Penile implant reservoir placement methods: is there a gold standard?

Abstract

Erectile dysfunction (ED), a condition affecting nearly 150 million men worldwide, is expected to impact over 300 million by 2025. Phosphodiesterase type 5 inhibitors (PDE5Is) remain the first-line treatment for ED, yet a subset of patients exhibit inadequate responses. For these individuals, the inflatable penile prosthesis (IPP) offers an effective alternative, with the three-piece IPP being particularly favored for its high satisfaction and low complication rates. However, the challenge of optimal reservoir placement, particularly in the extraperitoneal space of Retzius (SOR), has prompted investigations into alternative approaches. SOR placement is associated with complications, such as injury to iliac vessels, bladder puncture, and bowel perforation. Various alternative sites have been proposed, including epigastric extraperitoneal, intraperitoneal (IP), high submuscular (HSM), and lateral retroperitoneal (LRP) positions, each aiming to mitigate these risks while improving patient outcomes. Comparative studies have shown that methods such as IP and HSM reduce the risk of vessel compression and bladder injury, often yielding higher satisfaction rates compared with SOR. However, each technique carries unique drawbacks, including risks of palpability, improper placement, and longer operative times. This review synthesizes current evidence on reservoir placement strategies, evaluates their advantages and limitations, and highlights crucial considerations for patient selection, providing a comprehensive overview of IPP implantation techniques and their evolving roles in the management of ED.

INTRODUCTION

Erectile dysfunction (ED), defined as the persistent inability to achieve and sustain an erection adequate for satisfactory sexual intercourse, affects approximately 150 million men worldwide to varying degrees. This number is projected to exceed 300 million globally by 2025.1,2 Phosphodiesterase 5 inhibitors (PDE5Is) remain the most popular treatment option for ED due to their well-established efficacy, safety, and non-invasive nature. However, the increasing number of patients with minimal or no response to PDE5Is, along with the risk of adverse reactions, has spurred the development of alternative, more effective treatments.3 Since its initial description in 1974, the inflatable penile prosthesis (IPP) has emerged as an increasingly favored treatment for ED, largely due to its high patient satisfaction rates and low incidence of complications.4,5 IPP technology advances coupled with improved scientific knowledge of perioperative management and innovative surgical techniques have revolutionized penile prosthesis surgery over the past five decades.6

IPP devices are generally categorized into three types: single-piece, two-piece, and three-piece prostheses. Single-piece devices feature a small reservoir at the end of each cylinder, two-piece devices have the reservoir attached to the pump, and three-piece devices include a larger, separate reservoir connected to the pump.7 The three-piece inflatable prosthesis is currently the most common implant, and also the most highly rated in terms of patient satisfaction.8 The three-piece IPP allows for manual adjustment of penile thickness, length, and hardness, effectively simulating the natural erection process.6 Reservoir placement for the three-piece IPP is associated with specific surgical challenges and serious complications during the implantation procedure.9 Traditionally, surgeons place IPP reservoirs blindly in the retropubic extraperitoneal space of Retzius (SOR) via a penoscrotal incision which makes it one of the riskiest parts of the procedure.9 A cadaveric study has shown that the external inguinal ring is located only 2.5–4 cm from the external iliac vein and 2–4 cm from a non-decompressed bladder in patients with normal pelvic anatomy.10 These proximities to critical vascular and other organs along with blind placement of reservoir result in some of the most devastating complications including damage to the iliac vessels, bladder puncture, small bowel perforation, erosion or obstruction, and reservoir herniation.9,10

Over the years, various strategies have been developed to enhance patient safety and reduce complications in surgical practice. The SOR placement of the reservoir via a single penoscrotal incision is considered the most favorable method among patients. This approach allows the reservoir to be accommodated discreetly, making it neither visible nor palpable, while also minimizing skin scarring.4 However, blind reservoir placement can cause surgical anxiety during implantation. Due to a higher complication rate, inexperienced urologists may prefer to use malleable or two-piece prostheses to minimize the risks associated with blind reservoir placement. Meanwhile, higher levels of patient satisfaction are typically seen with the three-piece prosthesis.11 In fact, many urologists limit the implant models they offer to patients due to their inability to confidently perform the reservoir placement step of the procedure.12 Furthermore, obliteration of the extraperitoneal space and distortion of normal surgical planes caused by adhesion formation following prior surgeries, such as robotic-assisted laparoscopic prostatectomy (RALP), have introduced additional challenges in placing the reservoir in the SOR.13,14,15 Surgeons have several options to address these challenges, including choosing between ectopic and retropubic spaces, assessing both the left and right sides, slightly underfilling the reservoir when feasible, utilizing additional tools such as a nasal speculum, and even making a counter-incision to ensure proper placement and minimize the risk of complications.10

In this review, we summarize different strategies and techniques for IPP reservoir placement, their respective pros and cons, and special considerations for different populations undergoing IPP surgery in this regard. We will focus on the location of reservoir and the incisions required for its placement.

