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Decision tree–based machine learning analysis of intraoperative vasopressor use to optimize neurological improvement in acute spinal cord injury

Nitin Agarwal, Alexander A. Aabedi, Abel Torres-Espin, Austin Chou, Thomas A. Wozny, Praveen V. Mummaneni, John F. Burke, Adam R. Ferguson, Nikos Kyritsis, Sanjay S. Dhall, Philip R. Weinstein, Xuan Duong-Fernandez, Jonathan Pan, Vineeta Singh, Debra D. Hemmerle, Jason F. Talbott, William D. Whetstone, Jacqueline C. Bresnahan, Geoffrey T. Manley, Michael S. Beattie, and Anthony M. DiGiorgio

OBJECTIVE

Previous work has shown that maintaining mean arterial pressures (MAPs) between 76 and 104 mm Hg intraoperatively is associated with improved neurological function at discharge in patients with acute spinal cord injury (SCI). However, whether temporary fluctuations in MAPs outside of this range can be tolerated without impairment of recovery is unknown. This retrospective study builds on previous work by implementing machine learning to derive clinically actionable thresholds for intraoperative MAP management guided by neurological outcomes.

METHODS

Seventy-four surgically treated patients were retrospectively analyzed as part of a longitudinal study assessing outcomes following SCI. Each patient underwent intraoperative hemodynamic monitoring with recordings at 5-minute intervals for a cumulative 28,594 minutes, resulting in 5718 unique data points for each parameter. The type of vasopressor used, dose, drug-related complications, average intraoperative MAP, and time spent in an extreme MAP range (< 76 mm Hg or > 104 mm Hg) were collected. Outcomes were evaluated by measuring the change in American Spinal Injury Association Impairment Scale (AIS) grade over the course of acute hospitalization. Features most predictive of an improvement in AIS grade were determined statistically by generating random forests with 10,000 iterations. Recursive partitioning was used to establish clinically intuitive thresholds for the top features.

RESULTS

At discharge, a significant improvement in AIS grade was noted by an average of 0.71 levels (p = 0.002). The hemodynamic parameters most important in predicting improvement were the amount of time intraoperative MAPs were in extreme ranges and the average intraoperative MAP. Patients with average intraoperative MAPs between 80 and 96 mm Hg throughout surgery had improved AIS grades at discharge. All patients with average intraoperative MAP > 96.3 mm Hg had no improvement. A threshold of 93 minutes spent in an extreme MAP range was identified after which the chance of neurological improvement significantly declined. Finally, the use of dopamine as compared to norepinephrine was associated with higher rates of significant cardiovascular complications (50% vs 25%, p < 0.001).

CONCLUSIONS

An average intraoperative MAP value between 80 and 96 mm Hg was associated with improved outcome, corroborating previous results and supporting the clinical verifiability of the model. Additionally, an accumulated time of 93 minutes or longer outside of the MAP range of 76–104 mm Hg is associated with worse neurological function at discharge among patients undergoing emergency surgical intervention for acute SCI.

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Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study

Nitin Agarwal, Jacob Blitstein, Austin Lui, Abel Torres-Espin, Chalisar Vasnarungruengkul, John Burke, Praveen V. Mummaneni, Sanjay S. Dhall, Philip R. Weinstein, Xuan Duong-Fernandez, Austin Chou, Jonathan Pan, Vineeta Singh, Adam R. Ferguson, Debra D. Hemmerle, Nikos Kyritsis, Jason F. Talbott, William D. Whetstone, Jacqueline C. Bresnahan, Michael S. Beattie, Geoffrey T. Manley, and Anthony DiGiorgio

OBJECTIVE

Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco.

METHODS

TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher’s exact test, univariate analysis, and multivariable regression analysis were performed.

RESULTS

The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission.

CONCLUSIONS

Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

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Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI): an overview of initial enrollment and demographics

Rachel E. Tsolinas, John F. Burke, Anthony M. DiGiorgio, Leigh H. Thomas, Xuan Duong-Fernandez, Mark H. Harris, John K. Yue, Ethan A. Winkler, Catherine G. Suen, Lisa U. Pascual, Adam R. Ferguson, J. Russell Huie, Jonathan Z. Pan, Debra D. Hemmerle, Vineeta Singh, Abel Torres-Espin, Cleopa Omondi, Nikos Kyritsis, Jenny Haefeli, Philip R. Weinstein, Carlos A. de Almeida Neto, Yu-Hung Kuo, Derek Taggard, Jason F. Talbott, William D. Whetstone, Geoffrey T. Manley, Jacqueline C. Bresnahan, Michael S. Beattie, and Sanjay S. Dhall

OBJECTIVE

Traumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI).

METHODS

Data were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury.

RESULTS

One hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed.

CONCLUSIONS

The authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

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Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study

Austin Lui, Christine Park, Timothy Chryssikos, Hannah Radabaugh, Arati Patel, Alexander A. Aabedi, Adam R. Ferguson, Abel Torres Espin, Praveen V. Mummaneni, Sanjay S. Dhall, Xuan Duong-Fernandez, Rajiv Saigal, Austin Chou, Jonathan Pan, Vineeta Singh, Debra D. Hemmerle, Nikos Kyritsis, Jason F. Talbott, Lisa U. Pascual, J. Russell Huie, William D. Whetstone, Jacqueline C. Bresnahan, Michael S. Beattie, Philip R. Weinstein, Geoffrey T. Manley, and Anthony M. DiGiorgio

OBJECTIVE

Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database.

METHODS

The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality.

RESULTS

The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery–related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non–spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery.

CONCLUSIONS

Initiation of LMWH within 24 hours was associated with a low rate of spine surgery–related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.