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Priapism in children: a comprehensive review and clinical guideline

  • James F. Donaldson
    Correspondence
    Corresponding author. Tel.: +44 2380 777 222; fax: +44 2380 795 230.
    Affiliations
    Department of Paediatric Urology, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, Hampshire SO16 6YD, UK
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  • Author Footnotes
    1 Tel.: +44 2380 777 222; fax: +44 2380 795 230.
    Rowland W. Rees
    Footnotes
    1 Tel.: +44 2380 777 222; fax: +44 2380 795 230.
    Affiliations
    Department of Urological Surgery, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, Hampshire SO16 6YD, UK
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  • Author Footnotes
    1 Tel.: +44 2380 777 222; fax: +44 2380 795 230.
    Henrik A. Steinbrecher
    Footnotes
    1 Tel.: +44 2380 777 222; fax: +44 2380 795 230.
    Affiliations
    Department of Paediatric Urology, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, Hampshire SO16 6YD, UK
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  • Author Footnotes
    1 Tel.: +44 2380 777 222; fax: +44 2380 795 230.
Published:October 16, 2013DOI:https://doi.org/10.1016/j.jpurol.2013.07.024

      Abstract

      Objective

      We review the English literature between 1980 and 2013 and summarize the clinical classification, aetiology, physiology, and pathophysiology of paediatric priapism. We propose a clinical guideline for the management of priapism in children.

      Patients

      Male patients aged ≤18 years.

      Results

      Priapism, a prolonged penile erection lasting >4 h, is a rare condition in childhood. There are 3 widely accepted types of priapism: 1) ischaemic priapism, the commonest type seen in children; 2) stuttering priapism, recurrent, self-limiting prolonged erections; and 3) non-ischaemic priapism, rare in children, usually due to trauma. Neonatal priapism has also been described.
      Ischaemic priapism is a urological emergency causing fibrosis of the corpora cavernosa, subsequent erectile dysfunction and penile disfigurement. The commonest causes of priapism in children are sickle cell disease (65%), leukaemia (10%), trauma (10%), idiopathic (10%), and pharmacologically induced (5%).

      Conclusions

      Priapism in children must be assessed urgently. Rapid resolution of ischaemic priapism prevents permanent cavernosal structural damage and is associated with improved prognosis for potency later in life. Stuttering priapism requires careful counselling for episodic management. Chronic prophylaxis may be obtained using α-adrenergic sympathomimetics, phosphodiesterase type 5 inhibitors and, in sickle cell disease, hydroxyurea. Non-ischaemic and neonatal priapism may generally be treated less urgently.

      Keywords

      Introduction

      Priapism (International Classification of Diseases N48.3) [
      ] is a prolonged full or partial penile erection lasting ≥4 h unrelated to sexual stimulus [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. Priapism is a urological emergency. Its management aims to prevent penile disfigurement/shortening, erectile dysfunction (ED) and psychological sequelae [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. There are currently no widely accepted guidelines on the management of priapism in children.
      The term priapism is derived from the Greek and Roman mythological figure Priapus, son of Aphrodite and God of fertility who was depicted with a giant erect phallus and was a symbol for male generative power [
      • Cherian J.
      • Rao A.R.
      • Thwaini A.
      • Kapasi F.
      • Shergill I.S.
      • Samman R.
      Medical and surgical management of priapism.
      ]. References to priapism are made in Ebers' ancient Egyptian papyrus, and priapism was first described in the modern literature in 1616 by Petraens [
      • Cherian J.
      • Rao A.R.
      • Thwaini A.
      • Kapasi F.
      • Shergill I.S.
      • Samman R.
      Medical and surgical management of priapism.
      ]. However, it was not until 260 years later that priapism was first reported in a child [
      • Dust N.
      • Daboval T.
      • Guerra L.
      Evaluation and management of priapism in a newborn: a case report and review of the literature.
      ]. Priapism of the clitoris (“clitorism”) has also been described in a child but is beyond the scope of this article.
      In this article we comprehensively review the literature and describe the clinical classification, aetiology, physiology, pathophysiology and current management regimens of priapism in children. We suggest an algorithm for the clinical assessment and treatment of priapism in children.

      Materials and methods

      The electronic resources PubMed, Embase, Cochrane Database, and the Database of Abstracts and Reviews of Effects (DARE) were searched (1980–2013) using the medical subject heading (MeSH) “priapism”. Limitations included “all children (birth-18 years)” and English-language. All articles' abstracts were read to select significant articles for full text. All case series and significant case reports were identified and comprehensively reviewed. Where the relevance of a paper was unclear a review of the full paper was undertaken.
      The salient literature on priapism in adults was also reviewed including a PubMed search for the MeSH term “priapism” (2003–2013) for article types: clinical trial, guideline, meta-analysis, multicentre study, practice guideline, randomized controlled trial, review, and systematic review. The limitations adult (≥19 years) and English language were also applied. The references of selected papers were reviewed to identify potentially significant articles not included in the initial searches.

      Results

      A total of 337 abstracts were identified: 293 articles on priapism in children and 44 on adults. One randomized control trial (RCT) was identified but was not included as this studied only 11 adults with stuttering priapism.
      Articles selected for inclusion were reviewed, interpreted, and discussed by the authors to propose recommendations for clinical practice based on Level 4–5 evidence and therefore makes Grade C–D recommendations. The reported findings are summarized herein.

      Clinical classification

      There are three widely accepted types of priapism: ischaemic (low-flow, veno-occlusive), stuttering (intermittent, recurrent ischaemic), and non-ischaemic (high-flow, arterial). A fourth, neonatal priapism is also described.
      Ischaemic priapism is the commonest type seen in children and is typically painful. Sexual activity (including masturbation) and nocturnal erections are common precipitators. Marked rigidity of the corpora cavernosa with a flaccid glans and spongiosum is typical. Elevated interstitial pressures ensue, causing microvascular compromise and ischaemia: a compartment syndrome within the tunica albuginea.
      Stuttering priapism describes recurrent “unwanted and painful erections” which are often self-limiting but may precede an “unrelenting” ischaemic priapism [
      • Montorsi F.
      • Basson R.
      • Adaikan G.
      • Becher E.
      • Clayton A.
      • Giuliano F.
      • et al.
      Sexual medicine: sexual dysfunction in men and women; the third international consultation on sexual medicine.
      ]. Nocturnal erections are the most common trigger. It was first described by Emond [
      • Emond A.M.
      • Holman R.
      • Hayes R.J.
      • Serjeant G.R.
      Priapism and impotence in homozygous sickle cell disease.
      ] in 1980 in Jamaican sickle cell disease (SCD) patients, in whom they often start in childhood. Stuttering priapism has a significant effect on quality of life: recurrent visits to healthcare providers (often at night), sleep deprivation, embarrassment, and sexual performance anxiety [
      • Chow K.
      • Payne S.
      The pharmacological management of intermittent priapismic states.
      ].
      Non-ischaemic priapism is a partial erection due to unregulated cavernous arterial flow which is usually painless. Piesis sign (perineal compression resulting in penile detumescence which recurs after removal of perineal pressure) strongly suggests non-ischaemic priapism in children (less common in adults) [
      • Cherian J.
      • Rao A.R.
      • Thwaini A.
      • Kapasi F.
      • Shergill I.S.
      • Samman R.
      Medical and surgical management of priapism.
      ,
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ].
      Neonatal priapism is a prolonged (≥4 h) erection during the first 28 days of life; 18 cases have been reported [
      • Dust N.
      • Daboval T.
      • Guerra L.
      Evaluation and management of priapism in a newborn: a case report and review of the literature.
      ,
      • Aktoz T.
      • Tepeler A.
      • Gündoğdu E.O.
      • Ozkuvanci U.
      • Müslümanoğlu A.Y.
      Priapism in the newborn: management and review of literature.
      ]. It usually occurs in the first few days of life and persists for 2–12 days (average 5 days).

