Medical Management of the Patient with Acute Spinal Cord Injury

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Chapter 183 Medical Management of the Patient with Acute Spinal Cord Injury


Spinal cord injury (SCI) has an incidence of approximately 40 cases per million population per year, which in the United States translates to approximately 12,000 cases per year.1 In 2008, there were an estimated 259,000 people in the United States living with SCI. In addition to being one of the most profoundly disabling and psychologically devastating injuries, SCI has a substantial societal cost: the lifetime cost of caring for a patient who becomes paraplegic at 25 years of age is $1,055,869, and for a tetraplegic patient, $3,160,137.1 One 1994 estimate put the annual cost of caring for all SCIs in the United States at $4 billion.2

With the exception of age at injury, the epidemiology of SCI has remained fairly constant over time. In the United States, the most common cause of SCI is motor vehicle accidents (42.1%), followed by falls (26.7%) and violence (15.1%). Mean age at the time of injury has increased in recent decades, from 28 years in the late 1970s to 40 years from 2005 to 2009.1

The mortality rate of patients with traumatic SCI is high. An estimated 79% of patients die at the scene of the accident or on arrival at the hospital; for survivors at hospital admission, reported hospital mortality rates range from 4.4% to 16.7%.3 Predictably, long-term survival is lower than the general population; however, advances in medical care, and in urologic care in particular, have improved long-term survival considerably over the last half-century.4 Today, a person who becomes paraplegic at age 20 years has a mean life expectancy (years remaining) of 45.5 years; using the same age at injury, a person with a low tetraplegia (C5-8) has a mean life expectancy of 40.8 years, and a person with a high tetraplegia (C1-4) has a mean life expectancy of 36.9 years.1 A greater-than-expected number of deaths is found for virtually all causes, except ischemic heart disease. The greatest excess mortality occurs as a result of septicemia, deep venous thrombosis (DVT) and pulmonary embolism (PE), and pneumonia; compared with someone without SCI, an SCI patient between the ages of 25 and 54 years is 170 times more likely to die of septicemia, 63 times more likely to die of DVT/PE, and 50 times more likely to die of pneumonia.5,6 For those who survive the initial injury, medical management and the prevention of secondary complications will dictate long-term survival.

Medical care of the patient with acute SCI requires an understanding of the far-reaching pathophysiologic effects of the injury and an attention to detail. As with any traumatic injury, initial management focuses on maintaining adequate ventilation and ensuring adequate tissue perfusion. For injuries above the T6 level, this may be complicated by autonomic derangements and neurogenic shock. Physicians must be aware of the susceptibility of the injured or compressed spinal cord to ischemic damage and remain vigilant so that even brief periods of hypotension or hypoxia are avoided. Early consideration should be given to pharmacologic and surgical interventions to maximize neurologic recovery. Surgical considerations, such as the timing of decompression and strategies of spine stabilization, which have been the subject of extensive research and ongoing debate, are beyond the scope of this chapter and are discussed elsewhere.

After acute stabilization, attention is focused on preventing and treating the myriad secondary complications of SCI. A systems-based approach is essential because these complications may involve virtually every organ system. Broadly speaking, they can be divided into pulmonary complications, complications of autonomic disruption (sympathectomy), complications of immobility, and psychiatric complications.

This chapter is intended for the clinician caring for patients with SCI in the acute and subacute phases of their injury (i.e., during the first hospitalization). Although many of the management principles described here are also applicable to the chronic care of these patients, detailed discussion of subspecialty long-term care is beyond the scope of this chapter.


Acute SCI is really a two-stage process, consisting of a primary mechanical insult and a secondary cascade defined by tissue hypoxia and ischemia, edema, excitotoxicity, free radical activation, caspase activation, and, ultimately, cell death by apoptosis and necrosis.7 Despite ongoing research into neural regeneration and brain-machine interfaces, there is at present no therapy to reverse or circumvent the effects of the primary injury. Attention has therefore been focused on interventions to mitigate the deleterious effects of the secondary cascade.

