Medical Management of Adult and Pediatric Spinal Cord Injury

Pathophysiology

Acute spinal cord injury (SCI) consists of an initial traumatic primary injury followed by secondary injury occurring through a gradual cascade of tissue destruction and systemic autonomic consequences, resulting in disrupted spinal cord functionality and homeostasis. This section emphases the underlying pathophysiology of traumatic SCI, highlighting how neuronal destruction occurs by these mechanisms, and establishes a basis for further discussion regarding the role for medical management in dampening additional injury and optimizing neurological recovery.

Secondary Injury

After the primary injury event, disrupted spinal cord tissue is subjected to a cascade of pathophysiological processes that serves to expand the zone of neural tissue injury and further exacerbate neurological injury and deficits, thus constituting the secondary injury phase. ^{, ,} The secondary injury phase is progressive, and begins immediately after the primary injury and is subclassified into the immediate (≤2 hours), early acute (≤48 hours), subacute (≤2 weeks), intermediate (2 weeks to 6 months), and chronic (>6 months) phases ( Fig. 162.1 ).

Pathophysiological events that occur in the spinal cord after the primary injury include edema, disrupted microcirculation, loss of autoregulation, neuronal damage, and excitotoxicity. Acute cell death and dysfunction after the initial injury disrupt cellular membrane integrity and permeability, initiating a proapoptotic signaling cascade. Microvascular disruption of the blood–spinal cord barrier exposes injured tissue to edema, causing vascular congestion, thrombosis, and hypoxia. Because of the impaired blood–spinal cord barrier, there is an immense inflammatory cell migration of macrophages, microglial cells, T cells, and neutrophils that release numerous cytokines, such as tumor necrosis factor (TNF)–α and interleukin (IL)–1α, IL-1β, and IL-6 that mediate further inflammatory processes and present a harsh environment for the survival of neural tissue. ^, Cytokine levels peak at 6 to 12 hours postinjury and remain elevated up to 4 days after injury. ^, There is also release of reactive oxygen species from inflammatory and phagocytic cell infiltrates that cause DNA damage, protein oxidation, and lipid peroxidation, inducing necrosis, apoptosis, and progressive neurological deficit. ^{, ,}

Loss of ionic homeostasis causes hypercalcemia, thereby activating calcium-dependent proteases and causing mitochondrial dysfunction, which induces apoptotic cellular death. Oligodendrocytes are susceptible to apoptosis and have demonstrated apoptotic death at both the injury site and distant areas. Additionally, release of the excitatory amino acids glutamate and aspartate from injured cells causes excessive stimulation of excitatory amino acid receptors, producing excitotoxicity and propagating neuronal death.

Following the early phases of secondary injury, astrocytes at the periphery of the insult proliferate and commence forming a gliotic scar, which is a physical and chemical barrier prohibiting axonal regeneration. Subsequent glial scar maturation occurs and leads to the formation of cysts, often syrinxes. ^, Collectively, these interrelated processes magnify cascading systemic and cellular events that compose the secondary insult ( Table 162.1 ). There is optimism that cell-based regenerative strategies may hold promise in these later phases.

Table 162.1

Summarized Description of the Secondary Injuries Associated With Spinal Cord Injury

From Dumont RJ, Okonkwo DO, Verma S, et al. Acute spinal cord injury. Part I. Pathophysiologic mechanisms. Clin Neuropharmacol . 2001;24(5):254-264; Kwon BK, Tetzlaff W, Grauer JN, et al. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J . 2004;4(4):451-464.

Secondary Injury Events	Characteristics
Neurogenic shock	Bradycardia, hypotension, reduced peripheral resistance, decreased cardiac output, ischemia
Vascular disruption	Hemorrhagic and ischemic damage, disrupted microcirculation, hemorrhagic necrosis, vasospasm
Free radical generation and lipid peroxidation	Free radical production, oxidative stress, oxidation of proteins, lipids and nucleic acids, inactivation of mitochondrial respiratory chain enzymes, inhibited Na + -K + ATPase, Na + channel inactivation
Excitotoxicity and electrolyte imbalance	Excessive release of glutamate, NMDAR and AMPAR activation, cytotoxic edema, intracellular acidosis, accumulation of intracellular Ca 2+
Necrotic and apoptotic cell death	Swelling, damaged organelles, lysis, cellular shrinkage, nuclear fragmentation
Inflammation and immunological response	Neutrophil accumulation, macrophage and microglia migration, demyelination, Wallerian degeneration, scarring, mitochondrial damage, cytochrome C release, caspase activation

Na ⁺ -K ⁺ ATPase, Sodium- and potassium-activated adenosine triphosphatase; Na ⁺ , sodium; Ca ²⁺ , calcium; NMDAR , N-Methyl-D-aspartate receptor; AMPAR , α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor.

