ORTHOSTATIC HYPOTENSION FOR PEOPLE

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1 Literature Review Hong Kong Physiother J 2008;26:51 58 ORTHOSTATIC HYPOTENSION FOR PEOPLE WITH SPINAL CORD INJURIES Clare Y.L. Chao, 1,2 MSc; Gladys L.Y. Cheing, 2 PhD Abstract: Orthostatic (postural) hypotension (OH) is a clinical feature commonly seen in spinal cord injury (SCI) subjects with cervical and high thoracic lesions. It usually gets worse during head-up tilt postural change and is relieved by lying flat. The mechanisms of regulating the arterial blood pressure (BP) are complex. Normally, BP is maintained through a rapid and effective reflex adjustment of the autonomic nervous system, and with slower humoral compensatory changes to counteract the gravitational forces on blood. The leg muscle pumping mechanism also helps to facilitate venous return and improves BP. Failure of these mechanisms may lead to OH and orthostatic intolerance symptoms. The occurrence of OH may limit active participation in intense physical rehabilitation programmes by people with SCI, and facilitate the deterioration effects of immobilization and development of undesirable secondary medical complications. Advances in understanding the pathophysiology of OH are crucial for success in combating OH. Treatment usually includes both non-pharmacological and pharmacological measures. This article provides a review of the mechanisms of normal regulation of arterial BP, the pathophysiology of OH in SCI, and the common clinical management of OH. Key words: management, orthostatic hypotension, pathophysiology, spinal cord injury Introduction Spinal cord injury (SCI) persons with high cord level lesions usually have the accompanying problem of orthostatic hypotension (OH). Multiple mechanisms have been considered to explain this clinical sign. Deranged cardiovascular control in tetraplegic and high paraplegic individuals during orthostatic stress can be directly linked to sympathetic nervous system dysfunction and complete muscle paralysis below the level of the lesions [1,2]. The occurrence of OH may limit active participation in intense physical rehabilitation programmes by people with SCI and hasten their deterioration through immobilization and the development of undesirable secondary medical complications [1,3,4]. Advances in understanding the pathophysiology of OH are crucial for success in combating OH. This article provides a review of the mechanisms of arterial blood pressure (BP) regulation in both normal subjects and in people with SCI during orthostatic challenges, and the common clinical management of OH. Definition and Prevalence According to the American Autonomic Society and American Academy of Neurology in 1996 [5], OH is defined as a fall in systolic BP of at least 20 mmhg or in diastolic BP of at least 10 mmhg within 3 minutes of standing or during a head-up tilt of at least 60. OH may result from a variety of causes. This is particularly true for people with SCI with lesions at a level above the major sympathetic outflow to splanchnic vascular beds, i.e. at the thoracic 6 (T6) level or above [1,2,6], or for those with pure autonomic failure and multiple system atrophy [7]. The prevalence of OH in people with SCI is high. Among 14 patients with acute SCI, Illman et al [4] reported that OH occurred during 73.6% of physiotherapy mobilization treatments that involved sitting or standing. Symptomatic OH was reported in 58.9% of the treatments and were perceived as the limiting factor for continued treatment in 43.2% of the treatments. Cariga et al [6] demonstrated a high prevalence of OH 1 Physiotherapy Department, Queen Elizabeth Hospital, and 2 Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China. Received: 16 September 2008 Accepted: 20 December 2008 Reprint requests and correspondence to: Dr Gladys Cheing, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China. gladys.cheing@inet.polyu.edu.hk Hong Kong Physiotherapy Journal Volume Elsevier. All rights reserved.

