To cite this guideline:

• Bivalacqua TJ, Allen BK, Brock G et al: Acute Ischemic Priapism: an AUA/SMSNA Guideline. J Urol 2021; 206: 1114.

Español translated guideline courtesy of Confederacion Americana de Urologia (CAU) [pdf]

Trinity J. Bivalacqua, MD; Bryant K. Allen, MD; Gerald Brock, MD; Gregory A. Broderick, MD; Tobias S. Kohler, MD; Jeff Oristaglio, PhD; Leila L. Rahimi, MHS; John P. Mulhall, MD; Zora Rogers, MD; Ryan P. Terlecki, MD; Landon Trost, MD; Faysal A. Yafi, MD; Nelson E. Bennett, Jr., MD

Purpose

Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Although some forms of priapism are non-urgent in nature, prolonged (>4 hours) acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (i.e., hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction. All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event provided early intervention when indicated. This Guideline provides a clinical framework for the diagnosis, evaluation, and treatment (non-surgical and surgical) of acute ischemic priapism.

Methodolgy

A comprehensive search of the literature was performed by Emergency Care Research Institute who searched Medline and EMBASE for articles published between January 1, 1960 and April 28, 2020. Study designs included narrative reviews, systematic reviews, randomized controlled trials, controlled clinical trials, diagnostic accuracy studies, and observational studies (i.e., cohort studies, with and without comparison groups; case-control designs; case series). Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were ordered, and ultimately 137 unique articles were included in the report. These publications were used to create the majority of the clinical framework. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low), and evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed. Additional information is provided as Clinical Principles and Expert Opinions when insufficient evidence existed.

Guideline Statements

Diagnosis of Priapism

1. In patients presenting with priapism, clinicians should complete a medical, sexual, and surgical history, and perform a physical examination, including the genitalia and perineum. Clinical Principle
2. Clinicians should obtain a corporal blood gas at the initial presentation of priapism. Clinical Principle
3. Clinicians may utilize penile duplex Doppler ultrasound, when the diagnosis of acute ischemic versus non-ischemic priapism is indeterminate. Expert Opinion
4. The clinician should order additional diagnostic testing to determine the etiology of diagnosed acute ischemic priapism; however, these tests should not delay, and should be performed simultaneously with, definitive treatment. Expert Opinion

Initial Management of Acute Ischemic Priapism

5. Clinicians should counsel all patients with persistent ischemic priapism that there is the chance of erectile dysfunction. Moderate Recommendation; Evidence Level: Grade B
6. Clinicians should counsel patients with a priapism event >36 hours that the likelihood of erectile function recovery is low. Moderate Recommendation; Evidence Level: Grade B
7. In patients presenting with a prolonged erection of four hours or less following intracavernosal injection pharmacotherapy for erectile dysfunction, clinicians should administer intracavernosal phenylephrine as the initial treatment option. Expert Opinion
8. In a patient with diagnosed acute ischemic priapism, conservative therapies (i.e., observation, oral medications, cold compresses, exercise) are unlikely to be successful and should not delay definitive therapies. Expert Opinion

Pre-Surgical Management of Acute Ishemic Priapism

9. Clinicians should manage acute ischemic priapism with intracavernosal phenylephrine and corporal aspiration, with or without irrigation, as first line therapy and prior to operative interventions. Moderate Recommendation, Evidence Level: Grade C
10. In patients receiving intracavernosal injections with phenylephrine to treat acute ischemic priapism, clinicians should monitor blood pressure and heart rate. Clinical Principle

Surgical Management of Acute Ischemic Priapism

11. Clinicians should perform a distal corporoglandular shunt, with or without tunneling, in patients with acute ischemic priapism who have failed pharmacologic intracavernosal reversal and corporal aspiration, with or without irrigation. Moderate Recommendation, Evidence Level: Grade C
12. In patients with acute ischemic priapism who failed a distal corporoglanular shunt, the clinician should consider corporal tunneling. Moderate Recommendation, Evidence Level: Grade C
13. Clinicians should counsel patients that there is inadequate evidence to quantify the benefit of performing a proximal shunt (of any kind) in a patient with persistent acute ischemic priapism after distal shunting. Moderate Recommendation, Evidence Level: Grade C

