Chapter 183 Medical Management of the Patient with Acute Spinal Cord Injury
Epidemiology
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.
Neuroprotection
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.13–15 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.22–24 Magnesium sulfate has also shown significant improvement in motor scores and reductions in myelin loss and overall lesion size in rat models of SCI.25–27 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,30–33 human trials to date have been limited to small, noncontrolled case series,34–39 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.
Intubation
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
Prevention
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.
Diagnosis
The diagnosis of VAP can be challenging: fever is common in ventilated patients and may not be due to infection, and distinguishing pneumonia from bacterial colonization of the respiratory tract is often difficult. The process of establishing the diagnosis of VAP should begin with a chest radiograph and sampling of secretions from the lower respiratory tract. Sampling of secretions can be done with either bronchoscopy or endotracheal suctioning. There is some controversy about which method is preferable, but it is not clear that there is a difference in clinical outcome.44 If the chest radiograph reveals no infiltrates or the Gram stain of the sputum shows no organisms, it is unlikely that pneumonia is present.45 If there are new or progressive infiltrates on the chest radiograph along with two of the following, fever, leukocytosis, or purulent secretions, there is a strong likelihood of VAP.46
Treatment
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
Cardiovascular Complications
Hypotension
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,48–50 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 Functional electrical stimulation uses direct electrical stimulation of the lower extremity musculature to promote venous return. Its efficacy is supported by three small-scale, randomized, controlled trials.57–59 The most commonly used drug to treat OH is midodrine, an α-adrenergic agonist that has been tested in the SCI population in a number of small trials.60–62 Other medications that have been used to treat symptomatic OH, with varying success, include fludrocortisone, ephedrine, and dihydroergotamine.56
Arrhythmia
Sinus bradycardia is the most common arrhythmia after cervical and upper thoracic SCI, again because of unopposed parasympathetic outflow to the heart; however, supraventricular tachycardia and ventricular arrhythmias can also occur.63 Sinus bradycardia with hemodynamic compromise should be treated with atropine 0.5 mg IV. If it is ineffective or episodes are recurrent, aminophylline may be given as a bolus injection, followed by infusion.64,65 Aminophylline may be substituted with oral theophylline if chronotropic support is needed for a more prolonged period.61 Occasionally, the bradycardia can result in asystole. For severe or refractory bradyarrhythmias and ones that persist longer than 2 weeks, consideration should be given to pacemaker placement.66,67 Tachyarrhythmias are less common in the patient with acute SCI; when supraventricular tachycardia or ventricular tachycardia occurs, it is usually in the context of a midthoracic lesion.68 Treatment is governed by the specific electrophysiologic derangement involved, but will commonly include beta blockade, antiarrhythmic drugs, and, in the case of unstable, sustained ventricular tachycardia or ventricular fibrillation, defibrillation.
Autonomic Dysreflexia
Injuries above T6 may produce life-threatening episodes of autonomic dysreflexia, in which a stimulus below the level of the injury causes an increase in sympathetic activity. The most common triggers are sacral-level stimuli, such as bladder distention, bowel distention, and manual disimpaction, although mild cutaneous stimuli at any level below the injury may also cause this response. By definition, a dysreflexic episode is characterized by a minimum increase in systolic blood pressure of 20 to 30 mm Hg; blood pressure often becomes out of control, reaching the level of hypertensive emergency. In addition to hypertension, dysreflexic episodes are characterized by bradycardia and arrhythmia, diaphoresis above the level of the lesion, flushing, muscle spasm, and paresthesias. Although most episodes are short-lived, there are reports of dysreflexic episodes lasting for weeks.69
Dysreflexia is thought to result from changes in spinal and extraspinal autonomic circuits. Up-regulation of peripheral alpha receptors, in particular, is thought to play a role.70 It is more severe with more rostrally located lesions and with neurologically complete injuries. Autonomic dysreflexia is observed in 91% of patients with neurologically complete tetraplegia, but in only 27% of patients with incomplete tetraplegia.71
Autonomic dysreflexia is a medical emergency. Prompt treatment is essential to preventing hypertensive emergency and secondary intracranial hemorrhage, retinal hemorrhage, seizure, and death. The inciting stimulus should be identified and alleviated. If a stimulus is not immediately apparent, physical examination or bladder ultrasonography should be used to ensure that the bladder is adequately drained. The head of the bed should be elevated to an upright posture and clothing should be loosened. Multiple medications have been used to truncate dysreflexic episodes, including nitrates,72 prostaglandin E2,73 and sublingual captopril.74 Dysreflexic episodes may be prevented through mitigation of stimuli as well as prophylactic antihypertensive therapy. Current literature supports the use of prazosin75 and terazosin76 for prophylaxis. The use of nifedipine for prophylaxis also has evidentiary support, but its use has declined substantially in the wake of increased reports of adverse events and premature death associated with this medication.72,77
