Early complications of high-dose methylprednisolone in acute spinal cord injury patients

doi:10.1016/j.injury.2007.12.005

Injury

Volume 39, Issue 7, July 2008, Pages 748-752

https://doi.org/10.1016/j.injury.2007.12.005 Get rights and content

Summary

Background

To evaluate the early complications and effect on neurological outcome of methylprednisolone (MP) treatment in spinal cord injury (SCI) patients during the acute phase.

Methods

We retrospectively reviewed the whole cohort of patients admitted to our ICU between January 1994 and December 2005 due to acute SCI. Patients were grouped according to the medical treatment received (MP group versus no-MP group). Patient data as age, gender, Glasgow coma score (GCS), APACHE II, injury severity score (ISS) and ICU stay were recorded. Outcome at ICU discharge and neurological function based on Frankel grade was recorded at ICU admission and at ICU discharge. Early complications were also noted.

Results

There were no differences between both groups in ICU mortality (OR = 0.48; 95% CI: 0.08–3.64) nor neurological function at ICU discharge. (OR = 1.09; 95% CI: 0.35–3.66). MP group presented an increase in respiratory tract infections (OR = 8.19; 95% CI: 1.10–358.6) and in total infections (OR = 4.90; 95% CI: 1.46–18.83) compared to no-MP group during the ICU stay. There was a significant increase in the incidence of hyperglycaemia in the MP group (OR = 17.0; 95% CI: 4.52–66.3).

Conclusions

: The use of MP in patients with acute SCI is not associated with an improvement in outcome or neurological function at ICU discharge. Moreover, the use of MP is associated with an increased risk of infectious and metabolic complications during ICU stay.

Introduction

Few conditions are as devastating as traumatic spinal cord injury (SCI). This type of injury is a major cause of morbidity in young individuals and as a result has a major impact on society as a whole.¹¹ During most of the last century, the management of acute SCI has traditionally concentrated on preventive measures as well as conservative care.

In 1990, Bracken et al.¹ first reported the effectiveness of methylprednisolone (MP) treatment in recovery from SCI. After this study the use of intravenous high-dose MP in acute SCI became a standard aspect of care in these patients. A number of published critiques of the NASCIS II data and their presentation in support of the use of MP in the management of patients with acute SCI have been offered. Over the past 10 years, a lively debate has ensued in the literature over whether or not steroids should be used at all in SCI. Many authors have tried to further distil and objectify the results of the NASCIS studies, most with unfavourable conclusions.12, 20 Moreover, some authors have suggested that the use of high-dose MP in acute SCI is associated with an increase in complications.14, 19 Finally, the American Association of Neurological Surgeons Joint Section of Disorders of the Spine and Peripheral Nerves recommended the use of MP only as an option, not as a guideline or standard.¹⁷ Despite these considerations, many physicians continue to prescribe methylprednisolone for acute SCI even today.2, 13

We aimed to review the outcome of patients admitted to our intensive care unit (ICU) with SCI from 1994 to 2005, according to the use or not of MP (NASCIS II protocol).

Section snippets

Patients and methods

We retrospectively reviewed the whole cohort of patients admitted to our ICU between January 1994 and December 2005 due to SCI. Eligible patients were those who were older than 14 years and ICU hospitalisation within 8 h of vertebral trauma with spinal cord involvement. Patients were grouped according to the medical treatment received. Those patients who received MP according to NASCIS II protocol were considered as MP group, and patients who did not receive MP were considered as no-MP group. MP

Results

There were 59 patients in the MP group and 23 patients in the No-MP group. There was no significant difference in sex ratio or age between the groups (Table 1). All patients had a neurological deficit of varying degrees according to Frankel scale at ICU admission, and there was no difference between the groups (Table 2).

There were no differences between both groups in ICU mortality. Four patients died in MP group (6.7%) and 3 patients in No-MP group (13%) (OR = 0.48; 95% CI: 0.08–3.64). There

Discussion

The hope that administration of a drug delivered after acute SCI might improve neurological function has long been held. Although other substances, as naloxone and GM-1 ganglioside, have been tested in laboratory and in clinical investigations, corticosteroids, particularly methylprednisolone, have been the most extensively studied drugs in animal and human studies.10, 17 The precise mechanism of action is not completely known, but corticosteroids have the potential to stabilise membrane

Conflict of interest

None.