Post Shunting Management of Acute Ischemic Priapism

14. In an acute ischemic priapism patient with persistent erection following shunting, the clinician should perform corporal blood gas or color duplex Doppler ultrasound prior to repeat surgical intervention to determine cavernous oxygenation or arterial inflow. Moderate Recommendation, Evidence Level: Grade C

Penile Prosthesis

15. Clinicians may consider placement of a penile prosthesis in a patient with untreated acute ischemic priapism greater than 36 hours or in those who are refractory to shunting, with or without tunneling. Expert Opinion
16. In a patient with acute ischemic priapism who is being considered for placement of a penile prosthesis, clinicians should discuss the risks and benefits of early versus delayed placement. Moderate Recommendation, Evidence Level: Grade C

Priapism is a condition resulting in a prolonged and uncontrolled erection. Although the incidence is relatively low, because of its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Although some forms of priapism are non-urgent in nature, prolonged (>4 hrs) acute ischemic priapism represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction (ED).^1,2 Thus, all patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event provided early intervention when indicated.

Given the significant heterogeneity of men presenting with acute ischemic priapism, the current Guideline emphasizes that specific interventions should be individualized based on clinical history and findings. While less-invasive, stepwise methods may be appropriate for most situations, others may be best managed using expedited surgical interventions. Decisions must also be based onpatient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using this new, diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

Several other additions have been included in the guideline to address various diagnostic modalities. Specifically, the role of imaging (e.g., ultrasound, CT, MRI) is clarified during the initial diagnosis as well as post-treatment, such as with men exhibiting persistent pain or perceived rigidity post distal shunting.

New additions to the guideline also include greater detail on the role of:

1. adjunctive laboratory testing,
2. early involvement of urologists when presenting to the emergency room,
3. discussion of conservative therapies,
4. enhanced data for patient counseling on riskes of ED and surgical complications,
5. specific recommendations on intracavernosal phenylephrine with or without irrigation,
6. inclusion of novel surgical techniques (e.g., tunneling), and
7. early penile prosthesis placement

Because priapism is rare and unpredictable, there is a dearth of high-level evidence-based data available from which strong evidence-based recommendations may be derived. Rather, most series represent small, single-site, retrospective, outcomes-based reports, with limited follow-up available and inconsistencies in reporting of outcomes. Similarly, as acute ischemic priapism is associated with ED (whether treated or untreated) and is progressive in nature, outcome reporting of various treatment strategies is inherently biased. These limitations preclude the ability to compare different treatment approaches or provide definitive recommendations in many cases. However, as with other American Urological Association (AUA) Guidelines, a thorough review of the available literature was performed, with all relevant articles reviewed and considered during the creation of recommendation statements. In cases where the Panel did not feel there was enough information to warrant a particular statement, additional discussion was presented within the supporting text.

The objective of the current Guideline is to provide a practical guide which is directive in cases where evidence is more abundant while remaining flexible to allow for clinician judgment. As such, the Guideline does not establish a fixed set of rules for the treatment of priapism. Above all, it does not pre-empt physician judgment in individual cases. Variations in patient subpopulations, physician experience, and available resources will necessarily influence choice of clinical strategy. Adherence to the recommendations presented in this document cannot assure a successful treatment outcome.

Of note, the current Guideline only addresses acute ischemic priapism with limited discussion of non-ischemic priapism. Sections on non-ischemic priapism, stuttering/recurrent priapism, and sickle cell populations will be included in the coming months. The index patient used to establish recommendations was defined as an adult male presenting with a prolonged erection lasting >4 hours. For ease of review, recommendations are bolded and followed by supporting text. The level of evidence and overall strength of recommendation is also noted for each recommendation.

Definitions

Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. Typically, only the corpora cavernosa are affected. For the purposes of this Guideline, the definition of priapism is restricted to erections of >4 hours duration. In contrast, a ‘prolonged erection’ may be defined as an erection which persists longer than desired but <4 hours. There are two general classifications of priapism:

Acute Ischemic (veno-occlusive, low flow) a nonsexual, persistent erection characterized by little or no cavernous blood flow and abnormal cavernous blood gases (i.e., hypoxic, hypercarbic, acidotic). The corpora cavernosa are fully rigid and tender to palpation. Patients typically report pain. A variety of etiologic factors may contribute to the failure of the detumescence mechanism in this condition. Acute ischemic priapism is an emergency. As the natural history of untreated acute ischemic priapism includes days to weeks of painful erections followed by permanent loss of erectile function, the condition requires prompt evaluation and may require emergency management.

