n_dysautonomia

Autonomic dysfunction and autonomic neuropathy

Autonomic dysequilibrium:

  • The development of profound autonomic dysfunction and of neuroendocrine activation characterizes and possibly contributes to the progression of heart disease to congestive heart failure. Sympathetic activation is a generalized process and the proposed mechanisms for neurohumoral activation include decreased input from excitatory afferences and increased input from excitatory chemoceptors and metabaroceptor. These phenomena vary to a great extent in different subjects: in the more impaired patients, renal and cardiac overflow of catecholamines can increase three- and ten-fold, respectively, accounting for about 60% of the increase of noradrenaline in congestive heart failure. Efficient methods to quantify sympathetic cardiovascular influences and neuroendocrine indices have been developed and it has been recognized that sympathoneural activation independently predicts the survival of patients. The pathophysiological role and the clinical relevance of neuroadrenergic abnormalities also constitute the grounds for the understanding of the therapeutic benefit obtained with interventions aimed at mitigating the harmful consequences of adrenergic hyperactivity
  • Chronic imbalance of the autonomic nervous system is a prevalent and potent risk factor for adverse cardiovascular events, including mortality. Although not widely recognized by clinicians, this risk factor is easily assessed by measures such as resting and peak exercise heart rate, heart rate recovery after exercise, and heart rate variability. Any factor that leads to inappropriate activation of the sympathetic nervous system can be expected to have an adverse effect on these measures and thus on patient outcomes, while any factor that augments vagal tone tends to improve outcomes. Insulin resistance, sympathomimetic medications, and negative psychosocial factors all have the potential to affect autonomic function adversely and thus cardiovascular prognosis. Congestive heart failure and hypertension also provide important lessons about the adverse effects of sympathetic predominance, as well as illustrate the benefits of [beta]-blockers and angiotensin-converting enzyme inhibitors, 2 classes of drugs that reduce adrenergic tone. Other interventions, such as exercise, improve cardiovascular outcomes partially by increasing vagal activity and attenuating sympathetic hyperactivity.

Autonomic overactivity:

aetiology:

drugs:

Autonomic insufficiency:

aetiology:

primary autonomic insufficiency:
  • acute or subacute dysautonomia in healthy adults/children:
    • effects both parasympathetic & sympathetic systems
    • loss of: pupillary reflexes, lacrimation ,salivation, sweating;
    • impotence, paresis of bladder & bowel musculature
    • variant of acute idiopathic polyneuritis - lasts months Rx ? prednisolone
  • chronic post-ganglionic autonomic insufficiency in middle aged/elderly:
    • relatively benign & seemingly irreversible; men > women;
    • anhydrosis, impotence, sphincter disturbances, gastric paresis
    • resting levels of NA are subnormal due to failure of NA release
    • hypersensitivity to injected NA
    • Rx salt loading, stockings, fludrocortisone, mitodrine
  • chronic pre-ganglionic autonomic insufficiency:
    • lead to disability & often death within a few years
    • associated with 1 of 3 neurologic disorders:
      • Shy-Drager syndrome - tremor, extrapyramidal rigidity, akinesia
      • progressive cerebellar degeneration (may be familial)
      • a more variable extrapyramidal & cerebellar disorder (strio-nigral degeneration)
  • congenital hereditary autonomic disorders:
    • Riley-Day syndrome (familial dysautonomia):
      • autosomal recessive disorder in families of European Ashkenazi Jewish descent appearing in childhood
      • dry eyes, skin blotching, poor motor coordination, poor reflexes, insensitivity to pain, emotional problems
      • infants have feeding problems, aspiration pneumonia, episodic vomiting & sweating spells, breath-holding spells that cause syncope, seizures (50%); postural hypotension; hypertensive crises; impaired temp. regulation; hypotonia;
      • urinary VMA elevated but HVA decreased
    • many others
  • “dysautonomia syndromes”:
    • syndromes included in this category:
      • chronic fatigue syndrome
      • irritable bowel syndrome
      • inappropriate sinus tachycardia (ITS)
      • postural orthostatic tachycardia syndrome (POTS)
      • mitral valve prolapse syndrome (MVPS)
secondary autonomic insufficiency (common):
  • prolonged bed rest ie, cardiovascular deconditioning
  • systemic neuropathies:
    • diabetic, amyloidosis, beriberi, Adie syndrome, porphyria
    • infections: Chagas', HIV, leprosy, rabies
    • chronic uraemia or hepatic disease (usually subclinical dysautonomia)
  • immune disorders:
    • Guillain-Barre syndrome
    • paraneoplastic - esp. small cell lung Ca
    • Sjogren's syndrome
  • system degenerations:
    • idiopathic orthostatic hypotension
    • Parkinsonism DOPA responsive
    • mitochondrial (Myopathy and external ophthalmoplegia; Neuropathy; Gastro-Intestinal; Encephalopathy)
  • drugs & toxins:
    • polyneuropathy:
      • alcohol, amiodarone, cis-Platinum, Cyclosporine A, Perhexiline, Taxol, Vacor, Vincristine, arsenic, mercury, thallium, acrylamide, hexacrbons, B12 defic, 
    • pharmacologic:
      • L-dopa, ganglion blockers, alpha-blockers, bromocryptine, etc.

