of the corpora cavernosa to treat refractory ischemic priapism – back to the past

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Pathologic erections Vreugdenhil, Sanne

DOI:

10.33612/diss.95437816

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Publication date:

2019

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Vreugdenhil, S. (2019). Pathologic erections: historical, pathophysiological and clinical aspects.

Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.95437816

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135

of the corpora cavernosa to treat refractory ischemic priapism – back to the past

a concept study protocol based on a post-mortem study

CHAPTER 10

S. Vreugdenhil, M. El Moumni, D. Yakar, I.J. de Jong, M.F. van Driel

To be submitted

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137 Introduction and rationale

Priapism describes a persistent erection lasting >4-6 hours, arising from dysfunction of the mechanisms regulating penile tumescence and fl accidity. Priapism is I. not the result of sexual excitement or, if associated with erotic stimulation, lasts well beyond the original stimulus and II. is not relieved by orgasm or ejaculation. Priapism generally involves only the paired corpora cavernosa (CC), with the glans and the corpus spongiosum of the urethra remaining fl accid or softly distended without rigidity. Clinical causes of ischemic priapism can be of various origins, including hematological, infectious, metabolic, drug-related, malignancy, neurological and idiopathic.

Since priapism is a rare condition, the literature related to its management is neither voluminous nor accurate, comprising mostly case reports and small case series rather than controlled trials.

As a result, the relative effi cacy and safety of diff erent treatments is not always proven. This also means that any decision on the timing and indication of a surgical intervention after unsuccessful medical treatment is controversial.

Aspiration of ischemic blood followed by the intracavernous injection of phenylephrine is the standard initial treatment in ischemic priapism. However, this method is considered ineff ective when applied in a patient with a priapism of >36 hours duration, because the smooth muscle response to phenylephrine will then be impaired due to extreme local acidosis and glucopenia. (1) The objective of shunt surgery- which is the second step - is to bypass the veno-occlusive mechanism and facilitate blood drainage from the CC. This is achieved by creating a connection between the CC and the glans, corpus spongiosum or a vein. According to the most recent European guidelines it is not possible to give an evidence-based advice on which type of shunt is preferred over the other (Figure 1).

Particularly in the United States of America (USA), reasonable results have been reported in terms of resolution of the priapism and recovery of normal erectile function in patients who were treated by creating an opening between the distal ends of both corpora cavernosa and the glans penis, followed by a retrograde intracavernous insertion of a 7/8 Hegar dilator to release old congested viscous blood. (2)

Obviously, the success of this so-called T-shunt with `snake tunneling` will depend on the duration of the priapism. (3) If performed <24 hours after its onset the results were favorable, although 50% of the patients still ended up having erectile dysfunction. For those in whom the priapism lasted for >48 hours this technique failed to resolve the priapism and in 100% of them had erectile dysfunction due to smooth muscle necrosis. In conclusion, the European guideline states that any shunt procedure may only serve to limit pain sensations without preserving erectile functioning if the ischemic priapism lasted >36 hours before treatment was initiated. (4)

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138

Methods

To test the feasibility of unilateral fasciotomy of the CC in long-lasting priapism, we used a cadaver embalmed according to Walter Thiel’s technique. Thiel first described his embalming method in 1992 using mainly 4-chloro-3-methylphenol and various salts for fixation, boric acid for disinfection, and ethylene glycol for the preservation of tissue plasticity (Thiel, 1992;2002). The cadavers are perfused via the femoral or carotid artery with an intravascular solution containing 14300 ml of solution A, plus 500 ml of solution B and the addition of 700g of sodium sulfite as well as 300ml formalin for a body weight of 80kg. (5) The application of this formula results in a corpse with tissue color, -flexibility and -plasticity very similar to that of a living body. Table 1 summarizes the basic composition of the injection and immersion solutions.

The Thiel cadaver was positioned and covered on a surgical table at the Skills Centre of the Wenckebach’s Institute of the University of Groningen. A basic surgical set was used to perform the surgery. In order to provide penile erection, we first attempted to inject saline into the internal iliac artery, without success. In addition, we placed a 12 gauche needle into one corpus cavernosum and infused saline, resulting in a rigid penile erection. On the contralateral CC we performed the fasciotomy.