Genitourinary Complications
For SCI severe enough to cause urinary dysfunction, the initial stage of injury is that of an areflexic or acontractile bladder and loss of external urethral sphincter tone. This correlates with the period of spinal shock. For injuries located above the sacral cord level (i.e., upper motor neuron lesions), bladder contractions usually return within 6 to 8 weeks after injury4; conus and cauda equina lesions will remain in this acontractile state indefinitely. Typically, electromyographic activity and contractile function return first in the external urethral sphincter, followed some time later by the bladder. Once bladder reflexes have been restored, typically in the rehabilitation stage of treatment, patients should be followed by a urologist for urodynamic studies, consideration of anticholinergic therapy and restoration of voiding function, and management of chronic issues such as urinary tract infection and urolithiasis.
For the physician treating acute SCI, the central urologic question is when to transition from an indwelling urinary catheter to intermittent catheterization. An indwelling catheter is helpful during the period of acute management, when monitoring and treating hemodynamic instability or impaired tissue perfusion. Once this period has passed, there are multiple benefits to replacement of the indwelling catheter with a regimen of intermittent catheterization. First, periodic distention of the bladder wall may promote the early return of bladder reflex contractions, hastening recovery of voiding function.4 Second, the incidence of urinary tract infection, particularly upper urinary tract infection with secondary renal failure, is lower with intermittent catheterization.78,79 Third, other complications related to indwelling urinary catheters, such as urethritis, prostatitis, epididymo-orchitis, fistulae, and strictures may be reduced or avoided.4,80 It is believed that a substantial reduction in mortality related to SCI in the last half-century is due to a reduction in the use of indwelling catheters in the chronic SCI population.81 Thus, intermittent catheterization should be adopted as soon as is practically feasible.
Intermittent catheterization should be carried out every 4 hours, with bladder volumes kept to less than 400 mL to prevent overdistention. Once patients start to void, intermittent catheterization may be changed to every 6 to 8 hours, and the acceptable volume may be increased to 500 mL.82 If possible, fluid intake should be restricted to 1.5 L/24 hours; when urine volumes are greater than 500 mL/6 hours, the aforementioned regimen becomes impractical, and unless intake can be further restricted, intermittent catheterization should be delayed.82 While patients are in the hospital, sterile technique is recommended. Once out of the hospital, patients may use clean technique, in which the patient washes his or her hands, but does not don sterile gloves, and uses a clean, rather than sterile, catheter.4,79 No antiseptic preparation is required for clean catheterization. For patients unable to perform clean intermittent self-catheterization, a suprapubic cystostomy tube, combined with anticholinergic medication, frequent catheter changes, bladder washing, and volume maintenance procedures, may provide a morbidity profile comparable with clean intermittent catheterization.83
In the long term, the goals of urologic management include reduction of voiding pressure to less than 40 cm H2O, prompt treatment of urinary tract infection, prevention and treatment of urinary stones, and, when possible, attaining a catheter-free state. Elevated bladder pressures may be the result of hyper-reflexia and detrusor sphincter dyssynergia and, if prolonged, can lead to hydronephrosis and chronic renal failure. Treatment options include anticholinergic medication as well as transurethral sphincterotomy. Urinary tract infection results from upper and lower urinary tract stasis, vesicoureteral reflux, and chronic catheterization and is a significant cause of long-term morbidity. Complicating management is the difficulty of distinguishing between true infection and colonization. Undertreatment may result in upper tract infection and kidney damage, whereas overtreatment may lead to MDR bacteria. At present, most clinicians advocate treatment in the presence of fever, flank pain, hematuria, or pyuria (>10,000 leukocytes/mL urine).4,84 Recurrent infections should prompt evaluation with an intravenous urogram and urodynamic studies. Prophylactic antibiotics are ineffective in reducing the frequency of urinary tract infections and cause the emergence of antibiotic-resistant bacteria.85 Recent approaches to reduce the incidence of urinary tract infection have included the use of hydrophilic-coated catheters and bacterial interference.86,87 Urinary stones are another common complication with significant secondary renal morbidity. The incidence of stone disease is greatest during the first 3 months after injury. This early peak of “immobilization hypercalciuria” corresponds to a period of relative immobility and the development of nonoxalate calcium stones.88 Stone disease presenting after 3 months is more commonly the result of chronic infection and should prompt a search for such.