Orthostatic intolerance:

  • on standing, about 300 to 800 mL of blood is forced downward to the abdominal area and lower extremities. Within seconds of this sudden decrease in venous return, pressure receptors in the heart, lungs, carotid sinus and aortic arch are activated and mediate an increase in sympathetic outflow. Through vasoconstriction of capacitance and arteriolar vessels and through increased heart output, a healthy subject is able to reach orthostatic stabilization in 60 seconds or less. This neurally mediated mechanism is the only one by which we can adapt to the first few minutes of an upright position, and it remains the most important afterward. Orthostatic stress and sympathetic activity have been shown to increase with the angle of HUT testing. Hemodynamic and hormonal data suggest that this stress is exerted mostly between 60° and 90°.
  • it is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age with MVPS or the elderly with dysautonomia for a variety of reasons.

not everyone with a postural blood pressure drop requires treatment, nor does everyone with posturally induced symptoms have orthostatic hypotension.

Rx options of postural hypotension:

  • avoid exacerbating factors
  • stockings
  • reduce salt loss: fludrocortisone 0.05-0.10mg qd to qid
  • vasoconstriction:
  • prevent vasodilatation:
  • increase cardiac output: pindolol; xamoterol;
  • increase red cell mass: erythropoietin
  • reduce nocturnal polyuria: desmopressin
  • avoid supine hypertension:
    • reduce excessive fludrocortisone
    • no vasoconstrictors after 6pm
    • sleep with head of bed elevated
    • consider ACEI (eg. enalapril) with maximal dose at bedtime
  • Mx of resultant nocturia due to relocation of fluid from periphery: desmospressin

Post-prandial hypotension:

  • postprandial hypotension was first recognized as a clinical problem in 1977 in a patient with Parkinson disease.
  • analogous to orthostatic hypotension, postprandial hypotension is commonly defined in the literature as a decrease in systolic blood pressure of 20 mm Hg or more within 2 hours of the start of a meal. Postprandial hypotension also develops when the absolute level of systolic blood pressure after a meal decreases to less than 90 mm Hg and when the systolic blood pressure before a meal is greater than 100 mm Hg.
  • postprandial hypotension may result in syncope, falls, dizziness, weakness, angina pectoris, and stroke.
  • Postprandial hypotension is distinct from and probably more common than orthostatic hypotension.
  • Because meal-related hypotension is particularly common in older hypertensive patients, it has important implications for the evaluation and management of hypertension.
  • The mechanism of postprandial hypotension is not fully understood. Possible contributors include inadequate sympathetic nervous system compensation for meal-induced splanchnic blood pooling; impairments in baroreflex function; inadequate postprandial increases in cardiac output; and impaired peripheral vasoconstriction, insulin-induced vasodilation, and release of vasodilatory gastrointestinal peptides.
  • Although caffeine is often recommended as treatment for postprandial hypotension, available data do not support its use. *Octreotide, a somatostatin analog, has been shown to be effective, but it is expensive and must be given parenterally.