Based on this cadaver study we made an outline with regard of a possible in vivo study (Supplemental material).

Table 1. Basic composition of injection and immersion solutions described by W. Thiel in 1992.

Discussion

Ischemic priapism is a urological emergency with potentially devastating irreversible effects. It is caused by a failure of the detumescence mechanism due to obstruction of draining venules in combination with prolonged relaxation of the intracavernous smooth muscles. The current guidelines do not provide a fixed set of rules or define a legal standard of care for the treatment of priapism.

SOLUTION A Boric acid 3g Ethylene glycol 30ml Ammonium nitrate 20g Potassium nitrate 5g Hot water 100ml

INJECTION SOLUTION Solution A 14300ml Solution B 500ml Formaldehyde 300ml Sodium sulfate 700mg

IMMERSION SOLUTION Ethylene glycol 10ml Formaldehyde 2ml Solution B 2ml Boric acid 3g Ammonium nitrate SOLUTION B

Ethylene glycol 10ml 4-chloro-3-methylphenol 1ml

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139 Of critical importance for patients, spouses and physicians is a frank discussion about the goal(s) of any procedure and their outcome. When ED occurs, it is the result of the priapism itself and not of the surgery.

A major problem in daily clinical practice is that patients with priapism present too late. In the past 32 years we found an increased number of patients presenting with ischemic priapism after recreational use of intracavernous injections with illegally obtained vasodilating drugs.

This concerns a poorly informed group with a signifi cantly longer patient delay, probably due to shame and ignorance. In our opinion, these patients should be informed that after 36 hours shunt surgery will not be successful with regard erectile function. ED after unsuccessful treatment of priapism is an extremely diffi cult problem because of the considerable fi brosis of the erectile tissue that ensues as a result of it. These patients can be treated with a prosthesis in the early or in a later phase. However, implantation in a later phase will leave nearly all patients dissatisfi ed about the result with regard of the limited penile length that can be achieved with insertion of the prosthesis. This is a result of the shortening of the CC that occurs in all patients with refractory priapism. Sometimes, an infl atable prosthesis can’t even overcome the rigidity of the severe fi brosis and a semi-rigid model will be necessary.

For these reasons, experts advise to perform prosthesis implantation in the early phase; within 2-4 weeks after the onset of the priapism (Figure 3). (6) In this early phase it is possible to regain the original penile length. Obviously, the potential complications of early implantation should be discussed. Compared to virgin cases, there is a six times higher risk of infection due to the preceding intracavernous injections of phenylephrine and necrosis. Moreover, in case of preceding distal shunt surgery there is a 6 percent risk of erosion and urethral injury at the time of corporal dilatation, which is performed before the insertion of the cylinders of the prosthesis.

(6,7) At 16 months after early implantation of a prosthesis the revision rate will be as high as 12 %.

Another considerable risk of this early implantation is the overtreatment of patients who did not yet develop intracavernous necrosis. For this reason, we do not recommend to perform prosthetic surgery within 36 hours after the beginning of the priapism. In addition, a gadolinium-enhanced high defi nition magnetic resonance imaging (MRI) scan of the penis can be performed in order to make a deliberate decision about whether or not to proceed to prosthesis implantation. MRI of the penis has a 100% sensitivity when used for the detection of smooth muscle necrosis. [8]

Ischemic priapism is anyhow analogous to a muscle compartment syndrome. In that respect it is remarkable that anno 2019 the treatment is not analogous to that applied in for example a compartment syndrome of the arm or leg. An extended fasciotomy of the tunica albuginea of the CC was already described by Frank Hinman Sr more than 100 years ago. In those days infection was a common problem due to the lack of antibiotics. Since then fasciotomy was considered an inferior treatment method. However, in our opinion, it might be useful to revive this technique to treat patients with refractory priapism, on the condition that there is still a suffi cient amount of vital tissue in the CC.

