The clinical problem is rooted in simple mechanics. After traumatic impact, the spinal cord swells with edema and hemorrhage, yet it is confined within the rigid vertebral canal and an inelastic dural sac — a closed compartment with almost no room to spare. As pressure within the injured segment rises, it squeezes the small vessels supplying the cord from the outside, and blood flow falls. Starved of oxygen, neural tissue slides into a cascade of secondary injury: excitotoxic neurotransmitter release, mitochondrial failure, free radical generation, and progressive cell death that can convert a partial injury into a complete, permanent one. Guidelines already recognize the stakes, recommending elevated blood pressure targets after acute injury, because systemic perfusion is currently the only lever clinicians can pull. But without knowing the pressure inside the injured cord itself, every patient is treated with the same blunt instrument: push the mean arterial pressure up and hope. Neurosurgeons in the field have long argued that this is equivalent to managing traumatic brain injury without measuring intracranial pressure — a practice medicine abandoned decades ago after it became clear how dangerous flying blind could be.

The technology described in the new paper adapts a method proven in the brain. During the initial decompression and stabilization operation, surgeons insert a slim pressure transducer — essentially the strain-gauge technology long used for intracranial pressure monitoring — through the dura so that the sensor sits intrathecally at the injured cord segment. The device reports intraspinal pressure, the pressure within the dural tube surrounding the cord, continuously and in real time. From it flows a second, more meaningful number: spinal cord perfusion pressure, calculated as mean arterial blood pressure minus intraspinal pressure, a direct analogue of the cerebral perfusion pressure formula that anchors head-injury intensive care. Perfusion pressure is the driving force pushing blood through the cord’s microcirculation; when it falls too low, ischemia follows no matter how reassuring the systemic vital signs appear. Because the probe samples many times per second, clinicians can also derive indices of spinal cord autoregulation — the injured vasculature’s capacity to hold blood flow constant as blood pressure drifts. In earlier single-center work, higher intraspinal pressures and lower perfusion pressures tracked with worse neurological recovery, evidence that the measurements capture meaningful physiology rather than electronic noise.

Pressure is only the first layer of information. In most patients the teams added a microdialysis catheter: a fine hollow fiber tipped with a semipermeable membrane, perfused at an ultra-slow rate with sterile artificial cerebrospinal fluid. Small molecules in the injured cord’s extracellular space — glucose, lactate, pyruvate, glycerol, and the excitatory amino acid glutamate — diffuse across the membrane into the perfusate, which is collected in microvials changed at the bedside and analyzed. The lactate-to-pyruvate ratio serves as a sensitive flag for cellular energy failure, rising when mitochondria cannot exploit oxygen and cells fall back on anaerobic metabolism; glycerol signals membrane breakdown and cell death; glutamate marks excitotoxic stress. Roughly two in five patients in the new series also carried a third probe measuring tissue oxygen tension directly within the injured cord, converting the abstract idea of cord oxygenation into a number on a monitor. Together, the three probes turn the injury site into something closer to an instrumented organ: pressure, perfusion, oxygen, and metabolism, all sampled continuously through the most dangerous days after trauma.

What separates the new report — first authored by Love C. Ilochonwu — from earlier single-center studies is its scale and diversity. The analysis pooled experience from intensive care units at Aarhus University Hospital in Denmark, University Hospitals Leuven in Belgium, University Medical Centre Ljubljana in Slovenia, St George’s Hospital in London, and Hospital Universitario 12 de Octubre in Madrid. The researchers distributed a standardized questionnaire to all participating sites and retrospectively extracted each patient’s course from the medical record. The 109 adults had sustained acute, severe traumatic spinal cord injuries, and the cohort was severely affected: 58.7% were grade A on the American Spinal Injury Association Impairment Scale, meaning complete injury with no motor or sensory function preserved below the lesion; 19.3% were grade B, with sensory but no motor function spared; and 22.0% were grade C. The probes, placed during the initial surgery, stayed in situ for 5.3 ± 0.2 days on average — a window spanning precisely the period when cord swelling peaks and hemodynamic instability is most dangerous, and long enough to generate dense physiological datasets for every patient.

