- Email: [email protected]
Postural hypotension
Postural
Hypo tension
*
Report of a Case, with Hemodynamic Studies of Central, Peripheral and Pulmonary Artery Pressures ALAN
SOLOMON, New
M.D.
and LESLIE
KUHN,
M.D.
York, New York
ROFOUND alterations of the normal hemodynamic responses have been described in patients with postural hypotension, including abnormal changes referable to arteriolar resistance, venous tone, cardiac output and neurohormonal vasopressor substances. These changes generally have been related to the circulatory abnormalities occurring in the erect position. The purpose of this report is to present a patient with postural hypotension who had previously undescribed abnormal circulatory findings which were present in the recumbent as well as in the upright position, and to record the circulatory responses of this patient to posterior pituitary preparations and to desoxycorticosterone acetate (DOCA@).
The patient’s blood pressure in the recumbent position was 110/70 mm. Hg; in the sitting position it was 80/50 mm. Hg. On assuming the erect position, she became weak and dizzy, but did not lose consciousness; her blood pressure was unobtainable, but her pulse rate remained unchanged. Neurological examination revealed the deep tendon reflexes in the lower extremities to be absent, but sensation was intact. The peripheral sweating response was diminished. Routine studies of the blood and stool revealed no abnormalities. There was moderate acetonuria without glycosuria and a hypochloremic alkalosis, attributed to her recent vomiting. The cerebrospinal fluid protein content was increased to 67 mg. per 100 cc., but the spinal fluid was otherwise normal. Urinary catecholamines, calculated as norepinephrine, were 18 pg. per twenty-four hours, the lower limit of normal. Results of studies of adrenal cortical function, including a water-loading test, urinary 17ketosteroids and blood 17-hydroxycorticoids, were normal. Roentgenograms of the chest and gastrointestinal system showed no abnormalities. Studies of the central and peripheral pressure and of pulmonary artery pressure were carried out on a tilttable in order to investigate the patient’s severe, disabling postural hypotension. A No. 7 cardiac catheter was passed under fluoroscopic control from the right antecubital fossa to the right pulmonary artery. To record central arterial pressures, a polyethylene catheter was advanced to the ascending aorta just above the aortic valve through a thin-walled 18G needle inserted percutaneously into the left femoral artery. Peripheral arterial pressures were recorded via a Cournand needle inserted percutaneously into the left brachial artery. The zero point for all pressures was 5 cm. posterior to the sternal angle, irrespective of the position of the tilt-table. The systemic pressures were recorded simultaneously from a single base line by means of Statham strain gauges set at equal sensitivities. The catheterization studies are recorded in Figure 1. In the upper portion of the figure, the pronounced fall in both central and peripheral pressures is evident, the
P
CASE REPORT J. MC., a forty-two year old housewife, was admitted’ to The Mount Sinai Hospital on January 20, 1958, complaining of weakness and dizziness upon standing. In 1954, the patient was diagnosed as having diabetes mellitus and control of the diabetes was achieved with the administration of 20 units of NPH insulin daily. In October 1957, the patient first experienced weakness and dizziness upon standing. Her symptoms were immediately relieved by returning to the recumbent position. Concomitantly, severe vomiting developed and she was admitted to another hospital in diabetic acidosis. Treatment with intravenous fluids and additional insulin readily corrected the acidosis, but because of persistent vomiting an exploratory laparotomy was performed. A congenitally absent right adrenal gland and kidney were noted but no intra-abdominal disease was found. Postoperatively, the vomiting subsided; however, her incapacitating postural symptoms persisted, necessitating further hospitalization. On admission to The Mount Sinai Hospital, the patient was thin and appeared chronically ill. The physical examination was yithin normal limits with the exception of her response to the upright position. * From the Department
A.
of Medicine,
Mount Sinai Hospital,
328
New York, New
AMERICAN
York.
