Ahmad
HD Complications
• Treatment Related: Hypotension, Cramps, Nausea, vomiting etc.
• Water Related: Water Contaminants – Al, Cu, Fl etc.
• Machine & Set-up Related: Air Embolism, Anaphylactic Reactions etc.
Ahmad
Machine & Set-up Related
• Allergic Reactions • Air Embolism, Thrombo-embolism • Hemolysis • Blood Leak • In-appropriate Dialysate/Speed:
Dialysis Disequilibrium
Ahmad
Acute Allergic Reactions (Anaphylactoid Reactions)
• Severe (Type A): Dyspnea, angioedema, anxiety, impending doom, warmth over access/body, cardiac arrest, death
• Milder (Type B): Itching, urticaria, sneezing, cough, SOB, watery eyes, numbness of fingers/toes abdominal cramps, diarrhea
• Timing: First few to 30 minutes of HD or later
Ahmad
Incidence • Current incidence is unknown, older data
from ‘80s and 90s: – Severe reactions: 3 - 5 per 100,000 dialyzers
sold. – Milder reactions (type B): 3 – 5 per 100
dialyzers sold. • Milder forms often are not recognized; are
more common – 47% of patients developed significant
eosinophilia in the first 6 months of HD (Tielmans et al, NDT, 112-115, 1996)
Ahmad
Pathophysiology • Sterilant: from dialyzer, or from tubing
• Manufacturing Process • Reuse Process
• Other chemical impurity from the tubing or dialyzer
• Dialysate Contaminants, endotoxins • Heparin • Common in those with allergic nature
and eosinophilia • Problem: Improper Rinsing / Testing Manufacturing Process
Ahmad
Eto / others
Membrane
Factors Causing Reactions
- Membrane Material (s) - Chemicals used during Manufacturing Process
IgE antibody
Ahmad
Compounds in header / Housing/ Potting Material: Isopropyl Myristate, Phthalates, Isocyanates etc.
Heparin
Dialyaste Impurity
Ahmad
C3a, C5a C5b-9
Inciting Factor / M
embrane
Neutrophils
Pulmonary sequestration
Monocytes
Interleukins & TNF
Mast Cells
Histamine
Erythrocytes
Lysis?
(Bradykinin) ACEI:
Coagulation Cascade
Bradykinin Coagulation
Ahmad
Dialyzer Membrane
Complement & Cellular Activation Cellulosic – Free OH group
Substituted Modified Cellulosic – OH substituted With acetate or DEAE, CA CDA, CTA & Hemophane
Synthetic – Polycarbonate Polyamide, Polysulfone, PMMA, PAN
However – Even synthetic Membrane can cause Reactions Sometimes dialyzers with same membrane/Manufacturer
Cellulosic Substituted Cellulosic Synthetic
General Rule
Ahmad
Anecdotal Reports: Severe Reactions including cardiac shock – reported with synthetic membranes
• Reported with dialyzers: – with synthetic membrane such as PS – Sterilized by irradiation or steam (not Eto)
• Severe reactions to FX-60 but not with F6HPS, both PS, both from Fresenius
(Shu et al HDI, 2014; 18:835–845)
• Reaction to F160, Reaction minimized by using highly absorptive AN69 membrane
(Yang et al HDI 2005; 9: 120–126)
Ahmad
Possible inciting Factor(s) • Subtle differences in the membrane • Housing &/or potting material differences
(polypropylene, polycarbonate etc.) • PVP is added to PS membrane; Elutability
of PVP may be different in different dialyzers. Very small amount of PVP can cause cardiac response
• Chemicals used during manufacturing, packing or testing process: – Particulate impurity in storage fluid – PF5070
Ahmad
Reactions to Other Chemicals/Contaminants: Perfluorohydrocarbon (PF5070):
Clusters of deaths: 8/01 – Spain 10 px, died shortly p HD 10/1 - Croatia 23 px, unexplained deaths; same time USA, Italy, Taiwan, Colombia 20 additional deaths. All on single use dialyzers Clinical scenario similar: Shortness of breath to severe dyspnea, respiratory failure and vascular collapse; some px terminal event MI, others, inability to ventilate. Autopsy assessment: Croatian patients showed micro air embolization—no safety failure in machines seen. Equipment assessment: unusual presence of a liquid, PF5070 - is used to detect fiber leakage/repair/air extraction. It is liquid at room temperature, but vaporizes at body temp. If left in the dialyzer – cause micro-embolism in lungs
Ahmad
Formadehyde Exposure
• Acute issues: Burning at access or in arm, bitter taste, laryngeal spasm – Clamp venous line, stop dialysis, check for
residual formaldehyde – Use a new dialyzer – Optimal prophylaxis with compulsive
adherence to pre-dialysis procedure checklists
• Chronic issues: Itching: may be potential source of pruritus, clinical trial of alternate disinfectant worthwhile. – Anti-Nform antibody-mediated hemolysis.