The only pharmacologic intervention for acute SCI that is supported by randomized human trials is the administration of intravenous methylprednisolone. This was the subject of three National Acute Spinal Cord Injury Study (NASCIS) trials. NASCIS I was a negative study comparing methylprednisolone 1000 mg/day versus 100 mg/day for 11 days; there was no treatment effect seen at 6 weeks or 6 months postinjury.8 NASCIS II was a three-armed trial comparing a higher dose of methylprednisolone (30 mg/kg bolus followed by infusion of 5.4 mg/kg/hr for 23 hours), naloxone (5.4 mg/kg followed by 4.0 mg/kg/hr for 23 hours), and placebo.9 It found statistically significant improvements in motor score, pinprick sensation, and light touch at 6 months postinjury for the methylprednisolone group, when methylprednisolone was given within 8 hours of injury; benefit was seen in patients with complete as well as incomplete injuries. A 1-year follow-up of the same cohort found benefit for motor scores only.10 NASCIS III was another three-armed study in which all patients received a methylprednisolone bolus followed by a 24-hour infusion (5.4 mg/kg/hr NASCIS II protocol), or a 48-hour methylprednisolone infusion (5.4 mg/kg/hr), or tirilazad mesylate (2.5 mg/kg bolus every 6 hours for 48 hours); it did not include a placebo control. NASCIS III found comparable outcomes between the 24-hour and 48-hour infusions when therapy was initiated less than 3 hours after injury; when therapy was initiated between 3 and 8 hours after injury, patients receiving 48-hour infusions demonstrated improved motor scores and functional independence at 6 weeks and 6 months postinjury.11 Tirilazad mesylate resulted in outcomes comparable with the 24-hour methylprednisolone infusion, but because all patients had received a methylprednisolone bolus on presentation, it is unclear whether this outcome was the result of tirilazad or steroid administration. A 1-year follow-up of the NASCIS III cohort using intention-to-treat analysis did not demonstrate a statistical difference in motor scores between the 24-hour and 48-hour groups for the 3- to 8-hour treatment window; however, an analysis limited to compliant patients did demonstrate a small benefit for the 48-hour regimen over the 24-hour regimen.12 No difference in functional independence between the groups was seen at 1 year.

Despite their status as class 1 evidence, the NASCIS trials have been extensively criticized in the medical literature. Because NASCIS II is the basis for the use of methylprednisolone in SCI, it has been the subject of the most vigorous debate. The most common concern is that the authors’ choice of an 8-hour window is the result of a post hoc analysis rather than a prospectively defined end point. Others have questioned the inclusion of patients with minimal neurologic deficit, the use of right-sided motor scores only, the lack of a functional outcome measure, the lack of standardized medical or surgical therapies and the failure to control such variability, the small size of subgroups that formed the basis for the study’s determination of efficacy, the poor neurologic status of the control subgroup, and the medical risks associated with high-dose steroid therapy.1315 Reflecting this controversy, current guidelines from the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) Joint Section on Disorders of the Spine and Peripheral Nerves conclude that administration of methylprednisolone can be recommended only at the level of a treatment option.13

Further, the use of methylprednisolone for SCI appears to be diminishing, according to a number of recent physician polls and studies.16,17 Nevertheless, it remains the only therapy with evidentiary support of large-scale human trials.

A number of other candidate neuroprotective agents have undergone randomized, controlled trials in human subjects but have failed to show efficacy. Monosialotetrahexosylganglioside (GM-1) showed promise in animal models as an antiexcitotoxic, antiapoptotic, and proregenerative agent; it was the subject of two human trials. The first was a small study involving 37 patients who were randomized to receive either a test protocol of 100 mg of GM-1 intravenously per day for 18 to 32 doses, or placebo.18 Study subjects demonstrated significantly greater improvement in both Frankel grade and American Spinal Injury Association (ASIA) motor score at 1-year follow-up. This was the basis for a second, larger study involving 797 patients, the Sygen Multicenter Acute Spinal Cord Injury Study.19 In this study, all patients received methylprednisolone according to the NASCIS II regimen; after completion of the methylprednisolone infusion, patients were randomized to high-dose GM-1 (600-mg load followed by 56 days of 200 mg/day), low-dose GM-1 (300-mg load followed by 56 days of 100 mg/day), or placebo. The Sygen study failed to meet its primary end point; there was no difference in the proportion of patients with “marked recovery” (two-point improvement in the Modified Benzel Classification over baseline ASIA Impairment Scale) at 26 weeks postinjury. Current guidelines from the AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves list GM-1 as a treatment option without demonstrated clinical benefit.13 The N-methyl-d-aspartate (NMDA) glutamate receptor blocker gacyclidine was also the subject of a randomized, double-blind phase II clinical trial of over 200 patients.20 Outcome at 1 year failed to demonstrate improvement, and further development was halted. Because of the central role of calcium in both neuronal excitotoxicity and vasospasm-induced ischemia, calcium channel blockers have also received attention as candidate neuroprotectants. Nimodipine was the subject of a randomized clinical trial involving 106 patients split into four arms (nimodipine, methylprednisolone, both, or placebo).21 No benefit of nimodipine was demonstrated at 1-year follow-up.

