Clinical trial NCT03781505: Intravenous Paracetamol in Combination With Caudal Ropivacaine
Official title: Effect of Intravenous Paracetamol Combination With Caudal Ropivacaine on Quality of Postoperative Recovery in Pediatric Patients Undergoing Hypospadias Repair.A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Analgesia
Lead sponsor: Aga Khan University
Sponsor class: OTHER
First posted: 2018-12-20
Enrollment: 64
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized control trail
Primary purpose: TREATMENT

Brief summary: To investigate whether the addition of intravenous paracetamol with caudal ropivacaine leads to better quality of postoperative recovery in patients undergoing hypospadius repair than caudal ropivacaine alone. The quality of recovery will be judged by postoperative analgesia requirement and lesser agitation in the postoperative period.

Detailed description: After obtaining approval from Ethical Review Committee (ERC) of Aga Khan University Hospital Karachi (AKUH) and inform about the study to primary surgeon (who ever doing the surgical procedure on this time), informed written consent will be obtained from the parents of patients fulfilling the inclusion criteria schedule for surgical procedures on the day before surgery. Assent will be obtained from older children.

The patients will be assigned to one of the two groups by randomization through sealed opaque envelope technique. The envelopes will be prepared using a computer generated randomization table. Randomization envelopes will be used in consecutive order.

Patients will be allocated to either placebo group, who will not receive intravenous paracetamol, or group who will receive intravenous paracetamol.

All patient will be given general anesthesia as per standard of care. Anaesthesia will be standardized as follow. Anaesthesia will be induced by the inhalational route with application of facemask with 8% sevoflurane in 50% oxygen-nitrous oxide mixture. Airway will be managed by laryngeal mask airway (LMA) of appropriate size as recommended by manufacturer and anesthesia will be subsequently maintained with Minimum alveolar concentration 1-2% sevoflurane in 40% oxygen-nitrous mixture with spontaneous ventilation via LMA. Heart rate (HR), noninvasive blood pressure, core body temperature (oral/nasal probe), end-tidal carbon dioxide (ETCO2) and oxygen saturation by pulse oximetry (SpO2) will be monitored throughout.

After induction of anaesthesia, patients will be turned to lateral position and maximum safe dose of ropivacaine will be calculated (3mg/kg) and documented. After all aseptic measures, butterfly needle (size 23 gauge) will be inserted into the sacral hiatus. A total volume of 1 ml/kg of 0.25% ropivacaine solution will be injected in caudal space. The time of performing block will be noted. The success of caudal analgesia will be assessed by monitoring the parameters like heart rate (HR) and blood pressure (BP) in response to incision. In case of tachycardia (\>20% from baseline) and hypertension (\>20% from baseline), the concentration of sevoflurane will be adjusted. If tachycardia persists for more than 5 minutes despite increasing the sevoflurane concentration, rescue analgesia in the form of fentanyl 1mcg/kg will be administered.

Study drugs will be prepared and dispatch by Clinical Trial Unit (CTU) pharmacy. Eligible consecutive randomized patients belonging to study group will receive intravenous paracetamol approximately about an hour before the end of surgery with a dose of 15mg/kg over 15 to 20 minutes. While the patients belonging to other group will receive placebo. Time of intravenous paracetamol administration will be noted.

After emergence, the children will be taken to the postanesthesia care unit (PACU) where parents will be called to stay with their child. Time of arrival in the recovery room will be noted.The Mean arterial pressures (MAP), heart rate HR, oxygen saturation by pulse oximetry (SPO2), respiratory rate (RR), sedation, agitation, quality and duration of analgesia will be recorded at 15 and 30 minutes and will be followed by 1, 2, 4, and 6 hours following recovery from anaesthesia.

The analgesic status of the patient will be evaluated by trained Research Assistant in the PACU and in the ward by using Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). This includes crying, facial expression, verbal response, touching the wound and torso and leg movement. It is given in the Appendix.

Sedation will be assessed using a five point scale (0: awake; 1: mild sedation; 2: sleeping, but able to wake; 3: in deep sleep, unable to wake). These observations will be recorded by the same investigator blinded to the medication administered. Same observer will perform the measurements for all patients. A pain score lower than 4 will be considered adequate analgesia. Rescue analgesia will be provided by 0.1 mg/kg i.v. morphine in divided doses (0.025 mg aliquots) and time of doses will be noted on the form.

Analgesia requirement in the postoperative period will be define as a CHEOPS score of 7 or more. Time to the first analgesic requirement will be calculated as the time from the performance of caudal block to the first analgesic dose administered.

Complications like motor block, hypotension and urinary retention will be monitored and recorded in the postoperative period. Modified Bromage Scale will be used to assess motor block i.e 0= No block, 1= Able to move legs, 2= Unable to move legs.

Adverse effects:

Adverse Events are defined as 'Any untoward medical occurrence in a trial patient to whom a research treatment or procedure has been administered, including occurrences which are not necessarily caused by or related to that treatment or procedure.

Adverse effects associated with the paracetamol are rare \<1/10000, which includes malaise, increased level of hepatic transaminases and hypersensitivity reaction.

The following data will be collected by an observer in postoperative period: age, weight, height, surgical time, anesthesia time, recovery time, discharge time, need to increase sevoflurane concentration after incision, the need for rescue analgesia in operating room (OR) and PACU, time of voiding urine and time of taking oral fluids, while subjective complaint of heaviness in legs will be asked from children above 3 years only.

SAMPLE SELECTION Inclusion criteria

1. Age 3-10 years
2. American Society of Anesthesiologist class I and II
3. Undergoing hypospadias repair surgery

Exclusion criteria

1. Coagulopathy
2. Aspirin or any other analgesic ingestion in the preceding week
3. Preexisting neurological or spinal disease
4. Hepatic, renal disease and malnutrition

Eligibility criteria: Inclusion Criteria:

1. Age 3-10 years
2. ASA (American Society of Anesthesiologists) I and II
3. Undergoing hypospadias repair surgery

Exclusion Criteria:

1. Coagulopathy
2. Aspirin or any other analgesic ingestion in the preceding week
3. Preexisting neurological or spinal disease
4. Hepatic, renal disease and malnutrition
5. Severe hypovolemia
6. Uncontrolled convulsions
7. Refusal of the parents
8. Local Skin infection at the puncture site
9. Allergy to local anesthetics
10. Patient previously involved in other studies

Primary outcomes:
measure: Postoperative Analgesia Requirement
timeFrame: follow till 6 hours postoperatively
Secondary outcomes:
measure: Sedation
timeFrame: follow till 4 hours postoperatively
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University Hospital
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Muhammad S Yousuf, FCPS
role: PRINCIPAL_INVESTIGATOR
References:
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