1. No category

Yuh-Feng Lin MD
Acute Complications of
Hemodialysis
Yuh-Feng Lin M.D.
Director of Internal Medicine, Shuang-Ho
Hospital,Taipei Medical University; professor,
Tri-Service General Hospital
★
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
Risk Factors of Dialysis Hypotension

A third of dialysis patients

Low body mass

Poor nutritional status and hypoalbuminemia

Severe anemia

Advanced age (Age > 65 years old)

Cardiovascular disease

Large interdialysis weight gain

Low blood pressure (predialysis systolic BP <100 mm Hg)
Etiology of Dialysis Hypotension (I)

Excessive rate and degree of ultrafiltration

Inappropriate peripheral venodilation

Autonomic dysfunction

Inadequate vasoconstrictor secretion
Etiology of Dialysis Hypotensoin (II)

Acetate dialysate

Low calcium dialysate

Eat shortly before dialysis

Antihypertensive medications

LV dysfunction
PATHOGENESIS MEDIATORS
Ultrafiltration
Osmolality
Fall
Warm
Dialysate
Bio-incompatibility
Endotoxin
Acetate
Infusion
Volume
PATHOPHYSIOLOGY
CARDIAC
OUTPUT
Vasopressors
PATIENT
Heart Disease
Vascular
Disease
Autonomic
Dysfunction
Vasodilatator
PERIPHERAL
RESISTANCE
Cell
Dysfunction
Hormonal
Dysfunction
Medications
Complement
Activation,
Cytokine release
Sepsis
Infection
HYPOTENSiON
Hypoxemia
Vasovagal stim.
Table. Results of four tests of autonomic function in normotensive and hypotensive
patients on maintenance hemodialysis
Before Dialysis
Test
After Dialysis
Normotensive
Hypotensive
Normotensive
Hypotensive
-3.7 ± 2.7
-4.6 ± 1.6
-14.1 ± 2.6*
-11.5 ± 1.4*
-6.0 ± 2.7
-4.3 ± 1.7
-16.0 ± 3.1†
-10.0 ± 1.7†
30:15 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†
∆DBP (mmHg)
Cutaneous cold
∆SBP (mmHg)
5.8 ± 2.3
7.1 ± 0.7
7.2 ± 1.1
6.8 ± 0.7
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
Orthostasis (standing up)
∆SBP (mmHg)
∆DBP (mmHg)
Sustained handgrip (normal ≥ 15)
Lin YF, Wang JY et al., ASAIO 39:946-953, 1993.
5
BV (%)
0

-5
-10
-15
-40
-30
-20
-10
0

cGMP (pmol/ml)
Fig. Correlation between changes in blood volume and plasma
cGMP throughout HD.
Wann GL. Lin YF. ASAIO 44:M569, 1998.
Plasma NO2- + NO3- (mM/l)
80
70
60
50
40
30
20
10
0
Normotensive
Hypotensive
Fig. Plasma levels of nitrite and nitrate in hypotensive
and normotensive patients on hemodialysis.
Lin SH. ASAIO J 42:M895, 1996.
Accurate Estimation of Dry Weight

cGMP, ANP

IVCD

Continuous monitoring of BV

Bioimpedence ECF/TBW
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
Prevention and Management of
Dialysis Hypotension (II)

Switch to CAPD

Hyperoncotic albumin

Nasal oxygen

Mannitol infusion
Prevention and Management of
Dialysis Hypotension (III)






L-Carnitine therapy
Sertraline
Midodrine
Blood transfusion or erythropoietin therapy
Volume expansion
Vasoconstrictor
Number of Hypotensive episodes
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
p < 0.005
Pre-Sertraline
Sertraline
Fig. Number of hypotensive episodes per hemodialysis
session in the sertraline and pre-sertraline periods.
Dheenan S. AJKD 31:624, 1998.
MAP (mmHg)
100
*
90
*
*
80
*
*
70
60
50
-1
0
1
2
3
4
5
Hours
Figure. Serial changes in MAP HD before ( ) and after ( )midodrine therapy.
YF Lin et al. Am J Med Sci 2003;325:256-61.
Conclusion and clinical application