      Incidence and age distribution

      The incidence of priapism in males of any age is estimated at 0.3–1.5 per 100,000 per annum, most frequently affecting men in their fifth decade [
      • Kulmala R.V.
      • Lehtonen T.A.
      • Tammela T.L.
      Priapism, its incidence and seasonal distribution in Finland.
      ,
      • Eland I.A.
      • van der Lei J.
      • Stricker B.H.
      • Sturkenboom M.J.
      Incidence of priapism in the general population.
      ]. There are no generalizable data on the prevalence of priapism in all children, which is considered rare. However, paediatric priapism may be under-reported as embarrassment might prevent boys or parents seeking medical attention. Variables affecting the incidence and reporting of childhood priapism include population ethnicity (priapism's prevalence varies proportionately to SCD incidence) and the definition of priapism [
      • Burnett A.L.
      • Bivalacqua T.J.
      Priapism: current principles and practice.
      ].
      SCD is the commonest cause of priapism in children (Fig. 1). Adeyoju et al. [
      • Adeyoju A.B.
      • Olujohungbe A.B.
      • Morris J.
      • Yardumian A.
      • Bareford D.
      • Akenova A.
      • et al.
      Priapism in sickle-cell disease; incidence, risk factors and complications–an international multicentre study.
      ] conducted a detailed international multicentre survey of 130 patients with SCD aged 4–66 years (mean 25 years); 35% had experienced priapism; 72% of cases were stuttering. Mean age at first episode was 15 years. Perhaps surprisingly, 25% of children with SCD-related priapism are pre-pubertal [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. One study concluded that 90% of men with SCD experience priapism before their 20th birthday [
      • Mantadakis E.
      • Cavender J.D.
      • Rogers Z.R.
      • Ewalt D.H.
      • Buchanan G.R.
      Prevalence of priapism in children and adolescents with sickle cell anemia.
      ].
      Figure thumbnail gr1
      Figure 1Major causes of priapism and their frequencies. Data represent estimations from the literature search; adapted from Ref. 
      [
      • Burnett A.L.
      • Bivalacqua T.J.
      Priapism: current principles and practice.
      ]
      . SCD: sickle cell disease; Drugs: pharmacologically induced.
      Non-ischaemic priapism is uncommon in both adults and children: our understanding is based upon small case series. An observational study estimated neonatal priapism in 15 per 100,000 live births, suggesting it may also be underreported [
      • Merlob P.
      • Livne P.M.
      Incidence, possible causes and follow up of idiopathic prolonged penile erection in the newborn.
      ].

      Physiology

      Recent advances in ED have revealed the molecular basis for tumescence. Erections may be initiated by genital stimulation (reflexogenic), central stimulation (psychogenic: stimuli may be audiovisual, fantasy, or memory) or “central origination” (nocturnal: mediated by androgens during rapid eye movement sleep in adolescent boys) [
      • Dean R.C.
      • Lue T.F.
      Physiology of penile erection and pathophysiology of erectile dysfunction.
      ].
      Penile flaccidity is maintained by high resting arterial and cavernosal smooth muscle tone, limiting cavernosal arterial inflow. Resting tone may be further increased in cold conditions or after sympathomimetic intracorporeal injection (ICI) [
      • Dean R.C.
      • Lue T.F.
      Physiology of penile erection and pathophysiology of erectile dysfunction.
      ]. Tumescence is initiated by relaxation of cavernosal arteries and sinusoidal smooth muscle; increasing arterial inflow and capacitance (latent phase). Sinusoids trap blood and tumescence ensues, compressing subtunical venular plexi (tumescent phase). This stretches the tunica albuginea, which occludes emissary veins (full erection phase) [
      • Lue T.F.
      Male sexual dysfunction.
      ].
      Contraction of the ischiocavernous muscles further increases cavernosal pressure; which usually exceeds systolic blood pressure (rigid erection phase) for short periods [
      • Dean R.C.
      • Lue T.F.
      Physiology of penile erection and pathophysiology of erectile dysfunction.
      ]. The corpus spongiosum and glans are subject to similar increases in arterial inflow but lack a tunical covering so act largely as an arteriovenous shunt during erections.
      Parasympathetic and somatic neurons (arising from the second to fourth sacral segments) stimulate neuronal and endothelial (acetylcholine mediated) nitric oxide synthase (NOS) catalysing nitric oxide (NO) production from l-arginine and oxygen. NO acts on both cavernosal artery and sinusoidal smooth muscle, activating guanylate cylase and thus elevating cyclic guanosine monophosphate (cGMP). This in turn activates cGMP-dependent protein kinases, which reduce intracellular calcium levels and promotes smooth muscle relaxation.
      Sympathetic neurons (arising from the 12th thoracic to second lumbar segments) release noradenaline (norepinephrine) to increase cellular inositol triphosphate and diacylglycerol levels causing a rise in calcium [
      • Lue T.F.
      Male sexual dysfunction.
      ]. Type 5 phosphodiesterase (PDE-5) reduces cGMP, rendering it inactive. This heralds smooth muscle contraction which is propagated by the RhoA and Rho-kinase system as inhibition of myosin light chain kinases, and thus myosin-actin cross-bridge formation ensues [
      • Dean R.C.
      • Lue T.F.
      Physiology of penile erection and pathophysiology of erectile dysfunction.
      ].
      Androgens increase endothelial and neuronal NOS expression and activity (stimulating tumescence) but also enhance expression and activity of PDE-5 (promoting flaccidity). The antithetic actions of androgens are postulated to mediate the libido's effects on erections [
      • Donaldson J.F.
      • Davis N.
      • Davies J.H.
      • Rees R.W.
      • Steinbrecher H.A.
      Priapism in teenage boys following depot testosterone.
      ].
      Reflexogenic erections are physiological, even in neonates and pre-pubertal boys. Detumesence should occur after removal of the stimulus. Erections are commonly observed during bathing, diaper changing, urethral catheterization, and with a full bladder [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].