Acute Medical Management

Management of acute traumatic SCI begins immediately after the inciting injury. Patients should be thoroughly assessed in a judicious fashion with a systematic approach to rapid assessment of injuries and implementation of life-preserving therapy established in the Advanced Trauma Life Support Guidelines. Stabilization at the scene is imperative in the early treatment of the patient and is vital in limiting further primary and secondary injury. In 2019 the Congress of Neurological Surgeons provided guidelines for the neurological assessment of patients with thoracolumbar spine trauma. Airway maintenance, circulation, and transfer are of utmost importance. This section reviews the specific considerations for medical management of a patient with an acute SCI in the immediate postinjury period.

Airway Protection and Ventilation

Ventilatory insufficiency and impaired airway secretion clearance are frequent complications of SCI, which is the leading cause of death in both acute and chronic stages. Maintaining appropriate oxygenation and ventilation is of extreme significance in patients with SCI. Sufficient oxygenation ensures adequate oxygen delivery to spinal cord tissue to prevent further ischemic events and secondary injury mechanisms. ^,

Any patient exhibiting impaired upper airway reflexes or impending airway compromise should have a definitive airway established immediately. SCI above the level of C3 leads to loss of diaphragmatic function and immediate respiratory failure unless mechanical ventilation is initiated. Although diaphragm function is spared with injury below C3, ventilation remains compromised. Dysfunction of the muscles of inspiration and expiration caused by the primary injury may be further exacerbated by pulmonary injury, which leads to poor gas exchange and decreased lung compliance. ^{, ,} Clinicians must be aware of associated factors that may contribute to airway compromise, including diminished level of consciousness from traumatic brain injury or intoxication.

Inefficient ventilation that occurs following SCI is initially tolerated and is compensated for by an increase in respiratory rate. However, rapid and shallow breathing is difficult to maintain, leading to increased work of breathing, low lung volumes, poor gas exchange, and ultimately respiratory fatigue. Establishment of a definitive airway should also be considered early in the management of any patient with signs of impending airway compromise, such as increasing respiratory rate, hypercarbia, abnormal breath sounds, dysphonia, or soft tissue swelling of the neck. ^, In these events, definitive airway placement with positive pressure ventilation should be strongly considered to avoid hypoxemia and secondary injury.

Intubation

Intubation is ideally performed under a controlled setting rather than emergent. Approximately one-third of patients with cervical SCI require intubation within 24 hours of injury, and 90% of those patients developing respiratory failure do so within the first 3 days. Early intubation and ventilation are indicated in patients with high cervical injuries (C1‒C5) resulting in impaired diaphragmatic function, respiratory depression, and carbon dioxide retention. Maintaining spinal alignment of the potentially unstable spine is of the paramount importance, particularly in cervical SCI. When an urgent airway control is needed, rapid-sequence induction with manual in-line spinal immobilization is generally considered the standard of care. In patients without an emergent need for airway protection, fiberoptic tracheal intubation remains safest.

The induction agent of choice varies, but optimal agent properties should produce minimal hypotension and avoid harmful effects on the central nervous system (CNS). Propofol and thiopental are typically avoided, as they can exacerbate hypotension. Ketamine can cause hypertension; however, its use in patients with CNS injury is debated, owing to its effect of raising neuraxial pressure. Etomidate has minimal effect on hemodynamics and is a reasonable option; however, questions remain regarding its safety because it inhibits cortical synthesis and may be associated with adrenal dysfunction. Use of short-acting opioids is an option for analgesia to avoid prolonged apnea or hypoxemia in cases of difficult intubation. Succinylcholine is ideal in most cases of neuromuscular blockade within 48 hours of injury because of its rapid onset and short half-life; however, it should be avoided in SCI after more than 4 days because of the risk of potentially life-threatening hyperkalemia. ^, Nondepolarizing neuromuscular blocking agents such as rocuronium should be used beyond the 48-hour time window.

Hypotension and bradycardia must be expected during induction and endotracheal intubation of a patient with a high cervical SCI. Positive pressure ventilation can also instigate hypotension secondary to raised intrathoracic pressure, thereby impairing cardiac filling in the setting of low systemic vascular resistance. ^, Management of these factors can be attended to in a timely manner with fluids, vasoactive agents, and atropine, which are discussed in the following section.

