**2.2.4 Disadvantages of reuse dialyzers**

Reactions associated with the compounds used in chemical disinfection, side-effects of the volatile gases used during sterilization, allergic reactions, residual chemical infusion, sterilization in insufficient concentrations, pyogenic reactions, variations in the permeability of the membrane and failure to perform an efficient dialysis are seen more often (Twardowski, 2006).

### **2.3 Water system-related complications**

Patients receiving hemodialysis therapy become exposed to 18000 to 36000 liters of water a year during hemodialysis. The formation of dialysate involves water purification, distribution of the purified water to individual hemodialysis machines, concentrate preparation (acidic and basic concentrate) and finally mixing the concentrates with the purified water. While the acidic concentrate is not suitable for bacterial growth, the basic concentrate creates an environment suitable for bacterial growth. For this reason, dry powder cartridges are being used as basic concentrates recently; this allows online preparation of fluid bicarbonate in individual dialysis machines (Ward, 2004). A large portion of the water used in preparing the dialysate is the purified water produced in the water system. In case the hemodialysis water system fails to produce the proper water, patients can be exposed to various chemicals, bacteria and toxic contaminations (Montanari

During hemodialysis, Pa O2 drops to approximately 10-20 mmHg. While such decrease does not lead to significant clinical problems in patients with normal oxygenation, may produce catastrophic results in those with poor oxygenation (De Backer et al.,1983; Hakim & Lowrie,1982). One of the factors that is blamed in the etiology of hypoxemia that emerge during hemodialysis is dialysate containing acetate (De Backer et al.,1983). However, it was demonstrated that it could also be observed in dialysate with bicarbonate. Dialysate with acetate may induce hypoxia in two ways, first by increased oxygen consumption during acetate bicarbonate conversion and second by intradialytic loss of CO2 (Dolan et al.,1981; Oh et al.,1985). The biocompatibility of the membrane used is one of the most frequently blamed factors in hypoxemia (Graf et al.,1980). Especially the use of an acetate-containing dialysate together with a Cuprophan membrane increases hypoxemia (Vanholder et al.,1987). Hypocapnia associated with intradialytic loss of CO2 and adaptation to chronic metabolic acidosis lead to periodic shortness of breath and a tendency to sleep apnea

Increasing the level of CO2 in the dialysate by directly adding CO2 to it or by using a

Making appropriate ventilator settings for the patients who are known to have hypoxemia prior to the dialysis and are administered mechanical ventilation, nocturnal hemodialysis

New dialyzer syndrome, neutropenia and complement activation as well as reactions

Reactions associated with the compounds used in chemical disinfection, side-effects of the volatile gases used during sterilization, allergic reactions, residual chemical infusion, sterilization in insufficient concentrations, pyogenic reactions, variations in the permeability of the membrane and failure to perform an efficient dialysis are seen more often

Patients receiving hemodialysis therapy become exposed to 18000 to 36000 liters of water a year during hemodialysis. The formation of dialysate involves water purification, distribution of the purified water to individual hemodialysis machines, concentrate preparation (acidic and basic concentrate) and finally mixing the concentrates with the purified water. While the acidic concentrate is not suitable for bacterial growth, the basic concentrate creates an environment suitable for bacterial growth. For this reason, dry powder cartridges are being used as basic concentrates recently; this allows online preparation of fluid bicarbonate in individual dialysis machines (Ward, 2004). A large portion of the water used in preparing the dialysate is the purified water produced in the water system. In case the hemodialysis water system fails to produce the proper water, patients can be exposed to various chemicals, bacteria and toxic contaminations (Montanari

Using biocompatible membranes (De Backer et al.,1983; Hakim & Lowrie,1982),

may be appropriate for those with sleep apnea syndrome (Hanly&Pierratos, 2001),

**2.2.2 Hemodialysis-related hypoxemia** 

syndrome (De Broe & De Backer, 1989).

**2.2.3 Disadvantages of first-use dialyzers** 

**2.2.4 Disadvantages of reuse dialyzers** 

**2.3 Water system-related complications** 

(Twardowski, 2006).

associated with the use of ethylene oxide are seen more often.

**Treatment and prevention** 

dialysate containing bicarbonate,

et al.,2009). The water system technology used in the hempdialysis process is being improved from day to day to reduce such unwanted effects. Two types of water purification systems are being used, the Pure Water and the Ultrapure Water systems. The Pure Water system is used in the conventional hemodialysis process. The Ultrapure Water purification system is used in many dialysis modalities including online hemodiafiltration, online hemofiltration and high flux dialysis ([No authors listed] 2002).

The conventional hemodialysis water system conveys the water taken from the water supply into the hemodialysis unit after passing it through the mechanical filter, water softener, carbon filter, reverse osmosis and UV. An endotoxin filter is also available in some systems. In units with no online processing, the purified water is kept in big tanks before carried to the patients and then distributed to the hemodialysis machine of the patients via water tubes. Every part of this system may constitute a reservoir for bacteria. Moreover, chemical contamination can also occur. For this reason, the European Pharmacopeia has developed the hemodialysis water standards. According to these standards, the levels of microbial contamination and bacterial endotoxin are recommended to be < 100 CFU/ml and < 0.25 IU/ml respectively in the conventional regular hemodialysis water system (Lindley & Canaud,2002**)** and < 0.1 CFU/ml and < 0.003 IU/ml in the ultrapure water system ([No authors listed] 2002). The chemical contents of the recommended hemodialysis water are given in the table 1.


