Acute Complications of Hemodialysis

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Acute Complications of Hemodialysis
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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
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Risk Factors of Dialysis Hypotension

• A third of dialysis patients
• Low body mass
• Poor nutritional status and hypoalbuminemia
• Severe anemia
• Advanced age (Age gt 65 years old)
• Cardiovascular disease
• Large interdialysis weight gain
• Low blood pressure (predialysis systolic BP lt100
  mm Hg)

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Etiology of Dialysis Hypotension (I)

• Excessive rate and degree of ultrafiltration
• Inappropriate peripheral venodilation
• Autonomic dysfunction
• Inadequate vasoconstrictor secretion

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Etiology of Dialysis Hypotensoin (II)

• Acetate dialysate
• Low calcium dialysate
• Eat shortly before dialysis
• Antihypertensive medications
• LV dysfunction

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PATHOGENESIS
MEDIATORS
PATHOPHYSIOLOGY
PATIENT
Heart Disease
CARDIAC OUTPUT
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.
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Table. Results of four tests of autonomic
function in normotensive and hypotensive patients
on maintenance hemodialysis
Before Dialysis After Dialysis Test Normo
tensive 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 3015 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 39946-953, 1993.
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Fig. Correlation between changes in blood volume
and plasma cGMP throughout HD.
Wann GL. Lin YF. ASAIO 44M569, 1998.
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Plasma NO2- NO3- (mM/l)
Fig. Plasma levels of nitrite and nitrate in
hypotensive and normotensive patients on
hemodialysis.
Lin SH. ASAIO J 42M895, 1996.
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Accurate Estimation of Dry Weight

• cGMP, ANP
• IVCD
• Continuous monitoring of BV
• Bioimpedence ECF/TBW

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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

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Prevention and Management of Dialysis Hypotension
(II)

• Switch to CAPD
• Hyperoncotic albumin
• Nasal oxygen
• Mannitol infusion

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Prevention and Management of Dialysis Hypotension
(III)

• L-Carnitine therapy
• Sertraline
• Midodrine
• Blood transfusion or erythropoietin therapy
• Volume expansion
• Vasoconstrictor

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p lt 0.005
Number of Hypotensive episodes
Fig. Number of hypotensive episodes per
hemodialysis session in the sertraline and
pre-sertraline periods.
Dheenan S. AJKD 31624, 1998.
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Figure. Serial changes in MAP HD before ( ?) and
after (? )midodrine therapy.
YF Lin et al. Am J Med Sci 2003325256-61.
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Conclusion and clinical application

• Midodrine improves chronic hypotensin in HD
  patients by modulating autonomic function and its
  direct effects on peripheral vessels.

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Table. Carnitine levels in patients with (n8)
and without (n23) 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 lt 0.05, p lt 0.01 vs
without hypotension
Riley S. Clin Nephrol 48392, 1997.
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Hypoxemia

• Alkali attenuate hyperventilation
• Acetate dialysate
• Complement activation
• Pulmonary leukosequestration
• Actin polymerization
• Biocompatible hollow fiber

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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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?
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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

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Serum C3a (ng/ml)

Fig. Comparisons of serum C3a levels during
hemodialysis procedure with different
dialysis membrane. ( plt 0.05, plt0.01
vs baseline)
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WBC (/cumm)

Fig. Comparisons of WBC levels during
hemodialysis procedure with different
dialysis membrane. ( plt 0.05, plt0.01
vs baseline)
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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. plt0.01 between two hollow fibers,
plt0.001 among three time periods.
YF Lin. Am J Nephorl 16293, 1996.
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Table. Clinical relevance of cytokine production
in hemodialysis patients
Acute Chronic Fever Anemia Sleep
disorders Bone disease Hypotension Malnutrition I
mmunological dysfunction
Pertosa G KI 58 suppl 76S104, 2000.
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Fig. Relationship between interleukin-6 (IL-6)
production by peripheral blood mononuclear cells
(PBMC) and erythropoietin (EPO) requirements in
34 hemodialysis subjects (r0.384, p0.039)
Goicoechea M KI 541337, 1998.
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Serum b2 microglobulin (mg/L)




Fig. Comparisons of serum b2M during hemodialysis
procedure with different dialysis membrane. (
plt 0.05 vs baseline)
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Uremic Pruritus (I)
?

• 50-90 of dialysis patients
• Risk male, high serum BUN, Ca, P,
  ß2-microglobulin, duration of dialysis
• Diagnositc criteria

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Pathogenesis
?

• Pruritogenic substance?mast cell release
  histamine, IL-2, ?cascade of nerve conduction to
  induce in perception of itch

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Causes of itching in ESRD
?
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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
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Table. Degree of pruritus on capsaicin therapy
Degree of pruritus None Mild Moderate Severe Befo
re treatment 0 0 8 9 After treatment
5 9 1 2 8 weeks postreatment 4 5 5 3
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?-opoid receptor agonist-Nalfurafine
?
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Arrhythmia (I)
?

