Fluid Resuscitation

Anatomy and Physiology

Body fluids are distributed into intracellular and extracellular compartments. Intracellular compartment contributes to most total body water. Extracellular fluids are within the interstitial, intravascular, and trans-cellular spaces.[2] Predominant electrolytes in body fluids are sodium and potassium, where sodium is the dominant cation in the extracellular fluid and potassium is the dominant cation in the intracellular fluid. Sodium and magnesium are the other minor cations in the intracellular fluids and are electrochemically balanced by phosphate, sulfate, and bicarbonate anions. Calcium and magnesium are the other cations found in minor concentrations in the extracellular fluid, and they are balanced by chloride, bicarbonate, phosphate, and sulfate anions.[2]

Indications

Trauma

Trauma is the number one cause of death in the United States for individuals between 1 and 44 years of age. Among them, hemorrhagic shock is the primary cause of death for 30% to 40% in the first 24 hours following injury. Loss of blood triggers a compensatory hemodynamic response to restore volume. The compensatory mechanisms click in when there is acute blood loss of more than 5% to 10%. Blood losses of greater than 20% will require fluid resuscitation to support the continued delivery of oxygen to vital organs.[3]

Trauma and acute blood loss trigger compensatory mechanisms aimed at restoring volume deficits to maintain adequate perfusion of vital organs. Trans-capillary refill occurs first and involves the shift of fluid from the interstitial space into the intravascular space secondary to increased capillary permeability and decreased plasma colloid osmotic pressure. The resultant effect is the sequestration of about 1 liter of fluid into intravascular spaces. Activation of the renin-angiotensin-aldosterone system occurs next, activated by the reduction in renal perfusion and causing sodium and water retention by the kidneys.

The overall goal is to replace the fluid lost from the interstitial compartment to the intravascular spaces. But one must exercise caution, because an aggressive large volume fluid resuscitation may lead to hypothermia, acidosis, and coagulopathy.[3][4] Typical indications for resuscitation are a systolic blood pressure of less than 80 to 85 mm Hg or one that is rapidly decreasing and/or a decline in mental status without evidence of head trauma.[4]

Two major types of fluids used for resuscitation are colloids which specifically expand the intravascular volume and crystalloids, which briefly expand the intravascular volume and quickly re-distribute into the interstitial compartment. For resuscitation, crystalloids are given as 1- to 2-liter bolus in patients with hemorrhagic shock. However, recent studies using colloids favor permissive hypotension. For example, in patients with penetrating trauma, aggressive fluid resuscitation may exacerbate bleeding, so the emphasis is on administering small boluses of fluid (250mL) allowing a low systolic blood pressure equal to  90 mm Hg or mean blood pressure equal to 50 mm Hg until one achieves sustained hemorrhagic control. This strategy has been shown to improve survival and reduce the amount of fluid replaced.

It is important to remember that it is only safe to allow low blood pressures when there is good clinical evidence of adequate organ perfusion indicated through adequate urine output and mental status.[4] Crystalloids should ideally serve as a bridge to maintain perfusion until blood products are available in hemorrhagic shock. Hence, one should consider limited 500-ml bolus doses in patients without or impending shock until blood products become available.[5]

Sepsis

Sepsis is a leading cause of morbidity and mortality in critically ill patients with mortality ranging between 20% to 45%. Uncontrolled inflammation, tissue hypoperfusion, microvascular and micro-cellular level abnormalities, and dysfunction are critical determinants in the progression toward multiple organ failure, which predict poor outcomes. Septic shock is defined as refractory hypotension that results from a systemic inflammatory response syndrome (SIRS) caused by or suspected to be from an infection.[6]

The key characteristic of septic shock is systemic vasodilation which results in hypovolemia, decreased tissue perfusion and decreased oxygen delivery. The main aim of fluid resuscitation is to restore hemodynamics to optimize tissue perfusion and ultimately the tissue oxygen delivery.[6]