Table 1. Maximum water contaminant levels and methods of analysis recommended by the European Pharmacopoeia (No authors listed] 2002)

Acute Complications of Hemodialysis 259

Hemodialysis therapy requires a safe vascular access from which an adequate blood flow can be obtained. This is made possible by using arteriovenous fistulae (AVF) or synthetic grafts (AVG) made of poytetrafluoroethylene in chronic dialysis patients whereas central venous catheters (CVC) are used in patients with acute or chronic kidney failure who must

Although the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) recommends that the use of catheters in hemodialysis should remain below 10%, they are being used today in increasing amounts reaching a level of 21% (Chan, 2008; Pisoni et al.,2002). The reason for their being used so much is because they are placed easily, can be used immediately and enable a pain-free dialysis (Chan,2008). There are mainly two classes of CVCs. One is temporary, dual lumen, mostly non-tunneled catheters and the other is long-term tunneled catheters. The temporary catheters are usually preferred in patients whose hemodialysis must be started immediately, whose fistula has not matured yet or whose fistula cannot be used due to a problem. The long-term tunneled catheters, on the other hand, are used in patients for whom an AVF cannot be opened or whose fistula is thought to take long to mature (Wadelek, 2010). Hemodialysis catheters are placed in internal jugular, external jugular or femoral veins respectively. In recent years, subclavian vein catheters are not recommended because of the high possibility of stenosis. However, if catheters cannot be placed in the above mentioned veins, a temporary catheter may be

**2.4.1 Use of central venous catheters, their complications and treatment** 

placed in the subclavian vein opposite the AVF *(*Trerotola et al.,1997*)*.

the cardiac cavities or cardiac arrest (Chan,2008).

or ischemic chest pain (Yavascan et al.,2009).

**2.4.1.1 Early complications that develop during and after catheter placing** 

The catheter-related complications in hemodialysis usually develop during catheter placing. Such complications include cardiac arrhythmia, pneumothorax, pleural or mediastinal hematoma, air emboli, thoracic tract injury, nerve injury in the neck or thorax, puncture of

In a study made by Stuart RK et al atrial arrhythmia was seen in 41% of the cases and ventricular ectopia in 25% of the cases during placing of CVCs. Ventricular ectopia was more common in shorter patients in that study. Ventricular ectopia was seen in 43% of the cases when catheters were being placed in the right subclavian vein while it was seen in 10% of the cases when catheters were being placed in other areas. The patient's age and cardiac disease history, the procedure type or the levels of potassium did not affect the development of arrhythmia, but it was demonstrated that over-insertion of the guide wire triggered arrhythmia depending on the body structure of the patient (Stuart et al.,1990). The most important factor in preventing development of arrhythmia is to avoid overinsertion during catheter placing (Fiaccadori et al.,1996). First of all, the guide wire should be pulled back in a case of symptomatic dysrhythmia. A vagal maneuver should be attempted in supraventricular arrhythmia and if the arrhythmia persists, iv administration of adenosine or calcium channel blockers may be considered. A synchronized cardioversion may be attempted in patients with hypotension, lung edema

While pneumothorax was being observed in 1-6% of the cases when placing CVCs previously (Moini et al.,2009), the prevalence of it has been reduced considerably today as catheters are now placed with the help of ultrasonography. Farrell J et al, for example, did

**2.4 Vascular acces-related complications** 

urgently undergo dialysis.

In spite of these standards, the complications related to production of water is still being significant with the increased use of high-flux dialyzers, which increase the back-filtration of the dialysate, and the increased use of online hemodiafiltration process, which is based on allowing the blood compartment to contact large amounts of purified water (Brunet & Berland, 2000). The problems associated with the water purification process lead to short and long term complications. In short term complications, a serious septic episode may develop accompanied by tremble, fever, nausea, myalgia, headache, debility and even hypotension and shock when the patient is exposed to excessive amounts of bacteria or endotoxins (Dinarello et al.,1987). Therefore, it is of vital importance to detect in time any contaminant in the dialysis fluid or any formation of biofilm in the parts of the system (Glorieux et al.,2009).

Some problems arise if the chemical contents of the water system are not in desired limits. For example, a low level of sodium may cause hypotension, cramps and hemolysis while a high level of sodium may result in thirstiness and a disequilibrium-like episode. While low and high levels of potassium lead to cardiac arrhythmia, low levels of calcium cause hypotension, hyperparathyroidism, fasciculation, tetany and petechiae. Low levels of magnesium may cause hyperparathyroidism and high levels of it may lead to osteoporosis and osteomalacia, nausea, visual disorders, muscle weakness, ataxia and hypotension (Floege & Lonnemann, 2000)).

It is advisable to check the levels of certain chemicals or contaminants when some symptoms and signs exist. For example, in the case of anemia, the levels of aluminum, chloramines, nitrate, lead, copper, zinc and silicon; in the case of hypertension, the levels of calcium, magnesium and sodium; in the case of hypotension, the levels of bacteria, endotoxins and nitrate; in the case of muscle weakness, the levels of calcium and magnesium; in the case of nausea and vomiting, the levels of bacteria, endotoxins, chloramines, pH, nitrate, sulfate, calcium, magnesium, copper and zinc; and in the case of a neurological disorder, the levels of aluminum, lead, calcium and magnesium may be checked (Hoenich& Levin, 2003).