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140

We hypothesize that today, with broad spectrum antibiotics, fasciotomy may be the only possible treatment to preserve erectile function after >36 hours lasting ischemic priapism and may prevent precarious prosthesis implantation.

In our opinion, the potential to salvage any viable erectile tissue outweighs the potential risks of a fasciotomy in priapism patients with delayed presentation (>36 hours). If the priapism has been present for >72 hours with evidence of extended tissue necrosis on MRI, non- surgical management consisting out of pain control with or without psychological counseling or the early implantation of a prosthesis is indicated.

We propose to carry out this surgical intervention in study design. First it would involve a proof of concept study to assess the feasibility of performing a fasciotomy in patients with refractory priapism. Subjects will be included from the patients presenting at our emergency department or outpatient clinic with prolonged ischemic priapism. When a patient is referred by his general practitioner or urologist from elsewhere to our hospital with symptoms of ischemic priapism, the initial work-up will be performed according to the European guidelines. A schematic representation of the work-flow we intend to use during the inclusion for performing a fasciotomy can be found in Figure 1.

In order to be eligible to participate in this study a subject should meet all of the following criteria:

duration of the priapism is >36 hours, whether or not after unsuccessful medical treatment and/or shunt surgery, with a maximum duration of 72 hours

the patients is >18 years of age

gas measurement of blood aspirated from the CC should be compatible with ischemic priapism (pH <7.25, pO2 <4 kPa, pCO2 >8kPa)

A potential subject who meets any of the following criteria will be excluded from participation in this study:

duration of the priapism is < 36 hours or >72 hours

there is evidence of extended tissue necrosis on the MRI of the subjects’ penis at the time of presentation

subjects suffering from severe pre-existing erectile dysfunction (IIEF < 14 out of 30 Pts) subjects with any sign of neurological or psychiatric disorder that will preclude the patient from expressing its own free will and/or will impair its ability to understand and authorize written informed consent.

subjects with an estimated glomerular filtration rate of <15ml/min/1,7373m2 at first presentation

immune comprised patients (e.g. after organ transplantation, HIV/aids, use of immunosuppressive medication).

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141

patient with ischemic priapism

aspiration, irrigation, phenylephrine

deposition

MRI penis

permanent detumescence is achieved - patients aged <18 years

- patients with severe pre-existent erectile dysfunction - incompetent patiënt due to neurologic/psychiatric disease - immune comprised patient

early penile prosthesis implantation 36-72h

shunt surgery

<36h

fasciotomy absent/conﬁned

necrosis

diffuse necrosis failure to achieve

permanent detumescence

no consent after information about study procedure

>72h failure to achieve permanent

detumescence

Figure 1. Work-fl ow for patient inclusion from the ischemic priapism population

If there is extensive necrosis or the priapism exists for more than 72 hours the patient will be advised to have a penile prosthesis implanted in the semi-acute or in later phase. Follow-up will should be assessed concerning both erectile function using a validated questionnaire “International Index of Erectile Function” at 3 and 9 months follow-up. Viability of the corporal smooth muscle will be evaluated by performing an MRI of the penis 6 months after the surgery was performed and this will be compared to the one that was made before treatment was initiated.

In patients who are dissatisfi ed about their erectile function after 12-18 months follow-up a late implantation of an erection prosthesis will be off ered and performed if the patient wishes us to do so.

Next to the aforementioned “primary study parameters”, secondary parameters will also be assessed, including: the number of times the procedure needs to be repeated before permanent detumescence is achieved, hospital lay days, postoperative pain (according to the Numeric Rating Scale), number and nature of complications/serious adverse events (+Clavien Dindo classifi cation), the correlation between MRI observed perfusion, fi brosis/necrosis that is observed in the per-operatively taken histological biopsies and ED (according to the IIEF questionnaire).

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142

Moreover, one should consider potential confounding factors during the analysis, like: duration of the priapism, prior interventions before fasciotomy was performed, smoking, STDs, the use of anticoagulant medication, pre-existent blood clotting disorder, pre-existent cardiovascular disease or diabetes mellitus and pre-existent erectile function.