Gastrointestinal Complications: Ileus and Nutrition
Protein intake should be modulated with the understanding that muscle paralysis will inevitably result in catabolism and negative nitrogen balance; this cannot be reversed with nutritional supplementation.89,90 Protein requirements for the patient with acute SCI are typically estimated at 1.0 to 1.3 g/kg.91 In the acute phase, overall energy expenditure is also substantially less than that of other traumatically injured patients.92 The Harris-Benedict equation is a standardized means of assessing energy requirements and has been independently validated for this purpose in the SCI population.89 Nevertheless, indirect calorimetry remains the most accurate means of assessing nutritional needs and should be used whenever possible.93 For short-term, practical purposes, a reasonable shorthand estimate of caloric requirement is 20 kcal/kg ideal body weight.
It should be noted that early nutritional support of the trauma patient is supported by substantial medical literature.94,95 Though tempered by at least one report of increased incidence of infection among patients receiving early enteral nutrition, early feeding has become a common theme in trauma critical care.96 Whether this benefit accrues to the patient with SCI, given the specific metabolic concerns outlined previously, remains uncertain; however, studies are ongoing.91
Disorders of Thermoregulation and Sweating
Autonomic innervation to cutaneous blood vessels, sweat glands, and piloerectors is exclusively sympathetic. There is no opposing parasympathetic input. Hence, both vasodilation and vasoconstriction are lost, and the patient is rendered susceptible to thermal derangements in both directions. For lesions below T6, compensation by the trunk and upper limbs prevents significant hyperthermia or hypothermia except in conditions of strenuous exercise or extreme ambient temperatures.97,98 For patients with injuries above T6, particularly middle and high cervical injuries, attention must be paid to even moderate changes in ambient temperature; these patients are sometimes referred to as “partially poikilothermic.”98
In the hospital, this phenomenon usually manifests as fever of unknown origin, although hypothermia also occurs. Given their high risk for infection and DVT, the presence of elevated body temperature or hypothermia in patients with SCI should prompt a careful clinical investigation. Only after repeated negative workups should an autonomic cause be invoked. The converse concern of sympathetic denervation eliminating the febrile response, and thus masking infection, has not been borne out in clinical practice. This may be due to some heretofore-undefined humoral factor or pyrogen that is capable of transmitting hypothalamic signals to thermal effectors in the body, without neural transmission.98
Complications of Immobility
Deep Venous Thrombosis and Pulmonary Embolism
Deep venous thrombosis and PE represent a significant mortality risk for the patient with SCI, particularly in the period immediately after the injury. Within the first month after injury, a patient with SCI is 500 times more likely to die of DVT/PE than an age-matched control subject; between 1 and 6 months postinjury, the relative risk is 116, and for 6 months postinjury and beyond, it is reduced further to 20.5 Studies with routine screening for DVT have found a 60% to 100% prevalence of DVT in patients with SCI.99,100 Because of this risk and the level of evidence supporting prophylactic measures, the American College of Chest Physicians recommends routine thromboprophylaxis in the form of low-molecular-weight heparin (LMWH) or unfractionated heparin with compression stockings, recognizing that pharmacologic prophylaxis may be postponed because of epidural hematoma or other bleeding risk.101,102 Similarly, the AANS/CNS Joint Section currently recommends low-dose heparin and pneumatic compression devices as a standard of care in the cervical SCI population.13
Mechanical prophylaxis alone is not an adequate long-term strategy in the patient with SCI. The incidence of DVT when sequential compression devices are used in lieu of pharmacologic prophylaxis may be as high as 40%.103 Sequential compression devices and graded compression stockings represent a low-cost, low-risk adjunct to other measures of prevention, and in the patient with high bleeding risks, may be a useful short-term strategy while pharmacologic prophylaxis is withheld.
