Orthostatic hypotension: clinical review and case study

Prevalence

TLOC accounts for 3% of all attendance in emergency departments in the UK (Petkar et al, 2006) and has a lifetime prevalence of 50% (NICE, 2014). Data shows vast international differences in admission rates of patients presenting with TLOC, varying between 12% in Canada (Thiruganasambandamoorthy et al, 2013) and 86% in the USA (Birnbaum et al, 2008). A study in the UK reported a 49% rate of admission with subsequent 1 month cause of death or serious outcome occurring in 7.3% of patients (Reed et al, 2010).

Presentation

More than 90% of TLOC presentations are due to epileptic seizures, psychogenic seizures or syncope (Reuber et al, 2016). In England and Wales it has been estimated that 92 000 patients were incorrectly diagnosed with epilepsy in 2002 (Juarez-Garcia et al, 2006). A misdiagnosis of epilepsy is estimated at an additional annual cost to the NHS of up to £189 million (NICE, 2004). It is therefore vitally important to accurately distinguish TLOC aetiology, not only to provide appropriate management, but to also identify patients at risk of morbidity/mortality related to underlying disease (Petkar et al, 2006; Reuber et al, 2016). The development of evidence-based, clinical guidance (Van Dijk et al, 2008; NICE, 2014; Wardrope et al, 2018) seeks to reduce the incidence of misdiagnosis in TLOC, improve patient outcomes and enhance cost-effective care. However, in a recent systematic review, it was concluded that there remains a lack of validated diagnostic criteria to differentiate between causes of TLOC (Wardrope et al, 2018).

Orthostatic hypotension

Studies reveal that presenting syncope is often unexplained (Olde Nordkamp et al, 2009; Soteriades et al, 2002) with the most likely diagnosis being reflex syncope in patients of younger than 60 years old (Del Rosso et al, 2005). The second most common cause of syncope is OH, occurring in approximately 15% of syncopal presentations (Sutton, 2013). A recent meta-analysis suggested that OH is highly prevalent, affecting nearly one in five older adults (>60 years) living in the community and almost one in four older adults (>60 years) living in long-term care (Saedon et al, 2018). The presence of OH is independently associated with predicting all-cause mortality (Sasaki et al, 2005; Weiss et al, 2006; Ricci et al, 2015a), incidence of cardiovascular disease (Verwoert et al, 2008; Fagard and De Cort, 2010; Ricci et al, 2015a) and increased risk of major adverse cerebro-cardiovascular events (Hossain et al, 2001; Ricci et al, 2015a). Unexpectedly, and relevant in this case, a recent meta-analysis demonstrated a greater association between OH and all-cause death in individuals under 65 years (Ricci et al, 2015a). Similarly, Rose et al (2006) found that relative risk of stroke predicted by OH decreases with advancing age. OH is found to be more prevalent in hypertensive women, irrespective of treatment status (Kamaruzzaman et al, 2010). However, the varied heterogeneity of prevalence studies and variance in diagnostic assessment, provides an unclear picture (Lahrmann et al, 2005; Frith and Parry, 2017).

In relation to this case study, the patient was female and past medical history revealed hypertension, in which she was prescribed amlodipine 5mg once daily. Nursing staff found Ms Grey on the floor and had stated that she had been experiencing light-headedness and dizziness for a few days before this incident but had not collapsed previously.

Causes

OH is a common cardiovascular disorder that can be idiopathic or occur as a result of an underlying neurodegenerative disease, blood loss, dehydration, or antihypertensive medication use, as prescribed in this case study (Lahrmann et al, 2006; Gibbons et al, 2010; Ricci et al, 2015b). It is symptomatic of a structural or functional autonomic nervous system failure, typically occurring when cardiovascular adaptive mechanisms fail to adequately compensate for the reduction in venous return that normally happens on moving to an upright position (Goldstein et al, 2002; Ricci et al, 2015b). Orthostatic stress presents an ongoing challenge for the body, given that people often alter their posture between recumbent and upright positions regularly throughout the day. Kanjwal et al (2015) reported that orthostatic stabilisation is normally achieved within 1 minute of standing. However, when homeostatic mechanisms fail, this results in a transient or persistent state of hypotension, which in turn can lead to syncope, inducing a loss of consciousness (Naschitz and Rosner, 2007; Fedorowski and Melander, 2013; Ricci et al, 2015b).