2 of 57.1% in 28 SCI subjects during the head-up tilt manoeuvre. Sidorov et al [8] reported that OH persisted in 74% of cervical and 20% of upper thoracic motor complete SCI patients during the first month following SCI. OH may appear with or without symptoms. Clinical Features The orthostatic intolerance symptoms include dizziness, slight light-headedness, blurred vision, fatigue, palpitations, neck ache, and syncope [4]. It is most pronounced in the acute phase of SCI, but can persist for years after the occurrence of the injury [7]. It is classically provoked by a change in body position when moving from lying to sitting or sitting to standing, and is relieved by lying flat [9]. The magnitude of the drop in absolute BP is not the only factor responsible for the symptoms; they can also be caused by the rate at which the patient s BP has fallen and cerebral autoregulation [7]. It has been observed that many SCI individuals can tolerate a profound orthostatic drop in BP and do not experience symptoms [10]. However, a further small decrease in BP with an increase in functional demand may easily exceed the autoregulatory capacity of the brain or other vital organs, which potentially increase the risk of injury induced by persistent hypotension [10,11]. It has been demonstrated that cerebral autoregulation cannot function normally when cerebral perfusion pressure is 60 mmhg or below in normal subjects [11]. Mechanisms for Regulating Arterial BP in Normal Subjects When an individual assumes an upright position, a large proportion of the blood will have pooled in the venous system of the legs and abdomen owing to the effects of gravity [10,12]. Several dynamic circulatory responses occur immediately upon the assumption of the upright posture. The hydrostatic circulatory load passively dilates the blood vessels of the lower extremities and viscera [1]. The right atrial pressure falls and the blood redistributes itself towards the lower extremities. Fifteen percent of the total blood volume may pool in the legs and 10% of the plasma volume is lost to the tissue within minutes of passive standing [13]. Consequently, an immediate decrease in venous return, cardiac filling pressure, stroke volume and arterial pulse pressure occurs, leading to a reduction in cerebral perfusion [14, 15]. A major stress is thus imposed on the cardiovascular system, which elicits a series of powerful neurohumoral reflexes and mechanical adjustments to ensure a stable BP, such that adequate perfusion of the vital organs, especially the brain, is maintained [1,16]. With the reduction in venous return, arterial BP will be compromised if blood pooling persists. An important consequence of this altered cardiovascular function could be OH with fainting [12]. However, such an effect can be counterbalanced by the combined action of sympathetically medicated vasoconstriction and leg muscle pumping activity [7]. Role of the sympathetic nervous system The sympathetically mediated arterial baroreflex is the most important physiological mechanism for attenuating the effects of the rapid daily perturbation of BP [17]. With the change in posture from lying to standing, the sudden reduction in BP in such an upright position decreases the tension in the walls of the blood vessels, which stimulates the arterial baroreceptors located within the walls of the aortic arch and the carotid sinus [10,14,17,18]. This information is neurally encoded and relayed through afferent sympathetic pathways to the vasomotor centre in the brainstem. The vasomotor centre then sends out impulses via peripheral efferent sympathetic nerves to the heart, peripheral blood vessels, adrenals and kidneys, thereby causing an appropriate degree of compensatory vasoconstriction, increasing the concentration of norepinephrine and epinephrine, the heart rate and levels of plasma catecholamine, and activating the renin-angiotensin-aldosterone system [14,17]. The increase in sympathetic tone and the subsequent increase in norepinephrine cause a relative increase in total peripheral resistance and an increase in heart rate, which then helps to compensate for the hydrostatic dilation of the blood vessels in the lower extremities, and to prevent an exaggerated decrease in venous return that could lead to a smaller stroke volume and lowered BP [19,20]. BP is promoted by an increase in total peripheral resistance and a decrease in venous compliance. Therefore, the sympathetic nervous system helps to prevent an exaggerated change in venous return and BP, thus maintaining cardiovascular homeostasis [19,20]. Without such compensation, the act of standing would lead to a fall in the arterial pressure responsible for perfusing the brain, potentially resulting in dizziness, syncope or loss of consciousness [17]. Neurohumoral responses Humoral agents may also play an important role in the homeostatic regulation of BP. With the increase in sympathetic nervous activity that occurs in a condition of orthostatic stress, the plasma catecholamine level increases in normal subjects [14,19,20]. This, in turn, promotes vasoconstriction and leads to a decrease in venous pooling. Prolonged orthostasis also activates the reninangiotensin system and releases epinephrine and arginine vasopressin [13,14,19,20]. Arginine vasopressin plays a role in controlling urinary osmolality. It is the main factor that determines urine concentration and saves water on the assumption of upright posture [13]. The reduction in 52 Hong Kong Physiotherapy Journal Volume

