**Acute Complications of Hemodialysis**

Gülsüm Özkan and Şükrü Ulusoy

*Karadeniz Technical University, School of Medicine, Department of Nephrology Turkey*

#### **1. Introduction**

250 Technical Problems in Patients on Hemodialysis

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Chronic kidney disease (CKD) is a common public health problem, which occurs in many countries with an increasing prevalence. Over 50 million people throughout the world are known to have CKD, and of these, more than 1 million require renal replacement therapies such as dialysis and renal transplantation. In recent years , the rising incidence of diabetes and hypertension, the most common two causes of CKD, cause an increase in the prevalence of CKD**.** 

Hemodialysis, which is one of the renal replacement therapies, is a life-saving treatment. In the absence of this therapy, more than a million patients worldwide would have died within weeks. Hemodialysis was successfully performed for the first time in 1944 by Willem Kollf in patients with renal failure. However, hemodialysis is accompanied by several complications. During the first years following the introduction of hemodialysis, complications were common due to the technical drawbacks associated with the dialysis machines and water systems. Currently, the advances in technology, particularly those in the last 20 years, have reduced the complications. However, complications caused by the reasons other than the dialysis machine and water system remain as a significant cause of morbidity and mortality in hemodialysis patients.

Cardiovascular complications are currently the most common complication of hemodialysis. Among these complications, the rate of symptomatic intradialytic hypotension ranges between 20% and 50%, and it remains an important problem (Cruz DN et al., 1997). Another concern is the hemodialysis-associated arrhythmias, the rate of which was reported to be 5% to 75%. The common and lethal types of arrhythmias include ventricular arrhythmias and ectopies. The rate of hemodialysis-associated complex ventricular arrhythmia is around 35% (Burton JO et al., 2008). The second most common type of arrhythmia is the atrial fibrillation, the rate of which is 27% (Genovesi S et al., 2008). Sudden cardiac death accounts for 62% of cardiac-related deaths and it is usually attributed to arrhythmias (Herzog CA et al., 2008). The first year of hemodialysis is of vital importance with respect to sudden cardiac deaths, which was determined in 93 of 1000 patients in the first year of hemodialysis (Shastri S et al., 2010).

While cramps were observed in 24%-86% of the cases during the first years following the introduction of dialysis therapy, recently it has been shown that only 2% of the patients having ≥2 hemodialysis sessions in a week suffer from cramps (Kobrin SM et al., 2007). Other common complications include nausea, vomiting with a rate of 5%-15%, headache with a rate of 5%-10% and itching with a rate of 5%-10%( Jesus AC et al., 2009; Mettang T et al., 2002)**.** Although cramps, nausea-vomiting, headache and itching do not result in mortality, they substantially deteriorate the quality of life of the patients. Although more

Acute Complications of Hemodialysis 253

patients and reduce the amount of complications. However, the number of hemodialysis patients is increasing today and especially those with comorbid disorders need hemodialysis treatment. As a result of this situation, more research is being made to further

The functions of a hemodialysis machine include taking the patient's blood from the access by using a blood pump and extracorporeal tubing, passing it through the dialyzer and returning it to the patient, preparing the dialysate using purified water and concentration, circulating the dialysate along the dialyzer system and ultrafiltrating it, and enabling the blood and diaysate to circulate safely by means of control and alarm systems (Ward& Ronco,2006). Such control and alarm systems include an air detector, pressure monitor (for artery and vein pressure), heat detector, blood leakage detector, conductivity monitor, and

With the developments in technology, some dialysis machines now display blood flow rates corrected port the pressure at the pump inlet using software algorithm (Depner et al.,1990). Moreover, low pressure-sensitive blood tubing sets have been produced recently (Ahmed et al.,2004). Despite all these developments, it is of vital importance to know and prevent the

