Canine Heartworm Therapy

Adult heartworm infection continues to be an important clinical problem in enzootic areas, despite widespread availability of numerous effective preventatives. Melarsomine dihydrochloride (Immiticide-Merial Ltd., Duluth, GA) emerged as a novel organic arsenical heartworm adulticide in the mid-90s and is the only available drug approved for this purpose. Although melarsomine dihydrochloride has advantages over its predecessor, sodium thiacetarsamide (Caparsolate-Merial Ltd., Duluth, GA ), such as better safety and more efficacy, important complications still occur.^1-2 Understanding the types and causes of major complications can minimize the frequency and severity of these events and in some situations prevent them altogether.

Complications of adulticide therapy can be divided into two major categories: those associated with direct toxicity and those associated with efficacy. Direct toxicity most frequently manifests as local tissue reactions. Side effects associated with efficacy result from the demise of adult heartworms; these effects include pulmonary thromboembolism and, infrequently, congestive heart failure.

The composition of the product makes meticulous administration imperative. Although they are usually mild, local tissue reactions are among the most common adverse reactions. However, inadvertent injection of even a small amount of the product into the subcutaneous space can result in much more severe inflammation and, infrequently, local tissue necrosis (Figure 1). Hettlich and colleagues recently reported three cases in which severe neurologic signs, including marked motor and proprioceptive deficits, paraparesis, and seizures, were temporally related to administration of melarsomine.³ The article implied that imperfect injection technique may have played a role.

Prevention

Local ReactionsThe best way to prevent local reactions is strict adherence to injection technique guidelines. Explicit instructions on deep lumbar intramuscular administration technique are provided in the package insert, and the manufacturer has recently produced an instructional video to further reduce adverse postinjection events. We frequently use mild to moderate sedation in uncooperative patients to further reduce the likelihood of imperfect injection technique.

Pulmonary Thromboembolism Staging the severity of infection to determine which patients should be treated with a three-injection "split-dose" has been advocated as a means by which important pulmonary thromboembolism might be prevented (Table 1).^1,2 Severe adverse reactions may still be noted when dogs are categorized (incorrectly or correctly) as having class 1 or class 2 heartworm disease and are subsequently treated with the traditional two-injection regimen (Figures 2 and 3).

Three injection technique. To minimize the chance of thromboembolic complications, we have adapted an alternative approach, using the three-injection ("split-dose") method in all patients with class 1, 2, or 3 disease.^4,5 Dogs are placed into disease severity classes based on a combination of clinical parameters emphasizing physical examination, historical findings, routine laboratory tests, and results of thoracic radiography. Specific criteria for assigning a patient a specific disease classification are detailed in the Immiticide package insert. Studies have shown that patients treated with the split-dose regimen have a higher rate of seroconversion to a negative antigen status (89.7%) than those treated with either caparsolate (65.9%) or the standard melarsomine dosing regimen (76.2%).^1,2 In addition, a study of experimental heartworm infection in dogs showed that more effective adulticide activity did not appear to increase the severity of clinically apparent pulmonary hypertension or thromboembolism.

Corticosteroids. To further decrease clinical signs associated with worm embolization, the author advocates routine use of corticosteroids in patients receiving adulticide therapy. Steroids may also decrease the severity of local tissue inflammation associated with melarsomine injections.

Exercise restriction. The severity of thromboembolic complications can be further diminished by restricting exercise.⁶ The author recommends 1 month of extremely restricted exercise after adulticidal therapy. The method and degree of restriction varies with client needs and the pet's usual activity level but might include hospitalization, cage rest, sedation, housing in a restricted room of the house or garage, and use of only gentle leash walks.

Use of preventatives. Recent evidence has shown that many of the monthly preventatives, when administered continuously as directed, have some efficacy as adulticides.⁷ This has prompted the suggestion that certain monthly preventatives be administered continuously in lieu of specific adulticidal therapy, the argument being that gradual death of adult worms reduces the likelihood of important pulmonary thromboembolic complications. However, on the basis of current knowledge⁸ and the availability of a Food and Drug Administration-approved effective adulticidal product, neither the author nor the American Heartworm Society9 advocates this approach. The author believes that long-term administration of preventatives as an adulticidal strategy predisposes some dogs to important vascular changes that may result in pulmonary hypertension in later years.

Treatment

Local Tissue ReactionsNo specific therapy has been proven to decrease the severity of local injection reactions. These complications, as well as neurologic complications, are best handled with supportive measures. In a study of three dogs with neurologic complications, two recovered after aggressive supportive care but the third was euthanized due to the severity of the clinical signs.³

Pulmonary ThromboembolismA list of agents used to manage heartworm-associated pulmonary thromboembolism is given in Table 2. When signs of pulmonary thromboembolic disease are mild (i.e., limited to occasional cough without evidence of respiratory distress), specific therapy is probably unnecessary. In patients with respiratory compromise, supplemental oxygen administration is of paramount importance. Nasal insufflation is ideal to allow ongoing access to the patient without interruption of oxygen supplementation. Although corticosteroids have the potential to be procoagulant, they play a vital role in management of patients with heartworm-related pulmonary thromboembolism. Reduction of pulmonary parenchymal inflammation coupled with supplemental oxygen administration is the pillar of supportive care.

Although heartworm patients have an increased amount of pulmonary fluid and by definition pulmonary edema, it is due to increased vascular permeability rather than increased venous hydrostatic pressure. Aggressive diuretic therapy, therefore, is unlikely to benefit the patient and may even be detrimental by decreasing plasma volume and subsequently cardiac output.

The efficacy of thrombolytic agents (tissue plasminogen activator, streptokinase, urokinase) is unproven and not recommended; however, measures to prevent progressive clot formation, such as use of heparin, should be considered. In this situation, the utility of aspirin is questionable and its use is no longer advocated by the American Heartworm Society.⁹ Routine use of antibiotics in these patients is not supported by evidence or a logical rationale.

Congestive Heart FailureIn the rare cases of congestive heart failure developing after adulticide therapy, it is important to determine if pulmonary thromboembolism has caused severe pulmonary hypertension or whether therapy has resulted in worm migration. If worm migration has occurred such that a substantive worm biomass is in an accessible location, the mass should be extracted expeditiously (Figure 4). Specific therapy aimed at reducing pulmonary arterial pressure using potent vasodilators (hydralazine or diltiazem) is occasionally beneficial in patients with evidence of pulmonary hypertension and congestive heart failure. The most consistent reductions in pulmonary arterial pressure are seen secondary to supplemental oxygen administration. Systemic hypotension is an important side effect of potent vasodilators and may be compounded by concurrent use of diuretics. Recurrent ascites is usually best managed with conservative diuresis and periodic abdominocentesis.

Disease Prevention Is Paramount Even with strict adherence to pretreatment patient evaluation and meticulous administration of medications, important and occasionally life-threatening complications can occur. Understanding these complications should allow early recognition, if not prevention, in many cases. Ultimately, however, the most effective way to avoid complications with adulticide therapy is to ensure that any animal at risk for infection is receiving optimal preventive medication.