Sandbox Sepsis medical therapy

# Overview
The Surviving Sepsis Campaign was an international effort organized by physicians that developed and promoted widespread adoption of practice improvement programs grounded in evidence-based guidelines. The goal was to improve diagnosis and treatment of sepsis. Included among the guidelines were sepsis screening for high-risk patients; taking bacterial cultures soon after the patient arrived at the hospital; starting patients on broad-spectrum intravenous antibiotic therapy before the results of the cultures are obtained; identifying the source of infection and taking steps to control it (e.g., abscess drainage); administering intravenous fluids to correct a loss or decrease in blood volume; and maintaining glycemic (blood sugar) control. These and similar guidelines have been tested by a number of hospitals and have shown potential for decreasing hospital mortality due to sepsis.

# Medical Therapy
The delay in administering therapy after sepsis has been recognized, is the main problem in the adequate management of septic patients. For every hour delay in the administration of appropriate antibiotic therapy there is an associated 7% rise in mortality. A large international collaboration was established to educate people about sepsis and to improve patient outcomes with sepsis, entitled the "Surviving Sepsis Campaign".

## Early Goal Directed Therapy (EGDT)
Early Goal Directed Therapy (EGDT), developed at Henry Ford Hospital by E. Rivers, MD, is a systematic approach to resuscitation that has been validated in the treatment of severe sepsis and septic shock. It is meant to be started in the Emergency Department. The theory is that one should use a step-wise approach, having the patient meet physiologic goals, to optimize cardiac preload, afterload, and contractility, thus optimizing oxygen delivery to the tissues.
Although initial studies reported benefit from EGDT, the more recent ProCESS and ARISE trials failed to demonstrate any benefit. However, the outcomes in the control groups of these trials were much more favorable than in the earlier trials. The extent of protocol-based care in the 'usual care' of the control groups is not known.
In Early Goal Directed Therapy:
- Fluids are administered until the central venous pressure (CVP), as measured by a central venous catheter, reaches 8-12 cm of water (or 10-15 cm of water in mechanically ventilated patients).
- If the mean arterial pressure is less than 65 mmHg or greater than 90 mmHg, vasopressors or vasodilators are given as needed to reach the goal.
- The central venous saturation (ScvO2), i.e. the oxygen saturation of venous blood as it returns to the heart as measured at the superior vena cava, is optimized. If the ScvO2 is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the ScvO2 is optimized. Elective intubation may be performed to reduce oxygen demand if the ScvO2 remains low despite optimization of hemodynamics.
- Urine output is also monitored, with a goal of 0.5 mL/kg/h. In the original trial, mortality was cut from 46.5% in the control group to 30.5% in the intervention group.  The Surviving Sepsis Campaign guidelines recommends EGDT for the initial resuscitation of the septic patient with a level B strength of evidence.

## GENESIS Project
The protocol per the GENESIS Project is:
- Measure serum lactate
- Obtain blood cultures and administer broad-spectrum antibiotic within 3 hours of emergency department admission
- If hypotensive or serum lactate 4 mmol/L:
Administer 20 mL/kg of crystalloid
If needed, add vasopressors to keep mean arterial pressure >65 mm  Hg
If needed, aim for central venous pressure 8 mm Hg
If needed, aim for central venous oxygen saturation 70%
- Administer 20 mL/kg of crystalloid
- If needed, add vasopressors to keep mean arterial pressure >65 mm  Hg
- If needed, aim for central venous pressure 8 mm Hg
- If needed, aim for central venous oxygen saturation 70%
Standard treatment of infants with suspected sepsis consists of supportive care, maintaining fluid status with intravenous fluids, and the combination of a beta-lactam antibiotic (such as ampicillin) with an aminoglycoside such as gentamicin.

## Transfusion
In septic shock, leukoreduced erythrocyte transfusion is associated with similar clinical outcomes (90 day mortality and ischemic events) among patients who are administered erythrocyte transfusion at a hemoglobin threshold of 7 g/dL compared to those who receive it at a higher threshold of 9 g/dL.