Other therapies have shown promise in laboratory studies but have not yet been the subject of clinical trials. Polyethylene glycol is thought to confer neuroprotection through preservation of axonal cytoskeletal proteins, stabilization of the cell membrane, and preservation of mitochondria; multiple animal studies have shown reduction in cellular injury and modest improvement in functional outcome.2224 Magnesium sulfate has also shown significant improvement in motor scores and reductions in myelin loss and overall lesion size in rat models of SCI.2527 Finally, the resurgence of therapeutic hypothermia as a neuroprotectant after cardiac arrest has rekindled interest in potential application to SCI.28,29 Despite multiple animal studies showing therapeutic benefit,3033 human trials to date have been limited to small, noncontrolled case series,3439 from which it is difficult to draw any conclusions of efficacy. Indeed, widespread application of these experimental therapies to the patient with acute SCI will have to await positive results from well-designed human trials.

Pulmonary Management and Complications

Spinal cord injury is often accompanied by acute changes in respiratory function, and approximately one third of patients with acute cervical SCIs will require mechanical ventilatory support during the acute phase of injury.40

Respiratory Physiology

The process of inspiration involves the contraction and descent of the diaphragm and the expansion of the chest wall by the intercostal muscles. The action of these muscles creates a negative pressure so that air is drawn into the thoracic cavity. Expiration is mostly passive, but forced expiration and coughing are aided by the contraction of the abdominal muscles.

A complete injury above C3 usually results in apnea due to loss of innervation of the diaphragm. Lesions below this level will usually have retained diaphragm function but there will still be a significant reduction in ventilatory function. During the acute phase of SCI, there is flaccid paralysis of the muscles below the level of injury, and in cervical SCIs this paralysis results in loss of muscle tone in the intercostal muscles, which are innervated by the motor roots at each level of the thoracic spine. Thus, when the diaphragm contracts, the chest wall collapses instead of expanding. What is commonly observed, therefore, in a patient with an acute cervical SCI is paradoxical breathing: with each inspiration the chest wall collapses inward and the abdominal wall distends outward. There is a marked decrease in the ability to generate the negative intrathoracic pressure necessary to draw air into the lungs and vital capacity is reduced to about one third of the preinjury level.41 This reduction results in shallow breathing, and the respiratory rate is often elevated in an attempt to compensate for this. Shallow breathing is inefficient because a larger part of the air moved during each inspiration stays within the trachea and bronchi and does not reach the alveoli to participate in gas exchange. This in turn promotes alveolar collapse with progressive atelectasis and respiratory fatigue. The loss of function of the abdominal muscles results in a decreased ability to cough and clear secretions. Thus, some patients with an acute cervical SCI will appear to be breathing satisfactorily shortly after injury but over the next 24 to 48 hours develop progressive respiratory failure; therefore, careful sequential monitoring of respiratory function is important in the early phase of injury. It is preferable to perform intubation under controlled circumstances when personnel and equipment can be assembled, so it is best to make the decision to proceed with intubation before respiratory failure occurs.


During intubation of the patient with an acute cervical SCI, care should be taken to prevent further injury to the spinal cord. Intubation can be performed using direct laryngoscopy assisted by manual in-line traction, or fiberoptic laryngoscopy. Either option can be performed safely in the setting of SCI by experienced practitioners.42 The use of muscle relaxants is often a helpful adjunct to intubation; succinylcholine is an excellent choice in the acute period after injury but should not be used after the fourth postinjury day because of the risk of precipitating hyperkalemia.

