The (Quiet) Role of Crystalloids in Therapeutic Plasma Exchange

1 | A brief historical arc

In the early years of therapeutic plasma exchange (TPE), replacement was simple: plasma when coagulation factors were needed, 5 % albumin when they were not. Through the 1980s and 1990s, a few groups began experimenting with albumin–saline mixtures to stretch resources and probe the physiology of volume replacement.

The results were instructive. Larger saline fractions consistently lowered oncotic pressure, triggered transient hypotension, and produced mild metabolic acidosis. By the late 1990s, most centers had returned to albumin-dominant replacement, reserving plasma for specific indications and using small amounts of crystalloid only for circuit priming, rinseback, or minor volume adjustments.

2 | The physiology — why saline isn’t “neutral”

• Oncotic pressure: Albumin preserves intravascular volume; saline does not. When saline replaces plasma in large proportions, intravascular volume can fall even as total volume looks adequate.

• Chloride load and acid–base balance: 0.9 % NaCl carries 154 mmol/L of chloride and a strong-ion difference of 0, which drives hyperchloremic metabolic acidosis. Balanced crystalloids such as Lactated Ringer’s and Plasma-Lyte A include buffers (lactate, acetate, gluconate) and have positive SIDs, making them acid–base neutral or mildly alkalinizing.

• Renal perfusion: Hyperchloremia activates the macula densa and causes afferent arteriolar constriction, reducing glomerular filtration. That link between chloride load and renal perfusion is one reason large critical-care trials now favor balanced crystalloids over saline.

  
  

3 | Guidelines in brief

• ASFA 2023: Albumin and plasma remain the mainstays. Crystalloids appear only in technical notes, usually as minor adjuncts.

• Canadian Blood Services: “The most commonly used replacement fluid is 5 % albumin… some centres also use normal saline in combination with albumin or plasma, though this practice is increasingly uncommon.”

• AJKD Nephrology Core Curriculum 2023: For cost containment, mixtures such as 80:20 albumin:saline are acceptable, with a practical upper limit around 30 % crystalloid.

  
  

Across documents, the message is consistent: albumin for most indications, plasma when factors are needed, and crystalloids only in modest proportion.

4 | How crystalloids are used today

• Default:  100 % 5 % albumin for non-factor indications.

• Plasma:  for TTP and other settings requiring factor repletion.

• Crystalloids:  used mainly for

  • circuit priming and rinseback,

  • ≤ 20–30 % of the replacement volume when cost or volume considerations apply, and

  • preference for balanced crystalloids over saline to avoid chloride-driven acidosis.

Why not more saline? Beyond small fractions, you gain nothing physiologically and risk hyperchloremic acidosis, hypotension, and renal stress — all without oncotic support.

5 | Takeaway

Crystalloids do have a place in TPE — but it’s a supporting role. The foundation remains albumin, with plasma added when coagulation factors are required. When crystalloids are used, keep them to no more than about one-third of the exchange volume and choose balanced solutions like Plasma-Lyte A or Lactated Ringer’s whenever possible.

It’s a small composition detail in a large-volume therapy — but over several liters, those chloride ions and milliequivalents of buffer can make a measurable difference.