3 plasma volume during orthostatic stress reduces the glomerular filtration rate, which, in turn, stimulates the release of renin from the kidney. This then increases adrenergic nerve activity and catalyzes the formation of plasma angiotensin II [1]. An increase in angiotensin II level has several functions: (1) to increase tubular sodium ion reabsorption at the level of the kidney; (2) to cause vasoconstriction at the level of the vascular smooth muscle; and (3) to enhance norepinephrine release by action on the presynaptic noradrenergic neurons [13]. It also stimulates the secretion of aldosterone by the adrenal cortex, causing vasoconstriction and sodium and water retention, which lead to plasma volume expansion. Consequently, BP increases [1]. Circulatory responses Cardiac output is calculated as the product of stroke volume and heart rate. During stationary standing, there is an immediate downward translocation of blood to the peripheral veins owing to the effects of gravity, resulting in a decrease in venous return and stroke volume. This elicits a rapid circulatory adjustment by the vagally mediated rise of the heart rate in order to maintain adequate cardiac output [21]. Under normal circumstances, the heart rate is under the control of both the parasympathetic and sympathetic branches of the autonomic nervous system. Under the initial orthostatic challenge, the heart rate and cardiac output are increased through vagal withdrawal mediated by the parasympathetic nervous system [21]. However, with the fall in central venous pressure and arterial BP under orthostatic stress conditions, the low filling pressure of the heart greatly limits the extent to which cardiac output can be increased by the acceleration of the heart rate. Therefore, the rapid vagal effects on heart rate are of little value because of the almost immediate fall in right ventricular stroke volume [21]. The slower sympathetically mediated response of an increasing heart rate begins to rise when vagal withdrawal is nearly complete and the heart rate approaches 100 beats per minute. The indices for increased sympathetic control are splanchnic and renal vasoconstriction, increased plasma norepinephrine concentration, and increased plasma renin activity [21]. Activation of the skeletal muscle pump OH may also be caused by the lack of muscular pumping in the vascular beds, which leads to peripheral blood pooling, impaired venous return, and diminished cardiac output [22]. In the absence of any movement, skeletal muscle tone during upright standing has a critical influence on the quantity of blood displaced into the legs [21]. The muscular pumping mechanism has important functional connotations. The active contraction of voluntary muscles in the legs is a necessary step in activating the venous pump function to prevent stasis in venous blood flow during periods of inactivity and prolonged standing [23]. Even during periods of quiet standing without any conscious movement, rhythmic contraction in various antigravity muscles in normal subjects leads to a decrease in venous transmural pressure and, hence, in a decrease in venous pooling [21]. The pumping activity in leg muscles compresses the veins, drastically lowers venous and capillary pressure, and returns the blood volume contained within the veins of the legs [23]. It momentarily blocks arterial inflows and greatly increases the venous driving pressure back to the heart. Thus, the ventricular filling pressure and stroke volume are rapidly restored and BP is maintained [12,21]. The musculovenous pump also prevents the development of oedema in the lower extremities by promoting lymph flow in an upright posture [23]. Pathophysiology of OH in People with SCI Impaired sympathetic nervous system The sympathetic preganglionic neurons for the peripheral vasculature are found mainly in spinal cord segments T1 to L2 [18]. The splanchnic circulation, the largest single reservoir of blood available to the circulatory system, has a significant role in regulating systemic BP as it receives about 60% of the cardiac output and contains about one-third of the total blood volume [24]. The major sympathetic splanchnic outflow is from T5 to L2 [2]. In highlevel complete SCI, the efferent sympathetic pathway from the brainstem vasomotor centre to the preganglionic neurons can be permanently interrupted. The function of the isolated spinal cord below that lesion becomes independent of supraspinal control. With the loss in motor, sensory and autonomic function below the lesion in SCI individuals, none of the above mechanisms function to support the redistribution of blood volume [12,25]. SCI above the T6 level disrupts the discharge of efferents from the brain stem to the sympathetic nerve responsible for vasoconstriction in the critical splanchnic circulation and lower extremities, which leads to central baroreflex failure, seriously impairing the body s mechanism for the short-term control of BP [2,26]. With SCI below the T6 level, there is generally sufficient supraspinal neural control of sympathetic nervous system efferent flow to the large and crucial splanchnic circulatory bed, and the occurrence of OH is, therefore, less commonly seen [2]. Nevertheless, although sympathetic response to orthostasis is diminished in both paraplegics and tetraplegics [27, 28], Houtman et al [19,20] and Claydon and Krassioukov [29] found that only tetraplegics showed poorer cardiovascular homeostasis. It has been suggested that patients with paraplegia maintain cardiovascular homeostasis during head-up tilt without increased sympathetic nervous system activity. 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4 Apart from the reduced overall sympathetic activity, morphological changes in sympathetic preganglionic neurons were also observed in high-level SCI individuals [2,30]. The atrophy of the sympathetic preganglionic neurons in the acute stage of SCI may contribute to the condition of spinal shock, which results in a flaccid paralysis, temporary loss of most spinal reflexes and low systemic arterial BP [30]. With time, SCI individuals may demonstrate peripheral α-adrenoceptor hyperresponsiveness below the level of SCI and it may account for the excessive pressor responses observed in autonomic dysreflexia, a condition commonly observed in chronic SCI above the T6 level [2,30 32]. Mathias et al [33] showed enhanced pressor responses to noradrenaline in tetraplegia as compared to paraplegia. Arnold et al [34] demonstrated significant increase in α-adrenoceptor responsiveness in the dorsal foot veins of tetraplegic patients with a history of autonomic dysreflexia. Cerebrovascular autoregulation Cerebral autoregulation, the ability of the cerebral resistance vessels to maintain constant cerebral perfusion despite changes in mean arterial pressure, is the common pathway leading to syncope [35]. Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hypotension. Cerebral vasoconstriction may occur during OH, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. Levine et al [36] reported that cerebral vasoconstriction occurs in healthy humans during graded orthostatic stress, and the authors speculate that this degree of cerebral vasoconstriction is insufficient to cause syncope during orthostatic stress, but it may exacerbate the decrease in cerebral blood flow associated with hypotension if haemodynamic instability develops. Brown et al [35] reported that cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation even during high levels of orthostatic stress in normal healthy subjects [35]. Although the majority of patients with high SCI experiences hypotension during orthostatic challenge, there is a surprisingly low incidence of syncopal events despite low systemic BP. This observation led to the idea that cerebrovascular adaptation may exist in people with SCI. Only a few studies have reported on cerebral circulation in SCI individuals. Gonzalez et al [3] compared both systemic BP and cerebral blood flow in 10 symptomatic and 10 asymptomatic SCI individuals with lesion levels above T6. In an 80 head-up tilt, systemic BP decreased to a similar extent in both groups, but cerebral blood flow was significantly lower in the symptomatic group. The authors concluded that cerebral autoregulation and not maintenance of systemic BP was crucial in the prevention of syncope symptoms during orthostatic stress. However, they made no comparison with ablebodied subjects. The study of Houtman et al [37] did not support any advantages of cerebrovascular autoregulation in SCI individuals during orthostatic stress. The authors reported that the mean arterial pressure decreased significantly in SCI but not in able-bodied individuals during orthostatic stress. Although both cerebral blood flow velocity and cerebral oxygenation decreased in both SCI and able-bodied individuals, the decrement was greater in SCI individuals. It was suggested that although systemic circulation was less well regulated in SCI compared with able-bodied individuals, cerebral circulation in SCI was maintained as in able-bodied subjects. Nanda et al [38] reported similar cerebral autoregulation in both SCI and able-bodied individuals, but the authors compared the orthostatic stress in sitting to supine only, and this degree of orthostatic stress might not be large enough to show differences. Nevertheless, conclusive evidence of improved cerebral autoregulation in SCI individuals is still lacking. Concentration of humoral agents In contrast to normal subjects, those with tetraplegia have a lower resting level of catecholamine, and such a humoral agent seems unaffected by a change in posture [18,39]. Guttmann et al [39] found a relatively smaller