Clinical manifestations

Presentation and course

Micturition syncope is a fairly common disorder that occurs typically in men over a wide age span but can occur uncommonly in older women and rarely in children, particularly boys (39; 57; 03; 01; 48; 85). Micturition syncope represents perhaps 2% to 8% of cases of syncope, with more common causes being orthostatic hypotension and vasovagal syncope (47; 71; 32; 49).

Attacks in males may begin in the teenage years, and cases have rarely been reported as young as age 7 and 9 (48; 85). Particularly among older patients (over 55 years of age), micturition syncope typically occurs only when patients void immediately after arising from the supine position after prolonged recumbency (64; 81; 39). Thus, micturition syncope is most common in the evening or early morning (45; 71; 39; 79), especially in older patients (over 55 years of age). The circadian pattern of micturition syncope varies by age: in younger patients (less than 55 years of age), it tends to occur in the evening or nighttime before midnight, whereas in older patients, it tends to occur after midnight or early in the morning (81). Micturition syncope most often occurs at the termination of or just after urination (45; 71). A form of micturition syncope can also occur with intermittent catheterization, eg, in tetraplegic subjects (63; 82).

Although rare, paragangliomas of the urinary bladder warrant special mention, as they need to be considered when evaluating hypertensive patients with headache, palpitations, or syncope related to micturition (82; 31; 84; 88) (see Clinical vignette case 2). These are tumors of chromaffin tissue originating from the sympathetic innervations of the urinary bladder, and as such they may secrete catecholamines and give rise to a clinical presentation like that of a hyperfunctioning adrenal pheochromocytoma. They are typically recognized by their characteristic presentation of hypertensive crisis and postmicturition syncope (67; 66; 82; 31; 84; 88). Patients may present with episodes of headache, palpitations, hot flushes, sweating, and poorly controlled hypertension; such manifestations of hypertensive crises are at times associated with micturition or micturition syncope (occurring, though, typically at the end or shortly after micturition, accompanied by postmicturition hypotension) (66; 82). An additional symptom may be painless hematuria, which may be the presenting complaint (66).

Defecation syncope is a relatively rare disorder that occurs typically in middle-aged or older individuals and affects women somewhat more often than men (59; 37; 39; 57; 03). In general, the age distribution is older for patients with defecation syncope than those with micturition syncope (39; 03). About half of the patients with defecation syncope experience multiple episodes (37). Most patients are recumbent (either asleep or at bed rest) before getting up to have a bowel movement. Gastrointestinal symptoms before syncope can include a strong urge to defecate, abdominal cramps and bloating, nausea and vomiting, diarrhea, and constipation (37; 81). Unlike micturition syncope, there is no strong diurnal variation with defecation syncope (39).

With micturition and defecation syncopes, there may be associated brief jerking or rhythmic movements (ie, convulsive syncope), but there is no associated incontinence, tongue biting, or postictal state. Recovery usually occurs within seconds without vasomotor or other sequelae. Patients are amnestic for the period of lost consciousness. The clinical manifestations of syncope per se are described in the general chapter on Syncope.

Prognosis and complications

The long-term prognosis of syncope depends largely on the prognosis of the underlying condition, but syncope itself can result in severe bodily injury. In general, patients with micturition or defecation syndrome, like other situational syncopes, are typically older, more often male, have a higher prevalence of hypertension, seldom have prodromes, and experience more injuries at the time of syncope (89).

Younger men with micturition syncope typically have a benign self-limited condition, caused by a transient disturbance of normal physiologic functions (eg, from overindulgence in food and alcohol with inadequate sleep), but do not typically have significant underlying morbidity (64; 56; 78; 72; 22). In contrast, older male patients and female patients of any age with micturition syncope typically have significant medical comorbidities and a majority have orthostatic hypotension (36). Many patients have recurrent episodes (71).

Defecation syncope is not a “benign” isolated physiologic event (37), although it is sometimes dismissed as a benign neurally mediated syncope (21). Half of the patients with defecation syncope have recurrent syncope within 2 years, but most recurrences are not associated with defecation (37). Bilateral subcortical border-zone infarction has been reported following episodes of prolonged defecation syncope (80). More than one third of patients with defecation syncope die within 2 years of complications of their underlying diseases (37).