Taking samples from the water system for microbiological and chemical analysis may be done once a week when the water system is newly set up, but the sampling should not be done immediately after the sterilization process. The frequency of analysis may be decreased after making sure that water quality, but it is recommended not to exceed once a month. The quality of the water tank should be checked at least twice a year. The water system should be sterilized in certain intervals. The frequency of such sterilization should comply with the instructions of the manufacturer. It is also advisable to replace the active carbon filters and the membranes in the reverse osmosis (RO) unit as frequently as advised by the manufacturer (Hoenich& Levin, 2003). The samples for microbiological inspection should be taken into sterile cups of 50 ml from the RO unit, softening unit and water tank, and then from the water system components right before the connection to the dialysis machine. If endotoxins will be checked, samples should be taken into cups with no endotoxines and placed in the culture medium within 30 minutes **(**Alter et al., 2004).

In conclusion, the necessary care should be taken for the quality of water used in hemodialysis, the allowed levels of chemical contaminants should be maintained, the limits of the European Pharmacopeia should not be exceeded in the levels of microbiological contaminants, and proper samples should be taken and analyzed from various sections of the dialysis water system unit in regular intervals.

In spite of these standards, the complications related to production of water is still being significant with the increased use of high-flux dialyzers, which increase the back-filtration of the dialysate, and the increased use of online hemodiafiltration process, which is based on allowing the blood compartment to contact large amounts of purified water (Brunet & Berland, 2000). The problems associated with the water purification process lead to short and long term complications. In short term complications, a serious septic episode may develop accompanied by tremble, fever, nausea, myalgia, headache, debility and even hypotension and shock when the patient is exposed to excessive amounts of bacteria or endotoxins (Dinarello et al.,1987). Therefore, it is of vital importance to detect in time any contaminant in the dialysis fluid or any formation of biofilm in the parts of the system

Some problems arise if the chemical contents of the water system are not in desired limits. For example, a low level of sodium may cause hypotension, cramps and hemolysis while a high level of sodium may result in thirstiness and a disequilibrium-like episode. While low and high levels of potassium lead to cardiac arrhythmia, low levels of calcium cause hypotension, hyperparathyroidism, fasciculation, tetany and petechiae. Low levels of magnesium may cause hyperparathyroidism and high levels of it may lead to osteoporosis and osteomalacia, nausea, visual disorders, muscle weakness, ataxia and hypotension

It is advisable to check the levels of certain chemicals or contaminants when some symptoms and signs exist. For example, in the case of anemia, the levels of aluminum, chloramines, nitrate, lead, copper, zinc and silicon; in the case of hypertension, the levels of calcium, magnesium and sodium; in the case of hypotension, the levels of bacteria, endotoxins and nitrate; in the case of muscle weakness, the levels of calcium and magnesium; in the case of nausea and vomiting, the levels of bacteria, endotoxins, chloramines, pH, nitrate, sulfate, calcium, magnesium, copper and zinc; and in the case of a neurological disorder, the levels of aluminum, lead, calcium and magnesium may be

Taking samples from the water system for microbiological and chemical analysis may be done once a week when the water system is newly set up, but the sampling should not be done immediately after the sterilization process. The frequency of analysis may be decreased after making sure that water quality, but it is recommended not to exceed once a month. The quality of the water tank should be checked at least twice a year. The water system should be sterilized in certain intervals. The frequency of such sterilization should comply with the instructions of the manufacturer. It is also advisable to replace the active carbon filters and the membranes in the reverse osmosis (RO) unit as frequently as advised by the manufacturer (Hoenich& Levin, 2003). The samples for microbiological inspection should be taken into sterile cups of 50 ml from the RO unit, softening unit and water tank, and then from the water system components right before the connection to the dialysis machine. If endotoxins will be checked, samples should be taken into cups with no

endotoxines and placed in the culture medium within 30 minutes **(**Alter et al., 2004).

In conclusion, the necessary care should be taken for the quality of water used in hemodialysis, the allowed levels of chemical contaminants should be maintained, the limits of the European Pharmacopeia should not be exceeded in the levels of microbiological contaminants, and proper samples should be taken and analyzed from various sections of

(Glorieux et al.,2009).

(Floege & Lonnemann, 2000)).

checked (Hoenich& Levin, 2003).

the dialysis water system unit in regular intervals.

#### **2.4 Vascular acces-related complications**

Hemodialysis therapy requires a safe vascular access from which an adequate blood flow can be obtained. This is made possible by using arteriovenous fistulae (AVF) or synthetic grafts (AVG) made of poytetrafluoroethylene in chronic dialysis patients whereas central venous catheters (CVC) are used in patients with acute or chronic kidney failure who must urgently undergo dialysis.

