Autonomic dysreflexia in urological practice: pathophysiology, prevention and treatment considerations.

PURPOSE: Spinal cord injury (SCI) leads to sensorimotor impairments; however, it can also be complicated by significant autonomic dysfunction, including cardiovascular and lower urinary tract (LUT) dysfunctions. Autonomic dysreflexia (AD) is a dangerous cardiovascular complication of SCI often overlooked by healthcare professionals. AD is characterized by a sudden increase in blood pressure (BP) that can result in severe cardiovascular and cerebrovascular complications. In this review, we provide an overview on the clinical manifestations, risk factors, underlying mechanisms, and current approaches in prevention and management of AD. METHODS: After conducting a literature research, we summarized relevant information regarding the clinical and pathophysiological aspects in the context of urological clinical practice CONCLUSIONS: The most common triggers of AD are those arising from LUT, such as bladder distention and urinary tract infections. Furthermore, AD is commonly observed in individuals with SCI during urological procedures, including catheterization, cystoscopy and urodynamics. Although significant progress in the clinical assessment of AD has been made in recent decades, effective approaches for its prevention and treatment are currently lacking.

[Efficacy of fesoterodine for prevention of autonomic dysreflexia in patients with neurogenic dysfunction of the bladder after spinal cord injury].

AIM: to evaluate the effectiveness of fesoterodine for the prevention of autonomic dysreflexia (AD) in patients with neurogenic bladder dysfunction (NBD) after spinal cord injury (SCI). MATERIALS AND METHODS: a total of 53 patients with AD were included in the study. In the main group (n=33) patients received fesoterodine 4 mg per day for 12 weeks as a treatment for neurogenic bladder dysfunction and prevention of AD. In the control group (n=20), patients were monitored for 12 weeks without specific treatment. The assessment was based on the results of ADFSCI and NBSS questionnaires, daily blood pressure monitoring with the completion of a self-observation diary, cystometry with simultaneous monitoring of blood pressure and heart rate. RESULTS: In the main group there was a significant decrease in episodes and severity of AD according to ADFSCI questionnaire and an improvement in the quality of life according to NBSS questionnaire compared to the control group (p<0.001). Also, in the main group, the number of episodes of AD and systolic blood pressure decreased. The maximum bladder capacity and bladder compliance increased (p<0.001), and the maximum detrusor pressure and systolic blood pressure when the cystometric capacity was reached, decreased significantly (p<0.001) in the main group compared in comparison with the control group. CONCLUSION: Fesoterodine at a dosage of 4 mg for 12 weeks reduced the severity of symptoms of AD in patients with SCI and NBD, which was manifested by the stabilization of blood pressure and a decrease in the number of episodes of AD, which significantly improved the quality of life. Also, the drug led to a significant improvement in urodynamic parameters during cystometry, in the form of a decrease in detrusor pressure and an increase in cystometric capacity. We can conclude that fesoterodine is effective in the prevention of AD in patients with NBD after SCI.

Pharmacological Inhibition of Soluble Tumor Necrosis Factor-Alpha Two Weeks after High Thoracic Spinal Cord Injury Does Not Affect Sympathetic Hyperreflexia.

After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning ∼2 weeks post-injury (wpi). The neuroimmune system has been implicated in driving sympathetic hyperreflexia, as inhibition of the cytokine soluble tumor necrosis factor-alpha (sTNFα) using the biological mimetic XPro1595 beginning within days post-SCI has been shown to attenuate the development of AD. Here, we sought to further understand the effective therapeutic time window of XPro1595 to diminish sympathetic hyperreflexia, as indicated by AD. We delayed the commencement of continuous intrathecal administration of XPro1595 until 2 weeks after a complete, thoracic level 3 injury in adult rats. We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNFα inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNFα signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.

Reconstructive surgery and patients with spinal cord injury: Perioperative considerations for the plastic surgeon.

BACKGROUND: Patients with spinal cord injury (SCI) requiring reconstructive surgery, particularly for pressure ulcers, are ubiquitous in Plastic and Reconstructive Surgery practices. Much of the current literature focuses on operative techniques, antibiotic indications, sitting protocols, and dressing and bedding choices. METHODS: This paper reviews normal neuroanatomy, outlines changes in neurophysiology observed in spinal cord injury, and addresses concepts related to perioperative care that are highly relevant but often under-emphasised. RESULTS: Vascular disturbances such as autonomic dysreflexia and orthostatic hypotension are dangerous phenomena occurring in this patient population that, if not properly recognised and treated, may result in complications such as haematoma, flap loss, inadequate tissue perfusion, and death. The management of spasticity, deep venous thrombosis, and perioperative pain are also relevant and discussed in this paper. CONCLUSION: A basic understanding of these concepts is essential for the Plastic Surgeon involved in the care of patients with SCI and pressure ulcers, particularly before and after debridement or reconstruction.