Clinical vignette

Case 1. Catheterization-associated micturition syncope in a tetraplegic patient (63). A 47-year-old man with C7 tetraplegia developed occasional syncope several minutes after intermittent catheterizations in the sitting position associated with hypotension and bradycardia. Catheterization-associated syncope resolved on withdrawal of fluoxetine, which had been used for situational depression. However, some degree of catheterization-associated hypotension without syncope persisted. Subsequently, catheterization-associated hypotension resolved with management of bladder hyperreflexia with botulinum-A toxin injections into the detrusor. Important clinical lessons emphasized by this case include the following: (1) overdistention of the bladder should be avoided; (2) bladder volume should be gradually decreased, particularly if the bladder is overdistended; (3) bladder hyperreflexia should be carefully controlled in patients with cervical or thoracic myelopathy; and (4) medications with hypotensive side effects may contribute additively or synergistically with episodic hypotensive factors (eg, micturition) to collectively cause syncope.

Case 2. Micturition syncope and hypertensive crises due to a bladder paraganglioma (88). A 43-year-old man was admitted with a several-week history of frequent micturition syncope concomitant with hypertensive crises. Physical examination was normal.

Urine red blood cells were marginally elevated at 5.5/HPF (normal range ≤3/ HPF). Serum biomarkers included the following: normetanephrine 18,064 pmol/L (normal range ≤710 pmol/L), metanephrine 195 pmol/L (normal range ≤421 pmol/L), norepinephrine 8,591 pmol/L (normal range 414–4,434 pmol/L), epinephrine 152 pmol/L (normal range ≤606 pmol/L). Urine biomarkers included the following: normetanephrine in 24-hour urine 5,630 nmol/24 hours (normal range < 312 nmol/24 hours) and metanephrine in 24-hour urine 79 nmol/24 hours (normal range < 216 nmol/24 hours).

A computed tomography urography scan identified a bladder tumor (4.8 cm × 3.7 cm) in the right anterior wall of the bladder with heterogeneous enhancement in the arterial phase and decreased enhancement of venous phase and excretory phase. MRI also identified a bladder tumor with high signal intensity on T2-weighted imaging (4.9 cm × 3.8 cm) in the right anterior wall of the bladder.

Cystoscopy revealed a cauliflower-shaped mass with the right anterior wall of the bladder bulging inward and a tip in the right wall, approximately 0.8 cm in diameter.

The preoperative diagnosis was suspected bladder paraganglioma concomitant with bladder tumor.

The patient received preoperative phenoxybenzamine with aggressive volume repletion. He then underwent laparoscopic partial cystectomy combined with transurethral resection of the bladder tumor.

Postoperative pathology confirmed a bladder paraganglioma (T2N0M0, Stage II) concomitant with urothelial papilloma, a rare benign neoplasm composed of a delicate fibrovascular core covered by normal urothelium.

Immunohistochemistry of the bladder paraganglioma was positive for Ki-67 (15%), chromogranin A (CgA), succinate dehydrogenase B (SDHB), somatostatin receptor 2 (SSTR2), and synapsin (Syn) and negative for S-100 (a tumor marker that can be found in paraganglioma stromal cells).

Immunohistochemistry of the urothelial papilloma was positive for CK20 (umbrella cells) and Ki-67 (1%).

The final diagnosis was intermediate-risk functional bladder paraganglioma concomitant with urothelial papilloma. After recovery, he had normal urination without syncope.

Eight months after his surgery, he was examined because of a skull mass. 18F-FDG positron emission tomography (PET)/CT identified widespread metastases with multiple high-uptake lesions in the liver (2.8 cm × 2.4 cm), bilateral pulmonary nodules (maximum diameter 5 mm), and high-uptake masses and osteolytic bone destruction in the right parietal skull bone, vertebral body, and ilium.

Because of positive expression of SSTR2 with the original pathology, the patient underwent 18F-DOTATATE PET/CT targeted imaging. This showed multiple high-uptake nodules in the liver and lungs, and high-uptake masses with osteolytic bone destruction of the right parietal skull and iliac bones.

The patient received six courses of CVD chemotherapy [cyclophosphamide (1.4 g day 1), vincristine (2 mg day 1), and dacarbazine (0.4 g days 1 through 5)] every 16 to 26 days, plus octreotide LAR (30 mg intramuscularly every 4 weeks).

After finishing the sixth course of CVD chemotherapy, he continued octreotide therapy (30 mg intramuscularly every 3 months) to control his hormonally functional paraganglioma.

CT scans showed no significant progression in the size of the lung, liver, skull, and ilium metastases. Nevertheless, the levels of vanillylmandelic acid in 24-hour urine samples slowly declined, from 24.80 mg/24 hours (normal range ≤12.00 mg/24 hours), ultimately achieving a level of 17.10 mg/24 hours after 6 months.

