End Stage Renal Disease and Renal Replacement Therapies

Transcription

1 End Stage Renal Disease and Renal Replacement Therapies Alexander J. Ansara,, Pharm. D. St. Louis College of Pharmacy and St. Luke s Hospital Therapeutics 1 Fall 2003 Required Reading Materials Dipiro Chapter 47, pp Ifudu O. Care of Patients Undergoing Hemodialysis.. N Engl J Med 1998; 339: Supplemental Pastan S, Bailey J. Dialysis Therapy. N Engl J Med 1998; 338:

2 Epidemiology Overall incidence ESRD: 240/million pts 180/million caucasian patients 758/million african american patients US population with ESRD: > 200,000 pts on any dialysis 20,000 pts on peritoneal dialysis > 70,000 pts with functioning transplants Prevalence Increasing at 7-9% 7 per year Estimated 600,000 dialysis patients by 2010 # transplants remainining stable Increasing Prevalence

3 Mortality and Life Expectancy Importance of Prevention Prevention Cardiac deaths #1 cause Peritonitis #2 cause Limited availability of transplants Cost Cost Avg cost/pt/yr $45,000 US expenditure/yr: $15 billion Estimated cost by 2010: $28 billion

4 Treating ESRD Prevention Treat concurrent diseases HTN Diabetes Dialysis Hemodialysis (HD) Peritoneal Dialysis (PD) Renal transplantation Renal Replacement Therapy: Replacing Kidney Functions H 2 0 balance Electrolyte balance Acid/Base balance Waste Removal (urea, creatinine) Filter, reabsorb, secrete substances Plasma proteins, H 2 0, blood cells, amino acids, glucose, urea, mineral salts Endocrine functions Vitamin D activation Erythropoietin production

5 The Vowels of Renal Replacement Therapy INDICATION SETTING Acid Base Abnormality Electrolyte Disturbance Intoxication Fluid Overload Uremia Metabolic acidosis Hyperkalemia/ magnesemia Salicylates,, Li++, Meth- anol,, Ethylene Glycol Post-op op fluid gain, excessive IV fluids BUN accumulation Principles of Hemodialysis Hemodialysis: The removal of nitrogenous wastes, uremic toxins, and water from the blood via diffusion and convection Diffusion: The process of solute transfer from high concentration to low concentration until equillibrium Convection ( ultrafiltration ultrafiltration ): Primary means of removal of excess body H 2 0, maximized by: hydrostatic pressure permeability of membrane

6 Factors Affecting Diffusion Rate Concentration gradient Blood flow rate Dialysis flow rate Dialysis filter composition Solute characteristics Principles of Hemodialysis Hemodialysis: The removal of nitrogenous wastes, uremic toxins, and water from the blood via diffusion and convection Diffusion: The process of solute transfer from high concentration to low concentration until equillibrium Convection ( ultrafiltration ultrafiltration ): Primary means of removal of excess body H 2 0, maximized by: hydrostatic pressure permeability of membrane

7 Convection Low volume filtration: No significant clearance of toxins or drugs Performed to maintain fluid balance Ultrafiltration rate (UFR) < ml/hr Large volume filtration: Significant clearance of urea and drugs Must replace fluid loss to avoid major electrolyte disturbances UFR L/hr Vascular Access Permanent access to bloodstream necessary Native arteriovenous (AV) fistula Synthetic AV vascular grafts

8 Native AV Fistula Fistula between cephalic vein and radial artery 2 months to mature before use Low rate of complications Longest survival (of access) Used less frequently Native AV Fistula

9 Native AV Fistula Fistula between cephalic vein and radial artery 2 months to mature before use Low rate of complications Longest survival (of access) Used less frequently Synthetic AV Vascular Grafts Synthetic graft between brachial artery and basilic vein Made of polytetrafluoroethylene (PTFE), requires weeks to endothelialize Higher rates of infection and thrombosis Shorter device survival Most commonly used

