Adhesions Pelvic, Bladder Injury, Complications; Cesarean Section
Conditions
Brief summary
Part1:The healthy pregnant women with previous operative deliveries admitted for elective C-section will be counselled and conditioned informed consent will be taken to be included in either study group if dense pelvic adhesions will be found during their operation. Adhesiolysis will be performed using bladder retro-fill with 300cc saline in the cystoinflation group, and without retro-fill in control.Both groups will be observed for bladder injury rate,bloodloss,operativetime,urinary tract infection,micturition problems and fistula formation. Part2&3:Summary of Part 2 and 3 will be provided after publication
Detailed description
Part1:Investigators will conduct this study to find the effectiveness of cystoinflation to prevent bladder injury in women with adhesions of previous C-sections. This prospective analytic longitudinal study will be conducted in Lady Willingdon Hospital, a tertiary care teaching hospital affiliated with King Edward Medical University Pakistan, from August 2017 to July 2019, after approval by the institutional review board of King Edward Medical University, Pakistan. The subjects will be randomly allocated to cystoinflation and control groups. The healthy pregnant women with previous operative deliveries admitted for elective C-section will be counselled and conditioned informed consent will be taken to be included in either study group if dense pelvic adhesions will be found during their operation. Adhesiolysis will be performed using bladder retro-fill with 300cc saline in the cystoinflation group, and without retro-fill in control. We will assess primary outcome by observing bladder injury rate, blood loss and operative time. The secondary outcome will be assessed by Urinary tract infection, micturition problems and fistula formation during 3month follow up period. The cystoinflation will be considered effective if the proportion of bladder injury in the study group will be less than 50% of the control group. Part2&3:Details of part2&3 will be provided after publication
Interventions
PROCEDURECystoinflation
Bladder retrofill with 300cc saline to distend the bladder to recognize bladder outline
Sponsors
King Edward Medical University
Institute of Public Health, Pakistan
Shazia Saaqib
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The participants and outcome assessors are kept blind by just entering the random number assigned to the subject on the papers and notes are written without details of adhesiolysis. The completed outcome performas are sent to the assessors with the only random number entered and without the assigned group. The random number file is opened only after receiving results from the statistician. The care providers in theatre and principle surgeon cannot be blinded in this study.
Intervention model description
Subjects will be assigned into cystoinflation group and control group after parallel assignment. In the cystoinflation group, the intervention will be retro-fill of the bladder with 300cc saline and clamping the drainage port of the catheter till the completion of adhesiolysis. In contrast, the urinary catheter of control group patients will be put on free drainage.
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
Part1:Inclusion Criteria: * • Healthy pregnant women of any age * Two or more previous C-sections * Gestational age between 38-40 weeks (confirmed by dating scan) * Dense Adhesions of Tulandi scores four or more. * women who give informed consent to participate in the study
Exclusion criteria
:• Patients with medical disorders * Bladder injury before group assignment * Placenta previa * Subjects experiencing micturition problems (dysuria, frequency, urgency, urinary retention, incontinence) before the study. Eligibility criteria of part 2&3 will be provided after publication -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bladder Injury Rate | From the confirmation of adhesions to adhesiolysis and separation of bladder flap from uterus, before delivery of the baby during cesarean section.This time frame can range between 10-20 minutes. | The bladder injury will be detected by direct visualization in the cesarean section before delivery of the baby during adhesiolysis of dense adhesions of the lower uterine segment, which cover and obscure the bladder. The bladder injury outcome will be measured as the number(percentage) of subjects with injury. |
| Blood Loss | From the confirmation of adhesions to adhesiolysis and separation of bladder flap from uterus, before delivery of the baby during cesarean section.This time frame can range between 10-20 minutes. | Amount of blood loss during C-section will be increase in weight of sponges used during operation, taking 1gram equal to 1cc. |