      Aetiology and pathophysiology

      Ischaemic priapism

      Hinman's classic theory that “congestion and slowing of the blood stream” increases blood viscosity and subsequent ischaemia cause ischaemic priapism is supported by the presence of dark, deoxygenated blood when aspirating the corpora [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. The molecular basis of a “final common pathway” in ischaemic priapism is outlined in Fig. 2. Cavernosal smooth muscle necrosis leads to cavernosal fibrosis, which causes ED and penile distortion/shortening.
      Figure thumbnail gr2
      Figure 2The molecular pathophysiology of ischaemic priapism. A prolonged erection may be initiated by a variety of factors which affect central and peripheral neurotransmission and paracrine agencies within the corporal tissue or the hormonal axis. Prolonged veno-occlusion leads to aberrant nitric oxide production and disruption of the molecular signalling (including guanylate cyclise, cGMP, PDE-5, and thus calcium). This results in prolonged cavernosal smooth muscle hypoxia leading to acidosis and glucopenia and hence impaired smooth muscle contraction. This in turn prolongs the erection and hence hypoxia; ultimately resulting in smooth muscle necrosis which heralds cavernosal fibrosis. Adapted from Ref. 
      [
      • Bivalacqua T.J.
      • Burnett A.L.
      Priapism: new concepts in the pathophysiology and new treatment strategies.
      ]
      . CC: corpora cavernosa; NO: nitric oxide; SM: smooth muscle.
      SCD typically causes ischaemic or stuttering priapism, but has also been associated with non-ischaemic priapism. Deoxygenated haemoglobin S (HbS) causes sickling (adhesive interactions between erythrocytes, endothelial cells, and leucocytes) and thus microvascular obstruction. Vaso-occlusive episodes (painful sickle crises, osteonecrosis, and acute chest syndrome), seen in homogenous genotypes (SS), are no longer thought to explain priapism [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ].
      Sickling also stimulates haemolysis and thus increases serum free haemoglobin levels, which deactivate NO. Sickled erythrocytes also remove l-arginine (the substrate for NO synthesis) from plasma. NO is thus deactivated and depleted, known as haemolysis-associated endothelial dysfunction [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ]. Decreased NO availability also decreases PDE-5, RhoA, and Rho-kinase and disrupts adenosine signalling. These mechanism cause priapism, pulmonary hypertension, strokes, and leg ulcers.
      Thirteen cases of ischaemic priapism (including 1 child) have been associated with sickle cell trait (heterozygous genotype: AS); however, an alternative cause (e.g. pharmacological) is identifiable in the majority of these cases [
      • Birnbaum B.F.
      • Pinzone J.J.
      Sickle cell trait and priapism: a case report and review of the literature.
      ].
      Nocturnal erections, sexual activity, dehydration, fever, and exposure to cold are the most common precipitants of priapism in children with SCD [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. Anaemia and raised serum haemolysis markers (reticulocytes, indirect bilirubin, lactate dehydrogenase, and aspartate aminotransferase) are seen in SCD priapism [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ].
      Childhood leukaemias may cause priapism: hyperleucocytosis and thrombocytosis are usually present [
      • Castagnetti M.
      • Sainati L.
      • Giona F.
      • Varotto S.
      • Carli M.
      • Rigamonti W.
      Conservative management of priapism secondary to leukemia.
      ]. In hyperleucocytosis (white cell count ≥50–100 × 109/L), direct interaction between leukaemic blasts and endothelial cells causes a loss of vascular integrity, activating prothrombotic mechanisms, hence an increased risk of pulmonary or cerebral leucostasis. Cavernosal leucostasis may similarly lead to thrombus formation and venous outflow obstruction, activating the common pathway and hence ischaemic priapism [
      • Castagnetti M.
      • Sainati L.
      • Giona F.
      • Varotto S.
      • Carli M.
      • Rigamonti W.
      Conservative management of priapism secondary to leukemia.
      ].
      Other causes of priapism in children are listed in Table 1. Despite recent advances in our understanding of the pathophysiology of priapism, it remains idiopathic in 10% of children.
      Table 1Causes of priapism in children (in approximate order of frequency compiled from the literature search).
      IschaemicPharmacologically induced
      Haemaglobinopathy (SCD, thalassaemia, G6PD, CDA)

      Leukaemia (ALL, CML)

      Tumour (rhabdomyosarcoma, testicular)

      Infection

      Neurogenic (spinal cord injury, CES)

      Toxins (malaria, scorpion, spider)

      Henoch–Schönlein purpura

      Haemodialysis

      Parental nutrition
      PDE-5 inhibitors

      Hormones (e.g. testosterone)

      Anti-psychotics, anti-depressants

      Anti-hypertensives (inc. α-blockers)

      Erythropoietin

      Anaesthetic (inc. spinal)

      Recreational (alcohol, cocaine, marijuana)
      Non-ischaemicNeonatal
      Trauma

      Haematological (SCD, leukaemia)

      Fabry's disease
      Fabry's disease is a rare congenital glycosphingolipid metabolism disorder.


      Iatrogenic (aspiration/surgery)
      Polycythaemia

      Infection (syphilis, pyocavernositis)

      Cranial birth trauma (forceps)

      Respiratory distress syndrome

      Umbilical artery catheterization
      ALL: acute lymphoblastic leukaemia; CDA: congenital dyserythropoietic anaemia; CES: cauda equina syndrome; CML: chronic myeloid leukaemia; G6PD: glucose-6-phosphate dehydrogenase deficiency; PDE5: phosphodiesterase type 5; SCD: Sickle cell disease.
      a Fabry's disease is a rare congenital glycosphingolipid metabolism disorder.

      Stuttering priapism

      SCD is the commonest cause of stuttering priapism in children, suggesting a similar aetiology to ischaemic priapism, if less pronounced [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. However, its exact pathophysiology is poorly understood. It is postulated that cavernosal endothelial NO deficiency causes downregulation of protein kinase G (PKG), PDE-5, and Rho A/Rho-kinase [
      • Yuan J.
      • Desouza R.
      • Westney O.L.
      • Wang R.
      Insights of priapism mechanism and rationale treatment for recurrent priapism.
      ]. Tonic cavernosal smooth muscle tone is reduced without PDE-5 and other mechanisms to regulate cGMP levels, producing over-responses to sexual or androgenic stimulation and hence recurrent prolonged erections [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ].
      Other postulated mechanisms include impairment of adrenoceptors, upregulation of transforming growth factor (TGF)-β, scarring of intracavernous venules, and abnormal central neurological control mechanisms [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ,
      • Chow K.
      • Payne S.
      The pharmacological management of intermittent priapismic states.
      ].

      Non-ischaemic priapism

      Penile, perineal, or pelvic trauma (typically straddle or coital injuries) are the commonest cause of non-ischaemic priapism. Laceration of cavernous arterioles, usually in the crura or corporal bodies, may cause an arteriolar–sinusoidal fistula. Rarely, a cavernous or internal pudendal artery laceration can produce a fistula. The fistula causes a high in-flow state and pooling of blood in sinusoidal spaces. This causes mechanical stimulation of endothelial NOS, increasing NO/cGMP and thus smooth muscle relaxation [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ]. Non-ischaemic priapism is therefore self-propagating.
      The onset of priapism is typically delayed by a few days following trauma (3 h–7 days) [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ]. It is postulated that penile haemodynamic changes caused by a subsequent erection (typically nocturnal) rupture the clot formed following the initial injury and hence fistula formation. Non-ischaemic priapism without a fistula or a high-flow haemodynamic state of the cavernous arteries may also occur, the aetiology of which remains unclear. Non-ischaemic priapism has also been described following medical or surgical management of ischaemic priapism in adults [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].

