End-stage renal disease (ESRD) is a complication associated with diseases such as diabetes, hypertension, and other glomerulo­nephropathies associated with aging.¹ Annually, more than 350,000 persons require hemodialysis for ESRD in the United States. Within the next decade, this incidence is expected to nearly double.²

The financial implications associated with the management of vascular access for these patients is staggering; costs already exceed $1 billion annually and are expected to rise more than 6% per year.²

Vascular access options for hemodialysis include the placement of arteriovenous (AV) fistulas, AV grafts, and double-lumen, cuffed central vein catheters.³ Vascular access complications constitute one of the most common chief complaints of ESRD patients who present to the emergency department.⁴ The emergency physician must be comfortable managing hemodialysis access problems in order to maintain the long-term functionality of these dialysis access sites and prevent morbidity.⁵

Clotted Arteriovenous Graft/Fistula

An arteriovenous fistula is a surgical anastomosis of an artery with a vein, bypassing the capillary bed, to allow the faster flow rates needed for hemodialysis. Similarly, an arteriovenous graft serves the same function but utilizes a synthetic tube, not the patient’s naive blood vessels, to bridge arterial and venous flow while avoiding tiny capillaries.

Thrombosis represents a common complication contributing to frequent hospitalizations of dialysis-dependent patients.⁶ Between 85% and 90% of AV access thromboses are associated with venous outflow stenotic lesions caused by endothelial and fibromuscular hyperplasia. Physiologically, venous stenosis increases resistance to blood flow, which in turn results in increased venous pressure, decreased blood flow, and ultimately, thrombosis.⁷

Successful diagnosis of a malfunctioning AV graft or fistula mandates a proper evaluation of the dialysis access site. Upon examination, there will be loss of a thrill (a slightly prolonged, vibratory pulsation) or bruit (a “whooshing” sound heard on auscultation) over the access site that indicates stenosis or thrombosis.⁸ Once identified, immediate vascular surgical consultation is warranted in the emergency department.

Surgical thrombectomy has been the standard approach to thrombosed AV grafts/fistulas in the past.⁹ More recently, percutaneous procedures involving thrombolysis with streptokinase or tissue plasminogen activator (tPA) with or without angioplasty have been utilized with variable reported success rates. However, without appropriate specialty consultation, the emergency physician should avoid manipulation of either fistulas or grafts in an attempt to resolve the thrombosis.¹⁰

The 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that each institution should determine whether percutaneous thrombectomy with angioplasty or surgical thrombectomy with graft revision is preferred based on the expertise of the center.^6,11 Systemic thrombolysis or anticoagulation is not supported in this setting.

Clotted Vascular Access Catheters

Although many catheters are used on a temporary basis (Quinton catheter), a growing number of patients use vascular catheters as permanent hemodialysis access (permacath).¹² Thrombosis is a major cause of dysfunction in these catheters, likely secondary to activation of the contact coagulation cascade by a relatively bioincompatible device.¹³

The emergency physician should be familiar with the use of catheter-directed tPA as a solution to a mechanical malfunction of tunneled dialysis catheters.¹⁴ This is a simple technique that is easily done in any emergency department setting.

The minimum dose of tPA required to produce a clinically important thrombolytic effect is unknown. Success has frequently been achieved with administration of 2 mg tPA;¹³ however, there is some evidence that as little as 1 mg per lumen may be effective. Further investigation in this area is needed and would be quite feasible to perform.¹⁴

An example of catheter-directed tPA protocol is described in Table 1.¹⁵ The medication could be prepared in advance by the pharmacy department to be readily available for use in any emergency department.

Currently tPA is available only in 50-mg vials, so it must be divided into appropriately sized aliquots before use. Furthermore, these aliquots must be stored at –20°C until administration.

If the recommended treatments are unsuccessful or if the problem quickly recurs, a radiographic study using contrast should be performed and a catheter exchange should be done when appropriate. Although some institutions’ policy is to treat all catheters with poor blood flow rates with tPA as the initial intervention, the ultimate decision is made by the surgical or interventional radiology team.¹²

Vascular Access Hemorrhage

Although arteriovenous fistula thrombosis and stenosis are more frequently seen, hemorrhage from a vascular access can result in life-threatening blood loss. Dialysis access site hemorrhage typically occurs in the setting of aneurysms, anastomosis rupture, or over-anticoagulation.

ESRD patients also may have bleeding abnormalities stemming from transient thrombocytopenia from anticoagulation during their dialysis session, as well as inherent platelet dysfunction frequently seen in this patient population.¹⁶

Uremia can inhibit platelet aggregation and result in prolonged bleeding times even though other coagulation studies and the platelet count itself will be normal.¹⁷ An abnormal bleeding time, often greater than 15-30 minutes, is the most reliable means to distinguish which uremic patients are at an increased risk of bleeding.

To control hemorrhage, consider the following approaches:

Direct pressure. Any bleeding that warrants an emergency department visit should be immediately controlled with the application of direct digital pressure to the puncture site for 5-10 minutes. Once the bleeding abates, the patient should be observed for rebleeding or early thrombosis for 1-2 hours.

Protamine. Bleeding that occurs within hours of dialysis should prompt consideration of excessive heparin anticoagulation. Under these circumstances, the effects of heparin can be reversed with intravenous protamine administered over 10 minutes. The recommended dose is 1 mg of protamine for every 100 units of heparin given during dialysis.¹⁶ If the heparin dose is unknown, 10-20 mg of protamine should be sufficient.

