1. Intradialytic Hypotension Fadel A. AlRowaie, MD,FACP,FNKF Assistant Professor of Medicine (KSAU-HS) Consultant Nephrologist Head of Nephrology (KFMC)

2. Outline Introduction – Definition – Epidemiology – Clinical consequences Pathogenesis – Water movement and vascular refilling – Cardiovascular response to UF Interventions to reduce intra-dialytic hypotension

3. Schreiber MJ Jr. Am J Kidney Dis. 2001 Oct;38(4 Suppl 4):S37-47 Clinical scenario UF stopped Qb reduced IVF 250 cc 0.9NS

4. Introduction Hypotension that require nursing intervention or medical treatment occurs in 10-30% of hemodialysis treatment (HEMO study :18.3% vs. 16.8% ) McCausland FR, et al.Am J Nephrol. 2013;38(5):388-96

5. Intra-dialytic Hypotension (IDH) is defined as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg associated with symptoms & need for nursing intervention  K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005 Apr;45(4 Suppl 3):S1-153  Kooman J, Basci A et al. EBPG guideline on haemodynamic instability. Nephrol Dial Transplant. 2007 May;22 Suppl 2:ii22-44.

6. Clinical significance Increased mortality Access thrombosis Under-dialysis and volume overload Organs ischemia ( MI, CVA and ischemic bowel) Increase nursing intervention

7. Always consider and exclude the following serious conditions: Arrhythmia Pericardial tamponade Valvular disorders Myocardial infarction Hemolysis & hemorrhage Septicemia Air embolism

8. Shoji T. et al. Kidney Int. 2004 Sep;66(3):1212-20

9. Vascular access thrombosis is more frequent with grafts than with fistulas. Chang T I et al. JASN 2011;22:1526-1533 ©2011 by American Society of Nephrology

10. Subjects with more frequent episodes of intradialytic hypotension are more likely to experience vascular access thrombosis. Chang T I et al. JASN 2011;22:1526-1533 ©2011 by American Society of Nephrology

11. Pathogenesis of IDH

12. DialyzerECF ICF Water movementStep 1 Step 2 Step 3 Loss of urea/H2O 280 Osmolality 320 mosmol/kg Osmolality 320 mosmol/kg failing to 290 mosmol/kg as diffusion occurs Water movement during hemodialysis

13. Stroke volume X Heart rate

14. Cardiovascular responses to plasma volume depletion. Reilly R F CJASN doi:10.2215/CJN.09930913 ©2014 by American Society of Nephrology

15. Patients at risk of IDH 65 years or older age DM Patients with CVD: – LVH and diastolic dysfunction with or without CHF – LV systolic dysfunction and CHF – Valvular heart disease – Pericardial disease (constrictive pericarditis or pericardial effusion) Poor nutritional status and hypoalbuminemia Hyperphosphatemia Uremic neuropathy or autonomic dysfunction due to other causes Severe anemia Patients requiring high volume ultrafiltration; more than expected interdialytic weight gain Patients with predialysis SBP of <100 mm Hg

16. Acute Management of IDH Reduce the rate or stop the ultrafiltration Place patient in Trendelenburg position Reduce blood flow IVF 250 ml of 0.9 % NS bolus (can be repeated) / albumin & manitol are alternatives Exclude serious condition

17. Knoll GA. J Am Soc Nephrol. 2004 Feb;15(2):487-92 Albumin Vs. Saline for treatment of IDH

18. Interventions to reduce intra-dialytic hypotension Patient related intervention – Accurate setting of the "dry weight“ – Minimize inter- dialytic weight gain – Reduction of salt intake to 2g/ 90 mmol Na per day (6 g/d NaCl) – Avoidance of food during dialysis – Avoid antihypertensive medicines on dialysis day Dialysis related intervention – High dialysate Na / Na profiling – Sequential ultrafiltration and isovolemic dialysis – Blood volume monitoring & biofeed back dialysis – Low dialysate temperature – Bicarbonate buffer – High dialysate Ca++ – Hemofiltration and hemodiafiltration – Prolonged & frequent dialysis Pharmacological intervention – Midodrine – Carnitine

19. DialyzerECF ICF Water movementStep 1 Step 2 Step 3 Iso-osmotic loss of solutes/H2O Osmolality 320 mosmol/kg Osmolality 320 mosmol/kg with raising plasma oncotic pressure Water movement during isolated ultrafiltration

22. Change in Na & weight post dialysis

24. Reddan DN et al.J Am Soc Nephrol. 2005 Jul;16(7):2162-9

30. Nesrallah GE et al.Nephrol Dial Transplant. 2013 Jan;28(1):182-9 1 Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis

31. Guideline 3.1.2a Individualized, automatic BV control should be considered as a second-line option in patients with refractory IDH (Evidence level II). Guideline 3.1.2b Manual adjustment of ultrafiltration according to a fixed protocol based on changes in blood volume should not be performed (Evidence level II). Kooman J, Basci A et al. Nephrol Dial Transplant. 2007 May;22 Suppl 2:ii22-44.

