Acute Complications of Hemodialysis
Intradialytic hypotension ★ 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
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)
Etiology of Dialysis Hypotension (I) Excessive rate and degree of ultrafiltration Inappropriate peripheral venodilation Autonomic dysfunction Inadequate vasoconstrictor secretion
Etiology of Dialysis Hypotensoin (II) Acetate dialysate Low calcium dialysate Eat shortly before dialysis Antihypertensive medications LV dysfunction
CARDIAC OUTPUT PERIPHERAL RESISTANCE HYPOTENSiON PATHOGENESIS MEDIATORS PATHOPHYSIOLOGY PATIENT CARDIAC OUTPUT Heart Disease 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.
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.
BV (%) cGMP (pmol/ml) Fig. Correlation between changes in blood volume and plasma cGMP throughout HD. Wann GL. Lin YF. ASAIO 44:M569, 1998.
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.
Accurate Estimation of Dry Weight cGMP, ANP IVCD Continuous monitoring of BV Bioimpedence ECF/TBW
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
Prevention and Management of Dialysis Hypotension (II) Switch to CAPD Hyperoncotic albumin Nasal oxygen Mannitol infusion
Prevention and Management of Dialysis Hypotension (III) L-Carnitine therapy Sertraline Midodrine Blood transfusion or erythropoietin therapy Volume expansion Vasoconstrictor
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.
Figure. Serial changes in MAP HD before ( ) and after ( )midodrine therapy. YF Lin et al. Am J Med Sci 2003;325:256-61.
Conclusion and clinical application Midodrine improves chronic hypotensin in HD patients by modulating autonomic function and its direct effects on peripheral vessels.
Table. Carnitine levels in patients with (n=8) and without (n=23) 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.
Hypoxemia Alkali attenuate hyperventilation Acetate dialysate Complement activation Pulmonary leukosequestration Actin polymerization Biocompatible hollow fiber
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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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
** * 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)
* * ** WBC (/cumm) Fig. Comparisons of WBC levels during hemodialysis procedure with different dialysis membrane. (* p< 0.05, ** p<0.01 vs baseline)
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.
Sleep disorders Bone disease Hypotension Malnutrition 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.
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.
* * * * Serum b2 microglobulin (mg/L) Fig. Comparisons of serum b2M during hemodialysis procedure with different dialysis membrane. (* p< 0.05 vs baseline)
★ Uremic Pruritus (I) 50-90% of dialysis patients Risk: male, high serum BUN, Ca, P, β2-microglobulin, duration of dialysis Diagnositc criteria
Pathogenesis ★ Pruritogenic substancemast cell release histamine, IL-2, …cascade of nerve conduction to induce in perception of itch
Causes of itching in ESRD ★
★ Uremic Pruritus (II) Optimize the dialysis dose Treat anemia Treat 2nd hyperparathyroidism Ultraviolet B phototherapy Topical emollients Capsaicin Antihistamine Anti-serotonin agents 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
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
κ-opoid receptor agonist-Nalfurafine ★ κ-opoid receptor agonist-Nalfurafine
★ Arrhythmia (I) 30-48% of dialysis patients Risk factor: ▲ Compromised myocardium: CAD, Intermyocardiocytic fibrosis, Pericarditis ▲ Increased QT interval or dispersion
★ Arrhythmia (II) ▲ Electrolyte imbalance: hypokalemia, hyperkalemia, hypercalcemia, hypermagnesemia ▲ Anemia ▲ Increased LV mass ▲ Advanced age ▲ Acetate dialysate
350 400 450 500 P < 0.001 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. Contol (n=30) HD (n=42)
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.
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.