JOURNAL
OF
MEDICINE
Postural Hypotension-Solomon,
Kuhn
329
FIG. 1. Simultaneously obtained central aortic and brachial arterial pressure. The pulmonary arterial pressures were recorded immediately following recording of the systemic pressures. The systemic pressures were recorded from a single base line, the strain gauges being set at equal sensitivities. The central pressure is identified by its earlier onset. In the upper portion of the figure, the pronounced fall in arterial pressure with tilting is evident. In contrast to a normal patient, the central systolic pressure was slightly higher than the peripheral systolic pressure during recumbency. During tilting at 60 degrees, although the peripheral pressure was slightly higher than the central pressure, the difference between the two pressures was smaller than seen in normal patients. In the lower portion of the figure the changes occurring in the pulmonary arterial pressure are demonstrated. In contrast to the systemic circulation, the pressure in the pulmonary artery rises slightly during tilting.
most marked drop coming at a 60 degree tilt. These findings are of course definitely abnormal, the normal response to tilting being a slight fall in systolic pressure, a rise in diastolic pressure and a fairly constant mean pressure. The relationship of the central aortic to the peripheral arterial pressure in this patient is of interest. Whereas normally in the recumbent position the brachial artery systolic pressure exceeds the central aortic systolic pressure by about 10 per cent and the peripheral pulse pressure exceeds the central pressure by about 40 per cent [7], in this patient the central systolic pressure was slightly higher than the peripheral systolic pressure. During tilting of the normal patient the difference between the two pressures is markedly accentuated [I]. In this patient, although the peripheral pressure was slightly higher than the central pressure at 60 degrees, the difference between the two pressures was smaller than would be evident in a normal subject. The lower portion of Figure 1 shows the changes occurring in the pulmonary arterial pressure recorded immediately after recording of systemic pressure. In contrast to the systemic circulation, the pressure in the pulmonary artery rose slighfiy during tilting. The patient was given posterior pituitary preparaFEBRUARY,
1960
tions to evaluate the effect on her postural hypotension. A Pitressin@ infusion, 3 mu. (milliunits) per minute, produced a maximum pressor response in both the recumbent and erect positions. (Table I.) However, 5 units of Pitressin tannate in oil administered subcutaneously did not maintain her blood pressure while standing. The intravenous administration of 10 units of oxytocin had no effect on the blood pressure. Attempts to treat the patient’s postural hypotension with the use of elastic stockings, an abdominal binder, ephedrine 30 mg. four times daily, and atropine to tolerance were unavailing. The intramuscular administration of mephentermine (15 mg.) produced a pressor response in the recumbent position, but had no effect on the postural hypotension. (Table I.) DOCA (5 mg.) was administered intramuscularly twice daily. Within seventy-two hours a slight hypertensive effect was achieved in the recumbent position, and the patient’s blood pressure was maintained fairly close to normal levels in the erect position. For the first time in several months she was able to walk without difficulty. When the patient did not receive the drug for several days the postural hypotension returned. When DOCA therapy was reinstituted, the
Postural
Hypotension-dolomon,
TABLE I BLOODPRESSURERESPONSE TO VARIOUSPHARMACOLOGICAL AGENTS
IN
THE
RECUMBENT,
SITTING
AND
STANDING
POSITIONS
Blood Pressure
(mm. Hg) Data Standing
(
110/70
1 80/60
1
O/O
Pitressin (ZntrozxnousInfusion)
1 mU./min. 2 mU./min.. 3 mU./min.. 4mU./min..
.
160/110
_. _.
130/100
_.
_.
90/60 110/80 140/90 ) 125/90
Pitressin Tannate in Oil (5 Units Subcutaneously)
10 15 30 60
min.. min.. min.. min..
._
I _I 120/70 .I 100/70
_.
90/60 90179
O/O
o/o o/o o/o
oxytocin (10 Units Inlraoenocslv) L 30 sec..
60/40
1 min.:. 2 min..
_.
5 min..
70/50 85/70 95/70
Mephenterminc (75 mp. Intramuscularlv)
DOCA (5 mg. Intramuscularly)
Day 1. ...........
Day 2 ............ Day2 ............
120/70 130/80 150/90
100/70 110/70 120/80
80/60 80/60 80/70
beneficial therapeutic effect was again achieved without weight gain or other undesirable side effects of the drug. The patient was discharged from the hospital and took 15 units of NPH insulin daily and 2 and >$ mg. of sublingual DOCA twice daily. For a two-month period she continued to walk and function normally, but subsequently orthostatic hypotension developed again despite maintenance doses of DOCA. After an interval of several weeks she again responded satisfactorily to the administration of 5 mg. DOCA$daily.
