Cystoinflation to Prevent Bladder Injury in Obstetrics and Gynaecology Surgery Part 1-Cystoinflation in Repeat C-section Part 2- Cystoinflation in Abdominal Hysterectomy Part3- Cystoinflation in Placenta Accreta Spectrum Management
Phase: NA
Conditions: Bladder Injury, Complications; Cesarean Section, Adhesions Pelvic
Sponsor: Shazia Saaqib

 
 
1
Title of the study
A randomized controlled trial of 
Cystoinflation to prevent bladder injury in 
the adhesive disease of multiple caesarean 
sections 
Registration # 
NCT04302545 
ERB reg #
Reg # 216/RC/KEMU.
Document Date
March 27,2017
Principal Investigator: 
Shazia Saaqib, FCPS; Obstetrics & 
Gynaecology. Assistant Professor (Obstetrics 
& Gynaecology), King Edward Medical 
University /Lady Willingdon Hospital, 
Lahore, Pakistan 
 
Co-Investigators:  
 
 Dr Ayesha Iqbal, MS trainee (Obstetrics & 
Gynaecology), King Edward Medical 
University /Lady Willingdon Hospital, 
Lahore, Pakistan 
 Dr Munazza Naheed, FCPS trainee 
(Obstetrics & Gynaecology), King Edward 
Medical University /Lady Willingdon 
Hospital, Lahore, Pakistan 
 Dr Tayyaba Saeed, FCPS trainee (Obstetrics 
& Gynaecology), King Edward Medical 
University /Lady Willingdon Hospital, 
Lahore, Pakistan 
 Dr Mohammad Khalid, Director of Medical 
Education, Institute of Public Health 
Pakistan 
 
Settings:
Lady Willingdon Hospital Lahore, Pakistan
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Study protocol: “A randomized controlled trial of Cystoinflation to prevent bladder 
injury in the adhesive disease of multiple caesarean sections”  
 
Project summary  
Background: Repeated caesarean sections (C-section) carry the risk of bladder injury due to 
the formation of adhesions obscuring pelvic planes. Distension of Bladder by retrofill 
(Cystoinflation) is a useful technique to identify bladder margins. We hypothesize that 
cystoinflation can prevent bladder injury in dense adhesions of previous C-sections by 
improving identification of bladder outline. 
 
Method: We will find out the effectiveness of cystoinflation by conducting a prospective 
randomized controlled trial in Lady Willingdon Hospital, a university-affiliated teaching 
hospital in Pakistan, for two years, including a follow-up period of three months. The 
subjects of the study will be two hundred and fourteen healthy pregnant women with previous 
operative deliveries which during their C-section, prove to have dense bladder adhesions. The 
subjects will be randomized into cystoinflation and control groups. Preoperatively, the study 
team will counsel the women and take informed consent to include them in the study if dense 
adhesions were found during their C-section. The surgeon will perform adhesiolysis after 
identifying bladder during retro-fill (with 300cc saline) in the cystoinflation group and 
without retro-fill in control. The primary outcome will be assessed by bladder injury rate, 
blood loss and operative time and secondary outcome by postoperative urinary tract infection, 
micturition problems and fistula formation. Cystoinflation will be considered effective if the 
proportion of bladder injury in cystoinflation group will be less than 50% of the control. 
Discussion:  The routine practice of preoperative insertion of urinary catheter fails to prevent 
bladder injury in multiple C-sections. A few scientists have successfully used cystoinflation 
technique to prevent bladder injury in pelvic adhesive disease. In this study, we have used 
cystoinflation in dense adhesions of previous C-sections. The findings of this study may 
support the previous studies and may serve as a trigger for ongoing research of surgical 
techniques to prevent iatrogenic bladder injury.  
 
 
.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
3
 
 
Study protocol: “A controlled study of Cystoinflation to prevent bladder injury in the 
adhesive disease of multiple caesarean sections”  
 
erb registration: The institutional review board of King Edward Medical University, Pakistan                 
Reg # 216/RC/KEMU. 
 
Principal Investigator: Shazia Saaqib, FCPS; Obstetrics & Gynaecology. Assistant Professor 
(Obstetrics & Gynaecology), King Edward Medical University /Lady Willingdon Hospital, 
Lahore, Pakistan 
Co-Investigators:  
 Dr Ayesha Iqbal, MS trainee (Obstetrics & Gynaecology), King Edward Medical University 
/Lady Willingdon Hospital, Lahore, Pakistan 
 Dr Munazza Naheed, FCPS trainee (Obstetrics & Gynaecology), King Edward Medical 
University /Lady Willingdon Hospital, Lahore, Pakistan 
 Dr Tayyaba Saeed, FCPS trainee (Obstetrics & Gynaecology), King Edward Medical 
University /Lady Willingdon Hospital, Lahore, Pakistan 
 Dr Mohammad Khalid, Director of Medical Education, Institute of Public Health Pakistan 
Settings: Lady Willingdon Hospital Lahore, Pakistan 
Address: Ravi Road, Walled city of Lahore, Pakistan 
Phone: 092-(42)37659001 
Affiliated University: King Edward Medical University, Lahore, Pakistan (KEMU)  
Hospital type: Government Teaching Hospital 
 