Non-ischemic (arterial, high flow): a persistent erection which may last hours to weeks and which is frequently recurrent. Although the underlying physiology is incompletely understood, it likely results from unregulated control of arterial inflow and cavernous smooth muscle tone. Erections are nearly always non-painful, and cavernosal blood gas measurements are consistent with arterial blood. In contrast to acute ischemic priapism, the non-ischemic variant is not considered a medical emergency.

Resolution of acute ischemic priapism is characterized by the penis returning to a flaccid, nonpainful state, with restoration of penile blood flow. However, in many cases, persistent penile edema, ecchymosis, and partial erections can occur and mimic unresolved priapism. This often relates to the duration of priapism and may also signify segmental regions of cavernosal ischemia/necrosis.

Both acute ischemic and non-ischemic priapism may recur over time. The term stuttering priapism is used specifically with acute ischemic priapism, and signifies an intermittent, recurrent subtype, in which unwanted painful erections occur repeatedly with intervening periods of detumescence. Management of this condition requires not only treatment of acute episodes, but also focuses on future prevention and mitigation of an acute ischemic event necessitating surgical management.

Panel Formation

The Panel was created in 2018 by the American Urological Association Education and Research, Inc. This guideline was developed in collaboration with the Sexual Medicine Society of North America (SMSNA). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chairs who in turn appointed the additional panel members with specific expertise in this area, in conjunction with SMSNA. Additionally, the Panel included American College of Emergency Physicians (ACEP) and patient representation. Funding of the Panel was provided by the AUA; panel members received no remuneration for their work.

Methods and Methodology

Literature Search
A comprehensive search of the literature was performed by staff in the Clinical Excellence and Safety Group at the Emergency Care Research Institute (ECRI). ECRI searched Medline and EMBASE for articles published between January 1, 1960 and April 28, 2020. Study designs included narrative reviews, systematic reviews, randomized controlled trials (RCTs), controlled clinical trials, diagnostic accuracy studies, and observational studies (i.e., cohort studies, with and without comparison groups; case-control designs; case series).

Study Screening and Selection
Relevant references retrieved by the literature searches were loaded into Distiller SR, systematic review software (Evidence Partners, Ottawa, Ontario, Canada). All screening through the abstract level was performed in Distiller SR. One analyst (Dr. Oristaglio) performed initial title screening and his list of excluded studies was reviewed by Dr. Uhl to confirm that no potentially relevant studies had been excluded. One analyst (Dr. Oristaglio) performed screening at the abstract level. References deemed with potential to satisfy the inclusion criteria (outlined below) and provide evidence for addressing one or more of the key questions specified by the panel were retrieved in full text for review by the team. Five analysts participated in full-text screening and approximately 10% of the studies at this level were reviewed by at least two analysts (double-screening). Conflicting decisions between analysts were tracked, reviewed, discussed, and resolved by consensus before individual analysts were allowed to screen full-text studies independently. This assured that a suitable sample of studies covering most of the key questions were assessed by all analysts and that decisions on inclusion or exclusion were understood. For all excluded studies, we recorded the reason for exclusion, and whether the exclusion was based on abstract review or full text review.

Inclusion Criteria
General Criteria
To focus the analysis on the most relevant evidence, only peer-reviewed journal articles published in English from January 1, 1960 to April 28, 2020, reporting data on human subjects with relevance to one or more of the key questions were considered. With regard to enrollment size, only individual case studies (n=1 subject) were systematically excluded, though some studies of this type were allowed when the quantity of evidence for a particular question was very low.

In summary, general inclusion criteria were as follows:

• published, peer-reviewed full-length individual studies or systematic reviews,
• individual studies limited to those not included in relevant systematic reviews (to avoid double-counting of evidence),
• published guideline with systematic review and acceptable methodological details (including study quality assessment) and abstractable data,
• enrolled or analyzed human male participants,
• published in the English language, and
• a patient enrollment of ≥2 per group at follow-up (except in instances of very limited evidence).