Kuhn COMMENTS
Postural hypotension has been found as an isolated occurrence and in association with various endocrinological and neurological disease states. The association of postural hypotension with diabetes mellitus is well known and has been considered to be a form of autonomic neuropathy simulating a sympathectomy [Z-4]. This diabetic patient exhibited postural hypotension and in addition an abnormal sweating response, absent deep tendon reflexes in the lower extremities, pernicious vomiting and an elevated cerebrospinal fluid protein content. All these findings have been described as manifestations of diabetic neuropathy, and are more commonly found in patients with long-standing diabetes and diabetic complications of other organ systems [4]. Fagerberg [5] believes that the neuropathy is secondary to a specific vascular lesion, whereas Rundles [4] attributes its occurrence to the abnormal metabolic state of chronically unregulated diabetes. The precise cause of the syndrome in diabetic subjects, however, is not well known as morphological studies in these patients are scanty. Catheterization studies afforded the opportunity to identify further the abnormal circulatory phenomena occurring in these patients. The results in this patient differed considerably from those observed in the normal subject as reported by Kroeker and Wood [I]. As opposed to the normal response, in this patient central arterial systolic pressure exceeded pericheral arterial pressure in the recumbent position. After tilting to 60 degrees, both central and peripheral arterial pressures fell considerably, and the peripheral systolic, diastolic and mean pressures exceeded the corresponding central pressures. However, abnormalities in the relationship between the two pressures are evident at a 60 degrees tilt as well as during recumbency since the difference between the two pressures is considerably less than would be evident in a normal person, and the brachial and aortic pulse pressures remained equal. Since the normal differences in amplitude and contour between the central and peripheral arterial pulses are believed to be due to summation of the initial wave with the reflected wave from the periphery, and since the normal relationship between the two pressures during tilting is generally attributed to compensatory vasoconstriction, it probably can be assumed that in this AMERICAN JOURNAL
OF
MEDICINE
Postural
Hypotension-
patient peripheral vascular “tone” was considerably impaired in recumbency as well as during tilting. This implies a more faulty vasomotor state in this particular form of postural hypotension than has previously been stressed. In this regard, it is of interest that an increase in blood pressure with Pitressin infusion was obtained by Wagner and Braunwald [6] in patients with postural hypotension in the recumbent position whereas this drug had no effect in normal patients. Several investigators have demonstrated abnormal vascular responses in patients with postural hypotension. Stead and Ebert [7] and Ellis and Haynes [8] postulated that the fundamental physiological defect in these patients is failure to respond to the normal amount of venous pooling in the upright position with an appropriate degree of reflex arteriolar constriction. MacClean and Allen [9], on the other hand, concluded that the defect in postural adaptation is not due to failure of arteriolar constriction but is related to inadequate venous return and diminished cardiac output. Hickam and Pryor [IO] attempted to evaluate the relative importance of changes in cardiac output and of peripheral resistance in producing orthostatic fall in blood pressure. Although the results in their twelve patients were quite variable, significant postural hypotension was more consistently associated with failure of arteriolar constriction than with an abnormal decline in cardiac output. Nevertheless, they were able to prevent the drop in blood pressure in the erect position by serum albumin infusions. Loss of reflex venoconstriction in postural hypotension was postulated in these and in subsequent studies by Page and his associates [ 171. In regard to the pathogenesis of the postural hypotension in this patient, the changes recorded in the pulmonary artery pressure, as demonstrated in Figure 1, are of considerable interest. In contrast to the events occurring in the systemic circulation, the simultaneously obtained pressure in the pulmonary artery rose slightly during tilting. Although the significance of this finding is difficult to interpret without more data, it does suggest that there probably was not, at least initially, a large drop in venous return, because under such circumstances one would not expect the pulmonary arterial pressure to rise unless there were a marked concomitant increase in pulmonary vascular resistance. The possibility of selective “compensatory” pulFEBRVARY,
1960
331
.SoSolomon,Kuhn