Regulation of blood pressure

Normal regulation of blood pressure (BP) occurs via a range of physiological actions of the cardiovascular, neural, renal and endocrine systems (Chopra et al, 2011). Immediately upon assuming an upright stance, a gravitational displacement of approximately 500 ml of blood moves away from the thorax to the distensible venous capacitance system below the diaphragm known as venous pooling. Venous return is temporarily reduced, resulting in a decrease in cardiac stroke volume, reduced arterial BP and an immediate decline in blood flow to the brain (Olufsen et al, 2005). When the brain is insufficiently supplied with oxygenated blood, referred to as cerebral hypoperfusion, this manifests as feeling dizzy or lightheaded (Fedorowski and Melander, 2013; Serrador, 2019). This was the prodromal presenting symptom of this case study, experienced over a period of a few days before the incidence of syncope.

The reduction in systemic arterial BP is detected by the distensible baroreceptors located in the carotid and aortic walls, which note changes in the tension of the arterial walls (Gugger, 2011). Consequently, the autonomic nervous system, which is responsible for mediated changes in cardiac output and vascular tone to maintain BP homeostasis (Dampney et al, 2002; Ricci et al, 2015b), responds in two ways: parasympathetic withdrawal and sympathetic activation of the baroreflex-mediated autonomic regulation. Parasympathetic withdrawal is understood to induce a rapid increase in heart rate via its negative chronotropic and inotropic effects (Ripplinger et al, 2016). Whereas the sympathetic nervous system activates a slower increase in vascular resistance, vascular tone and cardiac contractility, increasing heart rate (Gordan et al, 2015). Concurrently, cerebral autoregulation, which is the ability of the brain to maintain cerebral blood flow to keep the brain perfused, maintains cerebral blood flow via a combination of neurogenic processes, myogenic tone and metabolic demand (Serrador, 2019).

Hydrostatic indifference point

The reference point for where pressure is independent of posture, is referred to as the venous hydrostatic indifference point (HIP) (Tortora and Derrickson, 2011). The HIP is considered to denote the circulatory balance between hydrostatic pressure and vasomotor activity. However, it is considered to underestimate the gravitational influence on blood volume distribution (Petersen et al, 2014). The venous system hosts approximately 70% of the total blood volume, with adjustable capacity according to haemodynamic conditions (Aya and Cecconi, 2019; Ricci et al, 2015b). Given that blood arrives in the venous system for transportation via the connective capillary system, venous return is determined to a certain degree by the regulation of capillary circulation. Every tissue within the body has a rapid response regulatory system governed by metabolic need to provide adequate localised blood flow (Aya and Cecconi, 2019). Haemodynamic stability is therefore directly influenced by the complexities of systemic circulation (Martini et al, 2015).

The anatomy and physiology can provide important insights into previously noted pathophysiological links between OH and negative outcomes (Hossain et al, 2001; Sasaki et al, 2005; Weiss et al, 2006; Verwoert et al, 2008; Fagard and De Cort, 2010; Ricci et al, 2015a). For example, the presence of higher diurnal variability and supine nocturnal hypertension in OH, may increase the risk of myocardial ischaemia and congestive heart failure as a result of intermittent episodes of increased afterload (Ricci et al, 2015b). Additionally, cerebrovascular or cardiovascular events can occur as a sequential product of orthostatic, neuroendocrine compensatory mechanisms, which try to maintain cardiac output but can over-activate, causing other biological effectors such as platelet formation and the coagulation cascade (Ricci et al, 2015b).

Importance of clinical history

Ascertaining an accurate clinical history (Table 1) and a sequential description of presenting symptoms has high diagnostic value in OH (Lahrmann et al, 2006; Freeman et al, 2011). This presenting case of potential TLOC was complicated by the fact that the event had resolved itself at the time of assessment (Japp and Robertson, 2018). This, alongside the absence of a witness to corroborate information related to the experience of TLOC, presented a diagnostic challenge (NICE, 2014). Staff found the patient sitting on the floor, fully conscious as denoted using the updated Glasgow Coma Scale (Teasdale et al, 2014). Ms Grey reported having felt dizzy when getting up from her bed and walking a short distance to then finding herself slumped on the floor, believing to have fainted. On the basis of this information and evidential loss of muscle control, guidelines indicate that TLOC must be assumed (Whinnery and Forster, 2017; Japp and Robertson, 2018).

