Acute Complications of Hemodialysis

1. Acute Complications of Hemodialysis

2. ★ Intradialytic hypotension • Definition: A decrease in systolic BP ≥20 mm Hg or a decrease in MAP ≥ 10 mm Hg associated with symptoms. • Complication: cardiac arrhythmias, coronary and/or cerebral ischemic events • Long-term side effects: volume overload due to suboptimal ultrafiltration, LVH, and interdialytic hypertension K-DOQI guildline

3. Risk Factors of Dialysis Hypotension • A third of dialysis patients • Low body mass • Poor nutritional status and hypoalbuminemia • Severe anemia • Advanced age (Age > 65 years old) • Cardiovascular disease • Large interdialysis weight gain • Low blood pressure (predialysis systolic BP <100 mm Hg)

4. Etiology of Dialysis Hypotension (I) • Excessive rate and degree of ultrafiltration • Inappropriate peripheral venodilation • Autonomic dysfunction • Inadequate vasoconstrictor secretion

5. Etiology of Dialysis Hypotensoin (II) • Acetate dialysate • Low calcium dialysate • Eat shortly before dialysis • Antihypertensive medications • LV dysfunction

6. PATHOGENESIS MEDIATORS PATIENT PATHOPHYSIOLOGY Heart Disease CARDIAC OUTPUT Volume Ultrafiltration Vascular Disease Osmolality Fall Vasopressors Autonomic Dysfunction Vasodilatator Warm Dialysate PERIPHERAL RESISTANCE Hormonal Dysfunction Cell Dysfunction Bio-incom- patibility Medications Complement Activation, Cytokine release Endotoxin Sepsis Infection HYPOTENSiON Acetate Infusion Hypoxemia Vasovagal stim.

7. Table. Results of four tests of autonomic function in normotensive and hypotensive patients on maintenance hemodialysis Before Dialysis After Dialysis Test Normotensive Hypotensive Normotensive Hypotensive Orthostasis (standing up) ∆SBP (mmHg) -3.7 ± 2.7 -14.1 ± 2.6* -6.0 ± 2.7 -16.0± 3.1† ∆DBP (mmHg) -4.6 ± 1.6 -11.5 ± 1.4* -4.3 ± 1.7 -10.0 ± 1.7† 30:15 ratio (normal ≥ 1.04) 1.045 ± 0.02 1.023 ± 0.014 1.036 ± 0.015 1.023 ± 0.011 Valsalva quotient (normal ≥ 1.21) 1.060 ± 0.025 1.024 ± 0.014 1.102 ± 0.028 1.012± 0.029† Sustained handgrip (normal ≥15) ∆DBP (mmHg)5.8 ± 2.3 7.1 ± 0.7 7.2 ± 1.1 6.8 ± 0.7 Cutaneous cold ∆SBP (mmHg) 6.8 ± 1.4 7.1 ± 1.2 5.9 ± 1.0 5.6 ± 0.8 ∆DBP (mmHg)5.1 ± 1.3 4.9 ± 1.4 4.5 ± 0.9 4.4 ± 0.7 Lin YF, Wang JY et al., ASAIO 39:946-953, 1993.

8. BV (%)  cGMP (pmol/ml)  Fig. Correlation between changes in blood volume and plasma cGMP throughout HD. Wann GL. Lin YF. ASAIO 44:M569, 1998.

9. Plasma NO2- + NO3- (mM/l) Fig. Plasma levels of nitrite and nitrate in hypotensive and normotensive patients on hemodialysis. Lin SH. ASAIO J 42:M895, 1996.

10. Accurate Estimation of Dry Weight • cGMP, ANP • IVCD • Continuous monitoring of BV • Bioimpedence ECF/TBW

11. Prevention and Management of Dialysis Hypotension (I) • Limiting sodium intake • Minimize interdialytic weight gain by education • Blood sugar control • Slow ultrafiltration • Sodium modeling • Raise dialysate calcium • Lower dialysate temperature

12. Prevention and Management of Dialysis Hypotension (II) • Switch to CAPD • Hyperoncotic albumin • Nasal oxygen • Mannitol infusion

13. Prevention and Management of Dialysis Hypotension (III) • L-Carnitine therapy • Sertraline • Midodrine • Blood transfusion or erythropoietin therapy • Volume expansion • Vasoconstrictor

14. p < 0.005 Number of Hypotensive episodes Fig. Number of hypotensive episodes per hemodialysis session in the sertraline and pre-sertraline periods. Dheenan S. AJKD 31:624, 1998.

