Early Blood Pressure Targets in Acute Spinal Cord Injury

Background

It’s pretty well agreed that management of blood pressure is really important in neurological injury. We usually think about this in terms of brain injury, but the general teaching is that the same applies to spinal cord injury too. It’s neurological tissue and connected to the brain, so it makes sense. It’s something we’ve talked about a lot on St Emlyn’s over the years, in the context of traumatic brain injury (TBI), stroke, and post–cardiac arrest care. The central principle is that injured neural tissue loses it’s normal homeostatic mechanisms for blood flow, and therefore becomes very sensitive to hypoperfusion, and secondary injury as a result.

Spinal cord injury (SCI) is usually considered in the same way, and guidelines in Virchester state that we follow the same BP targets in cord injury that we do for brain injury. The principle is that following the primary mechanical insult, a cascade of secondary injury evolves over hours to days, driven by ischaemia, inflammation, oedema, and microvascular dysfunction. Clinicians have assumed that maintaining a normal or supranormal mean arterial pressure (MAP) or systolic pressure (SBP) might preserve spinal cord perfusion and improve neurological recovery.

Guidelines have reflected this belief. The 2013 American Association of Neurological Surgeons and Congress of Neurological Surgeons guidelines recommended targeting a MAP of 85–90 mm Hg for seven days following acute SCI. More recent guidance softened this to targets around 75–80 mm Hg, but the underlying evidence base has remained weak, largely observational, and prone to confounding.

This should sound familiar. In traumatic brain injury, St Emlyn’s has repeatedly explored the dangers of extrapolating physiology into dogma without high-quality trial evidence. We’ve written extensively about how “higher is better” for blood pressure may not always hold true, and why accurate measurement (often via arterial lines) is essential if we’re going to pursue tight haemodynamic targets at all. There are whole bunch of trials in lots of other conditions (e.g. sepsis) where bigger is better has not turned out to be the case.

It’s great to see a multicentre randomised clinical trial by Sajdeya et al. that addressed exactly this issue. and puts the spotlight on our current dogma. The abstract is below, but as always please read the full paper yourself and come to your own conclusions.

Abstract

Objective To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

Design, Setting, and Participants This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

Interventions Patients were equally randomized to augmented (>85-90 mm Hg) or conventional (>65-70 mm Hg) mean arterial pressure for 7 days or until intensive care unit discharge.

Main Outcomes and Measures Primary end points were change in motor and sensory American Spinal Injury Association Impairment Scale scores from baseline to 6 months. Safety end points included organ dysfunction and complications.

Results The trial randomized 92 patients (mean [SD] age, 53.78 [18.74] years; 76 [83%] male). At 6 months, 38 patients had completed follow-up and 15 had died. Among survivors, there were no mean (SD) differences in change from baseline in upper extremity motor scores (34.95 [3.25] vs 32.95 [3.65]; difference, 2.48; 95% CI, −5.93 to 10.90; P = .55), lower extremity motor scores (18.53 [4.62] vs 19.95 [4.59]; difference, −4.56; 95% CI, −16.11 to 7.03; P = .43), or total sensory scores (108.47 [12.49] vs 130.89 [14.87]; difference, −32.00; 95% CI, −65.40 to 1.40; P = .06) comparing the augmented and conventional groups. The augmented group had higher mean (SD) modified Sequential Organ Failure Assessment scores (excluding cardiovascular components) at day 3 (1.65 [1.79] vs 0.80 [1.10]; difference, 0.85; 95% CI, 0.23-1.47; P = .008) and day 6 (1.55 [1.82] vs 0.80 [1.35]; difference, 0.74; 95% CI, 0.05-1.44; P = .04), longer mechanical ventilatory support (9.44 [15.27] vs 3.78 [8.42] days; difference, 5.67 days; 95% CI, 0.48-10.85 days; P = .03), and more respiratory complications (36 [78%] vs 18 [39%]; risk difference, 40%; 95% CI, 22%-58%; P < .001) than the conventional group. No differences in mortality or other secondary outcomes were observed.