Van Dijk et al (2008) stated that gathering an accurate clinical history can differentiate syncope from other forms of TLOC, including cardiac causes (Berecki-Gisolf et al, 2013). Nurses play an important role if they witness syncope in a patient, as information may be relayed to doctors to assist in the correct diagnosis and treatment of the syncope. Reuber et al (2016) explored the diagnostic potential of a self-reporting questionnaire to differentiate between TLOC cause. They concluded that clusters of self-reported symptoms can be effective in directing appropriate pathways of investigation and treatment. In the case of Ms Grey, the 86-item Paroxysmal Event Profile questionnaire was conducted (Reuber et al, 2016). On review, her feeling of being ‘lightheaded’ in the prodromal phase, no recall of falling during the event and mild, temporary confusion post-episode was concluded to be more consistent with a syncopal explanation of TLOC as opposed to epilepsy or psychogenic seizure. Given that potential adverse events are determined by the acute underlying disease as rather than the syncope itself, accurate diagnosis is crucial (Numeroso et al, 2016).

Risk stratification tools

Reed et al (2010) proposed a risk stratification protocol for presenting syncope, denoted as the ‘ROSE’ rule (Risk stratification Of Syncope in the Emergency department) aided by the mnemonic BRACES. They claim that use of this simple clinical decision aid is practical and will potentially reduce the number of unnecessary admissions (Box 1). Part application of this tool identified no clinical markers indicative of a transfer to the emergency department for admission. However, Brignole et al (2018) cautioned against using syncope risk stratification strategies independent of clinical judgement because there is no significant evidence of superiority in terms of predicting outcomes. The defining characteristics of syncope are low BP and cerebral hypoperfusion as a result of low peripheral resistance and/or reduced cardiac output (Brignole et al, 2018). In this case, the patient experienced no associated chest pain or new onset dyspnoea, and had no family or personal history of cardiac disease, aside from hypertension (Reed et al, 2010; NICE, 2014). This, alongside the absence of abnormalities on ECG and blood tests, allowed safe dismissal of arrhythmia and cardiac syncope (Del Rosso et al, 2005; Reed et al, 2010; Berecki-Gisolf et al, 2013; Brignole et al, 2018). Despite reflex syncope being the most common cause of TLOC in patients under 60 years of age (Del Rosso et al, 2005), this differential diagnosis was ruled out on the basis of incomparable prodromal and clinical features (Wieling et al, 2015; Brignole et al, 2018).

The ROSE rule with BRACES mnemonic

Admit if any of the following are present:

On further examination, a diagnosis of OH was confirmed in the case of Ms Grey by a drop in systolic BP of >20mmHg and diastolic BP of >10mm Hg within 3 minutes of standing (Freeman, et al, 2011). As previously discussed, OH is a common cardiovascular disorder that has been shown to have a greater association with all-cause death in patients over 65 years of age (Ricci et al, 2015b). Identification of the underlying cause in this case was therefore vital. On examination, there was no evidence of injury or blood loss and the inpatient nutritional chart indicated Ms Grey was sufficiently hydrated, therefore causative hypovolaemia was not considered to be a factor (Lahrmann et al, 2006; Gibbons et al, 2010).

Importance of medication history and review

A key consideration in this patient's medication history was secondary prescribing. Her GP managed her hypertensive medication and she saw a private psychiatrist for psychotropic medication management. She was admitted to an NHS acute psychiatric ward presenting with a risk to self in the form of suicidal ideation. On admission, contact was made with the private psychiatrist who shared clinical reasoning for the commencement of a monoamine oxidase inhibitor (MAOI) antidepressant and his plan for titration of phenelzine, the selected MAOI in this case. Given Ms Grey's presenting history of chronic depression, the plan in isolation made sense; however, it is not clear if the risk/benefit balance was considered in combination with prescribed antihypertensive and anti-psychotic medication (Duerden et al, 2013). Monitoring of BP is a requirement for patients prescribed phenelzine (Joint Formulary Committee, 2018); unfortunately, the patient's records did not reflect regular monitoring. Staff acknowledged that they were unfamiliar with the prescribing and monitoring of MAOIs. However, the monitoring of the physical health of mental health patients is a core component of delivering safe and effective healthcare (NHS England, 2018). Furthermore, given that the patient was owed a duty of care, it could be argued that potentially foreseeable harm was caused by omission of due consideration of the prescribing plan and inadequate monitoring, as discussed in the cases of Donoghue v Stevenson, 1932 and Caparo v Dickman, 1990. In this case, professional duty of candour (General Medical Council and Nursing and Midwifery Council, 2015) was applied.