15. Figure. Serial changes in MAP HD before ( ) and after ( )midodrine therapy. YF Lin et al. Am J Med Sci 2003;325:256-61.

16. Conclusion and clinical application • Midodrine improves chronic hypotensin in HD patients by modulating autonomic function and its direct effects on peripheral vessels.

17. Table. Carnitine levels in patients with (n=8) and without (n=23) intra-dialytic hypotension Without hypotension With hypotension Total carnitine (mml/l) 27.0 ± 2.7 18.4 ± 2.2* Free carinitine (mmol/l) 18.8 ± 2.0 10.9 ± 1.7** Acyl/free carnitine ratio 0.58 ± 0.06 0.78 ± 0.15 Values are mean ± SEM, * p < 0.05, ** p < 0.01 vs without hypotension Riley S. Clin Nephrol 48:392, 1997.

18. Hypoxemia • Alkali attenuate hyperventilation • Acetate dialysate • Complement activation • Pulmonary leukosequestration • Actin polymerization • Biocompatible hollow fiber

19. Muscle Cramps • 35-86%of hemodialysis patients • Lower extremities • Mechanisms: Rapid ultrafiltration, Intradialytic hypotension, tissue hypoxia • Treatment: Quinine, Vit E, L-carnitine, Creatine monohydrate, Sodium modeling, hypertonic solution

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21. Acute Allergic Reaction • First use syndrome • Burning retrosternal pain • Diffuse heat, cold perspiration, urticaria, pruritus, laryngeal strider, bronchospasm, loss of consciousness • Polyurethane function as a reservoir for ethylene oxide

22. ** * Serum C3a (ng/ml) ** Fig. Comparisons of serum C3a levels during hemodialysis procedure with different dialysis membrane. (* p< 0.05, ** p<0.01 vs baseline)

23. * * WBC (/cumm) ** Fig. Comparisons of WBC levels during hemodialysis procedure with different dialysis membrane. (* p< 0.05, ** p<0.01 vs baseline)

24. TNF-a (pg/ml/2 x 106 monocytes) Fig. Comparisons of TNF-a production by zymoxan-stimulationed Monocytes between Cuprophan and PMMA hollow fiber before, at the 15th minute of and at the end of dialysis. NC= Normal control. ** p<0.01 between two hollow fibers, +++ p<0.001 among three time periods. YF Lin. Am J Nephorl 16:293, 1996.

25. Table. Clinical relevance of cytokine production in hemodialysis patients Acute Chronic Fever Anemia Sleep disorders Bone disease Hypotension Malnutrition Immunological dysfunction Pertosa G KI 58 suppl 76:S104, 2000.

26. Fig. Relationship between interleukin-6 (IL-6) production by peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039) Goicoechea M KI 54:1337, 1998.

27. Serum b2 microglobulin (mg/L) * * * * Fig. Comparisons of serum b2M during hemodialysis procedure with different dialysis membrane. (* p< 0.05 vs baseline)

28. ★ Uremic Pruritus (I) • 50-90%of dialysis patients • Risk: male, high serum BUN, Ca, P, β2-microglobulin, duration of dialysis • Diagnositc criteria

29. ★ Pathogenesis • Pruritogenic substancemast cell release histamine, IL-2, …cascade of nerve conduction to induce in perception of itch

30. ★ Causes of itching in ESRD

31. ★ Uremic Pruritus (II) Topical treatment (a) Skin emollients (b) Capsaicin (c) Topical steroids Physical treatment (a) Phototherapy (b) Acupuncture (c) Sauna Systemic treatment (a) Low-protein diet (b) Primrose oil (c) Lidocaine and mexilitine (d) Opioid antagonists (e) Activated charcoal (f) Cholestyramine (g) Serotonin antagonists (h) Parathyroidectomy (i) Nalfurafine • Optimize the dialysis dose • Treat anemia • Treat 2nd hyperparathyroidism • Ultraviolet B phototherapy • Topical emollients • Capsaicin • Antihistamine • Anti-serotonin agents

32. Table. Degree of pruritus on capsaicin therapy Degree of pruritus None Mild Moderate Severe Before treatment 0 0 8 9 After treatment * 5 9 1 2 8 weeks postreatment 4 5 5 3

