Alcohol Potentiates Orthostatic Hypotension
Implications for Alcohol-Related Syncope
Krzysztof Narkiewicz, MD, PhD; Ryan L. Cooley, MD; Virend K. Somers, MD, PhD
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Background—Alcohol consumption may be linked to syncopal events. The mechanisms by which alcohol may induce
syncope are unknown. Impairment of the response to orthostatic stress may be involved. Using a double-blind,
randomized, placebo-controlled study, we tested the hypothesis that short-term alcohol intake causes orthostatic
hypotension because of an impairment in the vasoconstrictor response to orthostatic stress.
Methods and Results—We examined the effects of alcohol on blood pressure, heart rate, and forearm vascular resistance
(FVR) during orthostatic stress achieved by stepwise increases in lower-body negative pressure (LBNP) in 14 healthy
young volunteers. During the placebo session, blood pressure did not change significantly during LBNP at ⫺5, ⫺10,
and ⫺20 mm Hg. A significant decrease in blood pressure was evident only at ⫺40 mm Hg. In contrast, blood pressure
fell significantly at all levels of LBNP during the alcohol session. Compared with placebo, alcohol potentiated the
hypotensive responses to LBNP, particularly at ⫺40 mm Hg, when the decrease in systolic blood pressure after alcohol
intake (⫺14 mm Hg) was double that after placebo intake (⫺7 mm Hg). FVR increased with LBNP after placebo.
However, after alcohol intake, FVR did not increase during LBNP despite the potentiated decrease in blood pressure.
FVR responses during LBNP were reduced during alcohol compared with placebo consumption (P⫽0.04).
Conclusions—Short-term alcohol consumption elicits hypotension during orthostatic stress because of impairment of
vasoconstriction. These findings have implications for the understanding of the hemodynamic effects of alcohol and, in
particular, for understanding syncopal events that occur in association with alcohol intake. (Circulation.
2000;101:398-402.)
Key Words: alcohol 䡲 blood pressure 䡲 hypotension
A
response to alcohol. These precedents provide a rationale for
supposing that alcohol intake results in hypotension during
orthostatic stress.
Using a double-blind, randomized, placebo-controlled
study in healthy young volunteers, we tested the hypothesis
that short-term alcohol intake causes orthostatic hypotension
because of an impairment in the vasoconstrictor response to
orthostatic stress. We examined the effects of alcohol on
blood pressure, heart rate, and forearm vascular resistance
(FVR) during orthostatic stress achieved by graded and
increasing levels of lower-body negative pressure (LBNP).
lcohol consumption may be linked to syncopal events.
Studies of unexplained syncope implicate alcohol dependence1 or alcohol ingestion shortly before syncope.2
Alcohol has been incriminated in 10% of syncopal events in
young adults.3 Alcohol has also been implicated in micturition syncope,4 for which it may be the most common single
predisposing factor.5 The mechanisms by which alcohol may
induce syncope are unknown.
Impairment of the response to orthostatic stress may be
involved. First, in a cross-sectional study of elderly subjects,
the postural decrease in systolic pressure correlated positively
with a history of alcohol consumption.6 Second, in studies of
micturition syncope implicating alcohol as a predisposing
factor, a consistent finding was that the syncopal attacks
occurred within a short time of the erect posture being
assumed after a period of recumbency or sitting.5 Third,
although several studies report increases in supine blood
pressure after short-term alcohol ingestion,7–9 ambulatory
blood pressure measurements are decreased significantly
after alcohol.10 Hypotensive responses to frequent postural
changes during ambulatory blood pressure measurements
may explain this discordance in studies of the blood pressure
Methods
Subjects
We studied 19 normal subjects (18 men, 1 women) who were 26⫾2
(mean⫾SD) years of age. None was taking any medications. All
subjects were social drinkers only and had abstained from alcohol for
ⱖ48 hours before the study. Informed written consent was obtained
from all subjects. The study was approved by the Institutional
Human Subjects Review Committee.
Measurements
Measurements were obtained by use of a randomized, double-blind,
placebo-controlled design with 2 experimental sessions, a placebo
Received June 9, 1999; revision received August 15, 1999; accepted September 1, 1999.
From the Cardiovascular Division, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Correspondence to Virend K. Somers, MD, DPhil, Divisions of Hypertension and Cardiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
E-mail [email protected]
© 2000 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
398
Narkiewicz et al
TABLE 1.
