GENERAL SESSION 3
Management of Complications, section II

Role of Screening Tests for Deep Venous Thrombosis in Asymptomatic Adults who Undergo Thromboprophylaxis During the Acute Stage After Traumatic Spinal Cord Injury: An Evidence-Based Analysis
Julio C. Furlan, MD, MBA, PhD, and Michael G. Fehlings, MD, PhD, FRCSC
Krembil Neuroscience Centre, Spinal Program, Toronto Western Hospital, University Health Network; and Department of Surgery, Division of Neurosurgery, University of Toronto, Toronto, ON, Canada.

Objective: This systematic review examines the evidence to support practice guidelines for screening for deep venous thrombosis (DVT) in asymptomatic adults with acute traumatic spinal cord injury (SCI) who undergo thromboprophylaxis.

Design: Systematic review

Methods: MEDLINE, EMBASE and COCHRANE were searched from the earliest achievable date of each database to March 2005. Following a priori inclusion and exclusion criteria, the selected articles were retrieved and classified into quality categories by one abstracter (JCF).

Results: No study demonstrated the effectiveness of screening for asymptomatic DVT on mortality, prevalence of pulmonary embolism, quality of life or neurological recovery in the SCI population under thromboprophylaxis. However, one prospective study (II-3 evidence) using phlebography as screening test reported that 13% of SCI patients who underwent thromboprophylaxis showed asymptomatic DVT. Another 6 prospective studies (level II-3 evidence) using D-Dimer (3/6), ultrasound (1/6), 125I-labelled fibrinogen (1/6), and phlebography (1/6) demonstrated frequencies of asymptomatic DVT between 4% and 72%. Minor adverse effects were reported in 9.9% of SCI population in only one poor quality study using phlebography as screening test. The number of patients needed to screen for reduction of mortality in SCI population under thromboprophylaxis varied from123 to 454 asymptomatic SCI patients.

Conclusions: There is insufficient evidence to support (or refute) a recommendation for routine screening for DVT in adults with acute traumatic SCI under thromboprophylaxis. However, there is at least fair evidence that screening could detect asymptomatic DVT in 13% of those individuals. The results of this systematic review suggest that weekly use of ultrasound and/or D-Dimer assay during the first 14 weeks post-SCI represents an option in the SCI population, although further investigation is needed in order to develop practice guidelines.

Support: This work was supported by funds from the Krembil Chair in Neural Repair and Regeneration (MGF) and the Lawson Fellow-Neurology from The Toronto General & Western Hospital Foundation (JCF).

Objective: To determine whether there is an increased incidence of deep venous thrombosis (DVT) after prophylactic placement of an inferior vena cava (IVC) filter after acute spinal cord injury.

Design: Retrospective Chart Review

Participants/Methods: 190 consecutive charts from patients admitted to the spinal cord injury / multitrauma service of Kernan Hospital from January to December 2002 were reviewed. 65 subjects met inclusion criteria, namely an acute traumatic injury, length of stay greater than 7 days, and level of injury between C4 and T12. Subjects were classed into two groups, those who received a prophylactic IVC filter during their acute stay and those that did not. All patients were also treated with some other form of DVT prophylaxis. The occurrence of DVT during initial rehabilitation was collected as the primary outcome measure. Other information on age, ethnicity, level and extent of injury, etiology, acute hospital, type of DVT prophylaxis, presence of pulmonary embolism (PE), and length of stay were also collected.

Results: Of the 64 subjects that met inclusion criteria, 36 (56%) had prophylactic IVC filters placed. Of the 36 with filters, 8 (22.2%) experienced a DVT during their rehabilitation stay. Of the 28 without filters, only 2 (7.1%) experienced a DVT during rehabilitation (p = 0.16, Fisher’s exact test). Confounding factors that may have biased the results included severity of the injury and location of acute hospitalization. No individuals experienced PE during rehabilitation hospitalization.

Conclusion: Whereas prophylactic IVC filter placement may play a role in PE prevention in acute SCI, their presence may actually increase the risk of DVT which has its own associated morbidity.

Objective: To evaluate what tests best predict the ability of ventilator dependent tetraplegics to wean from the ventilator.