Exclusion criteria were as follows:

• studies not published in English,
• case reports (n=1 studies), except in instance of very limited evidence,
• narrative reviews
• guidelines or reviews with no systematic literature search or methodological details (e.g., risk of bias assessment),
• opinions/editorials/commentaries,
• conference abstracts, and
• in vitro studies or animal studies,

Assessment of Studey Quality

Ideally, different key questions required different types of evidence in terms of trial design and study type. However, realizing that the evidence base for this topic would be limited, very liberal inclusion criteria was adopted. The vast majority of studies were observational in design and most of these were retrospective. The criteria set for assessing the quality of different study designs, prior to our formal assessments, are listed below. Note that there were not any RCTs with comparisons that addressed any of the specified key questions. Because of this, while RCTs with relevant data were accepted, they were typically graded as observational studies.

For assessing randomized controlled trials, we used an adaptation of the Cochrane risk-of-bias instrument, assessing five of its seven domains:

• random sequence generation,
• allocation concealment,
• incomplete outcome data,
• selective outcome reporting, and
• other potential sources of bias (e.g., lack of balance in group baseline characteristics).

The Cochrane domains concerning blinding, which is not practically or ethically feasible for surgical interventions were not considered.

For non-randomized comparative trials, the following domains were assessed:

• prospective versus retrospective design,
• consecutive enrollment,
• baseline comparability of groups,
• use of statistical controls for confouding,
• incomplete outcome data,
• selective outcome reporting, and
• other portential threats to validitiy.

For diagnostic accuracy studies, appropriate items from the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) instrument were used:

• Was a consecutive or random sample of patients enrolled?
• Was a case-control design avoided (when the true status of patients was already known when they were enrolled)?
• Did the study avoid inappropriate exclusions (i.e., avoid spectrum bias)?
• Were the index test results interpreted without knowledge of the results of the reference standard?
• Was the reference standard likely to classify the target condition correctly?

Finally, and most importantly, for this evidence base, observational and single-arm studies, with the following domains:

• prospective versus retrospective design,
• consecutive enrollment,
• methodological detail (e.g., specification of follow-up time),
• incomplete outcome dtat,
• selective outcome reporting, and
• other potential threats to validity (e.g., lack of measures of dispersion; failure to use appropriate statistical techniques).

Determination of Evidence Strength

The AUA employs a three-tiered strength of evidence system to underpin evidence-based Guideline statements. In short, high certainty by GRADE (Grading of Recommendations Assessment, Development and Evaluation) translates to AUA A-category strength of evidence, moderate to B, and both low and very low to C (Table 1).

The AUA categorizes body of evidence strength as Grade A (well-conducted and highly-generalizable RCTs or exceptionally strong observational studies with consistent findings), Grade B (RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), or Grade C (RCTs with serious deficiencies of procedure or generalizability or extremely small sample sizes or observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data). By definition, Grade A evidence is evidence about which the Panel has a high level of certainty, Grade B evidence is evidence about which the Panel has a moderate level of certainty, and Grade C evidence is evidence about which the Panel has a low level of certainty.

Level B evidence may include observational studies rated as low quality if findings are consistent and of a strong treatment effect. Panelists can therefore make a stronger statement based on this evidence. In instances where evidence for a given question is rated as level C, this does not mean that the panel cannot make a statement based on the evidence, particularly if findings from included studies are not substantially different. Furthermore, in cases where studies show conflicting evidence or evidence is sparse, panelists may still use clinical judgment to inform a guideline statement. Note that the worst possible rating for RCTs is Level B. Therefore, evidence comprised of RCTs and systematic reviews that included only RCTs would be judged as either Level A or Level B.