Background 
The urinary bladder injury is a rare but important complication of caesarean section (C-
section). The decreasing trend of vaginal birth after C-section has led to an increased number 
of women with multiple C-sections.1 After caesarean delivery, adhesions may develop between 
bladder and uterus (46% - 65% after primary C-section) which cause difficulty in identification 
and dissection of the bladder flap during the next operative delivery.2,3 The rate of bladder 
injury increases with the increasing number of C-sections being 0.13% for the first C-section, 
0.09%  for the second, 0.28% for the third, 1.17% for the fourth, 1.94%for the fifth, and 4.49% 
for the sixth caesarean delivery.4The incidence of bladder perforation has been reported to be 
three times higher in women with the previous C-section compared to the women with first C-
section (0.81% vs. 0.27%).5 Most bladder injuries occurred secondary to the extensive adhesive 
disease at the time of opening the peritoneal cavity and during the creation of the bladder flap.5  
Bladder injury has been reported to occur with an overall incidence of 0.46% in a local 
Pakistani study, 0.44% in Saudi Arabia, 0.67% in Mumbai and 0.08 to 0.94% in international 
studies in C-section cases.6–11  
Tulandi and co-workers have proposed a scoring system of adhesions between bladder and 
uterus.12 
 
 
 
 
 

 
 
4
 
 
 
 
 
 
 
 
 
Tulandi, T. & Lyell, D.J. Gynecol Surg (2013) 10: 25. https://doi.org/10.1007/s10397-012-0765 
 
Bladder injury, although rare, has serious physical, social and psychological 
implications.13The injury leads to prolonged operative time, urinary tract infection (UTI), 
micturition problems and prolonged catheterization.3 A long complicated hospital stay 
creates an intense feeling of helplessness and anxiety.13 Moreover, unrecognized bladder 
perforation is a leading cause of morbidity due to the development of urinary ascites, 
peritonitis, and fistula formation. 14–16 
The adhesions are a major risk factor for bladder injury.17 Dye test with methylene blue is 
one of the methods used to identify bladder injury. 3 We observed that in women with intact 
bladder, it made the bladder outline prominent thus improving identification of bladder 
outline. This observation raised the question of whether improved identification of bladder 
margins by bladder retro-fill (cystoinflation) could decrease the occurrence of bladder injury 
in adhesions of previous C-sections. 
In literature, there is insufficient evidence to support the use of cystoinflation to prevent 
bladder injury. The routine practice of preoperative insertion of Foleys catheter is based on an 
old concept that bladder injury may occur by failure to empty the bladder preoperatively.18 The 
emptying of bladder improves visualization in the operative field but fails to prevent bladder 
injury in cases of adhesions.3 Presently, researchers are focussing on prevention of adhesion 
formation by the use of adhesive barriers and Aloe vera gel but evidence is still needed to 
prove their effectiveness.19,20 The omission of bladder flap formation is also under 
consideration but there is a lack of adequate evidence to support this method.21 The scientists 
have now started questioning the need for the routine use of an indwelling catheter. 22–25 The 
studies indicate that empty bladder is ineffective to avoid bladder injury. 22–25   
In 2009, cystoinsufflation study described complete prevention of bladder injury in 
gynaecological laparoscopic surgery by inflating bladder with CO2.26 There is evidence in the 
literature that the over-distension of bladder carries the risk of postoperative micturition 
problems esp urinary retention.27 This risk can be avoided by keeping the bladder empty during 
surgery with a urinary catheter and by performing bladder retrofill only during adhesiolysis, 
within the limits of its normal capacity(300-400cc).28In cystoinsufflation study, urinary 
complications have been completely avoided by this technique. 26 
This randomized controlled trial will share the results of the introduction of the practice of 
bladder retrofill to decrease bladder injury and blood loss by recognizing bladder outline in the 
adhesive disease of multiple C-sections. Cystoinflation can also prove useful in the fields of 
surgery, urogynecology, and urology, in open procedures as well as in laparoscopic surgery. 
The observations of this study will require confirmation with larger, well designed, 
international trials for generalization of results. 
 
 
 
 
References 
1. 
Mumtaz, S., Bahk, J. & Khang, Y.-H. Rising trends and inequalities in cesarean section 
rates in Pakistan: Evidence from Pakistan Demographic and Health Surveys, 1990-2013. 
PLoS One 12, e0186563 (2017). 
Adhesions of previous C-
section Between uterus 
and bladder 
Consistency of 
the adhesions 
<3 cm
3–
6 cm
>6 c
m 
Filmy 
1 
2 
 4 
Dense
4
8
16

 
 
