Dialyisis disequilibrium syndrome

Dialyisis disequilibrium syndrome

1. DIALYISIS DISEQUILIBRIUM SYNDROME

2. . The disequilibrium syndrome is a set of systemic and neurologic symptoms often associated with characteristic electroencephalographic findings that can occur either during or following dialysis The dialysis disequilibrium syndrome (DDS) is characterized by a range of mostly neurologic symptoms from mild to severe that affect patients on hemodialysis, particularly when they are first started on dialysis . A lso seen among patients who have missed multiple consecutive dialysis treatments.  Rare among patients with CRRT.

3. RISK FACTORS ● First hemodialysis treatment ● Markedly elevated blood urea nitrogen (BUN) concentration prior to a dialysis session ( eg , >175 mg/ dL or 60 mmol /L) ● Extremes of age ● Pre-existing neurologic diseases (head trauma, stroke, seizure disorder)

4. ●Concomitant presence of other conditions that could be associated with cerebral edema (such as hyponatremia, hepatic encephalopathy, or hypertensive emergency) ●Concomitant presence of another condition associated with increased permeability of the BBB (such as sepsis, vasculitis, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, encephalitis, or meningitis)

5. PATHOGENESIS Reverse osmotic shift due to urea   –RAPID AND ACUTE REDUCTION IN UREA AND OTHER SOLUTES-- TRANSIENT OSMOTIC GRADIENT BETWEEN PLASMA AND BRAIN CELLS- leads to water shift into neurons that produces cerebral edema . The change in the ratio of CSF to blood urea corresponded to an increase in CSF osmolality , thereby increasing intracranial pressure and leading to neurological manifestations

6. Urea is generally considered an "ineffective" osmole because of its ability to permeate cell membranes. However , equilibration of urea across cell membranes may take several hours to reach completion. In the setting of dialysis, where urea is swiftly moved out of the circulation, its continued presence in tissues including brain cells may exert an osmotic force, drawing water into the cells and producing cerebral edema . This force is further enhanced by an adaptive increase in the water channels and decrease in the urea channels in response to uremia

7. Reverse osmotic shift due to other osmoles  –  the fall in the intracellular pH of brain cells increase in brain organic osmolytes increase in carbon dioxide (CO2) retention after dialysis with a higher bicarbonate dialysate The fall in intracellular pH can cause sodium and potassium that are bound to proteins to dissociate, thereby rendering them osmotically active.

8. BACKGROUND The reflection coefficient of urea at the blood–brain barrier is 0.44.  Rapid urea transit across cell membranes is facilitated by urea transporters (UTs). There are essentially two classes of UTs, encoded by two genes, each having several isoforms. Urea transporter A (UT-A) localizing primarily to the kidneys, heart, liver, testis, and colon, whereas urea transporter B (UT-B) has two isoforms localizing to red blood cells, vasa recta and the brain. Renal failure results in accumulation of urea in the bloodstream and subsequent increase in brain and CSF urea concentrations.

9. In the brain, AQP1 localizes to the epithelial cells of the choroid plexus while AQP4 and AQP9 are found on astrocytes, ependymal cells Thus , AQPs are important for water movement across the blood–brain barrier and brain–CSF interface THUS THE SUDDEN REMOVAL OF UREA UPREGULATES BOTH AQP4 AND UT-B CHANNELS AND THUS DDS OCCURS

10. Mild symptoms are usually self-limited in most patients. They include headache , nausea, blurred vision, and restlessness that can progress to somnolence, confusion, disorientation, or mania. severe manifestations can include seizures, stupor, coma, and death .

11. DIAGNOSIS It is a clinical DIAGNOSIS The diagnosis of DDS is one of exclusion . Other disorders that must be excluded are conditions that cause altered mental status, such as uremia itself, subdural hematoma, cerebral infarction, intracerebral hemorrhage , meningitis, metabolic disturbances (hyponatremia, hypoglycemia ), posterior reversible encephalopathy syndrome, and drug-induced encephalopathy .

12. PREVENTION Limiting removal of urea by dialysis can prevent large osmotic shifts To initiate 1 st session of hemodialysis with a two-hour session using a blood flow of 150 to 250 mL/min and a dialysate flow that is two times the blood flow rate. ●To dialyze patients for their second and third session on consecutive days following their first session

13. Among patients who did not experience symptoms and signs of DDS during the first dialysis session, we increase the blood flow (and correspondingly the dialysate flow) by 50 mL/min and dialysis time by 30 minutes for the second treatment . If symptoms and signs of DDS occurred during the first session, we similarly increase the intensity but also perform sodium modeling. ●For the third treatment, we increase the blood flow to a maximum of 400 mL/min, dialysate flow to 800 mL/min, and dialysis time to a maximum of four hours and then continue it

14. ●If the dialysis machine has sodium modeling capability, then we use either linear or exponential modeling profiles. The initial and final dialysate sodium concentrations vary depending upon the expected urea clearance during the treatment. As an example, if 50 percent urea clearance is expected, we set the initial dialysate sodium to be 15 mEq /L higher than the patient's predialysis serum sodium and the final dialysate sodium to be 5 mEq /L higher than the patient's predialysis serum sodium . If more robust urea clearance is anticipated, we set higher values; if less urea clearance is expected, we set lower values .

15. ●If the dialysis machine does not have sodium modeling capability, then (if 50 percent urea clearance is expected) we dialyze using a dialysate sodium that is 10 mEq /L higher than the patient's predialysis serum sodium . As above, we use a higher sodium bath if more robust urea clearance is anticipated, and a lower sodium bath if less urea clearance is expected.

16. Additional measures in patients with carbon dioxide retention   chronic obstructive pulmonary disease ( COPD) use a dialysis bicarbonate concentration of 30 mEq /L rather than the standard 35 mEq /L. CO2 is a potent cerebral vasodilator and can provoke an increase in intracranial pressure .

17. TREATMENT Mostly symptomatic Spontaneous resolution within 24 hours Sodium modelling Among patients with persistent severe DDS (such as seizures, encephalopathy, or coma) despite the use of sodium modeling, a trial of hypertonic  saline  or  mannitol  is reasonable, To use either 5 mL of 23 percent saline or 12.5 g of mannitol to rapidly raise the serum osmolality and to prevent further osmotic shifts. 

18. Once hypertonic  saline  or  mannitol  has been administered, we stop dialysis and plan for daily, short low-efficiency dialysis sessions, similar to patients being newly initiated on dialysis

19. ACUTE DIALYSIS SETTING The target reduction in the plasma urea nitrogen level should initially be limited to about 40%. Use of a low-sodium dialysis solution (more than 2–3 mM less than the plasma sodium level) may exacerbate cerebral edema and should be avoided. In hypernatremic patients, one should not attempt to correct the plasma sodium concentration and the uremia at the same time. It is safest to dialyze a hypernatremic patient initially with a dialysis solution sodium value close to the plasma level and then to correct the hypernatremia slowly postdialysis by administering 5% dextrose.

20. CHRONIC DIALYSIS SETTING The incidence of disequilibrium syndrome can be minimized by use of a dialysis solution with a sodium concentration of at least 140 mM. Using a high dialysis solution sodium concentration (145–150 mM ) that declines over the course of treatment for patients has been advocated in this setting: the initially high dialysis solution sodium results in a rising plasma sodium that may counteract the osmotic effects of the initially rapid removal of urea and other solutes from plasma .