Volume Kinetics of Fluid Resuscitation in Early Sepsis

Adult patients admitted to the intensive care unit (ICU) with sepsis, as defined by the Sepsis-3 criteria, and exhibiting sepsis-induced hypoperfusion prior to receiving adequate volume resuscitation (i.e., 30 ml/kg of crystalloid), are administered Ringer's Lactate at a dose of 30 ml/kg. The initial 20 ml/kg is infused at a constant rate over the first 30 minutes, followed by a 30-minute pause, with an additional 10 ml/kg administered over the subsequent 15 minutes, completing the infusion within 75 minutes.

Up to 180 minutes post-infusion, no other fluids (e.g., gelatin, albumin) are administered except for antibiotics, sedatives, or vasoactive substances as needed. Ideally, only one catecholamine (e.g., norepinephrine) is administered. The volume and quantity of these substances are recorded. Arterial blood samples are collected for blood gas analysis, including hemoglobin levels. Urinary output is measured at 30, 60, and 180 minutes, and any blood loss, other than the 1.5 ml per sample collected, is quantified during hemoglobin monitoring. Additionally, urinary creatinine concentration is determined from urine samples collected at baseline.

The hemodilution data are utilized as input into a three-compartment model with microconstants for fluid redistribution and excretion.

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 are counted.
• Known pregnancy.
• Competing causes of lactic acidosis including: seizures within 3 hours of enrollment, use of linezolid or metformin or anti-retrovirals at the time of enrollment, carbon monoxide or cyanide poisoning, highly suspected or known ischemic bowel, 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 systolic dysfunction.
• Echocardiographic evidence of moderate or severe right ventricular systolic dysfunction.
• Hypoxemia index < 200 mmHg or sonographic evidence of bilateral B or C profile.
• Abdominal compartment syndrome.
• Post-cardiac arrest.