5
2. 
El-Mowafi, D. M. & Diamond, M. P. Are pelvic adhesions preventable? Surg. Technol. Int. 
11, 222–35 (2003). 
3. 
Tarney, C. Bladder Injury During Cesarean Delivery. Curr. Womens. Health Rev. 9, 70–76 
(2014). 
4. 
Silver, R. M. et al. Maternal Morbidity Associated With Multiple Repeat Cesarean 
Deliveries. Obstet. Gynecol. 107, 1226–1232 (2006). 
5. 
Rahman, M. S. et al. Bladder injuries during cesarean section in a university hospital: A 25-
year review. Obstet. Gynecol. Surv. 64, 436–437 (2009). 
6. 
Kafali, H. Bladder injury during cesarean section. Arch. Gynecol. Obstet. 278, 601 (2008). 
7. 
Phipps, M. G., Watabe, B., Clemons, J. L., Weitzen, S. & Myers, D. L. Risk Factors for 
Bladder Injury During Cesarean Delivery. Obstet. Gynecol. 105, 156–160 (2005). 
8. 
D Rajasekar, M. H. Urinary tract injuries during obstetric intervention. Br J Obs. Gynaecol 
104, 731–734 (1997). 
9. 
D Kaskarelis, J. S. D. A. S. M. J. Z. Urinary tract injuries in gynecological and obstetrical 
procedures. Int Surg 60, 40–43 (1975). 
10. 
Morris, S., Turocy, J., Dabney, L. & Hardart, A. Bladder Injury During Cesarean Delivery: 
A Retrospective, 15-Year Study [28C]. Obstet. Gynecol. 127, 33S (2016). 
11. 
Eisenkop, S. M., Richman, R., Platt, L. D. & Paul, R. H. Urinary tract injury during 
cesarean section. Obstet. Gynecol. 60, 591–596 (1982). 
12. 
Tulandi, T. & Lyell, D. J. Classification of intra-abdominal adhesions after cesarean 
delivery. doi:10.1007/s10397-012-0765-1. 
13. 
Pinto, A., Faiz, O., Davis, R., Almoudaris, A. & Vincent, C. Surgical complications and 
their impact on patients’ psychosocial well-being: A systematic review and meta-analysis. 
BMJ Open 6, (2016). 
14. 
Tai, C. K., Li, S. K., Hou, S. M. & Fan, C. W. Bladder injury mimicking acute renal failure 
after cesarean section: A diagnostic challenge and minimally invasive management. Surg. 
Laparosc. Endosc. Percutaneous Tech. 18, 301–303 (2008). 
15. 
Al-Mandeel, H. & Qassem, A. Urinary ascites secondary to delayed diagnosis of 
laparoscopic bladder injury. J. Minim. Access Surg. 6, 50–52 (2010). 
16. 
Ko, P. C., Lo, T. S. & Ashok, K. Urinary ascites with elevated blood creatinine following 
cesarean section indicating bladder injury. Taiwan. J. Obstet. Gynecol. 50, 537–539 (2011). 
17. 
Korniluk, A., Kosiński, P. & Wielgos, M. Intraoperative damage to the urinary bladder 
during cesarean section - literature review. Ginekol. Pol. 88, 161–165 (2017). 
18. 
Faricy, P. O., Augspurger, R. R., Kaufman, J. M. & Johnson, J. W. C. Bladder injuries 
associated with cesarean section. J. Urol. 120, 762–763 (1978). 
19. 
Poole, J. H. Adhesions following cesarean delivery: A review of their occurrence, 
consequences and preventative management using adhesion barriers. Women’s Heal. 9, 
467–477 (2013). 
20. 
Molazem, Z., Mohseni, F., Younesi, M. & Keshavarzi, S. Aloe Vera Gel and Cesarean 
Wound Healing; A Randomized Controlled Clinical Trial. Glob. J. Health Sci. 7, 203–209 
(2014). 
21. 
O’Neill, H. A., Egan, G., Walsh, C. A., Cotter, A. M. & Walsh, S. R. Omission of the 
bladder flap at caesarean section reduces delivery time without increased morbidity: A 
meta-analysis of randomised controlled trials. European Journal of Obstetrics and 
Gynecology and Reproductive Biology vol. 174 20–26 (2014). 
22. 
Li, L., Wen, J., Wang, L., Li, Y. & Li, Y. Is routine indwelling catheterisation of the 
bladder for caesarean section necessary? A systematic review. BJOG An Int. J. Obstet. 
Gynaecol. 118, 400–409 (2011). 
23. 
Acharya, S., Uprety, D. K., Pokharel, H. P., Amatya, R. & Rai, R. Cesarean section without 
urethral catheterization: A randomized control trial. Kathmandu Univ. Med. J. 10, 18–22 

 
 
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(2012). 
24. 
Abdel-Aleem, H., Aboelnasr, M., TM, J. & Habib, F. Indwelling bladder catheterisation as 
part of intraoperative and postoperative care for caesarean section ( Review ). TheCochrane 
Libr. 1, 1–42 (2014). 
25. 
Pandey, D., Mehta, S., Grover, A. & Goel, N. Indwelling catheterization in caesarean 
section: Time to retire it! J. Clin. Diagnostic Res. 9, QC01–QC04 (2015). 
26. 
O’Hanlan, K. A. Cystosufflation to Prevent Bladder Injury. J. Minim. Invasive Gynecol. 16, 
195–197 (2009). 
27. 
Joelsson-Alm, E., Nyman, C. R., Svensén, C. & Ulfvarson, J. Micturition Problems After 
Bladder Distension During Hospitalization in Sweden. Nurs. Res. 63, 418–425 (2014). 
28. 
Lukacz, E. S. et al. A healthy bladder: a consensus statement. Int. J. Clin. Pract. 65, 1026–
1036 (2011). 
 
 
Study design 
This study protocol describes the design of a prospective, randomized, single centred 
controlled trial. The study protocol conforms to the WHO Recommendations for Interventional 
Trials while this study will conform to the Consolidated Standards of Reporting Trials 
(CONSORT statement for reporting RCTs). The ethical Approval to perform the trial has been 
obtained from the institutional review board of King Edward Medical University, Pakistan.  
Setting: This trial will be conducted in lady Willingdon hospital, a tertiary care hospital in 
Pakistan affiliated with King Edward Medical University. 
Study period 
This study will be conducted over a time period of two years. This will include recruitment 
period of one year and nine months and follow up period of three months. If recruitment of 
subjects is not complete within the given period, period of study may be extended till the 
follow-up of the last subject is complete. 
 