One of the much-feared fatal complications of the hemodialysis therapy is the air embolism. There are ultrasonographic air detectors in hemodialysis machine trapping air bubbles to prevent air embolism. Such detectors sense the air bubbles in certain volumes and diameters and activate the control systems. The most common cause of air embolism is air entering in the system mostly from the pre-pump section where there is a negative pressure system and the access points of artery needles (Barak et al.,2008). The symptoms of an air embolism depend on the position of the patient at that moment. If he/she is in a sitting position, neurologic complications occur because the embolus will go into the cerebral system whereas symptoms such as shortness of breath and chest pain occur when the embolus goes into the lungs in the supine position. The first step in treatment is to clamp the vein tubing and stop the pump. The patient then should be laid on his/her left with his/her head and chest facing downwards and 100% oxygen should be given. If the embolus is in the heart, it can be removed with a needle percutaneously and a hyperbaric oxygen therapy may also be used. The clinical signs and therapies we mentioned above are for large air emboli. Besides this, creation of micro-bubbles is also possible during a hemodialysis therapy. The contemporary hemodialysis machines cannot detect any doses of air infusions less than 0,1 ml/k/minutes in bolus infusions and 0,03 ml/kg/minutes in continuous infusions and thus fail to activate the alarm system (Polaschegg, 2007). Therefore, the hemodialysis machines today remain ineffective in preventing microbubbles to enter the venous system. Micro-bubbles usually do not result in acute symptoms in patients, but are thought to cause pulmonary hypertension in the lungs and chronic changes in the brain in the long run. Various filters have been developed to prevent micro-bubbles to penetrate the venous system during hemodialysis. However, routine use of such filters has not approved as they cause an extra resistance before the blood flow and the patient's blood becomes exposed to various chemicals contained in the filters (Barak et al.,2008). There are efforts in recent years to develop new technologies to detect and eliminate micro-bubbles through ultrasonographic methods. Works on the issue is still in progress (Palanchon et al.,

develop the hemodialysis machine technology.

complications associated with the HD machines and equipment.

ultrafiltration control systems.

**2.1.1 Air embolism** 

2001; Versluis et al., 2010).

common during the first years following the introduction of dialysis, Disequilibrium syndrome and complications associated with dialyser, water systems and dialysis machines are currently uncommon but may have fatal consequences.

Hemodialysis cause many complications despite the advances in technology. It is of great importance to prevent the complications before they occur. Particularly, early recognition and correction of life-threatening complications save lives. Some complications may not threaten the patients' life but deteriorate the quality of life of the patients. The treatment of these complications provides a longer life and a better quality of life for the patients. Acute complications of hemodialysis can be classified as follows:

Complications associated with hemodialysis equipment

Hemodialysis device-related complications Membrane-related complications Water system-related complications Vascular acces-related complications

Cardiovascular complications

Hypotension Hypertension Arrhythmias Pericardial effusion Sudden death Chest pain

Neurological complications

Disequilibrium syndrome Cerebrovascular accident Consciousness changes Headache Seizure Tremor

Complications associated with use of anticoagulant therapy

Heparin associated thrombocytopenia Bleeding diathesis

Electrolyte abnormalities

Hematologic complications

Others

Nausea Vomiting Itching

#### **2. Complications associated with hemodialysis equipment**

#### **2.1 Hemodialysis device-related complications**

The basic principles of hemodialysis were established many years ago. Technology that developed over many years enabled hemodialysis machines to better meet the needs of

common during the first years following the introduction of dialysis, Disequilibrium syndrome and complications associated with dialyser, water systems and dialysis machines

Hemodialysis cause many complications despite the advances in technology. It is of great importance to prevent the complications before they occur. Particularly, early recognition and correction of life-threatening complications save lives. Some complications may not threaten the patients' life but deteriorate the quality of life of the patients. The treatment of these complications provides a longer life and a better quality of life for the patients. Acute

are currently uncommon but may have fatal consequences.

complications of hemodialysis can be classified as follows: Complications associated with hemodialysis equipment Hemodialysis device-related complications

Complications associated with use of anticoagulant therapy

**2. Complications associated with hemodialysis equipment** 

The basic principles of hemodialysis were established many years ago. Technology that developed over many years enabled hemodialysis machines to better meet the needs of

Heparin associated thrombocytopenia

**2.1 Hemodialysis device-related complications** 

Membrane-related complications Water system-related complications Vascular acces-related complications

Cardiovascular complications

Neurological complications

Bleeding diathesis Electrolyte abnormalities Hematologic complications

Headache Seizure Tremor

Others

Nausea Vomiting Itching

Disequilibrium syndrome Cerebrovascular accident Consciousness changes

Hypotension Hypertension Arrhythmias Pericardial effusion Sudden death Chest pain

patients and reduce the amount of complications. However, the number of hemodialysis patients is increasing today and especially those with comorbid disorders need hemodialysis treatment. As a result of this situation, more research is being made to further develop the hemodialysis machine technology.