Midodrine improves chronic hypotensin
in HD patients by modulating autonomic
function and its direct effects on
peripheral vessels.
Table. Carnitine levels in patients with (n=8) and without (n=23)
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 < 0.05, ** p < 0.01 vs without hypotension
Riley S. Clin Nephrol 48:392, 1997.
Hypoxemia

Alkali attenuate hyperventilation

Acetate dialysate

Complement activation

Pulmonary leukosequestration

Actin polymerization

Biocompatible hollow fiber
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
★
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
3000
Serum C3a (ng/ml)
HP
**
2500
SCA
CA
PMMA
2000
*
**
1500
PS-E
1000
500
0
0'
30'
120'
240'
Fig. Comparisons of serum C3a levels during hemodialysis
procedure with different dialysis membrane.
(* p< 0.05, ** p<0.01 vs baseline)
8
WBC (/cumm)
7
6
*
5
4
*
3
**
HP
SCA
CA
PMMA
PS-E
PS-S
2
1
0
0'
30'
120
240'
Fig. Comparisons of WBC levels during hemodialysis
procedure with different dialysis membrane.
(* p< 0.05, ** p<0.01 vs baseline)
TNF-a (pg/ml/2 x 106 monocytes)
2000
Cuprophan
PMA
1800
1600
1400
1200
1000
800
600
400
200
0
NC
Before
15th min
End
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.
** p<0.01 between two hollow fibers, +++ p<0.001 among three time periods.
YF Lin. Am J Nephorl 16:293, 1996.
Table. Clinical relevance of cytokine production in hemodialysis
patients
Acute
Fever
Sleep disorders
Hypotension
Chronic
Anemia
Bone disease
Malnutrition
Immunological dysfunction
Pertosa G KI 58 suppl 76:S104, 2000.
EPO dose (U/kg/week)
250
200
150
100
50
0
0
20
40
60
80
100
IL-6 (ng/ml)
Fig. Relationship between interleukin-6 (IL-6) production by
peripheral blood mononuclear cells (PBMC) and erythropoietin
(EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)
Goicoechea M KI 54:1337, 1998.
Serum b2 microglobulin (mg/L)
50000
CA
HP
SCA
PS-E
PS-S
40000
30000
*
*
20000
10000
*
*
0
0'
30'
120'
240'
Fig. Comparisons of serum b2M during hemodialysis procedure with
different dialysis membrane. (* p< 0.05 vs baseline)
★
Uremic Pruritus (I)

50-90% of dialysis patients

Risk: male, high serum BUN, Ca, P, β2-microglobulin,
duration of dialysis

Diagnositc criteria
★ Pathogenesis

Pruritogenic substancemast cell release
histamine, IL-2, …cascade of nerve
conduction to induce in perception of itch
★ Causes of itching in ESRD
★
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
Table. Degree of pruritus on capsaicin therapy
Degree of pruritus
None
Mild
Moderate
Severe
Before treatment
0
0
8
9
After treatment *
5
9
1
2
8 weeks postreatment
4
5
5
3
★ κ-opoid receptor agonistNalfurafine
★
Arrhythmia (I)

30-48% of dialysis patients

Risk factor:
▲ Compromised myocardium: CAD,
Intermyocardiocytic fibrosis,
Pericarditis
▲ Increased QT interval or dispersion
★
Arrhythmia (II)
▲ Electrolyte imbalance: hypokalemia,
hyperkalemia, hypercalcemia,
hypermagnesemia
▲ Anemia
▲ Increased LV mass
▲ Advanced age
▲ Acetate dialysate
500
P < 0.001
450
400
350
0
Contol
(n=30)
HD
(n=42)
Fig. Distribution of QTc values among hemodialysis patients and controls.
The mean value of QTc was significantly increased in hemodialysis patients
(432.6 ± 24.9 ms) compared controls (402.0 ± 21.0 ms) (p<0.01)
Suzuki R. Clin Nephrol 49:240, 1998.
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
0.0002
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 49:240, 1998.
Results of 24-Hour Holter ECG Monitoring
Arrhythmias Seen
No. of Tapes (%)
Ventricular ectopic beats (> 20/hr)
15 (24)
Ventricular ectopic beats (> 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 30:219, 1997.
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
Bleeding During Dialysis (II)