Sample size 
Based on previous statistics of the target population (women with adhesions) in our hospital, 
about 400 subjects are expected to present during the study period. With this population, the 
sample size is calculated to be 107 for each group at 95% confidence level and 80% power, 
allowing a 10% drop out rate (Raosoft, Inc 2004; online sample size calculator for 
proportions). Therefore, a total of two hundred and fourteen patients fulfilling the eligibility 
criteria will be included in the study. 
Subjects 
The subjects of the study will be selected in two steps. In the first step, the women who will 
meet the preoperative study criteria and give the preoperative informed consent will be invited 
to participate in the study. In the second step, during C-section, the volunteers who will fulfil 
the inclusion criteria of adhesions will be enrolled in the study. 
   Preoperative study criteria  
Inclusion criteria: 
 
Healthy pregnant women of any age  
 
Two or more previous C-sections  
 
Gestational age between 38-40 weeks (confirmed by dating scan)  
 
Provide written informed consent to participate in the study 
Exclusion criteria: 
 
Patients with medical disorders 
 
Placenta previa on Ultrasonography  

 
 
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 
Women experiencing micturition problems (dysuria, frequency, urgency, urinary 
retention, incontinence) before the study.  
 
Women who refuse to participate in the study. 
The perioperative criteria of the study are  
 Dense pelvic adhesions of Tulandi score 4 and above, 
 adhesions covering the bladder and lower segment of the uterus so that empty bladder 
will not be identified among the adhesions. 
 The lower segment cannot be approached without adhesiolysis.  
 Adhesions will be encountered either at entry into the peritoneal cavity or before the 
creation of the bladder flap. 
 The women with bladder injury prior to enrolment will be excluded from the study. 
  
Recruitment procedure and consent for the study 
The recruitment of subjects will be carried out over a period of 21months (one year and nine 
months). 
Subjects of the study will be selected in two steps.  
The first step of recruitment: we will select the women who will fulfil preoperative study 
criteria by convenient sampling. Patients coming to obstetric outdoor department at lady 
Willingdon hospital for elective C-section due to previous two or more operative deliveries 
will be admitted in antenatal ward. They will be hospitalized for at least 48hours before their 
operation. The women will undergo detailed history and examination, preoperative 
investigations i.e. blood group, complete blood, urine examination and blood sugar levels to 
determine their general health status and Ultrasound scan to confirm their gestational age. The 
women complying with the preoperative eligibility criteria will be invited to participate in the 
randomized controlled study. The indoor doctors involved in recruitment have been trained and 
instructed in the recruitment procedure to maximise the recruitment rate of study. 
Verbal information about the study and cystoinflation will be provided by the members of the 
study team in a quiet comfortable room during their stay at the hospital. They will have the full 
opportunity to know and discuss the outcome of cystoinflation with our study team members 
before the operation. 
Patients will be recommended to take at least 24 hours to consider and discuss with a relative 
or with our study members before deciding to participate in the study. 
The Principal investigator will contact the pregnant lady and ask whether she is willing to 
participate. If so, the volunteer will sign the conditioned consent form of participating in the 
study i.e. if selected for study during her C-section, the subject would be assigned to either 
group of study in the operation theatre. The participant can change her consent for 
participation in study before C-section and participation or non-participation will have no 
effect on her care in the hospital (See Consent_Form).  
The second step of recruitment: The subjects of the study will be selected during c-section 
by purposive sampling and only those subjects who will fulfil perioperative criteria of the 
study will be selected. The primary surgeons of the C-section will be 2nd and3rd-year residents 
of Lady Willingdon Hospital. If dense adhesions will be encountered during opening the 
peritoneal cavity or before the separation of bladder flap, the primary surgeons will hold the 
operation and call the principal surgeon (Assistant Professor Obstetrics and Gynaecology) to 
carry out adhesiolysis and complete the operation. The Principal surgeon will examine the 
adhesions and enrol the subjects in the study and perform randomization according to the 
random number envelop if perioperative criteria for adhesions will be fulfilled. (See 
Entry_Form) 

 
 
8
The same Principal surgeon will recruit subjects after carrying out grading of adhesions, 
perform adhesiolysis and complete the operation with primary surgeons to avoid bias.(See 
Fig_1) 
Randomisation procedure  
The Principal surgeon will randomize the calculated sample size into cystoinflation and control 
groups by parallel assignment. They will write the random numbers (downloaded from the 
internet) on closed envelopes with the assigned groups inside. The closed envelopes will be 
serially placed with the smallest number uppermost, in random number file. The file will be 
kept in the safe custody of theatre in-charge nurse before starting recruitment for the study. If 
the women will fulfil the eligibility criteria, the Principal surgeon will recruit her in the study. 
The theatre in charge nurse will take out uppermost envelope from the subject’s file. She will 
be open the envelope and disclose the group to the principal surgeon. Then, she will close the 
envelope again and place it below all the envelopes. The theatre staff nurse will also provide 
the setup for cystoinflation.  At the end of the operation, she will get the Entry Form signed by 
the Principal surgeon and hand it over to the study team. The study team medical officers in the 
theatre will enter the random number of each subject on her documents including Hospital 
Admission File, Consent Form, Trial Entry Form and Outcome Form.  
 