There is evidence to suggest that LMWH is more effective than unfractionated heparin in preventing venous thromboembolism. One randomized, controlled study comparing unfractionated heparin plus intermittent pneumatic compression stockings versus enoxaparin found a statistically significant reduction in pulmonary embolism from 18.4% in the unfractionated heparin group to 5.2% in the enoxaparin group.99 Superior efficacy of LMWH is also reflected in the trauma literature; one randomized, controlled study found relative risk reductions of 30% for DVT and 58% for proximal DVT when enoxaparin was used instead of unfractionated heparin after major trauma.58 In the chronic phase of treatment, LMWH may be continued or patients may be transitioned to an oral vitamin K antagonist (warfarin) with a target international normalized ratio of 2 to 3.101 The latter requires active management of dosing but is significantly less expensive than LMWH.
The presence of traumatic intracranial bleeding, spinal epidural hematoma, or other bleeding concern complicates the issue of pharmacologic prophylaxis. The most common concern is concomitant cerebral contusion or other intracranial hematoma, and at present no adequate studies have been done to address the questions of timing and choice of agent in this population. Studies of DVT prophylaxis after elective brain tumor resection suggest a higher incidence of postoperative bleeding with LMWH, but not with unfractionated heparin.104,105 Therefore, in this subpopulation, the use of unfractionated heparin combined with mechanical compression devices may be a reasonable choice in the short term.
Some have suggested the routine use of prophylactic inferior vena cava filters in patients with significant motor deficit after SCI.106 This practice is currently not supported by the American College of Chest Physicians because of the risk of major complications and cost-ineffectiveness.101 In the only randomized, controlled study of permanent inferior vena cava filter placement in patients with DVT and high risk of PE, the addition of filter placement to appropriate anticoagulation therapy reduced, but did not eliminate, the risk of PE (4.8% vs. 1.1% at 12 days and 6.2% vs. 15% at 8 years); there was no associated reduction in mortality risk, and filter placement was associated with a significantly higher risk of recurrent DVT (35.7% vs. 27.5% at 8 years).107,108 When bleeding concerns preclude appropriate pharmacologic prophylaxis during the acute phase of injury, there may be a limited role for filter placement. Retrievable filters, in particular, may be useful for this purpose.
There is no high-quality evidence to support or refute the use of screening tests to identify asymptomatic DVT in the SCI population. Screening methods include Doppler ultrasonography, compressed ultrasound, D-dimer assay, 125-I fibrinogen scanning, impedance plethysmography, or a combination of methods. A recent literature review and meta-analysis of nine small trials and case series found no differences among these methods in their ability to detect asymptomatic DVT in the SCI population.109 The mean pooled frequency of DVT detected by these methods was 16.9%, with all patients receiving pharmacologic thromboprophylaxis at the time. The noninvasive nature and relative ease of Doppler ultrasonography has made it the most common screening tool, but its sensitivity for proximal and distal DVT has been estimated at only 29%.99 Taking into account the imperfect sensitivities of screening tests and the relative infrequency of fatal and nonfatal PE, it is unlikely that a large enough trial will be undertaken to definitively establish the efficacy of DVT screening in reducing risk. The American College of Chest Physicians describes screening ultrasonography as a “reasonable consideration.”101 Because of the diminishing frequency of DVT/PE after SCI, any benefit of this practice will erode with time, and it is probably reasonable that screening, if undertaken, be discontinued 3 months after injury.109
PE may present with acute deterioration, characterized by hypotension, tachycardia, and hypoxemia, or it may present more insidiously, with one or more of these signs present only to a mild degree. The clinician should have a low threshold of suspicion because early identification and treatment of a small PE may stave off a second, more catastrophic event. When there is clinical suspicion for PE, a helical CT scan of the chest with contrast should be performed. Ventilation-perfusion scans have limited sensitivity and specificity and are used only when there is a contraindication to the administration of intravenous contrast. As noted earlier, ultrasonography of the legs is a relatively insensitive test and is incapable of identifying intrapelvic thrombus. When a diagnosis of PE is being entertained, a negative lower extremity duplex examination provides a false sense of security and should not be used for this purpose. Treatment of PE requires prompt heparinization and, in some cases, inferior vena cava filter placement. Long-term management typically involves transition to warfarin or continuation of a therapeutic-dose LMWH for 3 to 6 months.