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
Bleeding During Dialysis (II) Altered adhesive fibrinogen and vWf Impaired fibrinogen receptor (GPIIbIIIa) function Uremic toxin or inhibitors Erythropoietin augments GPIIbIIIa
Bleeding During Dialysis (III) Pack RBC Cryoprecipitate, FFP(VIII/vWF) dDAVP Estrogen
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
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
Dialysis Pericarditis II Precordial pain, hypotension, dyspnea, fever, weight gain Heparin free dialysis Intensive dialysis NSAID Subxiphoid pericardiostomy
Dialysis Disequilibrium (I) Headache, vomiting, seizure, delirium Rapid correction of marked azotemia Cerebral swelling Reverse urea effect Acidosis of the CSF
Dialysis Disequilibrium (II) Inefficient dialysis Shorten the duration Lower dialyzer blood flow Less efficient dialyzer Osmotic agents, high sodium IV diazepam
Metabolic Disorders Metabolic alkalosis Sodium citrate Falty delivery of a buffer base Fluoride poisoning Acute cupper intoxication
Sodium Disorders Conductivity limits are not adjusted Water intoxication Hyperkalemia Metabolic acidosis Correction of hyponatremia Drink water, 5% G/W for hypernatremia
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
Hyperkalemia Dietary intake GI bleeding Overheated or hypotonic dialysate Chloramine, sodium hypochlorite, fluoride Medications Metabolic acidosis
Hypophosphatemia Intensive dialysis Phosphorus binders Reduced intake Dysfunction of erythrocytes, CNS, skeletal and cardiac muscle Phosphorus rich food
Hypercalcemia (I) Liberation of calcium from bone Intradialytic gain Phosphorus binders Widespread use of calcitriol Aluminum poisoning
Hypercalcemia (II) Low dialysate calcium Phosphorus binders during meals Discontinue vitamin D Therapy Treat aluminum toxicity Pamidronate
Fluoride Contamination Faulty RO and deionization Bring down calcium and magnesium Vomiting, abdominal pain, cardiac irritability Muscle twitching, tetany, petechiae bleeding Respiratory failure, hypotension, cardiac arrest Metabolic, respiratory acidosis
Chloramine Contamination Less than 0.1 mg/L Oxidize hemoglobin to form methemoglobin Appropriate charcoal filters Vitamin C
Endotoxin Bacterial infections Bicarbonate dialysate conc. Endogenous pyrogens Header syndrome Disinfection of the O rings Backfiltration with high flux dialysis
Hypertensive Emergencies Paradoxical, hypertensive response Rise in plasma catecholamine Activation of renin-angiotensin system Antihypertensive withdrawal Sublingual captopril and nifedipine
Bowel Ischemia Abdominal pain, acute diarrhea Dialysis hypotension Digitalis, b blockers Occlusive and non-occlusive infarction (25 to 60%) Congestive heart failure Cardiac arrhythmia (esp. AF) ESRD Hyperkalemia, acidemia, leukocytosis elevated LDH and CPK
Table. Location of Mesenteric Infarction Location No. of Patients (n=12) Small bowel 1 Colon 1 Cecum 2 Sigmoid 3 Ileocecal and distal transverse colon 1 Diffuse involvement Large bowel 1 Small and large bowel 1 Distal ileum and right colon 1 Diamond SM. JAMA 256:2545, 1986.
Table. Pertinent History and Medications (I) Clinical Characteristic Bowel Infarction Controls Heart disease Coronary artery disease 7 8 By conornary angiography 4 3 Angina 5 4 Myocardial infarctions 2 1 Congestive heart failure 2 1 Atrial arrhythmias 3 2 Diabetics with heart disease 2 3 Diamond SM. JAMA 256:2545, 1986.
Table. Pertinent History and Medications (II) Clinical Characteristic Bowel Infarction Controls Cardiac medications, No. of patients 6 5 Digoxin 3 1 b-Blockers 2 1 Calcium antagonists 3 4 Episodes of hypotension when 4 3 undergoing dialysis Frequent and/or severe hypotension 4 1 when undergoing dialysis * Diagnosis of severe atherosclerosis 3 1 Diamond SM. JAMA 256:2545, 1986.
Table. Laboratory Values in Bowel Infarction Group Findings No. of Patients (n=12) White blood cell count > 15 000 mm3 ( >15 x 109 /L) 2 > 20 000 mm3 ( > 20 x 109 /L) 6 Hematocrit Increase by 10% (0.10) 1 Increase by 20% (0.20) 3 pH < 7.1 4 < 7.2 1 7.2-7.35 2 7.35-7.45 2 Potassium, mEq/L (mmol/L) > 7.0 4 > 5.0 2 Bicarbonate, mEq/L(mmol/L) < 10 5 < 15 1 < 20 4 Diamond SM. JAMA 256:2545, 1986.