| Operative Time | During Caesarean section | Time from incision till closure of skin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postmicturition Bladder Volume After C-section | upto 3months | Volume of urine retained in bladder after evacuation. Bladder distension will be diagnosed if volume retained in the bladder will be greater than 50cc measured on 4th postoperative day |
| Composite Micturition Problems During Hospital Stay | Complaint recorded during hospital stay (range between 4-21 days) | The micturition problems during the hospital stay investigated in this study were dysuria, feeling of incomplete evacuation, frequency, urgency, urethral and extra-urethral incontinence), Dysuria was expressed by the subject as painful micturition using an 11point visual analogue Scale from zero to ten and converted into severity scores from 0-3. Score 0 or no point= 0 point on scale Score1 or mild pain=1-3point Score2 or Moderate Pain=4-6points; Score 3 or Severe Pain=.7-10 Other micturition problems (feeling of incomplete evacuation, frequency, urgency, urethral and extra-urethral incontinence) were measured subjectively on a 4point Likert scale questionnaire according to severity ranging from 0-3 (0-never, 1-rarely, 2-sometimes, and 3-often). The micturition problems of each subject were summed up as composite variables and both groups were compared for the mean value of the composite variable and standard deviation in spss20 statistical software. |
| Duration of Urinary Catheterization | upto 3months | The time interval for which subject will be kept catheterized postoperatively. |
| White Blood Cells Count Per High Power Feild | 3rd postoperative day | The normal white cell count ranges between 4000-11000 per microlitre. The raised count is an indication of postoperative infection. |
| Number of Subjects With Urinary Fistula Formation | upto 3months | abnormal communication between genital tract nd urinary tract |
| Composite Micturition Problems After Discharge | upto 3months | IT is composit Likert score(range from 0-3) of micturition problems recorded by patient after discharge from the hospital to the completion of 3months postoperative(follow up period).The lower value of the score is associated with good outcome while higher value shows a poor outcome. |
| Duration of Hospital Stay | upto 3months | The time interval in days from the date of operation till discharge from the hospital. |
| Urine Culture Report for Micro-organisms | 2nd postoperative day | The outcome measure was the number(percentage) of subjects in which urine culture reports showed the growth of micro-organisms in the urine of the subjects sent for test on the second postoperative day. |
| Fever | upto 3months | Number of patients who presented with fever during hospital stay |
Countries
Pakistan
Participant flow
Recruitment details
The study was carried out in King Edward Medical University affiliated hospital/Lady Willingdon Hospital for a period of two years starting from August 1,2017 to July31,2019 including a 3month follow up period.
Pre-assignment details
Subjects admitted with full term pregnancy and previous 2 C-sections n=734 The study subjects were selected in two step assessment(a)preoperative (during operation). preoperatively Excluded n=346 due to medical disorders, placenta previa, bladder injury before group assignment, micturition problems before operation Declined to participate=5 During operation Excluded=174 as criteria of dense adhesions of bladder was not met with.
Participants by arm
| Arm | Count |
|---|---|
| Cystoinflation Group Cystoinflation: Bladder will be retro-filled with 300cc saline to distend the bladder to recognize bladder outline in cystoinflation group whenever dense adhesions will be encountered which obscure the bladder either before or after opening the peritoneal cavity. Bladder outline will be recognized by observing its gradual distension during bladder retro-fill .The outcome of cystoinflation group will be divided into distension arm(no bladder injury arm) and bladder injury arm. | 107 |
| Control Group In control group,Pelvic adhesiolysis will be performed with bladder put on free drainage by urinary catheter.The outcome of control arm will be divided into distension arm(no bladder injury arm) and bladder injury arm. | 107 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 |
Baseline characteristics
| Characteristic | Cystoinflation Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 107 Participants | 214 Participants |
| Age, Continuous | 32.19 years STANDARD_DEVIATION 2.3 | 31.73 years STANDARD_DEVIATION 2.4 | 31.96 years STANDARD_DEVIATION 2.388 |
| BMI kg/m^2 | 30.73 kg/m^2 STANDARD_DEVIATION 1.89 | 30.54 kg/m^2 STANDARD_DEVIATION 1.86 | 30.635 kg/m^2 STANDARD_DEVIATION 1.876 |