33. ★ κ-opoid receptor agonist-Nalfurafine

34. ★ Arrhythmia (I) • 30-48%of dialysis patients • Risk factor: ▲Compromised myocardium: CAD, Intermyocardiocytic fibrosis, Pericarditis ▲ Increased QT interval or dispersion

35. ★ Arrhythmia (II) ▲ Electrolyte imbalance: hypokalemia, hyperkalemia, hypercalcemia, hypermagnesemia ▲ Anemia ▲ Increased LV mass ▲ Advanced age ▲ Acetate dialysate

36. 500 P < 0.001 450 400 350 0 Contol (n=30) HD (n=42) Fig. Distribution of QTc values among hemodialysis patients and controls. The mean value of QTc was significantly increased in hemodialysis patients (432.6 ± 24.9 ms) compared controls (402.0 ± 21.0 ms) (p<0.01) Suzuki R. Clin Nephrol 49:240, 1998.

37. Table. Independent predictors of QTc interval by multivariate stepwise regression analysis Variable Coefficient Standard error T value P value Diabetes mellitus 25.773 6.203 4.155 0.0002 Ejection fraction -111.18 42.546 -2.613 0.0127 (Constant) 494.6 28.929 17.097 Independent factor: QTc interval R2 = 0.497 Suzuki R. Clin Nephrol 49:240, 1998.

38. Results of 24-Hour Holter ECG Monitoring Arrhythmias Seen No. of Tapes (%) Ventricular ectopic beats (> 20/hr) 15 (24) Ventricular ectopic beats (> 100/hr) 2 (3) Episodes of ventricular tachycardia 5 (8) Epidoses of supraventricular tachycardia 2 (3) Episodic atrial fibrillation 7 (11) Heart block (intermittent) 1 (1.6) Jassal SV AJKD 30:219, 1997.

39. Bleeding During Dailysis (I) • Platelet dysfunction • Impaired dense granule release of ATP and serotonin • Reduced synthesis of thromboxane A2 • Elevated platelet cytosolic cAMP and calcium • Impaired aggregation response

40. Bleeding During Dialysis (II) • Altered adhesive fibrinogen and vWf • Impaired fibrinogen receptor (GPIIbIIIa) function • Uremic toxin or inhibitors • Erythropoietin augments GPIIbIIIa

41. Bleeding During Dialysis (III) • Pack RBC • Cryoprecipitate, FFP(VIII/vWF) • dDAVP • Estrogen

42. Air Embolism • 1 ml/kg air may be fatal • Occlude RV outflow tract and pulmonary vascular bed • Thromboxane B2, endothelin • Trendelenburg position with left side down • Withdrawal of air from RA • Hyperbaric oxygen

43. ★ Dialysis Pericarditis I • Uremic pericarditis: pericarditis before RRT or within 8 weeks of its initiation. • Dialysis pericarditis: ≥ 8 weeks after initiation of RRT. • Incidence of dialysis pericarditis: 2-12% • Etiology: inadequate dialysis, volume overload, infection, autoimmune, drugs

44. Dialysis Pericarditis II • Precordial pain, hypotension, dyspnea, fever, weight gain • Heparin free dialysis • Intensive dialysis • NSAID • Subxiphoid pericardiostomy

45. Dialysis Disequilibrium (I) • Headache, vomiting, seizure, delirium • Rapid correction of marked azotemia • Cerebral swelling • Reverse urea effect • Acidosis of the CSF

46. Dialysis Disequilibrium (II) • Inefficient dialysis • Shorten the duration • Lower dialyzer blood flow • Less efficient dialyzer • Osmotic agents, high sodium • IV diazepam

47. Metabolic Disorders • Metabolic alkalosis • Sodium citrate • Falty delivery of a buffer base • Fluoride poisoning • Acute cupper intoxication

48. Sodium Disorders • Conductivity limits are not adjusted • Water intoxication • Hyperkalemia • Metabolic acidosis • Correction of hyponatremia • Drink water, 5% G/W for hypernatremia

49. Hypokalemia • Loss into dialysate, alkali therapy • Renal or extrarenal losses • Arrhythmia, hypotension, fatigue, weakness, paralysis • CAD, digitalis, hypercalcemia, hypomagnesemia, meta alkalosis • Adjust dialysate potassium and buffer

50. Hyperkalemia • Dietary intake • GI bleeding • Overheated or hypotonic dialysate • Chloramine, sodium hypochlorite, fluoride • Medications • Metabolic acidosis