Altered adhesive fibrinogen and vWf

Impaired fibrinogen receptor (GPIIbIIIa)
function

Uremic toxin or inhibitors

Erythropoietin augments GPIIbIIIa
Bleeding During Dialysis (III)

Pack RBC

Cryoprecipitate, FFP(VIII/vWF)

dDAVP

Estrogen
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
★
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
Dialysis Pericarditis II

Precordial pain, hypotension, dyspnea, fever,
weight gain

Heparin free dialysis

Intensive dialysis

NSAID

Subxiphoid pericardiostomy
Dialysis Disequilibrium (I)

Headache, vomiting, seizure, delirium

Rapid correction of marked azotemia

Cerebral swelling

Reverse urea effect

Acidosis of the CSF
Dialysis Disequilibrium (II)

Inefficient dialysis

Shorten the duration

Lower dialyzer blood flow

Less efficient dialyzer

Osmotic agents, high sodium

IV diazepam
Metabolic Disorders

Metabolic alkalosis

Sodium citrate

Falty delivery of a buffer base

Fluoride poisoning

Acute cupper intoxication
Sodium Disorders

Conductivity limits are not adjusted

Water intoxication

Hyperkalemia

Metabolic acidosis

Correction of hyponatremia

Drink water, 5% G/W for hypernatremia
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
Hyperkalemia

Dietary intake

GI bleeding

Overheated or hypotonic dialysate

Chloramine, sodium hypochlorite, fluoride

Medications

Metabolic acidosis
Hypophosphatemia

Intensive dialysis

Phosphorus binders

Reduced intake

Dysfunction of erythrocytes, CNS, skeletal
and cardiac muscle

Phosphorus rich food
Hypercalcemia (I)

Liberation of calcium from bone

Intradialytic gain

Phosphorus binders

Widespread use of calcitriol

Aluminum poisoning
Hypercalcemia (II)

Low dialysate calcium

Phosphorus binders during meals

Discontinue vitamin D Therapy

Treat aluminum toxicity

Pamidronate
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
Chloramine Contamination

Less than 0.1 mg/L

Oxidize hemoglobin to form
methemoglobin

Appropriate charcoal filters

Vitamin C
Endotoxin

Bacterial infections

Bicarbonate dialysate conc.

Endogenous pyrogens

Header syndrome

Disinfection of the O rings

Backfiltration with high flux dialysis
Hypertensive Emergencies

Paradoxical, hypertensive response

Rise in plasma catecholamine

Activation of renin-angiotensin system

Antihypertensive withdrawal

Sublingual captopril and nifedipine
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
Table. Location of Mesenteric Infarction
Location
Small bowel
Colon
Cecum
Sigmoid
Ileocecal and distal transverse
colon
Diffuse involvement
Small bowel
Large bowel
Small and large bowel
Distal ileum and right colon
No. of Patients (n=12)
1
1
2
3
1
1
1
1
1
Diamond SM. JAMA 256:2545, 1986.
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 256:2545, 1986.
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 256:2545, 1986.
Table. Laboratory Values in Bowel Infarction Group
Findings
White blood cell count
> 15 000 mm3 ( >15 x 109 /L)
> 20 000 mm3 ( > 20 x 109 /L)
Hematocrit
Increase by 10% (0.10)
Increase by 20% (0.20)
pH
< 7.1
< 7.2
7.2-7.35
7.35-7.45
Potassium, mEq/L (mmol/L)
> 7.0
> 5.0
Bicarbonate, mEq/L(mmol/L)
< 10
< 15
< 20
No. of Patients (n=12)
2
6
1
3
4
1
2
2
4
2
5
1
4
Diamond SM. JAMA 256:2545, 1986.
Thank You
for your
attention
Yuh-Feng Lin M.D.