Design: Retrospective review of patients prospectively evaluated.

Participants: Twenty-six ventilator dependent tetraplegics admitted to a university inpatient spinal cord injury rehabilitation unit, ASIA levels C2-C6 A or B.

Results: Paralysis of one diaphragm or at least moderate decreased recruitment with needle electromyography in both hemidiaphragms was predictive of failure to completely wean off of the ventilator. Phrenic nerve conduction studies would have predicted that all patients that weaned off the ventilator would have failed. Fluoroscopic examination of the diaphragm and bedside spirometry were not as good predictors of ability to wean, failing to accurately predict in 44% and 19% respectively. ASIA examination was also not entirely predictive and any outliers that may have been expected to wean based on ASIA examination (i.e., C4 or better neurological levels) were predicted not to wean by needle electromyography.

Conclusion: Diaphragm needle electromyography best predicted the ability to wean from the ventilator. Bedside spirometry(NIF and forced vital capacity) is an accurate bedside measure of a patient’s readiness to wean. Diaphragm fluoroscopy and phrenic nerve conduction studies were not helpful in determining weaning potential in ventilator dependent cervical spine injured patients.

Support: None.

Design: An animal study on expired pressure generated using microstimulator.

Participants/Methods: Studies were performed on nine anesthetized dogs. A thoracic laminectomy was performed on each dog, and was followed by spinal cord transection at T2. A total of 16 micrstimulators (supplied by the Alfred Mann Foundation, CA) were inserted percutaneously onto bilateral intercostal nerves about 3 cm distal to the neuroforamen from T7 to L1. The stimulation parameters were: a frequency of 20 Hz, pulse width of 200 ms, and stimulation burst of 2 seconds. The stimulation intensities were 3.78, 5.4, 8.1, and 10.8 mA. The pressure-generating capacity of the expiratory muscles was evaluated by the change in airway pressure (Paw), which was produced by the microstimulators during airway occlusion. The expiratory muscles were stimulated supermaximally at functional residual capacity which were expressed as the corresponding changes in Paw.

Results: As a general trend, the expired pressure generated using the microstimulators increased with increasing intensity and the number of spinal nerves recruited. The maximal expired pressures generated from one, two, three, four, five, six, seven, and eight pairs of spinal nerves were 8.4 ± 0.8, 12.2 ± 1.0, 14.6 ± 1.4, 17.8 ± 1.8, 23.0 ± 1.8, 27.7 ± 2.2, 35.2 ± 2.7, 40.4 ± 2.9 cmH2O, respectively. Bilateral stimulation of seven (from T8 to L1) and eight spinal levels (from T7 to L1) produced the highest changes in Paw. Stimulation of six or less spinal levels resulted in significantly lower Paw.

Conclusion: We conclude: (1) lower thoracic spinal nerve stimulation near neuroforamen using microstimulators produces significant expired pressure, (2) percutaneous placement of the microstimulators near neuroforamen is effective in producing expired pressure, and (3) percutaneous placements of the microstimulators for restoring cough may be used as a relatively non-invasive clinical tool for patients with spinal cord injury, and with other neurological or respiratory pathologies.

Support: This study was supported by a grant of Veteran Affairs Rehabilitation Research and Development Service.

Objective: Able bodied persons can sustain 70% of their maximal voluntary ventilation (MVV) for 5-20 min. As respiratory muscles of tetraplegic and paraplegic patients are paralyzed to different degrees depending on their lesion level, the aim of this study was to find the level of ventilation that tetraplegic and paraplegic patients can sustain for 10-20 min as this level can then be used for respiratory muscle endurance training (RMT).

Design: Pilot study; randomized crossover setting.

Participants/methods: 6 tetraplegic (C4-C7) and 8 paraplegic (Th4-L1) motor complete SCI patients participated 4-6 months after injury. Respiratory muscle endurance, i.e. the duration for which the specific intensity could be sustained, was assessed at 20, 40 and 60% MVV, on three different days, in randomized order, using partial rebreathing (SpiroTiger®). Tidal volume was set at 40-50% of the individual vital capacity and breathing frequency was adjusted accordingly. Respiratory endurance was compared between groups with tetraplegia and paraplegia using the Wilcoxon signed-ranks tests. Significance was accepted at p < 0.05.

