Argyro Zoumprouli

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.

The effect of traumatic spinal cord injury (TSCI) on spinal cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guideline of 85–90 mm Hg improves SCBF is also unclear. Here, we use laser speckle contrast imaging intraoperatively to visualize blood flow at the injury site in 22 patients with acute, severe spinal cord injuries (American Spinal Injuries Association Impairment Scale, grades A–C). In 17 of 22 patients, injury-site metabolism was also monitored with a microdialysis catheter placed intradurally on the surface of the injured cord. We observed three different SCBF patterns, characterized by distinct injury-site metabolic signatures, which we term necrosis-penumbra, hyperperfusion, and patchy-perfusion. The necrosis-penumbra pattern, only observed in thoracic injuries, had a core of low blood flow (necrosis) with regions of intermediate blood flow on either side (penumbra). The hyperperfusion pattern, only observed in cervical injuries, had very high blood flow throughout the injury site. The patchy-perfusion pattern, found in cervical and thoracic injuries, had irregular regions of low, intermediate, and high blood flow. Though intervention to increase MAP by 20 mm Hg increased overall blood flow at the injury site, in 5 of 22 patients, blood flow increased in some regions, but, surprisingly, decreased in other regions. We term this phenomenon blood pressure–induced local steal. In 7 of 19 patients with MAP 85–90 mm Hg, parts of the injury site were only perfused in systole, but not in diastole, which we term diastolic ischemia. We conclude that acute, severe TSCI produces three pathological blood flow patterns at the injury site. Intervention to increase blood pressure may elicit potentially detrimental SCBF responses in some patients.

We recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPP_opt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPP_opt can be predicted using clinical factors instead of ISP monitoring.

Objectives: To characterize the effect of fever after acute, traumatic spinal cord injury on injury site metabolism and patient outcome. Design: Longitudinal cohort study. In 44 patients (London cohort), we determined the effect of fever on intrathecal injury site metabolism by analyzing 1,767 hours of intraspinal pressure and 759 hours of microdialysis data. We also determined the effect of fever burden, computed for the first 2 weeks in hospital, on neurologic outcome. A distinct cohort of 33 patients (Berlin cohort) was used to independently validate the effect of fever burden on outcome. Setting: ICUs in London and Berlin. Patients: Seventy-seven patients with acute, traumatic spinal cord injuries. Interventions: In the London patients, a pressure probe and a microdialysis catheter were placed intradurally on the surface of the injured cord for up to a week. Measurements and Main Results: Fever (> 37.5°C) occurs frequently (37% of the time) after spinal cord injury. High-grade fever (≥ 38°C) was associated with significantly more deranged metabolite levels than normothermia (36.5–37.5°C), that is, lower tissue glucose (median 2.0 vs 3.3 mM), higher lactate (7.8 vs 5.4 mM), higher glutamate (7.8 vs 6.4 µM), and higher lactate-to-pyruvate ratio (38.9 vs 29.3). High-grade fever was particularly detrimental on injury site metabolism when the peripheral leukocyte count was high. In the London and Berlin cohorts, high fever burden correlated with less neurologic improvement. Conclusions: Early after spinal cord injury, fever is associated with more deranged injury site metabolism than normothermia and worse prognosis.

Impairment of gastrointestinal (GI) motility is an undesirable but inevitable consequence of surgery. This prospective randomised controlled study tested the hypothesis that postoperative thoracic epidural analgesia (TEA) with ropivacaine or a combination of ropivacaine and morphine accelerates postoperative GI function and shortens the duration of postoperative ileus following major thoracic surgery compared to intravenous (IV) morphine. Thirty patients scheduled for major thoracic surgery were randomised to three groups. All patients had bowel motility assessments 1 week preoperatively. All patients received general anaesthesia. Group Ep-R received TEA with ropivacaine; group Ep-RM received TEA with ropivacaine and morphine and group IV-M received IV morphine via patient controlled analgesia pump (PCA). Bowel motility was assessed by clinical examination in addition to oro-ceacal transit time (OCTT) on the first and third postoperative days and colonic transit time (CTT). Overall the OCTT demonstrated a 2.5-fold decrease in bowel motility on the first postoperative day. The OCTT test revealed statistically significant differences between all groups (Ep-R vs Ep-RM, p = 0.43/Ep-R vs IV-M, p = 0.039 / Ep-RM vs IV-M, p < 0.001). Also, very significant differences were found in the OCCT test between days (Ep-R vs Ep-RM, p < 0.001/Ep-R vs IV-M, p < 0.001 / Ep-RM vs IV-M, p = 0.014). There were no significant differences in the CTT test or the clinical signs between groups. However, 70% of the patients in the Ep-R group and 80% in the Ep-RM group defecated by the third day compared to only 10% in the IV-M group, (p = 0.004). Objective tests demonstrated the delayed motility of the whole GI system postoperatively following thoracic surgery. They also demonstrated that continuous epidural analgesia with or without morphine improved GI motility in comparison to intravenous morphine. These differences were more pronounced on the third postoperative day. ISRCTN number: 11953159 , retrospectively registered on 20/03/2017.

The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self‐organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self‐organizing topology‐preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near‐normal, ischemic, hypermetabolic, and distal. We then visualized how patients’ intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient‐specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near‐normal spinal cord metabolic states (7 ± 4% vs. 58 ± 12%, p < 0.01, mean ± standard error) and more variable injury site metabolic responses (metabolism spread in 70 ± 11 vs. 40 ± 6 hexagons, p < 0.05), compared with patients who have incomplete neurological deficits. We conclude that Kohonen maps allow us to visualize the metabolic responses of the injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries. image