Evaluating the use of a lower blood pressure target to guide drug treatment in critically ill children with low blood pressure

Plain English Summary

Background and study aims
In critically ill children, hypotension (low blood pressure) is common, especially in patients with severe infections and is a key feature of shock. Untreated, hypotension compromises tissue perfusion (blood flow) and organ function, with an increased risk of multiple organ failure. Vasoactive agents (which also stimulate the heart) and fluids are mainstays of treatment. Central venous catheters (a tube inserted into a large vein) are often used to help with treatment. Around 80% of the 20,000 children admitted to UK PICUs each year receive fluid bolus therapy and around 30% receive vasoactive drugs at some point during their intensive care stay.
Though interventions to treat hypotension may be lifesaving, there are also harms. Excessive fluids are associated with prolonged Pediatric Intensive Care Unit (PICU) stay and increased illness and death. Most vasoactive drugs induce vasoconstriction (constriction of blood vessels), which may reduce blood flow and cause other effects. Central venous catheters are usually sited to give the patient vasoactive drugs; these catheters are associated with an increased risk of thrombosis (blood clots) and infection, particularly in very small children.
Current guidelines recommend maintaining mean arterial pressure (MAP – mean arterial or average blood pressure) for children with sepsis around the 50th centile for age. However, these guidelines are based on low-quality evidence and no guidance is given for an upper MAP limit.
In adults with sepsis, the 5th centile value for mean blood pressure has been recommended. This strategy has been examined in a number of recent studies, all of which investigated a permissive blood pressure target in critically ill adults with a variety of pathology. None of these studies demonstrated any significant difference in the overall death rate between the lower and higher blood pressure target groups. However, a pooled analysis found an increased incidence of supraventricular tachycardia (abnormally fast heart rhythm) in the higher blood pressure target group and an increased death rate in those patients in the higher blood pressure target group enrolled after over 6 h of vasopressors (medicines that constrict blood vessels).
The aim of this study is to find out whether the benefits associated with a lower blood pressure target will outweigh the risks associated with lower MAP values and the medical interventions needed to raise blood pressure, improving outcomes and decreasing costs.

Who can participate?
Children under 16 years old admitted to one of the PICUs on invasive mechanical ventilation, who have started treatment with a vasoactive drug for hypotension in the last 6 hours and are expected to continue for at least 6 hours.

What does the study involve?
Patients will be randomly allocated between the intervention and control groups. The intervention group are treated with a permissive blood pressure target (MAP target of 5th centile for age). The permissive blood pressure target is to be followed at any point the patient needs vasoactive drugs during this critical care unit admission. The decision to discontinue vasoactive agents will be determined by the patients' ability to maintain the MAP target without vasoactive drugs. All other care will be at the discretion of the treating clinical team. The control group receive usual care. No specific blood pressure target will be set for usual care, with treating clinicians directed to follow their standard practice.

What are the possible benefits and risks of participating?
No promises will be made to participants. There are potential risks and benefits of being in both the intervention and control group but the overall effect is not known, which is why this study is needed. Very low blood pressure can be associated with organ damage or may even be life-threatening. However, interventions to treat hypotension may be lifesaving, there are also harms. Excessive fluids are now known to be associated with prolonged paediatric intensive care unit stay and increased death rate. Most vasoactive drugs commonly used in children cause vasoconstriction, which may reduce blood flow with secondary effects on organ function. Central venous lines are usually sited to administer vasoactive drugs; these are associated with an increased risk of thrombosis and infection, particularly in very small children in whom the central venous catheter may occupy most of the vessel lumen (the inside space). The results of this study will benefit critically ill children treated in PICU.

Where is the study run from?
Intensive Care National Audit & Research Centre (UK)

When is the study starting and how long is it expected to run for?
August 2020 to November 2026

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr David Inwald
di260@cam.ac.uk

Study website

Contact information

Dr David Inwald
Scientific

Paediatric Intensive Care Unit
Addenbrooke’s Hospital
Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom

ORCID ID	0000-0001-9518-7821
Phone	+44 (0)7917 373689
Email	di260@cam.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone	+44 (0)1223 217418
Email	research@addenbrookes.nhs.uk
Website	http://www.cuh.org.uk/
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

15/05/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 01/05/2024 to 30/11/2025.
2. The overall study end date was changed from 31/01/2025 to 30/11/2026.
3. The intention to publish date was changed from 31/01/2026 to 31/05/2027.
4. Publication reference added.
11/08/2023: The following changes have been made:
1. A drug/device/biological/vaccine name was added.
2. The study website was added.
3. The participant information sheet link was amended.
4. The inclusion criteria were updated.
5. The exclusion criteria were updated.
02/03/2022: The following changes have been made:
1. The recruitment start date has been changed from 02/08/2021 to 01/11/2021.
2. The recruitment end date has been changed from 02/02/2024 to 01/05/2024.
21/05/2021: Trial's existence confirmed by the NIHR.