Sepsis and Early Goal Directed Therapy : Approach in ED Faez Baherin MBBS (Jordan) ED HTAN Kuala Pilah
Outlines Introduction Definition Early Goal Directed Therapy (EGDT) and the theory behind it Component of EGDT Conclusion
Introduction Sepsis continues to be a major cause of mortality and morbidity throughout the world. The annual incidence of severe sepsis was approximately 3.0 cases per 1,000 of the population. In the United States alone, the incidence of severe sepsis will see an annual increase of 1.5% which may be attributable to an increasing ageing population. (1)1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology ofsevere sepsis in the United States: analysis of incidence, outcome, and associated costs of care. CritCare Med 2001;29:1303-10.
Introduction – cont’ Malaysia is not immune from the global burden of sepsis. In 2008, severe sepsis was the second leading cause of death in the Malaysian Ministry of Health hospitals. (2) To date, there have been no local studies on the implementation or challenges in applying EGDT in emergency departments (ED) until 2009 by UKMMC with a conclusion that EGDT can be implemented in ED Malaysia with current resources and expertise.2. Health Facts 2008. Health Informatics Centre. Planning and Development Division. Ministry ofHealth Malaysia [Online]. 2009 May 1
Definition by American College of Chest Physicians/Society of Critical Care Medicine3. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, Levy MM etal., Crit. Care Med. 2003, 31(4): 1250-1256)
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. (4)4. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal directed therapy inthe treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
What’s the theory behind Early Goal Directed Therapy?In sepsis, circulatory insufficiency (intravascular volumedepletion, peripheral vasodilatation and myocardialdepression), combined with an increased metabolic statecould lead to an imbalance between oxygen demandand delivery, resulting in anaerobic metabolism and thepotential development of multiple organ dysfunctionsyndrome.
Theory behind EGDT – cont’ Damage or impairment of the microvascular network is increasingly being recognised as having a key role in the development of organ dysfunction in patients with sepsis via impaired tissue oxygen transport. (5) Thus, although there may be adequate blood flow from the heart, there is physiological shunting at the level of microcirculation as a result of impeded flow, so the supply will be unable to meet oxygen requirements. It has been suggested that the benefits of EGDT may relate to beneficial effects on the microcirculation with adequate volume resuscitation, vasopressors to maintain MAP and blood transfusion, inotropes and vasodilators to ensure adequate global oxygen delivery.5. Bateman R M, Walley K R. Microvascular resuscitation as a therapeutic goal in severe sepsis. CritCare 2005. 9(Suppl 4)S27–S32.S32
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 that is central to the development of multiorgan dysfunction, by increasing the cardiac output and improving oxygen delivery to the tissues (6) Continued fluid challenges of 500-1000 ml of crystalloids or 300-500 ml of colloids over 30minutes and repeated as appropriate.Haupt M T, Gilbert E M, Carlson R W. Fluid loading increases oxygen consumption in septicpatients with lactic acidosis. Am Rev Respir Dis 1985. 131912–916.916
Fluid resuscitation – cont’ ultimate key to satisfactory fluid resuscitation ? - clinical, urine output, CVP, peripheral perfusion Crystalloid vs colloids ? - In many recent studies, there’s no apparent difference between crystalloids and colloid - no association with hospital/ICU mortality with type of fluid administered during initial resuscitation (7)7. McIntyre LA et al 2007 Canada
Fluid resuscitation – cont’ Bottomline : Both crystalloids and colloids can be used in the initial resuscitation of patients with severe sepsis. The most current Surviving Sepsis Campaign guidelines recommend giving fluid challenges of 1000ml of crystalloids or 300 – 500ml of colloids over 30mins to achieve a target CVP of 8mmH2o or more .(8)(9)8. Dellinger RP et al. Surviving sepsis campaign: International guidelines for management of severesepsis and septic shock 2008. Critical Care Medicine 2008; 36(1); 296-3279. Powell-Tuck J et al. British consensus guidelines on intravenous fluid therapy for adult surgical patients.GIFTASUP 2008
MAP and vasopressors Even after adequate fluid resuscitation many patients remain hypotensive or have inadequate tissue perfusion as a result of microvascular changes, myocardial depression, vasodilatation and maldistribution of cardiac output (10) MAP must be maintained at certain level even after adequate fluid resuscitation. Choice of dopamine vs noradrenaline10. Beale R J, Hollenberg S M, Vincent J ‐ L. et al Vasopressor and inotropic support inseptic shock: an evidence‐based review. Crit Care Med 2004. 32(Suppl)S455–S465.S465.
Dopamine Vs Noradrenaline Dopamine has been commonly used as a first- line therapy for shock at many hospitals for years Dopamine has dose related effect- dopaminergic, beta 1, alpha 1. Noradrenaline has effects on alpha 1, weaker beta 1 effect which is nullified by reflex bradycardia in response to blood pressure hence the unchanged overall heart rate
Dopamine vs Noradrenaline11. Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011, 4, 10, 571-574
Dopamine Vs Noradrenaline Bottomline 1. There is no significant mortality difference at 28 days in patients with septic shock treated with dopamine or noradrenaline. 2. Dopamine is associated with more arrhythmic events. 3. Noradrenaline might be preferred over dopamine as the first line vasopressor to avoid cardiovascular adverse events. 4. The recent SOAP II study challenges the guideline recommendation that dopamine should be one of two first line vasopressor agents in septic shock.11. Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011, 4, 10, 571-574
ScvO2 and blood transfusion Scvo2 – central venous oxygen saturation – reflects tissue perfusion
ScvO2 and blood transfusion In the instance of the central venous oxygen saturation (ScvO2) was still below 70% after adequate fluid and vasopressors, packed red cell transfusion will be given if the hematocrit <30%.
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 hrs was associated with an average decrease in survival of 7.6%.(12) A longer duration to antimicrobial therapy was also associated an increase in incidence of AKI AND AKI was associated with significantly higher odds of death Surviving Sepsis 2008 : “Begin IV antibiotics as early as possible and always within the first hour of recognizing severe sepsis and septic shock”12 . Kumar et al, Intens Care Med 2009
Conclusion Sepsis, severe sepsis and septic shock are amongst the leading cause of morbidity and mortality in Malaysia Early recognition of sepsis and activation of EGDT is crucial to improve the outcome Airway maintenance, early administration of 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.
Reference 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 Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011 Dellinger RP et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock 2008. Critical Care Medicine 2008 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, Levy MM et al., Crit. Care Med. 2003 Sarawak Medical Emergency Handbook