Gelatin sponges. Commonly seen in the emergency department as Gelfoam®, this adjunct may aid in the hemostasis of bleeding AV grafts. Although studies or case reports of this material being used in this setting are not found in the medical literature, our clinical practice has demonstrated success by including it in the management of this problem.

Gelfoam is a water-insoluble, pliable product that is prepared from purified porcine skin, gelatin granules, and water. Hemostasis is achieved as the gelatinous matrix provides a supporting structure to facilitate the actual clot formation. This mechanism of action does not rely on alteration of the coagulation cascade.¹⁸

To use Gelfoam, the sponge should be removed from its package, and it should be cut to an appropriate size. The sponge may either be applied dry or saturated with sterile, isotonic

sodium chloride solution. The sponge should then be applied with direct pressure to the site of bleeding. Apply sufficient pressure over the sponge to tamponade bleeding, but not so much pressure as to occlude the graft completely. The sponge should be held in place until hemostasis is reached.¹⁸

If an appropriate-sized piece of Gelfoam was utilized, the product should be absorbed completely with little tissue reaction. Once adequate hemostasis is achieved, a compressive bandage may be gently but firmly applied. Again, care should be taken not to occlude the AV graft with compression from this bandage. If one piece of Gelfoam did not achieve hemostasis, another piece may be added on top and the process repeated.

Topical thrombin. Long used in surgical hemostasis, topical thrombin has shown utility in the acute management of vascular access hemorrhage. At its inception, thrombin was bovine derived, but its use was complicated by antibody development that could cross-react with human anticoagulation factors, resulting in anaphylaxis and death. In an effort to minimize these risks, thrombin that is isolated from human plasma donors was developed. Use of human thrombin is limited by the possibility of transmitting blood-borne pathogens. Therefore, FDA-approved recombinant thrombin has recently been developed, with the specific advantages of being minimally antigenic and having less risk of viral disease transmission.¹⁹

Thrombin can be used alone or in combination with an absorbable hemostatic carrier such as Gelfoam, microfibrillar collagen, or oxidized regenerated cellulose. These agents are all structurally porous in nature, providing a framework for platelet and coagulation factor activation.¹⁹

Brand names for topical thrombin include Evithrom, Recothrom, Thombi-Gel, Thrombi-Pad, and Thrombin-JMI.²⁰ Dosing for any of these agents is dependent on the area to be treated and are applied to the bleeding or oozing surfaces directly.

The use of thrombin and absorbable hemostatic agents is well established in several surgical settings. This effectiveness in accelerating hemostasis in moderate to severe bleeding can be applied to the management of vascular access hemorrhage in the emergency department. However, the expense of these agents may prohibit their routine use in minor bleeding.

Desmopressin. Also known as 1-deamino-8-d-arginine vasopressin, DDAVP is a derivative of antidiuretic hormone. Although the literature does not describe DDAVP’s use for the specific management of bleeding AV grafts, there is evidence to support its use in this patient population when they present with other sites of bleeding.

Initially indicated for the treatment of hemophilia A and von Willebrand disease (vWD), today intravenous DDAVP may be used by the emergency physician to manage hemorrhage from either AV grafts or fistulae by negating the platelet dysfunction commonly seen in ESRD patients.

DDAVP’s mechanism of action is currently not well understood, though it has been shown to decrease both activated partial thromboplastin and bleeding times in uremic patients despite the actual platelet count being unaffected.¹⁸ It has also been shown to help prevent bleeding before invasive procedures in dialysis patients.²¹

These effects are likely caused by increases in factor VIII and von Willebrand factor (vWF). What has mystified researchers, however, is how DDAVP is successful in bleeding disorders other than hemophilia and vWD, where factor VIII and vWF are within normal limits.

Various theories exist for DDAVP’s success, including increased platelet adhesion to the vessel wall. These theories include heightened coagulability because of supranormal levels of factor VIII and by the fresh appearance of ultralarge vWF multimers in plasma.²² Regardless of the underlying mechanism, studies have shown the efficacy of DDAVP in providing hemostasis.

Treatment using DDAVP in the emergency department is best accomplished using an intravenous drip at a rate of 0.2-0.3 mcg/kg over 10 minutes; alternatively, the same dose can be diluted in 50-100 mL normal saline and infused over 15-30 minutes.^18,23 Maximum benefit will occur in approximately 30 minutes as peak levels of both factor VIII and vWF are achieved.

The use of DDAVP is contraindicated in cases of polydipsia, unstable angina, or severe congestive heart disease because of its antidiuretic effect. Adverse effects include facial flush, mild and transient headaches, small decreases in blood pressure and heart rate, hyponatremia, seizure, and thromboembolic episodes.²³

Life-Threatening Bleeding

A vascular surgeon should be emergently consulted if hemorrhage cannot be quickly controlled. An adjunctive suture may be placed if there appears to be a small laceration of the graft rather than a puncture wound. This suture is used only after other measures to control bleeding described above have also failed.²⁴

Worst-case scenario, a tourniquet or strong manual pressure can be applied proximal to the puncture site. This will invariably result in thrombosis formation within the graft or fistula, making it nonfunctional. Such extreme measures are rarely necessary, but may be life-saving in specific circumstances.

Conclusion

Vascular access complications are frequently encountered in the emergency department and often warrant an inpatient hospital stay. ESRD patients have coagulopathies that are associated with chronic renal failure or occurring because of repeated utilization of their access sites.²⁵

A more stress-provoking situation is the potential severe hemorrhage that can occur at dialysis access sites.

All bleeding does stop eventually; however, it is incumbent on the emergency physician to know how to manage such bleeding in the uremic patient using the most effective and least invasive method.

References

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