Conclusions Although underpowered, this randomized clinical trial of patients with spinal cord injury did not demonstrate better neurologic recovery comparing early augmented and conventional blood pressure and calls this practice into question. Further study is needed to identify groups who may benefit from augmenting blood pressure and determine potential harm mechanisms.

Trial Registration ClinicalTrials.gov Identifier: NCT02878850

What kind of study is this?

This was a multicentre, randomised clinical trial conducted across 13 major US trauma centres between 2017 and 2023. Of note these were ICU patients. Adult patients with acute traumatic spinal cord injury were randomised to one of two blood pressure strategies:

Augmented blood pressure (ABP): target MAP >85–90 mm Hg
Conventional blood pressure (CBP): target MAP >65–70 mm Hg

Targets were maintained for up to 7 days or until ICU discharge, using fluids and vasopressors as required.

The trial was prospectively registered, ethically approved, and reported in accordance with CONSORT guidelines. Outcome assessors for six-month neurological follow-up were blinded to group allocation, although treating teams could not be blinded for obvious practical reasons.

The primary outcome was change in American Spinal Injury Association (ASIA) motor and sensory scores at six months. Secondary outcomes included pain, functional independence, quality of life, and a comprehensive set of safety outcomes including organ dysfunction and respiratory complications.

Tell me about the patients

The study enrolled 92 adult patients with acute traumatic spinal cord injury involving the cervical or upper thoracic spine (C0–T8). All had new neurological deficits graded as ASIA Impairment Scale A, B, or C. It’s not entirely clear. but I think the patients were all recruited on the ICU. That’s important as it may be that there are differences with the impact of blood pressure control on the ICU, and around the time of injury itself. As I’m a PHEM/EM doc then this might not really be my group of patients.

This was a severely injured cohort:

Mean age ~54 years
83% male
Over half had complete injuries (AIS A)
Mean Injury Severity Score >23
Around one quarter required mechanical ventilation at baseline

Patients with penetrating injuries, cauda equina syndrome, injuries below T9, or severe traumatic brain injury were excluded. This is important: the findings apply to isolated traumatic SCI, not mixed neurotrauma.

Randomisation achieved good baseline balance between groups in terms of injury severity, neurological level, comorbidities, and initial haemodynamics.

What were the measured outcomes in this study?

These were analysed as change from baseline, adjusted for initial ASIA scores for upper and lower limbs, a global sensory score and AIS scores. If you need a reminder…

A: Complete. No sensory or motor function is preserved in the sacral segments S4-S5.

B: Sensory incomplete. Sensory but not motor function is preserved below the neurological level and includes the sacral segments S4-S5 (light touch, pin prick at S4-S5 or deep anal pressure), AND no motor function is preserved more than three levels below the motor level on either side of the body.

C: Motor incomplete. Motor function is preserved below the neurological level and more than half of key muscle functions below the single neurological level of injury (NLI) have a muscle grade less than 3.

D: Motor incomplete. Motor function is preserved below the neurological level and at least half of key muscle functions below the NLI have a muscle grade of 3 or greater.

E: Normal.

Secondary outcomes included:

Pain (International SCI Pain Basic Data Set)
Functional independence (Spinal Cord Independence Measure)
Quality of life
Mortality
ICU and hospital length of stay

Safety outcomes were particularly detailed and included:

Modified SOFA scores (excluding cardiovascular components)
Duration of mechanical ventilation
Respiratory complications (pneumonia, pulmonary oedema, ARDS)
Serious adverse events

What are the main results?

