Adverse Effect of Neurogenic, Infective, and Inflammatory Fever on Acutely Injured Human Spinal Cord

Abstract

This study aims to determine the effect of neurogenic, inflammatory, and infective fevers on acutely injured human spinal cord. In 86 patients with acute, severe traumatic spinal cord injuries (TSCIs; American Spinal Injury Association Impairment Scale (AIS), grades A-C) we monitored (starting within 72 h of injury, for up to 1 week) axillary temperature as well as injury site cord pressure, microdialysis (MD), and oxygen. High fever (temperature ≥38°C) was classified as neurogenic, infective, or inflammatory. The effect of these three fever types on injury-site physiology, metabolism, and inflammation was studied by analyzing 2864 h of intraspinal pressure (ISP), 1887 h of MD, and 840 h of tissue oxygen data. High fever occurred in 76.7% of the patients. The data show that temperature was higher in neurogenic than non-neurogenic fever. Neurogenic fever only occurred with injuries rostral to vertebral level T4. Compared with normothermia, fever was associated with reduced tissue glucose (all fevers), increased tissue lactate to pyruvate ratio (all fevers), reduced tissue oxygen (neurogenic + infective fevers), and elevated levels of pro-inflammatory cytokines/chemokines (infective fever). Spinal cord metabolic derangement preceded the onset of infective but not neurogenic or inflammatory fever. By considering five clinical characteristics (level of injury, axillary temperature, leukocyte count, C-reactive protein [CRP], and serum procalcitonin [PCT]), it was possible to confidently distinguish neurogenic from non-neurogenic high fever in 59.3% of cases. We conclude that neurogenic, infective, and inflammatory fevers occur commonly after acute, severe TSCI and are detrimental to the injured spinal cord with infective fever being the most injurious. Further studies are required to determine whether treating fever improves outcome. Accurately diagnosing neurogenic fever, as described, may reduce unnecessary septic screens and overuse of antibiotics in these patients.

Keywords: antipyretic; autonomic; critical care; management; monitoring; pyrexia.

FIG. 1.

Monitoring setup. (A) Pre-operative sagittal CT. (B) Pre-operative sagittal T2 MRI. (C) Intra-operative photo (dura exposed, microscope). (D) Intra-operative photo (wound closed). (E) Post-operative sagittal CT. (F) Post-operative coronal CT. (G) Simultaneously monitored signals from injury site: ISP (blue), SCPP (red), GLUC, (green), tissue LPR (purple), p_sctO₂ (orange). CT, computed tomography; GLUC, tissue glucose; ISP, intraspinal probe; LPR, lactate to pyruvate ratio; MD, microdialysis catheter; MRI, magnetic resonance imaging; p_sctO₂, tissue oxygen, Licox probe; SCPP, spinal cord perfusion pressure.

FIG. 2.

Characteristics of different fevers. (A) Temperature profiles of neurogenic (blue), inflammatory (orange), and infective (black) high fevers. (B) Percentage of hours each day after TSCI with neurogenic, inflammatory, and infective high fever. (C) Level of injury versus % of patients at each level who had high fever. P < 0.05*, 0.01**, 0.001^#, 0.0005^##. GLUC, tissue glucose; LPR, lactate to pyruvate ratio; p_sctO₂, tissue oxygen; TSCI, severe traumatic spinal cord injury.

FIG. 3.

Physiology and metabolism of injured cord during fever. (A) GLUC, tissue LPR, and p_sctO₂ (gray lines) monitored from the injured cord of a patient with neurogenic fever (green, <37.5; light red, 37.5 – 37.9; red, ≥38.0°C). Dotted lines are trendlines during the fever. Percentage of episodes of no fever (green), (B) versus neurogenic high fever (blue), or (C) versus inflammatory high fever (orange), or (D) versus infective high fever (black) associated with increase (), no change (), or decrease () in GLUC, tissue LPR, and p_sctO₂. P < 0.05*, 0.005***, 0.0001^###. GLUC, tissue glucose; LPR, lactate to pyruvate ratio; p_sctO₂, tissue oxygen.

FIG. 4.

Cytokines in injured spinal cord during fever. Percentage of change in the levels of GROα, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, and IL-10 in microdialysates collected from the injury site during high fever (≥ 38°C) versus normothermia. Neurogenic (blue), inflammatory (orange), or infective (black) fever. Dots are fever episodes; lines are medians, logarithmic scale; ns, not significant; P < 0.05*, 0.005***.

FIG. 5.

Distinguishing neurogenic from non-neurogenic fever. (A) Flow diagram. (B) Examples of fever episodes: left infective (black), middle left neurogenic (blue), middle right inflammatory (orange); then infective (black), right infective (black); then neurogenic(blue). “✓”, diagnosed correctly; “?”, cannot distinguish neurogenic versus non-neurogenic; CRP, C-reactive protein; PCT, procalcitonin; TSCI, severe traumatic spinal cord injury; WCC, white cell count.