Presented by Dr. Richard Ward A Webber Training Teleclass, March 11, 2004

Transcription

1 FLUID QUALITY: AN IMPORTANT PART OF THE PRESCRIPTION Dr. Richard A. Ward University of Louisville OVERVIEW WHAT IS THE ROLE OF FLUID (DIALYSATE) IN HEMO? WHY IS THE QUALITY OF THE FLUID IMPORTANT? Hosted by Paul Webber WHAT ADVERSE OUTCOMES MAY BE RELATED TO CONTAMINATED FLUID? HOW CAN SAFE LEVELS OF THESE CONTAMINANTS BE ASSURED? HEMO HEMO REPLACES THE EXCRETORY FUNCTIONS OF THE KIDNEY REGULATES BALANCE REGULATES ELECTROLYTE BALANCE ELIMINATES WASTE PRODUCTS OF METABOLISM DOES NOT REPLACE ENDOCRINE AND METABOLIC FUNCTIONS OF THE KIDNEY HCO3- C P FLUID BLOOD WASTE METABOLITES (UREA, CREATININE, URIC ACID) ELECTROLYTES (POTASSIUM, PHOSPHATE) C SEMIPERMEABLE MEMBRANE DIALYZER FLUID BLOOD TUBING ANTICOAGULATION BLOOD PUMP BLOOD ACCESS MACHINE PREPARATION OF FLUID FLUID DIALYZER FIXED (34 PARTS) FLUID PREPARATION ACID (1 PART) HEATER HCO 3 - (1.83 PARTS) C T DIALYSATE DYNAMIC ACID HCO 3 - DRAIN ACID CONCENTRATE HEATER DIALYSATE BICARBONATE CONCENTRATE C A C T page 1

2 36 l/wk TOXIC CONTAMINANTS CONTAMINANT SOURCE ADVERSE EVENT 14 l/wk ALUMINUM MUNICIPAL ENCEPHALOPATHY, BONE DISEASE, ANEMIA CHLORAMINES MUNICIPAL HEMOLYSIS GI TRACT NON-SELECTIVE MEMBRANE FLUORIDE MUNICIPAL FATAL ARRHYTHMIA, BONE DISEASE (?) CYANOTOXIN SOURCE LIVER FAILURE NITRATES SOURCE ANEMIA ENDOTOXIN UNIT PYROGENIC REACTIONS, CHRONIC INFLAMMATION COPPER UNIT HEMOLYSIS, NAUSEA, VOMITING URINARY EXCRETION ZINC UNIT HEMOLYSIS, NAUSEA, VOMITING CALCIUM, MAGNESIUM SOURCE, MUNICIPAL NAUSEA, VOMITING ANEMIA OR APPARENT ERYTHROPOIETIN RESISTANCE 8 CASES OF FATAL ENCEPHALOPATHY OBSERVED IN 22 MONTHS (38% OF ALL PATIENTS). COINCIDED WITH ADDITION OF ALUMINUM SULFATE AND SODIUM ALUMINATE TO THE CITY RESULTING IN FLUID ALUMINUM CONCENTRATIONS OF 2-1 µg/l (AVERAGE 675 µg/l), AND AN ESTIMATED LOAD OF ALUMINUM WITH EACH TREATMENT OF 3-16 mg. THE OUTBREAK ENDED AFTER INSTALLATION OF DEIONIZER THAT REDUCED FLUID ALUMINUM TO < 1 µg/l. CHLORAMINES OXIDIZES HEMOGLOBIN TO METHEMAGLOBIN INHIBITS ANTIOXIDANT PATHWAYS COPPER INHIBITS ANTIOXIDANT PATHWAYS DECREASES RBC DEFORMABILITY ZINC ALUMINUM DECREASES HEMOGLOBIN SYNTHESIS INTERFERES WITH IRON METABOLISM RBC HALF-LIFE (days) CHLORAMINE-INDUCED HEMOLYSIS [CHLORAMINE] = 3 mg/l 1 TAP DISTILLED SOURCE FOR DIALYSATE Kjellstrand C et al. Nephron 13:427, 1974 AAMI QUALITY STANDARDS - RD62:21 SUBSTANCES IN DIALYSATE SUBSTANCES TOXIC IN CALCIUM 2 ALUMINUM.1 MAGNESIUM 4 CHLORAMINES.1 SODIUM 7 FREE CHLORINE.5 POTASSIUM 8 COPPER.1 TOXIC SUBSTANCES (SDWA) FLUORIDE.2 ANTIMONY.6 NITRATE (as N) 2. ARSENIC.5 SULFATE 1 BERYLLIUM.4 ZINC.1 BARIUM.1 CADMIUM.1 MICROBIOLOGICAL CONTAMINANTS CHROMIUM.14 BACTERIA 2 LEAD.5 ACTION LEVEL 5 MERCURY.2 ENDOTOXIN 2 SELENIUM.9 ACTION LEVEL 1 SILVER.5 THALIUM.2 CHEMICAL CONCENTRATIONS IN mg/l, BACTERIA CFU/ml, ENDOTOXIN EU/ml page 2

