Ahmad

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.

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Machine & Set-up Related

• Allergic Reactions • Air Embolism, Thrombo-embolism • Hemolysis • Blood Leak • In-appropriate Dialysate/Speed:

Dialysis Disequilibrium

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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

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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)

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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

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Eto / others

Membrane

Factors Causing Reactions

- Membrane Material (s) - Chemicals used during Manufacturing Process

IgE antibody

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Compounds in header / Housing/ Potting Material: Isopropyl Myristate, Phthalates, Isocyanates etc.

Heparin

Dialyaste Impurity

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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

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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

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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)

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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

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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

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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

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Acute Reactions: Exposure to Eto & other chemicals is the most common

cause.

Usually, Improper rinsing & testing techniques are responsible

Ahmad Rinsing of Set up

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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.

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Other Chemical Exposures

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

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Acute Management of Reaction

• Stop dialysis, Clamp lines • Do Not return blood • According to severity use:

–Antihistamine, Steroids, Epinephrine

• Cardiopulmonry resuscitation if needed

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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

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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

Access (Art.)

Art. Line & Infusion sets

Side branches

Dialysate

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Position: Sitting

Air moves up to brain: Blocks the cerebral Venous circulation Loss of consciousness Convulsions Death

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Position: Recumbent Rt atrial, Rt ventricle Air blood foam Blocking the Rt vent. outflow

Chest pain, SOB, Cardio-vascular collapse

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Prevention

• Tighten connections, check • Avoid dialysis immediately after

multiple manipulations of catheter • Avoid using bottled solutions • DO NOT bypass air detector

system

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Management

-Stop the Pump -Clamp the Venous line

Patient in Trendelenburg Right Side Up

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-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

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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

Heater & Monitor Malfunction

Hot Dialysate >50 degree C

Overheated Dialysate

Proportioning

Proportioning & Conductivity Malfunction

Hypotonic Dialysate

Hypotonic Dialysate

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)

Dialysis Disequilibrium Syndrome (DDS)

Dreaded Complication Potentially Fatal

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