Norepinephrine for Prevention of Intraoperative Hypotension in Infants Undergoing Kasai Portoenterostomy

Prophylactic Use of Norepinephrine for Prevention of Intraoperative Hypotension in Infants Undergoing Kasai Portoenterostomy Operation for Biliary Atresia: Double Blinded Randomized Controlled Trial

This study aims to assess the efficacy and safety of prophylactic intraoperative norepinephrine infusion versus the standard technique on decreasing the incidence of intraoperative hypotension in infants undergoing Kasai portoenterostomy operation.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Pediatrics; Biliary Atresia
• Intervention / Treatment: Drug: Placebo; Drug: Norepinephrine Bitartrate

Detailed Description

All children will be anesthetized in accordance with the local policy of pediatric anesthesia unit in Abu El-Reesh pediatric hospital-Cairo university.

Upon arrival to the operating room heart rate HR, noninvasive blood pressure NBP and oxygen saturation SPO2 will be monitored using standard monitor (Dräger infinity vista XL) before inhalational induction of anesthesia using titration of sevoflurane in oxygen air mixture 60% (starting from 3% up to 8%) until the child is put to sleep.

After securing an intravenous line anesthesia will be completed with 2µg/kg of fentanyl and atracurium 0.5 mg/kg to facilitate endotracheal intubation. Anesthesia will be maintained by using 1.2 % isoflurane in a mixture of oxygen and air (50/50) and atracurium top ups at a dose of 0.1mg/kg every 30 minutes. Mechanical ventilation will be set to volume-controlled mode TV:8ml/kg, I/E ratio:1/2, PEEP: 3 cmH2o and respiratory rate will be adjusted to maintain ETCO2 30-35 mmHg. Nasopharyngeal temperature probe will be inserted for monitoring of core body temperature. 22 G arterial cannula will be placed in the radial artery for continuous monitoring of arterial blood pressure and management of intraoperative hemodynamics.

Central venous catheter will be inserted under complete aseptic condition using ultrasound guidance and a Foley's catheter will be inserted in the urinary bladder.

The concealed envelopes will then be opened by an anesthesia resident (who will not be involved in patient management to ensure the blinding) and he will be responsible for preparing norepinephrine infusion or placebo as instructed in the envelope as follow:

(Group N): 1 mg norepinephrine will be diluted in dextrose 5% in a 50 mL syringe using a nomogram based on the infant body weight so that 1mL= 0.05 µg/kg/min norepinephrine infusion.

(Group S): equivalent volume of saline will be prepared in 50 mL syringe. In both groups the attending anesthetist will be instructed to set the 2 syringe pumps on 2 mL/h continuous infusion following skin incision.

Intraoperative fluid management:

All children will receive a loading dose of 10 ml/kg of lactated ringer solution over 10 minutes after induction of anesthesia and will be maintained on 10 ml/kg/h lactated ringer solution using an infusion pump. Dextrose 1% will be transfused in a separate line and rate will be adjusted according to blood glucose level.

Packed RBCs will be transfused at a dose of 15mL/kg if intraoperative Hb dropped to 8 gm/dL.

Intraoperative hemodynamic management:

Episodes of hypotension defined as reduction of the mean ABP ≥20% of the baseline mean ABP recorded preoperatively will be managed by boluses of lactated ringer solution of 10 mL/kg that will be repeated up to 30 mL/kg, if hypotension persisted, norepinephrine bolus of 0.01 µg/kg bolus will be given, if hypotension persisted after 2 boluses the surgery will be stopped and the liver will be released into the abdominal cavity until the BP is restored. Total dose of norepinephrine will be recorded.

Hypertension defined as increase of mean ABP ≥20% of the baseline mean arterial pressure ABP will be treated by stopping the infusion pump until ABP return to baseline and then the infusion will be resumed to 1 mL/h. Bradycardia defined as HR less than 80 beat/min will be managed by atropine 0.01mg/kg.

Following release of the liver the norepinephrine infusion will be stopped gradually guided by the mean ABP.

At the end of the procedure an open transverses abdominis plane block TAPB will be given using 5 mL bupivacaine 0.25% before skin closure, inhalational anesthesia will be discontinued, infusion will be stopped and reversal of muscle relaxation with atropine (0.02 mg/Kg) and neostigmine (0.05 mg/Kg) will be administered IV after return of patient's spontaneous breathing and patients will then be transferred to PICU.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11559
    • Cairo University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 4 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants, ASA III, diagnosed as biliary atresia undergoing Kasai operation.

Exclusion Criteria:

• Parents refusal. Patients with complex cardiac anomalies. Patients requiring emergency or laparoscopic procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (Group N); 1 mg norepinephrine will be diluted in dextrose 5% in a 50 mL syringe using a nomogram based on the infant body weight so that 1mL= 0.05 µg/kg/min norepinephrine infusion and the syringe will be set on 2 ml/h	Drug: Norepinephrine Bitartrate; anesthesia resident (who will not be involved in patient management to ensure the blinding) will be responsible for preparing norepinephrine infusion or placebo as instructed in the envelope as follow: 1 mg norepinephrine will be diluted in dextrose 5% in a 50 mL syringe using a nomogram based on the infant body weight so that 1mL= 0.05 µg/kg/min norepinephrine infusion. the attending anesthetist will be instructed to set the 2 syringe pumps on 2 mL/h continuous infusion following skin incision.
Placebo Comparator: (Group S); equivalent volume of saline will be prepared in 50 mL syringe and the infusion will be set on 2ml/kg	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intraoperative hypotension	Incidence of intraoperative hypotension defined as persistent reduction of mean ABP ≥20% of the baseline mean ABP recorder preoperatively requiring release of the liver after initial resuscitation.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean arterial pressure (MAP)	mean arterial pressure (MAP) will be measured upon arrival to the operating room suite as baseline and every 5 minutes after induction of anesthesia and every 3 minutes during liver mobilization till the end of surgery.	4 hours
heart rate	will be measured upon arrival to the operating room suite as baseline and every 5 minutes after induction of anesthesia and every 3 minutes during liver mobilization till the end of surgery.	4 hours
Incidence of severe hypotension	Incidence of severe hypotension defined as reduction of mean ABP ≥30% of the baseline mean ABP recorder preoperatively.	4 hours
Incidence of hypertension	Incidence of hypertension defined as increase of mean ABP ≥20% of the baseline	4 hours
Total dose of rescue norepinephrine.	Total dose of rescue norepinephrine.	4 hours

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: Khaled Sarhan, MD, Cairo University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2022
• Primary Completion (Actual): July 8, 2024
• Study Completion (Actual): July 8, 2024

Study Registration Dates

• First Submitted: August 28, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 7, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: norepinephrine; hypotension; Kasai; biliary atresia
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Hypotension; Biliary Atresia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: MD-12-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No