CTRI/2022/07/044087 [Registered on: 18/07/2022] Trial Registered Prospectively
Last Modified On:
15/07/2022
Post Graduate Thesis
Yes
Type of Trial
Interventional
Type of Study
Other (Specify) [Fluid therapy]
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
The effect of usual versus limited fluid therapy in children undergoing abdominal, chest and genitourinary surgery.
Scientific Title of Study
The effect of standard versus restricted fluid therapy in pediatric patients undergoing major elective abdominal, thoracic and genitourinary surgery: a non-blinded randomized controlled trial
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Vignesh S
Designation
Junior Resident
Affiliation
AIIMS, New Delhi
Address
Department of Anaesthesiology, Pain Medicine and Critical care, AIIMS, Ansari Nagar East, New Delhi- 110029
South DELHI 110029 India
Phone
6380952391
Fax
Email
drrr.vicky1157@gmail.com
Details of Contact Person Scientific Query
Name
Rashmi Ramachandran
Designation
Professor
Affiliation
AIIMS
Address
Department of Anaesthesiology, Pain Medicine and Critical care,5th floor, room number:5007, AIIMS, Ansari Nagar East, New Delhi- 110029
South DELHI 110029 India
Phone
9868397812
Fax
Email
rashmiramachandran1@gmail.com
Details of Contact Person Public Query
Name
Vignesh S
Designation
Junior Resident
Affiliation
AIIMS
Address
Department of Anaesthesiology, Pain Medicine and Critical care, AIIMS, Ansari Nagar East, New Delhi- 110029
South DELHI 110029 India
Phone
6380952391
Fax
Email
drrr.vicky1157@gmail.com
Source of Monetary or Material Support
AIIMS, New Delhi
Primary Sponsor
Name
AIIMS New Delhi
Address
Ansari Nagar East, New Delhi 110029
Type of Sponsor
Research institution and hospital
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Vignesh S
AIIMS, New Delhi
Main OT 8th floor, AIIMS, Ansari Nagar East, New Delhi 110029 South DELHI
6380952391
drrr.vicky1157@gmail.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Institute ethics committee for postgraduate research, All India Institute of Medical Sciences, New Delhi
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: N281||Cyst of kidney, acquired, (2) ICD-10 Condition: N359||Urethral stricture, unspecified, (3) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis, (4) ICD-10 Condition: Q549||Hypospadias, unspecified, (5) ICD-10 Condition: N311||Reflex neuropathic bladder, not elsewhere classified, (6) ICD-10 Condition: K593||Megacolon, not elsewhere classified, (7) ICD-10 Condition: K23||Disorders of esophagus in diseasesclassified elsewhere, (8) ICD-10 Condition: J439||Emphysema, unspecified, (9) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, (10) ICD-10 Condition: B671||Echinococcus granulosus infectionof lung, (11) ICD-10 Condition: K440||Diaphragmatic hernia with obstruction, without gangrene, (12) ICD-10 Condition: N209||Urinary calculus, unspecified, (13) ICD-10 Condition: J989||Respiratory disorder, unspecified, (14) ICD-10 Condition: Q330||Congenital cystic lung, (15) ICD-10 Condition: Q338||Other congenital malformations oflung, (16) ICD-10 Condition: Q324||Other congenital malformations ofbronchus, (17) ICD-10 Condition: Q338||Other congenital malformations oflung, (18) ICD-10 Condition: Q391||Atresia of esophagus with tracheo-esophageal fistula, (19) ICD-10 Condition: Q401||Congenital hiatus hernia, (20) ICD-10 Condition: Q392||Congenital tracheo-esophageal fistula without atresia, (21) ICD-10 Condition: Q399||Congenital malformation of esophagus, unspecified, (22) ICD-10 Condition: Q399||Congenital malformation of esophagus, unspecified, (23) ICD-10 Condition: Q422||Congenital absence, atresia and stenosis of anus with fistula, (24) ICD-10 Condition: Q429||Congenital absence, atresia and stenosis of large intestine, part unspecified, (25) ICD-10 Condition: Q431||Hirschsprungs disease, (26) ICD-10 Condition: Q459||Congenital malformation of digestive system, unspecified, (27) ICD-10 Condition: Q430||Meckels diverticulum (displaced)(hypertrophic), (28) ICD-10 Condition: Q435||Ectopic anus, (29) ICD-10 Condition: Q433||Congenital malformations of intestinal fixation, (30) ICD-10 Condition: Q438||Other specified congenital malformations of intestine, (31) ICD-10 