Pathophysiology of Autonomic Dysreflexia: Long-Term Treatment With Terazosin in Adult and Paediatric Spinal Cord Injury Patients Manifesting Recurrent Dysreflexic Episodes

Abstract

Introduction Spinal cord injury (SCI) results in disruption of synaptic influences on the sympathetic preganglionic neurones. Remodelling of spinal cord circuits takes place in spinal neurones caudal to cord injury. There is an increased vascular alpha-adrenoceptor responsiveness, and peripheral afferent (bladder) stimulation in SCI subjects induces a marked noradrenaline spillover below the level of spinal lesion. These neurophysiological changes possibly contribute to the development of autonomic dysreflexia, a condition of sympathetic hyper-excitability that develops after cervical, or upper dorsal cord injury with resultant paroxysmal rise in arterial pressure, and provide the scientific basis for the use of terazosin, a once-a-day, selective alpha-one adrenergic blocking drug. Objectives The use of terazosin, a long-acting, alpha 1-selective blocking agent was investigated in SCI patients who developed recurrent symptoms of autonomic dysreflexia, eg headache, sweating flushing of the face together with an increase in the arterial pressure. Design An open, prospective study of the efficacy of terazosin in controlling recurrent autonomic dysreflexia in traumatic tetraplegic/paraplegic patients manifesting clinical features of dysreflexia in the absence of an acute precipitating cause such as a blocked catheter. Setting The initial assessment and treatment were carried out in the Spinal Injuries Centre. Subsequently, the patients were followed-up in the community. They were monitored by telephonic interviews, follow-up visits by the patients to the hospital, and home-visits by the staff of the spinal unit. Subjects Eighteen adults with tetraplegia (female: 1; male: 17), three children with ventilator-dependent tetraplegia and three adult male patients with paraplegia who exhibited recurrent features of autonomic dysreflexia in the absence of an acute predisposing factor for dysreflexia eg performance of an invasive procedure such as cystoscopy, digital evacuation of bowels, or acute urinary retention, were enrolled in this study. Intervention After discussion with the patients and their carers, terazosin was prescribed with a starting dose of 1 mg in an adult and 0.5 mg in a child administered nocte. The patients were observed for (1) drug-induced hypotension; (2) clinical symptoms due to side effects of terazosin; and (3) continued occurrence of dysreflexic symptoms. Step-wise increments of the dose of terazosin (1 mg in case of adults, and 0.5 mg in a child) was carried out at intervals of 3-4 days, if a patient continued to develop dysreflexia but did not manifest any serious side effect. Outcome measures Complete subsidence of dysreflexic symptoms, or development of an adverse event necessitating termination of the terazosin therapy was the clinical end point. Results The dysreflexic symptoms subsided completely with the terazosin therapy in all the patients. The twenty-one adult patients required a dose varying from 1-10 mg, whereas the paediatric patients required only 1-2 mg of terazosin. The side effects of postural hypotension and drowsiness were transient, and mild. One tetraplegic patient developed persistent dizziness and therefore, the drug therapy was discontinued. Conclusion In 21 adult and three paediatric spinal cord injury patients manifesting recurrent episodes of autonomic dysreflexia in the absence of an acute predisposing cause, the use of terazosin, a once-a-day, specific alpha-one blocker resulted in complete subsidence of the dysreflexic symptoms. However, one tetraplegic patient required termination of terazosin therapy because of persistent dizziness.