Acute Complication during Hemodialysis

Abstract

Haemodialysis was first done successfully in humans, in 1945, and since then a lot of technological advancements have been made, there are still common acute complications that are encountered by physicians during their routine practice. The common complications include intradialytic hypotension, hypertension, arrhythmias, muscle cramps, sudden cardiac death, headache, etc., occurring in about 10–70% of patients undergoing haemodialysis. The mechanism of these complications is multifactorial and treatment of these complications is important to prevent mortality of the patients. Prevention is important including multiple disciplinary approaches. Here we discuss some of the common complications that occur in routine haemodialysis sessions.

1. Introduction

Haemodialysis was first done successfully in humans, in 1945, and since then a lot of technological advancements have been made [1].

There are still common acute complications that are encountered by physicians during their routine practice. The common complications include intradialytic hypotension and hypertension, muscle cramps, clotting of the circuit and dialyzer reactions. Some are severe and lead to increase mortality of the patients hence they need to be identified and treated early, some are mild, which again need early identification and management to avoid cumbersome tests and intervention. These are discussed briefly below, under systematic headings.

2. Acute complications during haemodialysis

We will discuss some of the common acute complications that occur during routine haemodialysis sessions and are categorized as below:

2.1 Cardiovascular complications

The common cardiovascular complication that may occur during haemodialysis include:

2.1.1 Intradialytic hypotension(IDH)

IDH is defined as, decrease in systolic blood pressure by ≥20 mmHg or a decrease in MAP of ≥10 mmHg associated with symptoms of dizziness, restlessness or need for intervention by a supporting staff. It occurs in about 10–40% of dialysis treatment, the discrepancy in prevalence is not known exactly but may be due to use of various definition of IDH (Table 1) [1, 2].

	Decrease in SBP (mmHg)	Decrease in MAP (mmHg)	Symptoms or need for intervention
KDOQI clinical practice guidelines (2005)	≥20	≥10	Symptoms.
European Best practice (2007)	≥20	≥20	Symptoms and intervention.
UK renal association guidelines (2011)	Any	Any	Immediate intervention

Table 1.

Different definitions of intradialytic hypotension.

Pathogenesis of IDH is complex and includes:

1. Excessive ultrafiltration.

2. Reduce plasma filling.

3. Cardiac disease.

4. Dialyzer reaction.

5. Haemolysis.

Leading to reduced effective circulating volume and subsequently intradialytic hypotension.

Clinical features include; abdominal discomfort, nausea and vomiting, muscle cramp, dizziness and anxiety.

IDH is associated with several notable clinical consequences, the most common are cardiovascular events and mortality.

It is associated with myocardial stunning, a reversible phenomenon that occurs due to repetitive ischemia with each episode of IDH and may initiate myocardial fibrosis and irreversible systolic dysfunction. Similarly reduced cerebral perfusion with each episode of IDH is associated with an increased risk of new-onset dementia. IDH also accelerates the loss of residual renal function with repeated episodes of hypotension, and less commonly IDH is also associated with vascular access thrombosis and mesenteric and liver ischemia.

Management strategy includes:

Several approaches have been suggested to treat IDH which include:

1. Immediate treatment:

   • Placing the patient in Trendelenburg position.

   • I.V bolus of 0.9% normal saline >100 ml, and slowing the UF to allow time for plasma refill and restoration of B.P.

   • Observing for hemodynamic status and subsequently managing patient further.

2. Prevention

   • Adjusting dialysis prescription:

     1. A cool dialysate below core body temperature induces vasoconstriction and activates sympathetic nervous system decreasing the risk of IDH.

     2. Adjusting UF rate to ≤10 ml/kg/hr, as UF rate above >10 ml/kg/hr has been associated with an increased risk of a cardiovascular event and all-cause mortality.

     3. Adjusting dialysate sodium concentration has shown conflicting results, and hence no current recommendation can be given.

     4. Technique like hemofiltration outcome on mortality is still controversial and cannot be recommended for now.

     5. Use of drugs, midodrine an alpha 1 adrenergic receptor agonist, was associated with increased mortality and should not be used routinely.