Condition: Q459||Congenital malformation of digestive system, unspecified, (32) ICD-10 Condition: Q439||Congenital malformation of intestine, unspecified, (33) ICD-10 Condition: Q428||Congenital absence, atresia and stenosis of other parts of large intestine, (34) ICD-10 Condition: Q549||Hypospadias, unspecified, (35) ICD-10 Condition: Q620||Congenital hydronephrosis, (36) ICD-10 Condition: Q610||Congenital renal cyst, (37) ICD-10 Condition: Q618||Other cystic kidney diseases, (38) ICD-10 Condition: Q638||Other specified congenital malformations of kidney, (39) ICD-10 Condition: Q641||Exstrophy of urinary bladder, (40) ICD-10 Condition: Q643||Other atresia and stenosis of urethra and bladder neck, (41) ICD-10 Condition: Q647||Other and unspecified congenital malformations of bladder and urethra, (42) ICD-10 Condition: Q644||Malformation of urachus, (43) ICD-10 Condition: Q648||Other specified congenital malformations of urinary system, (44) ICD-10 Condition: Q649||Congenital malformation of urinarysystem, unspecified, (45) ICD-10 Condition: Q639||Congenital malformation of kidney,unspecified, (46) ICD-10 Condition: Q899||Congenital malformation, unspecified, (47) ICD-10 Condition: Q506||Other congenital malformations offallopian tube and broad ligament, (48) ICD-10 Condition: Q530||Ectopic testis, (49) ICD-10 Condition: Q539||Undescended testicle, unspecified, (50) ICD-10 Condition: Q519||Congenital malformation of uterusand cervix, unspecified, (51) ICD-10 Condition: Q559||Congenital malformation of male genital organ, unspecified, (52) ICD-10 Condition: Q338||Other congenital malformations oflung, (53) ICD-10 Condition: Q341||Congenital cyst of mediastinum, (54) ICD-10 Condition: Q349||Congenital malformation of respiratory system, unspecified, (55) ICD-10 Condition: Q348||Other specified congenital malformations of respiratory system, (56) ICD-10 Condition: K440||Diaphragmatic hernia with obstruction, without gangrene, (57) ICD-10 Condition: K449||Diaphragmatic hernia without obstruction or gangrene, (58) ICD-10 Condition: K210||Gastro-esophageal reflux disease with esophagitis, (59) ICD-10 Condition: K219||Gastro-esophageal reflux disease without esophagitis, (60) ICD-10 Condition: K765||Hepatic veno-occlusive disease, (61) ICD-10 Condition: K831||Obstruction of bile duct, (62) ICD-10 Condition: K87||Disorders of gallbladder, biliarytract and pancreas in diseases classified elsewhere, (63) ICD-10 Condition: K668||Other specified disorders of peritoneum, (64) ICD-10 Condition: K900||Celiac disease, (65) ICD-10 Condition: K929||Disease of digestive system, unspecified, (66) ICD-10 Condition: K624||Stenosis of anus and rectum, (67) ICD-10 Condition: N281||Cyst of kidney, acquired, (68) ICD-10 Condition: Q623||Other obstructive defects of renalpelvis and ureter, (69) ICD-10 Condition: Q631||Lobulated, fused and horseshoe kidney, (70) ICD-10 Condition: Q639||Congenital malformation of kidney,unspecified, (71) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis, (72) ICD-10 Condition: C689||Malignant neoplasm of urinary organ, unspecified, (73) ICD-10 Condition: C749||Malignant neoplasm of unspecifiedpart of adrenal gland, (74) ICD-10 Condition: C7A8||Other malignant neuroendocrine tumors, (75) ICD-10 Condition: D350||Benign neoplasm of adrenal gland, (76) ICD-10 Condition: Q436||Congenital fistula of rectum and anus, (77) ICD-10 Condition: Q437||Persistent cloaca, (78) ICD-10 Condition: Q439||Congenital malformation of intestine, unspecified, (79) ICD-10 Condition: Q458||Other specified congenital malformations of digestive system, (80) ICD-10 Condition: Q444||Choledochal cyst, (81) ICD-10 Condition: Q442||Atresia of bile ducts, (82) ICD-10 Condition: K835||Biliary cyst, (83) ICD-10 Condition: Q445||Other congenital malformations ofbile ducts, (84) ICD-10 Condition: Q443||Congenital stenosis and strictureof bile ducts, (85) ICD-10 Condition: Q429||Congenital absence, atresia and stenosis of large intestine, part unspecified, (86) ICD-10 Condition: Q445||Other congenital malformations ofbile ducts, (87) ICD-10 Condition: Q445||Other congenital malformations ofbile ducts, (88) ICD-10 Condition: Q445||Other congenital malformations ofbile ducts, (89) ICD-10 