### **2.4.1 Use of central venous catheters, their complications and treatment**

Although the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) recommends that the use of catheters in hemodialysis should remain below 10%, they are being used today in increasing amounts reaching a level of 21% (Chan, 2008; Pisoni et al.,2002). The reason for their being used so much is because they are placed easily, can be used immediately and enable a pain-free dialysis (Chan,2008). There are mainly two classes of CVCs. One is temporary, dual lumen, mostly non-tunneled catheters and the other is long-term tunneled catheters. The temporary catheters are usually preferred in patients whose hemodialysis must be started immediately, whose fistula has not matured yet or whose fistula cannot be used due to a problem. The long-term tunneled catheters, on the other hand, are used in patients for whom an AVF cannot be opened or whose fistula is thought to take long to mature (Wadelek, 2010). Hemodialysis catheters are placed in internal jugular, external jugular or femoral veins respectively. In recent years, subclavian vein catheters are not recommended because of the high possibility of stenosis. However, if catheters cannot be placed in the above mentioned veins, a temporary catheter may be placed in the subclavian vein opposite the AVF *(*Trerotola et al.,1997*)*.

#### **2.4.1.1 Early complications that develop during and after catheter placing**

The catheter-related complications in hemodialysis usually develop during catheter placing. Such complications include cardiac arrhythmia, pneumothorax, pleural or mediastinal hematoma, air emboli, thoracic tract injury, nerve injury in the neck or thorax, puncture of the cardiac cavities or cardiac arrest (Chan,2008).

In a study made by Stuart RK et al atrial arrhythmia was seen in 41% of the cases and ventricular ectopia in 25% of the cases during placing of CVCs. Ventricular ectopia was more common in shorter patients in that study. Ventricular ectopia was seen in 43% of the cases when catheters were being placed in the right subclavian vein while it was seen in 10% of the cases when catheters were being placed in other areas. The patient's age and cardiac disease history, the procedure type or the levels of potassium did not affect the development of arrhythmia, but it was demonstrated that over-insertion of the guide wire triggered arrhythmia depending on the body structure of the patient (Stuart et al.,1990). The most important factor in preventing development of arrhythmia is to avoid overinsertion during catheter placing (Fiaccadori et al.,1996). First of all, the guide wire should be pulled back in a case of symptomatic dysrhythmia. A vagal maneuver should be attempted in supraventricular arrhythmia and if the arrhythmia persists, iv administration of adenosine or calcium channel blockers may be considered. A synchronized cardioversion may be attempted in patients with hypotension, lung edema or ischemic chest pain (Yavascan et al.,2009).

While pneumothorax was being observed in 1-6% of the cases when placing CVCs previously (Moini et al.,2009), the prevalence of it has been reduced considerably today as catheters are now placed with the help of ultrasonography. Farrell J et al, for example, did

Acute Complications of Hemodialysis 261

Development of a thrombosis as a later-period complication of CVC is one of the significant causes of catheter malfunction. Catheter thromboses are divided into extrinsic and intrinsic thromboses. Extrinsic thromboses include mural thrombosis, central vein thrombosis and atrial thrombosis and intrinsic thromboses include intraluminal, catheter-type thrombosis and fibrin sheaths **(**Floege &Lonnemann, 2000*).* The percentage of catheter thromboses that may require removal of catheters is reported to be between 17 and 33% (Chan,2008). The risk factors involved in a catheter thrombosis are formation of a fibrin sheath, venous stasis, catheter malposition, a patient-related predisposing factor that creates tendency towards thrombosis, and failure to make sufficient heparinisation during the hemodialysis (Mandolfo et al., 2002; Dinwiddie, 2004). Central vein thrombosis is important in that it may prevent efficient dialysis in the clinic, produce tendency towards catheter infection and cause mortality and morbidity. Antiplatelet and anticoagulant drugs have been used in various trials to prevent catheter thrombosis. Buturovic et al compared heparin, citrate and polygeline for their efficacy in preventing catheter thrombosis and found that duration of using catheters was longer in the group taking citrate than in other groups (Buturovic et al., 1998). In a study conducted by Filiopoulos V et al, the efficacy of two groups of catheter lock solutions (gentamicin/heparin and taurolidine/citrate) in preventing catheter infection and thrombosis was assessed. Catheter-related bacteremia and thrombosis were seen in similar rates in both groups and catheters could be used for 3 months on the average without any thrombosis (Filiopoulos et al., 2011). Another trial investigated the efficacy of tPA in reducing catheter thrombosis and infection. The trial evaluated the difference between the use of heparin as a catheter lock solution 3 times a week and the use of rt-PA once a week plus heparin in the other days. It was observed after a 6-month monitoring that the rate of catheter-related thrombosis and bacteremia decreased with the use of rt-PA (Hemmelgarn et al.,2011). Another study assessed the efficacy of a solution containing 0.24 M (7.0%) of sodium citrate, 0.15% methylene blue, 0.15% methylparaben, and 0.015% propylparaben (C-MB-P) against heparin and revealed that the group taking C-MB-P experienced less catheterrelated infection and thrombosis (Maki et al.,2010). It can be concluded that the use of catheter lock solutions may be appropriate in preventing catheter-related infection and thrombosis. In treating catheter thrombosis, thrombolytics are administered using either an intraluminal lytic, intradialytic lock protocol, or an intracatheter thrombolytic infusion or interdialytic lock (NKF KDOQI,2006). It is recommended that the use of anticoagulants after a thrombolytic treatment is decided on the basis of a potential benefit and harm assessment

because they have plenty of side-effects (Mondolfo & Gallieni, 2010).

hospitalization and thus in costs (Ishani et al., 2005; Inrig et al.,2006).