Results: Mean respiratory endurance was 46.0±13.0, 19.0±14.4 and 4.2±3.3min at 20, 40 and 60% MVV in tetraplegic and 52.8±15.4, 38.8±17.9 and 12.2±9.0min in paraplegic patients, respectively. The difference between tetraplegic and paraplegic patients was significant at 60% MVV.

Conclusion: The optimal intensity to perform RMT should be set at minute ventilation of around 40% MVV for tetraplegic and around 60% MVV for paraplegic patients. Due to inter-individual variability, however, the optimal personal intensity should then be adjusted individually during the first training sessions.

Support: This project was funded by the Swiss Paraplegic Foundation (Nottwil). The SpiroTiger® devices were generously provided by Idiag (Fehraltorf, Switzerland).

Objective: To report verrucous carcinoma (VC) as another kind of malignant degeneration found in chronic pressure ulcers affecting traumatic spinal cord injury (SCI) patients. Other than one non-traumatic paraplegic with plantar VC, the SCI literature mentions squamous cell carcinoma as the type of malignant transformation (Marjolin’s ulcers) found in SCI patients with chronic pressure ulcers. These cancers (Marjolin’s ulcers) are considered a rare event in SCI (0.5%)

Design: Prospective study in a SCI service.

Participants/Methods: From 1998 through 2003 one hundred and fifty SCI patients underwent plastic surgery for their non-healing pressure ulcers. Multiple biopsies of the ulcers were taken for microscopic examination for every surgical procedure. Excision biopsies were done in two patients and repeated biopsies prior to surgery were done in another two.

Results: Verrucous carcinoma was diagnosed in five SCI males. Race: three white, two African American. Level of SCI: tetraplegic two, one complete, one incomplete and paraplegic three complete. Mean age: 52 years ranging from 33 to 74 years. Mean duration of SCI: 25 years ranging from 3 to 41 years. Mean skin lesion duration: 3 years ranging from 3 months to 7 years. Skin lesion location: sacral two, ischial two, plantar surface of the foot one.

Conclusions: In this study the finding of VC in five patients (7.5%) changes both the concept of Marjolin’s ulcer as a rare event (0.5%) and squamous cell carcinoma as the only malignant transformation of chronic pressure ulcers found in SCI patients. High awareness of this condition is needed for proper action.

Objective: Evaluate pressure ulcer rates in veterans with paraplegia and tetraplegia.

Design: Retrospective review of charts and administrative data

Participants/Methods: 78 patients were treated for pressure ulcer(s) by our SCI/D Center Clinical Wound Specialist during 2003-2004. National administrative data on 18,265 veterans with SCI identified 2635 seen as inpatients or outpatients in 2001 with a diagnosis code of pressure sore.

Results: 28 tetraplegics and 50 paraplegics were treated for pressure ulcers locally. With the administrative data, we found pressure sores in: 14.2% of paraplegics, who are not diabetic; 21.1% of paraplegia with diabetes; 11.9% of tetraplegia and not diabetic; and 15.0% for diabetic tetraplegia.

Conclusions: Contrary to clinical teaching, we find that paraplegics have a slightly higher rate of pressure sores compared to tetraplegics, and markedly higher if diabetes is also present. Tetraplegics functioning at their levels are dependent on others for their transfers and most of their ADLS. Their skin inspection is done by others and they are usually given specialized mattresses and adaptive equipment for transfers, thus decreasing their risks for shearing and frictional forces on their skin. Paraplegics are more independent and are not given as many adaptive equipment as they are taught how to do safe independent transfers, safe weight shifts, skin inspection, etc. Although there is an expectation that they would be less at risk for skin breakdown because of their higher functioning level, our data suggest this is not the case. With the healthcost burden of caring for decubitus ulcers in the SCI/D population (both economically and psychosocially), it is imperative that further work be done in this area.

Support: This project was supported by funding from Dr. Leonard Pogach’s and Dr. Thomas Findley’s VHA REAP Center for Healthcare Knowledge Management (HSRD REAP 427271).