The results answer the two questions skeptics ask first: do the probes work, and do they stay where surgeons put them? Every patient received an intraspinal pressure probe; 67.9% also received microdialysis, and 44.0% also received an oxygen probe. Signal quality was rated good most of the time in 89.0% of patients for pressure, 95.9% for microdialysis, and 79.2% for oxygen — a performance envelope comparable to established neuromonitoring in the brain. Placement was verified with computed tomography in 89.0% of patients, and the scans confirmed good probe position in every case but one. That record matters, because a probe that has migrated or malpositioned measures the wrong tissue or nothing at all, silently corrupting the numbers on which clinical decisions would rest. The oxygen sensors were the least consistent of the three technologies, but they still delivered good signals most of the time in nearly four of every five patients — a respectable figure for instruments that must function inside a swollen, moving, metabolically hostile environment for close to a week.

Safety was the study’s central question, and the findings are reassuring with important caveats. The most common complication was cerebrospinal fluid leak, seen in 20.8% of patients — an expected consequence of passing a probe through the dura. Most leaks were straightforward to manage: 81.8% required only bedside suturing, 9.1% needed temporary lumbar drainage of cerebrospinal fluid to offload pressure, and 9.1% required early removal of the probe. Pseudomeningocele, a pocket of cerebrospinal fluid collecting beneath the wound, developed in 10.4% of patients; 81.8% of these were asymptomatic and needed nothing more than observation, while 18.2% required surgery. Wound infections occurred in 4.7% of patients, resolving with antibiotics alone in 60.0% of cases and requiring surgical debridement in the remainder. Set against these manageable events is what the team never observed across the entire cohort: not one case of spinal cord damage from the probes themselves, not one meningitis, not one spinal hematoma. In the authors’ conclusion, the main risks of intrathecal monitoring are CSF leak, pseudomeningocele, and wound infection — recognizable, treatable complications — while the feared catastrophic events simply did not occur.

The most provocative material concerns what the probes reveal at the bedside. Although the signals in this series were collected primarily for research, the authors present examples of their potential clinical value: real-time visualization of spinal cord perfusion pressure, of cord autoregulation, and of tissue oxygenation and metabolism. In practice, that means an intensivist can watch whether raising blood pressure with fluids and vasopressors genuinely improves perfusion of the injured segment, or whether the cord’s vessels have lost the capacity to respond. It can expose the patient whose perfusion pressure looks adequate on paper while microdialysis shows a climbing lactate-to-pyruvate ratio — tissue starving despite acceptable numbers. It can reveal oxygen desaturation within the cord that no systemic monitor would detect. Earlier work by the London group found that intraspinal pressure and perfusion pressure measured in the first days after injury predicted neurological outcome, lending the signals prognostic weight as well as physiological meaning. The parallel with neurocritical care for the brain is hard to miss: intracranial pressure monitoring helped transform traumatic brain injury from intuitive management into protocolized, physiology-guided care, and spinal cord monitoring now stands roughly where brain monitoring stood a generation ago.

The authors are candid about limits. This was a retrospective case series without a control group; it establishes feasibility, signal quality, and safety, not benefit. Whether patients managed with monitoring-guided perfusion targets recover more function than those managed conventionally is precisely the question that prospective trials must now answer, and the multi-center infrastructure demonstrated here looks like scaffolding for exactly those studies. Retrospective data can also under-ascertain complications, although the thoroughness of the safety accounting and the consistency of results across five institutions, five surgical teams, and five intensive care cultures argue that the technique is robust beyond any single expert center. The research was supported by the Marie Skłodowska-Curie Actions SOPRANI network, Wings for Life, UK Research and Innovation, and the UK National Institute for Health and Care Research. For the hundreds of thousands of people who sustain traumatic spinal cord injuries worldwide each year, the immediate message is narrow but significant: the tools to see inside the injured cord exist, they work in ordinary intensive care units, and their risk profile is now quantified. The era of treating the injured spinal cord as a black box may finally be closing.

