IV fluid resuscitation has long been recognized to be an important treatment for patients with severe sepsis and septic shock. While under-resuscitation is known to increase morbidity and mortality, contemporary data suggests that overly aggressive fluid resuscitation may also be harmful. Currently, following an initial IVF resuscitation of 30 ml/kg, there is no standard of care and a lack of evidence to support a fluid restrictive or more liberal strategy. The investigators seek to determine if a fluid restrictive strategy reduces morbidity and mortality among patients with severe sepsis and septic shock.

Sepsis is one of the most common indications for intensive care unit admission world wide and the third leading cause of death in the United States. While IV fluid administration has been recognized as an important part of sepsis resuscitation for over 15 years, there is growing concern that overly aggressive IV fluid resuscitation may be harmful to patients with severe sepsis and septic shock.

The current standard of care for initial resuscitation is outlined in the 2016 Surviving Sepsis guidelines which recommends a 30mL/kg bolus of IV fluid for septic patients with hypotension (mean arterial pressure <65 mm Hg) or a lactic acid >4mmol/L within the first 3 hours of presentation. This standard is affirmed by the 2015 Centers for Medicare & Medicaid (CMS) SEP-1 guidelines. Afterwards, the guidelines advise the use of vasopressors to maintain a mean arterial pressure (MAP) of >65 mm Hg within the first 6 hours of patient care. Following the initial 30mL/kg bolus, there is no established standard of care for fluid administration; therefore there is significant variation in care between providers and institutions. Currently, there is no human data that indicates that larger volume (>30mL/kg) resuscitation strategy improves blood pressure or end organ perfusion , yet it is not uncommon for patients to receive large volumes of IV fluid (5-10 liters) in the early stages of resuscitation.

When considering how much IV fluids are typically administered to patients with septic shock, examination of the large EGDT RCTs provides a more informed picture. In the original Rivers study patients received approximately 70 mL/kg of IVF in the first 6 hours and additional 125 ml/kg in hours 7 to 72.3 Notably, this large volume resuscitation did not produce increased rates of clinically important heart failure and intubation. In the contemporary EGDT validation trials, patients received 60-70 ml/kg of IVF in the first 6 hours and only 60-70 ml/kg from hours 7 to 72.6,7,8 The contemporary alternative approach being advocated among critical care practitioners is to use vasopressors to maintain a mean arterial pressures above 65 mm Hg following the initial 30 ml/kg bolus, thereby maintaining organ perfusion, while limiting further IV fluid administration.9 Without clear evidence to guide physicians under current usual care the amount of IV fluid administration varies widely between providers and institutions when resuscitating patients with severe sepsis and septic shock.

The investigators hypothesize the use of a fluid restrictive strategy will result in a lower 28-day mortality, ICU length of stay and total number of ventilator days but will not reduce the number of patients who need hemodialysis or require intubation.

The primary outcome of the study is to assess if a restrictive IV fluid resuscitation strategy has a composite benefit of a reduced discharge mortality or Persistent Organ Dysfunction (POD) score compared to a usual care among patients with severe sepsis and septic shock. POD is defined by the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; and persistent respiratory/neuromuscular failure as defined by the ongoing need for mechanical ventilation (not including non-invasive ventilation modalities).

Inclusion Criteria:

1. The patients must be suspected by the treating physician to have sepsis causing their acute illness as exhibited by 2 or more of the following Systemic Inflammatory Response Syndrome (SIRS) criteria was well as a known or suspected infection at the time of screening:

   1. Temperature of > 38 C or < 36 C
   2. Heart rate of > 90/min
   3. Respiratory rate of > 20/min or PaCO2 < 32 mm Hg
   4. White blood cell count > 12000/mm3 or < 4000/mm3 or >10% immature bands.

2. Since approximately 12% of patients ultimately diagnosed with sepsis do not meet SIRS criteria , SIRS negative patients will be eligible for the study if the treating physician makes a clinical diagnosis of severe sepsis or septic shock.

3. Patients must be suspected of having severe sepsis or septic shock defined as refractory hypotension or a lactic acid>4 at the time of enrollment. Refractory hypotension is defined as having a SBP <90 or MAP <65, for 15 minutes, following 1000 mL of IV fluid or a blood pressure maintained by vasopressor administration.

4. Patients must have received less than 60ml/kg of intravenous fluid at time of study enrollment.

Exclusion Criteria:

1. Patients with a PRIMARY diagnosis of acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, active gastrointestinal bleeding, seizure, drug overdose, burn, trauma, requirement for immediate surgery, or undergoing extracorporeal membrane oxygenation.
2. Patients who have a diagnosis of severe sepsis or septic shock and additionally have an active fluid wasting process such as extensive diarrhea, diabetes insipidus, cerebral salt wasting, or an osmotic diuresis.
3. Patients who have a diagnosis of severe sepsis or septic shock who have a concurrent diagnosis of diabetic ketoacidosis, hyperosmolar non-ketotic hyperglycemia, or rhabdomyolysis.
4. Patients who have received >60 ml/kg of IVF resuscitation.
5. Patient who are <18 years old, pregnant, or incarcerated.