Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05271253 |
| Other study ID # |
0305085 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
April 10, 2021 |
| Est. completion date |
January 15, 2022 |
Study information
| Verified date |
January 2022 |
| Source |
Alexandria University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Up to date, Renal Cell carcinomas (RCC) are one of the prevalent primary renal neoplasms
affecting children & surgical radical nephrectomy is the conventional standard of care, as
the choice of non-surgical modalities like irradiation & hormono-chemotherapy is still a
subject of debate .
Worsening of postoperative renal function is not so far from these patients who underwent
nephrectomy for RCC, thus peri-operative preservation of renal function is a great challenge
facing anaesthologist aiming to abolishment of postoperative acute kidney injury (AKI)
development. AKI is a serious clinical diverse which increases morbidity and mortality &
enhances the risk of development of chronic kidney disease (CKD). A major advances have shown
that the associations between AKI and CKD after radical nephrectomy is as high as 65 %.
For years, the diagnosis of AKI was based on ordinary kidney function tests like serum
creatinine & blood urea nitrogen, which are not efficient nowadays, as they lack specificity
for renal damage, besides they are affected by many other factors apart from kidney injury.
Cystatin C is an endogenous protein with low molecular weight (13 k Da), that is freely
filtrated at the glomeruli and completely reabsorbed in the proximal renal tubules. It
indicates renal injury indirectly through decreased GFR .
Serum neutrophil gelatinase-associated lipocalin (NGAL) is a promising glycoprotein produced
by neutrophils and epithelial cells of the proximal convoluted tubule of the nephron cells.
After renal stress or nephrotoxic damage its peak plasma level is reached within 6 hrs, then
remains sustained for as long as 5 days.
Dexmedetomidine (Dex.) a newer, short acting, highly selective alph-2 agonist, that possess
potent analgesic, amnestic, hypnotic & sedative properties via actions on sleep-awake cycle
in the brain. Several evidences reported its possible ability for renal protection.
Caudal epidural blockade is well known efficient technique that offer postoperative analgesia
for multiple surgical procedures in children. Beside hemodynamic stability, they prevent
progression of acute postoperative pain to chronic pain.
The investigators hypothesized that uses of Dex infusion in a programmed fashion in children
undergoing RN, could produce optimum preservation of kidney function from the concurrent
perioperative insult even in a very early phase of renal stress, relative to ordinary used
protocols.
Description:
Aim of the study The primary goal was comparison between different anaesthesia techniques in
preservation of kidney function using early phase detectors cystatin C and NGAL. Secondary
goals included measurements of creatinine clearance, serum creatinine, and urinary output.
Postoperative pain assessment using visual analogue scale & sedation score were also
recorded.
3. Patients and methods
After approval of the Ethical committee of faculty of Medicine, Alexandria University and
obtaining an informed written consent from parents of the children included in the study, 75
patients aged 5-10 years undergoing elective RN were randomly enrolled using closed envelope
method. Sample Size was calculated according to the following equation:
n=(t^2×p(1-p))/m^3
The patients were excluded if they had history of use of α 2-agonists to treat hypertension,
renal impairment (creatinine clearance < 90 ml/min), and persistent intraoperative
hypotension [mean arterial blood pressure < 65 for > 20 min]. Also those with bleeding
disorders and skin lesion at puncture site.
Patients were randomly allocated into 3 equal groups (25 patients each): Group (C): caudal
group, where caudal anaesthesia was given using 1 mL/kg dose of 0.25% bupivacaine without
epinephrine. Dexmedetomidine (D) group, where Dex. (Precedex, hospira, Egypt) 0.8 μg/kg was
given intravenously over 10 min as a loading dose, and then infused at a rate of 0.4 μg/kg/h;
and Placebo (P) group, where normal saline instead of Dex was given in volume (ml) and rate
(ml/h) calculated related to the patient's body weight. The infusions were prepared by
independent participant & were started after induction of anaesthesia and continued 24 hrs
postoperatively. All children were assessed thoroughly preoperatively by history taking,
physical examination & laboratory investigations (complete blood count, coagulation profile
liver function & kidney functions.) At the night before surgery, base line value of serum
creatinine, creatinine clearance were obtained using standard laboratory methods. Also, base
line value of serum cystatin C and NGAL were obtained using commercially available kits
(Roche Diagnostics, Mannheim, Germany) & (Biosite Incorporated, San Diego, CA, USA)
respectively by ELISA method. Establishment of method and degree of sample dilution were
carried out prior to analysis according to manufacture instruction.
All children were premedicated orally with midazolam 0.5 mg/ k.g 30 minutes before induction,
and they were instructed to void just before admission to the operating room.
In the operating theater, all patients were monitored throughout surgery by continuous
electrocardiography, heart rate, pulse oximetry, non invasive blood pressure and end tidal
capnography by (Datex-Omeda model S/5) monitor. Induction was carried out with fentanyl
(1-1.5 μg/kg), and propofol (1-2 mg/kg). For facilitating endotracheal intubation, atracurium
was administered at an initial dose of 0.5 mg/kg followed by boluses of 0.03 mg/kg every
20-40 min. Under aseptic technique, an arterial line and central venous catheter were
inserted & Anaesthesia was maintained using isoflurane 1-2% in oxygen, and patients were
mechanically ventilated. Fentanyl and atracurium increments were given as required.
The diagnostic criteria of AKI was classified according to the Acute Kidney Injury Network
(AKIN) criteria as follows: the renal function decreased rapidly within 48 hours, the s Cr
level increased by ≥ 26.5 µ mol/L or ≥ 1.5 times from baseline, or urine output < 0.5 mL/kg/h
for > 6 hours. Oliguria is defined as urine output < 0.5 ml/kg/h. After exclusion of catheter
obstruction, patients were managed with good hydration. If it persists, 10 mg I.v Lasix was
given, that could be repeated twice. If no response, nephrology consultation was ordered. At
the end of surgery, muscle relaxants were reversed by neostigmine 0.04-0.06 mg/kg and
atropine 0.02 mg/kg, and then the patients were extubated after returning to full muscle
power. All patients were monitored in the intensive care unit for 2 days after surgery, with
attention to fluid balance and urine output. Serum creatinine, creatinine clearance, Cystatin
C and NGAL was assessed 24 hr before surgery, after induction of anaesthesia, 12 and 24 hrs
postoperatively. Urine output was assessed intraoperatively every 1 hr and postoperatively
every 6 hr in the first 24 hrs. Sedation was assessed during the first 5, 15, 30, and 60 mins
in the recovery room by the investigator using a five-point sedation scale. Sedation level:
Agitated = 4, Awake= 3, Drowsy= 2, Asleep= 1. A sedation score of 3 & above was considered as
unsatistisfactory while 1&2 is considered to be satisfactory. Postoperative pain was assessed
using the visual analog scale from 0-10, where 0= no pain and 10= unbearable pain.
Data management Data were fed to the computer and analyzed using IBM SPSS software package
version 20.0 (Armonk, NY: IBM Corp). Quantitative data were described using range (minimum
and maximum), mean, SD, and median. Significance of the obtained results was judged at the 5%
level.