     6. Lowering antihypertensive drugs on dialysis days can be an option that needs to be compared in randomized trials.

     7. Switching to PD is one of the alternatives to avoid intradialytic hypotension, as IDH is rarely seen in a patient undergoing PD.

2.1.2 Intradialytic hypertension

Intradialytic hypertension is a paradoxical rise in blood pressure that occurs during a haemodialysis procedure. it is another common complication that occurs in about 8–30% of dialysis sessions and is associated with high mortality [1, 3].

There are no accepted criteria, however, is commonly defined as a rise of systolic blood pressure >10 mmHg during HD, a rise of MAP > 15 mmHg during or immediately post-HD and/or any rise of blood pressure during HD.

Etiopathogenesis of interdialytic hypertension includes:

Pathogenesis of intradialytic hypertension is unknown. However, it represents a state of volume overload, sympathetic overactivity, RAAS activation, endothelial dysfunction, increased level of endothelin 1, ESAs and sodium loading during dialysis.

Treatment includes:

During dialysis treatment should be done once SBP >180 mmHg during dialysis.

Interdialytic hypertension is best treated with drugs like clonidine or RAAS blockers like enalapril, other antihypertensive agents can be used as well.

Preventive measures include:

1. Optimization of dry weight.

2. Adjustment of antihypertensive agents:

   There are several antihypertensive agents used in a patient under maintenance dialysis and the knowledge of dializability will help in adjusting the dose of drugs. The dialyzable drugs need to be repeated after a haemodialysis session (Table 2).

1. Adjustment of ESAs.

2. Consider low dialysate sodium about 136 mmol/l have shown to reduce incidence of intradialytic hypertension.

Antihypertensive agents	Dialysable	Not dialyzable
Calcium channel blocker
Amlodipine		√
Verapamil		√
ARBs
Losartan		√
Telmisartan		√
ACEi
Enalapril	√
Fosinopril		√
Beta-blocker
Carvedilol		√
Metoprolol succinate	√
Atenolol	√
Bisoprolol		√
Others
Clonidine		√
Prazosin		√

Table 2.

List of common antihypertensive drugs in haemodialysis patients.

In a study performed in haemodialysis patients, dry weight reduction in hypertensive haemodialysis patients (DRIP) suggested that optimal control of BP in HD is via control of extracellular fluid volume and not the use of antihypertensive agents [4].

2.1.3 Arrhythmias

Intradialytic arrhythmias are common and are often multifactorial in origin, it represents a bad prognostic sign hence early identification and treatment are of paramount importance [5].

Bradycardia and asystole are more common followed by ventricular arrhythmias.

Pathophysiology of intradialytic arrhythmias:

The pre-existing cardiac structural abnormality along with the acid-base disorder, electrolyte imbalance and dialysate component creates an arrhythmogenic milieu. And patients under maintenance dialysis are at increased risk of arrhythmias.

Clinical presentation can range from asymptomatic patients to patients presenting with palpitations, chest pain, dizziness, syncope and sudden cardiac death.

Management includes:

1. Immediate treatment: maintaining hemodynamic stability.

2. Preventive strategy includes:

   • Complete cardiac evaluation and treating the type of arrhythmias with anti-arrhythmic drugs or devices.

   • Adjusting dialysate content:

   • A low calcium dialysate of <2.5 mEq/L have been associated with an increased risk of sudden cardiac death.

   • A low potassium dialysate <2 mEq/L has been associated with an increased risk of sudden cardiac death.

   • A high bicarbonate dialysate should be avoided, the optimum level is chosen empirically to correct metabolic acidosis.

2.1.4 Sudden death

Cardiac arrest is more common in elderly, diabetes, and patient using central venous catheters [5].

Aetiology is complex and related to pre-existing cardiac disease coupled with uremic milieu, that is inappropriate management of fluid volume and inadequate uremic toxins clearance [3, 4].

When sudden cardiac arrest occurs during dialysis, an immediate decision is to be made whether it is due to intrinsic cardiac disease or technical errors like air embolism, line disconnection, or sterilant in the dialyzer [5].

If no obvious cause is identified, blood should not be returned to patient.

Standard CPR should be performed.

