Volume Kinetics of Fluid Resuscitation in Early Sepsis

Inclusion Criteria:

A diagnosis of sepsis, as defined by the Sepsis-3 criteria and exhibiting sepsis-induced hypoperfusion prior to the administration of adequate volume resuscitation:

• hypotension requiring norepinephrine to maintain a mean arterial blood pressure (MAP) either predefined by the clinician or at 65 mm Hg or higher and/or

• a serum lactate level >2 mmol/L (18mg/dL) and/or

• acute oliguria defined as urine output <0.5mL/kg/hr and/or

• mottled skin and/or

• capillary refill time > 3 seconds.

Exclusion Criteria:

• Administration of at least 1 L of IV fluid in the last 6 hours prior to screening.All crystalloids, colloids and blood products that the patient has received arecounted.

• Known pregnancy.

• Competing causes of lactic acidosis including: seizures within 3 hours ofenrollment, use of linezolid or metformin or anti-retrovirals at the time ofenrollment, carbon monoxide or cyanide poisoning, highly suspected or known ischemicbowel, and known mitochondrial disorders.

• End-stage renal disease that requires chronic dialysis.

• Concurrent haemorrhagic or obstructive shock.

• Increased risk of fluid intolerance:

• Echocardiographic evidence of moderate or severe left ventricular systolicdysfunction.

• Echocardiographic evidence of moderate or severe right ventricular systolicdysfunction.

• Hypoxemia index < 200 mmHg or sonographic evidence of bilateral B or C profile.

• Abdominal compartment syndrome.

• Post-cardiac arrest.