Bacteremia is seen in patients using CVCs 7.6 times as much when compared to patients using AVFs (Hoen et al., 1998). The average prevalence of catheter-related bacteremia is 3-4 episodes / 1000 catheter days; this rate is slightly higher in non-tunneled catheters (NKF KDOQI,2006; Battistella et al.,2011). Catheter-related bacteremia may often result in serious infections such as endocarditis, osteomyelitis, epidural abscess and septic arthritis (Hoen et al., 1998). In conclusion, the rate of mortality in patients using CVC was found to be 2.3 times as much in diabetic ones and 1.83 times as much in non-diabetic ones as compared to those using fistulas. The use of CVC also causes an increase in the frequency of

*2.4.1.2.2 Central venous catheter infections* 

*2.4.1.2.1 Thrombosis in central venous catheter* 

not observe any pneumothorax when placing 460 internal jugular dialysis catheters (Farrell et al.,1997).

Carotid artery puncture and hematoma during placing of CVCs occur less frequently when they are placed with the help of USG as is the case in other complications. For example, in the study carried out by Farrell J et al, carotid artery puncture was seen 7.6% of the whole patient group and hematoma in 12% of it whereas carotid artery puncture was not observed in patients whose catheters were placed under USG (Farrell et al.,1997). In the study where Oguzkurt et al made 220 internal jugular vein catheterizations under USG, 78% of the patients were under risk in terms of catheter complications such as hematologic complications and incompatibility. Yet, a 100% technical success was achieved in that study and only 4% minor complications developed. Carotid artery puncture was observed in 1.8% of the cases, leakage-like bleeding around the catheter in 1.4% of the cases and minor hematoma in 0.4% of the cases (Oguzkurt et al.,2005).

Air embolus is a rare complication that is seen during placing of catheters. It is only mentioned as case reports in the literature (Heckmann et al.,2000; Yu & Levy,1997). Intense cardiovascular and pulmonary changes typically occur after air emboli. Symptoms usually vary according to the amount of air, its diffusion in the body and its location (Orebaugh, 1992). Cerebral air emboli may also develop in patients with left-to-right shunts (Yu & Levy,1997). When treating it, air intake should be stopped immediately, air should be aspirated from the right ventricle if the catheter is still in place, the patient should be brought to an upside-down, on-the-left-side position and resuscitation process including cardiopulmonary resuscitation and oxygen support should be initiated (Heckmann et al.,2000).

Therefore, while the occurrence of complications is around 6% even in competent hands (Bour & *Weaver,* 1990), it comes down to 0.8% with the use of USG *(*Trerotola et al., 1997*)*. The said complication percentage is less in jugular vein catheterization than in subclavian vein catheterization (Feldman, 1996).

In addition to the complications developing during placing of catheters, the early catheter dysfunctions are usually associated with the patient's position, mechanical kink, bending of the catheter outside the right atrium and formation of fibrin sheaths. Fibrin sheaths are formed as a result of a pathologic process that follows the placing of a catheter, which is a foreign object for the body, in the vein and a damage occurring in vein endothelium. In general, a fibrin sheath develops within the first 24 hours after the placing of a catheter and in addition to inadequate functioning of the catheter, it may also result in a thrombus, catheter infection and pulmonary emboli after the catheter is removed (Alomari & Falk A, 2007). After any catheter malposition or kink formation is ruled out by radiological exam, 10 mg of saline is given through the catheter. Then the saline is aspirated. Fluid may be injected when a fibrin sheath is diagnosed, but it cannot be aspirated. Although formation of a fibrin sheath is observed as much as 100%, only a portion of them becomes symptomatic (Faintuch&Salazar, 2008). Prevention and treatment of fibrin sheath is similar to those of thrombosis (see below). In treating malpositioned catheters, repositioning or if appropriate replacement of the catheter through the sheath may be considered (National Kidney Foundation: K/DOQI Clinical Practice Guidlines for Vascular Access (NKF KDOQI), 2006).

#### **2.4.1.2 Complications of central venous catheter at later stages**

The CVC complications in later periods include thrombosis, infection and stenosis (Chan,2008).

not observe any pneumothorax when placing 460 internal jugular dialysis catheters (Farrell

Carotid artery puncture and hematoma during placing of CVCs occur less frequently when they are placed with the help of USG as is the case in other complications. For example, in the study carried out by Farrell J et al, carotid artery puncture was seen 7.6% of the whole patient group and hematoma in 12% of it whereas carotid artery puncture was not observed in patients whose catheters were placed under USG (Farrell et al.,1997). In the study where Oguzkurt et al made 220 internal jugular vein catheterizations under USG, 78% of the patients were under risk in terms of catheter complications such as hematologic complications and incompatibility. Yet, a 100% technical success was achieved in that study and only 4% minor complications developed. Carotid artery puncture was observed in 1.8% of the cases, leakage-like bleeding around the catheter in 1.4% of the cases and minor

Air embolus is a rare complication that is seen during placing of catheters. It is only mentioned as case reports in the literature (Heckmann et al.,2000; Yu & Levy,1997). Intense cardiovascular and pulmonary changes typically occur after air emboli. Symptoms usually vary according to the amount of air, its diffusion in the body and its location (Orebaugh, 1992). Cerebral air emboli may also develop in patients with left-to-right shunts (Yu & Levy,1997). When treating it, air intake should be stopped immediately, air should be aspirated from the right ventricle if the catheter is still in place, the patient should be brought to an upside-down, on-the-left-side position and resuscitation process including cardiopulmonary resuscitation and oxygen

