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Yuh-Feng Lin MD. Acute Complications of Hemodialysis. Director of Internal Medicine, Shuang-Ho Hospital,Taipei Medical University; professor, Tri-Service General Hospital. Yuh-Feng Lin M.D. ★. Intradialytic hypotension.

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Acute complications of hemodialysis
Acute Complications of Hemodialysis

Director of Internal Medicine, Shuang-Ho Hospital,Taipei Medical University; professor, Tri-Service General Hospital

Yuh-Feng Lin M.D.


Intradialytic hypotension

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
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
Etiology of Dialysis Hypotension (I)

  • Excessive rate and degree of ultrafiltration

  • Inappropriate peripheral venodilation

  • Autonomic dysfunction

  • Inadequate vasoconstrictor secretion


Etiology of dialysis hypotensoin ii
Etiology of Dialysis Hypotensoin (II)

  • Acetate dialysate

  • Low calcium dialysate

  • Eat shortly before dialysis

  • Antihypertensive medications

  • LV dysfunction


PATHOGENESIS

MEDIATORS

PATIENT

PATHOPHYSIOLOGY

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.


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.


BV (%) normotensive and hypotensive patients on maintenance hemodialysis

cGMP (pmol/ml)

Fig. Correlation between changes in blood volume and plasma cGMP throughout HD.

Wann GL. Lin YF. ASAIO 44:M569, 1998.


Plasma NO normotensive and hypotensive patients on maintenance hemodialysis2- + NO3- (mM/l)

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
Accurate Estimation of Dry Weight normotensive and hypotensive patients on maintenance hemodialysis

  • cGMP, ANP

  • IVCD

  • Continuous monitoring of BV

  • Bioimpedence ECF/TBW


Prevention and management of dialysis hypotension i
Prevention and Management of Dialysis Hypotension (I) normotensive and hypotensive patients on maintenance hemodialysis

  • 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
Prevention and Management of Dialysis Hypotension (II) normotensive and hypotensive patients on maintenance hemodialysis

  • Switch to CAPD

  • Hyperoncotic albumin

  • Nasal oxygen

  • Mannitol infusion


Prevention and management of dialysis hypotension iii
Prevention and Management of Dialysis Hypotension (III) normotensive and hypotensive patients on maintenance hemodialysis

  • L-Carnitine therapy

  • Sertraline

  • Midodrine

  • Blood transfusion or erythropoietin therapy

  • Volume expansion

  • Vasoconstrictor


p < 0.005 normotensive and hypotensive patients on maintenance hemodialysis

Number of Hypotensive episodes

Fig. Number of hypotensive episodes per hemodialysis session in the sertraline and pre-sertraline periods.

Dheenan S. AJKD 31:624, 1998.


Figure. Serial changes in MAP HD before ( normotensive and hypotensive patients on maintenance hemodialysis) and after ( )midodrine therapy.

YF Lin et al. Am J Med Sci 2003;325:256-61.


Conclusion and clinical application
Conclusion and clinical application normotensive and hypotensive patients on maintenance hemodialysis

  • 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
Hypoxemia (n=23) intra-dialytic hypotension

  • Alkali attenuate hyperventilation

  • Acetate dialysate

  • Complement activation

  • Pulmonary leukosequestration

  • Actin polymerization

  • Biocompatible hollow fiber


Muscle cramps
Muscle Cramps (n=23) intra-dialytic hypotension

  • 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


(n=23) intra-dialytic hypotension


Acute allergic reaction
Acute Allergic Reaction (n=23) intra-dialytic hypotension

  • 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


** (n=23) intra-dialytic hypotension

*

Serum C3a (ng/ml)

**

Fig. Comparisons of serum C3a levels during hemodialysis

procedure with different dialysis membrane.

(* p< 0.05, ** p<0.01 vs baseline)


* (n=23) intra-dialytic hypotension

*

WBC (/cumm)

**

Fig. Comparisons of WBC levels during hemodialysis

procedure with different dialysis membrane.

(* p< 0.05, ** p<0.01 vs baseline)


TNF- (n=23) intra-dialytic hypotensiona (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.