2.2 Neuromuscular complication

2.2.1 Muscle cramps

Muscle cramps are a common cause of intradialytic discomfort and a frequent complication with an incidence of 5–20% in haemodialysis sessions [6].

It frequently involves the leg and leads to premature termination of haemodialysis.

Pathogenesis is unknown and largely attributed to dialysis-induced volume contraction and hypo-osmolality.

Management strategy includes increasing plasma osmolality by infusion of hypertonic saline (15 ml of 23.5%), or 50% dextrose in water (25–50 ml), or mannitol 25% (50 ml) [6, 7]. Evaluating for other causes of muscle cramps like thyroid disorder and electrolyte disturbances.

Prevention includes dietary counselling about excessive weight gain.

Beneficial effects of quinine sulphate (250–300 mg) or oxazepam (5 mg) given two hours prior to dialysis have been seen in some studies.

In some of the studies, vitamins E, L-carnitine, and enalapril have been used with some success [7].

2.2.2 Restless leg syndrome (RLS)

It was described in 1944 by K. A. Ekbom and is frequently seen in CKD patients particularly women with crawling leg sensation in leg and a compulsive need to move the limbs, usually leg. It affects 6.6–62% of patients on long-term dialysis [8].

Etiopathogenesis:

It can be familial in about 50% of patients, other risk factors include iron deficiency or iron transport into the CNS, which led to defects in iron homeostasis and downregulation of striatal dopamine receptors.

Management includes:

1. Assess iron store and consider appropriate repletion.

2. Asses other co-existing sleep disorders and assess drugs causing RLS.

3. Non-pharmacologic treatment includes: avoid alcohol and caffeine.

Drugs: use of alpha2-delta calcium channel ligands such as gabapentin, pregabalin and dopamine agonist like pramipexole 0.125–0.5 mg at night are used, the mechanism of how they act is not known, and opioids have been used with some success.

Optimising dialysis with increased duration and frequency has been associated with a decreased incidence of RLS in FREEDOM study [9]. Middle molecules like alpha1 microglobulin have been linked to recurrence of restless leg syndrome in patient undergoing hemodialysis in small studies, however, more data are needed to reach into conclusion.

RLS improves in most of patients after kidney transplantation.

2.2.3 Seizures

It occurs in <10% of patients during dialysis and tends to be generalized. Focal seizure warrants evaluation for focal neurological cause [10].

Causes of seizure during haemodialysis include:

1. Drugs: erythropoietin, dialytic removal of anti-epileptics.

2. Metabolic: hypoglycaemia, hypocalcaemia, hypomagnesemia and hypernatremia.

3. Uremic encephalopathy.

4. Focal neurologic disease: haemorrhage.

5. Other: cardiac arrhythmia and hypertensive encephalopathy.

Treatment may require cessation of dialysis, maintenance of airway, i.v lorazepam and subsequent investigations.

2.2.4 Headache

It is one of the common complications during haemodialysis with a prevalence of 27–73% and consists of bilateral frontal discomfort that is accompanied by nausea and vomiting, but no visual disturbance [11].

Etiopathogenesis is not completely understood.

Management strategy includes:

Optimization of haemodialysis, avoidance of caffeine and blood pressure control.

However, no drugs have been compared in randomized trials to prevent dialysis-related headaches.

2.3 Haematological complication

2.3.1 Intradialytic haemolysis

Acute haemolysis during haemodialysis can be due to variety of causes, which include [12]:

1. Equipment related: faulty tubing, kinking, small size cannula, abnormalities of blood flow and pumps.

2. Toxins: chloramines, copper, zinc, formaldehyde, sodium hypochlorite, etc.

3. Patient related: uremia, infection, lack of erythropoietin, etc.

4. Drugs: aspirin, sulfonamides, penicillins, etc.

Diagnosis is evident with grossly translucent haemolysed blood observed in the tubing.

Evaluation should include, complete blood count, peripheral blood smear, reticulocyte count, haptoglobin, lactate dehydrogenase, coombs test and analysis of water and dialysis equipment.

