above– Organ dysfunction

-Hypotension: systolic <90 mmHg, MAP <65 mmHg, or a decrease in 40 mmHg from usual reading

-Lactate > 4mmol/L-Altered mental status-Hyperglycemia in the absence of diabetes-Hypoxemia, O2 < 93%-UOP <0.5 ml/kg/hr and/or raised urea or creatinine -Coagulopathy, INR >1.5

Types of sepsis

• Septic shock:– Severe sepsis

– Hypotension or raised lactate that does not improve with adequate fluid resuscitation

• Multiple organ dysfunction:– Perfusion is compromised, ischemia and hypoxia of organs

– Cardiovascular-Heart Failure, Neurological- change in LOC, Pulmonary-ARDS, Renal- Acute Renal Failure, Metabolic-acidosis, Hepatic- Liver Failure, Hematologic-Disseminated Intravascular Clotting

Wat gebeurt er bij (ernstige) sepsis?

• Lage perifere weerstand door lekkage van capillairen en vasodilatatie

• Initieel hoge cardiac output tot een kantelpunt

• Inadequate weefselperfusie en weefselhypoxie

• Gestoord zuurstofgebruik

• Anaerobe verbranding en lactaatacidose

• Oligurie

• Verwardheid

• Diffuus intravasale stolling

Waarom orgaanfalen?

Hoe meten we (ernstige) sepsis?

• Verhoogde infectieparameters

• Verhoogd lactaatgehalte

• Verlaagde veneuze zuurstofsaturatie

• Verlaagde bloeddruk

• Verlaagde urineproductie

• Diverse tekenen van orgaanfalen

Hoe ernstig is sepsis?

†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001;29(7):1303-1310.

AIDS* Colon BreastCancer§

CHF† Severe Sepsis‡

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Incidence of Severe Sepsis Mortality of Severe Sepsis

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Surviving Sepsis Campaign

A global program to:

• Reduce mortality rates•Improve standards of care•Secure adequate funding

6 Hour Resuscitation Bundle

• Early Identification

• Early Antibiotics and Cultures

• Early Goal Directed Therapy

Early Goal Directed Therapy• Early goal-directed therapy (EGDT) is a

haemodynamic optimization protocol that is proven to reduce mortality in cases of severe sepsis/septic shock.

• Early goal-directed therapy (EGDT) was proposed by Rivers et al in 2001. This protocol advocates aggressive treatment commencing in the emergency department to achieve certain haemodynamic goals.

• This achieved a 16% absolute risk reduction for in-hospital mortality.

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.

In sepsis, circulatory insufficiency (intravascular volume depletion, peripheral vasodilatation and myocardial depression), combined with an increased metabolic state could lead to an imbalance between oxygen demand and delivery, resulting in anaerobic metabolism and the potential development of multiple organ dysfunction syndrome.

What’s the theory behind Early Goal Directed Therapy?

Initial Resuscitation

Goals during first 6 hours:

• Central venous pressure: 8–12 mm Hg

• Mean arterial pressure 65 mm Hg (≈95/50)

• Urine output 0.5 mL kg-1/hr-1 (≈40ml)

• Central venous (superior vena cava) [SvO2] saturation 70%

Grade B

Components of EGDT

• Fluid resuscitation and CVP monitoring

• MAP maintenance and vasopressors

• ScvO2 monitoring and blood transfusion

+ Intravenous antibiotics administration early

Fluid resuscitation and CVP Monitoring

• Patients are usually fluid depleted – absolute vs relative

• Fluid resuscitation can help to reduce the global tissue hypoxia, by increasing the cardiac output and improving oxygen delivery to the tissues

• Continued fluid challenges of 500 ml

ScvO2

• Scvo2 – central venous oxygen saturation –reflects tissue perfusion

6 - hour Severe Sepsis/Septic Shock Bundle

• Early Detection:– Obtain serum lactate level.

• Early Blood Cx/Antibiotics:– within 3 hours of

presentation.

• Early EGDT: • Hypotension (SBP < 90, MAP

< 65) or lactate > 4 mmol/L:– initial fluid bolus 20-40 ml of

crystalloid (or colloid equivalent) per kg of body weight.

• Vasopressors:– Hypotension not

responding to fluid– Titrate to MAP > 65

mmHg.

• Septic shock or lactate > 4 mmol/L:– CVP and ScvO2 measured.– CVP maintained >8 mmHg.– MAP maintain > 65 mmHg.

• ScvO2<70%with CVP > 8 mmHg, MAP > 65 mmHg:– PRBCs if hematocrit < 30%. – Inotropes.

Sepsis Resuscitation Bundle

1. Measure serum lactate2. Blood cultures obtained prior to administration of antibiotic3. From time of presentation, broad spectrum antibiotics must be

administered within 3hrs of ED admission, or within 1hr of non-ED admission

4. In the event that hypotension and/or serum lactate >4mmola) Deliver initial minimum of 20ml/kg of crystalloid or colloid equivalent.b) Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain a MAP of ≥65mmHg.

5. Consider insertion of urinary catheter (measure UOP)6. If hypotension persists and serum lactate >4mmol despite fluid

resuscitation achievea) CVP ≥8mmHg andb) (ScvO2) of ≥70%.

Sepsis in the Emergency Department

The Importance of Early Goal-DirectedTherapy for Sepsis Induced Hypoperfusion

Adapted from Table 3, page 1374, with permission from Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med2001; 345:1368-1377

In-hospital mortality

(all patients)

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30

40

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60 Standard therapyEGDT

28-day mortality

60-day mortality

NNT to prevent 1 event (death) = 6-8

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Antibiotics Administration

– Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%

– Each hour of delay in antimicrobial administration over the ensuing 6 hrswas associated with an average decrease in survival of 7.6%.(12)

– Surviving Sepsis 2008 :

“Begin IV antibiotics as early as possible and always within the first hour of recognizing severe sepsis and septic shock”

Kumar et al, Intens Care Med 2009

Conclusion

• Sepsis, severe sepsis and septic shock are a serious cause of morbidity and mortality

• Early recognition of sepsis and activation of EGDT is crucial to improve the outcome

• Airway maintenance, broad spectrum antibiotics, fluid resuscitation and blood pressure maintenance are the components of EGDT that should be carried out for better survival chance of the patients.