• Crystalloids are solutions of water, electrolytes, and other nonprotein solutes. They are administered for volume replacement and expansion, electrolyte replacement, as a medication carrier, and for dilution of blood products during transfusion to decrease viscosity.
• Benefits include: Inexpensive, easy to store, long shelf–life, readily available, few adverse actions, available in a variety of formulations, do not require special compatibility testing, and there are no religious objections to their use.
• Crystalloids may be classified as hypertonic, isotonic, or hypotonic with respect to plasma osmolarity; some may also be described as "balanced" or "physiological" solutions with regard to their chloride concentration relative to plasma; unbalanced fluids have a proportionally high chloride concentration.

• Average 70 kg man has 42 L of total body water (TBW). The intracellular volume has 28 L (67% of TBW); the interstitial volume has 10.5 L (25% of TBW); and the intravascular volume has 3.5 L (8% of TBW).
• Electrolyte solutions distribute through these spaces; ~1/3^rd to 1/4^th will remain in the intravascular space following isotonic administration.
• Normal saline (0.9% NaCl); "unbalanced" solution
  • Sodium 154 mEq/L; greater than plasma
  • Chloride 154 mEq/L; significantly greater than plasma
  • Osmolarity 308 mEq/L; slightly greater than serum osmolarity (~285 mOsm/L).
• Lactated Ringer’s; "balanced" solution. pH 6.5
  • Sodium 130 mEq/L; less than plasma
  • Chloride 109 mEq/L; slightly greater than plasma
  • Potassium 4 mEq/L; similar to plasma
  • Calcium 3 mEq/L; similar to plasma
  • Lactate 28 mEq/L; hepatically metabolized to glycogen that is then oxidatively metabolized to CO₂ and H₂O. The CO₂ accepts a hydrogen ion (H⁺) to yield bicarbonate. Thus, lactate functions as an alternative source of bicarbonate. However, because the conversion takes ~1–2 hours, depending on the integrity of cellular oxidative processes, it is a less effective source of bicarbonate in lactic acidosis, shock, or decreased perfusion states.
  • Osmolarity: 275 mOsm/L; slightly less than plasma, hence hypotonic
• Normosol; "balanced." pH 7.4
  • Sodium 140 mEq/L; similar to plasma
  • Chloride 98 mEq/L; similar to plasma
  • Potassium 5 mEq/L; slightly greater than plasma
  • Magnesium 3 mEq/L; Mg⁺⁺ is the second most plentiful cation of intracellular fluid and plays an important role as a cofactor for enzymatic reactions and in neurochemical transmission and muscular excitability.
  • Acetate 27 mEq/L; CH₃COO^- is metabolized in the liver (even in severe disease) to become a source of H⁺ acceptors. Thus, it is an alternate source of bicarbonate.
  • Gluconate 23 mEq/L; a theoretical alternate metabolic source of bicarbonate ion. However, a significant antiacidotic action has not been established. Thus, the gluconate anion serves primarily to complete the cation–anion balance of the solution.
  • Osmolarity 295 mOsm/L; greater than plasma
• Plasmalyte; "balanced" solution
  • Sodium 140 mEq/L; similar to plasma
  • Chloride 98 mEq/L; similar to plasma
  • Potassium 5 mEq/L; slightly greater than plasma
  • Magnesium 3 mEq/L
  • Acetate 27 mEq/L; serves as a bicarbonate alternative or precursor
  • Gluconate 23 mEq/L; a theoretical alternative to bicarbonate
  • Osmolarity 294 mOsm/L; slightly greater than plasma
• Hypertonic saline 3%; pH 4.5–7
  • Sodium 513 mEq/L
  • Chloride 513 mEq/L
  • Osmolarity 1,027 mOsm/L; the hypertonicity creates an osmotic gradient for fluid to shift from the intracellular to interstitial and intravascular space, resulting in an increase in preload. It can also cause vasodilation from direct vascular smooth muscle relaxation with resultant improvement in capillary blood flow. Furthermore, hypertonicity can decrease endothelial cell volume (intracellular to extracellular flow) that increases capillary diameter and decreases vascular resistance.
• Dextrose 5% in water; D5W. pH 4.5
  • Dextrose 50 g/L; promotes glycogen deposition and decreases or prevents ketosis if sufficient doses are provided.
  • Osmolarity "inactive;" glucose is metabolized as an energy source and there is no sodium. Thus, the net effect is equivalent to giving pure water that is distributed throughout TBW with each compartment receiving fluid in proportion to TBW. A large percentage moves intracellularly.