Alcohol and Hypotension
399
Effects of Placebo and Alcohol Intake on Blood Pressure, CVP, and Heart Rate*
Placebo
Measurement
SBP, mm Hg
Alcohol
Before
After
Before
After
115⫾2
117⫾3
111⫾3
113⫾3
Session-by-Time
Interaction, P
0.72
DBP, mm Hg
62⫾2
65⫾2
61⫾2
61⫾2
0.23
MAP, mm Hg
81⫾2
84⫾2
79⫾2
80⫾2
0.49
CVP, mm Hg
8.6⫾1.3
9.0⫾1.3
8.9⫾1.4
9.4⫾1.3
0.92
HR, bpm
59⫾2
58⫾2
57⫾2
63⫾2
⬍0.001
SBP indicates systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; and HR, heart
rate.
*Values are mean⫾SEM; n⫽14 except for CVP (n⫽6). P values are for the session-by-time interaction term
(ANOVA).
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session and an alcohol session. Each session was conducted at the
same time of day on 2 separate days. Vasovagal responses or
discomfort during LBNP in 5 subjects resulted in completion of
studies examining the effects of both alcohol and placebo in only 14
subjects (13 men, 1 woman; mean age, 26⫾2 years).
Heart rate was measured continuously by an ECG. Systolic,
diastolic, and mean blood pressures were measured each minute by
an automatic sphygmomanometer (Life Stat 200, Physio-Control
Corp). Forearm blood flow was measured by venous occlusion
plethysmography as previously described.11 FVR was calculated by
dividing mean arterial pressure by flow and is expressed in arbitrary
units. In 6 subjects, measurements of central venous pressure (CVP)
were obtained during both placebo and alcohol sessions with a
catheter inserted percutaneously into an antecubital vein and advanced into an intrathoracic vein.
Protocol and Interventions
Subjects were studied in the supine position. After undergoing
baseline measurements for 10 minutes, alcohol (1.0 g/kg body
weight, diluted in 400 mL of water) or placebo (400 mL water) was
administered orally over a 30-minute period. A flavoring (Crystal
Light) was added to these solutions to prevent the subjects from
distinguishing alcohol from placebo. Ten-minute recordings were
performed 30 minutes after the subject finished drinking either
alcohol or placebo, immediately before initiation of LBNP. Hence,
LBNP was started 40 minutes after alcohol or placebo intake. LBNP
was applied for 6 minutes at each of the following levels: ⫺5, ⫺10,
⫺20, and ⫺40 mm Hg.
Statistical Analysis
Studies were analyzed by investigators blinded to session (alcohol or
placebo). Data were analyzed by repeated-measures ANOVA with
time as within-factor and session (alcohol versus placebo) as
between-factor variables. The key variable was the group-by-time
interaction, which determined whether alcohol affected the baseline
measurements differently than placebo and whether the responses to
LBNP were affected differently by alcohol than by placebo. Data are
presented as mean⫾SEM. A value of P⬍0.05 was considered
significant.
Results
Plasma Alcohol Levels
During the alcohol sessions, plasma alcohol increased from 0
to 105⫾5 mg/dL at 60 minutes after alcohol intake
(P⬍0.001). Alcohol produced only mild levels of intoxication. All subjects were able to walk after completion of the
study and were not inebriated. Plasma alcohol was undetectable during the placebo session.
Effects of Alcohol on Resting Measurements
Resting blood pressure, CVP, and FVR did not change
significantly after alcohol compared with placebo intake
(Table 1). Alcohol increased baseline heart rate from 57⫾2 to
63⫾2 bpm (P⬍0.001 versus placebo).
Effects of Alcohol on Responses to LBNP
CVP decreased progressively during graded LBNP (Table 2
and the Figure). Changes in CVP were similar after both
alcohol and placebo intake (Table 2).
During the placebo session, blood pressure did not change
significantly during LBNP at ⫺5, ⫺10, and ⫺20 mm Hg. A
significant decrease in blood pressure was evident only at
⫺40 mm Hg (Table 2). In contrast, blood pressure fell
significantly at all levels of LBNP during the alcohol session
(Table 2). Compared with placebo, alcohol potentiated the
hypotensive response to LBNP (Table 2 and the Figure),
particularly at ⫺40 mm Hg, when the decrease in systolic
blood pressure after alcohol consumption (⫺14 mm Hg) was
double that after placebo intake (⫺7 mm Hg).
FVR increased with LBNP after placebo intake (Table 2
and the Figure). After alcohol intake, however, FVR did not
change significantly during LBNP (Table 2), despite the
accompanying decrease in blood pressure. FVR responses
during LBNP were reduced during alcohol compared with
placebo intake (P⫽0.04; the Figure). Heart rate increased
during LBNP at ⫺40 mm Hg during both sessions (Table 2
and the Figure). Despite a significantly greater decrease in
blood pressure with orthostatic stress during the alcohol
session, the heart rate response was not statistically different
between the 2 sessions (Table 2). In a cross-sectional analysis, no relationship between alcohol concentration and hemodynamic responses was evident across subjects.