Therefore, while the occurrence of complications is around 6% even in competent hands (Bour & *Weaver,* 1990), it comes down to 0.8% with the use of USG *(*Trerotola et al., 1997*)*. The said complication percentage is less in jugular vein catheterization than in subclavian

In addition to the complications developing during placing of catheters, the early catheter dysfunctions are usually associated with the patient's position, mechanical kink, bending of the catheter outside the right atrium and formation of fibrin sheaths. Fibrin sheaths are formed as a result of a pathologic process that follows the placing of a catheter, which is a foreign object for the body, in the vein and a damage occurring in vein endothelium. In general, a fibrin sheath develops within the first 24 hours after the placing of a catheter and in addition to inadequate functioning of the catheter, it may also result in a thrombus, catheter infection and pulmonary emboli after the catheter is removed (Alomari & Falk A, 2007). After any catheter malposition or kink formation is ruled out by radiological exam, 10 mg of saline is given through the catheter. Then the saline is aspirated. Fluid may be injected when a fibrin sheath is diagnosed, but it cannot be aspirated. Although formation of a fibrin sheath is observed as much as 100%, only a portion of them becomes symptomatic (Faintuch&Salazar, 2008). Prevention and treatment of fibrin sheath is similar to those of thrombosis (see below). In treating malpositioned catheters, repositioning or if appropriate replacement of the catheter through the sheath may be considered (National Kidney Foundation: K/DOQI Clinical Practice Guidlines for Vascular Access (NKF KDOQI), 2006).

The CVC complications in later periods include thrombosis, infection and stenosis

hematoma in 0.4% of the cases (Oguzkurt et al.,2005).

support should be initiated (Heckmann et al.,2000).

**2.4.1.2 Complications of central venous catheter at later stages** 

vein catheterization (Feldman, 1996).

(Chan,2008).

et al.,1997).

#### *2.4.1.2.1 Thrombosis in central venous catheter*

Development of a thrombosis as a later-period complication of CVC is one of the significant causes of catheter malfunction. Catheter thromboses are divided into extrinsic and intrinsic thromboses. Extrinsic thromboses include mural thrombosis, central vein thrombosis and atrial thrombosis and intrinsic thromboses include intraluminal, catheter-type thrombosis and fibrin sheaths **(**Floege &Lonnemann, 2000*).* The percentage of catheter thromboses that may require removal of catheters is reported to be between 17 and 33% (Chan,2008). The risk factors involved in a catheter thrombosis are formation of a fibrin sheath, venous stasis, catheter malposition, a patient-related predisposing factor that creates tendency towards thrombosis, and failure to make sufficient heparinisation during the hemodialysis (Mandolfo et al., 2002; Dinwiddie, 2004). Central vein thrombosis is important in that it may prevent efficient dialysis in the clinic, produce tendency towards catheter infection and cause mortality and morbidity. Antiplatelet and anticoagulant drugs have been used in various trials to prevent catheter thrombosis. Buturovic et al compared heparin, citrate and polygeline for their efficacy in preventing catheter thrombosis and found that duration of using catheters was longer in the group taking citrate than in other groups (Buturovic et al., 1998). In a study conducted by Filiopoulos V et al, the efficacy of two groups of catheter lock solutions (gentamicin/heparin and taurolidine/citrate) in preventing catheter infection and thrombosis was assessed. Catheter-related bacteremia and thrombosis were seen in similar rates in both groups and catheters could be used for 3 months on the average without any thrombosis (Filiopoulos et al., 2011). Another trial investigated the efficacy of tPA in reducing catheter thrombosis and infection. The trial evaluated the difference between the use of heparin as a catheter lock solution 3 times a week and the use of rt-PA once a week plus heparin in the other days. It was observed after a 6-month monitoring that the rate of catheter-related thrombosis and bacteremia decreased with the use of rt-PA (Hemmelgarn et al.,2011). Another study assessed the efficacy of a solution containing 0.24 M (7.0%) of sodium citrate, 0.15% methylene blue, 0.15% methylparaben, and 0.015% propylparaben (C-MB-P) against heparin and revealed that the group taking C-MB-P experienced less catheterrelated infection and thrombosis (Maki et al.,2010). It can be concluded that the use of catheter lock solutions may be appropriate in preventing catheter-related infection and thrombosis. In treating catheter thrombosis, thrombolytics are administered using either an intraluminal lytic, intradialytic lock protocol, or an intracatheter thrombolytic infusion or interdialytic lock (NKF KDOQI,2006). It is recommended that the use of anticoagulants after a thrombolytic treatment is decided on the basis of a potential benefit and harm assessment because they have plenty of side-effects (Mondolfo & Gallieni, 2010).