In iatrogenic autonomic failure, reflex responses are compromised by drugs that reduce systemic vascular resistance (Hopson et al, 1993), causing syncope secondary to OH (Brignole et al, 2018). Meyer (2018) argued that the titration of MAOIs is balanced on tolerability probabilities, with orthostasis the primary dose limiting adverse effect. It is understood that rapid titration of a MAOI is not advised in older individuals or those prescribed an a1-adrenergic antagonist such as quetiapine, which is associated with a high incidence of OH (McEvoy et al, 2006). Anecdotal evidence would suggest that the presenting mental health condition with associated risk of suicide was the primary focus for staff, which may have influenced a faster titration regimen than was considered safe, when taking into consideration the risk of adverse effects. The medication history of this patient (Table 1) was of great importance in relation to the cumulative effects of prescribed medication on vascular resistance, in this case of presenting OH (Gugger, 2011). The key clinical feature indicative of syncope due to OH as evidenced in this case study was the temporal relationship, with onset of syncopal symptoms and a recent increase in prescribed vasodepressive medication (Brignole et al, 2018), namely phenelzine. Knowledge and understanding of medication interactions can present a challenge. The gravity of such interactions was highlighted by Freeman et al (2011) who reported that more than 250 medications cause OH.

Remarkably, the advisory goal of OH treatment is focused on improving functional capacity and quality of life, and preventing injury as opposed to achieving a target BP (Lahrmann et al, 2006). As previously discussed, the guidelines for the management of TLOC that is syncopal in nature is underpinned by risk assessment (Brignole et al, 2018). Given the numerous variables in aetiology, presenting symptoms and associated comorbidities, successful treatment of OH is, unsurprisingly, a challenge (Ejaz et al, 2004).

On confirmation of OH, Ms Grey and her husband were provided with information and advice on factors that influence BP (Lahrmann et al, 2006). It is important for nurses to know what advice to give to patients, carers and loved ones as patient and carer education is considered central to treatment efficacy, with a focus on promoting understanding of basic physiology, identifying aggravating factors and learning how to reduce incidence of decreased BP (Benditt and Nguyen, 2009; Wieling et al, 2015). Advice given included taking a staged, slow change in position from supine to standing and repeated contraction of lower leg muscles before and while standing (Brignole et al, 2018). The patient was subsequently able to recognise early warning signs in relation to haemodynamic changes, which provided an opportunity for her to implement physical countermeasures in a timely manner, reducing the risk of syncope and injury (Ricci et al, 2015a).

Deprescribing

Although non-pharmacological treatment intervention was indicated in this case in the form of patient education, given the concern related to the medication plan, deprescribing was considered at length. International guidance and expert consensus recommend the withdrawal of medication in OH, with specific focus on six classes of medication, including vasodilators, antihypertensives and antidepressants, particularly tricyclics including MAOIs (Lahrmann et al, 2006; Freeman et al, 2011). However, Frith and Parry (2017) reported evidential inconsistencies in withdrawing causative medication, further acknowledging that complex variables in methodological, clinical and statistical heterogeneity create problems in drawing comparative conclusions. In this case, prescribed medication for previous hypertension was withdrawn and Ms Grey noted a reduction in dizziness after 1 week. She experienced no further episodes of syncope and her blood pressure returned to within a normal range. She went on to make a reasonable recovery in mental health and is having regular BP monitoring from her GP.

Conclusion

This case study provides a critical review of the assessment, diagnosis and treatment of a female inpatient presenting with syncope. Given the numerous variables in aetiology, presenting symptoms and associated comorbidities, successful treatment of OH is a challenge. Nurses have a valuable role in being able to describe the type of syncope to doctors, if witnessed, as this can assist with the diagnosis and treatment. In the case of Ms Grey, a diagnosis of OH was confirmed, with prescribed medication considered to be the most likely aetiological factor, highlighting that nurses are often best placed to act as the patient's advocate and flag polypharmacy as a potential cause of OH. Medicines optimisation provided successful treatment, and no further incidence of syncope occurred. The patient suffered no lasting effects from the adverse event. Ms Grey and her husband were given informed advice on how to reduce the incidence of postural hypotension, emphasising the importance of nurses understanding the pathophysiology, the causes and aggravating factors of OH.

KEY POINTS

CPD reflective questions