Using drug therapy to treat priapism in two dogs

Priapism is a condition in male animals in which the penis is erect for more than four hours and is constantly engorged after the cause of the sexual excitement is no longer apparent.1 Penile desiccation and ischemic necrosis may develop as a result of chronic external exposure of the organ and subsequent stagnation of blood.

Benjamin H. Cassutto, DVM

In dogs, there is no standard medical treatment for this condition. If the underlying cause of the priapism cannot be corrected and the penis becomes irreparably damaged, perineal urethrostomy and penile amputation must be performed. However, in people, terbutaline, a beta-adrenergic agonist, has been used to successfully treat priapism.2-4 In this article, I describe the successful pharmacologic treatment of priapism in two dogs with a combination of anticholinergic therapy and terbutaline.

CASE REPORT 1

A 1-year-old miniature pinscher was presented to our hospital for treatment of priapism of three days' duration.

History

The owner had adopted the dog from a shelter one month earlier, and preventive care (vaccinations, deworming) had been performed before adoption. The dog was then neutered at the same facility. Instead of sutures, tissue glue was used to close the skin incision initially, and the dog had to be operated on again after reopening its incision.

One week later, the owner left the dog and an intact bitch together in the house. During that time, the patient was constantly after the female, mounting it and trying to breed. When the owner returned home, she removed the patient from the bitch and noticed that the patient was lethargic and its penis was completely out of the sheath and not able to be replaced. According to the owner, the dog was still eating but was polydipsic.

Physical examination

On physical examination, the dog was in excellent body condition and weighed 6 lb (2.7 kg), but it was depressed, dehydrated (6% to 8%), and febrile (103.9 F [39.9 C]). Oral examination revealed moderate dental tartar and tacky mucous membranes. On inspection of the genitalia, the penis was erect and out of its sheath. It was becoming desiccated and dirty and was unable to be replaced in its sheath. Examination of the surrounding area revealed a swelling just below the area of the bulbous penis. The incision from the neutering procedure was healing appropriately. The penis and incision did not seem painful. The rest of the physical examination results were unremarkable.

Initial diagnostic tests

The dog was hospitalized, and a complete blood count (CBC), serum chemistry profile, and urinalysis were performed (Table 1). The CBC revealed anemia, leukocytosis, monocytosis, and thrombocytosis. The serum chemistry profile results revealed azotemia, hyperamylasemia, and hyperglobulinemia. The urinalysis revealed hematuria, protienuria, and cocci.

Table 1 Abnormal Laboratory Findings

Radiographic examination of the spinal cord was recommended since it is indicated in suspected cases of priapism, but the owner declined any further tests.

Differential diagnosis

The primary differential diagnosis for priapism is paraphimosis, which is protrusion of the nonerect penis from the prepuce. This condition was considered to be unlikely in this case because the penis was erect and the arousal or sexual stimulation was no longer present.

Treatment

The penis was washed with a dilute chlorhexidine solution. Because of the hematuria and bacteriuria, the dog was given enrofloxacin (5 mg/kg intramuscularly). Diphenhydramine (2.2 mg/kg intramuscularly) was also administered, and an Elizabethan collar was placed on the dog. The dog was released to the owner, and she was instructed to administer enrofloxacin (5 mg/kg orally) once a day and chlorpheniramine (2 mg/kg orally) three times a day and to apply an antibacterial-plus-cortisone ointment to the dog's penis twice daily to manage inflammation and prevent infection. The owner was advised to bring the dog back to the hospital the next morning to recheck its condition.

The next day, the penis was still out of its sheath. At that time, the decision was made to administer atropine sulfate (0.022 mg/kg intravenously) to see if that would have any effect on the parasympathetic stimulation. An intravenous catheter was placed, and an intravenous dose was administered at 10 a.m. and at 12:30 p.m. The patient's heart rate was measured after atropine administration. The heart rate increased from 140 beats/min before atropine administration to 170 beats/min at 11:10 a.m., 170 beats/min at 12:10 p.m., and 150 beats/min at 3 p.m. Because of the prerenal azotemia, the dog was administered Normosol-R (Hospira; 200 ml subcutaneously) since it was still eating and drinking at home.

Since the two days of chlorpheniramine therapy along with the atropine given throughout the day had little immediate effect on the priapism, the decision was made to treat the dog with a beta-adrenergic agonist and the dog was discharged back to its owner for treatment at home. In addition to the enrofloxacin, chlorpheniramine, and antibacterial-plus-cortisone ointment, the dog was prescribed terbutaline sulfate (Brethine—Novartis; 1.25 mg orally b.i.d.) at the dose recommended for chronic bronchitis5 in a dog for one week to be started immediately that evening. The owner was counseled that if medical treatment of this condition did not quickly yield results, the dog would need surgery (penile amputation, perineal urethrostomy) to alleviate the condition and that typically medical therapy is not successful when instituted this late in a patient's condition. A recheck examination was scheduled for five days later.

