What are the recommendations for preventing and managing first use dialyzer syndrome (FUDS) in patients at risk?

First Use Dialyzer Syndrome: Prevention and Management

To prevent first use dialyzer syndrome (FUDS), dialysis centers should preprocess all new dialyzers before initial patient use, regardless of whether they practice routine dialyzer reuse. This single intervention has been shown to markedly diminish or eliminate the syndrome characterized by chest pain, back pain, dyspnea, and other intradialytic symptoms 1.

Understanding First Use Dialyzer Syndrome

FUDS encompasses two distinct reaction types 2:

• Type A reactions: Hypersensitivity/anaphylactic reactions (incidence: 4 per 100,000 dialysis sessions) 2
• Type B reactions: Nonspecific reactions (incidence: 3-5 per 100 dialysis sessions) 2

The syndrome manifests with chest pain (2.8 times more frequent with first use), back pain (6 times more frequent), and concurrent chest and back pain (42 times more frequent) compared to subsequent dialyzer uses 1. Additional symptoms include dyspnea, burning sensations, leukopenia, thrombocytopenia, and oxygen desaturation 2.

Primary Prevention Strategy

Mandatory preprocessing of all new dialyzers before first patient use is the most effective preventive measure 3, 1. This practice:

• Removes manufacturing residuals including ethylene oxide, bore fluids, potting compound (polyurethane) fragments, dialyzer membrane fragments, plastic components, and other noxious substances 3
• Eliminates the previously documented "first-use syndrome" when automated reprocessing systems are used 1
• Should be implemented regardless of whether the facility practices routine dialyzer reuse 3

Mechanisms and Causative Factors

Multiple mechanisms contribute to FUDS 2, 4, 5:

• Complement activation by unmodified cellulose membranes 3
• Residual ethylene oxide from sterilization 2, 4
• Leachable substances from the dialyzer membrane itself (particularly polysulfone) 4
• Noxious agents introduced during manufacturing or generated during storage 5
• Interaction between AN69 membranes and ACE inhibitors 2

Important caveat: FUDS can occur even with modern polysulfone membranes sterilized without ethylene oxide, indicating that membrane material itself or other leachable substances may be responsible 4.

Management of Acute Reactions

When FUDS occurs despite preprocessing 2, 4:

1. Immediate measures: Discontinue dialysis, provide supportive care for symptoms
2. For subsequent sessions:
   • Switch to alternative membrane types (e.g., cellulose triacetate if polysulfone caused reaction) 4
   • Use preprocessed dialyzers filled with disinfectant (e.g., renalin) 4
   • Implement double-rinsing protocols 2
   • Trial different sterilization methods (electron beam vs. gamma radiation) 2

Monitoring and Quality Assurance

Dialysis facilities must measure total cell volume (TCV) before first use to establish baseline dialyzer function 3. This measurement:

• Accounts for variability among dialyzers and dialyzer lots 3
• Cannot be substituted with average volumes from the same model or lot 3
• Ensures the preprocessing procedure is adequate 3

Alternative monitoring includes ionic clearance or urea clearance measurements, which correlate closely with TCV 3, 6.

Membrane Selection Considerations

Avoid unmodified cellulose dialyzer membranes due to complement activation and associated adverse biochemical changes 3, 6. Modern synthetic membranes (polysulfone, polyethersulfone) are preferred, though they still require preprocessing 3, 6.

Common Pitfalls to Avoid

• Never skip preprocessing: Even "biocompatible" synthetic membranes require preprocessing to remove manufacturing residuals 3
• Don't assume routine rinsing is sufficient: Standard preparation procedures may not completely remove noxious agents 5
• Recognize persistent reactions: If symptoms continue despite preprocessing and membrane changes, consider rare causes including dialysate contamination or pulmonary leukostasis 2
• Monitor for delayed reactions: Some patients may develop reactions only after switching from other renal replacement modalities (e.g., peritoneal dialysis to hemodialysis) 2

Implementation in Clinical Practice

Facilities should follow AAMI (Association for the Advancement of Medical Instrumentation) recommendations for dialyzer preprocessing 3, 6. The automated machine processing method is superior to manual processing for preventing FUDS 1. This approach has been adopted by CMS and represents the best available guidance 3.