The protocol was developed through the CLINICCA initiative, a global effort focused on the clinical use of continuous cerebral autoregulation information. A 2023 survey of 44 experts found that approximately half were already using an autoregulation index to influence clinical decisions, but only 39% of those clinicians had incorporated the information into a written local protocol. PRx was the most frequently used index among respondents. The new workgroup therefore invited clinicians who used PRx or PRx-derived cerebral perfusion pressure targets in adult or paediatric traumatic brain injury to edit a common template, share examples of local practice and, where available, submit written protocols. Eight invited experts responded from centres with established protocols or structured practice, while two additional clinicians contributed paediatric applications. After excluding practices unrelated to traumatic brain injury, the authors synthesised the feedback into a five-part framework.

PRx is designed to provide a continuous estimate of how well cerebral blood vessels react to changes in perfusion pressure. Under normal conditions, small arteries and arterioles in the brain constrict or dilate to help maintain relatively stable blood flow despite fluctuations in arterial blood pressure. This buffering process is known as cerebral autoregulation. When autoregulation is impaired after traumatic brain injury, changes in arterial pressure may be transmitted more directly to the cerebral circulation, increasing the risk of inadequate perfusion or pressure-driven swelling. PRx is calculated from slow waves in arterial blood pressure and intracranial pressure, using a moving Pearson correlation over roughly five minutes. A positive correlation generally suggests impaired pressure reactivity, whereas a lower or negative value is more consistent with preserved vascular responsiveness. Because the calculation is global and depends on high-quality, continuously streamed physiological signals, PRx should not be interpreted as a direct measurement of regional blood flow or tissue oxygenation.

The first component of the harmonised protocol uses an elevated or persistently abnormal PRx value as a trigger for clinical review. In the participating centres, a threshold near 0.3 was commonly used, although published studies have examined values ranging from approximately 0.2 to 0.5. When PRx indicates impaired reactivity, clinicians may check the patient’s head and neck position, verify arterial and intracranial pressure transducers, inspect signal quality and review intracranial pressure, cerebral perfusion pressure, carbon dioxide and brain-tissue oxygenation. Other possible contributors include fever, sedation changes, ventilator alterations, seizures, systemic hypotension and evolving intracranial pathology. The workgroup stresses that an abnormal PRx is a warning signal rather than an automatic instruction to intervene. If conventional physiological variables remain acceptable and no corroborating evidence of cerebral hypoperfusion or dangerous intracranial hypertension is present, some centres would continue observation rather than launch a treatment escalation.

The second component concerns intracranial hypertension management and reflects a counterintuitive feature of autoregulation-guided care. When PRx is impaired, raising arterial pressure may not produce the expected reduction in intracranial pressure and can potentially increase cerebral blood volume or worsen pressure transmission. Several contributors therefore consider reducing arterial pressure, cautiously and under defined safety conditions, when impaired reactivity accompanies intracranial hypertension. By contrast, preserved PRx may support a carefully monitored increase in arterial pressure or cerebral perfusion pressure as part of a “MAP or CPP challenge.” If the cerebrovascular bed can constrict appropriately, increasing perfusion pressure may improve vascular tone and help lower intracranial pressure. The protocol does not present either strategy as universal. Each decision must be considered alongside the patient’s neurological examination, imaging, systemic circulation, oxygen delivery and other neuromonitoring data.

The third and fourth components address cerebral perfusion pressure targets derived from PRx. Cerebral perfusion pressure is commonly approximated as mean arterial pressure minus intracranial pressure, and it is a key determinant of the pressure gradient driving blood through the brain. A fixed target may be useful, but it cannot account for the changing autoregulatory state that often follows severe brain injury. One derived target is CPPopt, or optimal cerebral perfusion pressure, the pressure associated with the lowest PRx over a range of observed perfusion pressures. Other approaches estimate the lower limit of reactivity, where autoregulatory capacity begins to fail, or the upper limit of reactivity, where pressure may become excessive. More than half of the contributing centres reported using one or more derived targets to optimise cerebrovascular physiology, although the specific algorithms, thresholds, timing and degree of clinical reliance varied substantially.

The protocol also recognises that perfusion targets may be used to reduce treatment burden rather than simply maximise physiological measurements. If a patient maintains stable cerebral autoregulation and other monitoring signals at a lower pressure, clinicians may be able to avoid unnecessary fluid loading, high doses of vasopressors or prolonged exposure to interventions that can damage the heart, lungs or kidneys. This approach seeks a balance between supporting the injured brain and limiting harm elsewhere in the body. However, the authors caution that PRx is a global summary measure and may behave differently in diffuse injury compared with focal contusions, haematomas or areas of infarction. A pressure that appears favourable globally may not guarantee adequate perfusion in every vulnerable region. For that reason, derived targets should be treated as dynamic decision-support information, not as rigid numbers that override the clinical picture.