3 TREATMENT SYSTEM PURIFICATION PROCESSES REQUIRED FOR ALL FACILITIES MUST PRODUCE OF APPROPRIATE QUALITY FROM THE WORST CASE FEED MUST MEET THE PEAK DEMAND FOR (SOME EXCESS CAPACITY IS DESIRABLE) SHOULD BE DESIGNED FOR EASE OF MAINTENANCE PROCESS CARBON ADSORPTION SOFTENER REVERSE OSMOSIS DEIONIZATION ULTRAFILTRATION CONTAMINANT CHLORAMINES, ORGANICS CALCIUM IONIC CONTAMINANTS, BACTERIA, ENDOTOXIN IONIC CONTAMINANTS BACTERIA, ENDOTOXIN PRIMARY PRE-TREATMENT PURIFICATION PRE-TREATMENT BLENDING VALVE REVERSE OSMOSIS PROTECTS THE PRIMARY PURIFICATION PROCESS INLET DEPTH FILTER DISTRIBUTION CARBON STATIONS SOFTENER 5µm FILTER STORAGE TANK DEPTH FILTER REMOVES LARGER PARTICULATES (> 15 µm) THAT CAN FOUL DOWN-STREAM PROCESSES SOFTENER REMOVES CALCIUM THAT CAN FOUL REVERSE OSMOSIS MEMBRANES CARBON REMOVES CHLORINE THAT CAN DEGRADE REVERSE OSMOSIS MEMBRANES ESTABLISHES OPTIMUM OPERATING CONDITIONS FOR PRIMARY PURIFICATION PROCESS PROTECTS PATIENTS BY REMOVING CHLORAMINE ULTRAFILTER REMOVAL OF CHLORAMINES CARBON ADSORPTION WITH GRANULAR ACTIVATED CARBON OR CATALYTIC CARBON IS GENERALLY THE MOST EFFECTIVE MEANS OF REMOVING CHLORAMINES CARBON ADSORPTION MAY NOT BE EFFECTIVE UNDER RARE CIRCUMSTANCES: HIGH LEVELS OF N-CHLORAMINES USE OF ORTHOPHOSPHATE TO REDUCE LEAD AND COPPER LEVELS IN THE MUNICPAL HIGH ph IN THE MUNICIPAL UNDER THESE CIRCUMSTANCES, CARBON ADSORPTION MAY NEED TO BE SUPPLEMENTED; FOR EXAMPLE, BY INJECTION OF METABISULPHITE PRIMARY PURIFICATION REVERSE OSMOSIS versus ION EXCHANGE REVERSE OSMOSIS REMOVES A WIDE RANGE OF IONIC AND NON-IONIC CONTAMINANTS (DOES NOT REMOVE CHLORAMINES) PROVIDES A BARRIER AGAINST MICROBIOLOGICAL CONTAMINANTS GENERALLY REQUIRES PRE-TREATMENT OF FEED (CALCIUM, CHLORINE, COLLOIDS) SIGNIFICANT CAPITAL COST, BUT LOW OPERATING COST ION EXCHANGE DOES NOT REMOVE NON-IONIC CONTAMINANTS (MAY LIMIT Al REMOVAL) HAS A FINITE CAPACITY PROMOTES BACTERIAL PROLIFERATION RISK OF ACUTE FLUORIDE TOXICITY IF ALLOWED TO EXHAUST LOW CAPITAL COST, BUT SIGNIFICANT OPERATING COST page 3

