Intravenous fluid therapy

Intravenous fluid therapy involves the intravenous administration of crystalloid solutions and, less commonly, colloidal solutions. The type, amount, and infusion rates of fluids are determined based on the indication for fluid therapy and specific patient needs. Crystalloid solutions are used to resuscitate patients who are hypovolemic or dehydrated, correct free water deficits, replace ongoing fluid losses, and meet the fluid requirements of patients who cannot take fluids enterally. The use of colloidal solutions is controversial and should be reserved for special situations (e.g., severe cases of low oncotic pressure). All patients should be closely monitored using a combination of clinical parameters and laboratory tests to determine therapeutic endpoints, and fluid therapy should be appropriately de-escalated for patients in recovery to avoid fluid overload.

Definitions ^[1][2]

• Crystalloids: solutions that contain small molecular weight solutes (e.g., minerals, dextrose)
• Colloids: solutions that contain larger molecular weight solutes (e.g., albumin and starch)
• Balanced IV fluid solutions: crystalloids or colloids that do not significantly alter the homeostasis of the extracellular compartment ^[2][3][4]

Osmolarity vs. tonicity of a fluid

• Osmolality: the concentration of dissolved particles per unit mass of solution (mOsm/kg); preferred term to describe the osmotic pressure of biological systems ^[5]
• Osmolarity: the concentration of solutes per unit volume of solvent (mOsm/L); often used interchangeably with osmolality in clinical practice
  • Preferred term to describe the osmotic pressure of parenteral fluids ^[5][6]
  • Takes into account all osmotically active particles, including those that enter cells (e.g., glucose, urea)
• Tonicity: the capacity of an extracellular fluid to create an osmotic gradient that will cause water to move into or out of the intracellular compartment; cannot be measured and has no units ^[7]
  • Reflects the osmotic effect of particles that cannot easily pass cell membranes, i.e., the effective osmotic pressure gradient
  • Describes what will happen to the equilibrium of a cell when it is placed in a certain solution

The osmolarity and tonicity of a solution are not the same thing! Administering solutions with inappropriate tonicity can lead to life-threatening fluid and electrolyte imbalances. ^[7]

The osmolarity of a parenteral solution takes into account the concentration of all the solutes, including those that enter cells (e.g., dextrose). The tonicity of a solution is determined by the solutes that do not enter the cell and are, therefore, osmotically active (e.g., sodium, potassium).

Crystalloid solutions ^[2][8]

• Aqueous solutions with varying concentrations of electrolytes
• The most commonly used fluids in a hospital setting
• Crystalloids increase intravascular volume; the extent to which they do this depends on their tonicity (effect on fluid compartments).
• Choose a solution based on treatment goals and patient characteristics (see “Principles of IV fluid therapy”).

Isotonic crystalloids

• Best solutions for IV fluid resuscitation
• Mixed isotonic solutions (i.e., containing glucose) are preferred as maintenance fluids (see “Mixed crystalloid solutions”).

Hypotonic crystalloids

Hypotonic crystalloids can be used to correct free water deficits and as a maintenance fluid if there is free water loss. ^[9]

Maintenance fluid therapy with hypotonic solutions can cause iatrogenic hyponatremia and cerebral edema. ^[9]

Hypertonic crystalloids

Hypertonic saline solutions must be administered with extreme caution because of the risk of rapid osmotic changes.

When administering hypertonic saline, frequent serum sodium controls must be conducted so that treatment can be adjusted accordingly. A rapid increase in serum sodium can lead to osmotic demyelination syndrome.

Mixed crystalloid solutions

The following list is not exhaustive, but it includes some very commonly used formulations.