Biological basis

Pathophysiology

Several pathophysiologic processes may cause or contribute to micturition- or defecation-related syncopes:

Several factors have been proposed to increase the likelihood that micturition will produce syncope:

Similarly, several factors have been suggested to increase the likelihood that defecation will produce syncope:

Several pathophysiologic processes may cause or contribute to micturition- or defecation-related syncopes:

Valsalva-induced decreased cardiac output. Micturition and defecation result from coordination of both voluntary and reflex activity. The Valsalva maneuver occurs during voluntary straining with the glottis closed, and can be repetitive and intense, causing large swings in arterial blood pressure and heart rate (50; 64; 65; 77). Valsalva during micturition is likely most common in patients with bladder outlet obstruction (17; 44; 32). Valsalva during defecation typically achieves intrathoracic pressures above 40 mm Hg (76; 77). The Valsalva maneuver causes increased intrathoracic pressures, which in turn cause decreased venous return to the atria with resultant decreased stroke volume, decreased blood pressure, and decreased cerebral blood flow. However, in contrast to the situation with cough syncope, it seems unlikely that a person could strain sufficiently during micturition or defecation to produce syncope by Valsalva alone (26). Other factors, such as an exaggerated lordotic posture during voiding, may also interfere with venous return and contribute to micturition syncope (26; 22).

Cardiac arrhythmias. Micturition and defecation can precipitate vagally mediated cardiac arrhythmias, including bradycardia, sinus arrest, and atrioventricular conduction block (50; 72; 37; 77). Similarly digital rectal examination, enemas, and colonoscopy can induce cardiac arrhythmias and syncope (20; 05; 60; 13; 37; 63). Vagal stimulation can also induce ventricular asystole in some patients, particularly if vagal tone has been accentuated by cholinergic agents (eg, acetylcholinesterase inhibitors), hypoxia, hypercapnia, or tracheal suctioning in the setting of respiratory infection (73; 42). In addition, patients with acute coronary syndrome are particularly vulnerable to syncope related to excessive straining during defecation (77); this may partly relate to decreased coronary artery blood flow and arrhythmias during Valsalva (77).

Orthostatic hypotension. Blood pressure falls during sleep without associated changes in heart rate, suggesting altered baroreceptor mechanisms during sleep and on rising (68; 26). Standing to void aggravates this impairment in postural blood pressure control. Preexisting medication-related or other orthostatic hypotension is a significant risk factor for both micturition and defecation syncopes (45; 44; 22; 91; 37; 71; 10; 25; 75).

Loss of pressor effect of distended bladder. Bladder distention is associated with increased muscle nerve sympathetic activity and elevated blood pressure (24; 19; 70). Blocking the afferent innervation of the bladder with instillation of procaine before bladder distention prevents the changes in sympathetic activity and blood pressure associated with bladder filling (19). Sudden decompression of a chronically distended bladder can produce hypotension (53; 74; 46; 26; 63). Loss of the pressor effect of a distended bladder may be more severe in the presence of a urinary tract infection (16) or pregnancy (75) or in tetraplegic patients with autonomic hyperreflexia (63).

Pulmonary embolism. This is one of the most commonly identified causes in patients with defecation-related syncope (38; 58). The act of defecation may facilitate embolization of a venous clot. Syncope has been identified as a common presentation of pulmonary embolism, but it is unclear how often this is precipitated by defecation (02; 62).

Functional inferior vena cava obstruction. Functional inferior vena cava obstruction at the diaphragmatic hiatus during Valsalva has been reported to cause defecation-related syncope, as a result of decreased venous return and secondary decreased cardiac output (09). The functional obstruction and the defecation-related syncope can be relieved with mobilization of the inferior vena cava and crural myotomy (09).

Functional obliteration of the right atrium. Excessive paradoxical elevation of the left hemidiaphragm during Valsalva, following surgical trauma to the left phrenic nerve, has been reported to cause defecation-related syncope, as a result of obliteration of the right atrial cavity and a secondary precipitous drop in cardiac output (87). Although the authors considered this a case of cardiac syncope mimicking defecation syncope, it meets the definition of defecation syncope and should instead be considered a rare cardiac mechanism for defecation syncope.

Cardioinhibitory situational vasovagal syncope. Vasovagal syncope has been postulated as a cause of syncope in some patients with micturition syncope, particularly when micturition syncope occurs in the absence of bladder outlet obstruction or significant straining (12; 44; 15; 35). Several cases of defecation syncope have been reported in which vasovagal syncope was the presumed mechanism of defecation syncope, including a patient diagnosed with splanchnic sympathetic dysfunction (52) and a patient found to have a Morgagni hernia (ie, an uncommon type of diaphragmatic hernia) (90).