** 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.


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 peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)b2 microglobulin (mg/L)

*

*

*

*

Fig. Comparisons of serum b2M during hemodialysis procedure with different dialysis membrane. (* p< 0.05 vs baseline)


Uremic pruritus i

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Uremic Pruritus (I)

  • 50-90%of dialysis patients

  • Risk: male, high serum BUN, Ca, P, β2-microglobulin, duration of dialysis

  • Diagnositc criteria


Pathogenesis

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Pathogenesis

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


Causes of itching in esrd

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Causes of itching in ESRD


Uremic pruritus ii

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Uremic Pruritus (II)

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

  • Optimize the dialysis dose

  • Treat anemia

  • Treat 2nd hyperparathyroidism

  • Ultraviolet B phototherapy

  • Topical emollients

  • Capsaicin

  • Antihistamine

  • Anti-serotonin agents


Table. Degree of pruritus on capsaicin therapy peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

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

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

κ-opoid receptor agonist-Nalfurafine


Arrhythmia i

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Arrhythmia (I)

  • 30-48%of dialysis patients

  • Risk factor:

    ▲Compromised myocardium: CAD, Intermyocardiocytic fibrosis, Pericarditis

    ▲ Increased QT interval or dispersion


Arrhythmia ii

peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

Arrhythmia (II)

▲ Electrolyte imbalance: hypokalemia, hyperkalemia, hypercalcemia, hypermagnesemia

▲ Anemia

▲ Increased LV mass

▲ Advanced age

▲ Acetate dialysate


500 peripheral blood mononuclear cells (PBMC) and erythropoietin (EPO) requirements in 34 hemodialysis subjects (r=0.384, p=0.039)

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 multivariate

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
Bleeding During Dailysis (I) multivariate

  • 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
Bleeding During Dialysis (II) multivariate

  • Altered adhesive fibrinogen and vWf

  • Impaired fibrinogen receptor (GPIIbIIIa) function

  • Uremic toxin or inhibitors

  • Erythropoietin augments GPIIbIIIa


Bleeding during dialysis iii
Bleeding During Dialysis (III) multivariate

  • Pack RBC

  • Cryoprecipitate, FFP(VIII/vWF)

  • dDAVP

  • Estrogen


Air embolism
Air Embolism multivariate

  • 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

multivariate

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 multivariate

  • Precordial pain, hypotension, dyspnea, fever, weight gain

  • Heparin free dialysis

  • Intensive dialysis

  • NSAID

  • Subxiphoid pericardiostomy


Dialysis disequilibrium i
Dialysis Disequilibrium (I) multivariate

  • Headache, vomiting, seizure, delirium

  • Rapid correction of marked azotemia

  • Cerebral swelling

  • Reverse urea effect

  • Acidosis of the CSF


Dialysis disequilibrium ii
Dialysis Disequilibrium (II) multivariate

  • Inefficient dialysis

  • Shorten the duration

  • Lower dialyzer blood flow

  • Less efficient dialyzer

  • Osmotic agents, high sodium

  • IV diazepam


Metabolic disorders
Metabolic Disorders multivariate

  • Metabolic alkalosis

  • Sodium citrate

  • Falty delivery of a buffer base

  • Fluoride poisoning

  • Acute cupper intoxication


Sodium disorders
Sodium Disorders multivariate

  • Conductivity limits are not adjusted

  • Water intoxication

  • Hyperkalemia

  • Metabolic acidosis

  • Correction of hyponatremia

  • Drink water, 5% G/W for hypernatremia


Hypokalemia
Hypokalemia multivariate

  • 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
Hyperkalemia multivariate

  • Dietary intake

  • GI bleeding

  • Overheated or hypotonic dialysate

  • Chloramine, sodium hypochlorite, fluoride

  • Medications

  • Metabolic acidosis


Hypophosphatemia
Hypophosphatemia multivariate

  • Intensive dialysis

  • Phosphorus binders

  • Reduced intake

  • Dysfunction of erythrocytes, CNS, skeletal and cardiac muscle

  • Phosphorus rich food


Hypercalcemia i
Hypercalcemia (I) multivariate

  • Liberation of calcium from bone

  • Intradialytic gain

  • Phosphorus binders

  • Widespread use of calcitriol

  • Aluminum poisoning


Hypercalcemia ii
Hypercalcemia (II) multivariate

  • Low dialysate calcium

  • Phosphorus binders during meals

  • Discontinue vitamin D Therapy

  • Treat aluminum toxicity

  • Pamidronate


Fluoride contamination
Fluoride Contamination multivariate

  • 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
Chloramine Contamination multivariate

  • Less than 0.1 mg/L

  • Oxidize hemoglobin to form methemoglobin

  • Appropriate charcoal filters

  • Vitamin C


Endotoxin
Endotoxin multivariate

  • Bacterial infections

  • Bicarbonate dialysate conc.

  • Endogenous pyrogens

  • Header syndrome

  • Disinfection of the O rings

  • Backfiltration with high flux dialysis


Hypertensive emergencies
Hypertensive Emergencies multivariate

  • Paradoxical, hypertensive response

  • Rise in plasma catecholamine

  • Activation of renin-angiotensin system

  • Antihypertensive withdrawal

  • Sublingual captopril and nifedipine


Bowel ischemia
Bowel Ischemia multivariate

  • 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 multivariate

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) multivariate

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) multivariate

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 multivariate

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 multivariate

Yuh-Feng Lin M.D.


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