Intracavernous Methoxamine in the Treatment of Priapism

Case Report Intracavernous methoxamine in the treatment of priapism

J Jara, I Moncada, G Bueno and C Hernandez

Urology Department, Hospital General Universitario, Madrid, Spain

Methoxamine is an alpha-adrenergic drug, its unique pharmacokinetics and mechanism of action on alpha-1 receptors lead to consider it, similarly to phenylephrine, as a ®rst-choice drug for treating drug-induced or veno-occlusive priapism. The experience obtained with its use in the management of three cases of priapism lasting over 7 h and one case of sustained rigid erection caused during anesthetic induction are reported.

Keywords: methoxamine; priapism; intracavernous drug therapy

Introduction adrenergic agents. In a later phase, cell ischemia and ®brosis takes place, making the smooth muscle irresponsive to pharmacologic agents. Since the introduction of intracavernous injections In this present study we report on the ef®cacy and of vasoactive drugs in clinical practice, the inci- safety of methoxamine, a selective alpha-1 adrener- dence of priapism have enormously increased, from gic agent, in the treatment of drug-induced pri- 1 being an occasional ®nding to be the most common apism. cause of priapism, according to Lue.2 The incidence of this untoward effect of intracavernous injections depends on the drug used, the dose administered and the underlying etiology of Case reports impotence. In a review of the literature,3 papaverine induced priapism in 9.5% of 2314 patients, the Case 1 combination of papaverine plus phentolamine in 5.3% of 2914 patients and PGE1 only in 2.4% of the A 44 y old male presented to the urology department 1284 patients revised. These values refer to priapism complaining of erectile dysfunction in the last year, occurring as a result of initial diagnostic tests, while with low-quality erections which prevented pene- only 0.4% occurred during the period of therapy tration, night erections were present, but without with self-injections at home, in which the appro- complete rigidity, he was a moderate smoker and priate dose for each patient is already known. had no other diseases referred. Physical examina- Regarding the etiology of impotence, it is recom- tion was normal and also blood biochemistry and mended to administer low doses of vasoactive drugs hormone laboratory tests. Penile Color Doppler when neurologic or psychogenic causes are sus- ultrasound with intracavernous injection (ICI) of pected since the hemodynamics of erection is intact. PGE1 at dose of 20 mcg was performed. Prior to this In most cases, drug-induced priapism can be procedure, the patient required admission to the resolved through the action of alpha-adrenergic psychiatry department due to a maniac crisis in substances, also administered directly to the corpora relation to a manic-depressive psychosis, an under- cavernosa of the penis. The ef®cacy of this treatment lying condition that he had not reported in the will depend on the duration of this drug-induced clinical history. The response to ICI was immediate, priapism. In the initial phase, when hypoxia and and a good arterial ¯ow (peak systolic velocity of acidosis are present, contractility of smooth muscle 35 cm/sg) with an apparently normal venous com- is depressed but may respond to high doses of petence (end-diastolic velocity of 1 cm/sg) was seen. Seven hours after the ICI, the psychiatry department consulted the staff urologist due to a sustained Correspondence: Dr J Jara, Urology Department, Hospital erection with complete and painful rigidity. General Universitario `Gregorio MaranÄ on', c/Doctor Esquerdo The patient was initially managed by anesthetiz- no. 42, 28007, Madrid, Spain. ing the base of the penis and with aspirating the Received 15 July 1996; accepted 20 March 1998 corpora cavernosa, obtaining a quite ¯uid blood Intracavernous methoxamine in the treatment of priapism J Jara et al 258 ¯ow. Nevertheless, a complete detumescence was with saline, an intracavernous injection of methox- not achieved and the erection recurred, so methoxamine was given, diluting 20 mg in 10 ml of saline amine was intracavernosally administered (4 cc of and injecting 5 ml of this solution. The erection the solution of a 20 mg ampoule in 10 cc saline). disappeared within one minute and blood pressure After this, the rigidity disappeared in less than and heart rate remained unchanged. 5 min. Blood pressure and heart rate were monitored and no changes were registered. Case 4