Circulatory Support

Damaged spinal cord tissue is susceptible to the deleterious effects of systemic hypoperfusion (hypoxia and ischemia), which should be avoided to prevent secondary injury. In the setting of trauma, it is imperative that other potential causes of hypotension and hemodynamic instability be addressed, such as hemorrhage, sepsis, tension pneumothorax, and cardiac tamponade. Hypotension and/or neurogenic shock should be treated with aggressive volume resuscitation. Adequate fluid resuscitation with isotonic crystalloids to restore intravascular volume is essential but must be managed cautiously to prevent fluid overload. Using lactate level and base deficit can act as surrogate markers for guiding fluid resuscitation. It is recommended that hypotension (systolic blood pressure [SBP] <90 mm Hg) be corrected as soon as possible, and mean arterial blood pressure (MAP) be maintained between 85 and 90 mm Hg for the first 7 days following an acute SCI. Suggested parameters to prevent hypotension include SBP 90 to 100 mm Hg, heart rate of 60 to 100 beats per minute, urine output greater than 30 mL per hour, and normothermia. ^{, ,} The joint guidelines of the American Association of Neurologic Surgeons and the Congress of Neurologic Surgeons for cervical spine injury management recommend MAP greater than 85 mm Hg and avoiding SBP less than 90 mm Hg for the first 5 to 7 days after SCI. Literature has shown that patients with complete SCI may obtain greater benefit from MAP augmentation.

Vasoactive agents should be considered early in the treatment algorithm of hypotension that is unresponsive to fluid resuscitation. Several agents have been used in various clinical settings, with the optimal choice remaining a matter of debate. The Consortium for Spinal Cord Medicine recommends vasopressor selection based on SCI level. Patients with injury above T6 should receive a vasoactive agent with both inotropic and chronotropic properties to offset the disrupted cardiac sympathetic innervation, as well as the vasoconstrictive properties of the disrupted thoracolumbar sympathetic outflow. Norepinephrine is frequently used, with dobutamine considered when increased cardiac output is required. Lesions below T6 require peripheral vasoconstriction activation, as inotropic and chronotropic input to the heart are unaffected. Phenylephrine is considered because it is specific for α1 receptors. However, phenylephrine should not be given to patients with SCI above T6 as it can potentially trigger reflex bradycardia. Epinephrine has been shown to be associated with increased rates of arrythmias and should be used cautiously. Vasopressin should be avoided in SCI patients because of its antidiuretic effects and propensity to induce hyponatremia and worsen spinal cord edema.

Bradycardia and Other Arrhythmias

Patients with high cervical SCIs often experience autonomic instability and are at increased risk for development of symptomatic bradycardia and have a greater need for cardiovascular interventions compared with patients with lower cervical SCI. Symptomatic bradycardia can lead to asystole, which can occur with vigorous endotracheal suctioning. Patients who are symptomatic should be treated with atropine to maintain cardiac output and perfusion. Refractory bradycardia may respond to aminophylline or enteral albuterol. If still unresponsive, then temporary cardiac pacing should be considered as an alternative. Bradyarrhythmias will typically resolve within a short time period, but pacemaker placement should be considered for patients with high cervical SCIs and ongoing symptomatic bradyarrhythmic events 2 weeks after the injury.

Transfer

Principles of spinal stabilization are well established and have changed marginally over time. Patients with acute SCI should be transferred to specialized level 1 trauma centers that are skilled in the management of these injuries, as improved neurological outcomes and fewer complications have been reported with early transfer to specialized centers. Such level 1 centers provide immediate neurosurgical consultation and can therefore more rapidly assess patients and intervene. Furthermore, evidence demonstrates that early surgical intervention improves neurological outcomes, and expeditious transport to a center capable of providing definitive care affords the opportunity for early intervention and improved outcomes. ^, Further, early transfer to a specialized pediatric center has been associated with significant reductions in mortality and length of stay and with improved neurological recovery. During transport, immobilization of the spine is required to limit spinal motion and prevent further injury. In 2013 the American Association of Neurologic Surgeons and Congress of Neurologic Surgeons Joint Guidelines Committee presented updated guidelines for the management of acute cervical spine and SCI. ^, The goals of immobilization in pediatric and adult patients are to prevent or limit secondary neurological injury in the presence of an unstable spine. Common measures include placement of a rigid cervical collar, suspension of the head between sandbags or supportive blocks, transportation on a rigid spine board, taping, and log rolling of the patient. Immobilization of the entire spine is recommended because spinal injury can occur at several noncontiguous levels until injury is ruled out with appropriate physical examination and spinal axis imaging. Attention to airway protection, adequate ventilation, and circulatory support are essential during the period immediately following the injury and during transport.