Early Resuscitation in Paediatric Sepsis using Inotropes and Metabolic Support – A Randomized Controlled Pilot Study (RESPOND)

Sepsis and serious infections are one of the most common reasons for children to present to Emergency Departments and Intensive Care Units.  Septic shock is the result of an infection, triggering a complex response by the body resulting in decreased blood pressure.  Decreased blood pressure can contribute to a decreased blood supply to organs and subsequently failure of one or more organs can result.  We know that early recognition and rapid initiation of treatment can improve outcomes for children with sepsis and/or septic shock.

When patients are admitted to hospital with sepsis and/or septic shock there are a variety of therapies they may receive. These include a combination of antibiotics, intravenous fluids (given through a drip), drugs to increase the blood pressures (inotropes), steroids (Hydrocortisone) and vitamins.   However, there is limited evidence and consensus around the current recommended management for sepsis in children. This is the reason why we need to do this study.

We aim to investigate in a multicentre pilot randomised controlled trial the use of intravenous fluids, early inotropes, steroids (Hydrocortisone) and vitamins in children with sepsis and/or septic shock.

Information for parents and guardians of our patients


RESPOND stands for Early Resuscitation in Paediatric Sepsis using Inotropes and Metabolic Support- A Randomized Controlled Pilot Study.

Fluid sparing and early Inotropes

Administration of intravenous fluids remains the foundation management of children with sepsis and/or septic shock requiring sepsis resuscitation. However, the timing and amount of fluids given during sepsis resuscitation remains controversial.  There is current evidence to suggest that large or excessive administration of intravenous fluids may potentially cause further complications and increase length of hospital stay/admission. In view of the potential harm associated with high volume fluid administration, this study proposes use of less fluid (fluid sparing) in combination with early administration of inotropes (drugs which increase blood pressure and work by increasing heart contractility) will improve outcomes in children with sepsis and/or septic shock.

Metabolic support:

In children with sepsis and/or septic shock, steroids (hydrocortisone) are often administered to improve circulation and restore blood pressure. The use of steroids for treatment of severe infections has been studied for more than fifty years.  Currently there is no agreement amongst doctors around the world if administration of steroids improves the overall recovery and survival of children with sepsis and/or septic shock.

Over the last few years, evidence has suggested that administering Vitamin C and Thiamine (Vitamin B1), enhances the effects of steroids (Hydrocortisone) when used in the treatment of children with sepsis and/or septic shock. Vitamin C and Thiamine are widely, and safety used in critically ill patients. Vitamin C is a powerful and naturally occurring antioxidant and in children with sepsis and/or septic shock, low levels of circulating Vitamin C are reported. During sepsis and/or septic shock Vitamin C is known to have effects on multiple effects on capillaries which is thought to contribute to improving blood flow, preventing organ failure. Thiamine is a water-soluble vitamin which plays an essential role in cellular metabolism.  In patients with sepsis and/or septic shock the role of Thiamine is not clear, however Thiamine deficiency is common. The combination of hydrocortisone and vitamins (Vitamin C and Thiamine) is termed ‘metabolic support’.  It is thought the treatment of sepsis and/or septic shock with early metabolic resuscitation is thought to improve patient outcomes.

Why are we conducting the RESPOND trial?

Currently we do not know what is the best treatment for children with sepsis and/or septic shock.  The purpose of this study is to compare if treatment with a reduced amount of fluids in combination with early administration of inotropes, hydrocortisone, and vitamins (Vitamin C and Thiamine) is associated with less complications, faster recovery and improved outcomes of children with sepsis and/or septic shock in comparison to standard treatment.

Who can take part in the trial?

Inclusion criteria for the RESPOND ED (early inotropes versus standard fluid resuscitation)
Children age ≥28days and <18 years which are recognized as sepsis or septic shock, with the decision of the treating physician to launch the sepsis treatment bundle are eligible if patients have received at least 20ml/kg fluid bolus(es) in the past four hours and the clinician decides to continue treating signs of shock.