monary vasoconstriction acting to sustain the pulmonary arterial pressure in the presence of impaired peripheral vasoconstriction is intcresting to consider, but data to confirm this hypothesis have not yet been obtained. Inasmuch as the physiologic mechanisms responsible for the symptoms of postural hypotension have not been precisely delineated, there have been varied approaches to therapy. Abdominal and leg binders have been suggested to prevent venous pooling but they were without effect in this patient, as were vasopressor agents. As emphasized in the report of Wagner and Braunwald [6], intravenously administered Pitressin was effective in relieving the postural hypotension of this patient, but it was not possible to work out a satisfactory and effective regimen of intramuscular injections. This might be a matter of precise adjustment of dosage, however. The use of DOCA in the treatment of orthostatic hypotension, which was effective in this patient, was previously reported by Spingarn and Hitzig [ 121 and by Gregory [ 731. The reason for the efficacy of DOCA in this syndrome is somewhat obscure, although it has been attributed to an increase in blood volume and also of extravascular volume which might act to prevent pooling of blood in dependent areas. Raab and his associates [74], however, found no significant increase in the body weight of normal subjects with DOCA-induced hypertension. They have also shown that the pressor effect of infused epinephrine and norepinephrine is potentiated in man by pretreatment with DOCA. This effect was further exaggerated by increasing the sodium intake, and diminished or abolished by rigid sodium restriction. The varying response of this patient to the same dose of DOCA may have been due to alterations in her salt intake, but this factor was not controlled accurately enough to provide precise information on this point. SUMMARY
A patient with dialjetic neuropathy and associated orthostatic hypotension is described. Cardiac catheterization studies of central and peripheral arterial pressures during various degrees of tilting revealed abnormal findings in the recumbent position as well as during tilting. Whereas normally the peripheral arterial pressure exceeds the central arterial pressure, in this patient the central arterial pressure was slightly
332
Postural Hypotension-Solomon,
higher than the peripheral arterial pressure in the recumbent position. During tilting, the peripheral arterial pressure exceeded the central arterial pressure but the difference between the pressures was considerably less than would be evident in a normal person. These findings were taken as evidence that peripheral vascular was impaired in this patient in re“tone” cumbency as well as during tilting. A simultaneously recorded pulmonary arterial pressure demonstrated a slight rise during tilting in contrast to the events in the systemic circulation, suggesting that there was no large initial fall in venous return. Pressor effects and relief of postural hypotension were obtained with Pitressin, administered intravenously, as well as with DOCA, administered intramuscularly. Sublingual administration of DOCA resulted in a prolonged remission. REFERENCES 1. KROEKER, E. J. and WOOD, E. H. Comparison of simultaneously recorded central and peripheral arterial pressure pulses during rest, exercise and tilted position in man. Circulation Res., 3: 623, 1955. 2. ODEL, H. M., ROTH, G. M. and KEATXNG, F. R. Autonomic neuropathy simulating the effects of sympathectomy as a complication of diabetes mellitus. Diabetes, 4: 92, 1955. 3. BERNER, J. H. Orthostatic hypotension in diabetes mellitus. Actn med. Scandinav., 143: 336, 1952.
Kuhn
4. RUNDLES, R. W. Diabetic neuropathy. Medicine, 24: 11, 1945. 5. FAGERBERG, S. Studies on the pathogenesis of diabetic neuropathy. Acta med. Scandinav., 157: 401, 1957. 6. WAGNER, H. N. and BRAUNWALD, E. The pressor effect of the antidiuretic principle of the posterior pituitary in orthostatic hypotension. J. C/in. Invest., 35: 1412, 1956. 7. STEAD, E. A. and EBERT, R. V. Postural hypotension: a disease of the sympathetic nervous system. Arch. Int. Med., 67: 546, 1941. 8. ELLIS, L. B. and HAYNES, F. W. Postural hypotension with particular reference to its occurrence in diseases of the central nervous system. Arch. Znt. Med., 58: 773, 1936. 9. MACCLEAN, A. R. and ALLEN, E. V. Orthostatic hypotension and orthostatic tachycardia. J. A. M. A., 115: 2162, 1940. 10. HICKAM, J. B. and PRYOR, W. W. Cardiac output in postural hypotension. J. Clin. Invest., 30: 401, 1951, 11. PAOE, E. B , HICKAM, J. B., SIEKER, H. O., McINTOSH, H. D. and PRYOR, W. W. Reflex venomotor activity in normal persons and in patients with postural hypotension. Circulation, 11: 262, 1955. 12. SPINDARN, C. L. and HITZIG, W. M. Orthostatic circulatory insufficiency: its occurrence in tabes dorsalis and Addison’s disease. Arch. Znt. Med., 69: 23, 1942. 13. GREGORY, R. The treatment of orthostatic hypotension. Am. Heart J., 29: 246, 1945. 14. RAAB, W., HUMPHREYS, R. J. and LEPESCHKIN, E. Potentiation of pressor effects of norepinephrine and epinephrine in man by desoxycorticosterone acetate. J. Clin. Invest., 29: 1397, 1950.