increase in catecholamine levels when tetraplegic patients tilted up their heads compared with normal subjects. Moreover, the plasma norepinephrine response to the head-up tilt posture may be normal or exaggerated in patients with paraplegia but is diminished or absent in tetraplegia [1]. Schmid et al [40] showed that epinephrine and norepinephrine concentrations were lower in tetraplegics at rest, and their levels were significantly higher in low paraplegics with lesion levels below T5 than in high paraplegics with lesion levels above T5. Claydon and Krassioukov [29] demonstrated that cardiovascular control during orthostasis was impaired in tetraplegia but not paraplegia. They reported that cervical SCI subjects had a lower supine heart rate and noradrenaline levels than those with thoracic SCI and control subjects. In addition, the upright catecholamine levels were also lower in cervical SCI subjects. The renin-angiotensin system can still be activated during the head-up tilt posture in patients with spinal cord transactions [9,39]. Renin is an enzyme released by the kidney [32]. The mechanism that controls such a release is not fully understood [39]. It is thought that the release of renin occurs normally in spite of injury to the spinal cord, which disrupts the connection between the brain and the peripheral efferent sympathetic pathways [18,39,41,42]. Johnson and Park [42] reported that both heart rate and plasma renin concentration were increased when changing the posture to vertical in tetraplegic persons. Mathias et al [43] showed that plasma noradrenaline and adrenaline levels did not change, but there was a marked increase in plasma renin activity in tetraplegic subjects during head-up tilt, 54 Hong Kong Physiotherapy Journal Volume

5 while both plasma adrenaline and renin levels were increased in normal subjects. In SCI individuals, renin is released at a higher level than in normal subjects during the head-up tilt posture because of the greater fall in BP [43,44]. Such elevated values may be part of a compensatory humoral response to maintain BP. The reduction in systemic and renal perfusion pressure probably provoke pronounced renal afferent arteriolar dilation, and may result in the stimulation of juxtaglomerular renin-secreting cells and higher levels of renin and, thus, of angiotensin II [44]. Renin acts on angiotensinogen in the plasma, forming angiotensin I, which in turn is converted to angiotensin II by angiotensin-converting enzyme [41]. This substance has a powerful vasoconstrictory effect on blood vessels and stimulates the release of aldosterone from the adrenal cortex [45]. Consequently, it causes salt and water retention, and leads to the expansion of plasma volume [44]. Although the release of renin appears to be independent of sympathetic activation, it has been suggested that intact peripheral efferent renal sympathetic nerves are necessary for the appropriate release of renin [42,44]. Nevertheless, the activation of this system alone may be inadequate for maintaining stable BP to prevent venous pooling in the legs and splanchnic region [42]. Lack of muscle pump activity The degree of muscle tone and intramuscular pressure are important determinants of venous transmural pressure and venous volume in dependent legs [21]. In SCI subjects with complete motor paralysis below the level of lesions, the reduction in muscle tone appears to be one of the greatest factors contributing to orthostatic intolerance [21]. Atrophy of the leg muscles may result in inadequate compression of the veins and, therefore, in less effective muscle pump activity. This will further hinder venous return and cause more pooling and extravasation of plasma in the dependent extremities, thus diminishing cardiac output [22]. Difficulties will then be encountered in the maintenance of cardiovascular homeostasis during orthostatic challenge caused by postural changes [12]. It has been found that venous atrophy may occur coincidentally with muscle atrophy in the paralysed limbs and cause reduced venous compliance. This may decrease the amount of blood being pooled in the veins of the legs during orthostasis [46]. Increased skeletal muscle tone over time may also improve OH. Nevertheless, chronic SCI individuals still demonstrate increased OH and intolerance [9]. Clinical Management of OH in People with SCI The key to maintaining a stable BP is to ensure that arterial BP remains at an adequate level for perfusion of the vital organs, especially the brain and heart, when functional demands increase. Severe persistent hypotension may increase the risk of injury, causing cerebral anoxia when BP is not restored. The main goals of managing OH are to improve BP and to relieve symptoms [10]. Treatment usually includes both non-pharmacological and pharmacological measures [14,47]. Non-pharmacological measures Several measures can minimize the effects of OH. Patient education is important. Patients should understand that BP is always higher in the lying flat position and lower in the upright position. To dispel a hypotensive attack