Condition: C229||Malignant neoplasm of liver, not specified as primary or secondary, (90) ICD-10 Condition: C228||Malignant neoplasm of liver, primary, unspecified as to type, (91) ICD-10 Condition: C222||Hepatoblastoma, (92) ICD-10 Condition: C227||Other specified carcinomas of liver, (93) ICD-10 Condition: C224||Other sarcomas of liver, (94) ICD-10 Condition: J439||Emphysema, unspecified, (95) ICD-10 Condition: K315||Obstruction of duodenum, (96) ICD-10 Condition: D157||Benign neoplasm of other specifiedintrathoracic organs, (97) ICD-10 Condition: K863||Pseudocyst of pancreas, (98) ICD-10 Condition: K862||Cyst of pancreas, (99) ICD-10 Condition: K808||Other cholelithiasis, (100) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, (101) ICD-10 Condition: B441||Other pulmonary aspergillosis, (102) ICD-10 Condition: D126||Benign neoplasm of colon, unspecified, (103) ICD-10 Condition: D152||Benign neoplasm of mediastinum, (104) ICD-10 Condition: K529||Noninfective gastroenteritis and colitis, unspecified, (105) ICD-10 Condition: K635||Polyp of colon, (106) ICD-10 Condition: K604||Rectal fistula, (107) ICD-10 Condition: K388||Other specified diseases of appendix, (108) ICD-10 Condition: K638||Other specified diseases of intestine, (109) ICD-10 Condition: Q401||Congenital hiatus hernia, (110) ICD-10 Condition: Q402||Other specified congenital malformations of stomach, (111) ICD-10 Condition: Q458||Other specified congenital malformations of digestive system,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Restricted fluid therapy
During intra-operative period, restricted fluid therapy group will receive maintenance and deficit correction as per Holliday-Segar formula and blood loss replacement (3:1 with Ringers lactate and 1:1 with blood according to anaesthesiologists decision). Fluid bolus will be given at 5ml/kg if stroke volume variation (SVV) in electrical cardiometry is more than 15% persistently for more than 5 min. At the end of surgery number of fluid boluses, serum lactate, sodium, potassium, calcium, blood urea and creatinine will be measured. Chest x ray will be taken in immediate post-operative period to look for signs of fluid overload. Assessment for nausea and vomiting will be done, weight will be checked if posssible. On post-operative day 2, blood urea and serum creatinine will be checked. Duration of hospital stay will be noted.
Comparator Agent
Standard fluid therapy
During intra-operative period, standard fluid therapy group will receive maintenance and deficit fluid correction as per Holliday-Segar formula, blood loss replacement and 3rd space loss replacement(4-7ml/kg for thoracotomy, 5-10ml/kg for abdominal surgery). Electrical cardiometry will be monitored in this group also. At the end of surgery number of fluid boluses, serum lactate, sodium, potassium, calcium, blood urea and creatinine will be measured. Chest x ray will be taken in immediate post-operative period to look for signs of fluid overload. Assessment for nausea and vomiting will be done, weight will be checked if posssible. On post-operative day 2, blood urea and serum creatinine will be checked. Duration of hospital stay will be noted.
Inclusion Criteria
Age From
1.00 Year(s)
Age To
10.00 Year(s)
Gender
Both
Details
1.Patients with parental consent
2.Age between 1 year and 10 years
3.ASA 1 & 2 patients
4.Major elective surgery- abdominal, thoracic and genitourinary open surgery
ExclusionCriteria
Details
1.Patients with electrolyte imbalances
2.Patients with altered hemodynamic status
3.Surgery duration <2 hours
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Sequentially numbered, sealed, opaque envelopes
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
1.Postoperative hypernatremia
2.Rise in serum lactate
3.Rise in blood urea
4.Rise in serum creatinine
At the end of surgery
Secondary Outcome
Outcome
TimePoints
1.Signs of fluid overload
2.Postoperative nausea and vomiting
3.Postoperative weight gain
4.Difference in amount of intraoperative fluid given in both the groups
5.Duration of hospital stay
6.Any delayed increase in blood urea and serum creatinine on post-operative day 2
At the postoperative period upto the discharge of the patient.