      Neonatal priapism

      Most neonatal priapism is idiopathic: subclinical perineal birth canal trauma is hypothesized to cause most cases [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. Other reported associations are cited in Table 1. SCD is not associated with neonatal priapism due to the presence of foetal haemoglobin (HbF). Ischaemic priapism has not been reported in a neonate and no cases are thought to have caused discomfort/agitation. Colour Doppler ultrasonography (CDU) in two newborns and cavernosal blood gas analysis in one support non-ischaemic priapism. Full functional recovery is reported in all cases, although follow-up is limited to ≤8 years [
      • Dust N.
      • Daboval T.
      • Guerra L.
      Evaluation and management of priapism in a newborn: a case report and review of the literature.
      ]. This suggests a favourable natural history and benign pathophysiology.

      Pharmacologically induced priapism

      Priapism is associated with a wide range of drugs in children (Table 1) administered therapeutically or following an overdose (intentional or accidental). PDE-5 inhibitors are used in pulmonary hypertension but have a 1% incidence of priapism at therapeutic doses [
      • Walker S.
      • Hanna B.D.
      • Meluskey H.
      • Ramsey E.
      • Dubey S.
      Sildenafil use in pediatric pulmonary hypertension: minimal risk.
      ]. Testosterone may cause stuttering, ischaemic, or rarely non-ischaemic priapism, usually 5–8 days after injection. Following testosterone deprivation, prolonged testosterone exposure is postulated to augment NOS expression more profoundly than PDE-5 [
      • Donaldson J.F.
      • Davis N.
      • Davies J.H.
      • Rees R.W.
      • Steinbrecher H.A.
      Priapism in teenage boys following depot testosterone.
      ].
      Anti-psychotics are the most frequent cause of pharmacologically induced priapism in adults (due to α-1 adrenergic antagonism); however, this is rare in children, typically only seen with polypharmacy. Illicit drug use, notably cocaine, is a common cause of priapism in adults.

      Management

      Priapism must be assessed and treated by experienced clinicians in a timely manner as ischaemic priapism may cause future ED, anxiety, attenuated sexual aversion behaviour, and intimacy avoidance due to a fear of recurrent priapic pain.

      The management of priapism in neonates

      Initial evaluation of prolonged erections in newborns should include clinical examination and/or ultrasonography, full blood count, and C-reactive protein [
      • Dust N.
      • Daboval T.
      • Guerra L.
      Evaluation and management of priapism in a newborn: a case report and review of the literature.
      ]. Urgent CDU should be performed. If ischaemic priapism cannot be excluded corporal aspiration and/or ketamine anaesthesia should be considered [
      • Aktoz T.
      • Tepeler A.
      • Gündoğdu E.O.
      • Ozkuvanci U.
      • Müslümanoğlu A.Y.
      Priapism in the newborn: management and review of literature.
      ]. However, corporal injection or surgical intervention have never been required in neonatal priapism.
      Red cell volume reduction (venesection) should be performed for polycythaemia [
      • Aktoz T.
      • Tepeler A.
      • Gündoğdu E.O.
      • Ozkuvanci U.
      • Müslümanoğlu A.Y.
      Priapism in the newborn: management and review of literature.
      ]. Careful observation alone is appropriate in most idiopathic neonatal priapism: the majority resolve spontaneously without sequelae [
      • Dust N.
      • Daboval T.
      • Guerra L.
      Evaluation and management of priapism in a newborn: a case report and review of the literature.
      ]. We advocate fortnightly CDU and clinical review in idiopathic neonatal priapism.

      Initial management in older children

      Initial management aims to assess the type of priapism and achieve detumescence (Fig. 3). Opiate analgesia is usually required in ischaemic priapism, which may inhibit tumescence [
      • Succu S.
      • Mascia M.S.
      • Melis T.
      • Sanna F.
      • Boi A.
      • Melis M.R.
      • et al.
      Morphine reduces penile erection induced by the cannabinoid receptor antagonist SR 141617A in male rats: role of paraventricular glutamic acid and nitric oxide.
      ]. “First-aid” measures include physical exercise (e.g. running up stairs), urination, a cold bath, ejaculation, and fluids [
      • Maples B.L.
      • Hagemann T.M.
      Treatment of priapism in pediatric patients with sickle cell disease.
      ].
      Figure thumbnail gr3
      Figure 3Management algorithm for priapism in children. Coag: coagulation studies; CRP: C-reactive protein; FBC: full blood count; LDH: lactate dehydrogenase; LFTs: liver function tests, U&Es: urea and electrolytes.
      Cold packs are analgesic, may have a cytoprotective effect (limiting ischaemic damage) and may cause vasoconstriction decreasing penile blood flow [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. However, cold may induce priapism in children with SCD [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. We offer cold packs (where tolerated) to boys in whom SCD is unlikely.
      For children responding to these measures careful counselling on what to do if a prolonged erection returns (including to seek urgent medical assessment ≥2 h) and potential sequelae are important. Prognosis is improved with early medical attention. Screening/follow-up must be arranged.
      In persistent cases, clinical features and identification of an underlying cause will guide management (Table 2). A blood panel should be sent to exclude haemoglobinopathies and leukaemia; of which priapism may be a presenting feature [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ].
      Table 2Differentiating ischaemic and non-ischaemic priapism. Normal values for mixed venous blood (in room air) are pO2 40 mmHg (5.3 kPa), pCO2 50 mmHg (6.6 kPa), pH 7.35 
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      . Note corporal aspiration is not required in typical cases of non-ischaemic priapism where urgent CDU is available.
      PainIschaemic (low flow)Non-ischaemic (high-flow)
      YesNo
      HistorySCD

      Recreational drug use

      Stuttering priapism
      Antecedent trauma
      ExaminationRigid (non-compressible)

      Bi-corporal (CC)
      Partial (compressible or pulsatile)

      May involve glans (tri-corporal)

      Ecchymosis (antecedent trauma)
      Blood gasHypoxic: pO2 < 5.3 kPa/40 mmHg

      Acidotic: pH < 7.25

      Hypercarbic: pCO2 > 7.98 kPa/60 mmHg

      Glucopenia (<3.5 mmol/L)
      Oxygenated: pO2 > 12 kPa/90 mmHg

      Neutral: pH 7.35–7.45

      Hypocarbic: pCO2<5.3 kPa/40 mmHg
      CC: Corpora cavernosa; SCD: Sickle cell disease.
      The absence of pain is an unreliable indicator of non-ischaemic priapism [
      • Donaldson J.F.
      • Davis N.
      • Davies J.H.
      • Rees R.W.
      • Steinbrecher H.A.
      Priapism in teenage boys following depot testosterone.
      ]. Corbetta et al. [
      • Corbetta J.P.
      • Durán V.
      • Burek C.
      • Sager C.
      • Weller S.
      • Paz E.
      • et al.
      High flow priapism: diagnosis and treatment in pediatric population.
      ] advocate routine corporal blood gas analysis. However, this nearly always necessitates general anaesthesia and is not therapeutic in non-ischaemic priapism. CDU has nearly 100% sensitivity and specificity in experienced hands [
      • Bastuba M.D.
      • Saenz de Tejada I.
      • Dinlenc C.Z.
      • Sarazen A.
      • Krane R.J.
      • Goldstein I.
      Arterial priapism: diagnosis, treatment and long-term followup.
      ]. In a classic case where a painless partial erection follows trauma, we advocate urgent CDU, if radiological expertise is readily available [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ]. If unavailable or equivocal, urgent corporal aspiration should be performed.