#### *2.4.1.2.2 Central venous catheter infections*

Bacteremia is seen in patients using CVCs 7.6 times as much when compared to patients using AVFs (Hoen et al., 1998). The average prevalence of catheter-related bacteremia is 3-4 episodes / 1000 catheter days; this rate is slightly higher in non-tunneled catheters (NKF KDOQI,2006; Battistella et al.,2011). Catheter-related bacteremia may often result in serious infections such as endocarditis, osteomyelitis, epidural abscess and septic arthritis (Hoen et al., 1998). In conclusion, the rate of mortality in patients using CVC was found to be 2.3 times as much in diabetic ones and 1.83 times as much in non-diabetic ones as compared to those using fistulas. The use of CVC also causes an increase in the frequency of hospitalization and thus in costs (Ishani et al., 2005; Inrig et al.,2006).

Acute Complications of Hemodialysis 263

the side of stenosis and administration of hemodialysis cause an increase in the symptoms and signs. The stenosis restricts blood flow in the hemodialysis access in the clinic and results in an insufficient hemodialysis (Agarwal et al., 2007; Kundu, 2010). Occurrence of AVF complications particularly in patients with a subclavian vein stenosis is more common and the gold standard for its diagnosis is the digital subtraction venography (Lumsden et

A percutaneous transluminal angioplasty with or without a stent is recommended for

Nonetheless, the CVCs are important instruments as they enable urgent initiation of a treatment in some hemodialysis patients and maintain a long-term therapy in the others. Therefore, in order to prevent catheter withdrawal we mentioned earlier and the complications that result in morbidity or even mortality in patients, it is necessary that blood is easily aspirated from the catheter of a patient at the beginning of a hemodialysis session, sufficient blood flow is attained during the session and the patient's hemodialysis efficiency is monitored. When there is a deviation in the monitoring parameters it is important to check the catheter for any dysfunction and to employ an appropriate treatment approach. Moreover, the target should be that the percentage of CVC usage in the

Use of AVF is recommended as it is superior in enabling sufficient blood flow in hemodialysis patient group and has fewer complications. NKF DOQI targets the percentage of AVF usage in hemodialysis units to be 65% (NKF KDOQI,2006). AVFs are more commonly preferred to AVGs. The reason for AVFs to be preferred more than grafts is that they have longer access life because there are fewer incidences of thrombosis or infection and fewer procedures requiring punctures, and the cost is less. It was shown in various studies that access-related complications were 3 to 7 times more in AVGs than in fistulae (Di Iorio et al., 2004; Enzler et al.,1996; Gibson et al., 2001a; Gibson et al., 2001b). The access potency was found in a study to be 85% in negative AVF while it was 40% in

Besides its advantages, AVFs also involve some complications. While a maturation defect in AVFs lead to venous stenosis and thrombosis, low dialysis blood flow and inefficiency in dialysis, the high flow rate in fistulae may cause a high-output heart failure. Besides these, access-related infections, steal syndrome and aneurism are other complications associated with AVFs. Arteriovenous fistulae are required to mature in 6 weeks on the average. The factors influencing development of a maturation defect include age, DM, obesity and female gender (Allon et al., 2000; Enzler et al.,1996; Lin et al., 1998). A fistulography may be attempted in cases involving immature fistulae (NKF KDOQI,2006). A cause-oriented

AVF thrombosis is the major cause of access failure. An average of 0.5 to 0.8 fistula thrombosis is observed per patient in a year (Fan & Schwab, 1992). The cause in 85% of the cases is venous stenosis resulting from neointimal hyperplasia (Bent et al., 2011). The other reasons that create a tendency to fistula thrombosis are excessive compression on the fistula after dialysis, hypotension, hypovolemia, susceptibility to hypercoagulation, arterial

al., 1997).

treating the stenosis (NKF KDOQI,2006).

**2.4.2.1 Arteriovenous fistula** 

grafts (Hodges et al., 1997).

treatment may be employed.

population of hemodialysis patients is less than 10%.

**2.4.2 Use, complications and treatment of arteriovenous fistula/graft** 

Central venous catheter infections are classified mainly in 3 groups.


The factors increasing the risk of a catheter infection include diabetes, peripheral atherosclerosis, previous history of bacteremia, being aged female gender, nasal carriage of Staphylococcus Aureus, long term use of a catheter, the catheter being used very frequently for infusion of various medications, and presence of local infections (NKF KDOQI,2006).

In order to reduce the risk of infection, the catheter exit-side should be checked by an experienced nurse or physician for infection symptoms in every dialysis session, the catheter outlet site should be dressed after every dialysis session and staff should observe the rules of asepsis and wear a mask when dealing with catheters (NKF KDOQI,2006). Catheter lock therapies involving antibiotics may be effective in preventing catheter infections. In the study made on the issue by Battistella et al in recent years, it was demonstrated that a tropical ointment containing polysporin triple ointment (500 U/g of bacitracin, 0.25 mg/g of gramicidin and 10000 U/g of polymixin B) (Lok et al., 2003; Battistella et al., 2011).

The treatment of infected hemodialysis catheters depends on the type and duration of the infection. All the catheter-related infections other than the infection in the exit-side should be treated with a parenteral antibiotherapy suitable for the suspected organisms. If there is growth in the culture taken from the exit-side, again a suitable antibiotherapy should be initiated. When the causative organism is isolated, the antibiotherapy should be adjusted accordingly. The catheters that are thought to have been infected should be replaced as soon as possible, often within 72 hours. A blood culture should be taken for checking a week after the completion of the antibiotics treatment (NKF KDOQI,2006).