The downside of ileocystoplasty for persons with cervical spinal cord injury and an indwelling urinary catheter.

PURPOSE: To explore the lived experience of persons with cervical spinal cord injury with a urinary catheter in situ, managing mucus in urine following ileocystoplasty METHOD: Descriptive qualitative methodology was employed. Semi-structured, one-to-one, audiotaped interviews with men (n=6) and a woman (n=1) with cervical-level spinal cord injuries (C4-C6). Analyses of transcribed verbatim transcripts was undertaken using thematic analysis. FINDINGS: There was a mean of 3.6 years since ileocystoplasty. Six major themes emerged from the data. All participants perceived the surgery had adversely affected their life, in part because regular intervention was needed to manage the significant problem of mucus. There was also an increase in autonomic dysreflexia episodes experienced due to mucus blocking bladder drainage. CONCLUSION: Consequences of mucus production have impacted negatively upon participants' health and their ability to participate in life situations, as well as increasing their dependence on others.

Transurethral sphincterotomy provides significant relief in autonomic dysreflexia in spinal cord injured male patients: long-term followup results.

PURPOSE: An evaluation of the results of transurethral sphincterotomy in spinal cord injured patients for the relief of autonomic dysreflexia is presented. MATERIALS AND METHODS: The study describes experience with the treatment of 46 consecutive spinal cord injured males presenting with frequent symptoms of autonomic dysreflexia and inadequate voiding. The selection criteria include patients injured above the thoracic 6 level with subjective symptoms of autonomic dysreflexia who did not want to be catheterized or were unable to perform intermittent catheterization. Patients were studied with complex urodynamics before and at least 3 months after undergoing transurethral sphincterotomy. During cystometrogram the maximum increase in systolic and diastolic blood pressure was recorded. After transurethral sphincterotomy patients were followed for a mean of 5.4+/-3.1 years (range 1 to 12). RESULTS: There was subjective relief in autonomic dysreflexia following transurethral sphincterotomy in all patients, which correlated well with a significant decrease in systolic and diastolic blood pressure (p<0.0001). Mean decrease in maximal systolic and diastolic blood pressure after transurethral sphincterotomy was 55+/-25 and 29+/-17 mm Hg, respectively. Mean post-void residual urine decreased significantly from 233+/-151 to 136+/-0.34 ml after transurethral sphincterotomy. However, there was no significant change in mean maximum voiding pressures. CONCLUSIONS: Blood pressure monitoring during cystometrogram provides an objective assessment of the presence of autonomic dysreflexia due to neurogenic bladder dysfunction, enabling better therapeutic management to control autonomic dysreflexia. Persistence of significant autonomic dysreflexia needs urodynamic evaluation if other factors for autonomic dysreflexia have been excluded.

Lidocaine anal block limits autonomic dysreflexia during anorectal procedures in spinal cord injury: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Autonomic dysreflexia is a common and potentially dangerous hypertensive response to stimulation below the level of injury that occurs in patients with spinal cord injury at T6 or above. Rectosigmoid distention and anal manipulation are among the stimuli that may precipitate autonomic dysreflexia. Instillation of topical local anesthetic into the rectum is the recommended prophylaxis against autonomic dysreflexia of anorectal origin. However, a previous randomized, double-blind, placebo-controlled trial showed that topical lidocaine in the rectum does not blunt the autonomic dysreflexia response to anorectal procedures. The purpose of this study was to determine whether lidocaine anal sphincter block would be effective in limiting anorectal procedure-associated autonomic dysreflexia. METHODS: We enrolled patients with chronic, complete spinal cord injury above T6, who were having anorectal procedures (flexible sigmoidoscopy and/or anoscopic hemorrhoid ligation). In a double-blind fashion, patients were randomized for intersphincteric anal block with 1 percent lidocaine or normal saline (placebo) before the procedure. Blood pressure was measured before, during, and after the block and procedure. RESULTS: Thirteen patients received lidocaine, and 13 received placebo. The groups were similar in age, level of injury, duration of spinal cord injury, type of procedure, and procedure duration. The mean maximal systolic blood pressure increase for the lidocaine group was 22 +/- 14 mmHg, significantly lower than the placebo group's 47 +/- 31 mmHg (P = 0.01). CONCLUSIONS: Lidocaine anal block significantly limits the autonomic dysreflexia response in susceptible patients undergoing anorectal procedures.