      Anaesthesia: local, conscious, or general?

      General anaesthesia (GA) is superior to sedation for painful procedures in children [
      • National Institute for Health and Clinical Excellence
      Sedation in children and young people: sedation for diagnostic and therapeutic procedures in children and young people.
      ]. Risks from GA are reduced above the age of 6–12 months [
      • American Academy of Pediatrics
      Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia.
      ]. However, children with SCD have increased GA risks (including acute chest syndrome), necessitating meticulous fluid balance and even preoperative transfusion [
      • Marchant W.A.
      • Walker I.
      Anaesthetic management of the child with sickle cell disease.
      ]. When choosing the optimal anaesthesia modality, the risk of lasting psychological damage, aspiration complications, anaesthetic risk, and delay that anaesthesia may incur (and thus the probability of ED) must be considered.
      Successful aspiration/injection is reported under conscious sedation with local anaesthesia (LA) in 4–18 year olds [
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      ]. This may be an appropriate alternative, particularly in hospitals without rapidly available paediatric anaesthetic expertise. Dissociative sedation (low-dose ketamine, propofol, fentanyl, or morphine) may be provided by paediatric anaesthetists [
      • National Institute for Health and Clinical Excellence
      Sedation in children and young people: sedation for diagnostic and therapeutic procedures in children and young people.
      ]. Ketamine is an established detumescence agent and may resolve priapism so should be used preferentially where appropriate expertise is available [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ].

      Corporal aspiration and lavage

      Lateral (3/9 o'clock) mid-shaft corporal needle access is obtained, avoiding the urethra or dorsal neurovascular bundle (Fig. 4). A 23–21 G (blue/green) butterfly needle should be used in pre-pubescent boys and 19 G (white) needle in adolescents [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ,
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      ] although larger needles may be required to evacuate clots. Minimizing needle passages using a three-way tap and applying pressure for 5 min after removal reduces haematoma rates (13% using a 23 G needle) [
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      ]. Rare complications include infection, urethral lesions and non-ischaemic priapism. Some authors advocate passing the needle through the glans which may reduce haematoma rates, although this could render a subsequent distal shunt procedure more awkward [
      • Hatch D.A.
      Preventing hematomas during artificial erection.
      ].
      Figure thumbnail gr4
      Figure 4Illustration of corporal aspiration. A butterfly needle is inserted laterally at the 3 or 9 o'clock positions avoiding damage to the corpus spongiosum/urethra and the dorsal neurovascular bundles. Blood is aspirated in a heparinized syringe before blood gas analysis is undertaken to delineate if the priapism is ischaemic or non-ischaemic.
      The presence of dark, deoxygenated blood (pO2 < 40 mmHg) confirms ischaemic priapism (Fig. 5, Table 2) [
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      ]. In ischaemic priapism the corpora should be immediately decompressed: 3–5-mL aliquots should be aspirated until bright red (oxygenated) blood is seen (not exceeding 10% of the circulating blood volume; 7.5 mL/kg in children aged ≥1 year) [
      • Jesus L.E.
      • Dekermacher S.
      Priapism in children: review of pathophysiology and treatment.
      ]. The corpora should then be flushed with warmed 0.9% saline.
      Figure thumbnail gr5
      Figure 5Deoxygenated blood. Two photographs of mid-corporal corporotomies demonstrating dark, deoxygenated blood seen in ischaemic priapism.

      Intracorporal injection

      If aspiration and irrigation do not achieve detumescence, sympathomimetic ICI should be performed with cardiovascular monitoring. The mechanism of action of sympathomimetics is strongly debated but is thought to be principally α-adrenergic-mediated cavernous smooth muscle contraction and cavernosal arterial vasoconstriction [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ,
      • Maples B.L.
      • Hagemann T.M.
      Treatment of priapism in pediatric patients with sickle cell disease.
      ] Side-effects are rare but include headache, dizziness, hypertension, reflex bradycardia, tachycardia, arrhythmias, and (in overdose) a subarachnoid haemorrhage [
      • Molina L.
      • Bejany D.
      • Lynne C.M.
      • Politano V.A.
      Diluted epinephrine solution for the treatment of priapism.
      ]. Injections must stop when detumescence is achieved.
      The American Urological Association (AUA) guideline recommends ICI of phenylephrine, a selective α-1 adrenergic agonist which lacks β-mediated cardiac ionotropic and chronotropic effects [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. This states that 100–500 μg should be injected in adults but “lower concentrations in smaller volumes” in children. There is no specific guidance on paediatric ICI dosages. We suggest using 100-μg aliquots of phenylephrine (0.5 mL of 200 μg/mL solution) at 5–10-min intervals in children aged ≥11 years (up to 10 times) (Table 3); there have been no reported complications.
      Table 3Suggested sympathomimetic preparation for intracorporal injection (ICI). This is an unlicensed indication and route of administration. When available phenylephrine should be used in boys aged ≥11 years; epinephrine should be used in boys ≤10 years. There are no reliable data on ICI ≤2 years: we recommend using a reduced dose of epinephrine (adrenaline). Sympathomimetics should be prepared prior to corporal aspiration to avoid repeated needle passages. ICI should be performed in a level 2–3 environment with ≥30 min monitoring (electrocardiogram, blood pressure, heart rate and pulse oximetry); at which point the patient may be discharged if detumescence persists
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      .
      DrugAvailable preparationsConcentrationAge and aliquotFurther doses
      Phenylephrine10 mg/mL (1%)0.1 mL + 4.9 mL 0.9% saline (200 μg/mL)≥11 yrs: 0.5 mL≤10 at 5–10 min (≤1 mg)
      Epinephrine (adrenaline)1 in 10,000 (100 μg/mL)1 mL + 99 mL 0.9% saline (1 in 1 000 000 or 1 μg/mL)≥11 yrs: 15 mL,

      3–11 yrs: 10 mL,

      <2 yrs
      See separate guidance regarding neonatal priapism.
      :

      2.5–5 mL
      ≤4 at 10 min
      1 in 1000 (1 mg/mL)1 mL + 1 L 0.9% saline (1 in 1 000 000 or 1 μg/mL)
      Etilefrine10 mg/mL (1%)None0–18 yrsa: 0.5 mg/mL≤2 at 10 min
      a See separate guidance regarding neonatal priapism.
      Children as young as 3 years have received ICI epinephrine (adrenaline) in a dilute solution (5–20 mL of 1 in 1,000,000) [
      • Mantadakis E.
      • Ewalt D.H.
      • Cavender J.D.
      • Rogers Z.R.
      • Buchanan G.R.
      Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.
      ,
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. This appears safe, having been reported in 45 children without side-effects. Etilefrine (available in Europe) has been used in 7 children as young as 2 years (5 mg, undiluted). Metaraminol (a pure α-agonist) should not be used because of its high cardiovascular complication rate [
      • Maples B.L.
      • Hagemann T.M.
      Treatment of priapism in pediatric patients with sickle cell disease.
      ]. Pragmatically, the sympathomimetic used must depend on what is readily available; suggested dosages, preparation and number of injections for different age groups are listed in Table 3.