and symptoms of intolerance, they need only immediately sit down or lie flat [10]. People with SCI are advised to avoid sudden changes in the head-up posture, excessive environmental heat or even hot baths [48,49]. Eating smaller meals more frequently and having a diet high in salt are also encouraged [14]. It is also suggested that people with SCI tilt up their headboard at night. This tilting will stimulate the reninangiotensin-aldosterone system and vasopressin secretions, causing vasoconstriction and sodium and water retention, and lead to an expansion in vascular volume, hence promoting BP [14,44]. In the management of OH, the past few years have seen the use of physical countermeasures, such as elastic stockings, abdominal binders and G-suits, in attempts to increase venous pressure and reduce venous pooling in the legs [10,14,47,50]. Elasticized garments extending from the foot to the costal margin allow a gradient of counterpressure to be applied, with maximum pressure at the ankles and slight counterpressure at the top [14]. However, the induced compression of the legs and abdomen may also increase systemic vascular resistance [51]. Denq et al [51] evaluated the effectiveness of compression of different capacitance beds (involving calf alone, thigh alone, low abdomen alone, calf and thigh, or all compartments) by a modified antigravity suit at a positive pressure of 40 mmhg during orthostatic challenge in people with pure autonomic failure, multiple system atrophy and diabetic autonomic neuropathy. They found that the combined use of abdominal compression and leg compression is particularly efficacious, followed by abdominal compression, whereas leg compression alone was less effective. If used alone, abdominal compression is more effective than leg compression. The major mechanism of improvement through the use of different physical countermeasures is an increase in total peripheral resistance presumably by reducing the vascular capacitance [48,49]. Gradual postural tilting using a tilt table is a conventional treatment for managing OH among people with SCI [1]. The act of tilting or standing is the most beneficial and appropriate intervention for improving orthostatic symptoms and tolerance, and decreases the risk of Hong Kong Physiotherapy Journal Volume

6 secondary medical complications for this patient group [1,51]. Also, as the combination of sympathetic denervation and the absence of regular orthostatic challenge contribute substantially to the loss of venous capacitance in SCI individuals [52], it has been suggested that orthostatic intervention together with or without regular physical activity may improve vascular compliance and, hence, peripheral and central venous pressures in individuals with SCI [53]. The purpose of postural tilting is to overcome orthostatic reactions to elevated postures and to enable early weight bearing and wheelchair mobility. Prolonged periods of regular standing will also help to improve both the physical and psychological fitness of people with SCI [54,55]. However, severe orthostatic symptoms in some SCI patients greatly limit the extent to which they can be maintained in an upright posture, and so they may first need to be mobilized in a wheelchair equipped with a reclining back and elevated legs before they can proceed to a vertical posture through tilting or standing. However, these procedures usually take quite some time before patients are able to achieve full vertical orthostatic tolerance. In recent years, it has been suggested that functional electrical stimulation (FES) to the lower extremities combined with passive tilting may be an alternate way of combating OH. As in individuals with high SCI, the complete muscle paralysis together with diminished sympathetic efferent activity results in excessive venous pooling in the lower extremities in an upright posture. Electrical stimulation has been reported to activate the skeletal muscle pump and to improve venous return [51,52]. The physiological muscle pump activated by FES then moves blood back to the central circulation and improves arterial flow to the heart [56 58]. Under low orthostatic situations, Davis et al [56,57] demonstrated that FES is effective for inducing rhythmic static contractions of paralysed leg muscles, thereby reactivating the skeletal muscle venous pump and augmenting cardiac output and stroke volume during arm crank exercise. Glaser et al [59] also observed that peripheral FES increased cardiac output and stroke volume at rest in able-bodied and paraplegic subjects in both the supine and upright seated postures. In agreement with these observations, Raymond et al [15] demonstrated that the electrical stimulation-induced muscle contraction was able to elicit an increase in cardiac output by 16% and stroke volume by 20% in individuals with paraplegia. The electrical stimulation-induced muscle contraction probably increased the venous driving pressure back to the heart, while the relaxation phase between contractions reduced venous pressure and allowed the movement of blood from the