Case 2 A 35 y old male with no relevant personal history, was admitted for internal urethrotomy of an urethral A 54 y old male attended the emergency room stenosis under general anesthesia. The patient complaining of a sustained, painful erection starting developed a rigid erection, lasting over 30 min, 18 h before. He denied any history of known which prevented us to perform the urethroscopy. neurological, cardiovascular or systemic diseases. An ICI of methoxamine was administered (2 cc of He was a smoker of 20 cigarettes/d and moderate the solution of a 20 mg ampoule in 10 cc saline). The alcohol consumption. He had multiple sexual erection subsided immediately, monitoring of heart relations with no stable partner. On admission, he rate and blood pressure showed no signi®cant reported to have been treated for several months for changes. erectile dysfunction at another center, where he received intracavernous self-injections. (He did not know the type of drug or the exact dose.) On his Discussion own, the patient had increased the dose prescribed, which caused a persistent, rigid erection the day before, the presence of pain led the patient to attend Phenylnephrine is usually considered the ®rst- choice drug for pharmacologic priapism.4±6 This the emergency room. 4 Aspiration of corpora cavernosa showed the would be justi®ed by its proven ef®cacy, as a result presence of viscous blood and saline ¯ushing was of its potent alpha-adrenergic activity, along with its ineffective. Therefore, ICI with methoxamine was minimal activity on beta-1 and beta-2 receptors, then performed (2 cc of the solution of a 20 mg which would minimize the risks of systemic side ampoule in 10 cc saline). Erection resolved within effects. However, due to the very few indications for 10 min, with complete detumescence and no its use, this drug is not easily available in some changes in blood pressure or heart rate. countries. Other drugs, such as ethylephrine, epinephrine, norepinephrine and metaraminol, have also been used as an effective therapy in priapism. The dosage Case 3 of some of these drugs are shown in Table 1. Nevertheless, their higher af®nity for beta-1 recep- A 63 y old male reported impotence starting 2 y tors may cause adverse effects, such as hypertensive before, with erections of reduced rigidity and short crises or acute pulmonary edema. In fact, two deaths due to the intracavernous use of metaraminol have duration, but preserved libido and ejaculation. 7 Clinical history included moderate smoking and been reported. Epinephrine does not seem to be the L4±L5 disk hernia surgically treated 2 y before. drug of choice for this condition either, due of its Physical examination was normal and laboratory intense beta-agonist effects, leading to a direct tests showed normal parameters. As part of the cardiotonic effects. Furthermore, the capacity of study, Color Doppler ultrasound of the cavernous this latter substance to achieve penile detumescence arteries was performed with ICI of PGE1 20 mcg, is not better than that attributed to phenylephrine. which showed a good arterial in¯ow. The clinical On the other hand, methoxamine, or beta-hydroxy- response was a good erection with signi®cant beta-(2,5 dimethoxyphenyl)-isopropylamine, is a rigidity. On the following visit, the patient reported sympathomimetic substance which has, as phenyl- that this erection had persisted for 5 h, and ®nally subsided spontaneously. With a diagnosis of erectile Table 1 Intracavernous drugs in the treatment of priapism dysfunction of probable neurological origin, training Phenylephrine 100±500 mcg/dose for self-injection started with only 5 mcg of PGE1 in Epinephrine 10±20 mcg/dose order to assess the response to this dose. Norepinephrine 10±20 mcg/dose Eight hours later, the patient was admitted to the Ephedrine 50±100 mg/dose emergency room presenting a rigid, painful erection Methoxamine 4±10 mg/dose in the absence of any sexual stimulus. After failed Injection can be repeated after ®ve minutes in an attempt to aspiration and ¯ushing of the corpora cavernosa recover penile detumescence. Intracavernous methoxamine in the treatment of priapism J Jara et al 259 ephrine, virtually only af®nity for alpha-1 receptors. tetracaine, which subsided with no local or systemic Its main effect, when injected by IR or IM route is a side effects.10 Therefore, it seems that this intra- blood pressure increase, which is totally due to operative complication, which appears to be more peripherally-induced vasoconstriction. When in- common in patients aged under 50 y, under general jected directly into the blood stream, this drug, like anesthesia with propofol or epidural anesthesia, can phenylephrine, stimulates minimally heart beta- be currently treated safely with intracavernous