2.3.2 Haemorrhage

It is associated with intradialytic use of heparin, a common anticoagulant used during haemodialysis. Bleeding can occur from any site like gastrointestinal, pleural, pericardial, retroperitoneal, etc. [13]. diagnosis includes measuring bleeding time despite limitations.

Management includes reversal of precipitating factor, use of erythropoietin stimulating agents, maintaining haematocrit value above 30%, use of i.v DDAVP at 0.3 mcg/kg and infusion of cryoprecipitate as required.

2.4 Pulmonary complications

2.4.1 Dialysis-associated hypoxemia

During dialysis arterial PaO₂ decreases by 5–20 mmHg reaching nadir at 30–60 minutes then resolves within 60–120 minutes after discontinuation of dialysis. This is usually of no significance unless patient has pre-existing cardiopulmonary disease [14].

In high-risk patients, preventive measures include intradialytic use of oxygen, conventional bicarbonate dialysate, and biocompatible membranes. Further optimizing haematocrit and performing sequential isolated UF followed by HD may reduce the likelihood of hypoxemia.

2.5 Technical malfunction

2.5.1 Air embolism

It is a fatal complication, though rare should be identified early and treated accordingly [15].

Most vulnerable source of air entry into extracorporeal circuit includes pre-pump tubing segment. Other sites include glass bottles, air bubbles in dialysate, and uncuff dialysis catheters.

Clinical manifestation depends on position of patient and includes:

1. Sitting position, seizure, and coma in absence of chest symptoms.

2. Supine position; obstructive shock, dyspnea, dry cough, and chest tightness.

Immediate management includes: clamping the venous blood line, stopping the blood pump, placing the patient in Trendelenburg position, providing CPR if required, aspirating air from right ventricle and/or hyperbaric oxygen therapy as required.

Preventive measures include checking air detecting alarm system prior to initiating haemodialysis, flushing dialysis catheter prior to dialysis, and dialyzer rinsing before use.

2.5.2 Incorrect dialysate composition

Life-threatening electrolyte disturbance can occur due to incorrect mixing and can be corrected by checking composition prior to initiating dialysis it is usually due to human error, however, nowadays there is a machine that automatically changes the mixing ratio of the concentrate until dialysate solution conductivity falls within the set limits [1, 16].

2.5.3 Clotting of dialysis circuit

Clotting of extracorporeal circuit is a common problem encountered during dialysis and warrants thorough evaluation [1].

Various causes are listed below:

1. Technical: inadequate or poor priming technique.

2. Incorrect heparin loading and maintenance.

3. Vascular access related: inadequate flow, excessive access recirculation and frequent interruption of blood flow.

Management includes prompt identification of cause and correcting it.

2.6 Dialysis reaction

Interaction between patients’ blood and dialyzer can lead to various adverse reactions [16].

The common dialyzer reactions include:

2.6.1 Type A dialyzer reaction

It was attributed to dialyzer sterilant ethylene oxide, which is rarely used now, and now it is recommended that dialyzers that are validated for re-use should be approved for re-use. The sterilization should be as per the manufacturer’s guidance by heat sterilization, gamma radiation or chemicals like formaldehyde, sodium hypochlorite or peracetic acid.

Symptoms usually develop early between 5 and 20 minutes after start of dialysis and include burning throughout the body and access site, dyspnea, chest tightness and angioedema.

Other symptoms like rhinorrhea, lacrimation, cough, pruritis, nausea and vomiting could also be seen.

Management includes cessation of dialysis, drugs like hydrocortisone, antihistamine and epinephrine with or without respiratory support.

Preventive measures include substituting ethylene oxide, biocompatible membranes and discontinuing reprocessing procedures.

2.6.2 Type B dialyzer reaction

It occurs between 20 and 40 minutes after initiation of dialysis.

The cause is attributed to complement activation.

Symptoms include: chest pain and back pain, which subsided with continuation of dialysis.

Preventive measures include automated cleansing of dialyzer and use of non-cellulose dialyzer.

2.6.3 Febrile reactions

It can be due to infection of microbial contamination of the dialysis apparatus.

Treatment: first asses the hemodynamic stability of patient, if the patient is hypotensive administer i.v fluid, cease the UF, discontinue dialysis, give antipyretic and evaluate the potential cause of infection.