Follow-up

Two days later, we received a telephone call from the owner reporting that the dog's penis was 90% back in its sheath. We asked her if she had started the terbutaline immediately the evening of discharge and she indicated that she had. We instructed her to continue administering all of the medications, including the terbutaline, at their prescribed intervals, to keep the Elizabethan collar on the dog, and to come in for the scheduled recheck appointment.

At the recheck appointment, the dog appeared less lethargic. The owner reported that the dog was eating and drinking and reported no adverse effects that would be expected with sympathomimetic agents such as excitability, increased heart rate, or tremors. Aside from an elevated body temperature (104.1 F [40 C]), the physical examination results were normal (heart rate = 160 beats/min) except for slight priapism (the penis was 95% in its sheath).

We questioned the owner about the dog's condition at home because of the fever and recommended a repeat CBC and possibly a urine culture, but she reported that the dog was behaving normally and declined any further tests. The owner was instructed to continue the terbutaline for seven days as well as all other medications, and we scheduled another recheck appointment in one week. We explained that the dog's increased temperature could mean that it still had an ongoing urinary tract infection, so the antibiotic therapy should be continued, and if the dog's condition worsened, she should let us know immediately.

The dog was examined one week later. It was bright and alert, and its temperature was normal (101 F [38.3 C]). The penis was completely in its sheath, and the owner reported that the dog was eating, drinking, urinating, and defecating normally. The owner was instructed to continue the enrofloxacin for two weeks until gone.

At the writing of this article, this dog has completely recovered without any need for surgery.

CASE REPORT 2

A 2-year-old neutered male Yorkshire terrier presented to our hospital for evaluation of priapism of two days' duration.

History

The owners indicated that their bitch had been in heat and that when that had occurred, the patient had an intermittent erection and was continually licking its penis. Then a few days before presentation to our hospital, after the female was out of heat, the dog's penis was completely out if its sheath, and the dog was still continually licking it.

Physical examination

On physical examination, the dog was in excellent body condition and weighed 6 lb (2.7 kg). Temperature, pulse, and respiratory rates were normal. The dog exhibited a popliteal lymphadenopathy. The penis was erect, out of the prepuce, and beginning to show signs of desiccation. The rest of the physical examination results, including the neurologic examination results, were unremarkable.

Initial diagnostic tests

The dog was hospitalized, and a CBC, serum chemistry profile, and urinalysis were performed. The CBC results showed lymphocytosis and eosinopenia (Table 1). The results of the serum chemistry profile, electrolyte measurement, and urinalysis were unremarkable. Abdominal and spinal radiography revealed no significant findings.

Treatment

An intravenous catheter was placed in a cephalic vein. The patient was then given intravenous diphenhydramine hydrochloride (2.2 mg/kg slowly). Then atropine sulfate (0.022 mg/kg) was drawn up in a syringe with normal saline to a total of 1 ml. Electrocardiography was performed during atropine treatment, and treatment was stopped when the heart rate went above 180 beats/min, resulting in a total of 0.16 mg of atropine given. Ampicillin (11 mg/kg subcutaneously) was administered. The penis was cleaned with a dilute chlorhexidine solution. A liberal amount of 50% dextrose was applied to the penile tissue to attempt to shrink the tissue via osmosis, and then a small amount of antibacterial-plus-cortisone ointment was applied.

At discharge, the dog's priapism had resolved slightly (30% to 40%). The owners were instructed to give cefadroxil (22 mg/kg orally b.i.d.), chlorpheniramine (2 mg orally b.i.d.), and terbutaline sulfate (1.25 mg orally b.i.d.) The owners were instructed to clean the affected area once a day with chlorhexidine solution and to apply the antibacterial-plus-cortisone ointment to the affected area twice a day. A follow-up examination was scheduled for the following day.

Follow-up

At the follow-up, the owners reported that the penis had come out of its sheath once the previous evening, and they had applied a small amount of antibacterial-plus-cortisone ointment and manually pushed it back in. The owners also reported that the dog was urinating normally. The physical examination showed that the patient was bright, alert, and responsive. The dog's heart rate while receiving terbutaline was 190 beats/min, but the owners reported no evidence of hyperexcitability.

The following day, the owners returned, stating that the penis was in its sheath about 90% of the time but then it would become erect and the dog would lick it. We cleaned the penis with chlorhexidine solution and placed it back in its sheath. An Elizabethan collar was placed on the dog to prevent licking. The owners were counseled about the possibility that the presence of other unneutered and unsprayed pets in the house may be leading to the erectile activity. The owners were counseled to try dog pheromones (D.A.P.—Ceva Santé Animale) to attempt to modify the behavior. Terbutaline and chlorpheniramine were continued for one week.