Rx of post-prandial hypotension:

  • avoid gastric filling - smaller, more frequent meals
  • adenosine receptor blockade: caffeine 250mg eg. strong coffee or tea before arising & with meals (? benefits not supported by data)
  • water drinking - acts within minutes, drink 120-480ml over 5min before meal; drink 2-3L/day; mediated via symp. activation via increased plasma NA;
  • peptide release inhibitors: octreotide - expensive & must be given parenterally
  • other: iboprofen 400mg; phenylpropanolamine 25mg; ergotamine i/nasal i-ii puffs;

Assessment of autonomic insufficiency:

Physiologic functional testing:

  • bedside postural assessment:
    • lying-standing BP & HR:
      • The normal physiologic response to the assumption of an upright posture is a small drop in blood pressure and a slight rise in pulse rate. Orthostatic hypotension is detected by measurement of blood pressure in two or more body positions. An abnormal blood pressure response can be observed with disorders such as syncope, falling, intravascular volume depletion, and autonomic dysfunction; with the treatment of maladies such as hypertension and heart failure; and with the use of several medications.
    • heart rate variability:
      • physiology:
        • 3 main periodic HR fluctuations:
          • thermoregulation-related heart rate variability: very-low-frequency (VLF) fluctuations, fewer than 3 per minute or 0.05 Hz;
          • baroreflex-related heart rate variability: low-frequency (LF) fluctuations, approximately 6 per minute or 0.1 Hz;
          • respiratory sinus arrhythmia: high-frequency (HF) fluctuations, equal to the respiratory rate, for example, 19/min or 0.32 Hz
        • the amount of heart rate variability is influenced by physiologic, maturational & pathological factors:
          • heart rate variability decreases with age however, the ratio between high- and low-frequency heart rate variability is stable with advancing age thus the parasympathetic-sympathetic balance does not change
          • angiotensin-converting enzyme blocking augments the low-frequency heart rate oscillations in dogs. Therefore it has been suggested that the renin-angiotensin system lowers LTV due to attenuation of fluctuations in peripheral vascular resistance.
          • body posture influences heart rate variability. In the upright position, baroreflex-related heart rate variability is enhanced due to an increased sympathetic tone. Respiratory sinus arrhythmia is augmented in the supine position.
          • circadian effect
          • iatrogenic factors:
            • drugs that act on autonomic system
          • pathologic factors:
            • cardiovascular disease eg. IHD, CCF, hypertension
            • autonomic dysfunction
      • respiratory sinus arrhythmia test:
        • the mean difference between maximal and minimal heart rate during six deep breaths with a frequency of six per minute
    • ECG R-R interval assessments:
      • time domain analysis:
        • beat-to-beat or short-term variability (STV) indices represent fast changes in heart rate:
          • standard deviation (SD) of beat-to-beat R-R interval differences within the time window
        • long-term variability (LTV) indices are slower fluctuations (fewer than 6 per minute:
          • the SD of all the R-R intervals
          • the difference between the maximum and minimum R-R interval length, within the window
      • spectral (frequency) domain analysis:
        • power spectrum graph can de displayed with the magnitude of variability as a function of frequency and normally displays 3 peaks corresponding to the 3 physiologic HR fluctuations
  • Head Upright Tilt-table (HUT) test
  • baroreceptor-vagal strength tests:
    • pharmacologic elevation of BP to determine the baroreceptor slope & thus strength of vagal response
    • bedside HR response to Valsalvre:
  • thermal reactivity of microcirculation:
    • axonal degeneration starts in the most distal parts of the axon due to impaired axonal transport. Therefore, the longest C-fibres, i.e. in the lower extremities, are affected first, and incipient changes are most prominent there. For this reason HLDF, a reflex response of the skin blood flow stimulated by heat, has advantages in assessment of early C-fibre dysfunction. Considering the fact that the afferent and efferent sympathetic C-fibres are involved in regulation of microcirculation, the skin blood flow regulation is investigated by means of laser Doppler flowmetry. The microcirculation is stimulated by heat and the reaction of microcirculation is assessed as a value for the function of afferent and efferent (sympathetic) C-fibres. The results of this method are in close correlation with electrophysiologic tests, which is not achieved with sudomotor function.

Biochemical:

  • 24hr urinary catecholamines:
    • VMA (metabolite of noradrenaline):
    • HMA (metabolite of dopamine):

References

n_dysautonomia.txt · Last modified: 2019/07/15 06:54 by gary1