Objective: The objective of this project was to examine the relationship between exercise and secondary conditions (e.g., skin breakdown or urinary tract infection) among adults with spinal cord injury (SCI).

Design: Cross-sectional study design.

Participants/Methods: Participants were adults with SCI who lived in the United States. Each participant completed a mail survey that inquired information of secondary conditions related to SCI, level of physical activity and exercise, community integration, and self-efficacy concerning exercise. Dependent variable was presence or absence of secondary conditions. Independent variable was regular exercise either at home or outside of the home. Covariates included injury and socio-demographic characteristics. Results were analyzed using descriptive analyses, chi-square tests, and multiple logistic regression analyses.

Results: Of 355 participants, the majority were male (60%) and White (89%). Average age was 46 years old (SD=13) while mean age at injury was 32 years old (SD=14). Their injury mostly occurred at cervical (47%) or thoracic segmental level (40%). More than half of the participants did not have total paralysis (53%). Chi-square tests showed that the presence of bladder or kidney stones, respiratory infection, urinary tract infection, and skin breakdown were significantly associated with the lack of exercise. Results from the multiple logistic regression analyses showed a significant decreased risk of bladder or kidney stones, respiratory infection, and skin breakdown among adults who exercised.

Conclusions: Exercise was significantly associated with reduced risks of certain SCI-related secondary conditions. A longitudinal study that would prospectively examine the same relationships was recommended.

Support: The project was funded as a NIDRR Rehabilitation Research and Training Center Grant (No. H133B031114).

Objective: Abnormal cardiovascular control following spinal cord injury (SCI) is well documented in animal models and humans, and has been attributed in part to injury-induced plasticity within the central nervous system. These studies assess the contribution of plasticity in sensory and sympathetic ganglia to autonomic dysreflexia (AD) following spinal cord injury (SCI) in rats and humans.

Design: Comparative histopathological rat and human study.

Participants/methods: Adult Wistar rats received a complete transection at the third thoracic segment (T3): survival times were one, two, or four weeks following SCI (n=8 per group). On the last day of the experiment, AD was examined in conscious rats by recording arterial pressure and heart rate during balloon distension of the colon. This stimulus resembles some of the stimuli, such as colon impaction, contraction, or irritation, that initiate AD clinically. Pressor responses to colon distension were also examined in a group of uninjured rats (n=6). After assessment of AD, rats were killed with an anesthetic overdose and transcardially perfused. Dorsal root ganglia (DRGs) and thoracolumbar paravertebral sympathetic ganglia rostral and caudal to SCI, as well as stellate and pelvic ganglia, were harvested. Immunohistochemical analysis was performed to characterize changes in intra-ganglionic axon density, as well as catecholamine and neuropeptide receptor expression following SCI. Human DRG specimens were selected and subjected to similar immunohistochemical characterization as rat DRGs.

Results: Tyrosine hydroxylase (TH) –expressing sympathetic axons invaded the rat DRG within two weeks following SCI. These axons infiltrated the DRG from its distal pole, the point at which the grey ramus joins the spinal nerve. TH-positve bouton-like structures apposed substance P-containing (small-diameter nociceptive) DRG neurons . We also found that substance P-containing (potentially sympathetic sudomotor) axons sprouted within the paravertebral sympathetic chain following SCI.

Conclusion: Peripheral sympathetic sprouting following SCI may form a novel anatomical substrate for AD.

Objective: To report the successful use of Desmopressin in the treatment of recumbent diuresis in spinal cord injury.

Design: Retrospective Case Series with review of the charts.

Participants/Methods: Spinal Cord Injury patients admitted to either University Hospital or Audie L Murphy VA hospital and who exhibited clinically significant diuresis. Chart Review of patients treated with Desmopressin.

Results: Subjects exhibiting clinically significant recumbent diuresis were initially managed with fluid restriction and increased frequency of clean intermittent catheterization(CIC). Patients who failed traditional management and continued to exhibit excessive bladder volumes at night were started on Desmopressin. These patients so treated showed a dramatic reduction in nocturnal bladder volumes eliminating concerns about bladder distention and reducing frequency of CIC. Side Effects noted included mild hyponatremia and salubrious increase in morning blood pressure facilitating mobilization with less orthostatic hypotension.

