Dialysis Disequilibrium Syndrome

If you have spent any time working in an emergency department in the U.S., you know that dialysis patients frequently present with complications from their medical conditions or their hemodialysis. The July issue of Emergency Medicine Practice was devoted to dialysis emergencies. It covered the array of complications a patient may experience, including one syndrome that many of us may not have seen: dialysis disequilibrium syndrome.

Pathophysiology & Epidemiology

The cause of dialysis disequilibrium syndrome (DDS) is thought to be a rapid change in osmotic gradient between the vascular space and the brain, leading to cerebral edema. Current literature supports the theory that this osmotic gradient occurs when urea is filtered from the blood rapidly, and high urea levels remain in the brain, resulting in fluid shifting into the extravascular space. However, competing theories suggest the syndrome may occur due to rapid electrolyte imbalances or CNS acidosis instead.¹

Although the exact mechanism is not clear, several risk factors have been identified:

• High Initial BUN Levels: Patients with very high pre-dialysis BUN levels are at increased risk as rapid reductions during dialysis may be more pronounced.⁹
• First Dialysis Sessions: Patients new to dialysis may take some time to acclimate to rapid changes in blood chemistry and are at higher risk.⁶
• Rapid Dialysis: Patients undergoing aggressive dialysis protocols that quickly reduce BUN levels are more likely to induce DDS.⁷
• Medical Conditions: Patients with malignant hypertension, seizure disorders, sepsis, meningitis, vasculitis (conditions thought to increase blood-brain barrier permeability), hypernatremia, hyperglycemia, and metabolic acidosis are at increased risk.¹

The literature highlights hemodialysis as the main culprit; however, there have been reports of dialysis disequilibrium syndrome occurring during peritoneal dialysis and continuous kidney replacement therapy (CKRT).¹

DDS demonstrates a bimodal distribution with reported cases occurring primarily in pediatric and geriatric patients. Thankfully, the incidence of severe disease is rare and appears to be dropping as dialysis technology improves. However, milder presentations are likely underreported. ¹

Preventive Measures

• Gradual Initiation of Dialysis: Starting with shorter and less intensive dialysis sessions can help the body gradually adapt to the changes in blood chemistry.⁹
• Monitoring BUN Levels: Regularly monitoring BUN levels and adjusting the dialysis prescription accordingly can help minimize the risk.⁶
• Use of Osmotic Agents: Administering osmotic agents like mannitol during dialysis can help mitigate cerebral edema by balancing the osmotic gradient.⁵

Symptoms

Symptoms attributed to dialysis disequilibrium syndrome present on a spectrum of severity.⁹ They include:

• Headache
• Nausea and vomiting
• Restlessness
• Hypertension (high blood pressure)
• Muscle cramps
• Blurred vision
• Seizures
• Coma
• Death

The diagnosis of DDS is clinical, based on symptoms and their relationship to dialysis. However, other potential causes of the symptoms should be ruled with a thorough medical evaluation.⁸

Treatment

Treatment is focused on alleviating symptoms and slowing or stopping the current dialysis session. Strategies include:

• Stop Dialysis: The first step is to immediately halt the dialysis session to prevent further fluid and electrolyte imbalances. Reducing the rate of dialysis to allow for a more gradual decrease in BUN levels is also an option in milder cases.⁹
• Supportive Care: Providing supportive care such as antiemetics for nausea and anticonvulsants for seizures. Intravenous fluids to restore blood volume in severe cases.⁸
• Osmotic Therapy: Using osmotic agents (mannitol) to reduce cerebral edema.⁷
• Monitoring: Closely monitoring vital signs and neurological function to track progress.

In most cases, prompt intervention and treatment lead to a full recovery from DDS.

Conclusion

Dialysis Disequilibrium Syndrome is a potentially life-threatening condition that requires prompt recognition and intervention. By understanding the underlying causes, recognizing the symptoms, and implementing preventive and therapeutic strategies, emergency medicine providers can significantly reduce the incidence and severity of DDS in patients undergoing hemodialysis.

For more information about dialysis emergencies and their treatment in the emergency department, read the July 2024 issue of Emergency Medicine Practice and listen to the July 2024 episode of the EMplify podcast.

References

1. Raina, R., Davenport, A., Warady, B., Vasistha, P., Sethi, S., Chakraborty, R., Khooblall, P., Agarwal, N., Vij, M., Schaefer, F., Malhotra, K., & Misra, M. (2021). Dialysis disequilibrium syndrome (DDS) in pediatric patients on dialysis: systematic review and clinical practice recommendations. Pediatric Nephrology, 37, 263-274. https://doi.org/10.1007/s00467-021-05242-1.
2. Chauhan, V. (2023, November 25). Dialysis Disequilibrium Syndrome: Causes and Risk Factors. Verywell Health.
3. Dialysis disequilibrium syndrome prevention and management. (2016). International Journal of Nephrology and Renovascular Disease, 9(1), 89–95.
4. Arieff, A. I., & Guisado, R. (1976). Effects on the brain of sudden changes in osmolality in the central nervous system. The American Journal of Medicine, 58(1), 108-122.
5. Baird, G. S., Hoffman, N. G., & Roberts, W. L. (2003). Cerebrospinal fluid and serum osmolality: Establishing reference intervals. Clinical Chemistry, 49(5), 760-764.
6. Davenport, A., & Tolwani, A. (2009). Hemodialysis prescription and delivery: Normothermic and cold dialysis. Seminars in Dialysis, 22(6), 653-659.
7. Tetta, C., Bellomo, R., & Ronco, C. (2003). Dialysis disequilibrium syndrome. Nephrology Dialysis Transplantation, 18(6), 1204-1207.
8. Krishnan, M., & Daugirdas, J. T. (2008). Osmotic agents in the management of dialysis disequilibrium syndrome. Seminars in Dialysis, 21(3), 217-219.
9. Himmelfarb, J., & Sayegh, M. H. (2014). Chronic Kidney Disease, Dialysis, and Transplantation: A Companion to Brenner & Rector’s The Kidney. Elsevier Health Sciences.