# Targeting spinal cord perfusion pressure in acute spinal cord injury through cerebrospinal fluid drainage: A prospective multi-center clinical trial

## TL;DR

A clinical trial tested if draining cerebrospinal fluid to increase spinal cord perfusion pressure improves recovery after spinal cord injury, but found no benefit compared to traditional blood pressure targets.

## Contribution

This study is the first to prospectively evaluate spinal cord perfusion pressure management via cerebrospinal fluid drainage in acute spinal cord injury across multiple centers.

## Key findings

- CSF drainage did not significantly alter spinal cord perfusion pressure or improve neurological recovery compared to conventional MAP management.
- Participants managed with SCPP protocols had more frequent pulsatile intrathecal waveforms and less vasopressor use.
- The relationship between CSF drainage volume and intrathecal pressure changes was unclear, suggesting complex pathophysiology in traumatic SCI.

## Abstract

The hemodynamic management of acute spinal cord injury (SCI) aims to improve perfusion and mitigate ischemic secondary injury to the injured spinal cord, traditionally through the augmentation of mean arterial pressure (MAP). Recently, there has been interest in managing spinal cord perfusion pressure (SCPP)—the difference between MAP and intrathecal pressure (ITP) —after acute SCI. SCPP may be more physiologically relevant than MAP for neurologic recovery after traumatic SCI. Drainage of cerebrospinal fluid (CSF) through a lumbar intrathecal catheter to reduce ITP and increase SCPP is commonly performed to reduce the risk of ischemic paralysis in thoracoabdominal aortic aneurysm (TAAA) surgery. We investigated a protocol for CSF drainage through intrathecal catheters to maintain SCPP ≥65 mmHg in participants with acute traumatic SCI. We sought to determine if managing SCPP was associated with better neurologic recovery compared to traditional MAP targets.

Fifty-eight participants with acute SCI (51 ± 19 years, 46M/12F) were enrolled across eight North American sites between August 2019 and May 2024 into this prospective single-arm multi-center clinical trial of CSF drainage for SCPP management (NCT03911492). Data were compared to data from a historical cohort of 86 participants (44 ± 19 years, 72M/14F) who had intrathecal catheters inserted for SCPP measurement only; these participants were managed according to conventional MAP guidelines with a target MAP of 85–90 mmHg (NCT01279811). MAP, ITP, SCPP, intrathecal waveform morphology, vasopressor use, and CSF drainage volume were reported for up to 7 days following SCI. Fifteen participants in the intervention group were lost to follow-up. Neurological assessments at enrollment and 6-months post-SCI were compared. The investigator team ended the trial when it was clear that adherence to the protocol was inconsistent across study sites. Participants managed according to the SCPP management protocol had an intrathecal catheter in place 138 hours (95% CI [129,147]) and 495cc (95% CI [350,641]) of CSF drained. No CSF was drained from seven participants. There were no significant differences in hemodynamic measures such as ITP and SCPP between groups, indicating that the SCPP management protocol did not alter the hemodynamic management. Subsequently, there were no differences in measures of neurological recovery between participants managed according to SCPP management protocol and conventional MAP guidelines (p = 0.897). Participants managed according to an SCPP target had more ITP waveform recordings noted as dampened or fully pulsatile suggesting a patent subarachnoid space (p = 0.006) and were administered vasopressors on fewer hourly observations (p = 0.004). Six reported adverse events were probably related to the intervention. Adherence to a protocol for managing SCPP through CSF drainage across multiple sites was challenging.

Ultimately, our protocol resulted in little CSF being drained, limited modification of ITP and SCPP, and no effect on neurological recovery. The relationship between CSF drainage volume and change in ITP was surprisingly unclear. This study revealed that draining CSF is more complex in traumatic SCI than in TAAA surgery patients. Future efforts to reduce ITP through CSF drainage likely need to address the occlusion of the subarachnoid space at the injury site through aggressive surgical decompression techniques.

The hemodynamic management of acute spinal cord injury is one of the mainstays of early management, with mean arterial pressure guidelines existing for almost 20 years. However, whether mean arterial pressure guidelines are the best target for enhancing the likelihood of recovery has been questioned.

Recent evidence indicates that spinal cord perfusion pressure—the difference between mean arterial and intrathecal pressure—may be a better predictor of neurological recovery than mean arterial pressure following spinal cord injury.

We aimed to test whether actively managing spinal cord perfusion pressure through a combination of mean arterial pressure augmentation and cerebrospinal fluid drainage was associated with better neurological recovery compared to conventional hemodynamic management.

We recruited 58 participants with acute spinal cord injury across 8 North American sites and monitored them for one-week post-injury. Participants had a lumbar intrathecal catheter inserted during surgery to monitor spinal cord perfusion pressure and to drain cerebrospinal fluid to reduce intrathecal pressure.

Data were compared to a historical cohort of 86 participants who were managed according to conventional mean arterial pressure guidelines for five days post-injury.

Ultimately, cerebrospinal fluid drainage was not associated with differences in spinal cord perfusion pressure between groups and there was no difference in neurological recovery between groups.

The relationship between the volume of cerebrospinal fluid drained and the change in intrathecal pressure was surprisingly unclear.

These findings highlight the importance of surgical decompression in drainage studies and suggest that alternative drainage protocols may be needed.

This study highlights the challenges in implementing multi-center studies in the critical care setting and with adhering to protocols across multiple sites.

Cameron M. Gee and colleagues not only report whether targeting spinal cord perfusion pressure via cerebrospinal fluid drainage after acute traumatic spinal cord injury leads to better neurologic recovery than standard mean arterial pressure targets, but also highlight the challenges of conducting multicenter studies in critical care settings and of adhering to protocols across multiple sites.