arteries to the veins. Consequently, it enhanced the emptying of the leg venous system [15]. Raymond et al [52] noted that the decrease in stroke volume during arm crank exercise under moderate orthostatic challenge was reversed via reactivation of the lower limb muscle pump and augmented venous return with electrical stimulationinduced leg muscle contraction. It has also been suggested that FES has potentially beneficial effects on haemodynamic responses in SCI individuals during orthostatic challenge [25,26,52,60]. SCI individuals generally demonstrated a better cardiovascular homeostasis when FES was applied to the lower extremity muscles during orthostatic challenge. Elokda et al [60] found a less pronounced decrease in both systolic and diastolic BPs with FES than without FES during the graded head-up tilt manoeuvre. Faghri et al [25] investigated the effects of FES on circulatory hypokinesis during active and passive standing in 14 chronic SCI individuals. The results showed a significant increase in heart rate in the paraplegics after 30 minutes of active standing with FES administered. The decrease in cardiac output, stroke volume and BP during passive standing was maintained during active standing. Sampson et al [26] compared the possibility of using FES to control OH in six acute and chronic SCI individuals with lesion level above T6. They reported a dose-dependent increase in BP despite its progressive fall with increasing angle of tilt during the gradual head-up tilt manoeuvre. They concluded that FES might be useful in managing OH. Chao and Cheing [61] reported that FES-induced leg muscle contraction is an effective adjunct treatment to delay OH caused by tilting, and it allows people with tetraplegia to stand up more frequently and for longer durations. Prolonged regular standing is also considered helpful to improve both physical and psychological fitness of people with SCI [54,55]. As reviewed by Gillis et al [62], it was reported that FES to the legs had the most promising results, among these non-pharmacological measures, in combating OH. Pharmacological measures Pharmacological measures should always be tried only after non-pharmacological measures have been attempted and proven to be not entirely successful, as most of the medications usually carry potential side effects. The aim of pharmacological treatment is generally to increase either the peripheral resistance or effective circulating blood volume [18]. Several agents are widely used to treat patients with OH. Sympathomimetic and other vasoactive agents have both a direct and indirect impact on vasoconstriction and can lead to an increase in peripheral resistance [18,44]. Adverse effects include headaches, tremors, muscular weakness, nausea, and vomiting [18]. Fludrocortisone, a mineralocorticoid, acts directly on the renal distal tubule and enhances the reabsorption of sodium and secretion of potassium, and ultimately expands plasma volume [7,18]. Adverse effects include hypokalemia and supine hypertension, contributing to left ventricular hypertrophy [10]. Midodrine, an α1-agonist, which is converted to the active product desglymidodrine to 56 Hong Kong Physiotherapy Journal Volume

7 increase venous vasomotor tone, limits the amount of venous pooling that occurs when the subject is in an upright posture [7,45]. Adverse effects include cutaneous tingling, pruritus, and urinary retention [45]. Ergotamine, a partial agonist for α-adrenergic receptors, increases vasoconstriction by inhibiting uptake by norepinephrine receptors at sympathetic nerve endings [18]. Adverse effects include allergic reaction, muscle pain and weakness, and changes in heart rate. Conclusion Several complex mechanisms counteract the gravitational forces on blood and maintain systemic arterial pressure and cerebral perfusion upon a person s assumption of an upright posture. In SCI individuals with lesions at a level of T6 or above, both the impaired sympathetically mediated vasoconstriction and the absence of pumping activity in the leg muscles cause an inability to regulate arterial BP upon the assumption of an upright posture. They are usually present along with symptoms of orthostatic intolerance of a certain degree of severity. These symptoms potentially limit the active participation of SCI patients in rehabilitation programmes. The main therapeutic strategies for managing OH include both nonpharmacological and pharmacological measures. The initial treatment strategy for OH is usually to adopt a non-pharmacologic approach, failing which pharmacologic management should be considered. The appropriate and successful management of OH can substantially improve the level of mobility and quality of life of people with SCI. References 1. Figoni SF. Cardiovascular and haemodynamic responses to tilting and to standing in tetraplegic patients: a review. Paraplegia 1984;22: Teasell RW, Arnold JM, Krassioukov A, et al. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil 2000;81: Gonzalez F, Chang JY, Banovac K, et al. 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