      Colour duplex ultrasonography

      CDU is simple, reproducible, cheap, non-invasive, and involves no radiation or contrast. CDU should be performed in the frog-leg position, in a comfortable room with distraction therapy. This facilitates high frequency (≥7.5 MHz) linear array transducer access to the perineum and penis, visualizing the corpora in longitudinal and axial planes.
      In ischaemic priapism cavernosal arterial flow typically demonstrates a “high resistance, low velocity” wave-form (Table 4, Figure 6, Figure 7) [
      • Halls J.E.
      • Patel D.V.
      • Walkden M.
      • Patel U.
      Priapism: pathophysiology and the role of the radiologist.
      ]. Arterial flow is usually absent. The “high-resistance, high-flow” ischaemic sub-group has persistent cavernosal arterial flow (low: 1–2 m/s) but this is insufficient for small vessel perfusion and there is usually negative end-diastolic velocity [
      • Halls J.E.
      • Patel D.V.
      • Walkden M.
      • Patel U.
      Priapism: pathophysiology and the role of the radiologist.
      ].
      Table 4Characteristic findings of ischaemic and non-ischaemic priapism on penile colour Duplex ultrasonography. The following findings, in the absence of sexual stimulus, are diagnostic for ischaemic and non-ischaemic priapism.
      IschaemicNon-ischaemic
      SinusoidsNon-compressible, low echogenicity (mixed if incomplete thrombus)Compressible, transonic (no thrombus)
      Peak systolic velocityAbsent (may be low)Normal or high
      Diastolic velocityAbsent or low; typically with negative end-diastolic velocityHigh end diastolic
      Dorsal vein flowAbsent or lowNormal or high, with prominent veins
      OtherFistula: hypoechoic lesion with colour blush
      Figure thumbnail gr6
      Figure 6Penile colour duplex sonograph demonstrating the corpora cavernosa (CAV-L: left, CAV-R: right) and spongiosum (SPONG). Left cavernosal arterial flow is demonstrated with negative end-diastolic flow. The right cavernosal arterial flow was absent, consistent with ischaemic priapism. cm/s: centimetres per second (the reader is referred to the web version of this article for colour duplex interpretation).
      Figure thumbnail gr7
      Figure 7Penile colour duplex sonograph demonstrating the corpora cavernosa (CAV) and spongiosum (SPONG). Arterial flow (red) is seen in the corpus spongiosum but no flow is demonstrated in the corpus cavernosum, consistent with ischaemic priapism. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
      In non-ischaemic priapism CDU demonstrates a low-resistance, high-flow arterial waveform. Reducing probe pressure demonstrates rapid engorgement. CDU detects nearly 100% of arteriosinusoidal fistulae [
      • Halls J.E.
      • Patel D.V.
      • Walkden M.
      • Patel U.
      Priapism: pathophysiology and the role of the radiologist.
      ]. A poorly circumscribed, hypoechoic cavernous lesion (greyscale) with a characteristic Doppler colour blush identifies the fistula, which later mimics a pseudoaneurysm [
      • Bertolotto M.
      • Quaia E.
      • Mucelli F.P.
      • Ciampalini S.
      • Forgács B.
      • Gattuccio I.
      Color Doppler imaging of posttraumatic priapism before and after selective embolization.
      ].
      CDU is also helpful in guiding ongoing management. Ischaemic priapism results in penile oedema, sometimes making it difficult to confirm detumescence by clinical examination. CDU can also assess the degree of fistula resolution or recanalization.

      Digital subtraction angiography

      Digital subtraction angiography (DSA) of the internal pudendal artery is invasive so should only be undertaken when concurrent embolization can be performed.

      The ongoing management of ischaemic priapism

      Corporal interstitial oedema is present at 12 h of ischaemic priapism and smooth muscle necrosis is seen by 48 h (in adults) [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. Intervention beyond 48–72 h is unlikely to restore normal erectile function although it may provide relief of the erection and pain [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].
      If repeated sympathomimetic ICI is unsuccessful a surgical fistula (“shunt”) should be formed, bypassing the pathological veno-occlusion and allowing blood drainage [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. Shunts can be distal (cavernoglanular: percutaneous – Winter/T-shunt, or open – Al-Ghorab), proximal (cavernospongiosal – Quackels) or cavernovenous (saphenous – Greyhack) [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].
      Distal shunts are simpler to perform, have better functional outcomes and lower complication rates [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. The commonest initial procedure at our institution is percutaneous bilateral distal fistulae formation using T-shunts (a modification of Winter shunts) (Fig. 8). Favourable subsequent erectile function rates are reported (75%) in adults [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ].
      Figure thumbnail gr8
      Figure 8T-shunt formation. A number 10 blade scalpel is inserted percutaneously to puncture the glans (lateral to the urethra) and distal ends of the corpora cavernosa bilaterally. Ninety degrees of lateral rotation of the scalpel helps maintain shunt patency. Thrombus can be milked out of the corpora prior to superficial wound closure.
      Classically proximal cavernospongiosal shunting procedures (Fig. 9) were undertaken when distal shunts proved unsuccessful. However, these have high ED rates (≥50%) and may result in a cavernourethral fistula, urethral strictures, and cavernositis [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. Historically a cavernovenous shunt would be performed in refractory cases, although this risks thromboembolic complications. A 14-year-old regained potency following cavernovenous shunting after 72 h of painful priapism [
      • Shah A.
      • Parashar K.
      • Chandran H.
      Paediatric priapism – treatment conundrum.
      ].
      Figure thumbnail gr9
      Figure 9Proximal cavernospongiosum (Quackles) shunt. A transverse ventral penoscrotal skin incision is made allowing access to the corpora. Both cavernosa and the spongiosum are then incised vertically and then sutured together, forming a proximal shunt.
      Alternatively, bilateral mid-corporal corporotomies (Fig. 10) can be performed in refractory cases. This allows corporal lavage and heparin flush. Gently expunging clot while assessing corporal stenosis using Hegar's dilators can be performed after corporotomy in a modification of the “corporal snake manoeuvre” [
      • Segal R.L.
      • Readal N.
      • Pierorazio P.M.
      • Burnett A.L.
      • Bivalacqua T.J.
      Corporal Burnett “Snake” surgical maneuver for the treatment of ischemic priapism: long-term followup.
      ]. Success rates of 80% have been reported in adults using this technique; however outcomes have not been reported in children [
      • Segal R.L.
      • Readal N.
      • Pierorazio P.M.
      • Burnett A.L.
      • Bivalacqua T.J.
      Corporal Burnett “Snake” surgical maneuver for the treatment of ischemic priapism: long-term followup.
      ]. Intermittent penile compression and/or anticoagulation to maintain fistula patency in adults is controversial and not reported in children.
      Figure thumbnail gr10
      Figure 10Mid-corporal corporotomy. A transverse skin incision is made on the ventral aspect of the penis, at the mid-corporal level. Bilateral vertical corporotomies allow the evacuation of clot and corporal washout. Further, a Hegar's dilator can be used, in a modified “corporal snake manouvre” to gently evacuate thrombus and encourage reperfusion.

