Markedly Deranged Injury Site Metabolism and Impaired Functional Recovery in Acute Spinal Cord Injury Patients With Fever

Gallagher, Mathew J.; Zoumprouli, Argyro; Phang, Isaac; Schwab, Jan M.; Kopp, Marcel A.; Liebscher, Thomas; Papadopoulos, Marios C.; Saadoun, Samira

doi:10.1097/ccm.0000000000003134

Cited by 17 publications

(20 citation statements)

References 44 publications

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“…Fever was particularly detrimental on injury site metabolism when the peripheral white cell count was high, which suggests that fever associated with infection may be more detrimental than neurogenic fever. In 2 TSCI patient cohorts, managed in London and Berlin [57], high fever burden correlated with less neurological improvement. Though further studies are required to determine the effect and temporal relations between the different types of fever (infection, neurogenic) and injury site metabolism, based on the data to date, we suggest prompt treatment of fever in TSCI patients with paracetamol, nonsteroidal anti-inflammatory drugs, or active cooling.…”

Section: Managing Fevermentioning

confidence: 98%

“…Fever is observed in up to 67% of patients with acute TSCI and may arise from infection or be neurogenic [53][54][55][56]. In TSCI patients, fever was associated with significantly more deranged metabolite levels than normothermia evidenced by lower tissue glucose, higher lactate, higher glutamate, and higher lactate-to-pyruvate ratio (LPR, a measure of anaerobic metabolism) [57]. Fever was particularly detrimental on injury site metabolism when the peripheral white cell count was high, which suggests that fever associated with infection may be more detrimental than neurogenic fever.…”

Section: Managing Fevermentioning

confidence: 99%

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Targeted Perfusion Therapy in Spinal Cord Trauma

Saadoun

Papadopoulos

2020

Neurotherapeutics

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We review state-of-the-art monitoring techniques for acute, severe traumatic spinal cord injury (TSCI) to facilitate targeted perfusion of the injured cord rather than applying universal mean arterial pressure targets. Key concepts are discussed such as intraspinal pressure and spinal cord perfusion pressure (SCPP) at the injury site, respectively, analogous to intracranial pressure and cerebral perfusion pressure for traumatic brain injury. The concept of spinal cord autoregulation is introduced and quantified using spinal pressure reactivity index (sPRx), which is analogous to pressure reactivity index for traumatic brain injury. The Ushaped relationship between sPRx and SCPP defines the optimum SCPP as the SCPP that minimizes sPRx (i.e., maximizes autoregulation), and suggests that not only ischemia but also hyperemia at the injury site may be detrimental. The observation that optimum SCPP varies between patients and temporally in each patient supports individualized management. We discuss multimodality monitoring, which revealed strong correlations between SCPP and injury site metabolism (tissue glucose, lactate, pyruvate, glutamate, glycerol), monitored by surface microdialysis. Evidence is presented that the dura is a major, but unappreciated, cause of spinal cord compression after TSCI; we thus propose expansion duroplasty as a novel treatment. Monitoring spinal cord blood flow at the injury site has revealed novel phenomena, e.g., 3 distinct blood flow patterns, local steal, and diastolic ischemia. We conclude that monitoring from the injured spinal cord in the intensive care unit is a safe technique that appears to enable optimized and individualized spinal cord perfusion.

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Section: Managing Fevermentioning

confidence: 98%

Section: Managing Fevermentioning

confidence: 99%

Targeted Perfusion Therapy in Spinal Cord Trauma

Saadoun

Papadopoulos

2020

Neurotherapeutics

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“…100-fold changes in metabolite concentration, and 10-fold changes in LPR, compared with the preceding hour, were excluded. We previously showed that our MD method measures injury site surface metabolism, which correlates well with intraparenchymal metabolism (r = 0.56-0.91), but differs from metabolites measured from the lumbar cerebrospinal fluid (CSF) (r = 0.23-0.50) [16][17][18] .…”