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Spinal cord is the major communicating system between the brain and the body, injury to the spinal cord will completely cut or damage the information and signal exchanges between brain and different parts of the body. Spinal cord injury (SCI) regulates the physical, cellular, and molecular function of the body. SCI could cause impairment in blood flow, breathing, temperature, body pressure and sensory appendages. Thus, serious steps must be taken to prevent and heal SCI in human body by severe damages and shocks. Nanoparticles are emerging in the field of biomedicine and gained attention as drug carriers, imaging, mediator for supportive chemical and accelerating the immunes cells. In recent time, nanoparticles are gaining interest towards improving or modifying the immune system for the treatment of SCI. The drug delivery efficacy of nanoparticles makes them easy to incorporate and load with molecules used for the treatment of SCI, also it enhances the recovery time by targeting localization, altering the signalling pathways and cellular uptake. Researchers are using nanoparticles with different synthesis methods, morphology, incorporating materials, stability and site of target. But exploring the ability of nanoparticles towards improving the healing mechanism, regeneration of SCI and accelerating the treatment time is the major necessity. Thus considering the lesser exposure of nanoparticles in the area of spinal cord injury and regeneration of cells, the present review give a brief knowledge about the different types of nanoparticles and its role in SCI therapy.
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This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.
Emerging Therapeutic Strategies for Traumatic Spinal Cord Injury
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Citation Excerpt :
However, several lines of evidence have shown that MP therapy within the first 8 hours after SCI failed to result in a statistically significant short-term or long-term improvement in patients’ overall motor or neurologic scores compared with controls who did not receive steroids.5-7 Moreover, steroid use was significantly associated with an increased risk of hyperglycemia in both randomized controlled trials2,8,9 and observational studies,10-15 and pneumonia based on data from observational studies.10-16 In the light of these observations, the risk/benefit ratio should be carefully considered before initiation of steroid therapy after SCI, and literature advocating routine use of MP after SCI should be strongly reconsidered.
Spinal cord injury (SCI) is a debilitating neurologic condition with tremendous socioeconomic impact on affected individuals and the health care system. The treatment of SCI principally includes surgical treatment and marginal pharmacologic and rehabilitation therapies targeting secondary events with minor clinical improvements. This unsuccessful result mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiologic changes that occur in the injured spinal cord. Once the nervous system is injured, cascades of cellular and molecular events are triggered at varying times. Although the cascade of tissue reactions and cell injury develops over a period of days or weeks, the most extensive cell death in SCI occurs within hours of trauma. This situation suggests that early intervention is likely to be the most promising approach to rescue the cord from further and irreversible cell damage. Over the past decades, a wealth of research has been conducted in preclinical and clinical studies with the hope to find new therapeutic strategies. Researchers have identified several targets for the development of potential therapeutic interventions (e.g., neuroprotection, replacement of cells lost, removal of inhibitory molecules, regeneration, and rehabilitation strategies to induce neuroplasticity). Most of these treatments have passed preclinical and initial clinical evaluations but have failed to be strongly conclusive in the clinical setting. This narrative review provides an update of the many therapeutic interventions after SCI, with an emphasis on the underlying pathophysiologic mechanisms.
The safety and efficacy of steroid treatment for acute spinal cord injury: A Systematic Review and meta-analysis
2020, Heliyon
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A total of 12 studies met the inclusion criteria and were incorporated into the meta-analysis. These included five randomized controlled trials (RCTs) [4, 8, 16, 17, 18] and seven observational studies (OBSs) [19, 20, 21, 22, 23, 24, 25]. The characteristics of the twelve studies are shown in Table 1.
The role for steroids in acute spinal cord injury (ASCI) remains unclear; while some studies have demonstrated the risks of steroids outweigh the benefits,a meta-analyses conducted on heterogeneous patient populations have shown significant motor improvement at short-term but not at long-term follow-up. Given the heterogeneity of the patient population in previous meta-analyses and the publication of a recent trial not included in these meta-analyses, we sought to re-assess and update the safety and short-term and long-term efficacy of steroid treatment following ASCI in a more homogeneous patient population.
A literature search was conducted on PubMed, EMBASE and Cochrane Library through June 2019 for studies evaluating the utility of steroids within the first 8 h following ASCI. Neurological and safety outcomes were extracted for patients treated and not treated with steroids. Pooled effect estimates were calculated using the random-effects model.