RESERVOIR LOCATION

Due to the risks associated with placing the reservoir in the classic SOR, alternative locations have been developed to make the procedure safer and easier. These approaches seek to reduce complications including bladder injury and vessel compression, especially in challenging anatomical cases.16

One of the first attempts to place the reservoir outside the SOR was described by Remenschneider17 who described positioning the reservoir in the epigastric extraperitoneal region through the second subcostal incision. He hypothesized that the epigastric extraperitoneal location offered the potential for more straightforward access and reduced interference with nearby pelvic structures, contributing to a less invasive procedure overall. Subsequently, in 2002, Wilson et al.18 introduced the technique of “ectopic” reservoir placement. This technique comprises creating a space through inguinal canal by dissecting anterior to the transversalis fascia and posterior to the abdominal wall muscle layers.

Over time, different alternative sites have been proposed and examined as potential reservoir placement options, including intraperitoneal (IP),19 high submascular (HSM),20 lateral retroperitoneum (LRP),21 posterior to the transversalis fascia (PTF), anterior to the transversalis fascia (ATF),22 low submuscular (LSM),23 subexternal oblique (SEO),24 and subcutaneous (SC),25 as shown in Figure 1.

Figure 1.

Various inflatable penile prosthesis reservoir placement sites.

Several studies have been conducted to evaluate these methods and compare the outcomes with the classic placement in the SOR (Table 1). Schreiter introduced a technique in which the reservoir was placed in the peritoneal cavity (intraperitoneal) without requiring the second incision. This method was advantageous because of the low pressure on the reservoir in this space and the absence of capsule formation around the device, which helped prevent auto-inflation, particularly before the advent of reservoirs with a “lock-out valve”.26,27 Although these data were not published as a paper, the method became popular and was adopted by several surgeons in Germany.28 A retrospective study of 52 patients with IPP found that those with the reservoir placed in the IP position (39 patients) had significantly higher mean scores in all quality of life (QoL) questionnaire domains (P < 0.001). The operative time was about 9 min longer in the IP group (mean ± standard deviation [s.d.]: 141 ± 33.8 min vs 132 ± 47.4 min), though the difference was not statistically significant. In the first post-operative month, nine patients (three from the SOR group and six from the IP group) reported feeling the reservoir, but by the 6-month follow-up, all were satisfied, and no corrections were needed. Additionally, two patients (15.3%) in the SOR group and one (2.6%) in the IP group experienced persistent discomfort due to reservoir palpability months after implantation, but none required replacement.19

Table 1.

Advantages and disadvantages of various reservoir placements

Location	Suitability for specific patient groups	Advantage	Disadvantage	More points
SOR	Patients with virgin pelvis (not oblitrated SOR due to previous RALP or radiotherapy)	Classic method (anatomically familiar) Reservoir concealment and decreased palpability Typically, without interference with visceral structures Providing a potential space with lower risk of autoinflation	Blind reservoir placement into the retropubic space Rare but devastating complications due to proximity to local structures (bladder, bowel and vascular injuries)	Modifications in SOR placement may reduce the risk of visceral injury, including counter incision, Trendelenberg patient position, using Jorgenson scissors and direct vision approach to SOR via penoscrotal incision or through the external oblique fascia.
Submascular	PTF: mostly in first-time implant patients	Avoiding the risk of catastrophic vascular injury	Reservoir herniation Possibility of bladder perforation	Probability of reservoir herniation is higher in ATF
	ATF: mostly in patients with anatomic issues	Avoiding possibility of bowel damage without the necessity of the second incision	Reservoir herniation Palpable or visible bulge	No clear item found No clear item found
HSM	Patients with history of pelvic surgery and oblitrated SOR Patients who need both AUS and IPP implantation	Avoiding visceral and vascular injuries associated with SOR or IP placement with comparable patient satisfaction Reduced palpability	Incorrect placement probability due to blind approach Risk of herniation and autoinflation due to increased pressure in submuscular space	Modified methods have been developed to increase efficacy of HSM RP (for instance, under direct vision transfascial or with counter incision)
LRP	Patients with all forms of urinary diversion	Facilitated replacement or removal of reservoir Concealability	Complications associated with counter incision Possibility of unintended IP placement	No clear item found No clear item found
IP	No clear item found	Low risk of abdominal or inguinal herniation	Reservoir migration and entanglement with bowels leading to intestinal erosions and peritonitis	Fixation of reservoir to abdominal fascia reduces migration risk
LSM	No clear item found	Ease of placement	Probably palpable or visible reservoir	No clear item found
SC	Obese patients	Better access in obese patients for reservoir placement/removal	Probably palpable or visible reservoir	No clear item found
SEO	Only used in patients with no prior inguinal canal surgery and inguinal hernia	Easy to carry out Low risk of visceral injury or palpability	Probability of improper placement of reservoir	No clear item found