      Penile prosthesis insertion

      Early penile prosthesis insertion in adults treats acute priapism and the ensuing ED and reduces complications and loss of penile length compared with delayed insertion, where fibrosis renders insertion technically difficult [
      • Ralph D.J.
      • Garaffa G.
      • Muneer A.
      • Freeman A.
      • Rees R.
      • Christopher A.N.
      The immediate insertion of a penile prosthesis for acute ischaemic priapism.
      ]. In adults after 48 h of ischaemia ED is deemed inevitable. However, it is harder to confidently predict ED in children. Physical and emotional immaturity may also preclude early prosthesis insertion. Prosthesis placement has been performed electively in teenagers (≥17 years) following priapism [
      • Herschorn S.
      • Ordorica R.C.
      Penile prosthesis insertion with corporeal reconstruction with synthetic vascular graft material.
      ].

      Ongoing systemic treatment in ischaemic priapism

      Where a systemic cause of ischaemic priapism is identified, adult guidelines recommend concurrent systemic and corporal therapy [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. However, this is controversial in children. The resolution of priapic pain (after discontinuation of analgesics) has been correlated with the resolution of ischaemia, leading some physicians to avoid corporal aspiration despite priapism lasting ≤13 days [
      • Castagnetti M.
      • Sainati L.
      • Giona F.
      • Varotto S.
      • Carli M.
      • Rigamonti W.
      Conservative management of priapism secondary to leukemia.
      ].
      Lower subsequent ED rates are reported in adults and children with SCD-related ischaemic priapism. However, priapic episodes cause scarring of intracavernous venules, disrupting regulatory mechanisms, and predisposing to future episodes, emphasizing the importance of prompt treatment [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ].

      Sickle cell disease

      The lifetime probability of ED secondary to priapism is over 30%, yet the management of ischaemic priapism in boys with SCD remains controversial. Initial management is similar to other sickle cell crises (hyperhydration, oxygen, and analgesia). Treatment with plasma alkalinisation may also be considered; however, systemic treatments must not delay corporal aspiration or surgical management [
      • Morrison B.F.
      • Burnett A.L.
      Priapism in hematological and coagulative disorders: an update.
      ].
      Recent evidence suggests exchange transfusions have limited efficacy in priapism [
      • Morrison B.F.
      • Burnett A.L.
      Priapism in hematological and coagulative disorders: an update.
      ]. This is congruent with the recently described pathophysiology of SCD priapism. Furthermore, the 21% risk of cerebrovascular accident must be considered (the association of SCD, priapism, exchange transfusion, and neurological events: ASPEN syndrome) [
      • Siegel J.F.
      • Rich M.A.
      • Brock W.A.
      Association of sickle cell disease, priapism, exchange transfusion and neurological events: ASPEN syndrome.
      ].

      Leukaemia

      There is a paucity of evidence on the treatment of childhood leukaemic priapism. Management without corporal aspiration but solely systemic anti-leukaemic therapies (chemotherapy and/or leucopheresis) and anticoagulation (low molecular weight heparin) has been advocated, with no ED reported in 4 cases with ≤8-year follow-up [
      • Castagnetti M.
      • Sainati L.
      • Giona F.
      • Varotto S.
      • Carli M.
      • Rigamonti W.
      Conservative management of priapism secondary to leukemia.
      ]. Penile radiotherapy was used historically [
      • Castagnetti M.
      • Sainati L.
      • Giona F.
      • Varotto S.
      • Carli M.
      • Rigamonti W.
      Conservative management of priapism secondary to leukemia.
      ]. However, in our experience surgical shunts and even prosthesis insertion have been required, illustrating the importance of concurrent cavernosal and systemic treatment.

      Testosterone-induced priapism

      Anti-androgens may be considered in the management of testosterone-induced priapism alongside penile treatments. However, anti-androgens are relatively contraindicated in boys who have not reached sexual or skeletal maturation [
      • Burnett A.L.
      • Bivalacqua T.J.
      Priapism: current principles and practice.
      ]: the type of priapism, age, and pubertal status of the child must be considered. The half-life of the testosterone preparation should be considered in the duration of treatment.

      The management of stuttering priapism

      The management of each prolonged erection in stutterers should not differ from that of ischaemic priapism. Patients/parents must be counselled regarding simple “fist-aid” measures and to obtain medical advice if they experience an erection lasting ≥2 h [
      • Maples B.L.
      • Hagemann T.M.
      Treatment of priapism in pediatric patients with sickle cell disease.
      ].
      The chronic management of stuttering priapism aims to reduce its frequency and prevent ischaemic priapism and its sequelae. How this is best achieved remains controversial in children and adults [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ]. Compliance can be challenging in young boys who are often uncomfortable addressing their sexual health with health providers, particularly females [
      • Chinegwundoh F.
      • Anie K.A.
      Treatments for priapism in boys and men with sickle cell disease.
      ]. The routine use of an erections diary (documenting duration and frequency of stuttering on a weekly basis) has been advocated in all boys with SCD to identify those at high risk [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ].
      α-Adrenergic sympathomimetics may augment corporal smooth muscle contraction: enhancing detumescence [
      • Muneer A.
      • Minhas S.
      • Arya M.
      • Ralph D.J.
      Stuttering priapism – a review of the therapeutic options.
      ]. Pseudoephedrine or etilefrine 0.5 mg/kg up to 30 mg each night should be given at night with careful blood pressure and side-effect monitoring (palpitations and tachycardia) [
      • Maples B.L.
      • Hagemann T.M.
      Treatment of priapism in pediatric patients with sickle cell disease.
      ].
      PDE-5 inhibitors have also been used with success, paradoxically, but should not be started during acute priapism [
      • Muneer A.
      • Minhas S.
      • Arya M.
      • Ralph D.J.
      Stuttering priapism – a review of the therapeutic options.
      ]. It is postulated that surges of cGMP go unchecked in SCD (as basal PDE-5 levels are downregulated) [
      • Broderick G.A.
      Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy.
      ]. Other proposed mechanisms include that chronic inhibition may enhance PDE-5 activity or improve penile oxygenation [
      • Muneer A.
      • Minhas S.
      • Arya M.
      • Ralph D.J.
      Stuttering priapism – a review of the therapeutic options.
      ]. Daily sildenafil (short-acting) can be trialled before changing to thrice weekly tadalafil (long acting).
      Hydroxyurea, which induces foetal haemoglobin synthesis, can also be used in SCD stuttering priapism: 10–35 mg/kg dose titration with 4-weekly blood counts (myelosuppression is a rare side-effect) [
      • Ware R.E.
      How I use hydroxyurea to treat young patients with sickle cell anemia.
      ]. There is also evidence that hydroxyurea may reduce other sickle crises and increase life expectancy in SCD [
      • Steinberg M.H.
      • McCarthy W.F.
      • Castro O.
      • Ballas S.K.
      • Armstrong F.D.
      • Smith W.
      • et al.
      The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: a 17.5 year follow-up.
      ].
      Oral β-agonists (e.g. terbutaline) have success rates ≥62% in adults; their mechanism of action of is unclear; α-adrenergic effects are postulated. Baclofen, a gamma-aminobutryric acid (GABA) receptor inhibitor is reported to have treated priapism successfully in a few children [
      • Moreira D.M.
      • Pimentel M.
      • da Silva Moreira B.F.
      • Stein A.C.
      • Koff W.J.
      Recurrent priapism in the young patient treated with baclofen.
      ], typically with spinal cord injury; however, its side-effect profile (drowsiness, nausea and ED) limits its use.
      Gonadotropin-releasing hormone agonists, anti-androgens, oestrogens, ketoconazole (testosterone synthesis inhibitor), and 5-α-reductase inhibitors have been used in adults but are not recommended for use in children [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ].
      Phenylephrine ICI at home (by patients or parents) has also been advocated [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. An implantable device used to administer intracaversonal phenylephrine has also been described in adults [
      • Muneer A.
      • Minhas S.
      • Arya M.
      • Ralph D.J.
      Stuttering priapism – a review of the therapeutic options.
      ]. However, we suggest that prevention (prophylaxis) is better than cure (managing each episode individually). ICI may also carry a significant risk of physical/psychological trauma in children.