Twelve studies, including five randomized controlled trials (RCTs) and seven observational studies (OBSs), were meta-analyzed. Overall, methylprednisolone was not associated with significant short-term or long-term improvements in motor or neurological scores based on RCTs or OBSs. An increased risk of hyperglycemia was shown in both RCTs (RR: 13.7; 95% CI: 1.93, 97.4; 1 study) and OBSs (RR: 2.9; 95% CI: 1.55, 5.41; 1 study). Risk for pneumonia was increased with steroids; while this increase was not statistically significant in the RCTs (pooled RR: 1.16; 95% C.I: 0.59, 2.29; 3 studies), it reached statistical significance in the OBSs (pooled RR: 2.00; 95% C.I: 1.32, 3.02; 6 studies). There was no statistically significant increased risk of gastrointestinal bleeding, decubitus ulcers, surgical site infections, sepsis, atelectasis, venous thromboembolism, urinary tract infections, or mortality among steroid-treated ASCI patients compared to untreated controls in either RCTs or OBSs.
Methylprednisolone therapy within the first 8 h following ASCI failed to show a statistically significant short-term or long-term improvement in patients' overall motor or neurological scores compared to controls who were not administered steroids. For the same comparison, there was an increased risk of pneumonia and hyperglycemia compared to controls. Routine use of methylprednisone following ASCI should be carefully considered in the context of these results.
Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury
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Therefore, prevention of secondary damage in the acute phase of spinal cord injury is of utmost importance, which offers the opportunity of functional improvement by disease-modifying interventions [7,13]. Until the recent past, steroids were applied for this purpose [14], although wide spread use has stopped due to limited effects and severe adverse effects [15,16]. In SCI, a therapeutic intervention combining both anti-inflammatory and regenerative properties is an unmet need.
Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100 μL suspension of 400,000 fresh human bone marrow-derived CD34⁺ and an equal number of CD105⁺ stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats. During the first 5 weeks after this intervention, NC significantly improved locomotor recovery and induced less injury-associated adverse events compared to vehicle-treated rats.
Histological analysis showed that NC reduced astrogliosis, and apoptosis early after administration (day 4), but not at a later stage (day 56) after SCI. Proteomic studies (at day 56) pointed to the release of paracrine factors and identified proteins involved in regenerative processes. As stem cells seem to reach their effects in acute lesions by mainly suppressing (secondary) inflammation, it is thus realistic to expect a lower magnitude of their eventual beneficial effect in T-cell deficient rats, a fact reinforcing the robustness of Neuro-Cells efficacy. Taken together, this study indicates that an intrathecal instillation of Neuro-Cells holds great promise as a neuro-regenerative intervention in a clinical setting with acute SCI patients.
Steroids in Acute Spinal Cord Injury: All But Gone Within 5 Years
2019, World Neurosurgery
Spinal cord injury (SCI) is a devastating event often leading to poor neurologic outcomes. One of the most widely practiced treatments has been the administration of methylprednisolone. However, today its use has been called into question over concerns of efficacy and safety. The present study evaluated the changes in the practice of steroid administration in acute SCI among members of the National Spinal Society in Poland in comparison with the results of the survey conducted in 2013.
The questionnaire, comprising 5 questions, was distributed among 240 spinal surgeons, members of the Polish Society of Spinal Surgery; of these, 97 (40%) responded. The results were compared with data from the previous survey conducted in 2013.
Over a period of 5 years, the prevalence of steroid administration in acute SCI has completely reversed; the proportion of steroid users declined from 73% to 27%. The main rationale for using it was belief in efficacy, rather than fear of litigation. The differences between specialization and age groups were not statistically significant in both administrations.
A significant decrease was observed in the number of surgeons using steroids in the acute SCI, similar to that reported in the literature. The critical appraisal of the existing clinical evidence, as well as the formulation of guidelines by professional organizations, exerted a profound impact on the practice pattern.

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Early complications of high-dose methylprednisolone in acute spinal cord injury patients

Summary

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Conflict of interest

NeuroRx

Injury

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study

N Engl J Med

Questionnaire survey of spine surgeons on the use of methylprednisolone for acute spinal cord injury

Spine

Current status of clinical trials for acute spinal cord injury

Injury

The role and timing of early decompression for cervical spinal cord injury: update with a review of recent clinical evidence

Injury

The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia

Paraplegia

Failure of methylprednisolone to improve the outcome of spinal cord injuries

Am Surg

Utilization and effectiveness of methylprednisolone in a population-based sample of spinal cord injured persons

Paraplegia

Consequences of high-dose steroid therapy for acute spinal cord injury

J Trauma

Post-traumatic inflammation following spinal cord injury

Spinal Cord