SOR: space of Retzius; PTF: posterior to the transversalis fascia; RALP: robotic-assisted laparoscopic prostatectomy; ATF: anterior to the transversalis fascia; HSM: high submascular; RP: reservoir placement; IP: intraperitoneal; AUS: artificial urinary sphincter; IPP: inflatable penile prosthesis; LRP: lateral retroperitoneal; LSM: low submuscular; SC: subcutaneous; SEO: subexternal oblique

Morey and colleagues20 described the HSM placement technique, where the reservoir is positioned higher by pushing it toward the umbilicus, just beneath the rectus sheath. This is achieved using a lung clamp or long sponge-stick forceps through a scrotal or infra-pubic incision.

To compare HSM and SOR reservoir placement, CT scans of 139 patients (32 with SOR, and 107 with HSM reservoir placement) were analyzed and compared. The findings showed that HSM reservoirs were positioned about five times farther from the bladder and iliac vessels than SOR reservoirs, significantly reducing the risk of bladder compression (9% vs 72%, P < 0.01). Additionally, while only 4% of HSM reservoirs had any impact on the iliac vessels—causing only mild compression when present, nearly one-third of SOR reservoirs compressed more than 50% of the vessel’s luminal diameter.29 Furthermore, another study reported that the satisfaction rate after HSM implantation was 88% compared with SOR placement with 81% (P < 0.001, Z score: 4.2). Nevertheless, HSM reservoir placement was associated with bothersome palpability of the reservoir in a number of cases. In this study, 58% of patients reported that they were able to feel and 5.3% said that they could visualize the reservoir. This palpability diminished by 80% in patients with body mass index (BMI) >26.5 kg m⁻² after capsule formation within 3 months.30

On the other hand, one of the most significant drawbacks of HSM implantation is the blind nature of the procedure, which can lead to improper positioning of the reservoir. This risk of imprecise placement is not uncommon and is a critical consideration when choosing this approach. For instance, in a cadaveric study, abdominal dissection was performed after bilateral reservoir placement by experienced implanters in 10 fresh cadavers (20 implantations). The results revealed that only 35% of the reservoirs were accurately positioned within the intended HSM space, 45% were located deep to the external oblique fascia and lateral to the rectus muscle, and alarmingly, 20% of the reservoirs were found to be intraperitoneal, retroperitoneal, and preperitoneal, far from their intended location.31

Several studies reveal that palpability, muscle discomfort and pain rarely necessitate revision surgery. Furthermore, removal of a reservoir from the HSM location just beneath the abdominal wall via a counter incision is faster and easier than SOR which is deep in the pelvis. However, if the reservoir is inadvertently placed intraperitoneally, the patient may be at risk of more severe complications, such as bowel injury, torsion, or mesenteric strangulation, all of which would require revision surgery.30,32,33

Other studies have explored alternative methods and techniques to overcome the drawbacks of blind reservoir placements, particularly in patients with a history of radical pelvic surgery. One of the more widely adopted approaches is the use of a counter incision (CI) for reservoir implantation. One such study involved 534 patients, with 51 cases in which a CI was made in the left lower quadrant.34 In these cases, the submuscular space was created during reservoir placement, and the tubing was tunneled to the penoscrotal incision. Additionally, four patients who were future candidates for renal transplant underwent a lower midline CI with submuscular reservoir placement to avoid interference with the transplant Gibson incision. The most common indications for using the CI technique were a history of radical prostatectomy (34 patients) and hernia repair (21 patients).