The functions of a hemodialysis machine include taking the patient's blood from the access by using a blood pump and extracorporeal tubing, passing it through the dialyzer and returning it to the patient, preparing the dialysate using purified water and concentration, circulating the dialysate along the dialyzer system and ultrafiltrating it, and enabling the blood and diaysate to circulate safely by means of control and alarm systems (Ward& Ronco,2006). Such control and alarm systems include an air detector, pressure monitor (for artery and vein pressure), heat detector, blood leakage detector, conductivity monitor, and ultrafiltration control systems.

With the developments in technology, some dialysis machines now display blood flow rates corrected port the pressure at the pump inlet using software algorithm (Depner et al.,1990). Moreover, low pressure-sensitive blood tubing sets have been produced recently (Ahmed et al.,2004). Despite all these developments, it is of vital importance to know and prevent the complications associated with the HD machines and equipment.

#### **2.1.1 Air embolism**

One of the much-feared fatal complications of the hemodialysis therapy is the air embolism. There are ultrasonographic air detectors in hemodialysis machine trapping air bubbles to prevent air embolism. Such detectors sense the air bubbles in certain volumes and diameters and activate the control systems. The most common cause of air embolism is air entering in the system mostly from the pre-pump section where there is a negative pressure system and the access points of artery needles (Barak et al.,2008). The symptoms of an air embolism depend on the position of the patient at that moment. If he/she is in a sitting position, neurologic complications occur because the embolus will go into the cerebral system whereas symptoms such as shortness of breath and chest pain occur when the embolus goes into the lungs in the supine position. The first step in treatment is to clamp the vein tubing and stop the pump. The patient then should be laid on his/her left with his/her head and chest facing downwards and 100% oxygen should be given. If the embolus is in the heart, it can be removed with a needle percutaneously and a hyperbaric oxygen therapy may also be used. The clinical signs and therapies we mentioned above are for large air emboli. Besides this, creation of micro-bubbles is also possible during a hemodialysis therapy. The contemporary hemodialysis machines cannot detect any doses of air infusions less than 0,1 ml/k/minutes in bolus infusions and 0,03 ml/kg/minutes in continuous infusions and thus fail to activate the alarm system (Polaschegg, 2007). Therefore, the hemodialysis machines today remain ineffective in preventing microbubbles to enter the venous system. Micro-bubbles usually do not result in acute symptoms in patients, but are thought to cause pulmonary hypertension in the lungs and chronic changes in the brain in the long run. Various filters have been developed to prevent micro-bubbles to penetrate the venous system during hemodialysis. However, routine use of such filters has not approved as they cause an extra resistance before the blood flow and the patient's blood becomes exposed to various chemicals contained in the filters (Barak et al.,2008). There are efforts in recent years to develop new technologies to detect and eliminate micro-bubbles through ultrasonographic methods. Works on the issue is still in progress (Palanchon et al., 2001; Versluis et al., 2010).

Acute Complications of Hemodialysis 255

Hemodialysis-related anaphylactoid reaction was first reported in 1975. A well-documented prospective study on its incidence is not available. However, according to the data from the Food and Drug Administration, a severe hypersensitivity reaction was reported in 3.5 of 100.000 dialysis sessions in 1982 (Ebo et al., 2006). Such reactions consisted of a series of incidences involving both anaphylactic reactions and reactions with unknown causes. The classification made by Daugirdas JT and associates is the one most commonly used for these reactions. The classification involves Type-A (hypersensitivity) reactions and Type-B (non-

The symptoms may start with dyspnea, fear of death, and a sensation of heat in the fistula site or the whole body and end with a complete anaphylactic episode. In less severe cases, there may be symptoms such as itching, coughing, sneezing, nasal discharge, nausea and vomiting. These generally occur at the very beginning of dialysis, but may also appear between the 15th and 20th minutes. Such reactions are seen more in patients with atopy

The criteria developed by Daugirdas and Ing. are mostly used in diagnosis. The major criteria include the reaction occurring in the first 20 minutes after the beginning of dialysis, dyspnea, sensation of burning or heating-up in the access site or diffused to the whole body and angioedema whereas the minor criteria include recurrence of the reaction during the next dialysis session when the same class or type dialyzer is used, urticaria, rhinorrhea or lacrimation, abdominal cramps and itching. Diagnosis is made when three major or two