Ventilator Management

More than half of patients with acute SCI will need mechanical ventilator support for more than 2 weeks.40 This is because improvement in respiratory function depends on the progression from flaccid to spastic paralysis: once the intercostal muscles become spastic, the chest wall becomes rigid and no longer collapses with inspiratory effort, and progressive improvement in negative inspiratory force and forced vital capacity occurs. This usually begins at about 3 to 5 weeks after injury.41 The management of the intubated patient with an acute cervical SCI is directed at preventing and treating complications while waiting for respiratory function to improve.

Ventilator-Associated Pneumonia


The development of pneumonia is a major source of morbidity in mechanically ventilated patients, and strategies to attempt prevention are important. The Society for Healthcare Epidemiology and the Infectious Diseases Society of America have published recommendations for the prevention of ventilator-associated pneumonia (VAP).43 The core recommendations are directed at the three most common mechanisms that lead to VAP: aspiration of secretions, colonization of the aerodigestive tract, and contamination of respiratory equipment. Elevation of the head of the bed to 30 degrees appears to reduce aspiration. Regular decontamination of the oral cavity with antiseptic solution should be used to prevent bacterial colonization of the upper airway. There is evidence that acid-suppressive therapy such as histamine receptor blocking agents or proton pump inhibitors used to prevent gastrointestinal bleeding may increase the colonization of the digestive tract with pathologic organisms, so the risk-benefit ratio must be individualized for each patient. Measures to prevent contamination of the respiratory circuit, such as removal of condensate and changing the ventilator circuit only when soiled or malfunctioning, are recommended.


Timely selection of appropriate antibiotic therapy is important in decreasing mortality from VAP. The American Thoracic Society and Infectious Diseases Society of America have issued guidelines for the treatment of VAP.47 While awaiting the results of sputum culture, the first step is to determine whether there is a likelihood of multidrug-resistant (MDR) organism involvement. The risk factors for this are recent exposure to antibiotics, hospitalization for greater than 5 days, immunosuppression, or a high incidence of MDR pathogens in the particular hospital or unit. If no risk factors are present, monotherapy with ceftriaxone, levofloxacin, moxifloxacin, ciprofloxacin, ampicillin/sulbactam, or ertapenem is acceptable. If risk factors for MDR pathogens are present, then combination therapy with three agents is appropriate. This includes the use of either vancomycin or linezolid to cover for methicillin-resistant Staphylococcus aureus; either an antipseudomonal cephalosporin, carbapenem, or piperacillin-tazobactam; and either ciprofloxacin, levofloxacin, or an aminoglycoside. Once the culture results are available, the antibiotics can be narrowed to cover the identified organism.

Complications of Autonomic Disruption

Autonomic Physiology and Pathophysiology

Autonomic effects of SCI have both immediate and long-term relevance. Understanding the effect of autonomic dysregulation on the cardiovascular, gastrointestinal, and urinary systems, in particular, requires an understanding of autonomic anatomy and physiology.

The parasympathetic nervous system is sometimes referred to as a craniosacral system. The cranial portion of this system, the vagus nerve, is unaffected by SCI; parasympathetic innervation to the heart and most abdominal visceral organs (pancreas, kidneys, liver, gallbladder, stomach, and intestine up to the splenic flexure) will be spared. However, outflow through the pelvic splanchnic nerves (S2-4) may be partially or completely disrupted by an SCI at any level; thus, parasympathetic innervation to the ureters, urinary bladder, urinary sphincter, anal sphincter, uterus, prostate, vagina, and penis are at risk. This distinction between the extraspinal cranial portion and the intraspinal sacral portion is central to the cardiovascular, urologic, and gastrointestinal phenomena that follow acute SCI.

The degree of sympathetic system disruption largely depends on the level and severity of injury. The sympathetic outflow to the body emanates from the spinal cord at levels T1 through L3. Preganglionic axons then enter the sympathetic chain, where they synapse on postganglionic neurons that are distributed among target organs, including the heart (cardiac accelerator nerves), blood vessels, skin, bronchial tree, esophagus, and large intestine, as well as papillary dilators and various glands in the head. Because of the anatomic differences between the sympathetic and parasympathetic systems, the effect of SCI on autonomic function and autonomic balance depends entirely on the level of the injury.

