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Read the PCCM Global Critical Care Article of the month | June 2026

We are excited to present the fourth edition of the PCCM Global Critical Care Article of the Month! Every 2 months, a team of pediatric intensive care experts from WFPICCS selects one outstanding paper from Pediatric Critical Care Medicine, the Official Journal of WFPICCS, to spotlight key advances, emerging evidence, and perspectives shaping our field.

This initiative aims to foster continuous learning and reflection, encouraging our global community to engage with the latest research that informs and improves the care of critically ill children worldwide.

The selected Article for June 2026 is Protocolized Evaluation of Permissive Blood Pressure Targets Versus Usual Care (PRESSURE): Statistical Analysis Plan for the PRESSURE Trial

Expert commentary by Janet Mattsson

Why This Question Matters

Hypotension, abnormally low blood pressure, is one of the most common and potentially life-threatening problems encountered in critically ill children admitted to a Paediatric Intensive Care Unit (PICU). When a child’s blood pressure drops dangerously low, every organ in the body is at risk of not receiving enough oxygen-rich blood.

To correct hypotension, clinicians currently use a combination of vasoactive drugs (medications that tighten blood vessels or strengthen heart contractions), intravenous fluids, and central venous catheters. Although these interventions can be life-saving, they each carry their own risks. Vasoactive drugs can reduce blood flow to the gut and skin; large volumes of IV fluid can cause harmful fluid overload; and central lines are associated with infection risk. A 2018 systematic review confirmed that fluid overload is independently linked to worse outcomes in critically ill children.1

A fundamental but unresolved clinical question is: how aggressively should we treat a low blood pressure reading? The threshold at which a clinician intervenes ,and how hard they push to normalise blood pressure, varies enormously between units, between clinicians, and between countries. There are no universally agreed, evidence-based blood pressure targets for ventilated children in intensive care. This variation in practice is not trivial: it directly determines how much vasopressor drug a child receives, how much fluid they are given, and for how long.

The PRESSURE trial was designed to answer this question head-on: is a ‘permissive’ blood pressure target ,one that tolerates a somewhat lower-than-normal mean arterial pressure (MAP), specifically just above the age-specific fifth centile ,as safe and effective as, or better than, usual care? The fifth centile means the bottom 5% of the normal range for a child of that age; targeting just above this point means accepting a blood pressure that, while low, is not critically so, and may allow clinicians to use fewer and lower doses of vasopressor drugs.2

 What Does This Study Add?

It is important to understand that this publication is not the clinical results paper ,those are yet to come. It is the pre-registered Statistical Analysis Plan (SAP) for the PRESSURE trial. Publishing the SAP before results are analysed is rigorous, trustworthy science: it prevents researchers from changing their analysis after seeing the data, eliminating the temptation to ‘cherry-pick’ results. The SAP follows published international guidelines for clinical trial reporting.3

Importantly, this paper does not provide evidence that permissive blood pressure targets improve clinical outcomes. Rather, it describes in advance how the forthcoming trial data will be analysed, thereby safeguarding methodological integrity and reducing the risk of analytical bias.

The SAP makes the following important contributions:

  • A rigorous primary outcome: The composite of 30-day mortality and duration of invasive mechanical ventilation (IMV) ,capturing both survival and the burden of intensive care. Patients who die are assigned the worst score, ensuring death is never obscured by ventilator duration alone.11
  • A pre-defined analysis method: The Wilcoxon–Mann–Whitney (rank-sum) test10, chosen because it can handle the combined outcome of death and ventilator days without imposing unrealistic statistical assumptions.
  • Transparent handling of adherence: The trial uses a ‘deferred consent’ model (consent sought after randomisation in emergency situations).7 The SAP specifies exactly how protocol deviations will be classified and accounted for in sensitivity analyses.
  • A comprehensive health economic analysis: Uniquely, the PRESSURE trial includes a full cost-effectiveness analysis ,calculating quality-adjusted life years (QALYs) using validated paediatric instruments8,9 and reporting incremental costs and net monetary benefit at 12 months, following NICE methodology.17
  • Power to detect clinically meaningful differences: The trial is powered (90%) to detect a 2% reduction in mortality (13% to 11%) and an 18-hour reduction in mean ventilator duration among survivors. This required a sample size calculation based on real-world observational data from 22 UK PICUs (the FEVER study).4 A total of 1,900 participants across 21 UK PICUs are required.
  • Subgroup and sensitivity analyses pre-specified: Interactions with age, presence of infection, neurological comorbidity, and severity of illness score (PIM-3)12 are pre-defined, following published guidelines for subgroup analysis.13,14,15

By publishing this plan before the trial completes recruitment, the PRESSURE team ensures that when results are announced, the world can trust they were not shaped by knowledge of what the data showed.