• Plasma electrolytes pass freely between the intravascular space and interstitial fluid. Plasma proteins are restricted to the intravascular space. Because of its abundance, sodium is the most important osmolar force in the interstitial space. Potassium and intracellular proteins are the most important oncotic forces in the intracellular space.
• The renin-angiotensin system affects cardiac output, BP, and fluid status. It is activated by decreased BP in the renal artery, decreased plasma sodium levels at the macula densa, and/or the surgical stress response.
• Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are proteins released by the cardiac atria and ventricles, respectively, when the chamber walls are distended due to increased volume and pressure. These peptides increase the glomerular filtration rate (GFR), sodium excretion, and water excretion. BNP is also utilized as a marker for congestive heart failure.
• Sympathetic nervous system fibers exit the spinal cord at the T1–L2 level. Neuraxial blockade induced sympathectomy occurs when T1–L2 fibers are blocked causing peripheral dilation and hypotension. Fluid is commonly administered for this perturbation.
• A neuraxial block affecting T1–T4 fibers affects the cardioaccelerator fibers and blunts the tachycardic response to hypotension. Fluid is commonly administered for this perturbation.

• Normal saline
  • Nongap hyperchloremic metabolic acidosis; previously believed to be secondary to "dilutional acidosis." NaCl dissolves into NaOH and HCl in plasma. The 154 mEq/L of chloride found in normal saline is much greater than that of plasma (100 mEq/L). This results in more hydrochloric acid as compared to sodium hydroxide and causes acidosis (1) [C]. NaCl + H₂O HCl + NaOH. Additionally, normal saline lacks a buffering salt such as lactate or acetate and bicarbonate is eliminated renally to maintain electrical neutrality.
• Lactated Ringer’s
  • In acidotic and anoxic states, lactate metabolism is affected.
  • Hyperkalemia can be worsened
  • Cannot be administered with blood products; calcium in solution can clot blood products.
  • Respiratory acidosis from carbon dioxide production can occur.
  • Mild hyponatremia
  • May be associated with panic attacks secondary to the complexing of calcium, despite the absence of serum levels or symptoms of hypocalcemia.
• Normosol and Plasmalyte
  • Hyperkalemia can be worsened
  • Cautious use with metabolic or respiratory alkalosis; the bicarbonate alternatives, acetate and gluconate, can exacerbate
  • Severe hepatic insufficiency may preclude the conversion of acetate and gluconate.
  • Dilutional hyponatremia
• D5W can cause hyperglycemia and hypotonicity. Hypotonicity can affect intracellular volume and cause cell lysis.
• Hypertonic saline
  • Central myelinolysis can result from the rapid increase in sodium. May be avoided by limiting sodium increases to a maximum rate of 0.5 mEq/L/hour, not to exceed 10–12 mEq/L in 24 hours.
  • Renal insufficiency and failure are seen with a higher incidence than with other crystalloids.
  • Hemorrhage secondary to excessive fluid resuscitation
  • Decreases in afterload can result; transient hypotension can be seen after boluses are administered.
  • Dilution of plasma constituents (coagulation factors) can occur with rapid intravascular volume expansion.
  • Hypokalemia or hyperchloremic acidosis
  • Rebound increases in ICP after boluses or when continuous infusions are stopped.
  • Phlebitis or tissue necrosis can result from hypertonicity; central lines are preferable.
• Anesthesia blunts the normal sympathetic tone and physiologic response to hypovolemia.
• Transurethral resection of the prostate (TURP) syndrome refers to hypotonic hypervolemic hyponatremia due to absorption of the free water surgical field irrigant during a TURP procedure. This can lead to sodium levels <125 mEq/L and symptoms of hyponatremia (neurologic symptoms, including seizures, confusion, lethargy) (2) [A].
• Overly aggressive fluid replacement can lead to the development of pulmonary edema and impaired oxygen/carbon dioxide exchange, particularly in patients with compromised cardiac performance such as neonates and the elderly.