In another study involving 456 virgin IPP implants with HSM reservoir placement (RP), 34 patients underwent reservoir placement using the CI technique, while 422 patients received the transinguinal (TI) technique.35 The CI-HSM technique resulted in a 19.9% longer median operative time, which, although statistically significant (81.5 min vs 68 min, P < 0.01), was clinically negligible. Herniation occurred in 12 patients in the TI-HSM group (2.8%) but was absent in the CI-HSM group (P > 0.99). The rates of device infection were similar between the two groups.

Another method to avoid blind HSM RP is direct vision transfacial (DVT) technique, in which the anterior rectus sheath is pierced, the rectus muscle is split, and the reservoir is directly embedded in the intended location. In 2022, a retrospective study was performed on 107 cases of DVT reservoir implantation.36 Abdominal imaging performed on 43 of the cases revealed that 79% of RPs were accurate. However, the study also found that the infection rate was higher than expected, and the technique did not entirely eliminate the risk of inaccurate reservoir placement. Despite being performed under direct vision, inaccurate RP placement was still a possibility.

Other submuscular approaches, such as ATF, PTF and SEO, have also been described as alternatives for RP. A retrospective study22 compared two groups of patients with ectopic reservoirs: one group underwent reservoir implantation anterior to the transversalis fascia (typically for patients with anatomic issues), whereas the other group had it placed posterior to the transversalis fascia (typically for virgin implants). The study identified complications in both groups, including bladder injury, reservoir herniation, the need for revision due to palpability, auto-inflation, and infection. The incidence of reservoir herniation was the only complication that reached statistical significance with an increased risk in ATF (P < 0.001). Although ATF implantation avoids injury to visceral structures and vessels without the need for a counter incision, the potential for herniation and reservoir palpability may lead to dissatisfaction and the need for surgical revision.

In another study,24 as an additional submuscular option for reservoir placement, some urologists suggest LSM placement with transfacial fixation (TFF). In a retrospective assessment,23 a total of 31 patients who had their reservoir placed in LSM location were followed up. The ease of placement and high satisfaction rate (4.1 out of 5) were noteworthy features. However, the main drawbacks were palpability and, in some cases, the visibility of the reservoir, which could affect patient comfort and satisfaction.

Some urologists have examined LRP as a potential space for RP. One study examined 31 patients who underwent the LRP technique for reservoir placement following radical prostatectomy, comparing them to a control group of 31 patients who had SOR placement. Over a 2-year follow-up, no intraoperative or postoperative complications were reported in the LRP group. While the LRP technique did result in a slightly increased operative time and some patient discomfort due to the second incision, these factors were considered statistically insignificant.21

Another study37 included a larger group of patients (266 LRP vs 321 SOR). It found that two patients (0.6%) in the SOR group and three patients (1.1%) in the LRP group experienced reservoir failure or leakage postoperatively. Additionally, one patient from each group reported feeling a bulge or pain at the reservoir location. The infection rate was higher in the SOR group, with 15 patients (4.7%) affected, compared to 5 patients (1.9%) in the LRP group. Although this difference was clinically significant, it did not reach statistical significance (P = 0.06).

A study38 involving 80 patients who underwent LRP of IPP following radical cystectomy and urinary diversion assessed outcomes after a mean follow-up of 53.9 (range: 6.5–150.7) months. The use of a CI was noted to make the removal or replacement of the reservoir safer and more efficient, as it facilitated immediate identification of any visceral injury.

Subcutaneous (SC) placement of reservoir could be also considered in obese patients, as the classic SOR or abdominal wall RP techniques can be challenging in these population. A study in 2016 evaluated outcomes in eight patients who underwent SC reservoir placement.25 None of the patients reported being able to palpate the reservoir postoperatively. One patient developed an infection, necessitating reservoir removal, which was performed without difficulty due to the SC location.