Blinding 
The study team members and operation theatre staff will conceal the group assignment from 
the subjects, the medical and paramedical staff outside the operation theatre and surgeons 
prior to operation. The operation theatre attendants will be specially trained to create noises 
during the operation of both groups so that the subject in theatre or relatives outside the 
theatre cannot predict the group. The medical officer of the study team carrying out follow 
up of the subject postoperatively and after discharge will also be kept unaware of the group 
allocation.  
At the end of study, the Principal surgeon will send the random number list, to the statistician 
of the study replacing the groups with any two alphabets (to blind the study for the 
statistician). 
 An independent statistician from another institution will perform the primary analysis of our 
randomized controlled trial. The subjects of the study will be completely blinded to the 
intervention and they will never be given any information about their study group, neither 
before nor after the operation.  
Interventions 
All the volunteers will receive standard preoperative care i.e. antibiotic cover with injection 
ceftriaxone 1gram IV stat and C-section under spinal anaesthesia. All the women will be 
catheterized before the operation.  
Catheterization: 
The women will be catheterized under spinal anaesthesia. We will train theatre staff nurses to 
perform catheterization for cystoinflation. The staff nurse will perform catheterization after 
scrubbing and wearing sterilized gloves. First of all, one of the primary surgeons will clean 
the abdomen, legs and perineum for C-section with Povidone-iodine. Then the subject will be 
put in supine position (with legs spread and feet together) for catheterization. The staff nurse 
will clean urethral meatus and labia with three small gauzes soaked in a bowl of sterile water. 
She will separate the labia with left hand and clean the urethral meatus from front backwards 
with the wet gauze piece held with sterilized sponge holder. After cleaning one-time, she will 
waste that gauze and clean the labia in the same way with the two other sterilized gauze 
pieces. After this, one of the primary surgeons will hold the ports and tubing of the catheter 
high above the perineum while the staff nurse will hold the tip of the catheter and insert the 
catheter into urethra well beyond the Foleys bulb without touching it elsewhere and hold it 

 
 
9
there while the surgeon holding the tubing will inflate the balloon of the urinary catheter with 
10cc distilled water. The theatre attendants will then correct the position of the patient again 
to straight leg position. The urinary catheter will be kept elevated as long as the patient will 
be draped with sterilized sheets for operation by the other surgeon. Then, the catheter end 
near the urinary port will be fixed to the patient sheet in front of the thigh to carry out 
cystinflation conveniently and attached to the urine bag for drainage. 
Adhesiolysis 
 If adhesions will be encountered during opening the peritoneal cavity or before the 
separation of bladder flap, the primary surgeons will hold the operation and call the principal 
surgeon to carry out adhesiolysis and complete the operation. The Principal surgeon will 
grade the adhesions according to Tulandi’s classification and if the woman will fulfil 
perioperative criteria for adhesions, the Principal surgeon will enrol her in the study as 
subject and perform randomization into cystoinflation and control groups according to her 
random number envelope. Adhesiolysis will be performed with the inflated bladder in 
cystoinflation group, and with the empty bladder in the control group. 
Cystoinflation group: The adhesiolysis in cystoinflation group will be performed by bladder 
retro-fill. Cystoinflation (bladder retrofill) will require normal saline drip and a 60cc bladder 
wash syringe and an artery clip. In cystoinflation group, the bladder will be retro-filled with 
300cc saline by the assigned house officer under strict aseptic measures at the rate of 60cc in 
one minute. Meanwhile, the principal surgeon will identify the margins of the bladder among 
adhesions. The catheter will be clamped with an artery clip after filling the bladder with 
5fillings of the syringe. The surgeon will stretch the adhesions by upward traction on the 
surface of the uterus with a sponge and counter-traction on adhesion with elices forceps or 
sponge and perform adhesiolysis by sharp dissection with a fine dissecting scissor. The 
adhesiolysis will be performed until the bladder surface can easily be pushed down. 
Thereafter, the house officer will attach the urine drainage port of the catheter with the tubing 
of the urine bag and remove the artery clip to empty the bladder. The surgeon will then push 
the bladder downward with Doyen’s retractor to improve visualization in the surgical field 
and complete the C-section.  
.  
Control group: The subjects assigned to the control group will undergo no intervention. The 
Principal surgeon will perform adhesiolysis by the same traction counter-traction method 
with urinary catheter put on free drainage throughout the C-section. 
If there will be a suspicion of bladder injury in either group, it will be confirmed by 
performing the retrograde dye test with methylene blue and injury will be repaired by the 
Principal surgeon.  
Crossover  
There is no possibility of crossover in this study as subjects will be selected during operation 
and the women who refuse to be included in either group preoperatively will be excluded from 
the study before group assignment. 
Data collection procedure 
Data will be collected at the time of admission (baseline), during surgery, on the 3rd 
postoperative day, at the time of discharge from the hospital and the end of three month 
follow-up period (for those enrolled in the study). The subjects will be advised to report for 
any postoperative fever or micturition problem during follow-up. Their visits will be 
recorded on follow up form by the study team medical officers specifically trained in 
correctly interpreting the problems of the subjects and filling the outcome form (See 
Outcome Form). 
Baseline Data 

 
 
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The entry form will include baseline data consisting of demographic features and 
characteristics of the subjects recruited in the study. The demographic features will include 
age, gestational age, parity, socioeconomic status, and the number of previous C-sections. 
The other characteristics will be the score of adhesions and preoperative postmicturition 
bladder volume. The allotted random number will be entered in entry form of the subject and 
will be signed and kept in a locked place by study team manager in the theatre. (See ENTRY 
FORM) 
Outcome  
Primary outcomes will be the bladder injury rate, the extent of the injury, operative time, 
blood loss and proportion of subjects receiving blood transfusion.  
   The bladder injury: The bladder injury will be detected by direct observation during 
surgery. The suspected bladder injury will be confirmed with the dye test and will be 
reported as the bladder injury rate and extent of injury.  
A. Bladder injury rate will be recorded as the percentage of subjects with bladder injury in 
each group. 
B. The extent of the injury will be analyzed by the size, site and depth of injury.  
i. The size of the injury will be measured in centimetres with a sterilized scale.  
ii. The site of injury can either be the dome of the bladder, the posterior bladder wall, the 
trigone or one or both ureters.  
iii. Depth of injury will be taken as layers involved i.e. either involving muscular layer 
partly or completely with intact mucosa or full depth injury (perforation). 
iv.  
Operative Time: The staff nurse will record the duration of surgery as time in minutes 
from incision to closure of the skin. 
  