To implicate the MRI of the penis in this study we designed a protocol, based on earlier ones described in five studies concerning the application of MRI to asses intracavernous necrosis in patients with priapism. (8-12)

No such protocol has yet been developed in this country.

Protocol MRI of the penis

Details

Fixate penis in dorsiflexed position against the lower anterior abdominal wall in the midline. Ask patient to take off his underpants. Put a rolled towel between his legs to support the scrotum. Instruct patient to adhere to chest-breathing as much as possible, to avoid motion of the abdomen.

Indication Refractory low-flow priapism

Preparation • I.V. access Coil & positioning • Feet first supine

• MR4: small flex Flex alone, no spine!

Sequences Localizer Spin echo sequences

1. Loc_sag

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143 2. T2_tse_sag

1. T2_tse_cor

2. T2_tse_tra

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144

Details

Fixate penis in dorsiflexed

position against the lower anterior abdominal wall in the midline. Ask patient to take off his underpants.

Put a rolled towel between his legs to support the scrotum. Instruct patient to adhere to chest- breathing as much as possible, to avoid motion of the abdomen.

Indication Refractory low-flow priapism

Preparation • I.V. access

Coil & positioning • Feet first supine

• MR4: small flex Flex alone, no spine!

Sequences Localizer Spin echo sequences

1. Loc_sag

2. T2_tse_sag

Future prospects

The abovementioned study protocol has already been submitted to the medical ethical committee.

Approval was given to perform this study in a proof-of-concept design. If the suggested surgical intervention turns out to be safe and effective, a more extended, probably multi-center, study will be developed with the aim to provide a chance of preserving erectile function in patients with refractory ischemic priapism.

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145 References

MuneerA,MinhasS,FreemanA,KumarP,RalphDJ.Investigatingtheeff ectsof high-dose phenylephrine in the management of prolonged ischaemic priapism. J Sex Med 2008;5:2152-2159.

Burnett AL, Pierorazio PM. Corporal “snake” maneuver: Corpoglandular shunt surgical modifi cation for ischemic priapism. J Sex Med 2009;6:1171-6.

Zacharakis E, Raheem AA, Freeman A, Skolarikos A, Garaff a G, Christopher AN, Muneer A, Ralph DJ. The effi cacy of the so-called T-shunt procedure and intracavernous tunneling (snake maneuver) for refractory ischemic priapism. J Urol 2014;191:164-8.

Salonia A, Eardley I, Giuliano F, Hatzichristou D, Moncada I, Vardi Y, Wespes E, Hatzimouratidis K; European Association of Urology. European Association of Urology guidelines on priapism. Eur Urol 2014;65:480-9.

OttoneNE,VargasCA,FuentesR,DelSolM.WalterThiel’sembalmingmethod. Review of solutions and applications in diff erent fi elds of biomedical research. Int. J. Morphol, 2016. 34(4):1442-54.

Garaff aG,RalphD.Penileprosthesisimplantationinacuteandchronicpriapism. Sex Med Rev 2013;1:76-82.

Ralph DJ, Garaff a G, Muneer A, Freeman A, Rees R, Christopher AN, Minhas S. The immediate insertion of a penile prosthesis for acute priapism. Eur Urol 2009;56:1033-8.

Ralph DJ, Borley N, Allen C, Kirkham A, Freeman A. Minhas S, Muneer A. The use of high- resolution magnetic resonance imaging in the management of patients presenting with priapism. BJU Int 2010;106:1714-8.

Pretorius ES, Siegelman ES, Ramchandani P, Banner MP. MR Imaging of the penis. RadioGraphics 2001;21:283-99.

Pegios W, Rausch M, Balzer JO, Wolfram M, Bentas W, Jonas D, Vogl TJ. MRI and color- coded duplex sonography: diagnosis of partial priapism. Eur Radiol 2002;12:2532-5.