10 Synthetic AV Vascular Grafts Synthetic AV Vascular Grafts Synthetic graft between brachial artery and basilic vein Made of polytetrafluoroethylene (PTFE), requires weeks to endothelialize Higher rates of infection and thrombosis Shorter device survival Most commonly used Fistula

11 Choosing a Route of Access Immediacy of need for dialysis Acute dialysis, may use central line; used for months as bridge for permanent access Adequacy of vascular access Complications Infection Thrombosis Stenosis 20-40% of hospitalizations Hemodialysis Blood pumped to dialyzer Blood and electrolyte solution (dialysate( dialysate): Seperated by semi-permeable membrane Pumped in countercurrent directions Solutes exchanged until equilibruim Protein bound drugs not removed Low permeability membrane (low to medium flux) HD

12 Goals of Dialysis Achieve desired dry weight Adequate removal of waste products Prevent sequelae of electrolyte disturbances Reduce morbidity and mortality

13 The Hemodialysis Rx Dialyzer manufacturer and size Amount of weight/fluid to remove Duration Frequency Blood flow rate: mL/min Dialysate Composition Flow rate: 500 ml/min Hemodialysate Composition Component (mmol/l) Sodium Potassium Calcium Magnesium Chloride Bicarbonate Glucose (g/dl dl) Hemodialysate Range Typical

14 The Hemodialysis Rx Dialyzer manufacturer and size Amount of weight/fluid to remove Duration Frequency Blood flow rate: mL/min Dialysate Composition Flow rate: 500 ml/min Hemodialysis Flow Rates Conventional Rapid-high efficiency High flux dialysis Blood flow rate (ml/min) Dialysate flow rate (ml( ml/min) Urea clearance rate (ml( ml/min) < 200 > 220 > 220 Required Time 4-55 hrs < 3 hrs < 3 hrs

15 Dosing Dialysis Individualized per patient Survival improves with higher doses Expressed as: Urea-reduction reduction ratio (URR) or Kt/V urea Urea Reduction Ratio Not 100% accurate Does not account for convective removal of urea Urea demonstrates two-compartment behavior (redistributes after dialysis) URR = (pre-dialysis BUN) (post-dialysis BUN) pre-dialysis BUN

16 Kt/V urea Unitless parameter Measures fraction of total body water cleared of urea during a dialysis session Kt/V urea = (urea clearance)(time) urea distribution volume K= dialyzer clearance of urea (L/h) t = duration of dialysis (h) V= urea volume of distribution (calculated) Goal Kt/V urea Values HD (non-diabetic) = 1.2 HD (diabetic) = High-flux dialysis (HFD) = 1.5 CAPD = 1.7/week NIPD and APD = 2.2/week Acute renal failure = much higher

17 Complications of Hemodialysis Fewer with high-flux dialysis Less hypotension with bicarbonate in dialysate Itching Hypotension Cramps Nausea/vomiting Headache Disequillibrium syndrome Dialyzer reactions Anaphylactic (Type A) Nonspecific (Type B) Complications of Hemodialysis Complication Itching Hypotension Cramps Nausea/ Vomiting Headache Incidence (%) Etiology/Risk Factors Uremic toxins, dry skin, Ca/PO 4 product, allergy Excessive UF, low target wt, vasodilation 2/2 acetate, meds or food, bleeding Hypotension, dehydration, low Na + in dialysate,, idiopathic Hypotension, disequilibrium syndrome Idiopathic, vasodilation 2/2 acetate, caffeine withdrawal

18 Anaphylactic Dialyzer Reactions Type A Response to ethylene oxide or heparin Worse with pts on ACEIs Nonspecific Type B More common, less severe Chest pain, back pain within minutes of dialysis Lowest incidence with synthetic high-flux membrances Disequilibrium Syndrome Definition: A central nervous system disorder characterized by neurologic symptoms caused by cerebral edema Sx: Nausea, vomiting, headache, seizures, obtundation,, coma; EEG changes Risk Factors: new dialysis patients, age (old or young), pre-existing existing neurological disorders, metabolic acidosis Treatment: prevention, use of UF, reducing URR, maintaining Na + and glucose levels in dialysate