      The management of non-ischaemic priapism

      When non-ischaemic priapism has been confirmed, its management is not urgent. However, all children with perineal or penile trauma should undergo a full primary and secondary survey. Priapism may be a missed sign of spinal trauma [
      • Sneed R.C.
      • Stover S.L.
      Undiagnosed spinal cord injuries in brain-injured children.
      ]. Although no priapic child protection cases are reported in the literature, children with genital/pelvic trauma should be assessed by a paediatric specialist.
      Fifty-five cases of childhood non-ischaemic priapism are reported; management options include conservative, mechanical, pharmacological, radiological embolization, or surgical ligation [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ,
      • Corbetta J.P.
      • Durán V.
      • Burek C.
      • Sager C.
      • Weller S.
      • Paz E.
      • et al.
      High flow priapism: diagnosis and treatment in pediatric population.
      ]. However, follow-up in children lacks longevity and reliably completed erectile function questionnaires [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ].

      Conservative

      Initially expectant management is advised in both adults and children [
      • Montague D.K.
      • Jarow J.
      • Broderick G.A.
      • Dmochowski R.R.
      • Heaton J.P.
      • Lue T.F.
      • et al.
      American urological association guideline on the management of priapism.
      ]. The natural history of non-ischaemic priapism is unclear (lasting 36 years in an adult). The social unacceptability of priapism and hypothesized high oxygen tension-related fibrosis or secondary vascular changes may precipitate intervention [
      • Corbetta J.P.
      • Durán V.
      • Burek C.
      • Sager C.
      • Weller S.
      • Paz E.
      • et al.
      High flow priapism: diagnosis and treatment in pediatric population.
      ]. We advocate fortnightly CDU and clinical examination up to at least 6 weeks prior to considering active management on an individual basis.

      Mechanical

      Perineal compression or ice packs may reduce blood supply through the fistula, heralding thrombus formation and resolution of priapism. Refinement using CDU with sedation has been reported in a few cases with successful outcomes [
      • Imamoglu A.
      • Bakirtas H.
      • Conkbayir I.
      • Tuygun C.
      • Sarici H.
      An alternative non-invasive approach for the treatment of high flow priapism in a child: duplex ultrasound-guided compression.
      ]. These strategies are unlikely to cause harm, provided they are well tolerated.

      Pharmacological

      ICI of α-adrenergic agonists and methylene blue (a guanylate cyclase inhibitor) have been reported with limited success [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ]. Androgen blockade reduces nocturnal erections and has good success rates in adults but is not advisable in most children [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].

      Radiological embolization

      Internal pudendal artery DSA (via femoral access) can accurately locate a fistula, allowing superselective embolization with autologous clot or synthetic material (e.g. gelatine foam). This allows temporary obstruction; allowing the fistula to heal before blood flow later returns, enabling future erectile function. Embolization is reported in 30 children, with an 80% first embolization success rate [
      • Mockford K.
      • Weston M.
      • Subramaniam R.
      Management of high-flow priapism in paediatric patients: a case report and review of the literature.
      ]. Failure was successfully treated with repeat embolization using non-absorbable material in 5 out of 6 cases (the remaining child was managed conservatively). Embolization therefore has an overall success rate of a 97%. No other complications are reported in children, although ED is not uncommon following embolization in adults [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].

      Surgical

      Open surgical transcorporal fistula ligation with intraoperative CDU in long-standing non-ischaemic priapism (where a pseudo-capsule around the fistula has developed) carries a high risk of subsequent ED and should only be considered in refractory cases or where embolization is unavailable [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ].

      Conclusion

      Ischaemic priapism is a urological emergency. Left untreated it leads to necrosis, fibrosis and invariably future ED. Rapid resolution of ischaemic priapism prevents permanent cavernosal structural damage and is associated with improved prognosis for potency later in life [
      • Broderick G.A.
      • Kadioglu A.
      • Bivalacqua T.J.
      • Ghanem H.
      • Nehra A.
      • Shamloul R.
      Priapism: pathogenesis, epidemiology, and management.
      ]. Psychological sequelae may also be reduced with early intervention.
      Where haematological or systemic disorders precipitate ischaemic priapism their treatment should not preclude or delay targeted corporal measures to reduce the child's priapism. We advocate timely assessment by experienced clinicians using the algorithm outlined in this article.
      Children and their parents are often not comfortable discussing the child's sexual health. Coupled with a current lack of robust evidence for its management, treating paediatric stuttering priapism is challenging. Oral sympathomimetics or PDE-5 inhibitors should be trialled, coupled with hydroxylurea in SCD, with close monitoring.
      Non-ischaemic and neonatal priapism may be treated less urgently if benign in aetiology, when initial expectant management is appropriate after confirmation with CDU. Compression may be trialled prior to embolization when the patient, parents, or clinician no longer find persistent priapism acceptable.
      There is currently a paucity of understanding and evidence-based medicine in paediatric priapism, the management of which is, in part, therefore based around findings in adults. Differences compared to guidelines for adults include the volume of intracorporal blood aspirated, dosage of sympathomimetic ICI, anaesthesia modalities required for aspiration/injection, success rates of perineal compression in non-ischaemic priapism, and the management of neonatal priapism. Penile prosthesis insertion and anti-androgen therapy are inappropriate in most children.

      Conflict of interest

      None.

      Funding

      None.

      Ethical approval

      Ethical approval was not required for this review. All authors have read the policy of the journal on ethical consent and the standards of animal care.

      Acknowledgements

      We thank Mr Douglas R. Donaldson for providing all illustrations (Figure 4, Figure 8, Figure 9, Figure 10). Thanks to Paul Manson and Craig Rore for their assistance with our electronic literature search.

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