All over the MAP: describing pressure variability in acute spinal cord injury.

STUDY DESIGN: Observational study. OBJECTIVES: To examine the feasibility of meeting the current clinical guidelines for the hemodynamic management of acute spinal cord injury (SCI) which recommend maintaining mean arterial pressure (MAP) at 85-90 mmHg in the days following injury. METHODS: This study examined data collected minute-by-minute to describe the pressure profile in the first 5 days following SCI in 16 patients admitted to the Intensive Care Unit at Vancouver General Hospital (40 ± 19 years, 13 M/3 F, C4-T11). MAP and intrathecal pressure (ITP) were monitored at 100 Hz by arterial and lumbar intrathecal catheters, respectively, and reported as the average of each minute. Spinal cord perfusion pressure was calculated as the difference between MAP and ITP. The minute-to-minute difference (MMdiff) of each pressure variable was calculated as the absolute difference between consecutive minutes. RESULTS: Only 24 ± 7% of MAP recordings were between 85 and 90 mmHg. Average MAP MMdiff was ~3 mmHg. The percentage of MAP recordings within target range was negatively correlated with the degree of variability (i.e. MMdiff; r = -0.64, p < 0.008) whereas higher mean MAP was correlated with greater variability (r = 0.57, p = 0.021). CONCLUSIONS: Our findings point to the 'real life' challenges in maintaining MAP in acute SCI patients. Given MAP fluctuated ~3 mmHg minute-to-minute, maintaining MAP within a 5 mmHg range with conventional volume replacement and vasopressors presents an almost impossible task for clinicians and warrants reconsideration of current management guidelines.

Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study.

There is currently a lack of information regarding neuropathic pain in the very early stages of spinal cord injury (SCI). In the present study, neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) for the patient's worst pain within the first 5 days of injury (i.e., hyperacute) and on follow-up at 3, 6, and 12 months. Within the hyperacute time frame (i.e., 5 days), at- and below-level neuropathic pain were reported as the worst pain in 23% (n = 18) and 5% (n = 4) of individuals with SCI, respectively. Compared to the neuropathic pain observed in this hyperacute setting, late presenting neuropathic pain was characterized by more intense painful electrical and cold sensations, but less itching sensations. Phenotypic differences between acute and late neuropathic pain support the incorporation of timing into a mechanism-based classification of neuropathic pain after SCI. The diagnosis of acute neuropathic pain after SCI is challenged by the presence of nociceptive and neuropathic pains, with the former potentially masking the latter. This may lead to an underestimation of the incidence of neuropathic pain during the very early, hyperacute time points post-injury. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01279811) PERSPECTIVE: This article presents distinct pain phenotypes of hyperacute and late presenting neuropathic pain after spinal cord injury and highlights the challenges of pain assessments in the acute phase after injury. This information may be relevant to clinical trial design and broaden our understanding of neuropathic pain mechanisms after spinal cord injury.

Empirical targets for acute hemodynamic management of individuals with spinal cord injury.

OBJECTIVE: To determine the hemodynamic conditions associated with optimal neurologic improvement in individuals with acute traumatic spinal cord injury (SCI) who had lumbar intrathecal catheters placed to measure CSF pressure (CSFP). METHODS: Ninety-two individuals with acute SCI were enrolled in this multicenter prospective observational clinical trial. We monitored mean arterial pressure (MAP) and CSFP during the first week after injury and assessed neurologic function at baseline and 6 months after injury. We used relative risk iterations to determine transition points at which the likelihood of either improving neurologically or remaining unchanged neurologically was equivalent. These transition points guided our analyses in which we examined the linear relationships between time spent within target hemodynamic ranges (i.e., clinical adherence) and neurologic recovery. RESULTS: Relative risk transition points for CSFP, MAP, and spinal cord perfusion pressure (SCPP) were linearly associated with neurologic improvement and directed the identification of key hemodynamic target ranges. Clinical adherence to the target ranges was positively and linearly related to improved neurologic outcomes. Adherence to SCPP targets, not MAP targets, was the best indicator of improved neurologic recovery, which occurred with SCPP targets of 60 to 65 mm Hg. Failing to maintain the SCPP within the target ranges was an important detrimental factor in neurologic recovery, particularly if the target range is set lower. CONCLUSION: We provide an empirical, data-driven approach to aid institutions in setting hemodynamic management targets that accept the real-life challenges of adherence to specific targets. Our results provide a framework to guide the development of widespread institutional management guidelines for acute traumatic SCI.