AUA Nomenclature: Linking Statement Type to Evidence Strength

The AUA nomenclature system explicitly links statement type to body of evidence strength, level of certainty, magnitude of benefit or risk/burdens, and the Panel’s judgment regarding the balance between benefits and risks/burdens (Table 2). Strong Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is substantial. Moderate Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate. Conditional Recommendations are non-directive statements used when the evidence indicates that there is no apparent net benefit or harm, when benefits and harms are finely balanced, or when the balance between benefits and risks/burden is unclear. All three statement types may be supported by any body of evidence strength grade. Body of evidence strength Grade A in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances and that future research is unlikely to change confidence. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence could change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence is likely to change confidence. Conditional Recommendations also can be supported by any evidence strength. When body of evidence strength is Grade A, the statement indicates that benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is unlikely to change confidence. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances and better evidence could change confidence. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens; therefore, alternative strategies may be equally reasonable, and better evidence is likely to change confidence.

Where gaps in the evidence existed, the Panel provides guidance in the form of Clinical Principles or Expert Opinions with consensus achieved using a modified Delphi technique if differences of opinion emerged.³⁸ A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence.

Results

Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full text publications for the remaining 432 articles were ordered, and ultimately 137 unique articles were included for this report.

Peer Review and Document Approval

An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and management of Priapism. In addition to reviewers from the AUA PGC, Science and Quality Council, and Board of Directors, the document was reviewed by representatives from SMSNA, ACEP, and external content experts. A call for reviewers was placed on the AUA website from April 14 - May 3, 2021 to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation to open the document further to the patient perspective. The draft guideline document was distributed to 55 peer reviewers, including 9 external reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 41 reviewers provided comments. At the end of the peer review process, a total of 519 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, Science and Quality Council, Board of Directors, and the governing bodies of SMSNA.

1. In patients presenting with priapism, clinicians should complete a medical, sexual, and surgical history and perform a physical examination, including the genitalia and perineum. Clinical Principle

2. Clinicians should obtain a corporal blood gas at the initial presentation of priapism. Clinical Principle

3. Clinicians may utilize penile duplex Doppler ultrasound, when the diagnosis of acute ischemic versus non-ischemic priapism is indeterminate. Expert Opinion

4. The clinician should order additional diagnostic testing to determine the etiology of diagnosed acute ischemic priapism; however these tests should not delay, and should be performed simultaneously with, definitive treatment. Expert Opinion

5. Clinicians should counsel all patients with persistent ischemic priapism that there is the chance of erectile dysfunction. Moderate Recommendation; Evidence Level: Grade B

6. Clinicians should counsel patients with a priapism event >36 hours that the likelihood of erectile function recovery is low. Moderate Recommendation; Evidence Level: Grade B

7. In patients presenting with a prolonged erection of four hours or less following intracavernosal injection pharmacotherapy for erectile dysfunction, clinicians should administer intracavernosal phenylephrine as the initial treatment option. Expert Opinion

8. In a patient with diagnosed acute ischemic priapism, conservative therapies (i.e., observation, oral medications, cold compresses, exercise) are unlikely to be successful and should not delay definitive therapies. Expert Opinion

9. Clinicians should manage acute ischemic priapism with intracavernosal phenylephrine and corporal aspiration, with or without irrigation, as first line therapy and prior to operative interventions. Moderate Recommendation, Evidence Level: Grade C

10. In patients receiving intracavernosal injections with phenylephrine to treat acute ischemic priapism, clinicians should monitor blood pressure and heart rate. Clinical Principle

11. Clinicians should perform a distal corporoglandular shunt, with or without tunneling, in patients with acute ischemic priapism who have failed pharmacologic intracavernosal reversal and aspiration, with or without irrigation. Moderate Recommendation, Evidence Level: Grade C

12. In patients with acute ischemic priapism who failed a distal corporoglanular shunt, clinicians should consider corporal tunneling. Moderate Recommendation, Evidence Level: Grade C

13. Clinicians should counsel patients that there is inadequate evidence to quantify the benefit of performing a proximal shunt (of any kind) in a patient with persistent acute ischemic priapism after distal shunting. Moderate Recommendation, Evidence Level: Grade C

14. In an acute ischemic priapism patient with persistent erection following shunting, the clinician should perform corporal blood gas or color duplex Doppler ultrasound prior to repeat surgical intervention to determine cavernous oxygenation or arterial inflow. Moderate Recommendation, Evidence Level: Grade C