AMERICAN
JOURNAL
OF MEDICINE
Hypo tension
*
Report of a Case, with Hemodynamic Studies of Central, Peripheral and Pulmonary Artery Pressures ALAN
SOLOMON, New
M.D.
and LESLIE
KUHN,
M.D.
York, New York
ROFOUND alterations of the normal hemodynamic responses have been described in patients with postural hypotension, including abnormal changes referable to arteriolar resistance, venous tone, cardiac output and neurohormonal vasopressor substances. These changes generally have been related to the circulatory abnormalities occurring in the erect position. The purpose of this report is to present a patient with postural hypotension who had previously undescribed abnormal circulatory findings which were present in the recumbent as well as in the upright position, and to record the circulatory responses of this patient to posterior pituitary preparations and to desoxycorticosterone acetate (DOCA@).
The patient’s blood pressure in the recumbent position was 110/70 mm. Hg; in the sitting position it was 80/50 mm. Hg. On assuming the erect position, she became weak and dizzy, but did not lose consciousness; her blood pressure was unobtainable, but her pulse rate remained unchanged. Neurological examination revealed the deep tendon reflexes in the lower extremities to be absent, but sensation was intact. The peripheral sweating response was diminished. Routine studies of the blood and stool revealed no abnormalities. There was moderate acetonuria without glycosuria and a hypochloremic alkalosis, attributed to her recent vomiting. The cerebrospinal fluid protein content was increased to 67 mg. per 100 cc., but the spinal fluid was otherwise normal. Urinary catecholamines, calculated as norepinephrine, were 18 pg. per twenty-four hours, the lower limit of normal. Results of studies of adrenal cortical function, including a water-loading test, urinary 17ketosteroids and blood 17-hydroxycorticoids, were normal. Roentgenograms of the chest and gastrointestinal system showed no abnormalities. Studies of the central and peripheral pressure and of pulmonary artery pressure were carried out on a tilttable in order to investigate the patient’s severe, disabling postural hypotension. A No. 7 cardiac catheter was passed under fluoroscopic control from the right antecubital fossa to the right pulmonary artery. To record central arterial pressures, a polyethylene catheter was advanced to the ascending aorta just above the aortic valve through a thin-walled 18G needle inserted percutaneously into the left femoral artery. Peripheral arterial pressures were recorded via a Cournand needle inserted percutaneously into the left brachial artery. The zero point for all pressures was 5 cm. posterior to the sternal angle, irrespective of the position of the tilt-table. The systemic pressures were recorded simultaneously from a single base line by means of Statham strain gauges set at equal sensitivities. The catheterization studies are recorded in Figure 1. In the upper portion of the figure, the pronounced fall in both central and peripheral pressures is evident, the
P
CASE REPORT J. MC., a forty-two year old housewife, was admitted’ to The Mount Sinai Hospital on January 20, 1958, complaining of weakness and dizziness upon standing. In 1954, the patient was diagnosed as having diabetes mellitus and control of the diabetes was achieved with the administration of 20 units of NPH insulin daily. In October 1957, the patient first experienced weakness and dizziness upon standing. Her symptoms were immediately relieved by returning to the recumbent position. Concomitantly, severe vomiting developed and she was admitted to another hospital in diabetic acidosis. Treatment with intravenous fluids and additional insulin readily corrected the acidosis, but because of persistent vomiting an exploratory laparotomy was performed. A congenitally absent right adrenal gland and kidney were noted but no intra-abdominal disease was found. Postoperatively, the vomiting subsided; however, her incapacitating postural symptoms persisted, necessitating further hospitalization. On admission to The Mount Sinai Hospital, the patient was thin and appeared chronically ill. The physical examination was yithin normal limits with the exception of her response to the upright position. * From the Department
A.
of Medicine,
Mount Sinai Hospital,
328
New York, New
AMERICAN
York.
