Common Clinical Problems in Hemodialysis

Reactions Associated With the Dialysis Circuit

Allergic reactions occurring during dialysis are best classified by timing and severity: type A reactions occur within the first 5 to 20 minutes of the HD session with typical anaphylaxis-type symptoms, while type B reactions occur later in the session with milder symptoms. Type A reactions are likely immunoglobulin E (IgE)–mediated, while type B reactions are anaphylactoid and may be related to activation of the complement cascade. In the past, reactions to the dialysis membrane or sterilization technique were common, but most U.S. dialysis facilities now utilize synthetic biocompatible membranes (composed of polymethylmethacrylate, polyethersulfone, polysulfone, or polyacrylonitrile [PAN]), which are irradiated and have a lower risk of reactions. A current reaction of interest is with the use of PAN. In the 1990s, severe anaphylactoid reactions were reported in patients dialyzed with PAN membranes who were taking angiotensin-converting enzyme (ACE) inhibitors. The interaction between the use of ACE inhibitors and PAN membranes may be related to significant increases in bradykinin levels. It is recommended that ACE inhibitors be stopped at least 24 hours prior to the use of a PAN membrane or that alternative dialyzers be utilized.

Rare reactions to dialysis membranes of the polyarylsulfone family (polysulfone, polyethersulfone) have been reported. An analysis of these reactions could not isolate the sterilization method, housing materials, or potting materials as etiologies. Importantly, 85% of these patients also reacted to other dialysis membranes of the same chemical family, and thus, the use of alternative membranes (PAN, substituted cellulose, or polymethylmethacrylate) is needed for these patients.

Reactions Associated With Drugs and Other Exposures

During a dialysis session, patients receive several medications (heparin, erythropoietin, iron compounds), as well as drugs given sporadically for specific indications (antibiotics). Patients can develop reactions to these medications, and a review of medication administration is required for all patients developing a reaction.

There are reports of heparin-induced thrombocytopenia (HIT)-associated anaphylactoid reactions in HD patients occurring 5–30 minutes after intravenous (IV) or subcutaneous administration of either unfractionated heparin (UFH) or low-molecular-weight heparins (LWMH). Clinical features include abrupt falls in platelet counts (consistent with HIT), hypotension or hypertension, wheezing, dyspnea, and cardiovascular collapse. These patients have been found to have anti–platelet factor (PF)-4/heparin antibodies. In addition, both UFH and LWMH have been linked to episodes of typical anaphylaxis during HD. Heparin “allergy” in an HD patient may also be caused by preservatives in the heparin preparation such as paraoxybenzoic esters.

IV iron compounds administered during HD can be associated with a range of adverse reactions, including severe, life-threatening events. The prevalence of hypersensitivity reactions to IV iron preparations is very low (0.01% to 0.1%). IV iron reactions do not appear to be IgE mediated and are likely nonimmune in nature. These reactions can range from minor symptoms such as pruritus, flushing, arthralgias, and myalgias to more significant symptoms such as chest pain, persistent hypotension, shortness of breath, and cardiovascular collapse.

Approach to the Dialysis Patient With a Reaction

A rapid assessment of the patient, as well as a review of the dialysis session, including the medications administered, is a critical first step in responding to a patient reaction. The dialysis procedure should be halted immediately, and blood should not be returned to the patient. Dialysis-related factors such as hemolysis, air embolism, or a pyrogenic reaction should be assessed (see later) before determining that the patient may be suffering from either a dialyzer- or medication-related event. For those patients with signs and symptoms of anaphylaxis, rapid administration of subcutaneous epinephrine, IV corticosteroids, and antihistamines (H ₁ and H ₂ antagonists) should occur, along with respiratory support if needed.

Reactions Associated With Microbiological Contamination

Naturally occurring water bacteria commonly found in HD water systems include gram-negative bacteria (GNB) and nontuberculous mycobacteria. GNB releases endotoxin or lipopolysaccharide (LPS) and other bacterial products. The accepted standards for water purity are those recommended by the Association for the Advancement of Medical Instrumentation (AAMI) and the European Pharmacopeia, which respectively allow bacterial growth of < 200 and < 100 colony-forming facilities (CFU)/mL and an endotoxin concentration of < 2 and < 0.25 IU/mL.

Outbreaks of clusters of infection in HD patients have been ascribed to bacterial contamination that can occur at multiple places along the HD circuit, including the dialysate (bicarbonate solutions are potentially at risk for contamination), carbon filters, inadequate disinfection, and other sources. The passage of endotoxin from the dialysate into the blood can occur by diffusion or convection. High-flux dialyzers increase the risk of passage of endotoxin, particularly lipid A (~ 2000 Da), the active moiety of LPS, from dialysate into blood. This may cause a transient febrile reaction associated with rigors and hypotension. In these cases, careful examination of the dialysis access is warranted, and blood cultures should be obtained. An outbreak of bacteremia among several patients involving a similar organism should prompt a thorough search for bacterial contaminants of the dialysis equipment and water treatment units.

Muscle Cramps

Muscle cramps are defined as prolonged and painful involuntary skeletal muscle contractions and are a common occurrence that has been reported in as many as 33% to 86% of HD treatments. There is little research to guide our understanding of the pathophysiology, therapy, and prevention of muscle cramps. Muscle cramps typically occur near the end of the HD session and most often involve the muscles of the lower extremity. Lower dialysate sodium levels and higher ultrafiltration rates appear to be risk factors.

Acute management often includes transiently slowing or stopping ultrafiltration as well as intradialytic massage and stretching of the affected muscle groups. . For those patients who develop hypotension along with muscle cramps, prompt attention to raising blood pressure (BP) (slowing or stopping ultrafiltration, slowing blood flow rate, placing the patient in Trendelenburg position, and even midodrine) should be the first course of action.

Several strategies have shown variable efficacy in the prevention of muscle cramps. For patients who seem to develop muscle cramps associated with the need for high ultrafiltration rates (such as greater than 10–13 mL/kg/h), minimizing interdialytic weight gains is critical but often difficult to achieve. The length of the HD session could also be increased. Minimizing episodes of intradialytic hypotension (IDH) and the use of sodium modeling may also be effective in some patients. It also may be reasonable to empirically increase the target weight by 0.5 kg to see if this lowers the frequency of muscle cramps. While controversial, L-carnitine supplementation (administered intravenously [20 mg/kg] after HD or orally [330 mg two to three times per day]) in those patients with low levels may decrease the frequency of muscle cramps. Vitamin E supplementation has also shown variable efficacy. There are very limited data on a variety of other therapies, including the use of gabapentin, short-acting benzodiazepines, and phenytoin.