19 Management of Hypotension Acute - Trendelenburg position - ultrafiltration rate ml saline bolus - mannitol 12.5 grams IV ml 23.4% saline over min Non-pharm Prevention - Set accurate dry weight - Use steady UFR - Keep dialysate Na + > serum Na + - Use bicarbonate dialysate - Avoid food before HD - Maintain Hct > 33% Pharmacologic Prevention - Caffeine 250 mg po 2 hrs into dialysis - Carnitine 20mg/kg during dialysis - Midodrine 5-10 mg 30min before HD Management of Cramps Acute mL saline bolus - 50mL hypertonic glucose mL 23.4% saline over min Non-pharm Prevention - set accurate dry wt - stretching - keep dialysate Na + > serum Na + - stationary bike at bedtime Pharmacologic Prevention - Diphenhydramine - Hydroquinine - Oxazepam - Prazosin - Quinine - Vitamin E

20 Management of Itching Non-pharm Prevention - deliver adequate Kt/V urea - use biocompatible dialyzers - diet phosphate compliance - maintain Hct > 33% - uv B light treatment - acupuncture Pharmacologic Prevention* - Topical emollients or capsaicin BID - hydroxyzine - cyproheptadine - loratidine/fexofenadine - cholestyramine - activated charcoal *Poor response to antihistamines suggests histamine not predominant mediator Peritoneal Dialysis Three components of dialysis: 1) Dialysate filled compartment 2) Blood filled compartment 3) Semi-permeable membrane No way to regulate blood flow, so PD less efficient than HD Larger molecules permitted to pass in PD compared to HD Solute profiles level out, similar to endogenous renal function

21 The Peritoneal Procedure Dialysate flows into peritoneal cavity by gravity over 15 minutes Toxins from blood cross peritoneal membrane and enter dialysate Dialysate removed and exchanged for new dialysate solution Thirty minutes for entire process Peritoneal Dialysis Types of PD Continuous Ambulatory (CAPD) 3 exchanges during waking hours Automated or Alternative (APD) Nocturnal Intermittent (NIPD) No exchange during day, at night via cycling machine Nocturnal Tidal (NTPD) No exchange during day, at night each hour with a constant volume of 1,500 ml in peritoneal cavity Continuous Cyclic (CCPD) Dialysate instilled in AM, dwells during day, removed prior to bed

22 The Peritoneal Rx Dose altered by osmotic gradient across peritoneum ultrafiltration and diffusion 1) # of bag exchanges per day 2) volume of each exchange 3) strength of dextrose in dialysate Recommended Kt/V urea = 1.7/week Must determine total volume drained Multiply x 7 for weekly Kt/V value Kt/V in PD Kt = D/P x volume drained (L/day) Divide by V to give Kt/V per day Multiple x 7 for weekly dose of Kt/V Patients on PD have some Kt/V contributed by residual renal function Initially Kt/V total = Kt/V PD + Kt/V renal As renal fxn declines and reach zero Kt/V total = Kt/V PD

23 Complications of PD Mechanical Medical Infectious Mechanical Complications of PD Kinking of catheter Inflow/outflow obstruction Catheter motion tissue aggravation Pain from catheter tip Rapid dialysate flow inflow pain

24 Medical Complications of PD CAUSE Glucose load COMPLICATION DM exacerbation TREATMENT IP insulin Fluid overload Electrolyte disturbances PD additives Malnutrition Unknown CHF exacerbation, edema, pulmonary congestion Hyper/hypocalcemia Chemical peritonitis Albumin and amino acid loss, muscle wasting, fat tissue Fibrin formation in dialysate UF rate Alter dialysate content Discontinue additives Dietary changes Parenteral nutrition Discontinue PD IP heparin Infectious Complications of PD: Bacterial Peritonitis Major cause of morbidity, mortality, and loss of PD access 40-60% of patients in 1 st year Mean incidence: 1 event Q mos Highest risk: Elderly Diabetic