Mujais S, Ing T, Kjellstrand T: Acute Complications of HD; in Replacement of Renal Function by Dialysis, 4th Edition, Jacob, Koch, Kjellstrand, and Winchester, Eds; Kluwer,Dordrecht, 1996
Ahmad
Acute Reactions: Exposure to Eto & other chemicals is the most common
cause.
Usually, Improper rinsing & testing techniques are responsible
Ahmad
Prevention • Proper Rinsing Technique • In sensitive patients: Rinse with Iso-osmolar
NaHCO3 solution? Reduces Bradykinin generation,
• Adequate Volume of rinse & Time of rinsing • Clamp Side Branches Close to Blood Tubing • Unclamp and Flush & Re-clamp heparin line • Proper Testing for Sterilant –
Formaldehyde/Renalin • Do not infuse priming fluid back to patient • Do not return fluid if the set-up has been sitting
for a long time.
Heparin Allergic Reactions: Urticaria, nasal congestion,
wheezing, anaphylaxis Thrombocytopenia: I & II Heparin-induced thrombocytopenia type II can
also cause a ‘‘pseudo-pulmonary embolus’’syndrome. Fever, tachycardia, flushing, headache, chest pain, and
dyspnea; or even acute respiratory distress, transient global amnesia, and cardio-pulmonary arrest.
Activation of Cells/Immune System
Heparin & Degranulation of PMNs (MPO)
0
20
40
60
80
100
120
140
160
t0 fistula t1 ven t30art t210art
HepDalteprinCitrate
MPO, ug/l
p<0.03 ns
Gritters M, NDT, 21:153, 2006
N=8, Chr.HD pts. 3 anticoagulation Methods for one week. F60 NR
Ahmad
Acute Management of Reaction
• Stop dialysis, Clamp lines • Do Not return blood • According to severity use:
–Antihistamine, Steroids, Epinephrine
• Cardiopulmonry resuscitation if needed
Ahmad
Long term Management (Prevention is best)
• Identify & remove the cause – Dialyzer – NonEto sterilized, Reuse – Heparin – Stop heparin /LMWH – Membrane – Switch membrane/dialyzer – ACEI – Membrane/Stop ACEI; Try ARB
instead – Appropriate water treatment (Impurity) – Ultrapure dialysate
• Adherance to Proper Rinsing & Testing
Ahmad
Air Embolism
• Dreaded complication • HD system has redundant safeguards
to prevent it. It can happen: – Set-up manipulation – Vascular access problems (catheters) – Non-collapsible bottles
• 1 ml/Kg air is potentially fatal • Vigilance is necessary
Ahmad
Position: Sitting
Air moves up to brain: Blocks the cerebral Venous circulation Loss of consciousness Convulsions Death
Ahmad
Position: Recumbent Rt atrial, Rt ventricle Air blood foam Blocking the Rt vent. outflow
Chest pain, SOB, Cardio-vascular collapse
Ahmad
Prevention
• Tighten connections, check • Avoid dialysis immediately after
multiple manipulations of catheter • Avoid using bottled solutions • DO NOT bypass air detector
system
Ahmad
-Trendelenburg -Right side up -Air trapped in Rt ventricle -Prevents migration to brain -Avoids outflow obstruction. -Can be aspirated
-Administer O2 -Hyperbaric chamber Helps reduce bubble size
Ahmad
Embolism • With modern machines significant air
embolism is very rare • However, showering of small clots during
HD can occur • Exact incidence is unknown, often it is
asymptomatic • Compared to general population, P.E. is
more prevalent in HD. About 12% of HD population has clinical PE (0.07%, gen pop.)
