【教学】血管迷走神经性晕厥

weisskopf

question of the week!

weisskopf

Profound vasodilation has been considered the final common pathway leading to vasovagal syncope, and as such, is the focus of many investigations. While alterations in autonomic tone are generally accepted to be important to the vasodilatory response, it remains unclear whether these changes promote or follow the vasovagal response. Although earlier work noted that vasodilation promoted the onset of syncope, more recent work has suggested that syncope occurs prior to vasodilation (1). Most investigators rectify this information by suggesting that it represents an initial exaggerated sympathetic output followed by parasympathetic activation and then sympathetic withdrawal (2). Further evidence will be necessary to corroborate and reproduce these effects with diagnostic head-up tilt table testing.

weisskopf

Science's former molecule of the year appears to be involved with all things interesting, and its involvement in the role of vasovagal syncope is no exception. While the presence of nitroxidergic nerves in skeletal muscle (3) and increased nitric oxide metabolism in patients experiencing syncope on tilt table testing has been observed (4), the role of nitric oxide is not definitive. Infusion of a nitric oxide blocker, for instance, did not prevent vasodilation during syncope (5). Further investigations will need to the extent of nitric oxide's role in vasovagal syncope.

weisskopf

Many recent investigations have attempted to move away from the idea that decreased venous return and ventricular volume (with the resulting Bezold Jarisch refle are responsible for vasovagal syncope. Shen et al. noted that vasovagal syncope could be induced with an isoproterenol-mediated increase in cardiomotor tone and a decrease in afterload, with no significant decreases in preload. Additional mechanisms and triggers are currently being investigated.

weisskopf

As specific triggers for vasovagal syncope have not been clearly identified and may be variable, treatment is largely empirical and based on putative (but unproven) mechanisms .For infrequent episodes associated with a warning prodrome, counseling and observation have been suggested as a worthy regimen. In the perioperative setting, the patient should be placed (if not already so) in a recumbent position and monitored. As decreased preload is believed at least partially responsible, intravenous fluids, if not contraindicated, should be given. Few recommend the cancellation of a surgical case, unless significant and prolonged hemodynamic aberrations are noted.

For more frequent episodes, although a number of agents have been suggested, including increasing preload (through salt and diet modifications), vasoconstrictors, anticholinergic agents, negative cardiac inotropes, central nervous system agents, and mechanical devices (i.e. pacemakers), the majority of these therapies are supported by observational, unblinded, and/or uncontrolled studies .A recent review found only 3 agents (see below) which have undergone prospective, randomized, placebo-controlled clinical trials .

weisskopf

Although randomized and controlled trials have been performed for alpha-agonists (midodrine, etilefrine), sertotonin reuptake blockers (paroxetine) and an anticholinergic (disopyramide), significantly more symptom free days were noted only with midodrine  and paroxetine . These studies however, were in small samples of patients and thus remain underpowered to make significant conclusions on these therapies

weisskopf

The difficulty in studying this patient population (and analyzing the results of any studies) include differences in the use of:
• diagnosis (especially with an entity of variable expression and incidence)
• patient selection criteria
• size and statistical power
• study end points
• study duration
• pharmacologic targets

weisskopf

The use of permanent pacing for the treatment of vasovagal syncope has been advocated and supported by an anecdotal series .In attempting to more robustly demonstrate the benefits of pacing therapy in this population of patients, the North American Pacemaker Study enrolled patients with at least 6 lifetime episodes of syncope and positive tilt table testing results, to receive a permanent pacemaker randomly assigned to include (or not to include) a “rate-drop” feature. This specific pacer feature provided high-rate pacing if a predetermined precipitous drop in heart rate occurred (rate-drop response). With the main outcome being the time to first recurrence of syncope, the study was terminated at the first formal interim analysis of 54 (of 284 planned) patients, due to the marked reduction in the postrandomization risk of syncope in pacemaker (with rate drop feature) patients (relative risk reduction 85.4%, 95% confidence interval 59.7% to 94.7%; p=0.000022). While interesting, the study has been criticized for the small patient population, lack of a true control group (pacemakers were implanted in all patients to prevent bradycardia in all, but only half with the rate drop feature), and the lack of standardized medical therapy .A second trial is now under way.

weisskopf

The head-up tilt table testing is performed using a specially designed tilting table in which, when the patient is tilted from supine to upright positions, vasovagal syncope is precipitated in predisposed patients. The test has been thought to provoke vasovagal syncope by allowing venous pooling and decreased return to the heart, thus triggering the Bezold-Jarisch mechanism .
Patients with a clinical history of vasovagal syncope have been reported to have a positive tilt testing result in 30-85% of cases .

weisskopf

Interpreting and comparing the results of tilt testing has been made difficult by the myriad of protocols that have been utilized. As the duration of recumbency prior to tilting and angle of the tilt are not standardized, they vary considerably. Most recent reports appear to use a recumbent duration of 30-45 minutes and tilt angles of 60-80 degrees .In addition, questions regarding the specificity, sensitivity, and reproducibility of this method have made it difficult to interpret the data and apply the results clinically.

weisskopf

The addition of pharmacologic agents can often increase the positive yield of tilt table testing. Agents are selected for their specific effects, especially on the autonomic system. Isoproterenol, adenosine, nitroglycerin and edrophonium are common agents employed. The outcomes, however, have not been consistent, and vary according to the baseline symptomology, the tilt testing protocol, and the doses of the agents.

weisskopf

Are there any guidelines for tilt testing? More specifically what patients should not be tested in this manner?[/COLOR]

The American College of Cardiology has published guidelines for head up tilt-table testing .Head up tilt table testing is not warranted in patients who have experienced a single syncopal episode without injury in an intermediate or low risk setting. In addition, this form of testing is contraindicated for patients with critical obstructive cardiac or cerebrovascular diseases. Overall the ultimate usefulness of the head up tilt table has not been definitively demonstrated, however, further work, with standardized protocols will hopefully demonstrate whether this technique should be embraced or abandoned.