25 Signs and Symptoms of Peritonitis Sign/Sx Sx Cloudy effluent Abdominal tenderness Fever Nausea/Vomiting Chills Incidence (%) Diagnosing Peritonitis Cloudy dialysate Signs and symptoms Culture dialysate WBC > 100/mm 3 > 50% neutrophils Gram s stain

26 Microbiological Etiology Organism Staphylococcus epidermidis Staphylococcus aureus Streptococci Enterococci Escherichia coli Pseudomonas aeruginosa Enterobacter Acinetobacter Klebsiella Proteus Mixed infections Fungi % of Episodes Treatment of Peritonitis Empiric antibiotic therapy Gram positive culture Gram negative culture

27 Empiric Antibiotics for Peritonitis

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29 Catheter-related related Infections 1 per patient year Nasal carries of S. aureus at highest risk Organism Staphylococcus aureus Staphylococcus epidermidis Pseudomonas aeruginosa Enteric Gram ( )( ) rods Incidence (%)

30 Advantages and Disadvantages of Hemodialysis Advantages Disadvantages High solute clearance Multiple visits/week Clear adequacy Long adjustment for paramters complications Complement activating Low failure rates membranes Better correction of Vascular access hemostasis infections Close monitoring of Faster decline of patient residual renal fxn than PD Advantages and Disadvantages of Peritoneal Dialysis Advantages Disadvantages Patient can do alone High risk of peritonitis No electricity or H 2 O Patient self-image Portable Transport of materials No anticoagulant High protein losses needed Lower urea clearance Minimal CV stress than HD No blood loss Patient burnout IP drug delivery Excessive glucose Clearance of larger absorption obesity solutes Mechanical problems

31 The Pharmacist s Role Knowing pharmacokinetic alterations Adjustment of doses in renal failure Proper use of expensive drugs Antibiotics Epogen IV iron products Replacement of dialyzed drugs Antibiotics Water-soluble vitamins ( Nephrocaps Nephrocaps ) Factors Increasing Drug Removal Dialyzer-specific pore size surface area charge membrane binding Dialysis-specific specific blood flow rate duration dialysis flow rate countercurrent flow Drug-specific molecular wt charge V D concentration gradient (high steady state level) hydrophilicity protein binding

32 Protein Binding Only unbound drugs eliminated by RRT Ability of drug to be filtered determined by sieving coefficient (SC), or non-bound fraction SC determined by: % protein binding membrane charge (i.e. binding to membrane) porosity of membrane Sieving Coefficient SC = C uf /C P SC = sieving coefficient uf = conc. of drug in ultrafiltrate (waste) C P = conc. of drug in plasma (blood) C uf If SC = 1, drug freely filtered If SC = 0, drug not filtered (highly protein bound)

33 Drug Dosing Drugs with renal clearance > 30% of total body clearance require replacement Loading doses: No adjustments necessary Depends on target blood level LD (mg) = desired C P (mg/l) x V d (L) LD = loading dose C P = plasma concentration V d = volume of distribution Drug Dosing Example: Vanco loading dose Pt wt = 65kg V d = 0.7 L/kg C P = 35mg/L LD (mg) = desired C P (mg/l) x V d (L) Vanco dose = 35 mg/l x (65kg x 0.7 L/kg) = 35 mg/l x 45.5 L = mg = 1500mg

34 Drug Dosing Maintenance Dosing Maintain therapeutic levels Use therapeutic drug monitoring (TDM) if possible (i.e. vanco/gent drug levels) Creatinine clearance method Estimates rate of drug removal Does not account for residual renal clearance (unless anuric) ) or non-renal clearance Creatinine Clearance Method CrCl = SC x UFR SC = sieving coefficient UFR = ultrafiltration rate (rate of waste into bag)

35 Creatinine Clearance Method Example: CrCl method for renal clearance Patient on CVVH with an UFR of 1.8 L/hr SC = 1.0 UFR = 1.8 L/hr CrCl = SC x UFR CrCl = 1.0 x 1.8 L/hr = 1,800 ml/hr = 30 ml/min Questions?