Early goal-directed therapy
Early goal-directed therapy was introduced by Emanuel P. Rivers in The New England Journal of Medicine in 2001 and is a technique used in critical care medicine involving intensive monitoring and aggressive management of perioperative hemodynamics in patients with a high risk of morbidity and mortality. In cardiac surgery, goal directed therapy (GDT) has proved effective when commenced after surgery. The combination of GDT and Point-of-Care Testing has demonstrated a marked decrease in mortality for patients undergoing congenital heart surgery. Furthermore, a reduction in morbidity and mortality has been associated with GDT techniques when used in conjunction with an electronic medical record.
Early goal-directed therapy is a more specific form of therapy used for the treatment of severe sepsis and septic shock. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with an increased oxygen demand before surgery.
Three trials published in 2014/2015 have shown that early goal directed therapy should be abandoned (see challenges against).
In the event of hypotension and/or lactate greater than 4 mmol/L, initial management includes a minimum fluid challenge of 30 ml/kg of crystalloid solution. Crystalloid solutions are recommended over colloid solutions given the cost and lack in difference of mortality benefit. Albumin may be considered if large amounts of crystalloid solution is needed.
Indications of a positive response to fluid resuscitation may include:
If hypotension persists despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dl), goals in the first 6 hours of resuscitation include:
- Achieve CVP of 8-12 mmHg. Mechanical ventilation, increased abdominal pressure, and preexisting impaired ventricular compliance may require higher CVP targets of 12-15 mmHg
- Achieve superior vena oxygen saturation (ScvO2) of > 70% OR mixed venous oxygen saturation (SvO2) of > 65%. If initial fluid resuscitation fails to achieve adequate oxygen saturation additional options include dobutamine infusion (maximum 20 µg/kg/min) or transfusion of packed red blood cells to a hematocrit ≥ 30%. If a ScvO2 is unavailable, lactate normalization may be used as a surrogate marker. A reduction in lactate by ≥ 10% is noninferior to achieving a ScvO2 of ≥ 70% 
- Achieve mean arterial pressure (MAP) ≥ 65mmHg The presence of atherosclerosis or pre-existing uncontrolled hypertension may necessitate a higher MAP target.
- Achieve urine output ≥ 0.5 mL/kg/h
Successful targeting the above goals in the first 6-hour period results in a 15.9% absolute reduction in 28-day mortality rate.
In October 2014, results of the ARISE trial were published in the New England Journal of Medicine which demonstrated that use of early goal-directed therapy for patients presenting to the emergency department with early septic shock did not reduce all-cause mortality at 90 days. 
In March, 2015, another study in the New England Journal of Medicine suggested that early goal-directed therapy did not improve mortality or outcomes. It demonstrated no significant differences in any other secondary outcomes, including rates of serious adverse events, and health-related quality of life. On average, EGDT increased costs and the likelihood that it was cost-effective was less than 20%.
In 2014 the ProCESS study was published. Process enrolled 1,341 patients, of whom 439 were randomly assigned to protocol-based EGDT (Rivers EGDT), 446 to protocol-based standard therapy, and 456 to usual care. There was no significant difference in 90-day and 1 year mortality between groups. However, in the sickest sub-group of patients (those with a baseline lactate >5.3 mmol/L) the mortality was significantly higher in the EGDT group as compared to usual care (38.2 vs. 26.4; p = 0.05).
- Gordon, AC; Russell, JA (2005). "Goal directed therapy: How long can we wait?". Critical Care (Commentary). 9 (6): 647–8. doi:10.1186/cc3951. PMC . PMID 16356258.
- Rossi, AF; Khan, DM; Hannan, R; Bolivar, J; et al. (January 2005). "Goal-directed medical therapy and point-of-care testing improve outcomes after congenital heart surgery". Intensive Care Medicine. 31 (1): 98–104. doi:10.1007/s00134-004-2504-1. PMID 15650863.
- Rossi, AF; Khan, D (June 2004). "Point of care testing: Improving pediatric outcomes". Clinical Biochemistry. 37 (6): 456–61. doi:10.1016/j.clinbiochem.2004.04.004. PMID 15183294.
- Rivers, E; Nguyen, B; Havstad, S; Ressler, J; et al. (November 2001). "Early goal-directed therapy in the treatment of severe sepsis and septic shock". The New England Journal of Medicine. 345 (19): 1368–77. doi:10.1056/NEJMoa010307. PMID 11794169.
- Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup; Dellinger, R.P.; Levy, M.M.; Rhodes, A.; et al. (2013). "Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012" (PDF). Critical Care Medicine. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. PMID 23353941 – via Surviving Sepsis Campaign.
- Emergency Medicine Shock Research Network (EMShockNet), Investigators; Jones, AE; Shapiro, NI; Trzeciak, S; et al. (February 24, 2010). "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial". JAMA. 303 (8): 739–46. doi:10.1001/jama.2010.158. PMC . PMID 20179283.