Evaluation of a Clinical Protocol to Assess and Diagnose Neuropathic Pain During Acute Hospital Admission: Results From Traumatic Spinal Cord Injury.

OBJECTIVES: A clinical protocol was developed for clinicians to routinely assess and initiate treatment for patients with neuropathic pain (NP) in an acute care setting. The objectives of this study were to: (1) determine the incidence and onset of NP in patients with traumatic spinal cord injury during acute care and (2) describe how the implementation of a clinical protocol impacts the assessment and diagnosis of NP. MATERIALS AND METHODS: The study was a cohort analysis with a pre-post-test utilizing a historical control. Data were retrospectively collected from a patient registry and charts. Participants were randomly selected in cohort 1 (control) and cohort 2 (NP clinical protocol). RESULTS: The incidence of NP was 56% without significant difference between the cohorts (P=0.3). Onset of NP was 8 days (SD=14) across the study and >85% of the participants with NP were diagnosed within 2 weeks. Participants with incomplete injuries had a significant earlier onset than participants with complete injuries (6.2±12.8, 10.9±15.8 d; P=0.003). The mean number of days from hospital admission to initial assessment decreased with use of the NP clinical protocol (3.7±5.7 d; P=0.02). DISCUSSION: This study demonstrates a high incidence and early onset of NP in traumatic spinal cord injury during acute hospital care, with an earlier emergence in participants with incomplete injury. The NP clinical protocol ensured continuous assessment and documentation of NP while decreasing the time to an initial screen, but did not impact diagnosis.

Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury.

OBJECTIVE: To determine whether spinal cord perfusion pressure (SCPP) as measured with a lumbar intrathecal catheter is a more predictive measure of neurologic outcome than the conventionally measured mean arterial pressure (MAP). METHODS: A total of 92 individuals with acute spinal cord injury were enrolled in this multicenter prospective observational clinical trial. MAP and CSF pressure (CSFP) were monitored during the first week postinjury. Neurologic impairment was assessed at baseline and at 6 months postinjury. We used logistic regression, systematic iterations of relative risk, and Cox proportional hazard models to examine hemodynamic patterns commensurate with neurologic outcome. RESULTS: We found that SCPP (odds ratio 1.039, p = 0.002) is independently associated with positive neurologic recovery. The relative risk for not recovering neurologic function continually increased as individuals were exposed to SCPP below 50 mm Hg. Individuals who improved in neurologic grade dropped below SCPP of 50 mm Hg fewer times than those who did not improve (p = 0.012). This effect was not observed for MAP or CSFP. Those who were exposed to SCPP below 50 mm Hg were less likely to improve from their baseline neurologic impairment grade (p = 0.0056). CONCLUSIONS: We demonstrate that maintaining SCPP above 50 mm Hg is a strong predictor of improved neurologic recovery following spinal cord injury. This suggests that SCPP (the difference between MAP and CSFP) can provide useful information to guide the hemodynamic management of patients with acute spinal cord injury.

Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.

Neurologic impairment after spinal cord injury (SCI) is currently measured and classified by functional examination. Biological markers that objectively classify injury severity and predict outcome would greatly facilitate efforts to evaluate acute SCI therapies. The purpose of this study was to determine how well inflammatory and structural proteins within the cerebrospinal fluid (CSF) of acute traumatic SCI patients predicted American Spinal Injury Association Impairment Scale (AIS) grade conversion and motor score improvement over 6 months. Fifty acute SCI patients (29 AIS A, 9 AIS B, 12 AIS C; 32 cervical, 18 thoracic) were enrolled and CSF obtained through lumbar intrathecal catheters to analyze interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tau, S100ß, and glial fibrillary acidic protein (GFAP) at 24 h post-injury. The levels of IL-6, tau, S100ß, and GFAP were significantly different between patients with baseline AIS grades of A, B, or C. The levels of all proteins (IL-6, IL-8, MCP-1, tau, S100ß, and GFAP) were significantly different between those who improved an AIS grade over 6 months and those who did not improve. Linear discriminant analysis modeling was 83% accurate in predicting AIS conversion. For AIS A patients, the concentrations of proteins such as IL-6 and S100ß correlated with conversion to AIS B or C. Motor score improvement also was strongly correlated with the 24-h post-injury CSF levels of all six biomarkers. The analysis of CSF can provide valuable biological information about injury severity and recovery potential after acute SCI. Such biological markers may be valuable tools for stratifying individuals in acute clinical trials where variability in spontaneous recovery requires large recruitment cohorts for sufficient power.