Kirkham APS, Illing RO, Minhas S, Allen C. MR Imaging of non-malignant penile lesions.

RadioGraphics 2008;28:837-53.

Kirham APS. MRI of the penis. Br J Radiol 2012;85:86-93.

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147 Supplemental material – Surgical procedure protocol

1. Antibiotic prophylaxis

a. Antibiotic prophylaxis (if not already started at presentation); 30 minutes before the start of the incision, to continue until the fasciotomy has been closed à cefuroxime 1500mg intravenous (i.v.) in a onetime dose, followed by 1500mg 3 times a day.

2. Anaesthesia

a. General anaesthesia will be used during the operation

b. An epidural catheter will be placed pre-operatively for adequate postoperative pain management

3. Positioning and asepsis

a. Patient will be positioned in lithotomy position

b. Local disinfection using 0.5% chloralhexidine/1% (polyvidone)iodine will be applied c. Sterile covering of the patient

4. Surgical procedure

a. Perform a circumcision (if possible; this may be problematic in case of infl ammation and oedema of the penile tissue)

b. Insert of a transurethral catheter (Charrière 14, to prevent urethral damage during procedure) c. Strip down the penile skin (if possible) to expose the tunica albuginea of the CC

d. Fill the bladder with 400cc of saline and perform a punction of/for a suprapubic cystostomy e I-III. Perform a (transdermal) bilateral longitudinal incision of the tunica albuginea of the CC at 3 and 9 o’clock position; extending from the corona glandis up to the suspensory ligament.

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f I-II. Perform an incision of the median-dorsal part of both crura (the proximal parts of the CC), via a perineal approach. Extend it down to the suspensory ligament until there is a connected incision over the full length of the CC.

g. Take biopsies from the erectile tissue at the distal, middle and proximal part of the CC h. Perform an extensive debridement of old blood and necrotic erectile tissue

i. If major bleeding occurs, this can be controlled by covering the wounds with gauzes wetted in diluted adrenaline solution.

4c

4e II

4e I

4e III

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149 5. Primary post-operative wound care (<36 hours after the operation)

Leave the wound open to prevent pressure from rebuilding within the CC and secure the oxygenation of the erectile tissue

a. Drape wet gauzes over the incision wounds of the tunica albuginea (and skin) b. Redress the penile fascial (and skin) layers

c. Remove the transurethral catheter

d. Wrap a non-compressing bandage around the penis 6. Secondary wound care (>36 after the operation): closure

a. Take a second look after 24-36 hours and perform a second debridement if needed b. Close the incision sites with either:

I: sutures (Vicryl 6-0) to continuously close the penile fascial layers (and skin) or

II: V-locks (90) and approximate the wound margins during the next 48 hours

c. If circumcision and degloving of the penis was successfully performed: redress the skin and sew the edges of the shaft skin to the new preputial collar using fi ne absorbable sutures (5- 0) d. Remove the suprapubic catheter after full recovery of the wounds

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6. Secondary wound care (>36 after the operation): closure

a. Take a second look after 24-36 hours and perform a second debridement if needed b. Close the incision sites with either:

I: sutures (Vicryl 6-0) to continuously close the penile fascial layers (and skin) or

II: V-locks (90) and approximate the wound margins during the next 48 hours

c. If circumcision and degloving of the penis was successfully performed: redress the skin and sew the edges of the shaft skin to the new preputial collar using fine absorbable sutures (5- 0) d. Remove the suprapubic catheter after full recovery of the wounds

7. Follow-up

a. Evaluate wound healing and offer sexological counselling at the outpatient clinic at least one week after the patient was discharged from the urological ward. Repeated visits if necessary.

b. At 3 and 9 months post-operative revision at the outpatient clinic to evaluate sexual function including an assessment of the questionnaire International Index of Erectile Function (IIEF) c. Perform a repeated MRI of the penis at 6 months follow-up to evaluate the effect of the treatment on intracavernous fibrosis

d. Last visit at 12 months post-operative if the patient is dissatisfied about his sexual function (ED) to inform him on penile prosthesis implantation

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