Evaluation of dialysate, water source, vascular access. Identify the potential source of infection and treat.

2.7 Miscellaneous complications

2.7.1 Post-dialysis fatigue

It is an ill-defined term, suggesting washed-out feeling or malaise during or after hemodialysis by the patient. It is seen in about one-third of the hemodialysis patients and is multifactorial in origin [17].

Reduced cardiac output, peripheral vascular disease, depression, poor conditioning, post-dialysis hypotension, hypokalemia and hypoglycemia are suggested risk factors.

Management include:

Increasing frequency and duration of dialysis have been suggested to reduce post-dialysis fatigue.

L-carnitine supplementation 20 mg/kg/day has been shown benefit in reducing the recovery time in hemodialysis patients.

Post-dialysis fatigue is associated with an increase risk of mortality, the higher the post-dialysis recovery time the higher the mortality risk.

2.7.2 Pruritis

It is a common and troubling symptom of itching, which patients experience during and after haemodialysis, the symptom of which cannot be attributed to other causes [18].

It has a prevalence of 22–48% in haemodialysis patients.

Cause is often multifactorial and includes: xerosis, hyperparathyroidism, neuropathy, immune dysregulation and inadequate dialysis.

The two major hypotheses of pathogenesis of uremic pruritis include:

1. Opiod hypothesis: it proposes that over-expression of opioid μ receptors in dermal cells and lymphocyte predisposes to uremic pruritis.

2. Immune hypothesis: it proposes that uremic pruritis is an inflammatory state rather than local skin disorder.

Other proposed theories include toxin deposition, based on observation that pruritis was associated with underdialysis and CKD-MBD.

Treatment involves:

1. Optimising dialysis: Achieving dialysis adequacy of Kt/V of >1.2 has been associated with reduced incidence of itching.

   Expanded haemodialysis is a new concept in haemodialysis with medium cut-off membrane, which increases the clearance of middle and large molecules without significant albumin loss, compared to conventional haemodialysis, which clears only small molecules. This might help patients with severe pruritic symptoms and other complications of CKD (Table 3) [19].

2. Optimising CKD-MBD disorder.

   1. Skin emollients.

   2. Antihistamines like montelukast or cetirizine.

   3. Phototherapy: UV B (wavelength 280–315 nm) is effective in treatment of pruritis.

   4. Opioid receptor agonist: nalfurafine given iv after HD improved patient experience.

   5. Nalfurafine is an orally active kappa opioid receptor agonist which has shown benefit in treatment of uremic pruritis.

   6. Gabapentin: given 300 mg after HD was effective in reducing pruritis.

   7. Other therapies include capsaicin, long-chain fatty acids and immunosuppressants.

Molecules	Chemicals	Clinical effect
Small molecule (<500 Da)	Urea, creatinine, uric acid, β-lipoprotein	Uremic toxicity
Middle molecule (500–25 kDa)	β-2-microglobulin, leptin, κ-FLC	Amyloidosis, CV disease, malnutrition.
Large molecule (25–45 kDa)	IL-6, TNF-α, prolactin	Atherosclerosis, CV disease, sepsis, endothelial dysfunction.

Table 3.

Various sizes of uremic toxins and their clinical effect.

3. Conclusions

The prevalence of common acute complication of haemodialysis is high ranging from 10 to 70%, despite improvements in technology and knowledge of haemodialysis. Hence, we need to identify the complications as early as possible to treat them and apply preventive measures to improve the outcome of the patients.

Acknowledgments

I would like to thank my professors, colleagues and staff and the patients who helped me to gain experience in haemodialysis.

Conflict of interest

None.

Acronyms and abbreviations

CKD

chronic kidney disease

CPR

cardiopulmonary resuscitation

CNS

central nervous system

ESAs

erythropoietin stimulating agents

HD

haemodialysis

IDH

intradialytic hypotension

MAP

mean arterial pressure

MBD

mineral and bone disorder

PD

peritoneal dialysis

RAAS

renin-angiotensin-aldosterone system

RLS

restless leg syndrome

SBP

systolic blood pressure

UF

ultrafiltration