15. Clinicians may consider placement of a penile prosthesis in a patient with untreated acute ischemic priapism greater than 36 hours or in those who are refractory to shunting, with or without tunneling. Expert Opinion

16. In a patient with acute ischemic priapism who is being considered for placement of a penile prosthesis, clinicians should discuss the risks and benefits of early versus delayed placement. Moderate Recommendation, Evidence Level: Grade C

Priapism remains an understudied area of sexual medicine, with several areas of future research required:

• Basic translational science of the pathophysiology of priapism to identify the most effective therapeutic targets.
• Preventative medical and interventional strategies for stuttering priapism, especially in the sickle cell population.
• Identifying the timeline of acute ischemic priapism and permanent corporal fibrosis with subsequent erectile dysfunction in various clinical and etiologic settings.
• Defining risks and benefits of penile prosthetics placement in acute ischemic priapism, including patient reported outcomes, complications, prosthesis durability, and role of malleable versus inflatable devices.
• Methods of controlling thrombosis, including preserving shunt patency.
• Comparisons of surgical techniques: distal versus penoscrotal approaches to distal shunts; distal shunting with or without tunneling.
• Comparison of embolization techniques and materials, including short- and long-term outcomes including patient reported outcomes.
• Comparative, prospective protocols for both acute ischemic and non-ischemic priapism management to better identify optimal management strategies.
• Identifying a role of sexual health counselor in patients with acute ischemic priapism undergoing surgery and how this affects short- and long-term mental health.

As noted above, there are numerous areas where additional research is warranted to improve our understanding and treatment of priapism. Fundamental basic science investigations are necessary to identify pathophysiologic mechanisms and potential treatment targets. The enhanced understanding of mechanisms and pathways of priapism would allow for new pharmacologic treatment strategies to prevent and terminate priapism early in its course. Although a base-level understanding of disease mechanisms currently exists with priapism in general, more nuanced evaluations and research separating subtypes of priapism (e.g., ICI-induced, oral medication-induced, sickle-cell, idiopathic) may provide for a more customized treatment approach. This is particularly relevant with cases of stuttering priapism, where management includes not only the acute phase but also long-term prevention strategies. Research in this area may expand to include the study of the sleep cycle, neurologic perturbations, and ‘backward engineering’ from medications which have shown some efficacy, including baclofen, anti-androgens or anxiolytics, among others.

Another critical question which remains outstanding relates to the timeline and progression of irreversible corporal damage related to priapism. The issue is further challenged by inaccuracies of estimated duration, possibility of intermittent periods of complete or partial priapism, underlying health of the corporal tissue (i.e., patient age, prior erectile dysfunction, comorbid conditions), prior episodes of priapism, various subtypes (e.g., sickle cell), and interventions performed. For example, a 50-year-old diabetic patient with persistent, untreated priapism lasting 72 hours likely will have a different outcome compared to an 18-year-old sickle cell patient with episodic priapism of a similar duration. This is particularly relevant as providers consider earlier definitive interventions such as placement of a penile prosthesis, wherein confidence is required that spontaneous recovery of erectile function is not possible. Future research into imaging studies, biopsies, adjunctive laboratory testing, or other modalities may help to better inform these decisions. However, at the present time, data are clearly lacking to quantify the true risks and benefits of early, definitive surgical interventions including distal shunting and prosthesis placement in men with acute ischemic priapism.

A third area where future research may benefit outcomes is with anti-thrombotic therapies. As prolonged priapism is associated with cavernosal thrombosis, these therapies may have roles in both the early and late phases of treatment. Specifically, further research is required to determine if anti-thrombotics reduce the frequency of stuttering priapism, minimize the extent of ischemia in active priapism, and/or prevent closure of surgical shunts. Currently, there are very limited data on these topics, however, given the pathophysiology of priapism, the ability to control or regulate corporal thrombosis has inherent appeal.