Integumentary Complications
Multiple studies have attempted to establish risk factors for decubitus ulcer formation; a recent review and meta-analysis synthesized this disparate literature and found the following risk factors to be significant: neurologically complete lesion, hypotension on presentation, degree of mobility deficit, decreasing albumin level, and duration of stay on a neurosurgical ward.110 The following variables were found not to be associated with increased risk: tetraplegia versus paraplegia, smoking status, complete blood count, pulse oximetry measurements, and arterial blood gas measurements.110 The Braden, Norton, and Waterlow scales are all established instruments for decubitus ulcer risk assessment; the Spinal Cord Injury Pressure Ulcer Scale (SCIPUS) and SCIPUS-A are newer instruments devised specifically for SCI, but they have yet to be independently validated.111 The incorporation of one of these instruments into standard nursing documentation focuses attention on this pivotal aspect of nursing care for the patient with SCI.
Heterotopic Ossification
Heterotopic ossification (HO) is the presence of lamellar bone in soft tissue structures where bone is not normally present. It is distinct from metastatic calcification, which results from hypercalcemia, and dystrophic calcification as a result of tumor. The precise mechanism of HO is unknown. Current evidence suggests that it results from the differentiation of pluripotential mesenchymal stem cells into osteoblasts.112 Factors believed to play a role in this process include a permissive HLA genotype, overexpression of bone morphogenetic proteins (BMP; particularly BMP-4), tissue hypoxia, changes in sympathetic tone, as well as immobility.113
The prevalence of HO in the SCI population is approximately 25%.114 It typically becomes manifest about 4 months after injury, with increased joint stiffness, decreased range of motion, warmth, swelling, and erythema. The early inflammatory phase is often confused with phlebitis/DVT, septic arthritis, or tumor.113 Joint stiffness may be difficult to detect with the onset of spasticity. Radiographic workup of HO includes serum alkaline phosphatase levels and three-phase bone scintigraphy. CT and MRI have little role early in the course of the disease. Treatment includes nonsteroidal anti-inflammatory medications, local radiation, and, in severe cases, surgical excision.
For the physician treating acute SCI, preventative strategies are the most relevant. The efficacy of range-of-motion exercises in HO continues to be debated. Data on the subject are sparse and divergent. Some authors recommend that once early signs of HO are evident, an aggressive regimen of passive, progressive range-of-motion exercises may mitigate its ultimate effects,115 whereas others believe such a regimen exacerbates the underlying pathophysiology.116 Recent evidence suggests that passive range-of-motion exercises are also ineffective in preventing flexion contracture after SCI117–119; however, abandonment of this practice in the early stage after injury should await further, confirmatory study.
Psychiatric Complications
Spinal cord injury prompts a grief reaction very similar to that experienced by terminally ill patients. The grieving process of denial, anger, sadness, and, it is hoped, acceptance is experienced not only by the patient but by his or her family. These monumental emotional issues must be recognized and addressed by the physicians and nurses caring for the patient. Unfortunately, this is often difficult and unnatural. Because SCI victims are often young and previously healthy, the psychological barrier between “us” and “them” is diminished; this proximity, combined with the horrible nature of the injury (particularly with cervical SCI) makes empathy and forthrightness emotionally taxing for the physician. Clinicians may find themselves fighting the urge to avoid the patient or the family, or else focusing discussion solely on medical issues, without addressing the “elephant in the room.” However, ignoring the long-term significance of the injury and its emotional toll comes with a significant price. The patient and family are deprived of a shepherd during a period of severe psychological trauma. Nurses and staff may feel victimized as the patient and family externalize their anger on them. And, at the most practical level, patient care may be compromised by the interpersonal conflicts that result. Recognizing the stages of grief and their manifestations is an important first step toward overcoming our natural aversions in this regard.
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Ball P.A. Critical care of spinal cord injury. Spine (Phila Pa 1976). 2001;26(Suppl 24):S27-S30.
Crosby E.T. Airway management in adults after cervical spine trauma. Anesthesiology. 2006;104:1293-1318.
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