Throughout the high-energy, medical staff staged a "criminal investigation drama" to track down the "real culprit" of hemodialysis allergies through 2 cases

Allergic reactions associated with hemodialysis are rare but potentially life-threatening complications. However, for patients with end-stage renal disease (ESKD), hemodialysis is unavoidable. Therefore, if there is an allergic reaction related to hemodialysis, in addition to first aid, it is more important to find the allergen.

In January 2022, BMC nephrology published two cases. These two cases not only show how to rescue hemodialysis-related allergic reactions, but also record how medical staff incarnated as "Sherlock Holmes", stripped away the cocoon, tracked down the "murderer (allergen)" and "brought to justice".

Case 1

Patient, 65 years old, Chinese female, with advanced stages of chronic kidney disease (CKD). She was admitted to the hospital for acute kidney injury (AKI) and needed dialysis. A known history of allergy is penicillin. Due to metabolic acidosis and uremia, she underwent her first hemodialysis. Dialysis duration 2.5 h, blood flow 150 ml/min, dialysate flow 300 ml/min, no anticoagulation. There were no complications throughout the dialysis treatment.

In the second dialysis, the patient received anticoagulation (500 U of heparin, and a maintenance dose of 500 U / h). However, she developed generalized pruritus within 1 hour of dialysis and stopped heparin.

After a 2-day break, the patient begins the 3rd dialysis session, and after 2 minutes develops shortness of breath, flushing, and tachycardia. Dialysis treatment is terminated. However, due to the allergic reaction that occurred on the previous dialysis, heparin anticoagulation was not used this time. The patient's symptoms disappear after urgent injections of hydrocortisone and diphenhydramine.

It is worth noting that the instrument used in the above 3 dialysis sessions is a polysulfone membrane dialyzer (also known as a hollow fiber dialyzer). Doctors believed that the "killer" might be a polysulfone membrane dialyzer, so the dialyzer was replaced.

In subsequent dialysis treatment, a cellulose triacetate membrane (CTA) dialyzer was used in medical institutions. In a review of their in-hospital and in-hospital drug use, physicians found that patients were not using angiotensin-converting enzyme inhibitors (ACEIs) or penicillin-like antibiotics. Laboratory tests also do not show an increase in eosinophil count. The doctor initially determined that the "murderer" was a polysulfone membrane dialyzer.

However, the truth is often not so simple...

After 5 successful dialysis sessions, the patient developed allergic symptoms. Seven minutes after the start of the 9th dialysis treatment, the patient developed generalized erythema, pruritus, and angioedema. At this point, the patient is referred to a medical institution that is more experienced in allergic reactions.

In the new hospital, medical staff conducted a detailed review of the patient's case and found that the polysulfone membrane dialyzer and the CTA dialyzer that caused allergic reactions were disinfected with chlorhexidine, while the CTA dialysis that successfully underwent dialysis used γ radiation disinfection.

The medical staff said: "There is only one truth!" The murderer is chlorine."

Unsurprisingly, the patient had a positive chlorhexidine skin test. Subsequently, the dialyzers that the patient receives hemodialysis treatment are sterilized by radiation instead of chlorhexidine. In subsequent hemodialysis treatment, the patient did not re-develop allergic reactions.

Case 2

The patient, 60 years old, female, has a medical history of diabetic nephropathy and started haemodialysis 8 months ago. Patients are referred for carpal vasculitis associated with arteriovenous fistulas. After being transferred to the hospital, physicians reviewed the medications used by the patient, including aspirin, atorvastatin, calcium acetate, furosemide, bisoprolol, omeprazole, glipizide, erythropoietin, and vitamins.

After 2min of routine dialysis therapy, the patient developed severe hypotension, treatment was terminated, and referral to the Intensive Care Unit (ICU) for continuous renal replacement therapy (CRRT).

Upon arrival at the ICU, the patient's clinical condition improved spontaneously and there was no longer a need for assisted breathing. The next day, after trying to use intermittent hemodialysis in the ICU, no abnormalities were found, so he was transferred back to the general ward. After 2 days, the patient developed hypotension, hypoxia, and urticaria again during dialysis. The paramedics terminated the dialysis and sent her to the ICU again.

Similar to the previous situation, the patient's clinical condition improved spontaneously after being admitted to the ICU, and when the ICU received dialysis, the patient did not have any adverse reactions. After being transferred to the general ward again, the patient's serum trypsin is elevated, suggesting a hypersensitivity reaction. However, it is unclear what causes allergies in patients.

What's more, while on dialysis, nurses found that patients developed hypotension, hypoxia, and generalized urticaria before connecting the patient's catheter to the dialysis machine. This led the paramedics to narrow down the list of "suspects". The narrowed list of "suspects" is skin disinfectant, the environment of the dialysis room, and dialysis catheters.

As a result, the medical staff passed the skin test and single "interrogated" the various "suspects". The positive substances for the skin test are chlorhexidine, while the negative substances are citrate, cleaning agents used in dialysis rooms, dust commonly found in dialysis rooms, and fungi. Subsequently, the dialysis chamber replaces the chlorine disinfectant with a povidone iodine disinfectant. Physicians require patients to avoid chlorhexidine during dialysis treatment. Since then, the patient has not experienced any more allergic reactions.

It is worth noting that the dialysis center has not been using chlorhexidine as a disinfectant, but was replaced 3 months ago. That is, the patient was already exposed to chlorhexidine 3 months ago!

Discussion and summary

Chlorhexidine-related dialysis allergy is an extremely rare dialysis-related allergy, however the results can be extremely severe. In particular, some patients experience type A allergic reactions. However, in the face of each "victim", even the "modus operandi" of the same "murderer" is different. Some patients (case 1) develop an allergic reaction within a few days of exposure to chlorhexidine, while others (case 2) are exposed for several months. Physicians believe that this is related to individual differences and medication history.

It is worth noting that both patients were on hemodialysis through a catheter, which means that the skin barrier function is impaired. The review by Heinemann et al. highlights that in patients with skin damage, chlorhexidine may trigger an immediate hypersensitivity reaction.

In addition, allergen concentrations are also one of the factors that cause allergic reactions in patients. Chlorhexidine concentrations in the ICU may be lower compared to dialysis chambers. In the choi et al. study, they found a direct correlation between aerosol concentrations and the risk of allergic reactions. This may be the reason why Case 2 does not have an allergic reaction in the ICU.

In general, medical staff not only need "benevolent magic", but also "spiegel hanging". For dialysis-related allergies, medical staff not only need to know how to give first aid, but also need to become a "detective" to find the "real culprit" in the long list of "suspects" so that patients can avoid recurrence of allergic reactions!

Typography: Don

Proofreading: Sam

bibliography:

1.TanJN, Yi, Haroon S, Lau T. Chlorhexidine - a commonly used but often neglectedculprit of dialysis associated anaphylactic reactions (case report). BMCNephrol. 2022 Jan 6;23(1):18.