Hemolysis Subclinical hemolysis often is un-
noticed Clinically overt hemolysis is a
medical emergency Three broad sets of circumstances: Blood Pathway related: Faster flow
through narrow pathway/obstruction Failure of rinsing of contaminants Dialysate & Water related factors
Mechanical: Blood Circuit Fast pump speed
through narrow arterial needle (Ap in excess of -160 mmHg) Misaligned pump
head & blood tubing Kink in the line may
cause RBC damage Faulty blood line (venous segment
connecting dialyzer to venous drip chamber)
Ahmad
UF Controller
Balancing Chamber
UF Pump
Dialysate related factors:
Proportioning Heater
Temp. Sensor
Proportioning
Heater
Water contaminants: Chloramines Copper, Fluoride, Nitrate, Zinc
Contaminants
Other contaminants: Formadehyde, Bleach
Chemical Contaminants Causing Hemolysis
Bacterial fragments
Clinical Manifestations & Consequences
Symptoms: Chest tightness, back pain & SOB Signs: Intensifying of skin
pigment, pink plasma, venous blood line turns port wine in color Consequences: hypoxemia,
anemia, HYPERKALEMIA, arrhythmia, death
Management
Stop blood pump immediately Don’t return blood – high K Check EKG, K, Hct, blood gas,
hapto, LDH metHb Treat hyperkalemia Consider admitting patient,
delayed hemolysis and hyperkalemia
Management (Contd.)
If no obvious cause check water for chloramine, fluoride. Check water treatment system. Avoid exposing other patients –
stop using the water system.
Blood Leak
• Blood leak across the dialyzer membrane • Blood leak detector on the dialysate
outflow – alarms • Stop the dialysis • Risk of dialysate contaminating the blood
– Significant leak, do not return the blood • Start the dialysis with a new dialyzer • Prevention: Avoid high TMP (>500 mmHg)
DDS • Acute neurological symptoms developing
during or immediately after HD. • Early mild: headache, nausea, disorient-
ation, restlessness, blurred vision, asterixis.
• More severe: confusion, seizures, coma, and even death.
• Often milder manifestations with dialysis e.g. muscle cramps, anorexia, dizziness developing near the end of a dialysis treatment — may be part of this syndrome
• Caused by brain edema (Rapid dialysis)
Rapid HD
Rapid Dialysis (drop in osm.): Increased ICF Osmolarity (Rapid fall of ECF osmoles) Causes water moving into neurons Brain edema DDS Prevention: Slower HD - Avoid low Na bath - Urea in the bath
D – HCO3 = 35
HCO3 = 5 pCO2 = 12 pH = 7.22
HCO3 = 25 pCO2 = 40 pH = 7.41
HCO3 = 8 pCO2 = 40 pH < 6.0
Brain Dysfunction ?Swelling DDS
Rapid HCO3 Increase
Prevention of DDS
• Slower dialysis – slower osmolar drop • Urea in the bath (same amount as BUN)
– Consider the dilutional effect on Na • In severe acidosis, use lower dialysate
bicarbonate • If volume is an issue try isolated UF alone • Consider PD • Management: Supportive
Machine, Set-up Complications • Dialysis machines have adequate safeguards • Serious equipment related complications are
rare. However: – Allergic Reactions may be exception – Subclinical – DDS, Embolism, Hemolysis?
• Serious complications often are a result of inappropriate rinsing and testing procedures
• Most serious exposure to a large number of patients are related to water problems or central dialysate delivery system
• Nephrologists need to be more aware & involved