receptors. Additionally, it causes little or no central injections of these agents, as shown in one of our nervous system (CNS) stimulation.8 In Spain it is cases. normally available as methoxamine hydrochloride There is no clear data, in the literature, regarding in a 20 mg/ml solution. the dose of methoxamine for its intracavernous Methoxamine, after its intracavernous injection administration. However, it is well known that activates alpha-1 post-synaptic receptors. Its action methoxamine can be administered at doses of 10± is exerted through protein Gp, to which these 20 mg for intramuscular injection.8 Assuming this, receptors are bound, this protein, in turn, stimulates we have observed that 4±10 mg is an effective dose, phospholipase C and causes the transformation of with no side effects. After diluting an ampoule inositol diphosphate to inositol triphosphate plus (20 mg) in 10 ml of saline, 2±5 ml (2/1000 solution) diaglycerol. These two substances can increase the are utilized. We use a 25 G insulin needle, or the bioavailability of intracellular calcium in the butter¯y needle (14±16 G) used for the previous smooth muscle cell which activates the kinase of aspiration and ¯ushing, as described in the cases the myosin light chain, promoting its sliding over reported in this paper. actin. This mechanism leads to the contraction of the muscular cell, terminating, therefore, the sustained relaxation state that caused priapism. This action can be achieved even in long-term Conclusion priapism, as seen in case report 1. Some authors do not consider drug-induced priapism as true priap- In our experience, methoxamine is a highly safe and ism, and report these cases as `prolonged erections', effective drug for inducing penile detumescence, assuming that they have a different outcome, with- achieving the resolution of long-term priapism out hypoxia and no tissue acidosis or ®brosis, since without adverse side effect. many of them are self-limited. However, a recent study on erections induced by vasoactive drugs lasting over 24 h9 reported that these erections behave as any other low-¯ow `true priapism' of a References similar duration, leading to ischemic changes and ®brosis if left untreated for enough time. Intraoperative tumescence also entails a con¯ict- 1 Winter ChC, McDowell G. Experience with 105 patients with priapism: update review of all aspects. J Urol 1988; 140: ing problem if transurethral endoscopic surgery is to 980±983. be performed. Among the great variety of therapeu- 2 Lue TF. Physiopathology of erection and physiopathology of tic options discussed to resolve this intraoperative impotence. In: Walsh PC, Retik AB, Stamey ThA, Vaughan ED, complication, the use of vasodilators such as amyl eds. Campbell Urologia. 6th edn. Ed Medica Panamericana nitrite has been mentioned, but its poor action and SA: Buenos Aires, 1994, pp. 697±716. 3 Juneman KP, Alken P. Pharmacotherapy of erectile dysfunc- potential side effects in the elderly advise against its tion: a review. Int J Impot Res 1989; 1: 71±78. use. Other measures with a doubtful ef®cacy, such 4 Azocar G et al. Tratamiento del priapismo mediante fenile- as irrigation of the perineum with cold water or the frina. Arch Esp de Urol 1994; 47: 785±787. application of ethyl chloride on the glans penis to 5 Dittrich A et al. Treatment of pharmacological priapism with achieve a vasoconstrictive effect due to cold, have phenylephrine. J Urol 1991; 146: 323±324. 6 Staerman F et al.. Treatment of intraoperative penile erec- been ®nally rejected after documenting the ef®cacy tion with intracavernous phenylephrine. J Urol 1995; 153: and safety of the intracavernous injection of alpha-1 1478±1481. adrenergic agents. 7 Stanners A, Colin-Jones D. Metaraminol for priapism (letter). Staerman6 reported on the treatment of 23 cases Lancet 1984; 2: 978. of intraoperative erection during penile or endo- 8 Weisner N. Noradrenalina, adrenalina y aminas simpatomi- meÂticas. In: Goodman LS, Gilman A, eds. Bases FarmacoloÂgi- scopic surgery, which were successfully resolved cas de la TerapeÂutica. 6th edn. Ed Medica Panamericana SA: with an injection of 0.2 mg phenylephrine. The Buenos Aires, 1982, pp. 150±186. hemodynamic changes evidenced, a transient in- 9 Kulmala RV, Tamella TLJ. Effects of priapism lasting 24 hours crease in blood pressure, were not important even in or longer caused by intracavernosal injection of vasoactive drugs. Int J Impot Res 1995; 7: 131±136. the elderly. The use of methoxamine for this 10 Davila PA, Martin P, Madrid JL. Ereccion del pene: complica- purpose has been reported previously in our country cion de la cirugia transuretral. Estudio de un caso tratado con in one case of erection after spinal blockage with metoxamina. Rev Esp Anestesiol Reanim 1988; 35: 159±160.