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

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.

Removal or retention of minimally invasive screws in thoracolumbar fractures? Systematic review and case-control study.

BACKGROUND: There is uncertainty regarding delayed removal versus retention of minimally invasive screws following percutaneous fixation for thoracolumbar fractures. We conducted a systematic review and case-control study to test the hypothesis that delayed metalwork removal following percutaneous fixation for thoracolumbar fractures improves outcome. METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Our case-control study retrospectively evaluated 55 consecutive patients with thoracolumbar fractures who underwent percutaneous fixation in a single unit: 19 with metalwork retained (controls) and 36 with metalwork removed. Outcomes were the Oswestry Disability Index (ODI), a supplemental questionnaire, and complications. RESULTS: The systematic review evaluated nine articles. Back pain was reduced in most patients after metalwork removal. One study found no difference in the ODI after versus before metalwork removal, whereas three studies reported significant improvement. Six studies noted no significant alterations in radiological markers of stability after metalwork removal. Mean complication rate was 1.7% (0-6.7). Complications were superficial wound infection, screw breakage at the time of removal, pull-out screw, and a broken rod. In the case-control study, both groups were well matched. For metalwork removal, mean operative time was 69.5 min (range 30-120) and length of stay was 1.3 days (0-4). After metalwork removal, 24 (68.6%) patients felt better, 10 (28.6%) the same and one felt worse. Two patients had superficial hematomas, one had a superficial wound infection, and none required re-operation. Metalwork removal was a significant predictor of return to work or baseline household duties (odds ratio 5.0 [1.4-18.9]). The ODI was not different between groups. CONCLUSIONS: The findings of both the systematic review and our case-control study suggest that removal of metalwork following percutaneous fixation of thoracolumbar fractures is safe and is associated with improved outcome in most patients.

Monitoring Spinal Cord Tissue Oxygen in Patients With Acute, Severe Traumatic Spinal Cord Injuries.

OBJECTIVES: To determine the feasibility of monitoring tissue oxygen tension from the injury site (pscto2) in patients with acute, severe traumatic spinal cord injuries. DESIGN: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and pscto2. We analyzed 2,213 hours of such data. Follow-up was 6-28 months postinjury. SETTING: Single-center neurosurgical and neurocritical care units. SUBJECTS: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A-C. Probes were inserted within 72 hours of injury. INTERVENTIONS: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter. MEASUREMENTS AND MAIN RESULTS: pscto2 was significantly influenced by ISP (pscto2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs pscto2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (pscto2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs pscto2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (pscto2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (pscto2 25.3 ± 0.4 mm Hg at LPR > 30 vs pscto2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (pscto2 28.8 ± 0.5 mm Hg at cord temperature 37-38°C vs pscto2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio2 by 0.48 increases pscto2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in pscto2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26). CONCLUSIONS: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.

Acute, severe traumatic spinal cord injury: improving urinary bladder function by optimizing spinal cord perfusion.

OBJECTIVE: The authors sought to investigate the effect of acute, severe traumatic spinal cord injury on the urinary bladder and the hypothesis that increasing the spinal cord perfusion pressure improves bladder function. METHODS: In 13 adults with traumatic spinal cord injury (American Spinal Injury Association Impairment Scale grades A-C), a pressure probe and a microdialysis catheter were placed intradurally at the injury site. We varied the spinal cord perfusion pressure and performed filling cystometry. Patients were followed up for 12 months on average. RESULTS: The 13 patients had 63 fill cycles; 38 cycles had unfavorable urodynamics, i.e., dangerously low compliance (< 20 mL/cmH2O), detrusor overactivity, or dangerously high end-fill pressure (> 40 cmH2O). Unfavorable urodynamics correlated with periods of injury site hypoperfusion (spinal cord perfusion pressure < 60 mm Hg), hyperperfusion (spinal cord perfusion pressure > 100 mm Hg), tissue glucose < 3 mM, and tissue lactate to pyruvate ratio > 30. Increasing spinal cord perfusion pressure from 67.0 ± 2.3 mm Hg (average ± SE) to 92.1 ± 3.0 mm Hg significantly reduced, from 534 to 365 mL, the median bladder volume at which the desire to void was first experienced. All patients with dangerously low average initial bladder compliance (< 20 mL/cmH2O) maintained low compliance at follow-up, whereas all patients with high average initial bladder compliance (> 100 mL/cmH2O) maintained high compliance at follow-up. CONCLUSIONS: We conclude that unfavorable urodynamics develop within days of traumatic spinal cord injury, thus challenging the prevailing notion that the detrusor is initially acontractile. Urodynamic studies performed acutely identify patients with dangerously low bladder compliance likely to benefit from early intervention. At this early stage, bladder function is dynamic and is influenced by fluctuations in the physiology and metabolism at the injury site; therefore, optimizing spinal cord perfusion is likely to improve urological outcome in patients with acute severe traumatic spinal cord injury.