Beyond the Research, in the Clinical Setting

In everyday PICU practice, blood pressure management is often driven by habit, local culture, and clinical instinct rather than by robust evidence. Clinicians look at a blood pressure reading, compare it with an internal reference, and decide whether to increase a vasopressor infusion or give more fluid. This decision, made dozens of times a day across every PICU in the world, has never been subjected to a properly powered randomised trial in ventilated children.

Although highly pragmatic, the trial has inherent limitations. Blinding is not feasible, usual care is intentionally heterogeneous, and blood pressure alone may not fully reflect tissue perfusion. Consequently, interpretation of the final results will need to consider the broader haemodynamic context.

The PRESSURE trial’s intervention is deliberately simple: in the permissive arm, clinicians aim to keep MAP just above the age-specific fifth centile (a threshold that indicates the child is not in critical haemodynamic collapse), while actively avoiding the escalation of vasopressor therapy if blood pressure sits in this lower-but-acceptable range. In the usual care arm, clinicians manage blood pressure according to their normal practice, without a protocolised target. This design mirrors real-world clinical decision-making and makes the results directly applicable to bedside practice.2

If the results show that permissive targets are as good as, or better than, usual care in terms of mortality and ventilator duration, then clinicians will have powerful, trial-level evidence to justify a fundamental shift in practice. This strategy may reduce exposure to vasoactive drugs and fluid administration while maintaining comparable clinical outcomes. This is not about neglecting sick children, it is about giving only what is necessary and avoiding the harms that come from over-treating.

The 21 UK PICUs participating in the trial represent the full diversity of paediatric critical care provision in the NHS, from large tertiary referral centres to smaller regional units, making the results applicable across a wide range of clinical settings. The use of deferred consent7 allows enrolment of even the most critically ill children, including those who may not survive long enough for their parents to give traditional prospective consent, ensuring the trial captures the highest-risk patients in whom the question matters most.

Why this Matters to Children

Every child admitted to a PICU with hypotension on a ventilator is in a vulnerable and frightening situation. The drugs and procedures used to treat low blood pressure ,vasopressors, large-volume intravenous fluid boluses, and central venous catheters ,are themselves a source of harm. Fluid overload is associated with worse outcomes in critically ill children1; high-dose vasopressors can reduce blood flow to the gut, skin, and kidneys; and central lines carry infection risk. Every extra day on a mechanical ventilator increases the risk of ventilator-associated complications and delays the child’s recovery.

If permissive blood pressure management allows vasopressors to be weaned sooner without worsening outcomes, children could:

  • spend fewer days on mechanical ventilation
  • receive lower cumulative doses of vasoactive drugs
  • have fewer complications from fluid overload and line-associated infections
  • be more alert and comfortable during their ICU stay
  • be discharged to the ward, and ultimately home, sooner

The trial also captures functional status changes between PICU admission and discharge using validated paediatric tools, the Paediatric Cerebral Performance Category and the Paediatric Overall Performance Category, which assess the child’s neurological and overall physical function. Health-related quality of life will be measured at 12 months using age-appropriate questionnaires completed by the child or their parents8,9, providing a long-term view of whether the treatment strategy affected the child’s life beyond the ICU.

For families, a shorter PICU stay and lower burden of invasive treatment translates directly into less anxiety, fewer days away from home and siblings, and faster return to normal family life. The health economic analysis will also quantify the value of any quality-of-life gains in a way that is meaningful to healthcare systems and to families alike.

What can PICU’s Around the World Learn?

Although PRESSURE is a UK-based trial, its implications are global. Hypotension in critically ill children is managed in PICUs on every continent, and the fundamental clinical question, how low is too low?, is universal. Several key lessons can be drawn now, even before the results are published.