4 INLET REVERSE OSMOSIS DEPTH FILTER CARBON SOFTENER 5µm FILTER DISTRIBUTION LOOP WHAT ABOUT FLUID QUALITY? STATIONS STORAGE TANK ULTRAFILTER FLUID QUALITY AAMI RD52 - DIALYSATE FOR HEMO PROPOSED LIMITS FOR CHEMICAL CONTAMINANTS SAME AS FOR (RD62:21) PROPOSED LIMITS FOR MICROBIOLOGICAL CONTAMINANTS BACTERIA: 2 CFU/ml ACTION LEVEL: 5 CFU/ml ENDOTOXIN: 2 EU/ml ACTION LEVEL: 1 EU/ml FLUID DEFINITIONS OF MICROBIOLOGICAL QUALITY Bacteria (cfu/ml) Endotoxin (EU/ml) AAMI Recommended 2 2 Practice (Proposed) ERA-EDTA Best Practice 1.25 Guidelines Ultrapure.1 <.3 Sterile 1-6 <.3 SEPTICEMIA AND PYROGENIC REACTIONS BACTERIA DO NOT CROSS DIALYZER MEMBRANES MAY INFECT BLOOD COMPARTMENT DURING PROCESSING OF DIALYZER FOR REUSE CAN CAUSE SEPSIS CHARACTERIZED BY - BORNE ORGANISMS ENDOTOXIN FRAGMENTS MAY CROSS DIALYZER MEMBRANES MAY CONTAMINATE BLOOD COMPARTMENT DURING PROCESSING OF DIALYZER FOR REUSE CAUSE PYROGENIC REACTIONS CHARACTERIZED BY SHAKING CHILLS, FEVER AND HYPOTENSION INTRADIALYTIC PYROGENIC REACTIONS PYROGENIC REACTION RATE (%) > 1 DIALYSATE BACTERIA (CFU/ml) Favero MS et al. Trans Am Soc Artif Int Organs 2: , page 4

5 INFLUENCE OF PRACTICES ON PYROGENIC REACTIONS DIALYZER REUSE: OUTBREAKS OF SEPTICEMIA AND PYROGENIC REACTIONS NUMBER OF CENTERS (%) No Yes * DIALYZER REUSE HIGH-FLUX BICARBONATE * * INCORRECT GERMICIDE CONCENTRATION 5/1 INAPPROPRIATE GERMICIDE 2/1 USE OF TAP TO CLEAN OR RINSE DIALYZERS 3/1 USE OF MULTIPLE GERMICIDES 1/1 USE OF NOT MEETING AAMI STANDARDS 1/1 Tokars JI et al. ASAIO J 4:12-131, 1994 Arduino MJ et al. Dial Transplant 22: , 1993 CHRONIC INFLAMMATION CYTOKINE-INDUCING SUBSTANCES (ENDOTOXIN FRAGMENTS, PEPTIDOGLYCANS, MURAMYL DIPEPTIDES, EXOTOXINS) CROSS LOW- AND HIGH-FLUX MEMBRANES STIMULATE MONONUCLEAR CELL CYTOKINE PRODUCTION ARE ASSOCIATED WITH INCREASED LEVELS OF ACUTE PHASE PROTEINS (C-REACTIVE PROTEIN) PRODUCE A MICROINFLAMMATORY STATE THAT MAY PLAY A ROLE IN β 2 -MICROGLOBULIN AMYLOIDOISIS, ATHEROSCLEROSIS, AND MALNUTRITION RISK OF DEVELOPING -ASSOCIATED AMYLOIDOSIS WITH CONTAMINATED FLUID ODDS RATIO (95% CI) β 2-MICROGLOBULIN AMYLOIDOSIS 3.38 ( ) p =.31 BONE CYSTS 1.85 ( ) p =.47 CARPAL TUNNEL SYNDROME 2.86 ( ) p =.6 ARTHROPATHY 9.4 ( ) p =.4 N = 89 1 YEAR FOLLOW-UP CONTAMINATED FLUID: 55 CFU/ml STANDARD FLUID: 65 CFU/ml Schiffl H et al. Nephrol Dial Transplant 15:84-845, 2 POTENTIAL ADVANTAGES OF AND FLUID OF HIGH MICROBIOLOGICAL PURITY LESS INFLAMMATORY STIMULUS REDUCED INCIDENCE OF β 2 - MICROGLOBULIN AMYLOID DISEASE IMPROVED RESPONSIVENESS TO ERYTHROPOIETIN IMPROVED NUTRITIONAL STATUS BETTER PRESERVATION OF RESIDUAL RENAL FUNCTION Tubing from a dialysis machine with > 1 6 CFU/ml P. aeruginosa, Enterobacter cloacae and Candida parapsilosis Carr J. Hospital Infections Program, CDCP page 5

