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 PATHOPHYSIOLOGY PATIENT

Heart Disease
Ultrafiltration Volume CARDIAC
OUTPUT
Vascular
Osmolality Disease
Vasopressors
Fall
Autonomic
Vasodilatator Dysfunction
Warm
Dialysate PERIPHERAL
RESISTANCE Hormonal
Cell Dysfunction
Bio-incom-
Dysfunction
patibility
Medications
Complement
Endotoxin Activation, Sepsis
Cytokine release
Infection
Acetate HYPOTENSiON
Hypoxemia
Infusion Vasovagal stim.
Table. Results of four tests of autonomic function in normotensive and hypotensive
patients on maintenance hemodialysis
Before Dialysis After Dialysis
Test Normotensive 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
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
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 39:946-953, 1993.

 5

0
BV (%)

-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.
 80
70
Plasma NO2- + NO3- (mM/l)
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
 1.8

Number of Hypotensive episodes

p < 0.005
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Pre-Sertraline Sertraline
Fig. Number of hypotensive episodes per hemodialysis
session in the sertraline and pre-sertraline periods.
Dheenan S. AJKD 31:624, 1998.
 100

MAP (mmHg) 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
HP
Serum C3a (ng/ml) 2500 ** SCA
CA
2000 PMMA
* PS-E
1500 **

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
7
6
WBC (/cumm)

*
5
* HP
4 SCA
3 ** CA
PMMA
2
PS-E
1 PS-S
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)
 2000
Cuprophan
TNF-a (pg/ml/2 x 106 monocytes)
1800
PMA
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 Chronic

Fever Anemia
Sleep disorders Bone disease
Hypotension Malnutrition
Immunological dysfunction
Pertosa G KI 58 suppl 76:S104, 2000.
 250
EPO dose (U/kg/week) 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

40000 CA
HP
30000 SCA
PS-E
PS-S
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, 2-microglobulin,
duration of dialysis

Diagnositc criteria
 Pathogenesis

Pruritogenic substancemast 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
 -opoid receptor agonist-
Nalfurafine

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 HD
(n=30) (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 No. of Patients (n=12)
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 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 No. of Patients (n=12)
White blood cell count
> 15 000 mm3 ( >15 x 109 /L) 2
> 20 000 mm3 ( > 20 x 109 /L) 6
Hematocrit
Increase by 10% (0.10) 1
Increase by 20% (0.20) 3
pH
< 7.1 4
< 7.2 1
7.2-7.35 2
7.35-7.45 2
Potassium, mEq/L (mmol/L)
> 7.0 4
> 5.0 2
Bicarbonate, mEq/L(mmol/L)
< 10 5
< 15 1
< 20 4
Diamond SM. JAMA 256:2545, 1986.
Thank You
for your
attention

Yuh-Feng Lin M.D.