• Dextrose in saline solutions
  • Composition and osmolarity
    • 5% dextrose in 0.9% NaCl (D5NS); isotonic: dextrose: 5 g/dL; Na⁺: 154 mEq/L; Cl^-: 154 mEq/L; osmolarity: 560 mOsm/L
    • 5% dextrose in 0.45% NaCl (D5½NS); hypotonic: dextrose: 5 g/dL; Na⁺: 77 mEq/L; Cl^-: 77 mEq/L; osmolarity: 406 mOsm/L
  • Clinical applications
    • Fluid replacement therapy
    • Fluid maintenance therapy
• Isotonic bicarbonate (1.3% NaHCO₃)
  • An isotonic balanced solution prepared by adding 150 mL of 8.4% NaHCO₃ to 850 mL of D5W or sterile water (total volume = 1 L)
  • Composition and osmolarity
    • Na⁺: 150 mEq/L; HCO₃^-: 150 mEq/L; ± dextrose 42.5 g/L
    • Osmolarity
      • If D5W used as solvent: 514 mOsm/L
      • If sterile water is used: 300 mOsm/L
  • Adjust treatment frequently (monitor HCO₃^- levels and pH). ^[14]
  • Clinical applications
    • Correction of severe metabolic acidosis ^[15][16][17]
    • Urinary alkalinization: to decrease the toxicity of specific drugs (e.g., salicylate toxicity, chemotherapy, IV contrast)
    • Consider for patients with true HCO₃^- deficit
  • Risks
    • Metabolic alkalosis
    • Hypernatremia
    • Hyperglycemia
    • Should not be administered with solutions containing calcium

The tonicity of a mixed solution is determined by the concentration of solutes that cannot cross the membranes freely (e.g., Na⁺ and Cl^-).

Concentrated crystalloid solutions

• 8.4% sodium bicarbonate: a solution that contains 8.4 g/dL (1 mEq/mL) of NaHCO₃; typically available in ampules of 50 mL (50 mEq)
  • Composition and osmolarity: Na⁺: 1 mEq/mL; HCO₃^-: 1 mEq/mL; osmolarity: 2000 mOsm/L
  • Tailor treatment to the patient's bicarbonate deficit and monitor HCO₃^- levels and pH frequently (e.g., initially every 2 hours). ^[14]
  • Clinical applications
    • Antidote for sodium channel blocker toxicity (e.g., TCA overdose)
    • Severe metabolic acidosis (e.g, during cardiorespiratory arrest, hyperglycemic crisis) ^[15][16][17]
  • Risks
    • Metabolic alkalosis
    • Hypernatremia
    • Should not be administered with solutions containing calcium
• 50% dextrose in water (D50W): typically available in ampules of 25 mL or 50 mL
  • Composition and osmolarity: dextrose: 50 g/dL; osmolarity: 2525 mOsm/L
  • Clinical applications ^[18]
    • Rapid reversal of hypoglycemia (see “Treatment” in “Hypoglycemia”)
    • Adjunctive treatment of hyperkalemia when combined with insulin (see “Treatment” in “Hyperkalemia”)
  • Risk of hyperglycemia

Concentrated crystalloids are typically administered like medications rather than fluids, e.g., as an antidote to a toxin or a reversal agent for an acute metabolic disturbance.

Colloidal solutions ^{[3][19][20][21]}

• High molecular weight substances that mostly remain confined to the intravascular compartment and thus generate oncotic pressure
  • Natural colloids: albumin, fresh frozen plasma (FFP)
  • Artificial colloids: gelatins, dextrans, hydroxyethyl starch (HES)
• Colloids have a greater effect on intravascular volume than crystalloids.
• Do not use colloids routinely for fluid resuscitation.

Avoid the use of colloids unless guided by a specialist or under specific circumstances (e.g., albumin for cirrhosis). ^[3]

Natural colloids

• Human albumin ^[8]
  • 25% Human albumin: Na⁺: 130–160 mEq/L; K⁺: < 2 mEq/L; albumin: 25 g/dL ; osmolarity: 312 mOsm/L
  • Indications
    • Cirrhosis: e.g., spontaneous bacterial peritonitis, paracentesis, hepatorenal syndrome ^[22]
    • Critically ill patients: e.g., ARDS, severe burns, hypovolemia, sepsis, and septic shock ^[23][24][25]
    • Other: e.g., diuretic resistant nephrotic syndrome, hemodialysis, and during plasmapheresis as an exchange fluid
  • Effect on fluid compartments: ↑ extracellular volume
  • Risks
    • Fluid overload
    • Allergic reactions
    • High costs
• Fresh frozen plasma: See “Transfusion” for more information.

Artificial colloids ^[3][8]

The use of artificial colloids is controversial because their advantage over crystalloids has not been proven and their side effects, e.g., decreased blood coagulability, pose certain risks. They should only be prescribed in consultation with a specialist. ^[20][21]

• Hydroxyethyl starch (HES): derived from amylopectin (a highly branched starch)
• Dextran: highly branched polysaccharide molecules
• Gelatins: synthesized through the hydrolysis of collagen

• Peripheral IV access: The intravenous route is most commonly used for administering fluids and/or medication.
• Intraosseous access: In “difficult/collapsed” peripheral veins, IO (intraosseous) access is preferred to central venous access for resuscitation.
• Central venous access: typically longer length than most peripheral IV and IO access catheters
• See also “Choice of vascular access” for further details on the suitability of different devices for individual patient needs.