Decreased cerebral blood flow. Valsalva during defecation or micturition may further impair cerebral circulation in patients with already compromised cerebral blood flow because of extracranial or intracranial arterial stenosis or occlusion (37). Several factors may act synergistically in such cases, including decreased cardiac output as a result of Valsalva-induced decreased venous return, increased cerebrospinal fluid pressure transmitted from increased intra-abdominal and intrathoracic pressures (27; 28), and secondary hypocapnia causing cerebral arterial vasoconstriction. However, empiric support for this mechanism is weak in patients with micturition or defecation syncopes.

Seizure. Rarely, micturition or defecation, and their associated changes in cerebral blood flow or other pathophysiologic processes, may actually trigger a reflex seizure with resultant loss of consciousness followed by a postictal state (95; 29).

Generalized autonomic dysfunction. Patients with multisystem atrophy may be prone to micturition syncope (86). Such patients have lower baseline blood pressure, small blood pressure and heart rate increases during bladder filling, and an abnormally increased fall in blood pressure for a longer duration after voiding. They may also have increased abdominal straining because of difficulty in voiding, which acts to decrease venous return to the heart.

Alcohol intake. Alcohol intake is an important precipitating factor for micturition syncope in younger patients (less than 55 years of age) (81; 03) but is rarely a factor associated with defecation syncope (39; 03) or with common vasovagal syncope (03).

Catecholamine release. Functional paragangliomas of the urinary bladder are rare tumors that can release catecholamines and precipitate syncope during micturition (14; 04; 92; 31; 84; 88). The term paraganglioma includes all the tumors deriving from the body's paraganglion system, which are categorized as intra-adrenal (pheochromocytoma) and extra-adrenal or paraganglion (54). About 10% of all extra-adrenal paragangliomas involve the bladder and can be functional and nonfunctional (54). Early preoperative diagnosis of functional paragangliomas of the urinary bladder is difficult, but these tumors should be suspected in patients with the typical symptom profile, which can include micturition-induced syncope, often associated with headache, diaphoresis, palpitations, and hematuria (92; 84; 88). A similar situation of catecholamine release and syncope can occur in tetraplegic patients with autonomic dysreflexia during intermittent catheterization (63).

Epidemiology

In a retrospective study of 3140 patients who underwent head-up tilt testing, 354 (11%) were diagnosed with situational syncope (96). Micturition syncope (50.85%) represented only about 51% of situational syncope, whereas defecation syncope represented only about 16% of situational syncope. Patients with syncope triggered by micturition were more likely to be men.

Differential diagnosis

Confusing conditions

Micturition and defecation syncopes may be confused with epilepsy, particularly as the syncopal attacks may be associated with secondary arrhythmic convulsive jerks of the extremities (ie, convulsive syncope) (30; 18). However, there is no associated aura, postictal confusion, tongue biting, or incontinence. Furthermore, the syncope improves or resolves without recourse to anticonvulsants. Rare patients with micturition- or cough-associated syncope may have interictal epileptiform activity on electroencephalograms, postictal symptoms, and apparent control of syncope with anticonvulsants, and in such rare cases, micturition- or defecation-triggered changes in cerebral blood flow or other factors may actually trigger a seizure (29).

Diagnostic workup

The diagnostic work-up varies by the clinical circumstances and the clinically suspected etiologies of micturition or defecation syncopes. Lung function, cardiac function, orthostatic pulse and blood pressure, and blood volume should be assessed clinically. An electrocardiogram should be obtained.

If the history and examination do not suggest an underlying significant comorbidity in a man with micturition syncope, particularly a man younger than 50 years of age, further diagnostic studies are usually unrevealing (45; 22; 36).

In an emergency setting, a boy with a classical micturition syncope presentation (ie, first void after waking, while standing, with spontaneous recovery within a few minutes) with both normal clinical examination and electrocardiogram results and without any “red flags” can reasonably be discharged without any further examinations (48). Proposed “red flags” for micturition syncope in childhood include (1) event history of exertional syncope or syncope precipitated by noise or emotion; (2) medical history of congenital heart disease, cardiac surgery, or Kawasaki disease; (3) known familial ventricular arrhythmias, sudden cardiac death, or unexplained death in a first- or second-degree relative before 50 years of age, or cardiomyopathy or heart failure in a first- or second-degree relative; and (4) cardiovascular examination findings of tachycardia or tachypnea, irregular cardiac rhythm, a pathological murmur (including a dynamic murmur), gallop, or click, or a loud or single second heart sound (S2) (48).