Blood Loss: The estimated blood loss will be determined by the increase in weight of 
sponges used during the operation, taking 1gram equal to 1cc of blood and the number of 
subjects who received blood transfusion during operation. 
 
Secondary Outcomes  
Postoperatively, subjects will be assessed for urinary tract infection (UTI), micturition 
problems, and fistula formation during the hospital stay and for the next three months. 
Duration of catheterization and hospital stay will also be recorded. The outcome of each 
subject will be noted on a Performa by assigned medical officers during the hospital stay and 
the follow-up period and entered in SPSS20 datasheet. 
                                                  
1-Urinary tract infection (UTI) markers will be more than 10pus cells/hpf in urine or urine 
showing infectious organisms on culture on the third postoperative day.  
A. 
Dysuria will be expressed by the subject as painful micturition using an 11point 
Numeric Rating Scale ICCs (.673-.825), r=.7-.99.  (0 No Pain, 1-3 Mild Pain, 4-6 Moderate 
Pain, 7-10 Severe Pain). 
B. 
Other micturition problems (feeling of incomplete evacuation, frequency, 
urgency, urethral and extra-urethral incontinence) will be measured subjectively on Likert 
scale questionnaire (0-never, 1-rarely, 2-sometimes, and 3-often) and analyzed as a composite 
variable in spss. Urinary retention will be diagnosed if post-micturition bladder volume is 
>50cc on ultrasonography on the day of discharge from the hospital. 

 
 
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I. 
Feeling of incomplete evacuation: It is the feeling created by incomplete 
emptying of the bladder. The subject will be inquired about the feeling of full bladder 
accompanying it. 
II. 
Urgency will be diagnosed as a sudden urge to urinate. 
III. 
Frequency Needing to pass urine more than seven times in 24hours. 
IV. 
Vesicovaginal or uretro-vaginal Fistula: In subjects with the complaint of 
urinary incontinence, the fistula formation i.e. abnormal communication of urinary 
bladder or ureter with vagina will be ruled out by three swab test and retrograde 
cystography.  The follow up of fistula cases is outside the scope of this study so it will 
not be included in description or analysis. 
 
C. 
Duration of Foleys catheter and hospital stay: The Foley’s catheter will be 
removed after 24 hours in distension arms of both groups and subjects stay in the hospital for 
four days. In the bladder injury arms, the catheter will be kept in situ for 7days to give rest to 
the bladder for the healing of repair of muscularis disruptions, for 10 days in case of repair of 
perforations smaller than1cm, and for14 days for repair of perforations greater than 1cm. After 
removal of the catheter, the subjects will be kept in the hospital for twelve hours and then 
discharged if there will have no subjective urinary complaint. 
The finding of subjects will be noted on output form by assigned trainees. The participant’s 
first entry on follow up form will be completed on the third postoperative day; second entry 
will be at the time of discharge from the hospital and last entry at the end of three months 
postoperative period. In between, they will be advised to visit our team whenever a problem 
emerges during the postoperative period and their findings will be recorded on the output form. 
In subjects complaining of urinary incontinence, the fistula formation will be ruled out first 
by three swab test and then by retrograde cystography. The postoperative visit at the end of 
3months will be mandatory. During this visit, all the subjects will be analyzed for 
postoperative micturition problems and their retrograde cystography will be performed to rule 
out fistula formation. The subjects with fistula will be referred to the urologist for further 
management.  The last entry at the end of three months will also be mandatory for the 
inclusion of participant outcome after discharge in results. The participants will be advised to 
visit the researcher team at the end of 3months period. They will be reminded for their visit 
on phone call after week if they do not come for follow-up (See Outcome).  
Statistical analysis  
We will perform Statistical analysis by using IBM spss statistics 20 (SPSS Inc, Chicago, IL, 
USA). The characteristics of the subjects will be analyzed as continuous data or ordinal data. 
Normality of continuous data will be analyzed by the Shapiro Wilk test. The normal baseline 
data will be compared by T-test, non-normal data by Mann Whitney U test and ordinal data 
with the chi-square test. The outcome of both groups will be calculated as numbers 
(percentages) by descriptive statistics. The effect of cystoinflation on outcome data will be 
analyzed using regression analysis. The same problem experienced by the same subject will 
be recorded only once on the spss datasheet. There will be no second entry if the subject 
presents with the same problem again. The data for any subject who do not come for follow 
up after discharge will be used and analyzed in study characteristics but will be excluded 
from the analysis of results. The power of the study for bladder injury will be calculated with 
statistical software G’Power version3.1.                                                                                                              
Adverse events 
The study team will be responsible to record all adverse events and serious adverse events to 
the subjects of the study, related to or not related to the intervention. The team members will 
ask open probing questions to enhance the quality of the collected data. An adverse event is 

 
 