At the recheck examination one week later, the penis was completely in its sheath, and the owners reported no clinical signs of hyperexcitability from the terbutaline therapy. At the writing of this article, this dog has completely recovered without any need for surgery.

DISCUSSION

To understand the pathophysiology and pharmacology of potential drugs given to treat priapism, a brief discussion of erectile physiology is necessary. During the normal process of erection, relaxation of the sinusoidal smooth muscle and increased blood flow through the arteries and arterioles facilitate rapid filling of the sinusoidal system, which in turn compresses the venous channels and occludes outflow. During the process of detumescence, the trabecular smooth muscle contracts, enabling the venous channels to reopen, and the trapped blood is expelled. The neurophysiology of erection includes sympathetic innervation provided by the hypogastric nerve, parasympathetic innervation provided by the pelvic nerve, and somatic and sensory input provided by the pudendal nerve.

Parasympathetic innervation is considered responsible for stimulating erection, and sympathetic innervation is responsible for inhibiting erection and stimulating ejaculation. Priapism occurs rarely in dogs and cats.6 However, when it does occur, it must be corrected promptly because stagnated blood in the cavernous sinuses will eventually clot, which will not resolve even when venous drainage is reestablished.

Some high-strung dogs transiently develop erections when they are excited for any reason. That is not priapism, and these transient erections usually subside with age or neutering.7 Priapism is also different from the erection that persists in some dogs after copulation or semen collection. In these cases, if the bitch is still present, it should be removed from the premises. The male dog should be taken out of the room where the semen collection or copulation took place. If this is not sufficient, then sedation or application of cold compresses could be considered.

In the case of true priapism, idiopathic priapism should be differentiated from other causes such as vascular or neoplastic causes. Priapism should also be differentiated from other causes of penile swelling such as hematoma or edema. In the cases reported in this article, there was no evidence of penile hematoma, but the presence of one in case report 1, which occurred after neutering, cannot be ruled out. Paraphimosis, the condition that causes the inability of a dog's distended penis to retract properly, causes edema, which can be a result of the extended erection or other causes of paraphimosis such as a narrowed preputial opening, injury or fracture to the organ, or the tangling of hair around the base of the penis.

Simple visual inspection of the penis is usually sufficient to differentiate these conditions. In the cases reported in this article, priapism was diagnosed through visual inspection and based on the history that the erection was still present long after the initial stimulation had been removed. An ultrasonographic or color-flow Doppler examination can differentiate priapism from other causes of penile swelling, but it was not performed in these cases.

Classification and etiology

In men, priapism is classified as high flow when an increase in arterial blood flow overrides venous drainage and low flow when neural mediation of vascular tone is altered or primary vascular or hematologic alterations have occurred.6

The causes of priapism in men include spinal cord trauma, general anesthesia, phenothiazine administration, thromboembolism, hematologic dyscrasias, nonhematologic malignancies, pelvic or perineal trauma, erectile dysfunction pharmacotherapy, pharmacologic exposure to phosphodiesterase type 5 inhibitors, or idiopathic circumstances.8,9 The causes of priapism in dogs include spinal cord lesions, spinal surgery, constipation, trauma while mating, chronic distemper encephalomyelitis, penile thromboembolism, meningomyeloceles, syringomyelia, and idiopathic causes.1,10,11

In the cases reported here, physical examination did not reveal any evidence of neurologic disease. In case report 1, the dog was allowed to mount an intact female after neutering, which could have contributed to the condition. Furthermore, the dog most likely received repeated doses of acepromazine and general anesthesia for the initial neutering and repeat operation. (Acepromazine is a common preanesthetic tranquilizer used at the shelter facility where the patient was neutered.) Phenothiazine tranquilizers are reported to cause priapism by blocking sympathetic impulses that initiate detumescence while causing paralysis of the retractor penis muscle.12 Furthermore, in an experiment in 14 dogs, when administered through intracorporeal injection, chlorpromazine induced erection, which is postulated to occur through a local effect.13

Conventional treatment

In one report, priapism was successfully treated in a dog by incising the penis over the bulbus glandis and pars longa glandis and through the tunica albuginea, after which pressure was applied to expel free blood and thrombi from the corpus cavernosum penis.10 In another case, small incisions were made over the tunica albuginea and corpus cavernosum penis, and then the penis was decompressed and irrigated with heparinized saline solution.14 This treatment resulted in the successful replacement of the penis in its sheath.

Oral drug therapy

Various oral drugs have been used to successfully treat priapism, including benztropine,12 pseudoephedrine,1 and terbutaline.2-4

Benztropine. The antihistamine and anticholinergic drug benztropine mesylate (Cogentin—Merck) has been used to successfully treat priapism in two horses and in men.12 It contains the active portions of atropine and diphenhydramine and is thought to be effective because of its central anticholinergic properties. Treatment must be initiated within a few hours of the onset of the condition.12

Pseudoephedrine. Pseudoephedrine is a sympathomimetic amine that causes vasoconstriction through the release of endogenous norepinephrine which stimulates adrenergic receptors in the lining of blood vessels.