Evidence-based thresholds matter

The fifth-centile MAP target used in PRESSURE is physiologically grounded and age-adjusted, it can be applied in any setting where non-invasive or invasive blood pressure monitoring is available. Blood pressure is only one component of haemodynamic assessment and should always be interpreted alongside markers of tissue perfusion. PICUs should consider the importance of age-adjusted blood pressure assessment rather than relying on fixed MAP thresholds. PICUs that currently use arbitrary fixed thresholds (e.g., MAP > 50 for all ages) should consider moving towards age-adjusted targets regardless of the PRESSURE result, as these better reflect the physiology of children at different developmental stages.

Less is sometimes more

The permissive philosophy challenges the instinct to aggressively normalise every abnormal number. In resource-limited settings, reducing unnecessary vasopressor use has obvious practical benefits: lower drug costs, reduced central-line placement, and fewer iatrogenic complications. Even in well-resourced systems, there is a growing recognition that ‘treatment burden,’ the accumulation of drugs, lines, and interventions, is itself a source of harm.1

Protocol-driven care reduces unwarranted variation

The PRESSURE trial demonstrates how a simple, standardised protocol can be implemented across 21 diverse units without disrupting clinical workflows. Any PICU could adopt a similar protocolised approach to blood pressure management, using the age-specific fifth centile as a floor rather than a fixed arbitrary target. The trial’s deviation classification framework2 also provides a practical model for monitoring adherence in quality improvement initiatives.

Statistical analysis plan transparency as a global standard

The publication of a prospective SAP sets a methodological benchmark for paediatric critical care research.3 Trials that pre-specify their primary outcome, analysis method, and subgroup analyses are far less susceptible to bias. PICUs and research groups worldwide should advocate for this standard in all future randomised trials, not just in paediatric intensive care.

Health economics cannot be ignored

Even in well-funded healthcare systems, demonstrating cost-effectiveness is increasingly required before new treatments or treatment strategies are adopted at scale. The inclusion of a full economic evaluation17,18,19, measuring QALYs and incremental net monetary benefit at 12 months ,sets a standard that future paediatric critical care trials should aspire to meet.

Consent models in emergency paediatric research

The PRESSURE trial’s use of deferred consent, randomising before consent in life-threatening emergencies, is an ethically approved model7 that other countries are increasingly adopting. This approach is essential for conducting rigorous RCTs in critically ill children, where the window for enrolment may be very narrow and the child’s condition too unstable to allow for traditional prospective consent processes.

Take Home Message

The PRESSURE trial is asking one of the most fundamental questions in paediatric critical care: should we accept a lower blood pressure in a ventilated child rather than escalating vasopressor drugs to achieve a higher target? The hypothesis, that the harms of aggressive vasopressor therapy may outweigh the risks of a permissive blood pressure approach, is scientifically plausible, clinically important, and, until now, unanswered by rigorous evidence.

This statistical analysis plan paper3 is the methodological foundation that will allow the world to trust the PRESSURE trial’s results. By pre-specifying every analysis,primary, secondary, sensitivity, subgroup, and health economic, before the data are unblinded, the PRESSURE investigators have committed to a level of scientific transparency that is the gold standard for clinical trial reporting. The SAP defines how 30-day mortality and mechanical ventilation duration will be combined into a single composite outcome, how missing data will be handled, and how cost-effectiveness will be measured.

For clinicians at the bedside, this trial matters because the treatment of hypotension in mechanically ventilated children has never been subjected to a properly powered randomised controlled trial. Decisions made many times every day, whether to increase a vasopressor infusion, give another fluid bolus, or accept a MAP reading just above the fifth centile, will, for the first time, be informed by high-quality trial evidence when results are published.

PRESSURE has the potential to redefine haemodynamic management in ventilated children if the trial demonstrates non-inferiority or superiority of the permissive strategy.

For the 1,900 children who will be enrolled4, and for the tens of thousands who will be treated in PICUs globally once results are available, PRESSURE offers the prospect of care that is both better and kinder, less treatment where less is sufficient, and more confidence in every clinical decision.

References

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  2. Darnell R, Brown A, Laing E, et al; PRESSURE Trial Investigators on behalf of the PCCS-SG. Protocol for a randomized controlled trial to evaluate a permissive blood pressure target versus usual care in critically ill children with hypotension (PRESSURE). Pediatr Crit Care Med. 2024;25:629–637.
  3. Gamble C, Krishan A, Stocken D, et al. Guidelines for the content of statistical analysis plans in clinical trials. JAMA. 2017;318(23):2337–2343.
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  17. NICE. Health technology evaluations: the manual. Available at: https://www.nice.org.uk/process/pmg36. Accessed August 28, 2025.
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