Epinephrine vs Norepinephrine as the Initial Vasoactive Agent in Pediatric Septic Shock: A Feasibility Randomized
Rajeshwari Nataraj1, Parth Dalal1, Bharath Kt Vijayaraghavan2
1Department of Paediatric Intensive Care, Apollo Children's Hospital, Chennai, Tamil Nadu, India.
Background And Aims:
Pediatric guidelines recommend initial resuscitation of septic shock using either epinephrine or norepinephrine as first-line support. However, there are no trials comparing these two agents. The primary aim of this randomized controlled trial was to test the feasibility of a study protocol, specifically in terms of recruitment rates and protocol adherence, comparing epinephrine and norepinephrine as first-line vasoactive agents in pediatric septic shock.
Patients And Methods:
A double-blinded, randomized controlled single-center study was conducted in the Emergency Medicine Department (ED) and pediatric intensive care unit (PICU) at a tertiary referral hospital in India. Thirty children aged between 1 month and 17 years with suspected septic shock, in whom signs of shock persisted after the initial fluid bolus, were recruited.
Participants Were Randomized:
1:1 to receive either epinephrine or norepinephrine (each 15), initiated at 0.05-0.1 µg/kg/min. Feasibility outcomes were recruitment rates, randomization to study-drug initiation time, and adherence to protocol. Exploratory clinical outcomes included proportion of shock resolution, adverse events, and hospital mortality.
Results:
Of 44 screened patients, 10 met exclusion criteria and 4 declined consents, with a recruitment rate of 3.2 patients/month. The median time to vasoactive initiation after randomization was 12 minutes (IQR 8-15). The median time for shock resolution was 31 hours (IQR 10.8-51.2) and 14 hours (IQR 11.5-16.5) in the epinephrine and norepinephrine groups, respectively. Adverse events meeting pre-determined stopping criteria occurred in 7/16 and 1/15 in the epinephrine and norepinephrine groups, respectively. One patient in each group died.
Conclusions:
A protocol randomizing children with septic shock to epinephrine vs norepinephrine was feasible in terms of protocol adherence and recruitment rates. These findings can inform the design of a definitive multicenter trial powered for patient-centered endpoints.
How To Cite This Article:
Nataraj R, Dalal P, Vijayaraghavan BKT, Venkatachalam P, Kumar V, Lakshmanan L, et al. Epinephrine vs Norepinephrine as the Initial Vasoactive Agent in Pediatric Septic Shock: A Feasibility Randomized Controlled Trial for Recruitment Rates and Protocol Adherence, the Epinephrine vs Norepinephrine in Pediatric Septic Shock Trial. Indian J Crit Care Med 2025;29(9):737-745.
More Related Videos
10:02Event Related Potentials ERPs and other EEG Based Methods for Extracting Biomarkers of Brain Dysfunction: Examples from Pediatric Attention Deficit/Hyperactivity Disorder ADHD
Published on: March 12, 2020
09:45Measuring Cardiac Autonomic Nervous System ANS Activity in Children
Published on: April 29, 2013
Related Concept Videos
01:30Adrenergic Agonists: Therapeutic Uses
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
01:28Adrenergic Agonists: Mixed-Action Agents
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...
01:30Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
01:25Cardiopulmonary Resuscitation IV: Pharmacological Management
01:18Adrenergic Agonists: Therapeutic Classification
Vasopressor or pressor agents: They increase blood pressure and function as cardiac stimulants. Examples include endogenous catecholamines (norepinephrine and dopamine) and synthetic agents (phenylephrine).
Bronchodilators: β2-agonists can relax bronchial muscles and widen airways. They are commonly used for treating obstructive pulmonary...
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...