Tertbutaline. Terbutaline, a beta2-adrenergic agonist, has also been used successfully to treat priapism in men.2-4 It is possible that it stimulates the sympathetic nervous system. It is reported to cause smooth muscle relaxation, particularly of the bronchioles and uterus,3 and is widely prescribed to treat bronchial asthma.

Parenteral terbutaline has also been used successfully to treat an intraoperative penile erection.2 Its most likely mechanism of action for any persistent erection would be to relax the smooth muscle of cavernous tissues, arteries, veins, and polsters in the blood vessels and Buck's fascia.3 In the normal situation, the cavernous smooth muscles are not only mechanically stretched because of the rapid filling of blood, but they also contract (like a stretched spring) against the blood, providing rigidity. Terbutaline probably acts by relaxing the stretched corporeal smooth muscles, relaxing the polsters in the penile veins, widening the diameter of the corporeal draining veins, and removing the impediment of venous blood flow created by contracting polsters, resulting in penile flaccidity.3

A controlled, randomized study involving 68 men was conducted to study the effect of oral terbutaline on prolonged erection after intracavernosal injection of a vasoactive agent. Detumescence was achieved in 42% of the men receiving terbutaline and 15% of the men receiving the placebo.3

In a controlled study, 75 patients with pharmacologically induced prolonged erections were randomized to receive tertbutaline, pseudoephedrine, or placebo.4 Thirty-six percent of patients receiving terbutaline achieved detumescence, compared with 12% for placebo and 28% for pseudoephedrine. The authors reported that because of the results of the study, they recommended that terbutaline should be the first-line treatment in pharmacologically induced priapism.4

In the guidelines concerning priapism in men, terbutaline is not recommended for the treatment of ischemic priapism.15 If the cause of the priapism in a dog can be determined not to be thromboembolic, medical studies done in men indicate that terbutaline is effective at relieving prolonged erection and may be useful in treating dogs with priapism.3

Pharmacologic therapy used in these cases. Low-flow priapism may respond to pharmacologic treatment. Initially, acepromazine was considered as a treatment in case report 1 to cause vasodilation of the arterial supply, but because of its well-known effect of causing irreversible priapism in horses, its use was quickly ruled out. Since the hospital formulary did not have benztropine, it was decided that treatment with atropine sulfate and antihistamines (diphenhydramine, chlorpheniramine), which have a central anticholinergic effect,1 should have a similar mechanism of action. Treatment with these agents in case report 1 caused a slight improvement by the end of the second day, but it was feared that surgery still might be needed. The addition of terbutaline to the treatment plan resolved the priapsim so that no surgery was needed. In case report 2, the atropine and diphenhydramine had a positive effect more quickly than they did in case report 1. It is not known if the atropine-diphenhydramine combination, given immediately, acted in a similar fashion to benztropine.

Treatment with terbutaline in the cases reported in this article did not cause any adverse effects that the owners reported, and upon repeat physical examination while receiving the drug, the dog in case report 1 had a normal heart rate while the dog in case report 2 had a mild tachycardia but no clinical signs of hyperexcitability. This drug had better results than atropine and diphenhydramine-chlorpheniramine alone, which had little effect on the condition by the end of the second day in case report 1. Atropine would also be impossible to administer on an outpatient basis.

CONCLUSION

Priapism is a rare disorder in dogs. However, when it is diagnosed, if the condition does not subside quickly (within 24 to 48 hours), surgical treatment is usually the only option. Reported pharmacologic treatments and supportive care for this condition in dogs include pseudoephedrine, lubricants, topical anti-inflammatories, oral and injectable antibiotics, penile injections of phenylephrine, anticholinergics (e.g. benztropine, atropine, and diphenhydramine), Elizabethan collars to avoid self-mutilation, and, possibly, terbutaline.

Case reports 1 and 2 detailed here are cases of successful treatment of priapism in dogs with terbutaline, which has been shown to be effective in randomized controlled trials in men. This is the first report of the use of terbutaline for priapism in dogs. The limitations of these case reports are clearly that they were not randomized, controlled studies, and combinations of therapies used to treat priapism of other species (men, horses) were used concurrently. However, because of the infrequency of this condition in companion animals, it is unlikely that any larger-scale randomized, controlled studies will be performed.

Despite this, I hope that practitioners faced with this disorder will attempt to use these pharmacologic treatments (after discussing the extralabel usage with owners and getting informed consent), including terbutaline, before subjecting patients to penile amputation.

Benjamin H. Cassutto, DVM

Lightbeacon Veterinary Services

18 Ward Way

Millsboro, DE 19966

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