12
defined as any undesirable experience during follow-up leading to contact with the healthcare 
system (general practitioner or hospital). If adverse event results in hospitalisation, prolonged 
inpatient hospital care, result in re-surgery, or if an adverse event is life-threatening, result in 
death, permanent disability or damage, they will be categorised as serious adverse events.  
Adverse Events will be recorded in the adverse events reporting register. The study team will 
report all expected and unexpected adverse events in the study population to the principal 
investigator in monthly meetings to assess their potential consequences. 
Data Management Plan  
Documents safety  
All the documents, together with the numbered envelops and the completed forms will be 
stored in folders that will be kept in the locked research office of the principal investigator with 
access limited to authorised persons. The study team will ensure that all variables from the 
completed forms are continuously entered into SPSS 20 datasheet.  
Data monitoring  
The study will not have a formal data monitoring committee as no serious adverse events are 
related to or have been observed previously by implication of this intervention in the hospital. 
Any unexpected serious adverse events or outcomes will be discussed by the trial 
management committee (study team). Furthermore, the trial management committee will 
monitor recruitment, intervention and follow up rates and any concerns related to the study.  
Data safety  
Once the trial is completed, all material belonging to the study will be stored in the research 
office. Collected data will be retained in the custody of the principal investigator till 
compilation of results by statistician so that any missing piece of information can be acquired 
from the data file. 
Data Destruction Plan: To minimize the risk of breach of confidentiality, we will not use 
the subject’s name or hospital number to identify them on any study records. Instead, a study 
number will be assigned to each subject according to the random number envelope. This 
number will be used to study documents that relate to the subject and to enter data in spss. 
We will keep the list of random number groups in a secure, locked location.  At the end of the 
project, this list will be destroyed. All personal data will also be destroyed at the end of the 
trial to protect confidentiality before, during and after the trial.  
Quality assurance:  The study team will arrange a monthly quality assurance meeting with 
the principal investigator. All the problems faced during the consent, theatre management and 
conducting the postoperative surveys of the patient will be discussed. The solutions should be 
sought for each problem and refinements will be implemented if needed. The data collection 
and management procedures of the study have been approved by the king Edward medical 
university, Pakistan. 
Ethics, dissemination and perspectives of the study 
Ethics  
The study is a part of the project “Cystoinflation Versus deflation to prevent bladder injury in 
OBG (obstetrics and gynaecology) surgery” approved by the ethical committee of King 
Edward Medical University, Pakistan with ERB#216/RC/KEMU  on 27 March2017and will 
be conducted in accordance to the Helsinki declaration. Personal information about patients 
will be kept separate from the main dataset and will not be shared.  

 
 
13
Dissemination  
The results of this study will be submitted for publication to an international, peer-reviewed 
journal, regardless of whether the results are positive, negative or inconclusive concerning the 
study hypothesis. Authorship eligibility will be based on the recommendations from the 
International Committee of Medical Journal Editors (ICMJE). 
Perspectives of the study 
This study is a small, single centred controlled trial. It is among one of the initial studies to 
test cystoinflation to prevent bladder injury. If cystoinflation proves significantly effective in 
this study, the evidence provided by this study will not be enough in this era of evidence-
based medicine. Nevertheless, this research can serve as a foundation to initiate a much larger 
high-quality multicentre trial in the support of cystoinflation to prevent bladder injury. This 
technique if proved effective can also be useful in all fields of pelvic surgery especially 
urology, urogynecology, and general surgery. 
Potential Risks 
 Participation in this study poses a risk for breach of confidentiality.   
 Catheterization procedure is mandatory in this study. Approximately two out of 
hundred women may develop a bladder infection. The researchers will use proper 
sterilization and clean procedure of the insertion of the catheter according to the study 
protocol to minimize the risk of developing a bladder infection. 
 Subjects of the study should not take part in more than one study at the same time as 
the outcome of the study can be disturbed by this approach.  
Problems Anticipated during the study: 
 If recruitment of subjects will not be complete during the anticipated study period, then the 
period of study may be extended from three months to one year or any further time till the 
recruitment of study is complete. 
 In case of any unexpected outcome that may endanger the subject physically or 
psychologically, the study may be stopped any time.  
 As the study is non-funded, the subjects will not be paid for participation in the study. The 
subjects belonging to the poor socioeconomic group and coming from distant areas will need 
thorough counselling for compliance to follow up visits.  
  
Acknowledgements: Theatre staff helping in cystoinflation study will be acknowledged in 
the publication. 
Project Management:  
Shazia Saaqib is the Corresponding Author and chief investigator.  She has conceived the 
project and she will write and review the manuscript and will create Figures and tables. She 
will hold a monthly meeting of the research team to evaluate any difficulties encountered 
with study design and to find a solution to the problems. 
 Ayesha Iqbal will counsel the subjects, participate in preparing random numbers file, 
conduct surveys to collect preoperative and postoperative data in wards, participate in 
Manuscript writing and review the manuscript. 
Munazza Naheed will counsel the subjects, participate in preparing random numbers file, 
manage cystoinflation in theatre, perform follow up of the subjects and conduct the survey in 
the hospital to collect data after discharge, and will review the manuscript.  
Tayyaba Saeed will collect all preoperative and postoperative data, enter it into SPSS data 
sheet and hand it over to statistician and review the manuscript. 
Mohammad Khalid will perform statistical calculations and will review the manuscript. 
Collaboration with other scientists: To avoid Bias, the research team will shift data in spss 
datasheet to Dr Mohammad Khalid for the compilation of results on an individual level. 

 
 
14
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cystoinflation study consent form-lady Willingdon Hospital 
Dr Shazia Saaqib, Department of Obstetrics and Gynaecology 
Lady Willingdon Hospital Unit I, King Edward Medical University, Ravi Road Lahore 
Tel:0334 7598481   Email:shaziasaaqib@gmail.com 
 
 
 
CONSENT FORM FOR THE PATIENT of CYSTOINFLATION STUDY 
Title of Research: A randomized controlled trial of Cystoinflation to prevent bladder 
injury in the adhesive disease of multiple caesarean sections 
 
Patient hospital ID 
number 
 
Principal Investigator Dr Shazia Saaqib 
Name of the patient 
 
Randomization 
number 
 
 
 
1-I confirm that I have understood the information given to me verbally for the  
above study and have had the opportunity to ask questions. 
 