Target Sample Size
Total Sample Size="60" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 4
Date of First Enrollment (India)
20/07/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NIL
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The main purpose of perioperative fluid therapy is to maintain hemodynamic stability and adequate tissue perfusion. Fluid overload will lead to pulmonary oedema, cardiac complication such as myocardial stress, electrolyte imbalance like dilutional hyponatremia and weight gain. Hyponatremia is the most common electrolyte disorder in postoperative period. On the other hand, inadequate fluid infusion will lead to hypovolemia, inadequate tissue perfusion and organ dysfunction. Standard fluid therapy in pediatric patients includes infusing maintenance and deficit fluid according to Holliday-Segar formula and replacing third space blood losses. Holliday-Segar formula is known as 4-2-1 rule which is still widely used for fluid therapy in paediatric patients. Third space loss is the supposed seepage of fluid around the surgical site from vascular space, it’s replacement depends on the tissue exposure related to surgery i.e. 2ml/kg/hr for superficial surgery, 4-7ml/kg/hr for thoracotomy and 5-10ml/kg/h for abdominal surgery. Recently, its replacement has being questioned and is being mentioned as arbitrary. Restrictive fluid therapy is similar to standard fluid therapy but without third space loss replacement. Goal directed fluid therapy (GDT) is the fluid administration based on hemodynamic parameters and guided by cardiac output monitoring. The purpose of GDT is to avoid overloading the patient with fluids and at the same time not compromising tissue perfusion. GDT showed decreased postoperative morbidity and mortality in adults. In children, however, it is not well researched. Electrical cardiometry is a non-invasive technique for hemodynamic monitoring. It determines stroke volume, stroke volume variation, cardiac output, cardiac index based on changes in electrical conductivity within the thorax., i.e. Thoracic Electrical Bioimpedance. It has been validated against gold standard methods such as thermodilution. It is FDA approved and validated for neonates, children and adults. Studies are lacking regarding the effect of restrictive fluid therapy in paediatric patients. This study will try to explore the various effects of standard fluid therapy with replacement of calculated third space losses against restrictive fluid therapy in paediatric patients undergoing major abdominal, thoracic and genitourinary surgery.
STUDY PROTOCOL
Pre-operative evaluation
The detailed pre-anaesthesia checkup will be done including history, treatment history, airway examination and systemic examination, body weight estimation. Fasting guidelines (i.e., 8 hrs for solids, 6 hrs for formula feeds, 4hrs for breast milk, 2 hrs for clear liquids) will be explained to parents and informed written consent will be obtained from them. Investigations such as serum sodium, potassium, calcium, CBC, blood urea, serum creatinine, chest x ray will be done.
Intraoperativecare
Patients will be randomised into 2 groups (Standard and restricted fluid therapy group). After ensuring adequate NPO status patient will be shifted to operating room and ASA standard monitors such as pulse oximeter, NIBP, electrocardiography will be attached and baseline values of pulse rate, SpO2, blood pressure, ECG will be recorded. Cardiometry will be attached and its baseline readings of cardiac output, cardiac index, stroke volume and stroke volume variation will be recorded. Anaesthesia will be induced by either inhalational anaesthetic agents or intravenous induction agents. IV cannula will be secured before or after induction depending upon the co-operation of the patient. Intravenous isotonic fluid (Ringer’s Lactate) will be started as per Holliday-Segar formula. Muscle relaxants will be injected and patient will be intubated with appropriate sized endotracheal tube. Surgery will be allowed to start once all the monitors are in place and the baseline values have been taken. Patients in the standard fluid therapy group will receive maintenance and deficit fluid according to Holliday-Segar formula, replacement for 3rd space loss and ongoing blood losses, whereas patients in restricted fluid therapy group will be infused with maintenance fluid, deficits and ongoing blood losses without replacement for 3rd space loss. Ongoing blood loss will be replaced 3:1 with isotonic fluids (Ringer’s Lactate) and 1:1 with blood according to the anaesthesiologists’ decision. Third space loss will be given according to the data in Table 1. Monitoring of cardiometry, type and volume of IV fluid given, ongoing blood losses, hemodynamic status assessment will be done. If any major blood loss occurs and blood transfusion is needed, those patients will be excluded from the study. During surgery if any patient develops major hemodynamic changes needing continuous infusion of vasopressors they will be excluded from the study. In both the groups if the SVV is more than 15% persistently for more than 5 min at any time intra-operatively fluid bolus will be given at 5ml/kg. Number of such fluid boluses will be recorded. At the end of surgery venous blood will be collected to measure serum lactate, sodium, potassium, calcium, blood urea and serum creatinine.
Table 1
Type of surgery
Third space loss replacement
Thoracotomy
4-7ml/kg/h
Abdominal surgery
5-10ml/kg/h
Post operative care
After completion of surgery, patient will be extubated and shifted to recovery room. Post operative weight will be taken for patients if possible. Post-operative nausea and vomiting will be assessed using Five-point scale (Table 2). Chest x ray will be done immediately in the postoperative period to look for any signs of fluid overload. Values of blood urea and serum creatinine will be taken on post-operative day 2. Duration of post-operative stay will be noted.