1.Sepsis and Early Goal DirectedTherapy : Approach in EDFaez Baherin MBBS (Jordan) ED HTAN Kuala Pilah

2. Outlines Introduction Definition Early Goal Directed Therapy (EGDT) and thetheory behind it Component of EGDT Conclusion 3. 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. 4. 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 5. 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) 6. 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. 7. Whats the theory behind Early GoalDirected 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. 8. Theory behind EGDT cont Damage or impairment of the microvascular network isincreasingly being recognised as having a key role in thedevelopment of organ dysfunction in patients with sepsis viaimpaired tissue oxygen transport. (5) Thus, although there may be adequate blood flow from theheart, there is physiological shunting at the level ofmicrocirculation as a result of impeded flow, so the supply willbe unable to meet oxygen requirements. It has been suggested that the benefits of EGDT may relate tobeneficial effects on the microcirculation with adequatevolume resuscitation, vasopressors to maintain MAP andblood transfusion, inotropes and vasodilators to ensureadequate global oxygen delivery.5. Bateman R M, Walley K R. Microvascular resuscitation as a therapeutic goal in severe sepsis. CritCare 2005. 9(Suppl 4)S27S32.S32 9. Components of EGDT Fluid resuscitation and CVP monitoring MAP maintenance and vasopressors ScvO2 monitoring and blood transfusion+ Intravenous antibiotics administration early 10. Fluid resuscitation and CVP Monitoring Patients are usually fluid depleted absolute vsrelative Fluid resuscitation can help to reduce the globaltissue hypoxia that is central to the developmentof multiorgan dysfunction, by increasing thecardiac output and improving oxygen delivery tothe tissues (6) Continued fluid challenges of 500-1000 ml ofcrystalloids or 300-500 ml of colloids over30minutes 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. 131912916.916 11. Fluid resuscitation cont ultimate key to satisfactory fluid resuscitation ?- clinical, urine output, CVP, peripheral perfusion Crystalloid vs colloids ? - In many recent studies, theres 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 12. Fluid resuscitation contBottomline : 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 13. MAP and vasopressors Even after adequate fluid resuscitation manypatients remain hypotensive or have inadequatetissue perfusion as a result of microvascularchanges, myocardial depression, vasodilatationand maldistribution of cardiac output (10) MAP must be maintained at certain level evenafter 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 evidencebased review. Crit Care Med 2004. 32(Suppl)S455S465.S465. 14. 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, weakerbeta 1 effect which is nullified by reflexbradycardia in response to blood pressure hencethe unchanged overall heart rate 15. Dopamine vs Noradrenaline11. Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011, 4, 10, 571-574 16. 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 17. ScvO2 and blood transfusion Scvo2 central venous oxygen saturation reflects tissue perfusion 18. 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