Discussion
One important and novel finding of this study is that mild
orthostatic stress (LBNP of ⫺5 to ⫺20 mm Hg) lowers blood
pressure significantly in healthy subjects after alcohol but not
placebo intake. Another is that alcohol results in a 2-fold
increase in the hypotensive response to more marked orthostatic stress (LBNP of ⫺40 mm Hg). A third is that alcohol
disrupts the vasoconstrictor response to orthostatic stress.
During LBNP (which should stimulate cardiopulmonary reflex vasoconstriction) and despite the accompanying lower
400
Circulation
February 1, 2000
TABLE 2. Effects of Graded LBNP on Blood Pressure, FVR, CVP, and Heart Rate During
Placebo and Alcohol Sessions*
LBNP, mm Hg
0
⫺5
⫺10
⫺20
⫺40
Session-by-Time
Interaction, P
SBP, mm Hg
Placebo
117⫾3
115⫾2
114⫾2
113⫾3
110⫾3‡
Alcohol
113⫾3
110⫾3‡
108⫾3§
106⫾3§
99⫾3§
Placebo
65⫾2
64⫾2
62⫾2
62⫾2
60⫾2†
Alcohol
61⫾2
59⫾2†
59⫾2†
57⫾2†
53⫾2‡
Placebo
84⫾2
83⫾2
81⫾2
81⫾2
80⫾3†
Alcohol
80⫾2
78⫾2‡
77⫾2‡
75⫾2§
72⫾2§
Placebo
42⫾4
50⫾5
51⫾5
61⫾7‡
60⫾6‡
Alcohol
50⫾7
45⫾5
50⫾6
53⫾6
55⫾5
Placebo
9.0⫾1.3
7.5⫾1.1‡
6.1⫾1.0§
4.1⫾1.2§
1.5⫾0.5§
Alcohol
9.4⫾1.3
7.7⫾1.6†
6.2⫾1.5‡
3.9⫾1.3§
1.7⫾0.6§
Placebo
58⫾2
57⫾2
58⫾2
60⫾2
77⫾2§
Alcohol
63⫾2
62⫾2
63⫾2
67⫾2
88⫾3§
⬍0.001
DBP, mm Hg
0.25
MAP, mm Hg
0.01
FVR, U
0.04
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CVP, mm Hg
0.98
HR, bpm
0.07
Abbreviations as in Table 1. *Values are mean⫾SEM; n⫽14 except for CVP (n⫽6). P values are for the
session-by-time interaction term (ANOVA).
†P⬍0.05, ‡P⬍0.01, §P⬍0.001 for comparison with 0 mm Hg LBNP.
blood pressure (which should trigger arterial baroreflex mediated vasoconstriction), there was no vasoconstrictor response evident after alcohol. This blunted response is in
striking contrast to the effects of LBNP after placebo, when
forearm vasoconstriction was clearly present, even though
blood pressure was much higher during placebo and LBNP.
Previous studies examining the effects of alcohol ingestion
on erect blood pressure in normal subjects report conflicting
results, showing either a decrease12 or no change13 in blood
pressure. A low dose of alcohol (0.5 g/kg body weight)
tended to lower systolic blood pressure after 10 minutes of
45° head-up tilt, but this decrease was not statistically
significant.14 In the present study, we used higher doses of
alcohol (1.0 g/kg body weight). Thus, the potentiated de-
crease in orthostatic blood pressure after alcohol may be dose
dependent. Levels of alcohol consumption and blood alcohol
levels achieved during this study were relatively modest and
are frequently exceeded in real-life situations. Thus, excessive alcohol consumption may elicit more profound disruption of orthostatic tolerance and consequent symptomatic
hypotension15 than described in this article. Within our
subject group, however, a cross-sectional analysis revealed
no relationship between hemodynamic responses to LBNP
and plasma alcohol levels.
It is important that alcohol induces orthostatic hypotension
even in young, healthy subjects. These responses may vary in
subjects who are habitual drinkers or in whom other disease
states are present. In the setting of preexisting impairment of
Changes in mean arterial pressure (MAP), FVR,
and heart rate (HR) in response to LBNP during
placebo (E) and alcohol (F) sessions. Decreases
in MAP were greater and increases in FVR were
smaller during alcohol than during placebo session. Data are mean⫾SEM. *P⬍0.05 for sessionby-time interaction for all levels of LBNP.