It is mostly caused by sterilization using ethylene oxide, other reasons being the use of an AN69 membrane, reuse, complementary fragment release and eosinophilia (Shaldon &

The dialysis must immediately be discontinued and the blood in the blood tubing set must not be given back to the patient. Antihistaminic, adrenalin or steroid may be administered

It can be considered to sufficiently wash the dialyzers before using them for each patient, to use a dialyzer sterilized by γ-rays or steam if the reaction was due to the use of a dialyzer sterilized by ethylene oxide, to use a membrane that activates the complement more mildly or to make a transition from those using Angiotensin Converting Enzyme (ACE) inhibitor to those using Angiotensin Receptor Blockers (ARB) (Dumler et al., 1987;

Their primary symptoms are chest pain and lower back pain. They appear after 20 to 40 minutes after the beginning of dialysis. The symptoms alleviate or disappear in the progressing hours of the dialysis. Complement activation may be blamed of them although the etiology is not fully known (Jaber&Pereira, 1997). The treatment is similar to that in

type-A reactions and is adapted depending on the intensity of the symptoms.

**2.2.1 Dialyzer reactions** 

**Type-A reactions** 

Koch, 1995). **Treatment** 

**Prevention** 

Daugirdas & Ing, 1988).

**Type-B reactions** 

specific) reactions (Daugirdas & Ing, 1988).

and/or eosinophilia (Walter &Taraba, 1991).

depending on the severity of the reaction.

major and 1 minor criteria are met (Daugirdas & Ing, 1988).

#### **2.1.2 Complications resulting from manual setup of the machines or not following the instruction manual**

Despite the technological developments in hemodialysis machine, some complications arise due to failure to follow their instruction manuals or setting the alarm limits manually by individuals (Davenport, 2006). For example, one of the errors is to set up artery tubing which does not fit the diameters of the blood pump. This may result in hemolysis by increasing the pre-pumping pressure. Another error occurs when lowering the temperature of the dialysate especially in patients with intradialytic hypotension. In such a case when the hemodialysis machine is reset to stop the alarm, the temperature changes may go unnoticed even at very high or low levels due to a problem in the machine. Very low temperatures make the patient feel cold and very high temperatures may cause serious hemolysis. Most of the hemodialysis machine can automatically perform disinfection through heat or chemicals, but if the user manually restricts the disinfection process, this may cause hemolysis and the resulting symptoms as some of the compounds used in disinfection cannot be removed adequately. In some instances, the venous needle comes loose, but the hemodialysis machine cannot sense this and give the necessary alarm in time, or when the venous alarm limits are changed or the alarm is disabled by the user, an abundant loss of blood from the patient may not be sensed. Considering the above mentioned complications, it would be advisable not to disable the alarm systems of the hemodialysis machine or in cases of necessity to employ close monitoring.

In a recent study, the effect of the age and maintenance status of a hemodialysis machine on the satisfactoriness of dialysis was examined. The study showed that technical maintenance of the machines in regular intervals had a significant effect on the efficacy of the hemodialysis therapy (Azar, 2009). Therefore, it should remembered that in order to reduce the number of complications and to give the patient the targeted dose of dialysis, calibrations and service maintenance of hemodialysis machine should be regularly made, the machines should be used according to their instruction manuals, and as manual adjustments may harm the patient, the patients in such situations should be monitored closely.

#### **2.2 Membrane-related complications**

During hemodialysis, the patient's blood passes through many extracorporeal compartments. These include the dialyzer, the blood tubing set, the chemicals used during sterilization of the dialyzer and the dialysate. The dialyzer contains a dialysis membrane and sterilization products used during its manufacturing. Dialyzers come in two geometries as hollow-fiber and parallel plate dialyzers according to their membrane structure. In hollow-fiber dialyzers with thousands of tiny hollow fibers, blood flows into the compartment at one end of the cylinder-shaped case and passes through thousands of tiny capillaries. Dialysis solution flows in the opposite direction of the blood flow around the capillaries. Blood passing through the capillaries is collected in the compartment at the other end of the dialyzer and returned to the patient.

Membranes also come in various types with respect to the material used in them; they can be cellulosic, cellulose/synthetic (semi-synthetic), synthetic and bioactive (in dialyzers covered by vitamin E). They can be referred to as being reusable or not and biocompatible or not in the terminology. The most commonly used ones are the synthetic membranes today.(Twardowski, 2008).