For resuscitation, one should give crystalloids at a dose of 30 mL/kg of ideal body weight as early as possible, typically within the first 3 hours. Central venous pressure (CVP), mean arterial pressure (MAP), and central venous oxygen saturation (ScvO2) can guide fluid resuscitation if shock (mean arterial blood pressure - MAP less than 65 mm Hg or lactate level greater than 4.0 mmol/L) persist. Within the first 6 hours of initial resuscitation, one should aim for a CVP target between 8 to 12 mm Hg in spontaneously breathing patients and CVP between 12 to 15mm Hg in mechanically-ventilated patients; a MAP greater than 65 mm Hg and ScvO2 greater than 70% have been shown to improve mortality. Lactate level should be monitored during resuscitation since increases may reflect a decrease in tissue perfusion.[6]

Contraindications

0.9% saline should be used with caution in patients with subarachnoid hemorrhage or postoperative acute kidney injury (AKI) as these conditions can themselves cause alterations in serum sodium concentration (hypo or hypernatremia).[7][8]

Colloids such as hydroxyethyl starch (HES) should be avoided in septic shock because of their adverse effects on coagulation and renal function. A blinded, randomized, controlled trial of 800 severely septic intensive care unit (ICU) patients in Scandinavia found that 6% HES is associated with an increase in death at 90 days compared to Ringer’s acetate.[7][9][8]

Intravenous albumin is contraindicated in patients with traumatic brain injury.[10]

Complications

Large amounts of intravenous fluids can cause hypervolemia and potentially electrolyte imbalance. In septic shock, overzealous use of intravenous fluids for a prolonged period can cumulatively increase the total body water, especially in patients with compromised renal, cardiac or hepatic function. This excess free water often accumulates in the extravascular lung (pulmonary edema) and subcutaneous tissues (pedal or sacral edema) and poses problems during recovery, for example, failure to wean from the ventilator and muscle weakness, both of which will cause prolongation of hospital stay and increase the associated risk of nosocomial complications. A 0.9% saline causes hyperchloremic acidosis following excess use and is associated with nephrotoxicity.

Clinical Significance

The goal of fluid resuscitation is to maintain homeostasis. This goal requires not only administering enough fluid volume to optimize hemodynamics and perfusion but also to maintain electrolyte balances. Maintenance fluids are given for select indications such as prolonged fasting for planned surgical procedures and conditions limiting oral fluid intake (severe nausea, vomiting, diarrhea). Maintenance fluid volume requirements in children is based on body weight with 100 ml/kg per day for the first 0 to 10 kg, an additional 50 ml/kg per day for the next 10 to 20 kg, and 20 ml/kg/day for weight greater than 20 kg. In adults, maintenance fluid is typically 35 ml/kg per day. One must also consider electrolyte replacement besides maintaining the required fluid volumes. Sodium is required at a concentration of 1 to 2 mEq/kg per day and potassium is replaced at a rate of 0.5 to 1 mEq/kg per day.[2][1]

Enhancing Healthcare Team Outcomes

Additional components for consideration in trauma resuscitation are to minimize the use of crystalloid fluid due to the potential for increasing the inflammatory response. Studies have also shown early use of blood products improve outcomes in trauma patients.[4] The PROPPR (Pragmatic Randomized Optimal Platelet and Plasma Ratios, 2016) study assessed 1:1:1 versus 1:1:2 ratios of plasma to platelets to red blood cells in severely injured patients and found that there were earlier hemorrhage control and decreased deaths secondary to exsanguination in the first 24 hours in the 1:1:1 group.[4] In pediatric patients, fluid resuscitation is indicated in the presence of hemorrhagic shock. An initial bolus of 20 mL/kg of either warmed 0.9% saline or lactated ringers is given. A repeat bolus of 20 mL/kg can be given if there is a transient or no response to initial bolus and then switch to resuscitation with blood products (10 mL/kg). There is no evidence to support permissive hypotension or damage control resuscitation in pediatric patients.[4][2]

Choices of fluid for septic shock resuscitation vary. Crystalloids are the fluids of choice in septic shock resuscitation, but no crystalloid solution is specifically favorable over the other due to a lack of evidence of direct comparisons in septic shock patients.[2][1][7] The Crystalloid versus Hydroxyethyl Starch Trial (CHEST) which was a blinded, randomized, controlled trial of 7000 ICU patients found that 6% HES was not associated with a significant increase in death at 90 days but was associated with an increase in the renal-replacement therapy rate. The Saline versus Albumin Fluid Evaluation (SAFE) Trial in Australia and New Zealand found a correlation between albumin resuscitation and a decrease in the adjusted risk of death at 28 days in septic patients.[8][11]