32. Low dialysate temperature There are two different ways of reducing dialysate fluid temperature: Empiric fixed reductions of dialysate temperature Isothermic dialysis, a technique in which body temperature remains constant via the use of a biofeedback temperature-controlled device

33. Jost CM et al.Kidney Int. 1993 Sep;44(3):606-12.

34. Selby NM et al.Nephrol Dial Transplant. 2006 Jul;21(7):1883-98

35. Bicarbonate dialysate vs. Acetate Thaha M. et al.Acta Med Indones. 2005 Jul-Sep;37(3):145-8

36. High calcium dialysate & Ca profiling Kyriazis J et al. Kidney Int. 2002 Jan;61(1):276-87

38. Alappan R et al. Am J Kidney Dis. 2001 Feb;37(2):294-9. The addition of High Dialysate Ca to midodrine and/or cool dialysate further improves blood pressure in patients with IDH. However, this therapy did not reduce symptoms or interventions required for IDH. In addition, hypercalcemia complicated this therapy in 22% of the patients.

39. Midodrine Midodrine is an oral prodrug with selective α-1 adrenergic agonist activity. The drug was released into clinical practice in 1996 as a new treatment for patients with symptomatic orthostatic hypotension. is rapidly absorbed in the GIT and converted to the active metabolite, desglymidodrine, in the systemic circulation The prodrug achieves peak levels in 60 minutes. The absolute bioavailability of desglymidodrine is 93% for oral tablets, and it reaches peak levels in approximately 60 to 90 minutes. Excretion of the drug is primarily renal, the half-life of desglymidodrine, is 3.5 hours on HD & 9 hours on nondialysis days The major adverse events were piloerection (13%) and pruritis (10%) Midodrine is an oral prodrug with selective α-1 adrenergic agonist activity. The drug was released into clinical practice in 1996 as a new treatment for patients with symptomatic orthostatic hypotension. is rapidly absorbed in the GIT and converted to the active metabolite, desglymidodrine, in the systemic circulation The prodrug achieves peak levels in 60 minutes. The absolute bioavailability of desglymidodrine is 93% for oral tablets, and it reaches peak levels in approximately 60 to 90 minutes. Excretion of the drug is primarily renal, the half-life of desglymidodrine, is 3.5 hours on HD & 9 hours on nondialysis days The major adverse events were piloerection (13%) and pruritis (10%) Perazella MA.Am J Kidney Dis. 2001 Oct;38(4 Suppl 4):S26-36

40. Prakash S. Nephrol Dial Transplant. 2004 Oct;19(10):2553-8

41. Comparison between various interventions to prevent IDH Dheenan S. Kidney Int. 2001 Mar;59(3):1175-81

43. o First-line approach o Dietary counselling (sodium restriction). o Refraining from food intake during dialysis. o Clinical reassessment of dry weight. o Use of bicarbonate as dialysis buffer. o Use of a dialysate temperature of 36.5°C. o Check dosing and timing of antihypertensive agents o First-line approach o Dietary counselling (sodium restriction). o Refraining from food intake during dialysis. o Clinical reassessment of dry weight. o Use of bicarbonate as dialysis buffer. o Use of a dialysate temperature of 36.5°C. o Check dosing and timing of antihypertensive agents Second-line approach o Try objective methods to assess dry weight. o Perform cardiac evaluation. o Gradual reduction of dialysate temperature from 36.5°C downward (lowest 35°C) or isothermic treatment (possible alternative: convective treatments). o Consider individualized blood volume controlled feedback. o Prolong dialysis time and/or increase dialysis frequency. o Prescribe a dialysate calcium concentration of 1.50 mmol/l. Second-line approach o Try objective methods to assess dry weight. o Perform cardiac evaluation. o Gradual reduction of dialysate temperature from 36.5°C downward (lowest 35°C) or isothermic treatment (possible alternative: convective treatments). o Consider individualized blood volume controlled feedback. o Prolong dialysis time and/or increase dialysis frequency. o Prescribe a dialysate calcium concentration of 1.50 mmol/l. Third-line approach (only if other treatment options have failed) o Consider midodrine. o Consider l-carnitine supplementation. o Consider peritoneal dialysis. Third-line approach (only if other treatment options have failed) o Consider midodrine. o Consider l-carnitine supplementation. o Consider peritoneal dialysis. EBPG guideline on haemodynamic instability Kooman J, Basci A et al. Nephrol Dial Transplant. 2007 May;22 Suppl 2:ii22-44.

44. Dialysate sodium Guideline 3.2.1 : Although sodium profiling with supraphysiological dialysate sodium concentrations and high sodium dialysate (≥144 mmol/l) are effective in reducing IDH, they should not be used routinely because of an enhanced risk of thirst, hypertension and increased inter-dialytic weight gain (Evidence level II).

45. falrowaie@kfmc.med.sa @fadelrowaie