• Crystalloid versus colloid resuscitation: Crystalloids are significantly less expensive. Resuscitation requiring volume replacement does not show a benefit of colloids over crystalloids (3) [A].
• SAFE study: Prospective randomized controlled trial comparing colloids versus crystalloids for fluid resuscitation in critical care patients: No significant difference is found in clinical outcome between colloid and crystalloid groups (4) [A].
• Normal saline. Hyperchloremic acidosis has been shown to decrease mucosal perfusion, profoundly affect eicosanoid release in renal tissue that leads to vasoconstriction and decreased GFR, inactivate membrane calcium channels, and inhibit norepinephrine release from sympathetic nerve fibers resulting in redistribution of cardiac output away from internal organs. Attempts to correct this abnormality may actually be the main adverse effect. Acidosis is often seen as a reflection of poor organ perfusion or poor myocardial function. A negative base excess may prompt more saline boluses containing fluids that exacerbate acidosis, the use of blood products, escalation of inotropic support, and initiation of ventilator support. Furthermore, when coupled with acidosis from a different source (e.g., lactic acidosis from tissue hypoperfusion) this can further complicate the management of patient care.
• Hypertonic saline. May be useful in cerebral edema, burn injuries, or trauma; outcome studies are currently underway.
  • Cerebral edema. Increased osmolarity can draw fluid from brain cells into the intravascular space; this results in decreased cerebral water content, edema formation, and ICP. Increased intravascular volume may lead to an autoregulatory decrease in intracerebral blood volume (assuming autoregulation remains intact). Studies have demonstrated improved survival in traumatic brain injury.
  • Burn injuries. The physiochemical interaction with glycocalyx may result in a less "leaky" vascular endothelium. Studies have shown that severe burns have a decreased incidence of abdominal compartment syndrome, possibly from decreased capillary leak (less bowel wall and intra-abdominal fluid accumulation)
  • Trauma. Can increase BP with small volume resuscitation and may increase survival. This is attributed to the avoidance of hemodilution seen with excess amounts of isotonic fluids, hypothermia, acidosis, coagulopathy, and sustained hyperosmolar state.

• Plasma osmolarity (mOsm/L) = ([Na⁺] × 2) + (BUN/2.8) + (glucose/18) where BUN and glucose are mg/dL (normal plasma osmolarity ~285 mg/dL)
• Maintenance fluids can be administered using the 4-2-1 rule: 4 mL/kg/hr for first 10 kg, 2 mL/kg/hr for next 10 kg, and 1 mL/kg/hr for each kg above 20 kg.
• Fluid deficit calculations. Initial fluid deficit due to NPO status: Number of hours NPO × maintenance rate, administer ½ during the first hour of procedure, 1/4 during the second hour, and 1/4 during the third hour. Third spacing/evaporative surgical field losses should be corrected at 0–10 mL/kg/hr depending on the degree of tissue exposure (e.g., 2–4 mL/kg/hr for open cholecystectomy and 4–8 mL/kg/hr for bowel resection). Replace blood loss with crystalloid fluid in a 1:4 ratio until transfusion of blood products is indicated.
• Free water deficit (useful with hypernatremia) = 0.6 × (weight in kg) × ([serum sodium/140]–1). Can replace deficit over 2–3 days with free water enterally, or with isotonic/hypotonic solutions intravenously.

• Colloids
• Insensible Fluid Losses
• Plasma Osmolarity
• TURP Syndrome

Trent Emerick , MD

James Cain , MD