Finally, significantly more research is required comparing various treatment strategies. Because priapism is an unpredictable and rare event, nearly all research reports are retrospective in nature and do not include comparison groups. Prospective, comparative protocols are warranted to better define optimal treatment approaches. These may include differing surgical techniques (e.g., proximal versus distal approaches, tunneling versus no tunneling, specific methods of shunting); preventative medications; agents and protocols for embolization; imaging modalities; customized algorithms based on etiology and clinical factors; and efficacy of conservative therapies. Outcomes-based assessments and longer-term follow-ups are also merited, as it is not uncommon to see restoration of excellent erection post priapism management in one setting, while another results in clustered recurrence of priapic episodes in another. Although the ideal research protocol would include development of a national priapism registry, in its absence, ambitious clinicians and scientists should consider beginning an institutional database tracking priapism patients and outcomes with pre-defined protocols and standardized follow-up assessments. The development of such protocols would be expected to greatly enhance our understanding of priapism and help provide the data necessary to further refine the next set of guidelines.

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Dosing and Administration of Phenylephrine

The optimal regimen for phenylephrine dosing, frequency, and method of administration has not been clearly defined in the scientific literature. As such, the recommendations which follow are all based on expert opinion and recommendations. Clinicians should consider blood pressure monitoring in men undergoing repeated injections and in those with underlying, relevant comorbid conditions (e.g., hypertension). Monitoring seems especially prudent in patients with a history of cardiovascular disease, hypertension, prior stroke, and those using medications such as monoamine oxidase inhibitors (MAOI). Phenylephrine is a direct-acting sympathomimetic (alpha-1 selective) with end organ selectivity, and there are no reports of toxicity when used for priapism in men using MAOI. Potentiation of phenylephrine effects by prior administration of MAOI is most significant with use of oral phenylephrine, which is dissimilar from intracavernosal administration. When parental use of phenylephrine has been deemed necessary in patients on MAOI, recommendations have included use of low starting doses, thus gradual dose escalation may be reasonable when treating priapism in men using these medications. Should blood pressure spike, this would be detected by monitoring and appropriate medical intervention could be performed.

Although there is no upper limit to the number of injections which may be performed, injections should be stopped if blood pressure changes are detected. Similarly, if the erection persists despite repeated attempts with injections and aspiration/irrigation over a period of one hour or more, the panel recommends proceeding with more definitive therapy (i.e., shunting procedure). Indeed, some clinical scenarios may be more appropriate for a more rapid transition to surgical procedures, without prolonged attempts at phenylephrine and aspiration/irrigation (e.g., priapism >36 hours).

Dosing and instructions:

• Phenylephrine 100-500 mcg doses suspended in 1 ml of normal saline (optimally premixed by pharmacy to minimize risks of miscalculation/overdose)
• Doses administered ≥5 minutes apart
• Administered intracavernosally (not subcutaneously)
• Administered laterally (3 or 9 o’clock position) near the base of the penile shaft
• May be continued for up to 1 hour (see commentary above)
• Small needles may be used (e.g., 27G)
• Consider performing a penile block with local anesthetic prior to beginning
• In cases where the combination of phenylephrine and aspiration/irrigation are performed, aspiration should precede phenylephrine administration to permit fresh, oxygenated blood to fill the corpora and potentially improve the yield of phenylephrine administration

Sample Protocol for Aspiration and Irrigation:

The following protocol is one potential example of aspiration/irrigation with instillation of phenylephrine. However, this should not be considered the gold-standard approach, as there are currently no publications which have identified any method which is superior to another. Similarly, the decision as to when to stop performing aspiration/irrigation with phenylephrine will depend on clinical factors, including response to aspiration/irrigation and time since priapism onset, among others.

Steps for aspiration/irrigation with phenylephrine administration:

1. Perform a penile block with local numbing medication (if not previously performed).
2. Place a 16-18 gauge butterfly needle in the 3 or 9 o’clock position on the penis near the base.
3. Connect the butterfly needle to a 30-60 cc Luer Lock syringe.
4. Alternate between aspiration of blood clots and instillation of saline (chilled if available and if the patient does not have sickle cell disease) until some degree of detumescence can be achieved.
5. Instill phenylephrine.
6. Allow 3-5 minutes of time to pass.
7. Repeat steps 4-6 until detumescence is achieved or until the decision has been made to proceed with surgical shunting.
8. If temporary detumescence is achieved with aspiration followed by a rapid refilling of blood despite multiple attempts of phenylephrine instillation, consideration may be given to placement of a firm penile wrap at the time of aspiration to maintain detumescence.