Development and assessment of a community follow-up questionnaire for the Rick Hansen spinal cord injury registry.

OBJECTIVE: To develop a comprehensive community follow-up questionnaire for participants enrolled in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). DESIGN: Development and preliminary assessment of measurement properties (reliability and validity) of instruments used during a community follow-up and aligned with the International Classification of Functioning, Disability and Health (ICF). SETTING: General community setting. PARTICIPANTS: People with spinal cord injury (N=50) living in the community. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A comprehensive follow-up questionnaire, referred to as the RHSCIR Community Follow-up Questionnaire Version 2.0 (CFQ-V2.0), includes 8 instruments. Four new instruments were developed, 2 existing instruments were modified, and 2 previously published instruments were included. RESULTS: Intra- and interrater reliability statistics (Gwet's AC1) support the measurement properties of the new and modified instruments. Correlations between new and existing instruments and between groups based on the severity of injury support the construct validity of the secondary complications and person-perceived participation instruments. CONCLUSIONS: The RHSCIR CFQ-V2.0 is a comprehensive community follow-up questionnaire that aligns to the ICF. Initial study results suggest that it covers all relevant aspects of community living, and the measurement properties are promising.

Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury.

There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.

Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial.

OBJECT: Ischemia is an important factor in the pathophysiology of secondary damage after traumatic spinal cord injury (SCI) and, in the setting of thoracoabdominal aortic aneurysm repair, can be the primary cause of paralysis. Lowering the intrathecal pressure (ITP) by draining CSF is routinely done in thoracoabdominal aortic aneurysm surgery but has not been evaluated in the setting of acute traumatic SCI. Additionally, while much attention is directed toward maintaining an adequate mean arterial blood pressure (MABP) in the acute postinjury phase, little is known about what is happening to the ITP during this period when spinal cord perfusion pressure (MABP - ITP) is important. The objectives of this study were to: 1) evaluate the safety and feasibility of draining CSF to lower ITP after acute traumatic SCI; 2) evaluate changes in ITP before and after surgical decompression; and 3) measure neurological recovery in relation to the drainage of CSF. METHODS: Twenty-two patients seen within 48 hours of injury were prospectively randomized to a drainage or no-drainage treatment group. In all cases a lumbar intrathecal catheter was inserted for 72 hours. Acute complications of headache/nausea/vomiting, meningitis, or neurological deterioration were carefully monitored. Acute Spinal Cord Injury motor scores were documented at baseline and at 6 months postinjury. RESULTS: On insertion of the catheter, mean ITP was 13.8 +/- 1.3 mm Hg (+/- SD), and it increased to a mean peak of 21.7 +/- 1.5 mm Hg intraoperatively. The difference between the starting ITP on catheter insertion and the observed peak intrathecal pressure after decompression was, on average, an increase of 7.9 +/- 1.6 mm Hg (p < 0.0001, paired t-test). During the postoperative period, the peak recorded ITP in the patients randomized to the no-drainage group was 30.6 +/- 2.3 mm Hg, which was significantly higher than the peak intraoperative ITP (p = 0.0098). During the same period, the peak recorded ITP in patients randomized to receive drainage was 28.1 +/- 2.8 mm Hg, which was not statistically higher than the peak intraoperative ITP (p = 0.15). CONCLUSIONS: The insertion of lumbar intrathecal catheters and the drainage of CSF were not associated with significant adverse events, although the cohort was small and only a limited amount of CSF was drained. Intraoperative decompression of the spinal cord results in an increase in the ITP measured caudal to the injury site. Increases in intrathecal pressure are additionally observed in the postoperative period. These increases in intrathecal pressure result in reduced spinal cord perfusion that will otherwise go undetected when measuring only the MABP. Characteristic changes in the observed intrathecal pressure waveform occur after surgical decompression, reflecting the restoration of CSF flow across the SCI site. As such, the waveform pattern may be used intraoperatively to determine if adequate decompression of the thecal sac has been accomplished.