Cardiovascular Complications


Injuries above T6 may disrupt sympathetic cardiac and vascular control but leave parasympathetic (vagal) tone intact, often resulting in hypotension. In this setting, hypotension (systolic blood pressure <90 mm Hg) may be the result of bradyarrhythmia or distributive pathophysiology, or both.

The term neurogenic shock is applied when hypotension is accompanied by impaired tissue perfusion and other causes of shock have been addressed or ruled out. The latter point is important: internal hemorrhage, tension pneumothorax, cardiac tamponade, and other causes of hypotension in the trauma patient can have disastrous consequences if not detected in a timely fashion. Clinically, neurogenic shock has a more varied presentation than other forms of shock. Distributive/hypovolemic pathophysiology is belied by a normal or low heart rate and warm skin. Above the level of the injury the patient will often be diaphoretic, whereas below the injury the skin may be dry. This confusing clinical picture, combined with a high probability of other, concurrent shock physiology, makes neurogenic shock a diagnosis of exclusion.

It is worth distinguishing between the terms neurogenic shock and spinal shock, which are often confused in the literature. The term neurogenic shock refers to a distributive and/or cardiogenic hypotension as a result of acute sympathectomy in SCI; it is a cardiovascular phenomenon and lasts for a mean of 4 to 6 weeks after injury. The term spinal shock refers to a flaccid, areflexic period after acute SCI that precedes the gradual transition to spasticity; it is a neurologic phenomenon and its end is heralded by the return of various spinal reflexes (bulbocavernosus reflex after approximately 2 days, deep tendon reflexes after approximately 2 weeks, bladder reflex after 2 months).

Initial management of hypotension resulting from acute SCI should be directed toward volume resuscitation of the expanded intravascular volume and correcting bradycardia. If 1 to 2 L of intravenous fluid fails to normalize blood pressure, consideration should be given to vasopressor and chronotropic support. A mixed α- and β-adrenergic agonist is recommended because of the need to restore both peripheral arteriolar tone and heart rate. A pulmonary artery catheter may be useful in directing therapy. As with any shock state, the restoration of tissue perfusion may be assessed by examination of the extremities, mental status, and urine output.

It is not known whether a higher blood pressure target should be sought in the setting of SCI. Because of the exquisite sensitivity of the injured spinal cord to ischemia, some authors have recommended using fluids and pressor support to maintain higher-than-usual target mean arterial pressures (MAPs) in the acute phase of injury. Although the avoidance of hypotension in acute SCI is supported by animal research,4850 there is a dearth of evidence to support any particular target. Of the uncontrolled case series in the current literature, strategies have included target MAPs greater than 85 mm Hg51,52 and greater than 90 mm Hg.53 Reflecting the lack of rigorous human studies, the AANS/CNS Joint Section currently lists the avoidance of hypotension and maintenance of MAP at 85 to 90 mm Hg for 7 days after injury as options for treatment.54

In the subacute and chronic phase of injury, orthostatic hypotension (OH) may be a persistent problem. It is defined as a decrease in systolic blood pressure of 20 mm Hg or more or a decrease in diastolic blood pressure of 10 mm Hg or more upon transition from a supine to an upright position. Using this definition, the prevalence of OH after SCI is 82% in tetraplegia and 50% in paraplegia.55 It results from venous pooling in the lower extremities with secondary loss of preload and reduction in end-diastolic volume. In cervical SCI, this is exacerbated by sympathetic denervation of the heart and difficulty compensating with increased heart rate. OH is associated with light-headedness or other symptoms in over half of the SCI population.55 Treatment may include volume expansion, pressure devices, functional electrical stimulation, exercise, and pharmacologic therapy. Volume expansion may be accomplished with increased dietary salt and oral fluids, or with sodium-retaining drugs such as fludrocortisone. It should not be undertaken in patients with a history of congestive heart failure. Pressure devices include abdominal binders and compression stockings; success from these measures alone has been limited.56

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