**2.2 Iatrogenic iron overload**

Iron overload has for a long time been considered rare in hemodialysis patients especially currently where erythropoiesis-stimulating agents (ESA) are regularly used to manage anemia in hemodialysis patients [19]. Treatment with these agents can, however, cause functional iron deficiency, necessitating iron supplementation [20]. Most studies in the past two decades focused on the detection and management of iron deficiency among dialysis patients. It was not until recently that iron overload among dialysis patients received attention [21]. Iron overload was generally considered to be more prevalent during the pre-ESA era, and anemia was often treated with blood transfusion. Fewer than 10% of patients in this era were dependent on transfusion, but over time, these patients developed iron overload, making this a problematic clinical issue [22].

Although further investigation is needed, a positive correlation has been reported between serum ferritin and LIC determined by MRI T2\* and that serum ferritin of more than 290 mcg/L is equivalent to severe iron overload on MRI T2\* [23]. A study conducted among Australian dialysis patients with a median ferritin of 782 lg/L by [24] using relaxometry showed that two-thirds of the patients had a hepatic iron overload. In another study, liver iron concentration (LIC) among 119 hemodialysis patients receiving both parenteral iron and ESA was measured by means of T1 and T2\* contrast magnetic resonance imaging (MRI) without gadolinium [25]. The findings showed that only 19 out of 119 hemodialysis patients exhibited normal hepatic iron stores, while the rest of the patients (84%) had mild to severe hepatic iron overload. The iron dose infused per month was strongly correlated with both the overall and monthly increase in LIC in 11 patients who were monitored closely during parenteral iron therapy. Additionally, the MRI showed anomalies in the spleen a sign

of secondary hemosiderosis in several patients [25]. Reported a case of a 68-year-old woman with CKD receiving dialysis and iron supplementation who presented to the hospital with symptoms whose diagnosis revealed a case of porphyria cutanea tards. Upon examination, extremely high serum ferritin levels (6000μg/L), suggesting iron overload, were observed. Oral iron supplementation was immediately discontinued, and iron chelators were administered to the patient. After four-month follow-up, normal ferritin level (97.7 μg/L) and improvement in the cutaneous manifestations of porphyria cutanea tarda were observed [26].

Since the body has no natural way to get rid of iron, excessive intravenous iron can lead to iron overload. According to Aldwairi & Yassin [19], excessive iron infusions can result to cardiovascular events and mortality among hemodialysis patients. Excess iron may accumulate in the heart, liver and endocrine organs, leading to cirrhosis of the liver, heart failure, arrhythmia, diabetes mellitus, increased risk of infection and numerous endocrinopathies [27–30]. The adverse effects of iron supplementation can be attributed to the elevated oxidative stress as well as the induction of mononuclear cell adhesion to endothelial cells, which is a critical stage in the pathogenesis of atherosclerosis [31]. Given these findings, there might be a need to revise the guidelines on iron therapy in hemodialysis, especially in terms of the amount of iron infused.

#### **2.3 Iatrogenic pseudoaneurysm**

Generally, native autogenous arteriovenous fistula (AVF) is the first choice in vascular access for end-stage renal disease (ESRD), patients who need RRT. This is because fistulas have lower complication rates and better longevity compared to prosthetic grafts [32, 33]. Since the AVF needs time before it can be used, the central venous catheter (CVC) is recommended as the alternative hemodialysis access [34]. In some instances, medical staff and patients usually prefer hemodialysis access with a direct puncture in peripheral vascular while waiting for AVF maturation. A direct puncture and insufficient therapy afterward result in a higher risk of pseudoaneurysm [33]. Iatrogenic pseudoaneurysm (PSA) occurs when the puncture site in an artery fails to heal completely causing a leakage of blood to the surrounding tissue, which manifests in the form of a pulsatile hematoma. It can present as a new thrill, bruit, pulsatile swelling, marked pain or tenderness [35]. The rate of PSA occurrence has been reported at approximately 2–10% [33].