INCISION STRATEGIES AND USE OF COUNTER-INCISION

The location of the main incision varied across studies, with the penoscrotal approach being the most commonly employed. Many authors, including Grimberg et al.,34 Kava et al.,39 and Morey et al.,20 utilized a penoscrotal incision as the primary surgical site due to its accessibility and versatility. This approach allowed direct placement of the reservoir into submuscular spaces or the space of Retzius with minimal complications. Kava et al.36 highlighted the elastic properties of the scrotal skin, which facilitated elevation above the symphysis pubis, enhancing exposure for reservoir placement. Infrapubic incisions were also utilized, particularly in cases requiring lateral retroperitoneal or Retzius space placement, as described by Loh-Doyle et al.38 and Stember et al.22

The use of counter-incisions was another noteworthy point of debate across studies, but its application varied depending on patient-specific factors and surgical challenges. Several studies reported the routine use of counter-incisions in high-risk cases, particularly in patients with prior pelvic surgeries or anatomical complexities. For instance, Loh-Doyle et al.37 recommended CIs for lateral retroperitoneal reservoir placement to reduce the risk of injury to adjacent organs, such as the intestine or urinary diversion. Similarly, Stember et al.22 utilized CIs in 17% of cases where anatomical factors, such as prior prostatectomy or hernia repairs, complicated reservoir placement. Hernández et al.32 also emphasized the importance of CIs in high submuscular placements to overcome challenges posed by prior surgeries or radiation therapy.

Some studies also reported more details about the CI based on the patients’ condition, such as a 3-cm incision between the umbilicus and iliac spine for laparoscopic-like reservoir insertion, as described by Natali et al.19 The technique of Hartman et al.21 also used the anterior superior iliac spine as a landmark for accessing the retroperitoneum.

In contrast, other studies demonstrated that CIs were unnecessary in standard cases. Morey et al.20 reported successful reservoir placement through a single penoscrotal incision without requiring additional incisions, highlighting the safety and efficiency of this approach for patients without significant anatomical challenges. However, some groups emphasized the importance of CIs for improved visualization and safety in challenging scenarios. For example, Roth et al.4 advocated for CIs to enable direct visualization during reservoir placement in the SOR, reducing the risk of complications from blind insertion. Loh-Doyle et al.37 further noted that counter-incisions facilitated immediate recognition of complications, such as colon injury, and minimized contamination risks during surgery.

Overall, the surgical approach to reservoir placement demonstrated significant flexibility, with decisions regarding incision location and CIs tailored to the patient’s history and anatomical considerations. While the penoscrotal incision was the dominant choice due to its accessibility and ease of use, CIs were primarily reserved for high-risk or anatomically challenging cases. In standard cases, single-incision techniques proved effective and avoided the need for additional surgical sites. Across all techniques, emphasis was placed on ensuring safety, minimizing complications, and maintaining surgical precision.

DISCUSSION

The choice of reservoir placement in a patient depends on their history of pelvic or abdominal surgeries and prior radiotherapy, which may also influence the type of incision used. For this reason, the authors reviewed incision considerations alongside reservoir placement. The goal is to minimize intraoperative harm, provide better access for placing all components with minimal tissue damage, reduce early and late postoperative complications, and ensure long-term comfort and esthetic outcomes. Further themes may be considered as other items of the above list, but we believe that all crucial concerns can be included under one of these four items. Any method proposed for a better result in perioperative and late postoperative time frame should consider the necessity of all these items and an emphasis on one or two of them may result in improper attention to the others. Extreme focus on cosmetic result for example, may increase the risk of improper intraoperative access and postoperative complications.

Ectopic places for implant reservoir placement now include several names, coined during more than two decades by several authors. The pioneer of the idea of ectopic placement was Steven Wilson who described a version of low submuscular placement.18 However, the proposed spaces gradually increased in number and definition during the next years. The main goals for all of these ectopic placement techniques have been to eliminate the need for the second incision on the lower abdomen and to decrease the rate of rare major complications like damage to the bladder, intestine and large pelvic vessels. In 2017, Garaffa and Ralph40 in a short review concluded that despite the potential value of these attempts, the ectopic reservoir placement is still away from becoming standard of care, since we have no enough data, especially in long term evaluations for this claim. In 2022, Tomada and Egydio41 said in a review that the ectopic reservoir placement needs more data to be named as a “paradigm change”. Most of the studies and reviews declare that the results of ectopic placement in many aspects can be considered “as safe as” the SOR placement. Obvious evidence of superiority for ectopic techniques is lacking. Van Dyke et al.42 concluded in a crucial review in 2021 that surgeons should be familiar with the different techniques and decide on the best option regarding the patients’ preferences as well as the anatomical and medical conditions. To date, this is possibly the most precise statement based on the available data.