JOURNAL
OF
MEDICINE
Postural Hypotension-Solomon,
Kuhn
329
FIG. 1. Simultaneously obtained central aortic and brachial arterial pressure. The pulmonary arterial pressures were recorded immediately following recording of the systemic pressures. The systemic pressures were recorded from a single base line, the strain gauges being set at equal sensitivities. The central pressure is identified by its earlier onset. In the upper portion of the figure, the pronounced fall in arterial pressure with tilting is evident. In contrast to a normal patient, the central systolic pressure was slightly higher than the peripheral systolic pressure during recumbency. During tilting at 60 degrees, although the peripheral pressure was slightly higher than the central pressure, the difference between the two pressures was smaller than seen in normal patients. In the lower portion of the figure the changes occurring in the pulmonary arterial pressure are demonstrated. In contrast to the systemic circulation, the pressure in the pulmonary artery rises slightly during tilting.
most marked drop coming at a 60 degree tilt. These findings are of course definitely abnormal, the normal response to tilting being a slight fall in systolic pressure, a rise in diastolic pressure and a fairly constant mean pressure. The relationship of the central aortic to the peripheral arterial pressure in this patient is of interest. Whereas normally in the recumbent position the brachial artery systolic pressure exceeds the central aortic systolic pressure by about 10 per cent and the peripheral pulse pressure exceeds the central pressure by about 40 per cent [7], in this patient the central systolic pressure was slightly higher than the peripheral systolic pressure. During tilting of the normal patient the difference between the two pressures is markedly accentuated [I]. In this patient, although the peripheral pressure was slightly higher than the central pressure at 60 degrees, the difference between the two pressures was smaller than would be evident in a normal subject. The lower portion of Figure 1 shows the changes occurring in the pulmonary arterial pressure recorded immediately after recording of systemic pressure. In contrast to the systemic circulation, the pressure in the pulmonary artery rose slighfiy during tilting. The patient was given posterior pituitary preparaFEBRUARY,
1960
tions to evaluate the effect on her postural hypotension. A Pitressin@ infusion, 3 mu. (milliunits) per minute, produced a maximum pressor response in both the recumbent and erect positions. (Table I.) However, 5 units of Pitressin tannate in oil administered subcutaneously did not maintain her blood pressure while standing. The intravenous administration of 10 units of oxytocin had no effect on the blood pressure. Attempts to treat the patient’s postural hypotension with the use of elastic stockings, an abdominal binder, ephedrine 30 mg. four times daily, and atropine to tolerance were unavailing. The intramuscular administration of mephentermine (15 mg.) produced a pressor response in the recumbent position, but had no effect on the postural hypotension. (Table I.) DOCA (5 mg.) was administered intramuscularly twice daily. Within seventy-two hours a slight hypertensive effect was achieved in the recumbent position, and the patient’s blood pressure was maintained fairly close to normal levels in the erect position. For the first time in several months she was able to walk without difficulty. When the patient did not receive the drug for several days the postural hypotension returned. When DOCA therapy was reinstituted, the
Postural
Hypotension-dolomon,
TABLE I BLOODPRESSURERESPONSE TO VARIOUSPHARMACOLOGICAL AGENTS
IN
THE
RECUMBENT,
SITTING
AND
STANDING
POSITIONS
Blood Pressure
(mm. Hg) Data Standing
(
110/70
1 80/60
1
O/O
Pitressin (ZntrozxnousInfusion)
1 mU./min. 2 mU./min.. 3 mU./min.. 4mU./min..
.
160/110
_. _.
130/100
_.
_.
90/60 110/80 140/90 ) 125/90
Pitressin Tannate in Oil (5 Units Subcutaneously)
10 15 30 60
min.. min.. min.. min..
._
I _I 120/70 .I 100/70
_.
90/60 90179
O/O
o/o o/o o/o
oxytocin (10 Units Inlraoenocslv) L 30 sec..
60/40
1 min.:. 2 min..
_.
5 min..
70/50 85/70 95/70
Mephenterminc (75 mp. Intramuscularlv)
DOCA (5 mg. Intramuscularly)
Day 1. ...........
Day 2 ............ Day2 ............
120/70 130/80 150/90
100/70 110/70 120/80
80/60 80/60 80/70
beneficial therapeutic effect was again achieved without weight gain or other undesirable side effects of the drug. The patient was discharged from the hospital and took 15 units of NPH insulin daily and 2 and >$ mg. of sublingual DOCA twice daily. For a two-month period she continued to walk and function normally, but subsequently orthostatic hypotension developed again despite maintenance doses of DOCA. After an interval of several weeks she again responded satisfactorily to the administration of 5 mg. DOCA$daily.