A prospective cross-sectional study conducted by Lone et al. [35] on the characteristics of pseudoaneurysms in North India showed that two of the patients had pseudoaneurysms in relation to arterialized cephalic vein post-radio-cephalic AV fistula at cannulation site for hemodialysis (one of them with multiple pseudoaneurysms along the course of an arterialized cephalic vein), one patient had a pseudoaneurysm linked with brachial artery at brachiocephalic arteriovenous (AV) fistula site for hemodialysis, and another one exhibited pseudoaneurysm in relation to carotid artery after their carotid artery was punctured while placing a central line. Similarly, reported the case of a patient requiring hemodialysis referred for a fistulogram to evaluate his right-arm hemodialysis fistula. Imaging revealed an aneurysmal dilatation of the arteriovenous anastomosis of the right brachial artery and right median cubital vein.

Pseudoaneurysm complications include local pain, neuropathy, distal embolization, rupture, and local skin ischemia. It may also lead to local sepsis and abscess formation, which may rupture and cause hemorrhage [36]. Factors that result in pseudoaneurysms include poor puncture techniques, use of large caliber needles, and premature puncturing of the fistula after surgery [32]. Other factors reported

*Iatrogenic Errors in Hemodialysis Practices DOI: http://dx.doi.org/10.5772/intechopen.109493*

to contribute are catheterization for vascular intervention, arterial gas sampling, penetrating and blunt trauma, and drug abuse [32, 37–39]. The different forms of venous pseudoaneurysm are mainly diagnosed by ultrasound AVF monitoring that is especially important when the pseudoaneurysm is deep and not visible [40]. Treatment options for pseudoaneurysms include surgical repair, endovascular treatment, and minimally invasive percutaneous treatments [41]. In the case of femoral artery pseudoaneurysm, ultrasound-guided manual compression is a well-accepted treatment option, but it is seldom reported in hemodialysis arteriovenous fistula [40].

#### **2.4 Iatrogenic infective endocarditis (IE) in hemodialysis patients**

Despite preventive measures implemented by nephrologists, the incidence of IE in CHD remains high. The prevalence of IE in CHD patients is estimated at 2.9% with the incidence being 50–60 times higher than in the general population [40, 42]. The first evidence of IE because of CHD has been described in 1966 and after that, several cases have been reported [40]. A study conducted among French hemodialysis patients showed an overall IE incidence of 2 per 1000 patients, which was 50 times higher than in the general population. The United States healthcare system similarly reported that the incidence of IE among hemodialysis patients was 18 times than that of the general population [43].

It is worth noting that susceptibility to endocarditis in patients undergoing hemodialysis is multifactorial, with numerous factors playing a significant role in the predisposition and development of IE [44]. These factors include those related to the patient's intrinsic susceptibility due to older age and several comorbidities such as hyperuricemia-induced immunosuppression, high exposure to pathogenic microorganisms during hemodialysis sessions following repeated manipulations of their vascular access and the quality of heart valves [44, 45]. The most common location of IE among chronic hemodialysis patients is the left heart and different researchers have reported 80–100% prevalence of left valve involvement. More than 50% of IE cases in CHD are preceded by an episode of bacteremia that originates in more than 70% of cases in a central venous catheter for hemodialysis.

Although international recommendations advocate for use of catheters in less than 10% of patients in a hemodialysis center, this has been difficult to achieve. Catheterrelated bacteremia (CRB) is the most common and most dreaded of complications, with an incidence of 2.5–5.5 episodes per 1000 catheter days. CRB is among the highest contributors to IE development and reducing the frequency of CRB would drastically diminish the occurrence of IE.

#### **2.5 Dialysis-induced hypotension (DIH)**

Dialysis-induced hypotension (DIH) is one of the most frequent complications in RRT and a very serious clinical problem [46]. Dialysis hypotension occurs in one of three clinical patterns including episodic (acute) hypotension, which involves a sudden drop of systolic blood pressure below 90 mmHg or at least 20 mmHg alongside clinical symptoms, recurrent hypotension, which also involves drops in systolic blood pressure to similar levels as acute hypotension but prevailing in at least 50% of dialysis sessions and chronic hypotension whereby less than 90–100 mmHg interdialytic systolic blood pressure is maintained [47]. Intradialytic hypotension occurs in 15–30% of conventional dialysis treatments and approximately 35% of other techniques such as therapeutic apheresis [46, 48]. The incidence of acute DIH has risen to 50% owing to the increasing number of elder and diabetic patients in the hemodialysis population while that of chronic dialysis hypotension is estimated to occur in 3–5% of dialyzed patients [46].

