Microdialysis to Optimize Cord Perfusion and Drug Delivery in Spinal Cord Injury

Abstract

OBJECTIVE:There is lack of monitoring from the injury site to guide management of patients with acute traumatic spinal cord injury. Here we describe a bedside microdialysis monitoring technique for optimizing spinal cord perfusion and drug delivery at the injury site.METHODS: 14 patients were recruited within 72 hours of severe spinal cord injury. We inserted intradurally at the injury site a pressure probe, to monitor continuously spinal cord perfusion pressure, and a microdialysis catheter, to monitor hourly glycerol, glutamate, glucose, lactate and pyruvate. The pressure probe and microdialysis catheter were placed on the surface of the injured cord. RESULTS:Microdialysis monitoring did not cause serious complications. Spinal cord perfusion pressure 90 -100 mmHg and tissue glucose >4.5 mM minimized metabolic derangement at the injury site. Increasing spinal cord perfusion pressure by ~10 mmHg, increased the entry of intravenously administered dexamethasone at the injury site three-fold. INTERPRETATION:This study determined the optimum spinal cord perfusion pressure and optimum tissue glucose concentration at the injury site. We also identified spinal cord perfusion pressure as a key determinant of drug entry into the injured spinal cord. Our findings challenge current guidelines, which recommend maintaining mean arterial pressure at 85 -90 mmHg for a week after spinal cord injury. We propose that future drug trials for spinal cord injury include pressure and microdialysis monitoring to optimize spinal cord perfusion and maximize drug delivery at the injury site.

Intraspinal pressure and spinal cord perfusion pressure predict neurological outcome after traumatic spinal cord injury

“…Spinal cord microdialysis indicates that high ISP and low SCPP are associated with injury-site ischaemia,5 which likely causes secondary damage. Since only one patient had mean SCPP >100 mm Hg, it is impossible to determine what happens to neurological outcome when mean SCPP is >90–100 mm Hg.…”

Microdialysis Monitoring in Clinical Traumatic Brain Injury and Its Role in Neuroprotective Drug Development

“…This allowed the physicians to guide the spinal perfusion pressure and spinal ECF glucose, as deviations from 90-100 mmHg and 4.5 mmol/L, respectively, resulted in an increase of the LPR in the damaged area (19). The authors also noted that dexamethasone penetration into the tissue increased with increasing spinal perfusion pressure, prompting future trials in spinal cord injury to better monitor the affected area.…”

“…In a recently published clinical study, patients suffering from severe spinal cord injury were monitored using MD implanted intradurally at the site of injury (19). This allowed the physicians to guide the spinal perfusion pressure and spinal ECF glucose, as deviations from 90-100 mmHg and 4.5 mmol/L, respectively, resulted in an increase of the LPR in the damaged area (19).…”

“…Here, microdialysis (MD) is playing an important role in many NCCUs today for patients suffering from TBI and subarachnoid haemorrhage (SAH) (16), but is also actively researched in other CNS conditions such as bacterial meningitis (17,18) and spinal cord injury (19).…”

Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction

“…Following traumatic injury to the spinal cord or brain, a complex combination of pathological processes develop, in which cerebral energy perturbations and cellular metabolism play a key role 1–5 . Despite modern advances in acute neurocritical care, many traumatic brain injury (TBI) or spinal cord injury (SCI) patients who survive the injury experience long-term disability.…”