The Effect of Elevated Mean Arterial Blood Pressure in Cervical Traumatic Spinal Cord Injury with Hemorrhagic Contusion

Objective

Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied.

Methods

A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months.

Results

A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm². Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87–0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99–1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination.

Conclusion

The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

Introduction

Spinal cord injury (SCI) is a devastating disease, with an estimated global prevalence of 236–4187/1 million persons, leaving one third of these patients tetraplegic.^1,2 The incidence of SCI is expected to increase owing to falls among the aging populations in high-income countries and motor vehicle accidents in low- and middle-income countries.¹ SCI treatment in the acute setting includes spine immobilization, resuscitation, modern intensive care management, and spinal stabilization/decompression.³ After the primary mechanical injury, numerous secondary injury mechanisms will be initiated within the first hours to weeks, which have been documented in both preclinical animal models and histological studies.^4,5 Among the earliest injuries will be microvascular dysfunction and endothelial cell loss, resulting in edema, ischemia, and progressive hemorrhagic necrosis.⁴ Additionally, vasospasm and the loss of autoregulation will further reduce the blood flood to the spinal cord, accelerating neuronal and glial cell death.⁶

To prevent the secondary insult of vascular compromise, increasing the blood pressure parameters in the intensive care unit has been widely implemented. Maintaining the mean arterial pressure (MAP) at >85 mm Hg for 7 days after SCI was initially described by Levi et al.⁷ in 1993 and Vale et al.⁸ in 1997. These prospective studies demonstrated improvement in the long-term neurological outcomes with elevated MAP goals. Since then, 6 other retrospective studies have investigated MAP pushes in SCI, of which 3 supported the role of increased MAP goals to treat patients with SCI.⁹

Compared with the SCI literature, elevated blood pressure parameters to treat intracranial hemorrhage have been well studied relative to the pathology. For traumatic brain injury (TBI), the well-established recommendation from the Brain Trauma Foundation has been to avoid hypotension with a systolic blood pressure (SBP) of 100–110 mm Hg to improve the neurological outcomes. The effects of maintaining an elevated blood pressure in patients with TBI and intraparenchymal hemorrhage have been shown by multiple studies to have no significant effects on the hemorrhagic progression of contusion.10, 11, 12, 13, 14

Upper limit blood pressure parameters associated with spontaneous intracranial hemorrhage have also been well described. The relationship between the SBP and mortality in patients with intracerebral hemorrhage (ICH) has been established, with excessive SBP elevation associated with increased mortality.^13,15 The INTERACT2 (second intensive blood pressure reduction in acute cerebral haemorrhage trial) randomized controlled trial found favorable functional outcomes after ICH in patients who had received medical therapy with a target SBP of <140 mm Hg.¹⁶ However, that study did not reveal a significant effect on hematoma growth with increased blood pressure control. In contrast, multiple meta-analyses related to ICH and blood pressure control have demonstrated a reduction in hematoma growth.^17,18

Although sustaining an increased MAP has been the standard of care for patients with SCI, its effects in the setting of hemorrhagic contusion have remained unknown. Previous clinical studies have reported an association between the presence of hemorrhagic contusion and neurological outcomes. However, they had relied on a basic assessment (binary) and had not thoroughly investigated the variables related to hemorrhagic contusion.19, 20, 21, 22, 23 In animal studies, increased blood pressure values were related to the progression of cervical hemorrhagic contusion.²⁴ At present, no similar studies of humans have been performed, and the effects of elevated blood pressure parameters on spinal hemorrhagic contusion remain unknown.

The present study investigated the effects of elevated MAP goals in a subset of patients with cervical SCI (CSCI) with hemorrhagic contusion and determined whether an elevated MAP would predict for the expansion of these contusions. Furthermore, we assessed the predictors of long-term neurological outcomes at the final ≥6-month examination in patients with hemorrhagic contusions.