• 30-48 of dialysis patients
• Risk factor
• ? Compromised myocardium CAD,
  Intermyocardiocytic fibrosis, Pericarditis
• ? Increased QT interval or dispersion

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Arrhythmia (II)
?

• ? Electrolyte imbalance hypokalemia,
  hyperkalemia, hypercalcemia, hypermagnesemia
• ? Anemia
• ? Increased LV mass
• ? Advanced age
• ? Acetate dialysate

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(No Transcript)
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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 0.000
2 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 49240, 1998.
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Results of 24-Hour Holter ECG Monitoring
Arrhythmias Seen No. of Tapes () Ventricular
ectopic beats (gt 20/hr) 15 (24) Ventricular
ectopic beats (gt 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 30219, 1997.
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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

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Bleeding During Dialysis (II)

• Altered adhesive fibrinogen and vWf
• Impaired fibrinogen receptor (GPIIbIIIa) function
  
• Uremic toxin or inhibitors
• Erythropoietin augments GPIIbIIIa

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Bleeding During Dialysis (III)

• Pack RBC
• Cryoprecipitate, FFP(VIII/vWF)
• dDAVP
• Estrogen

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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

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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

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Dialysis Pericarditis II

• Precordial pain, hypotension, dyspnea, fever,
  weight gain
• Heparin free dialysis
• Intensive dialysis
• NSAID
• Subxiphoid pericardiostomy

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Dialysis Disequilibrium (I)

• Headache, vomiting, seizure, delirium
• Rapid correction of marked azotemia
• Cerebral swelling
• Reverse urea effect
• Acidosis of the CSF

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Dialysis Disequilibrium (II)

• Inefficient dialysis
• Shorten the duration
• Lower dialyzer blood flow
• Less efficient dialyzer
• Osmotic agents, high sodium
• IV diazepam

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Metabolic Disorders

• Metabolic alkalosis
• Sodium citrate
• Falty delivery of a buffer base
• Fluoride poisoning
• Acute cupper intoxication

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Sodium Disorders

• Conductivity limits are not adjusted
• Water intoxication
• Hyperkalemia
• Metabolic acidosis
• Correction of hyponatremia
• Drink water, 5 G/W for hypernatremia

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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

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Hyperkalemia

• Dietary intake
• GI bleeding
• Overheated or hypotonic dialysate
• Chloramine, sodium hypochlorite, fluoride
• Medications
• Metabolic acidosis

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Hypophosphatemia

• Intensive dialysis
• Phosphorus binders
• Reduced intake
• Dysfunction of erythrocytes, CNS, skeletal and
  cardiac muscle
• Phosphorus rich food

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Hypercalcemia (I)

• Liberation of calcium from bone
• Intradialytic gain
• Phosphorus binders
• Widespread use of calcitriol
• Aluminum poisoning

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Hypercalcemia (II)

• Low dialysate calcium
• Phosphorus binders during meals
• Discontinue vitamin D Therapy
• Treat aluminum toxicity
• Pamidronate

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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

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Chloramine Contamination

• Less than 0.1 mg/L
• Oxidize hemoglobin to form methemoglobin
• Appropriate charcoal filters
• Vitamin C

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Endotoxin

• Bacterial infections
• Bicarbonate dialysate conc.
• Endogenous pyrogens
• Header syndrome
• Disinfection of the O rings
• Backfiltration with high flux dialysis

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Hypertensive Emergencies

• Paradoxical, hypertensive response
• Rise in plasma catecholamine
• Activation of renin-angiotensin system
• Antihypertensive withdrawal
• Sublingual captopril and nifedipine

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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

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Table. Location of Mesenteric Infarction
Location No. of Patients (n12) Small
bowel 1 Colon 1 Cecum 2 Sigmoid 3 Ileocecal
and distal transverse colon 1 Diffuse
involvement Small bowel 1 Large
bowel 1 Small and large bowel 1 Distal ileum
and right colon 1
Diamond SM. JAMA 2562545, 1986.
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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 2562545, 1986.
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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 2562545, 1986.
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Table. Laboratory Values in Bowel Infarction Group
Findings No. of Patients (n12) White blood
cell count gt 15 000 mm3 ( gt15 x 109 /L) 2 gt 20
000 mm3 ( gt 20 x 109 /L) 6 Hematocrit Increase
by 10 (0.10) 1 Increase by 20 (0.20) 3 pH lt
7.1 4 lt 7.2 1 7.2-7.35 2 7.35-7.45 2 Pota
ssium, mEq/L (mmol/L) gt 7.0 4 gt
5.0 2 Bicarbonate, mEq/L(mmol/L) lt 10 5 lt
15 1 lt 20 4
Diamond SM. JAMA 2562545, 1986.