Topical lidocaine does not limit autonomic dysreflexia during anorectal procedures in spinal cord injury: a prospective, double-blind study.

BACKGROUND AND AIMS: Autonomic dysreflexia is a common and potentially dangerous response in patients with spinal cord injury at T6 or above. Acute blood pressure elevation may be precipitated by rectosigmoid distention and anal manipulation. Topical anesthetics are widely recommended to minimize the incidence and severity of autonomic dysreflexia, although no scientific evidence supports or refutes this practice. This study tested whether topical lidocaine would prevent or limit anorectal procedure-associated autonomic dysreflexia. PATIENTS AND METHODS: We enrolled patients with chronic, complete spinal cord injury scheduled for anoscopy and/or flexible sigmoidoscopy. In a double-blind fashion they were randomized to receive either 2% lidocaine jelly (n = 18) or nonmedicated lubricant (control; n = 32) just prior to the procedure. We measured blood pressure before, during, and after procedures. RESULTS: Mean maximal systolic blood pressure increased 35 +/- 25 mmHg in the lidocaine group vs. 45 +/- 30 mmHg in the control group (NS). However, there was a significant difference between anoscopic procedures and flexible sigmoidoscopies without anoscopy (49 +/- 29 vs. 25 +/- 20 mmHg). CONCLUSION: Topical lidocaine did not significantly limit or prevent autonomic dysreflexia in susceptible patients. Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. Anoscopy, which involves stretching of the anal sphincters, was a more potent stimulus for autonomic dysreflexia than flexible sigmoidoscopy, which involves gaseous distention of the rectosigmoid. Anal sphincter stretch and rectosigmoid distention, rather than a mucosal stimulus, are likely nociceptive triggers for procedure-associated autonomic dysreflexia.

Neutralizing intraspinal nerve growth factor with a trkA-IgG fusion protein blocks the development of autonomic dysreflexia in a clip-compression model of spinal cord injury.

Increased intraspinal nerve growth factor (NGF) after spinal cord injury (SCI) is detrimental to the autonomic nervous system. Autonomic dysreflexia is a debilitating condition characterized by episodic hypertension, intense headache, and sweating. Experimentally, it is associated with aberrant primary afferent sprouting in the dorsal horn that is nerve growth factor (NGF)-dependent. Therapeutic strategies that neutralize NGF may ameliorate initial apoptotic cellular responses to the injury and aberrant afferent plasticity that occurs weeks after the injury. Subsequently, the development of autonomic disorders may be suppressed. We constructed a protein including the extracellular portion of trkA fused to the Fc portion of human IgG and expressed it using a baculovirus system. Binding of our trkA-IgG fusion protein was specific for NGF with a K(d) = 4.26 x 10(-11) M and blocked NGF-dependent neuritogenesis in PC-12 cells. We hypothesized that binding of NGF in the injured cord by our trkA-IgG fusion protein would diminish autonomic dysreflexia. Severe, high thoracic SCI was induced with clip compression and the rats were treated with intrathecal infusions (4 microg/day) of trkA-IgG or control IgG. At 14 days post-SCI, the magnitude of autonomic dysreflexia was assessed. Colon distension increased mean arterial pressure (MAP) in control rats by 46 +/- 2 from 96 +/- 5 mmHg. In contrast, MAP of rats treated with trkA-IgG increased by only 30 +/- 2 mmHg. Likewise, the MAP response to cutaneous stimulation was also reduced in rats treated with trkA-IgG (20 +/- 1 vs. 29 +/- 2). In contrast, trkA-IgG treatment had no effect on heart rate responses during colon distension or cutaneous stimulation. These results indicate that treatment with trkA-IgG to block NGF suppresses the development of autonomic dysreflexia after a clinically relevant spinal cord injury.

Autonomic dysreflexia and foot and ankle surgery.

Autonomic dysreflexia is a syndrome of massive imbalance of reflex sympathetic discharge occurring in patients with spinal cord injury with a lesion above the splanchnic outflow (Thoracic 6). Autonomic dysreflexia is characterized by a sudden and severe rise in blood pressure and is potentially life threatening. Because the onset of this entity is rapid and the potential morbidity is severe, it is important for those caring for spinal cord injury patients to be aware of this syndrome. The paper presents a review of the literature, and familiarizes one with the diagnosis, pathophysiology, and treatment. Two illustrative case reports are also presented.