We, however, want to go a step further and revise some aspects and possible consequences of the SOR reservoir placement and the variety of ectopic placement techniques.

Major complications

There are small series and case reports addressing major complications related to reservoir placement.28,43,44 Most of them report late-onset problems like erosion into bladder (a neobladder or bowel),44 bowel obstruction,45 migration,46 herniation or discomfort needing revision surgery, deep venous thrombosis due to pelvic vein compression,47 twisting and folding,48 and other physical reasons for malfunction. It is hard to evaluate the role of orthotopic or ectopic placement in these serious complications, since almost all of these are related to different techniques. One important note here is to feel free to do a CI which logically may decrease the risk of improper location, folding, and migration. Even though the ectopic placement techniques were to decrease the need for a CI, there are series that placed ectopic reservoirs through a CI in several cases.34 Furthermore, some of the complications seem to be specifically or mainly related to some of the ectopic placement methods.

Pseudocapsula formation

One reason for long-term malfunction of the implant is formation of a pseudocapsula which may restrict the free filling and emptying of the reservoir. This restriction can be a cause for improper function, although this is especially true about the artificial urinary sphincter. Some of the ectopic locations may have a further potential for restricting pseudocapsula, while the SOR, intraperitoneal, and even lateral retroperitoneal space seem to be better in this aspect. There are very few data in this field, and since this is a matter of long-term evaluation, data concerning this feature of comparison may help us decide reliably in the future.

Complex cases

There has been a long debate on difficulty of SOR placement in patients who have pelvic surgery or radiotherapy. The main challenging pelvic surgeries are radical prostatectomy or cystectomy, kidney transplantation and hernia repair, especially with mesh or patients with previous bilateral hernia surgery. Although there is a consensus about difficulty of this procedure in such conditions, literature is not homogenous in terms of possibility of reservoir placement in SOR in patients with the same safety levels achievable in the virgin cases. Many experts believe, however, that a CI in lower abdomen can be beneficial,35 although some others have reported that safe SOR placement of reservoir is feasible through the first incision in many patients with prior pelvic procedures.49 We encourage doing the second incision when necessary, in order to be accurate and safe for the sake of long-term viability of the implant and appropriate anatomical positioning both in SOR and in ectopic positions. Of course, in our experience, like many other high-volume centers, in most of the patients a reservoir can be placed easily in the SOR with a single penoscrotal incision. The added time to do a counter incision is ignorable and the complication rate due to the incision itself is minimal.35

Implant revision surgery and other unrelated procedure in the region

One problem with at least some of the ectopic reservoirs is the feasibility of safe removal/revision surgeries and other abdominal procedures. The wide variety of ectopic places can make it difficult for the surgeons, especially non-urologic surgeons, to figure out the borders of the reservoir and to treat the surrounding structures safely. There are some reports related to this concerns in the literature. Even out of the reports, the authors have witnessed rare cases of reservoir puncture in a later laparoscopic procedure, and interestingly, by insulin needle when injected subcutaneously in a patient with submuscular placement.

One question to be noticed at the end is: in spite of several methods for ectopic placement which seem convincing in some aspects, why many high-volume implant surgeons in the world still use SOR for most of the patients? The answer for this question may partially include the surgeon’s convenience and longer experience with this standard technique. But it seems wise to think about other possible answers that can help us figure out the big picture in this regard.

CONCLUSIONS

The SOR placement of the IPP reservoir is considered a standard method in spite of the advent of more recent “ectopic” techniques. SOR placement is still a method of choice for many renowned implanters and the method to which other techniques are compared, and none of these reports of ectopic placement is obviously better. Penoscrotal incision is a frequently selected approach for the main incision according to the publications from high-volume centers. In patients with prior radical prostatectomy, radical cystectomy with neo-bladder reconstruction, kidney transplantation, inguinal hernia repair and pelvic radiotherapy, the authors recommend to implement a CI when necessary, to achieve a higher patient safety.

AUTHOR CONTRIBUTIONS

OS, FS, and F Tondroanamag contributed significantly to the conception and design of the study. MZ and F Tahmasbi contributed to acquisition of data, analysis and interpretation of manuscripts, and drafting the manuscript. NB, AG, AT, IA, AS, and SJH contributed to the interpretation of available publications and critically revised the manuscript for important intellectual content. CB, DJR, and OS provided guidance throughout the study, supervision of the research group, ensuring the accuracy and integrity of the work, and critical revision of the manuscript. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.