Disabling postural hypotension complicating diabetic autonomic neuropathy.

A 35-year-old Type 1 diabetic man with severe disabling postural hypotension was studied for physiological abnormalities, precipitating factors, and effect of current treatment. A 24-h blood pressure profile indicated a diurnal variation in systolic blood pressure with the lowest values recorded between 0100 and 0600 h, during which the patient often lost consciousness on standing (mean standing systolic pressure 78 mmHg at night vs 105 mmHg in the afternoon, p less than 0.001). Food induced a profound fall in systolic pressure, both while supine and while standing erect. The systolic pressure fall during euglycaemia was 49 mmHg vs 3 mmHg during hypoglycaemia. Plasma noradrenaline and adrenaline levels were low during euglycaemia, but increased during hypoglycaemia. Therapeutic manoeuvres aimed at increasing heart rate (by atrial tachypacing) and reducing the peripheral pooling of blood (vasoconstricting drugs and gravity suit), together with the somatostatin analogue octreotide, proved ineffective. These observations demonstrate the phenomenon of post-prandial exacerbation of postural hypotension in a Type 1 diabetic patient, and indicate that despite failure of conventional methods of treatment, hypoglycaemia increased plasma catecholamines and was effective in abolishing the blood pressure fall on standing.     

Hypertension in orthostatic hypotension and autonomic dysfunction

Disabling orthostatic hypotension dominates the clinical picture of autonomic failure. Nonetheless, severe supine hypertension is observed in about 50% of patients. In patients with multiple system atrophy (Shy-Drager syndrome), supine hypertension is explained by residual sympathetic tone because it can be eliminated with the ganglionic blocker trimethaphan. The cause of hypertension in patients with pure autonomic failure is not known and its understanding may be relevant to essential hypertension. Supine hypertension complicates the treatment of these patients but can be managed by overnight administration of antihypertensive medications.     

Clinico-pathological features of postural hypotension in diabetic autonomic neuropathy.

We report the clinico-pathological features and management of a 49-year-old male with a 30-year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 micromol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed.     

Short-term postural reflexes in diabetic patients with autonomic dysfunction

Aims/hypothesis Assessment of autonomic dysfunction provides prognostic data in diabetic patients. Clinical tests are limited to heart rate variability and blood pressure measurements. We investigated whether a detailed analysis of postural reflexes of patients during short-term head-up tilting and standing erect (both for 3 min) would provide useful clinical data.Methods We studied 14 control subjects and 56 patients with Type 2 diabetes, stratified into four matched groups: uncomplicated, micro-albuminuria, marco-albuminuria and autonomic neuropathy, who were tilted 55° three times and were standing erect. Non-invasive finger plethysmography blood pressure measurements, using the Portapres, and impedance cardiac output measurements, using the RheoCardioMonitor, were continuously recorded throughout the study. Wavelets of the response to tilting and standing were drawn. The wavelets for the three tilts were combined to improve definition. The degree of autonomic dysfunction was quantified by calculating the baroreflex sensitivity index from the heart-rate and blood-pressure variability data.Results Baroreflex sensitivity data confirmed that autonomic dysfunction increased as diabetic complications worsened (p<0.001). Both standing and tilting resulted in an initial decrease in blood pressure followed by recovery, an increase in heart rate which was more pronounced with standing and a decrease in stroke volume. Characteristic and incremental changes in these responses were noted as the complications of diabetes worsened (p<0.001). These were a greater decrease in blood pressure with loss of the recovery phase, a reduced heart-rate response and paradoxically an increase in stroke volume.Conclusion/interpretation Non-invasive blood-pressure and stroke-volume measurements recorded during short-term tilting and standing promises to be useful in assessing diabetic autonomic dysfunction.Abbreviations UAER urinary albumin excretion rate - HR heart rate - SAP systolic arterial blood pressure - MAP mean arterial blood pressure - SV stroke volume - CO cardiac output - TPR total peripheral resistance - D diabetic patients without complications - DI diabetic patients with micro-albuminuria - DA diabetic patients with macro-albuminuria - AN diabetic patients with autonomic neuropathy     

The time course and diurnal variation of postural hypotension in diabetic autonomic neuropathy

Nine diabetic patients (age range 23-67y) with autonomic neuropathy and symptomatic postural hypotension were studied. The time course of the postural drop in blood pressure (BP) was documented firstly at 0900h, prior to breakfast and insulin, and secondly in the afternoon. Seven patients were symptomatic in the morning but only one in the afternoon. The systolic nadir in the morning was lower (p less than 0.02) than in the afternoon. The mean systolic pressure in the first 3 min after standing was no different in the afternoon but it was lower in the 2nd (p less than 0.05), 3rd (p less than 0.02), and 4th (p less than 0.02) 3-min intervals in the afternoon. The time taken to reach the systolic nadir was variable, ranging from 1-12 min. It is concluded that the assessment of the postural fall in BP may be underestimated if measured immediately after standing or if it is measured in the afternoon.     

Potassium supplementation in the treatment of idiopathic postural hypotension

We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.     

Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension

OBJECTIVES: This study was designed to establish a patient-controlled, ambulatory norepinephrine treatment of refractory orthostatic hypotension due to primary autonomic failure. BACKGROUND: Autonomic dysfunction leads to disabling postural hypotension. Particularly in primary autonomic dysfunction, repeated syncope and immobilization can be the result. Medical treatment of orthostatic hypotension often fails in advanced cases. METHODS: Ambulatory, patient-controlled norepinephrine therapy was initiated in six patients with orthostatic hypotension due to primary autonomic failure that had been refractory to conventional treatment. Before this therapy, three patients were bedridden; one was immobilized in a wheelchair. All had recurrent syncope and tolerated upright tilt-table testing for less than 15 min despite extensive medical treatment. For ambulatory treatment, a port-a-cath system was implanted and, using a CADD ambulatory infusion pump, norepinephrine was infused in individually adjusted dosages. RESULTS: Norepinephrine infusion therapy enabled all patients to sit, stay and walk around for more than 45 min. One patient died after a five-year treatment period, another after nine months because of nonhemorrhagic brain stem infarctions, both in the absence of norepinephrine treatment. The remaining four patients are still mobile after a period of 19, 10, 9 and 7 months, respectively. None of them has suffered complications due to arterial hypo- or hypertension, and there has been no infection of the infusion system. CONCLUSIONS: In these selected patients with refractory orthostatic hypotension due to primary autonomic dysfunction, ambulatory norepinephrine infusion therapy has proved to be a promising new therapeutic option. Further long-term studies including more patients are necessary to assess additional indications, reliability and safety of this new method.     

Management of postural hypotension

Several mechanisms counteract the gravitational forces on blood and maintain systemic arterial pressure and cerebral perfusion upon assumption of the upright posture. Failure of these mechanisms can lead to a postural decrease in blood pressure. Postural hypotension is defined as a reduction of at least 20 mm Hg in systolic blood pressure or at least a 10 mm Hg decrease in diastolic blood pressure. Acute postural hypotension is usually due to fluid or blood loss and responds well to fluid repletion. Chronic postural hypotension is due to drugs or endocrine or neurogenic disorders. A functional classification based on severity of symptoms is useful in monitoring the patient‘s condition and documenting improvement with treatment. Whenever possible, the reversible causes of chronic postural hypotension should be treated. For symptomatic treatment, a stepped approach starting with nonpharmacologic measures is recommended. Fludrocortisone, midodrine, indomethacin, and atrial tachypacing are recommended, in that order, for patients in whom nonpharmacologic measures prove insufficient. Other drugs can be added if necessary. The goal of treatment is to make the patient as ambulatory and symptom-free as possible without causing supine hypertension.     

Aging and postural hypotension. An update

Postural hypotension is a common clinical problem in elderly patients. Reported studies have investigated the epidemiology and mechanisms of this disorder. However, many of these data are based on subjects with diseases and medications also known to cause this disorder, which confuses the relative contributions of normal aging, disease, and medication effects. This review critically evaluates published studies on measurement, epidemiology, and mechanisms of postural hypotension in screened and unscreened elderly populations. Pertinent age-related changes in physiology and the relationship of postural hypotension in the elderly to other models of postural hypotension are reviewed. Areas of current and future research are outlined.     

Assessment of postural hypotension in elderly patients

Change in blood pressure on standing was measured in 23 geriatric inpatients during the morning. The fall in systolic blood pressure was found to be greatest 30 s after standing, at 9.3 +/- 3.3 (SEM) mmHg and had returned to the supine levels within 2 min. In contrast, the diastolic pressure rose to a maximum of 9.7 +/- 1.8 mmHg by 2 min. In 13 patients the measurements were repeated in the afternoon after lunch. The systolic blood pressure drop was significantly greater: 20.8 +/- 3.6 against 7.1 +/- 2.0 mmHg in the morning (p = 0.01). Standardization of the time after standing and time of day of measurement may allow more precise comparisons of different studies.     

Haemodynamic response to postural stress in the elderly with and without postural hypotension

The haemodynamic response to postural stress (60 degrees foot-down tilt) was measured by impedance cardiography in six elderly cardiovascular-normal patients and 39 with symptomatic postural hypotension (systolic blood pressure drop greater than or equal to 20 mmHg or more). In the normal elderly the mean increase in heart rate, fall in blood pressure and cardiac output, and rise in peripheral resistance was less than that described in younger subjects. The changes were at their maximum in 1 min, and there was little further change over the next 5 min. In those with postural hypotension, orthostatic reduction (or failure to rise) of the peripheral resistance was the mechanism in 83% of cases, whatever the cause, and the time course of the haemodynamic changes was the same in the majority as in the normals. Serial tests in patients whose postural hypotension was controlled (by cessation of causal drugs, often multiple, by fludrocortisone, or by dihydroergotamine) showed return to normal.     

Diagnosis and treatment of supine hypertension in autonomic failure patients with orthostatic hypotension

Orthostatic hypotension is seen in various medical conditions. It can be secondary to medications or volume depletion. It can also be due to autonomic neuropathy secondary to other diseases, such as diabetes mellitus, or to primary degenerative processes of the autonomic nervous system. Orthostatic hypotension dominates the clinical picture of patients suffering from autonomic failure. Paradoxically, about one half of these patients also suffer from supine hypertension, which induces pressure natriuresis, worsening orthostatic hypotension. It also complicates the treatment of orthostatic hypotension. Supine hypertension is mediated by an increase in peripheral vascular resistance. This is due to residual sympathetic tone in patients with multiple system atrophy (Shy-Drager syndrome), but the cause is not known in patients with pure autonomic failure, who have increased vascular resistance despite very low levels or plasma norepinephrine and renin activity. The recent observation that patients with supine hypertension develop left ventricular hypertrophy suggests they should be treated. During the day, avoiding the supine position is often all that is required. Short-acting vasodilators (e.g., transdermal nitroglycerin) can be used during the night.