#### *2.4.1.2.3 Stenosis associated with the use of central venous stenosis*

Prevalence of central venous stenosis (CVS) was reported to be as much as 30% in the literature (Lumsdenet al., 1997). The risk factors for developing a stenosis include a history of placing more than one catheter, the location of the placed catheter in the body and the catheter being with the patient for a long time. There is also a risk of stenosis when the catheter is placed in the subclavian vein (Agarwal al., 2007). While the prevalence of CVS after placing the catheter in the subclavian vein is 42%, it remains around 10% after placing it in the internal jugular vein (Schillinger et al.,1991).

Central venous stenosis is asymptomatic; it can be detected coincidentally or it may give signs depending on the site where it is placed. A subclavian vein stenosis usually causes a swelling in the arm of the same side and the breast tissue. The bilateral innominate vein stenosis in particular may lead to a vena cava superior syndrome. Insertion of an AVF on

1. **Infection in catheter exit-side:** A generally exudative lesion localized at the catheter exit-side (suspicion) and growth in the culture taken from this lesion (definite

2. **Infection in tunnels:** Signs of infection such as pain and swelling along the tunel of the catheter and purulent discharge from the exit-side (suspicion) and growth in the culture

3. **Catheter-related bacteremia:** Growth in 2 or more blood cultures, but no infection signs exit-side the catheter (suspicion) and colonial unit growth 10 or more times as much in the catheter culture taken concurrently with the blood culture (Division of Nosocomial and Occupationl Infectious Diseases, Bureau of Infectious Diseases, Laboratory Centre

The factors increasing the risk of a catheter infection include diabetes, peripheral atherosclerosis, previous history of bacteremia, being aged female gender, nasal carriage of Staphylococcus Aureus, long term use of a catheter, the catheter being used very frequently for infusion of various medications, and presence of local infections (NKF

In order to reduce the risk of infection, the catheter exit-side should be checked by an experienced nurse or physician for infection symptoms in every dialysis session, the catheter outlet site should be dressed after every dialysis session and staff should observe the rules of asepsis and wear a mask when dealing with catheters (NKF KDOQI,2006). Catheter lock therapies involving antibiotics may be effective in preventing catheter infections. In the study made on the issue by Battistella et al in recent years, it was demonstrated that a tropical ointment containing polysporin triple ointment (500 U/g of bacitracin, 0.25 mg/g of

The treatment of infected hemodialysis catheters depends on the type and duration of the infection. All the catheter-related infections other than the infection in the exit-side should be treated with a parenteral antibiotherapy suitable for the suspected organisms. If there is growth in the culture taken from the exit-side, again a suitable antibiotherapy should be initiated. When the causative organism is isolated, the antibiotherapy should be adjusted accordingly. The catheters that are thought to have been infected should be replaced as soon as possible, often within 72 hours. A blood culture should be taken for checking a week after

Prevalence of central venous stenosis (CVS) was reported to be as much as 30% in the literature (Lumsdenet al., 1997). The risk factors for developing a stenosis include a history of placing more than one catheter, the location of the placed catheter in the body and the catheter being with the patient for a long time. There is also a risk of stenosis when the catheter is placed in the subclavian vein (Agarwal al., 2007). While the prevalence of CVS after placing the catheter in the subclavian vein is 42%, it remains around 10% after placing

Central venous stenosis is asymptomatic; it can be detected coincidentally or it may give signs depending on the site where it is placed. A subclavian vein stenosis usually causes a swelling in the arm of the same side and the breast tissue. The bilateral innominate vein stenosis in particular may lead to a vena cava superior syndrome. Insertion of an AVF on

for Disease Control, Health Canada. (CCDR) 1997; NKF KDOQI,2006).

gramicidin and 10000 U/g of polymixin B) (Lok et al., 2003; Battistella et al., 2011).

the completion of the antibiotics treatment (NKF KDOQI,2006). *2.4.1.2.3 Stenosis associated with the use of central venous stenosis* 

it in the internal jugular vein (Schillinger et al.,1991).

Central venous catheter infections are classified mainly in 3 groups.

diagnosis)

KDOQI,2006).

(definite diagnosis)

the side of stenosis and administration of hemodialysis cause an increase in the symptoms and signs. The stenosis restricts blood flow in the hemodialysis access in the clinic and results in an insufficient hemodialysis (Agarwal et al., 2007; Kundu, 2010). Occurrence of AVF complications particularly in patients with a subclavian vein stenosis is more common and the gold standard for its diagnosis is the digital subtraction venography (Lumsden et al., 1997).

A percutaneous transluminal angioplasty with or without a stent is recommended for treating the stenosis (NKF KDOQI,2006).

Nonetheless, the CVCs are important instruments as they enable urgent initiation of a treatment in some hemodialysis patients and maintain a long-term therapy in the others. Therefore, in order to prevent catheter withdrawal we mentioned earlier and the complications that result in morbidity or even mortality in patients, it is necessary that blood is easily aspirated from the catheter of a patient at the beginning of a hemodialysis session, sufficient blood flow is attained during the session and the patient's hemodialysis efficiency is monitored. When there is a deviation in the monitoring parameters it is important to check the catheter for any dysfunction and to employ an appropriate treatment approach. Moreover, the target should be that the percentage of CVC usage in the population of hemodialysis patients is less than 10%.
