Medline ® Abstracts for References 2-6

The dialysis disequilibrium syndrome is a rare but serious complication of hemodialysis. Despite the fact that maintenance hemodialysis has been a routine procedure for over 50 years, this syndrome remains poorly understood. The signs and symptoms vary widely from restlessness and headache to coma and death. While cerebral edema and increased intracranial pressure are the primary contributing factors to this syndrome and are the target of therapy, the precise mechanisms for their development remain elusive. Treatment of this syndrome once it has developed is rarely successful. Thus, measures to avoid its development are crucial. In this review, we will examine the pathophysiology of this syndrome and discuss the factors to consider in avoiding its development.

Dialysis Disequilibrium Syndrome (DDS) is characterized by neurological symptoms caused by rapid removal of urea during hemodialysis. It develops primarily from an osmotic gradient that develops between the brain and the plasma as a result of rapid hemodialysis. This results in brain edema that manifests as neurological symptoms such as headache, nausea, vomiting, muscle cramps, tremors, disturbed consciousness, and convulsions. In severe cases, patients can die from advanced cerebral edema. Recent advancements in cell biology implicate the role of urea disequilibrium (with a smaller contribution from organic osmolytes) as the pathophysiological mechanism responsible for this syndrome. In this review, we discuss the pathogenesis, clinical features and prevention of DDS.

BACKGROUND: Dialysis disequilibrium syndrome (DDS) is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD). We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD.

CASE PRESENTATION: A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L). Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L) (urea-reduction-ratio 71%). Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared.

CONCLUSIONS: Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

The methodology, prescription, and delivery of acute renal replacement therapy are rapidly evolving areas. Recent clinical trials have provided clearer guidance around dosing targets for both therapy prescription and delivery. In this article, we discuss dialysis efficiency which is an area that subserves dialysis dose and pertains to manner in which a given dose is delivered. Dialysis efficiency directly effects the measurement and calculation of dose, and the occurrence of dialysis disequilibrium and hemodynamic instability. We provide recommendations around selecting the most appropriate clinical scenario and patients for higher-efficiency versus lower-efficiency therapy, and the implementation of therapy to achieve a given efficiency.