The fifth component places PRx within multimodality monitoring, combining it with measurements such as brain-tissue oxygen tension, transcranial Doppler, near-infrared spectroscopy, electroencephalography, arterial carbon dioxide and end-tidal carbon dioxide. In one possible decision pathway, a low brain-tissue oxygen signal accompanied by impaired PRx could prompt assessment of perfusion pressure, oxygen delivery and intracranial pressure together rather than isolated treatment of any single value. Preserved PRx may support a cautious perfusion-pressure challenge when oxygen delivery appears pressure-dependent. Paediatric centres described particularly intensive use of multimodal information, including PRx, transcranial Doppler, near-infrared spectroscopy and brain-tissue oxygenation, to balance sufficient cerebral perfusion against control of intracranial volume. Yet multimodal strategies were among the least consistently adopted elements of the survey, reflecting differences in equipment, staffing, expertise and confidence in how the signals should be combined.

A major message from the workgroup is that technical reliability is inseparable from clinical interpretation. PRx requires continuous acquisition of arterial blood pressure and intracranial pressure at adequate sampling rates, correct signal calibration, reliable time synchronisation and effective removal or recognition of artefacts. Disconnections, damping, flushing, waveform distortion, patient movement and abrupt therapeutic changes can create misleading correlations. The calculation also depends on slow spontaneous fluctuations; a flat or highly unstable signal may generate a number without providing meaningful physiological information. Derived CPP targets can be similarly unreliable when the data contain insufficient variation, when autoregulation is changing rapidly or when the algorithm is applied without quality-control indicators. The supplementary technical addendum accompanying the article provides practical advice for data acquisition, preprocessing and bedside interpretation, but the authors note that standardisation across devices and software remains incomplete.

The workgroup’s findings are likely to attract attention because they capture a field already moving into clinical practice before definitive outcome evidence has arrived. Observational studies have linked cerebrovascular reactivity with prognosis after traumatic brain injury, and a phase-two randomised feasibility trial found that targeting CPPopt was safe and feasible in selected adults. Nevertheless, no strong evidence yet demonstrates that treating patients according to PRx improves long-term neurological outcomes compared with conventional management. The new protocol therefore serves two purposes: it offers clinicians a transparent starting point for local implementation, and it exposes the areas where practice is most uncertain. Agreement was strongest around using PRx to prompt reassessment and to inform intracranial-hypertension management. The greatest variation involved CPP-derived targets and multimodal algorithms. By making these differences visible, the CLINICCA workgroup hopes to encourage collaboration, improve reproducibility and support future prospective trials capable of testing whether autoregulation-guided care can change the course of traumatic brain injury.

Subject of Research: Use of continuous cerebral autoregulation monitoring and the pressure reactivity index (PRx) to guide management of adult and paediatric traumatic brain injury patients with intracranial pressure monitoring.

Article Title: A Harmonised Protocol for the Use of PRx in Adult and Paediatric TBI Patients with ICP Monitoring: CLINICCA Workgroup Output

Article References: Beqiri E, Lavinio A, Dias C, et al. “A Harmonised Protocol for the Use of PRx in Adult and Paediatric TBI Patients with ICP Monitoring: CLINICCA Workgroup Output.” Neurocritical Care (2026). Related references include Czosnyka et al., “Continuous assessment of the cerebral vasomotor reactivity in head injury,” Neurosurgery (1997); Tas et al., the COGiTATE feasibility randomized controlled trial, Journal of Neurotrauma (2021); and Beqiri et al., studies of CPPopt and the lower limit of reactivity.

Image Credits: AI Generated

DOI: 10.1007/s12028-026-02595-z

Keywords: PRx, CPPopt, cerebral perfusion pressure, cerebral autoregulation, traumatic brain injury, intracranial pressure, paediatric neurocritical care, multimodal monitoring, lower limit of reactivity, upper limit of reactivity.