| Number of previous C-sections previous2 | 46 Participants | 43 Participants | 89 Participants |
| Number of previous C-sections previous3 | 52 Participants | 54 Participants | 106 Participants |
| Number of previous C-sections previous4 | 6 Participants | 7 Participants | 13 Participants |
| Number of previous C-sections previous5 | 3 Participants | 3 Participants | 6 Participants |
| Parity para2 | 35 Participants | 33 Participants | 68 Participants |
| Parity para3 | 60 Participants | 60 Participants | 120 Participants |
| Parity para4 | 10 Participants | 10 Participants | 20 Participants |
| Parity para5 | 2 Participants | 4 Participants | 6 Participants |
| Preoperative postmicturition bladder volume | 15 ml | 20 ml | 15 ml |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 107 Participants | 107 Participants | 214 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Pakistan | 107 participants | 107 participants | 207 participants |
| Score of adhesions 16 | 16 Participants | 15 Participants | 31 Participants |
| Score of adhesions 4 | 53 Participants | 56 Participants | 109 Participants |
| Score of adhesions 8 | 38 Participants | 36 Participants | 74 Participants |
| Sex: Female, Male Female | 107 Participants | 107 Participants | 214 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Socioecnomic status high (per capita family income Rupees 5,000/month | 13 Participants | 12 Participants | 25 Participants |
| Socioecnomic status low (per capita family income <Rupees3000/month) | 39 Participants | 41 Participants | 80 Participants |
| Socioecnomic status medium (per capita family income<Rupees3000-5000/month | 55 Participants | 54 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 107 | 0 / 107 |
| other Total, other adverse events | 0 / 107 | 1 / 107 |
| serious Total, serious adverse events | 3 / 107 | 22 / 107 |
Outcome results
Primary
Bladder Injury Rate
The bladder injury will be detected by direct visualization in the cesarean section before delivery of the baby during adhesiolysis of dense adhesions of the lower uterine segment, which cover and obscure the bladder. The bladder injury outcome will be measured as the number(percentage) of subjects with injury.
Time frame: From the confirmation of adhesions to adhesiolysis and separation of bladder flap from uterus, before delivery of the baby during cesarean section.This time frame can range between 10-20 minutes.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cystoinflation Group | Bladder Injury Rate | 3 Participants |
| Control Group | Bladder Injury Rate | 22 Participants |
Comparison: Null Hypothesis: During the cesarean section of women with adhesions of the previous cesarean section that obscure the bladder, the bladder injury rate is not significantly decreased in cystoinflation group compared to the control.~In this study, the bladder injury rate was seven times lesser in cystoinflation group compared to the control, thereby strongly supporting our hypothesis. The power of the study for bladder injury was 0.988, calculated with statistical software G'Power version 3.1.p-value: <0.000195% CI: [-0.261, -0.094]Regression, Linear
Primary
Blood Loss
Amount of blood loss during C-section will be increase in weight of sponges used during operation, taking 1gram equal to 1cc.
Time frame: From the confirmation of adhesions to adhesiolysis and separation of bladder flap from uterus, before delivery of the baby during cesarean section.This time frame can range between 10-20 minutes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Blood Loss | 585.32 ml | Standard Deviation 152.52 |
| Control Group | Blood Loss | 797.10 ml | Standard Deviation 385.09 |
p-value: <0.000195% CI: [-290.7, -132.84]Regression, Linear
Primary
Operative Time
Time from incision till closure of skin
Time frame: During Caesarean section
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Operative Time | 45 minutes | Standard Deviation 8.66 |
| Control Group | Operative Time | 45 minutes | Standard Deviation 16.99 |
Comparison: Null Hypothsis:Cystoinflation is ineffective to prevent bladder injury in adhesions of previous C-section.The cystoinflation was to be cosidered ineffective if proportion of bladder injury in study group was less than %0% of the control.The power of the study for bladder injury prevention was.988,calculated with statistical software G'Power version3.1.p-value: 195% CI: [-3.634, 3.634]Regression, Linear
Secondary
Composite Micturition Problems After Discharge
IT is composit Likert score(range from 0-3) of micturition problems recorded by patient after discharge from the hospital to the completion of 3months postoperative(follow up period).The lower value of the score is associated with good outcome while higher value shows a poor outcome.