Inclusion criteria RESPOND PICU (metabolic resuscitation versus shock treatment)
Children age ≥28 days and <18 years which are admitted to the Paediatric Intensive Care Unit with a diagnosis of suspected septic shock requiring vasopressors/inotropes for >2 hours.

What does be part of RESPOND involve?

Children admitted to PICU/ED requiring medical treatment for septic shock, who meet the above inclusion criteria could be enrolled in this project. There is a 50/50 chance (coin toss) to either one of two (2) treatment groups and a portion of blood will be sampled.

  1. Fluid Sparing and Early Inotropes: small fluid bolus and commencement of inotrope infusion.
  2. Current Standard Care Fluid Management: large fluid bolus, prior to consideration of inotropes.

If there is no improvement in your child’s condition after the above treatment and they are admitted to the intensive care unit, they will then be eligible for the next intervention of the study. For the next part of the study your child will be randomly assigned again to either one of two (2) treatment groups

  1. Early Metabolic Treatment: receive Hydrocortisone, Vitamin C and Thiamine.
  2. Current Standard Care Treatment : ‘Standard Treatment’ does not include Hydrocortisone, Vitamin C or Thiamine. However, the standard treatment group can receive Hydrocortisone, Vitamin C or Thiamine if clinically indicated at the discretion of the Intensive Care medical team

When children may have suspected or known sepsis and/or septic shock, blood is sampled, and routine testing is conducted.  When routine sampling of bloods is occurring an additional small portion of blood will be collected and stored for future diagnostic discovery and validation of novel markers of sepsis and sepsis severity.

We will follow up the child at hospital discharge, one month and six months after their enrolment on the study to see how they are going. We will try and do this via a phone call, or mail unless the child is still in hospital. The one month follow up will include a brief five-minute questionnaire on how the child is going. The six month follow up will include surveys and questionnaires for parents to complete to help us understand how their child and family are going and the support needed for families that have a child who experienced sepsis. We will be asking you questions around your child’s development and quality of life. These questions will take approximately two hours to complete and parents will have the option to do so online, on paper or on the phone.

This study may not have any direct benefits for child enrolled, however it will help us find out if the management of sepsis and/or septic shock in children using the proposed treatment of fluid-sparing and metabolic support reduces complications, hospital length of stay and improves outcomes for children.


Where possible, we will talk to parents/guardians before starting the treatment and get the consent to include their child in the trial. However, due to the emergency nature of sepsis and septic shock, it is anticipated that in certain situations timely informed consent may not be feasible in which case consent to continue (delayed consent) will be used.  Our Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee has given this study special approval, whereby children can be included in the study before you have given consent. This is because the RESPOND Study does not put child at risk of any harm. Informed consent will be sought from the parent/guardian as soon as possible once the child has been stabilized and the parent/guardian has had time to adjust to the emergency environment.

The Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) has approved this study. If you have any concerns and/or complaints about the project, the way it is being conducted or your child’s rights as a research participant, and would like to speak to someone independent of the project, please contact the HREC Coordinator.
t: 3069 7002
e: CHQETHICS@health.qld.gov.au

Participating sites

  • Queensland Children’s Hospital, Brisbane, Queensland, Australia
  • Gold Coast University Hospital, Gold Coast, Queensland, Australia
  • Sunshine Coast University Hospital, Birtinya, Queensland, Australia
  • Westmead Children’s Hospital, Sydney, New South Wales, Australia
  • Randwick Children’s Hospital, Sydney, New South Wales, Australia
  • Princess Margaret Children`s Hospital, Perth, Western Australia
  • Starship Children’s Hospital, Auckland, New Zealand


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Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
Paediatric Critical Care Research Group
Level 6, 62 Graham Street
South Brisbane, Qld, 4101

Central team (CCHR – Brisbane)

For study queries contact

Study Coordinators

Zoe Sever
e: z.sever@uq.edu.au
Natalie Sharp
e: natalie.sharp2@health.qld.gov.au

e: respond@uq.edu.au

Principal Investigator

Dr Sai Raman
e: sainath.raman@uq.edu.au