Kuhn COMMENTS
Postural hypotension has been found as an isolated occurrence and in association with various endocrinological and neurological disease states. The association of postural hypotension with diabetes mellitus is well known and has been considered to be a form of autonomic neuropathy simulating a sympathectomy [Z-4]. This diabetic patient exhibited postural hypotension and in addition an abnormal sweating response, absent deep tendon reflexes in the lower extremities, pernicious vomiting and an elevated cerebrospinal fluid protein content. All these findings have been described as manifestations of diabetic neuropathy, and are more commonly found in patients with long-standing diabetes and diabetic complications of other organ systems [4]. Fagerberg [5] believes that the neuropathy is secondary to a specific vascular lesion, whereas Rundles [4] attributes its occurrence to the abnormal metabolic state of chronically unregulated diabetes. The precise cause of the syndrome in diabetic subjects, however, is not well known as morphological studies in these patients are scanty. Catheterization studies afforded the opportunity to identify further the abnormal circulatory phenomena occurring in these patients. The results in this patient differed considerably from those observed in the normal subject as reported by Kroeker and Wood [I]. As opposed to the normal response, in this patient central arterial systolic pressure exceeded pericheral arterial pressure in the recumbent position. After tilting to 60 degrees, both central and peripheral arterial pressures fell considerably, and the peripheral systolic, diastolic and mean pressures exceeded the corresponding central pressures. However, abnormalities in the relationship between the two pressures are evident at a 60 degrees tilt as well as during recumbency since the difference between the two pressures is considerably less than would be evident in a normal person, and the brachial and aortic pulse pressures remained equal. Since the normal differences in amplitude and contour between the central and peripheral arterial pulses are believed to be due to summation of the initial wave with the reflected wave from the periphery, and since the normal relationship between the two pressures during tilting is generally attributed to compensatory vasoconstriction, it probably can be assumed that in this AMERICAN JOURNAL
OF
MEDICINE
Postural
Hypotension-
patient peripheral vascular “tone” was considerably impaired in recumbency as well as during tilting. This implies a more faulty vasomotor state in this particular form of postural hypotension than has previously been stressed. In this regard, it is of interest that an increase in blood pressure with Pitressin infusion was obtained by Wagner and Braunwald [6] in patients with postural hypotension in the recumbent position whereas this drug had no effect in normal patients. Several investigators have demonstrated abnormal vascular responses in patients with postural hypotension. Stead and Ebert [7] and Ellis and Haynes [8] postulated that the fundamental physiological defect in these patients is failure to respond to the normal amount of venous pooling in the upright position with an appropriate degree of reflex arteriolar constriction. MacClean and Allen [9], on the other hand, concluded that the defect in postural adaptation is not due to failure of arteriolar constriction but is related to inadequate venous return and diminished cardiac output. Hickam and Pryor [IO] attempted to evaluate the relative importance of changes in cardiac output and of peripheral resistance in producing orthostatic fall in blood pressure. Although the results in their twelve patients were quite variable, significant postural hypotension was more consistently associated with failure of arteriolar constriction than with an abnormal decline in cardiac output. Nevertheless, they were able to prevent the drop in blood pressure in the erect position by serum albumin infusions. Loss of reflex venoconstriction in postural hypotension was postulated in these and in subsequent studies by Page and his associates [ 171. In regard to the pathogenesis of the postural hypotension in this patient, the changes recorded in the pulmonary artery pressure, as demonstrated in Figure 1, are of considerable interest. In contrast to the events occurring in the systemic circulation, the simultaneously obtained pressure in the pulmonary artery rose slightly during tilting. Although the significance of this finding is difficult to interpret without more data, it does suggest that there probably was not, at least initially, a large drop in venous return, because under such circumstances one would not expect the pulmonary arterial pressure to rise unless there were a marked concomitant increase in pulmonary vascular resistance. The possibility of selective “compensatory” pulFEBRVARY,
1960
331
.SoSolomon,Kuhn