Neurological outcomes

At six months, there was no statistically significant difference between the augmented and conventional blood pressure groups in:

Upper extremity motor scores 34.95 for ABP vs 32.95 for CBP
Lower extremity motor scores 18.53 for ABP vs 19.95 for CBP
Total sensory scores 108.47 for ABP vs. 130.89

The confidence intervals were wide, reflecting the small sample size. So overall there did not appear to be that much benefit in the headline figures. That said, the graphical representation of how the group turned out does suggest there might be a difference in the number of patients with an A outcome (fewer in the ABP group)., but that was not the intended analysis. See what you think based on the graphic tweeted out by JAMA looking at the AIS scores.

Safety and complications

Patients in the augmented blood pressure group experienced:

Higher organ dysfunction scores at days 3 and 6
Longer duration of mechanical ventilation 9.44 days vs. 3.78 days.
Fewer respiratory complications occurred in 78% of the augmented group versus 39% of the conventional group. Pneumonia and pulmonary oedema were both significantly more common. Interesting, but what’s the biological plausibility here?

Mortality at six months was similar between groups, but this study was not powered to detect mortality differences.

How robust are the results?

This is an important trial, but I do have some concerns. It’s great to see an RCT on this topic, especially a multicentre one in a well performing system. The blinded assessments and patient orientated outcomes are good and they looked for harm too. So loads of positives, but there are some fairly fundamental issues.

Numbers is the big issue. The trial was underpowered as (as with many trials) COVID got in the way, but also because the drop out rate was really high. Of the 92 patients recruited, by 6 months, 15 patients (16%) had died, 38 (41%) had completed the ASI assessment, 48(52%) had completed study questionnaires, and 27(29%) were lost to follow-up. That drop out rate means that we need to be super cautious about the outcome data as even a small number of patients could skew the results dramatically if their follow up data had been available. Now hopefully in an RCT the characteristics of those who drop out are similar in both sides of the trial, but in small studies, and this is a small study drop outs can have a profound impact on the results.

The biggest problem is numbers though. Just 38 of the 92 patients completed follow up. In addition the 92 was smaller than intended but owing to COVID and other reasons it was stopped at 92. So this is a seriously under-powered trial.

The higher complication rates are also interesting. I guess if you spend more time on the ICU with monitoring you might get more respiratory complications, but I’m struggling to see the biological plausibility link there. Maybe others can enlightenme on that one.

From my perspective these are not my patients as I don’t work on the ICU. I see these patients in the minutes and hours after injury where it may (or may not) be more important to manage blood pressure and to maintain a higher MAP. We just don’t know, but this trial does not help me in that time period.

Should we change practice based on this study?

I don’t think so at this stage as the loss to follow up is a real issue in an underpowered trial. For me, it’s not the same patients I see in PHEM/EM either so no change for me or others in the same clinical practice. However, it does once again make us think about generalised BP targets for everyone, or whether we need a more nuanced, individualised and monitored (art lines) approach in these patients. That’s what we think at St Emlyn’s and this study has not really changed that. My ICM collegues may feel differently and this study may give them some lee-way in difficult cases (but I would be cautious)

Summary

This multicentre randomised trial compared augmented (MAP >85–90 mm Hg) and conventional (MAP >65–70 mm Hg) blood pressure targets in acute traumatic spinal cord injury. It found no improvement in six-month neurological outcomes with blood pressure augmentation, but the findings are not especially robust and not directly relevant to PHEM/EM practice.

References and further reading

Sajdeya R, Yanez ND, Kampp M, Goodman MD, Zonies D, Togioka B, et al. Early blood pressure targets in acute spinal cord injury: a randomised clinical trial. JAMA Netw Open. 2025;8(9):e2525364. ICM paper 3 spinal cord BP targ…
Walters BC, Hadley MN, Hurlbert RJ, Aarabi B, Dhall SS, Gelb DE, et al. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery. 2013;72(Suppl 2):82–91.
Kwon BK, Tetreault LA, Martin AR, Fehlings MG. A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on hemodynamic management. Global Spine J. 2024;14(3 Suppl):187S–211S.