6 BIOMASS FROM MACHINE TUBING CFU/cm 2 TOTAL BACTERIA/cm 2 STRATEGIES FOR BACTERIAL CONTROL TUBING FROM PATH x 1 5 BICARBONATE PATH x 1 5 FLUID PATH x 1 5 SYSTEM DESIGN SYSTEM OPERATION DISINFECTION FLUID N = 3 Adapted from Man N-K et al. Artif Organs 22:596-6, 1998 DESIGN TO LIMIT BACTERIAL PROLIFERATION USE A DISTRIBUTION LOOP AVOID STAGNANT FLOW NO DEAD ENDS, PRESSURIZING TANKS, OR MULTIPLE BRANCHES SIZE PIPES TO MAINTAIN VELOCITY > 3 ft/sec INCLUDE BACTERIAL CONTROL DEVICES ULTRAFILTERS ON-LINE HOT DISINFECTION IF A STORAGE TANK IS USED MINIMUM SIZE NEEDED TO ENSURE TURN-OVER OF TIGHT-FITTING LID WITH A HYDROPHOBIC.2 µm FILTER AIR VENT CONICAL BOTTOM WITH DRAIN AT LOWEST POINT ADEQUATE DISINFECTION MECHANISM DISINFECTION DISINFECTION SCHEDULES SHOULD BE DESIGNED TO PREVENT, NOT ELIMINATE, CONTAMINATION WITH BACTERIA AND BIOFILM. DISINFECTION SHOULD INCLUDE THE STORAGE AND DISTRIBUTION SYSTEM, CONCENTRATE PREPARATION AND DISTRIBUTION SYSTEM, AND THE PROPORTIONING SYSTEM. MONITORING WITH CULTURES AND ENDOTOXIN LEVELS IS INTENDED TO VERIFY THE ADEQUACY OF DISINFECTION, NOT INDICATE WHEN DISINFECTION IS NEEDED. NO MAN S LINE MONITORING FOR COMPLIANCE WITH AAMI STANDARDS CULTURING CONDITIONS TECHNIQUE MEMBRANE FILTER, SPREAD PLATE MEDIUM TRYPTIC SOY AGAR OR EQUIVALENT TEMPERATURE C TIME 48 hours ENDOTOXIN MEASUREMENT TECHNIQUE LIMULUS AMEBOCYTE LYSATE ASSAY page 6

7 ALTERNATIVES TO SPREAD-PLATE CULTURES CALIBRATED LOOP STANDARD TECHNIQUE IN CLINICAL LABORATORIES SAMPLE VOLUME IS TOO SMALL FOR REQUIRED SENSITIVITY SPECIFICALLY PROHIBITED FOR APPLICATIONS PADDLES CONVENIENT FOR ON-SITE TESTING REQUIRE A MAGNIFIER AND LIGHT-SOURCE FOR ACCURATE ENUMERATION OF COLONIES MAY GIVE AN APPARENT FALSE NEGATIVE WITH HEAVILY CONTAMINATED SAMPLES MEMBRANE FILTRATION VERY SENSITIVE REQUIRES FILTRATION SYSTEM AND LARGE SAMPLE VOLUMES EFFECT OF CULTURE CONDITIONS ON COLONY COUNT IN DIALYSATE BACTERIA (log CFU/ml) BLOOD AGAR 37 C TSA 37 C Ledebo I, Nystrand R. Artif Organs 23:37-43, 1999 TGEA 37 C TGEA 2 C SUMMARY HEMO PATIENTS ARE HIGHLY SENSITIVE TO CONTAMINANTS IN THE USED FOR FLUID AND DIALYZER REPROCESSING CONTAMINANTS CAN CAUSE MANY PROBLEMS COMMON IN HEMO PATIENTS, INCLUDING ANEMIA, BONE DISEASE, AND INTRA-DIALYTIC NAUSEA AND VOMITING NO SUPPLY CAN BE CONSIDERED SUITABLE FOR APPLICATIONS WITHOUT PURIFICATION AVOIDING COMPLICATIONS FROM CONTAMINANTS REQUIRES CONSTANT ATTENTION TO QUALITY Continuing Education Certificate To find out how to get a Continuing Education Certificate for this teleclass contact... certificates@webbertraining.com page 7