A wider lumen and a shorter catheter tube allow for a higher flow rate.

Rapid introduction of large volumes of fluid through multiple large-bore (16G or wider) peripheral venous catheters is preferred to resuscitate patients with hypovolemic shock.

General indications for parenteral fluid therapy

Intravenous fluid management is one of the most common in-hospital interventions. Patients may present with multiple indications for IV fluid therapy, which can evolve over the course of their illness and response to treatment. These include: ^[2][3]

• Fluid resuscitation
• Replacement of:
  • Fluid losses or free water deficit
  • Baseline fluid needs (e.g., maintenance fluids)
• Correction of electrolyte imbalances (e.g., hyponatremia, hypokalemia, hypocalcemia)
• IV medication delivery

Hypovolemic patients with significant or active bleeding should receive transfusions of blood products as soon as possible. Parenteral fluids are only a temporizing measure in the management of hemorrhage.

Prescribing parenteral fluids

• IV fluids should be prescribed as any other drug.
• The phases of IV fluid treatment and the 4 Ds can be used as guiding principles.
• Patients receiving IV fluids should be evaluated continuously (at least daily).

The 4 Ds of fluid prescription: ^[3]
• Drug: Prescribe the type of fluid.
• Dosing: Indicate the amount of fluids and the rate.
• Duration: Monitor the response and determine the minimum and maximum duration of therapy.
• De-escalation: Taper and eventually discontinue the fluid.

Dynamic phases of IV fluid treatment ^[2][3][8]

• Patient rescue phase (minutes): life-saving intervention for patients with severe shock (i.e., fluid resuscitation)
• Organ rescue phase (hours): maintenance of tissue perfusion in patients with or at risk of hemodynamic instability (i.e., IV fluid challenges , titration of maintenance fluids to maintain tissue perfusion)
• Organ support phase (days): management of IV fluids in stable patients (i.e., maintenance fluid therapy, replacement of ongoing losses) and prevention of unnecessary fluid accumulation (i.e., switch to oral/enteral hydration)
• Organ recovery phase (days to weeks): reduction of IV fluids and evacuation of fluid overload

Monitoring and evaluation include baseline evaluations and frequent reassessments of clinical (e.g., pulse, blood pressure, capillary refill time, JVP assessment) and diagnostic parameters (e.g., biomarkers, imaging) depending on the patient's status, therapeutic goals, and response.

Clinical evaluation

Consider a fluid challenge to differentiate between hypovolemia and euvolemia if other clinical signs are unclear or cannot be assessed.

The steps required for a fluid challenge can be recalled with TROL: Type of fluid, Rate, Objective, and Limits.

Diagnostic evaluation

Laboratory studies

• CBC (e.g., to check for hemoconcentration, and screen for anemia or occult blood loss)
• BMP
  • Glucose
  • Urea/creatinine
  • Electrolytes
• Serum lactate: See “Lactate-guided fluid resuscitation strategy.”
• See also “Laboratory findings in dehydration and hypovolemia.”

Imaging assessment of volume status

• CXR: useful to detect signs of volume overload
• Echocardiography ^[8][29]
  • Assessment of intravascular volume and fluid responsiveness
    • Volume status can be estimated using the size of the heart ventricles, the stroke volume, and/or the cardiac output.
    • Fluid responsiveness can be assessed using a passive leg raise test
      • A test used to predict a patient's response to IV fluid therapy (and risk of fluid overload)
      • Both legs are raised to 45° for ∼ 1 minute, which increases venous return (preload) by ∼ 150–300 mL
      • Cardiac output and vital signs are assessed for a positive response (e.g., increase in stroke volume by ≥ 10%)
      • Differs from a fluid challenge in that no exogenous fluid administration is required (i.e., it is a self-volume challenge) and it is easily reversible
  • Identification of the type of shock (see “Rapid assessment by cardiac echocardiography”)
• POCUS: assessment of fluid volume and fluid responsiveness; FAST scan for trauma

• Definition: : the use of glucose-free isotonic fluid boluses to replenish the intravascular fluid compartment.
• Goal: prevention of organ failure and death (i.e., patient rescue and organ rescue phases)
• General approach
  • Aggressively replace fluids in patients with hypovolemic shock.
  • Replace fluid more judiciously in patients who have dehydration or hypovolemia without frank shock, e.g., moderate fluid loss.