2-I understand that my participation is voluntary and that if adhesions are found  
during my C-section, I will be assigned to either group and I will not be paid for  
participating in the study. 
 
3-I understand that the investigator team will need information about me after my  
operation for which I will remain in contact with them. I allow them to keep my 
 record with them and waste it after completing the study. 
 
4-I agree to take part in the above study, the cystoinflation study. 
 
 
 
Name of Patient 
 
 
Date 
 
 
 
Signature/thumbprint  

 
 
15
 
 
Name of person taking consent 
 
Date 
 
 
signature 
 
 
Name of principal investigator 
 
Date 
 
 
signature 
 
A randomized controlled trial of Cystoinflation to prevent bladder injury in the adhesive disease of multiple 
caesarean sections 
 
 
 
 
ENTRY FORM OF CYSTOINFLATION STUDY 
 
Country 
Pakistan 
Hospital 
Lady Willingdon Hospital 
Unit 
1 
Patient Profile 
Patient name 
 
Age
 
Gestational age
 
Parity 
 
Socioeconomic status 
 
BMI 
 
Examination 
Pulse
 
BP
 
Temperature
 
Pallor 
 
Chest 
 
CVS 
 
P/A 
 
Investigations 
Blood Group
 
C/E blood
 
C/E Urine 
 
BSL(F) 
 
Obstetric USG 
 
Randomization 
Date of operation
 
Time of operation
 
Grade of adhesions 
 
Eligible 
 
Consent for study 
 
Random number 
 
Signature of the Principal 
 

 
 
16
surgeon
 
 
Store the original completed form in the Principal investigator study file. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A randomized controlled trial of Cystoinflation to prevent bladder injury in the adhesive disease of multiple caesarean sections 
 
 
OUTCOME FORM 
 
 
 
Operative Findings 
 
Bladder injury 
 
        No 
    Yes 
Size 
 
 
Site 
 
 
Depth 
 
 
Operative time 
 
 
Blood loss 
 
 
blood transfusion 
 
 
Operative time 
 
 
Blood loss 
 
 
blood transfusion 
 
 
 
Postoperative Follow up on 3rd postoperative day 
 
Follow up 
No 
Yes 
WBC count 
Urine culture
_ive
+ive

 
 
17
fever
No
Yes
Dysuria 
0
1
2
3
4
5
6
7
8
9
10
Frequency of micturition 
0
1
2
3
Urgency of micturition  
0 
1 
2 
3 
Feeling of urinary 
retention 
0 
1 
2 
3 
Urethral incontinence  
0 
1 
2 
3 
fistula 
No 
Yes 
 
Postoperative Follow up on the day of discharge from hospital 
 
Follow up 
No 
Yes 
Postoperative 
Postmicturition bladder 
volume  
fever
No
Yes
Dysuria 
0
1
2
3
4
5
6
7
8
9
10
Frequency of micturition  
0 
1 
2 
3 
Urgency of micturition  
0 
1 
2 
3 
Feeling of urinary 
retention 
0 
1 
2 
3 
Urethral incontinence  
0 
1 
2 
3 
fistula 
No 
Yes 
 
Postoperative Follow up from 1-6weeks  
 
Came for follow up 
No 
Yes 
fever
No
Yes
Dysuria 
0
1
2
3
4
5
6
7
8
9
10
Frequency of micturition  
0 
1 
2 
3 
Urgency of micturition  
0 
1 
2 
3 
Feeling of urinary 
retention 
0 
1 
2 
3 
Urethral incontinence  
0 
1 
2 
3 
fistula 
No 
Yes 
 
Postoperative Follow up from 6weeks -3months  
 
Came for follow up 
No 
Yes 
fever
No
Yes
Dysuria 
0
1
2
3
4
5
6
7
8
9
10
Frequency of micturition  
0 
1 
2 
3 
Urgency of micturition  
0 
1 
2 
3 
Feeling of urinary 
retention 
0 
1 
2 
3 
Urethral incontinence  
0 
1 
2 
3 
fistula 
No 
Yes 
 
Follow up at the end of 3months 

 
 
18
 
Came for follow up 
No 
Yes 
fever
No
Yes
Dysuria 
0
1
2
3
4
5
6
7
8
9
10
Frequency of micturition  
0 
1 
2 
3 
Urgency of micturition  
0 
1 
2 
3 
Feeling of urinary 
retention 
0 
1 
2 
3 
Urethral incontinence  
0 
1 
2 
3 
Fistula confirmed by 
retrograde cystography 
No 
Yes 
 

 
 
19
 
Figure 1: 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
              Figure1. Consort Diagram. Patient assignment to groups, follow up and analysis 
 
 
The participants to be excluded  
 
Not meeting preoperative 
inclusion criteria  
 
Decline to participate 
Enrolment 
Assessment of Volunteers for 
perioperative criteria of adhesions
Volunteers to be Excluded if study 
criteria for adhesion are not met 
Subjects of study for Randomization 
Allocation to the control group (n=107)
Allocation to the cystoinflation group (n=107) 
Allocation
Lost of Follow up  
Lost of Follow up 
Follow up
Primary Outcome  
Primary Outcome  
Secondary outcome in hospital  
Follow up after leaving hospital  
Secondary outcome in hospital 
Follow up after leaving hospital  
Analysis
Selection of participants with 
previous two or more C-sections