DIH is usually associated with symptoms such as nausea and vomiting, vertigo, muscle cramps, dyspnea, anxiety, abdominal and chest pain light-headedness, weakness, paleness, and sweating, thus diminishing the quality of life of patients. Further, dialysis hypotension may result in the collapse of the arterial and venous fistula (AVF) and is an independent risk factor for mortality among hemodialysis patients [49]. The pathophysiology of DIH has been reported to be multifactorial and is associated with both host-related factors like cardiovascular diseases and hemodialysis factors like the volume and velocity of the ultrafiltration fluid [48]. The main contributors to hypotension during dialysis include incorrect calculation of ideal weight (dry weight) for the patients leading to high filtration rates, dialysis with acetate buffer, autonomic neuropathy especially among elderly patients with diabetes, non-biocompatible materials used in the production of dialysis equipment, low sodium and high calcium or high magnesium dialysate concentration, chronic inflammation caused by dialysis, and high dialysate temperature [46, 48].

Efficient treatment of DIH is still a great challenge to nephrologists. Sufficient therapy is difficult and needs a multilevel strategy. Nephrology staff and patients need to be well informed regarding the possibilities of hypotension, its symptoms, and its effects on dialysis therapy [50]. Emergency management of DIH includes reduction or cessation of ultrafiltration rate and reduction of blood flow rate. Common measures of long-term treatment and prevention of DIH include accurate determination and frequent evaluation of patients' dry weight, educating patients to avoid excessive interdialytic weight gain, prevention of excess salt and fluid intake (sometimes it is essential to skip or reduce drug dose on the day of dialysis session), ensuring proper dialysis fluid temperature, use of bicarbonate dialysate buffer (instead of acetate) and biocompatible membranes, preventing food intake during dialysis, avoiding the use of low-sodium and low-calcium dialysis fluid, and dose adjustments of anti-hypertensive medications [51, 52].

#### **2.6 Iatrogenic cerebral air embolism**

Air embolism is a known iatrogenic clinical problem causing serious morbidity and mortality. It entails the introduction of air into the venous and arterial circulation, which can occur through a myriad of intravascular surgeries and procedures such as hemodialysis [53]. The entrance of air into the systemic veins results in venous air embolism, while entrance into the pulmonary system causes arterial air embolism [54]. Air embolism during renal dialysis is a rare occurrence but potentially catastrophic and often fatal when it occurs [53, 55]. Despite advanced safeguards in procedural techniques and medical hardware, errors may still occur, causing fatal outcomes. Several cases of cerebral embolism during hemodialysis have been reported [55–58].

A case presented by Hysell [57] described a patient with a medical history significant for chronic myeloid leukemia, chronic right foot osteomyelitis, hypertension, and end-stage renal disease on hemodialysis. The patient presented for evaluation of altered mental status alongside acute visual loss after exhibiting symptoms of acute "sleepiness" during dialysis, repetitive speech, and blindness in both eyes upon being aroused. There was no prior history of visual loss and no signs of acute trauma. After examination and considering recent hemodialysis, a head computed tomography

#### *Iatrogenic Errors in Hemodialysis Practices DOI: http://dx.doi.org/10.5772/intechopen.109493*

(CT) scan gave findings consistent with air in vascular structures. The patient was placed on 100% oxygen through a nonrebreather and placed in trendelenburg position, and thereafter transferred to a hyperbolic center for definitive management. This case demonstrates an iatrogenic error where the air was introduced into a patient's vascular system during dialysis. In this case, it was found that the dialysate fluid was changed during the dialysis procedure without pausing the dialysis [56].

Air bubbles can be introduced into the dialysis circuit in numerous ways including pre-existing gas bubbles in dialysis tubing and dialyze, pressure or temperature gradients between the patient and the dialysis machine, turbulent blood flow surrounding venous access sites, and introduction of air during connection/disconnection of dialysis tubing [59]. Although there are protocols in place for proper flushing of lines and catheters, as well as patient positioning, the occurrence of air embolism in hemodialysis remains possible and has proven to be lethal when emboli occlude cardiac, neurologic, and pulmonary vasculature. Furthermore, despite being equipped with air traps and ultrasonic detectors, hemodialysis devices are not infallible in filtering microbubbles coming from Luer lock connector tubing or inadequate priming of dialysis hardware [59–61]. The bubbles might move through the circuit without triggering the system alarm, especially when the bubbles have a diameter of less than 50 μL or the flow rates are below the International Electrotechnical Commission infusion pumps and dialysis machines' standard (0.1ml/kg body weight for bolus infusion or 0.03ml/kg/minute for continuous infusion) [59, 62].