Spinal Cord Perfusion Pressure Correlates with Anal Sphincter Function in a Cohort of Patients with Acute, Severe Traumatic Spinal Cord Injuries.

BACKGROUND: Acute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site. METHODS: We recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A-C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures. RESULTS: Data were collected from 14 patients with consecutive traumatic spinal cord injury aged 22-67 years. The mean resting anal pressure was 44 cmH2O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH2O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (Ȓ2 = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH2O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH2O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70-90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry. CONCLUSIONS: Our data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence.

Acute Spinal Cord Injury: Correlations and Causal Relations Between Intraspinal Pressure, Spinal Cord Perfusion Pressure, Lactate-to-Pyruvate Ratio, and Limb Power.

BACKGROUND/OBJECTIVE: We have recently developed monitoring from the injury site in patients with acute, severe traumatic spinal cord injuries to facilitate their management in the intensive care unit. This is analogous to monitoring from the brain in patients with traumatic brain injuries. This study aims to determine whether, after traumatic spinal cord injury, fluctuations in the monitored physiological, and metabolic parameters at the injury site are causally linked to changes in limb power. METHODS: This is an observational study of a cohort of adult patients with motor-incomplete spinal cord injuries, i.e., grade C American spinal injuries association Impairment Scale. A pressure probe and a microdialysis catheter were placed intradurally at the injury site. For up to a week after surgery, we monitored limb power, intraspinal pressure, spinal cord perfusion pressure, and tissue lactate-to-pyruvate ratio. We established correlations between these variables and performed Granger causality analysis. RESULTS: Nineteen patients, aged 22-70 years, were recruited. Motor score versus intraspinal pressure had exponential decay relation (intraspinal pressure rise to 20 mmHg was associated with drop of 11 motor points, but little drop in motor points as intraspinal pressure rose further, R2 = 0.98). Motor score versus spinal cord perfusion pressure (up to 110 mmHg) had linear relation (1.4 motor point rise/10 mmHg rise in spinal cord perfusion pressure, R2 = 0.96). Motor score versus lactate-to-pyruvate ratio (greater than 20) also had linear relation (0.8 motor score drop/10-point rise in lactate-to-pyruvate ratio, R2 = 0.92). Increased intraspinal pressure Granger-caused increase in lactate-to-pyruvate ratio, decrease in spinal cord perfusion, and decrease in motor score. Increased spinal cord perfusion Granger-caused decrease in lactate-to-pyruvate ratio and increase in motor score. Increased lactate-to-pyruvate ratio Granger-caused increase in intraspinal pressure, decrease in spinal cord perfusion, and decrease in motor score. Causality analysis also revealed multiple vicious cycles that amplify insults to the cord thus exacerbating cord damage. CONCLUSION: Monitoring intraspinal pressure, spinal cord perfusion pressure, lactate-to-pyruvate ratio, and intervening to normalize these parameters are likely to improve limb power.

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

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 IL1ß, IL8, MCP, MIP1α, MIP1ß). 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 IL1ß, 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.

Acute Spinal Cord Injury: Monitoring Lumbar Cerebrospinal Fluid Provides Limited Information about the Injury Site.

In some centers, monitoring lumbar cerebrospinal fluid (CSF) is used to guide management of patients with acute traumatic spinal cord injuries (TSCI) and draining lumbar CSF to improve spinal cord perfusion. Here, we investigate whether the lumbar CSF provides accurate information about the injury site and the effect of draining lumbar CSF on injury site perfusion. In 13 TSCI patients, we simultaneously monitored lumbar CSF pressure (CSFP) and intraspinal pressure (ISP) from the injury site. Using CSFP or ISP, we computed spinal cord perfusion pressure (SCPP), vascular pressure reactivity index (sPRx) and optimum SCPP (SCPPopt). We also assessed the effect on ISP of draining 10 mL CSF. Metabolites at the injury site were compared with metabolites in the lumbar CSF. We found that ISP was pulsatile, but CSFP had low pulse pressure and was non-pulsatile 21% of the time. There was weak or no correlation between CSFP versus ISP (R = -0.11), SCPP(csf) versus SCPP(ISP) (R = 0.39), and sPRx(csf) versus sPRx(ISP) (R = 0.45). CSF drainage caused no significant change in ISP in 7/12 patients and a significant drop of <5 mm Hg in 4/12 patients and of ∼8 mm Hg in 1/12 patients. Metabolite concentrations in the CSF versus the injury site did not correlate for lactate (R = 0.00), pyruvate (R = -0.12) or lactate-to-pyruvate ratio (R = -0.05) with weak correlations noted for glucose (R = 0.31), glutamate (R = 0.61), and glycerol (R = 0.56). We conclude that, after a severe TSCI, monitoring from the lumbar CSF provides only limited information about the injury site and that lumbar CSF drainage does not effectively reduce ISP in most patients.