Conclusion: Nocturnal diuresis is a common presentation after spinal cord injury, especially in patients with acute spinal cord injury or in patients with high paraplegia or tetraplegia. Excessive nocturnal urine production can lead to bladder distention. incontinence, and often demands higher frequency in CIC, which can add to the burden of the patient or caregiver. The precise mechanism of the increase in nocturnal urine output has yet to be determined, but the pathophysiology of a similar phenomenon of immersion diuresis seen in swimmers or SCUBA divers has implicated Atrial Natriuretic Factor as the primary humoral mediator of this diuresis. Desmopressin has been used successfully in children to treat nocturnal enuresis as well as neurogenic bladder in patients with Multiple Sclerosis or spinal cord injury. This case series documents the successful use of Desmopressin to treat recumbent diuresis in spinal cord injury patients.

Support: N/A

Objective: To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI).

Design: This was a multicentre, randomised, double-blind, placebo0-controlled, flexible dose, parallel group study conducted at 66 centres in North America, Europe and Asia Pacific

Methods: In this multicentre, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged ³18 years with ED >6 months consequent to SCI were randomised to vardenafil (n=207) or placebo (n=211) (10 mg for 4 weeks, then maintained or titrated to 5 mg or 20 mg at Weeks 4 and 8). Efficacy assessments included the ‘Erectile Function’ (EF) domain score of the International Index of Erectile Function questionnaire, and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation.

Results: Baseline patient characteristics were similar in the vardenafil and placebo groups (mean age 40 and 39 years, respectively). Mean baseline EF domain scores were 11.6 and 12.1 (moderate ED) in the vardenafil and placebo groups, respectively. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward, compared with 13.5 in the placebo group (p<0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%) and ejaculation (19% vs 10%) success rates were significantly greater in the vardenafil group compared with placebo (all p<0.001). The most frequently reported drug-related adverse events were headache (15% and 4%), flushing (6% and 0%), nasal congestion (5% and 0%) and dyspepsia (4% and 0%) with vardenafil and placebo, respectively.

Conclusion: Vardenafil significantly improved erectile and ejaculatory function, and was generally well tolerated in men with ED due to SCI.

Support: This project was funded by GlaxoSmithKline. The abstract was presented by Professor Francois Giuliano at the EAU (European Association of Urology) Congress in Istanbul on Friday 18 March ('Influence of spinal cord injury severity on erectile and ejaculatory function with vardenafil in men with ED due to spinal cord injury').

Objective: To evaluate the efficacy of endoscopic sub-uretheral injection of biocompatible material in SCI patients with persisting (VUR) either with high dosage of oxybutinine 15 mg/day or after intra-detrusor injection of botulinum-A (BTX-A).

Materials: 18 SCI patients, mean age 37.5 years, had persisting grade II-IV reflux; 16 had monolateral high pressure reflux > 50 cm H20, while 2 showed low pressure reflux, 1 of whom bilateral. Median follow-up was 39 months. All the high-pressure VUR but one were treated either with an intra-detrusor injection of 300 I.U. of American or 750 I.U of English BTX-A. In 1 patient the increase to 15 mg/day of oxybutinine wassufficient to decreasebladder pressure. During the videourodynamic investigation all patients showed a low pressure bladder and VUR at low filling volume. The 18 subjects were treated by a transurethral sub-uretheral injection of Durosphere TM In all cases, follow-up included renal sonography, urodynamics and cystography at 3 and 12 months, and then at least every year following the procedure.

Results: The mean amount of Durasphere TM per injection was 0.9 (0.5-1.5 ml). 13 refluxing subjects were cured after a single injection. 2 subjects (1 with bilateral reflux) showed recurrence of VUR in the first follow-up which was resolved after a second injection. In 1 subject improved after 2 injections, but not achieve complete remission (1 st degree VUR) . In 2 subjects a recurrence of VUR was observed after 3 years and they were submitted to a new injection of Durosphere TM. In the follow-up 15 patients required re-injections of BTX-A overall. No complications were observed.

Conclusion: Endoscopic sub-uretheral bulking agent injections can be regarded as effective and safe for VUR in patients with overactive bladder after detrusor paralysis.

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