According to Bessereau [63], long-term data from a tertiary center specializing in managing venous air embolism cases showed a 25% mortality rate for patients affected by air embolus with about 50% of the survivors suffering from neurological sequelae permanently. It is worth noting that diagnosis can be difficult, as only 75% of cerebral air embolism patients will manifest visible air on CT [57]. Given the notoriously dreary consequence of venous air embolism despite aggressive treatment, the importance of proper preventive measures can not be overstated. Cerebral air embolism is deemed an emergency and therapy follow guidelines for other air embolus cases including interruption of the dialysis procedure, efforts to aspirate intravascular gas, external cardiac massage, immediate oxygenation, at best under hyperbaric conditions (HBO) and treatment with benzodiazepines, or barbiturates for patients exhibiting seizures [56, 63, 64]. Additionally, positioning the patient in a head-down trendelenburg position has been suggested, preventing intracardiac air from traveling out to the lungs although some studies have demonstrated a lack of clinical improvement with such exercises. This practice should be avoided in patients with cerebral air embolism as it may potentially exacerbate cerebral edema [54, 57].

Research and development of endovascular therapy as a potential treatment for cerebral air embolism is underway with a single case report documenting the capability of using reperfusion techniques to access affected cerebral vessels, mechanically extracting occluding air bubbles. Moreover, balloon-assisted flow reversal, coupled with suction aspiration, has also been demonstrated [65, 66].

#### **2.7 Major bleeding in hemodialysis**

Generally, hemodialysis patients are at a high risk of bleeding due to numerous factors including anemia, uremic platelet dysfunction, and heparin use during dialysis [67]. A retrospective cohort study showed that 1 out of 7 ESRD patients on dialysis experiences a major hemorrhage within 3 years of dialysis initiation [68]. Bleeding in uremia entails an acquired defect of primary hemostasis as a result of platelet



#### **Table 1.**

*Summary of iatrogenic complications, their causes, preventive measures and management and treatment.*

dysfunction, altered interaction between the platelets and vessel wall and systemic anticoagulation caused by intermittent administration of heparin [67, 68]. In addition to hemostatic changes caused by uremia in hemodialysis patients, hemodialysis therapy itself contributes to various hemostatic changes. These include a decrease in the negative effects on platelet functions of middle molecule uremic toxins, assumed to be eliminated during hemodialysis, coagulation cascade activation due to contact between blood elements and the dialysis membrane, and the effect of anticoagulants used to prevent coagulation resulting from the cascade activation [69].

In conventional hemodialysis, heparin is used to prevent clotting in the extracorporeal circuit by inhibiting the intrinsic coagulation pathway. Although the information on the efficacy of the utilization of antiplatelet and anticoagulation agents among hemodialysis patients is scarce, a few studies have reported that their prescription may cause harm [70]. The systemic anticoagulative effect of heparin presents a bleeding risk. To prevent thrombosis or fistula, health providers may prescribe coumarins and aspirin to hemodialysis patients but these further increase the risk of bleeding. In CKD patients, this risk of bleeding may be worsened by insufficient control of hypertension, diabetic retinopathy, gastrointestinal lesions, and renal cystic disease. For patients without ESRD, antithrombotic agents like oral anticoagulants (OAC) are often administered to prevent stroke in atrial fibrillation, while anti-platelet agents (APA) are indicated for preventing myocardial infarction and cardiovascular death. A study by Elliott [71] showed that in ESRD patients, warfarin doubled the risk of major bleeding. Another study among 255 dialysis patients showed that warfarin increased the risk of bleeding up to four times, while aspirin increased the risk by five times [72]. In addition to its effect on platelet function, it may trigger gastric erosions [72]. These studies emphasize the likelihood that anticoagulation and antiplatelet drugs may have a different risk profile in hemodialysis patients and their use singly or in combination might be contraindicated for patients who are already using heparin at every treatment and have known intrinsic platelet dysfunction when receiving dialysis (**Table 1**) [70].