Additional studies should be considered selectively. Electroencephalography and echocardiography are usually normal in patients with micturition or defecation syncope. In selected cases, Holter monitoring can be helpful in identifying associated cardiac arrhythmias. In some patients with suspected vagally mediated arrhythmias, vagal maneuvers can be considered to determine if increased vagal tone can precipitate related clinical outcomes (eg, sinus arrest, atrioventricular block, hypotension, or syncope); such maneuvers can include carotid sinus massage and eyeball compression, but the vast majority of reported cases of micturition or defecation syncope did not have abnormal findings on such maneuvers. More sophisticated cardiac electrophysiologic studies are rarely needed. Tilt table testing may have some utility, possibly utilizing a series of Valsalva maneuvers, although available data are insufficient to recommend this as a routine study (61). The frequency of abnormal tilt table studies was more common in older patients (over 55 years of age) than in younger patients with micturition syncope (81), but it does not differ between patients with micturition and defecation syncope (39). To assess for possible bladder paraganglioma, plasma, and 24-hour urinary catecholamine levels should be obtained in patients with micturition syncope in association with hypertensive crises.

In an anecdotal report, a patient with defecation syncope associated with splanchnic sympathetic dysfunction had resolution of this problem after permanent pacemaker insertion (52).

Some cases of micturition or defecation syncope may require consultation by a gastroenterologist, cardiologist, general surgeon, or urologist, depending on the clinically suspected underlying etiologies identified.

Newer technology to noninvasively and simultaneously monitor cerebral hemodynamics, blood pressure, and other important parameters at high temporal resolution (250 Hz sampling rate) have been shown to be useful in preliminary studies (93).

Management

Management of micturition and defecation syncope focuses on treatment of the underlying conditions.

Men with recurrent micturition syncope should be encouraged to sit while urinating (10). This not only lessens the likelihood of injury in the event of syncope but also helps to maintain blood pressure while voiding (10). Patients with micturition syncope, particularly older patients, may require management of orthostatic hypotension, cardiac arrhythmias, urologic disorders (including bladder outlet obstruction and urinary tract infections), and other comorbid and contributing conditions (55). Avoidance of excess alcohol should be strongly encouraged.

Patients with defecation syncope may require management of orthostatic hypotension, cardiac arrhythmias, intestinal disorders, deep venous thromboses and pulmonary emboli, and other comorbid and contributing conditions (37; 38). As in patients with micturition syncope, avoidance of excess alcohol should be strongly encouraged. A patient diagnosed with defecation syncope and splanchnic sympathetic dysfunction, with persistent bradycardia during symptom reproduction with colonoscopy, had resolution of symptoms with pacemaker implantation (52). Defecation syncope resulting from functional inferior vena cava obstruction can be relieved with mobilization of the inferior vena cava and crural myotomy (09). Defecation syncope related to structural gastrointestinal lesions (eg, Morgagni hernia, Meckel diverticulum, ruptured appendix, etc.) may require surgery (37; 90). Defecation syncope related to autonomic dysfunction in patients with end-stage liver disease may benefit from orthotopic liver transplantation (58).

No randomized controlled trials of pacing have been conducted in patients with micturition syncope, defecation syncope, or other situational syncopes, but results of randomized trials for vasovagal syncope are at best inconsistent, and there has been an increasing shift away from using pacing for such clinical situations (23; 11; 41). Permanent cardiac pacing should generally be reserved for patients with little or no prodrome and significant bradycardia or asystole at the time of syncope who have failed other interventions (51; 23). Other indications can include frequent cardioinhibitory syncope (more than five attacks per year), severe physical injury or accident, and age greater than 40 years (08; 07).

Surgery and adjuvant therapies are effective treatments for paraganglioma of the urinary bladder (an extra-adrenal catecholamine-producing tumor). These tumors can generally be completely resected via transurethral resection of bladder tumor, en bloc transurethral resection with thulium-YAG laser, or partial cystectomy (66; 92; 33; 82; 31; 84; 88). Compared with open surgery, laparoscopic partial cystectomy, and robot-assisted laparoscopic partial cystectomy are advantageous in the treatment of paraganglioma of the urinary bladder (92; 82; 31; 84; 88). Because bladder paragangliomas are likely to recur and metastasize, lifelong clinical follow-up, annual measurement of plasma and urinary catecholamine levels, and cystoscopy are essential (66).