monary vasoconstriction acting to sustain the pulmonary arterial pressure in the presence of impaired peripheral vasoconstriction is intcresting to consider, but data to confirm this hypothesis have not yet been obtained. Inasmuch as the physiologic mechanisms responsible for the symptoms of postural hypotension have not been precisely delineated, there have been varied approaches to therapy. Abdominal and leg binders have been suggested to prevent venous pooling but they were without effect in this patient, as were vasopressor agents. As emphasized in the report of Wagner and Braunwald [6], intravenously administered Pitressin was effective in relieving the postural hypotension of this patient, but it was not possible to work out a satisfactory and effective regimen of intramuscular injections. This might be a matter of precise adjustment of dosage, however. The use of DOCA in the treatment of orthostatic hypotension, which was effective in this patient, was previously reported by Spingarn and Hitzig [ 121 and by Gregory [ 731. The reason for the efficacy of DOCA in this syndrome is somewhat obscure, although it has been attributed to an increase in blood volume and also of extravascular volume which might act to prevent pooling of blood in dependent areas. Raab and his associates [74], however, found no significant increase in the body weight of normal subjects with DOCA-induced hypertension. They have also shown that the pressor effect of infused epinephrine and norepinephrine is potentiated in man by pretreatment with DOCA. This effect was further exaggerated by increasing the sodium intake, and diminished or abolished by rigid sodium restriction. The varying response of this patient to the same dose of DOCA may have been due to alterations in her salt intake, but this factor was not controlled accurately enough to provide precise information on this point. SUMMARY
A patient with dialjetic neuropathy and associated orthostatic hypotension is described. Cardiac catheterization studies of central and peripheral arterial pressures during various degrees of tilting revealed abnormal findings in the recumbent position as well as during tilting. Whereas normally the peripheral arterial pressure exceeds the central arterial pressure, in this patient the central arterial pressure was slightly
332
Postural Hypotension-Solomon,
higher than the peripheral arterial pressure in the recumbent position. During tilting, the peripheral arterial pressure exceeded the central arterial pressure but the difference between the pressures was considerably less than would be evident in a normal person. These findings were taken as evidence that peripheral vascular was impaired in this patient in re“tone” cumbency as well as during tilting. A simultaneously recorded pulmonary arterial pressure demonstrated a slight rise during tilting in contrast to the events in the systemic circulation, suggesting that there was no large initial fall in venous return. Pressor effects and relief of postural hypotension were obtained with Pitressin, administered intravenously, as well as with DOCA, administered intramuscularly. Sublingual administration of DOCA resulted in a prolonged remission. REFERENCES 1. KROEKER, E. J. and WOOD, E. H. Comparison of simultaneously recorded central and peripheral arterial pressure pulses during rest, exercise and tilted position in man. Circulation Res., 3: 623, 1955. 2. ODEL, H. M., ROTH, G. M. and KEATXNG, F. R. Autonomic neuropathy simulating the effects of sympathectomy as a complication of diabetes mellitus. Diabetes, 4: 92, 1955. 3. BERNER, J. H. Orthostatic hypotension in diabetes mellitus. Actn med. Scandinav., 143: 336, 1952.
Kuhn
4. RUNDLES, R. W. Diabetic neuropathy. Medicine, 24: 11, 1945. 5. FAGERBERG, S. Studies on the pathogenesis of diabetic neuropathy. Acta med. Scandinav., 157: 401, 1957. 6. WAGNER, H. N. and BRAUNWALD, E. The pressor effect of the antidiuretic principle of the posterior pituitary in orthostatic hypotension. J. C/in. Invest., 35: 1412, 1956. 7. STEAD, E. A. and EBERT, R. V. Postural hypotension: a disease of the sympathetic nervous system. Arch. Int. Med., 67: 546, 1941. 8. ELLIS, L. B. and HAYNES, F. W. Postural hypotension with particular reference to its occurrence in diseases of the central nervous system. Arch. Znt. Med., 58: 773, 1936. 9. MACCLEAN, A. R. and ALLEN, E. V. Orthostatic hypotension and orthostatic tachycardia. J. A. M. A., 115: 2162, 1940. 10. HICKAM, J. B. and PRYOR, W. W. Cardiac output in postural hypotension. J. Clin. Invest., 30: 401, 1951, 11. PAOE, E. B , HICKAM, J. B., SIEKER, H. O., McINTOSH, H. D. and PRYOR, W. W. Reflex venomotor activity in normal persons and in patients with postural hypotension. Circulation, 11: 262, 1955. 12. SPINDARN, C. L. and HITZIG, W. M. Orthostatic circulatory insufficiency: its occurrence in tabes dorsalis and Addison’s disease. Arch. Znt. Med., 69: 23, 1942. 13. GREGORY, R. The treatment of orthostatic hypotension. Am. Heart J., 29: 246, 1945. 14. RAAB, W., HUMPHREYS, R. J. and LEPESCHKIN, E. Potentiation of pressor effects of norepinephrine and epinephrine in man by desoxycorticosterone acetate. J. Clin. Invest., 29: 1397, 1950.
AMERICAN
JOURNAL
OF MEDICINE