Time frame: upto 3months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Composite Micturition Problems After Discharge | .0047 score | Standard Deviation 0.034 |
| Control Group | Composite Micturition Problems After Discharge | .0701 score | Standard Deviation 0.222 |
p-value: 0.00395% CI: [-0.108, -0.023]Regression, Linear
Secondary
Composite Micturition Problems During Hospital Stay
The micturition problems during the hospital stay investigated in this study were dysuria, feeling of incomplete evacuation, frequency, urgency, urethral and extra-urethral incontinence), Dysuria was expressed by the subject as painful micturition using an 11point visual analogue Scale from zero to ten and converted into severity scores from 0-3. Score 0 or no point= 0 point on scale Score1 or mild pain=1-3point Score2 or Moderate Pain=4-6points; Score 3 or Severe Pain=.7-10 Other micturition problems (feeling of incomplete evacuation, frequency, urgency, urethral and extra-urethral incontinence) were measured subjectively on a 4point Likert scale questionnaire according to severity ranging from 0-3 (0-never, 1-rarely, 2-sometimes, and 3-often). The micturition problems of each subject were summed up as composite variables and both groups were compared for the mean value of the composite variable and standard deviation in spss20 statistical software.
Time frame: Complaint recorded during hospital stay (range between 4-21 days)
Population: Subjects of both cystoinflation and control groups during the postoperative hospital stay.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Composite Micturition Problems During Hospital Stay | .077 score | Standard Deviation 0.633 |
| Control Group | Composite Micturition Problems During Hospital Stay | .47 score | Standard Deviation 1.63 |
p-value: 0.02195% CI: [-0.725, -0.06]Regression, Linear
Secondary
Duration of Hospital Stay
The time interval in days from the date of operation till discharge from the hospital.
Time frame: upto 3months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Duration of Hospital Stay | 4.18 Days | Standard Deviation 1.156 |
| Control Group | Duration of Hospital Stay | 5.50 Days | Standard Deviation 3.506 |
p-value: <0.000195% CI: [-2.021, -0.614]Regression, Linear
Secondary
Duration of Urinary Catheterization
The time interval for which subject will be kept catheterized postoperatively.
Time frame: upto 3months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Duration of Urinary Catheterization | 1.25 Days | Standard Deviation 1.626 |
| Control Group | Duration of Urinary Catheterization | 3.14 Days | Standard Deviation 4.575 |
p-value: <0.000195% CI: [-2.813, -0.963]Regression, Linear
Secondary
Fever
Number of patients who presented with fever during hospital stay
Time frame: upto 3months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cystoinflation Group | Fever | 2 Participants |
| Control Group | Fever | 13 Participants |
p-value: 0.00395% CI: [-0.171, -0.035]Regression, Linear
Secondary
Number of Subjects With Urinary Fistula Formation
abnormal communication between genital tract nd urinary tract
Time frame: upto 3months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cystoinflation Group | Number of Subjects With Urinary Fistula Formation | 0 Participants |
| Control Group | Number of Subjects With Urinary Fistula Formation | 1 Participants |
Secondary
Postmicturition Bladder Volume After C-section
Volume of urine retained in bladder after evacuation. Bladder distension will be diagnosed if volume retained in the bladder will be greater than 50cc measured on 4th postoperative day
Time frame: upto 3months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | Postmicturition Bladder Volume After C-section | 15.56 ml | Standard Deviation 4.968 |
| Control Group | Postmicturition Bladder Volume After C-section | 14.91 ml | Standard Deviation 4.952 |
p-value: 0.33695% CI: [-0.682, 1.991]Regression, Linear
Secondary
Urine Culture Report for Micro-organisms
The outcome measure was the number(percentage) of subjects in which urine culture reports showed the growth of micro-organisms in the urine of the subjects sent for test on the second postoperative day.
Time frame: 2nd postoperative day
Population: The population included all cases of both cystinflation group and control group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cystoinflation Group | Urine Culture Report for Micro-organisms | 2 Participants |
| Control Group | Urine Culture Report for Micro-organisms | 18 Participants |
p-value: <0.000195% CI: [-0.226, -0.073]Regression, Linear
Secondary
White Blood Cells Count Per High Power Feild
The normal white cell count ranges between 4000-11000 per microlitre. The raised count is an indication of postoperative infection.
Time frame: 3rd postoperative day
Population: This analysis will be carried out in postoperative subjects of both groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystoinflation Group | White Blood Cells Count Per High Power Feild | 6.26 count/hpf | Standard Deviation 1.003 |
| Control Group | White Blood Cells Count Per High Power Feild | 7.36 count/hpf | Standard Deviation 3.063 |
p-value: 0.00195% CI: [-1.708, -0.479]Regression, Linear