Hemodynamically unstable patients ^[2]

See also “Immediate hemodynamic support”.

• Indications
  • Hypovolemic shock
  • Initial treatment of distributive shock and select cases of preload-dependent cardiogenic shock or obstructive shock
• Approach to fluid administration ^[2][30]
  • Administer rapid fluid bolus (i.e., within 10–30 minutes)
    • Adults: NS or LR 500–1000 mL IV bolus ^[2]
    • Children: NS or LR 10–20 mL/kg IV bolus ^[9][31]
  • Repeat as needed based on response (see “Hemodynamic monitoring parameters”). ^[32]
• Clinical deterioration
  • Consider the use of vasopressors and/or inotropes.
  • Consider other causes of shock besides hypovolemia (e.g., cardiogenic shock, distributive shock, obstructive shock).
  • Administer blood products if hypovolemia is due to hemorrhage (see “Transfusion”).
• Clinical improvement: See “Hemodynamically stable patients.”

Patients in shock require monitoring of hemodynamic parameters, e.g., heart rate, blood pressure (MAP), CVP, lactate, and urine output.

Hemodynamically stable patients ^[2]

See also “Initial fluid therapy in hypovolemia and dehydration.”

• Indications
  • Mild fluid loss or moderate fluid loss in patients with:
    • Inability to tolerate enteral fluid therapy
    • Dehydration or hypovolemia refractory to ORS
  • Optimization of treatment after stabilization of shock
• Approach to fluid administration
  • Identify risk factors for fluid overload or clinical signs of hypervolemia.
  • Assess for fluid responsiveness: i.e., PLR test or fluid challenge.
  • Administer replacement fluids more judiciously: e.g., 500 mL in adults or 5–10 mL/kg in children ^[2]
  • Titrate IV fluids based on hemodynamic monitoring parameters, e.g., repeat fluid challenge.
• Clinical deterioration: See “Hemodynamically unstable patients.”
• Clinical improvement
  • Manage continued fluid needs.
    • Replacement of ongoing fluid loss
    • Correction of free water deficit
    • Maintenance fluid therapy (see also “Daily fluid requirements for special patient populations”)
  • Transition to enteral fluid replacement as soon as tolerated.

Replacement of ongoing fluid loss

Fluids are also indicated in the postresuscitation phase, when the patient is no longer hypovolemic but still has ongoing abnormal fluid loss that cannot be compensated for by oral intake alone.

• Goal: Match the amount and rate of ongoing fluid loss (organ support phase).
• Indications: conditions associated with an ongoing fluid loss
  • Burns
  • Acute pancreatitis
  • Significant ongoing gastrointestinal loss (vomiting, diarrhea)
  • Surgical drains or fistulas
  • Polyuria (high output renal failure, diabetes insipidus)
• Approach to fluid administration
  • Identify and treat the underlying cause (i.e., stop fluid loss).
  • Match volume and composition (e.g., K⁺, HCO₃^-) of replacement fluid to that of the lost fluid.
    • Consider insensible fluid losses.
    • Monitor serum and urinary electrolytes.
  • See the “Parkland formula" for recommended fluid volumes in patients with burns.
• Next steps: Proceed to maintenance fluid therapy or de-escalation of IV fluid treatment once losses have stopped.

Correction of free water deficit

Replacement of free water is indicated to treat hypernatremia (organ support phase).

• Hypotonic solutions are preferred if parenteral fluid is required (e.g., 5% dextrose or hypotonic saline).
• Free water can also be replaced enterally (consider enteral tube placement as needed).
• See “Calculation of free water deficit in hypernatremia.”