Section: Cooling Cathetermentioning

confidence: 92%

“…The ISP probe and MD catheter were sutured to the skin. These techniques are described in detail in our earlier publications [16][17][18][19][20][21][22][23] .…”

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confidence: 99%

Effects of local hypothermia–rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord

Gallagher

Hogg

Kearney

et al. 2020

Sci Rep

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In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI. Hypothermia is being investigated as a potential therapy for traumatic brain injury (TBI) 1 and traumatic spinal cord injury (TSCI) 2 based on compelling evidence from several laboratories and animal species that hypothermia is neuroprotective. In animal models of TBI, hypothermia has been shown to target many pathological processes including reducing the metabolic rate, inflammation, edema, oxidative stress, excitotoxicity, electrolyte imbalance as well as apoptotic and necrotic cell death in vulnerable tissue 3-8. Despite the encouraging findings of animal studies, randomized controlled human trials have failed to show functional benefit of hypothermia in TBI patients 1,9,10. Therapeutic hypothermia is also beneficial in animal models of TSCI: rodent models of TSCI show improved histological and functional outcomes after hypothermia 11,12. Small, non-randomized studies of TSCI patients also suggest improved functional outcomes after local 13,14 or systemic hypothermia 2,15. To date, there are no published randomized controlled trials of hypothermia for TSCI. Despite the wide interest in therapeutic hypothermia for CNS injuries, there is paucity of mechanistic data from humans regarding the effect of hypothermia on the injury site. In TSCI patients, the effect of cooling and rewarming on cord swelling, metabolism and inflammation are unknown. It is thus unclear if hypothermia and

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“…Following the primary injury, further cord damage may occur e.g. from ongoing cord compression, low blood pressure 5 , peripheral infections 6 and fever 7 .…”

Section: Introductionmentioning

confidence: 99%

Visibility Graph Analysis of Intraspinal Pressure Signal Predicts Functional Outcome in Spinal Cord Injured Patients

Chen

Gallagher

Hogg

et al. 2018

Journal of Neurotrauma

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To guide management of patients with acute spinal cord injuries, we developed intraspinal pressure monitoring from the injury site. Here, we examine the complex fluctuations in the intraspinal pressure signal using network theory. We analyzed 7097 h of intraspinal pressure data from 58 patients with severe cord injuries. Intraspinal pressure signals were split into hourly windows. Each window was mapped into a visibility graph as follows. Vertical bars were drawn at 0.1 Hz representing signal amplitudes. Each bar produced a node, thus totalling 360 nodes per graph. Two nodes were linked with an edge if the straight line through the nodes did not intersect a bar. We computed several topological metrics for each graph including diameter, modularity, eccentricity, and small-worldness. Patients were followed up for 20 months on average. Our data show that the topological structure of intraspinal pressure visibility graphs is highly sensitive to pathological events at the injury site, including cord compression (high intraspinal pressure), ischemia (low spinal cord perfusion pressure), and deranged autoregulation (high spinal pressure reactivity index). These pathological changes correlate with long graph diameter, high modularity, high eccentricity and reduced small-worldness. In a multivariate logistic regression model, age, neurological status on admission, and average node eccentricity were independent predictors of neurological improvement. We conclude that analysis of intraspinal pressure fluctuations after spinal cord injury as graphs, rather than as time series, captures clinically important information. Our novel technique may be applied to other signals recorded from injured central nervous system (CNS); for example, intracranial pressure, tissue metabolite, and oxygen levels.

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Markedly Deranged Injury Site Metabolism and Impaired Functional Recovery in Acute Spinal Cord Injury Patients With Fever

Abstract: Early after spinal cord injury, fever is associated with more deranged injury site metabolism than normothermia and worse prognosis.

Cited by 17 publications

References 44 publications

Targeted Perfusion Therapy in Spinal Cord Trauma

Targeted Perfusion Therapy in Spinal Cord Trauma

Effects of local hypothermia–rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord

Visibility Graph Analysis of Intraspinal Pressure Signal Predicts Functional Outcome in Spinal Cord Injured Patients

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