Maintenance fluid therapy ^[3][9]

• Goal: Maintain adequate hydration and organ perfusion (organ support phase).
• Indications: patients who cannot or are not allowed to meet their daily fluid requirements enterally
• Approach to fluid administration
  • First-line fluid for all age groups: isotonic crystalloids with dextrose to prevent starvation ketosis (e.g., D5NS) ^[8]
  • Switch to isotonic crystalloids with no glucose once the patient has specialized nutritional support.
  • Increased maintenance fluid requirement: fever, tachypnea
  • Decreased maintenance fluid requirement: risk factors for fluid overload present: e.g., congestive cardiac failure, low output renal failure
  • See also “Daily fluid therapy requirements for special patient populations” below.
• Special considerations
  • Adding electrolytes to the maintenance fluid
    • If the patient has electrolyte deficiencies: Replace electrolytes separately from the maintenance fluid (see “Electrolyte repletion”).
    • Consider adding potassium (e.g., KCl 40 mEq/L) to maintenance fluid to meet requirements and monitor potassium levels frequently (see also “Hypokalemia” and “Potassium repletion”).
  • Patients on maintenance fluids alone for more than 3 days require specialized nutrition. ^[8]
• Next steps: Once the patient is hemodynamically stable with enteral or oral intake, proceed to de-escalation of IV fluid treatment.

For most patients that require maintenance IV fluids, dextrose in isotonic crystalloids is a reasonable choice that prevents starvation ketosis as well as iatrogenic hyponatremia. However, maintenance fluids alone with dextrose do not fulfill a patient's nutritional requirements.

If potassium is added to a solution, it cannot be infused at a rate > 10 mEq/hour via a peripheral line or > 40 mEq/hour via a central line, as it may lead to cardiac arrhythmias if infused too quickly.

The maintenance fluid requirement per kg of weight is higher in children than in adults.

Special patient groups ^[9]

• Conditions with decreased water (and potentially decreased solute) requirements, including:
  • Edematous states
  • CNS disease
  • Euvolemic states with ↑ ADH
  • Oliguric or anuric states
• Conditions with increased water (and potentially increased solute) requirements, including:
  • Concentrating defects
  • Solute diuresis

• Goals (organ recovery phase) ^[2][3]
  • Weaning from IV fluids
  • Mobilization of accumulated fluid to achieve normovolemia
  • Prevention of prolonged or worsening fluid overload
• Indications: patients in recovery
  • Hemodynamically stable, with adequate tissue perfusion
  • Capable of enteral/oral feeding and hydration
• De-escalation: Continue oral/enteral hydration and consider restricting IV fluids until they are suspended completely.
• Evacuation of excess fluids: Strategies should be tailored to the patient. ^[2]
  • Allow spontaneous diuresis of excess fluid in patients with adequate kidney function.
  • If spontaneous diuresis is deficient:
    • Consider diuretics with or without albumin.
    • Consult nephrology for early RRT if there is intractable fluid overload.
    • Set objective goals and monitor carefully to prevent harm from excessive fluid removal (e.g., hypotension, acute kidney injury).

De-escalate IV fluids in patients who are stable (e.g., weaned from ventilator and vasopressors) and are capable of meeting their fluid needs orally/enterally.

Fluid overload ^[3]

• Risk factors for fluid overload ^[9]
  • Special patient populations: e.g., elderly, pediatric, or pregnant patients
  • Acute disease: e.g., critical illness, malnourishment, edematous states (e.g., decompensated cirrhosis, nephrotic syndrome, CHF)
  • Chronic disease: e.g., CKD, cardiopulmonary diseases (e.g., cardiomyopathy, COPD)
  • Iatrogenic: e.g., transfusion of blood products, fluid creep
• Findings: clinical signs of hypervolemia (e.g., crackles on pulmonary auscultation)
• Management
  • Reduce infusion rate (de-escalation of treatment) and limit oral fluid intake if possible.
  • Respiratory support as needed (see “Respiratory support in acute heart failure”)
  • Fluid evacuation ^[3]
    • Diuretics: e.g., loop diuretics (see “Diuretic therapy in acute heart failure” for agents and doses)
    • Indications for early RRT ^[3]
      • Intractable electrolyte imbalances
      • Life-threatening fluid accumulation
      • Refractory oliguria
      • Patient already on ECMO

Hyperchloremic metabolic acidosis ^[36]

• Commonly caused by the use of large volumes of solutions containing Cl^- (e.g., normal saline)
• Management
  • Reduce infusion rate (de-escalation of treatment).
  • Change to balanced solutions (e.g., LR).

Electrolyte imbalances ^[19][36][37]

• Hospital-associated hyponatremia
  • Causes include use of hypotonic solutions, SIADH, hypervolemic hyponatremia, and diuretic use (e.g., thiazides). ^[38]
  • Stop hypotonic fluids: See “Hyponatremia.”
• Hospital-associated hypernatremia
  • Caused by free water deficit and possibly high solute administration
  • Manage with hypotonic solutions and oral/enteral water (see “Treatment of hypernatremia”)

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