Narkiewicz et al
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orthostatic responses, such as in elderly subjects and diabetics, we speculate that orthostatic hypotension after alcohol
intake may be especially pronounced. Furthermore, effects of
orthostatic hypotension on cerebral perfusion may be exacerbated in patients with underlying cerebral vascular disease
and consequent impaired cerebral autoregulation. Indeed, in
patients with primary autonomic failure, alcohol enhanced the
decrease in blood pressure during head-up tilt.16 In patients
with congestive heart failure, short-term alcohol intake decreased blood pressure even in patients in the supine position.17 Systematic studies in patients with neurally mediated
syncope show an attenuation of the sympathetic vasoconstrictor response to orthostatic stress.18 –20 Thus, in these and other
populations, orthostatic stress after alcohol intake may result
in significant hypotension and frank syncope.
Important strengths of this study include the double-blind
study design and the graded levels of orthostatic stress.
Simultaneous measurements of FVR allowed us to identify
the impaired vasoconstriction as a key component in orthostatic hypotension after alcohol. CVP changes with LBNP
were very similar during both placebo and alcohol intake.
Therefore, the blunted vasoconstriction after alcohol was not
explained by higher cardiac filling pressures after alcohol
compared with placebo consumption. However, our data do
not clarify whether the impaired vasoconstriction is secondary to an attenuated sympathetic vasoconstrictor response to
orthostatic stress or whether the sympathetic response is
preserved but the vasoconstriction attenuated by direct vasodilator effects of alcohol. Previous studies indicated that
short-term alcohol administration impairs baroreflex sensitivity.21,22 In the present study, sympathetic traffic was not
measured, and baroreflex function was not formally tested.
However, the heart rate response to the decreased blood
pressure during LBNP suggests possible blunting of the
baroreflex by alcohol administration. A reduced baroreflex
gain after alcohol ingestion would also contribute to the
impaired vasoconstriction observed in our study.
The augmented hypotension evident during orthostatic
stress may thus result from an interaction between several
potential mechanisms. Direct vascular effects of alcohol
would elicit vasodilation. The consequent reduction in blood
pressure could potentially be augmented by impairment of
reflex cardiopulmonary and/or arterial baroreceptor responses, which may themselves be attenuated by effects of
alcohol on their sensory afferents or on central brainstem
mechanisms modulating these reflexes. An additional consideration is the possibility that alcohol may conceivably act
peripherally to attenuate the vasoconstrictor and/or chronotropic responses to sympathetic activation.
Our findings have several important implications. The first
involves our understanding of the hemodynamic effects of
alcohol in the ambulatory setting. During ambulatory blood
pressure measurements, repeated hypotension in response to
standing may explain why alcohol raises supine blood pressure7–9 but lowers ambulatory blood pressures.10 The second
involves our understanding of the possible mechanisms underlying micturition syncope. Bladder distention (due in part
to the diuretic effect of alcohol) induces increases in blood
pressure,23 which would oppose any alcohol-induced postural
Alcohol and Hypotension
401
hypotension. We speculate that micturition, and consequent
bladder emptying, would thus remove the pressor effect of
bladder distention, allowing unopposed alcohol-induced postural hypotension with consequent syncope.5 Third, our results may help in the understanding of some cases of
unexplained syncope. In an overview of syncopal events of
obscure nature, Fisher2 has noted in a number of cases the
involvement of a combination of alcohol intake and subsequent assumption of the erect posture.
In summary, these data demonstrate that in healthy young
subjects, short-term alcohol consumption elicits hypotension
during orthostatic stress because of impairment of vasoconstriction. These findings have implications for understanding
of the hemodynamic effects of alcohol, particularly for
understanding the syncopal events that occur in association
with alcohol intake.
Acknowledgments
Dr Narkiewicz, a visiting research scientist from the Department of
Hypertension and Diabetology, Medical University of Gdansk,
Gdansk, Poland, was a recipient of an International Research John E.
Fogarty Fellowship (NIH 3F05 TW05200) and a Perkins Memorial
Award from the American Physiological Society. Dr Somers is an
Established Investigator of the AHA and a Sleep Academic Awardee of
the NIH. Other support includes HL61560 and HL65176 (NIH). We
thank Diane Davison, RN, MA, for technical assistance.
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Alcohol Potentiates Orthostatic Hypotension: Implications for Alcohol-Related Syncope
Krzysztof Narkiewicz, Ryan L. Cooley and Virend K. Somers
Circulation. 2000;101:398-402
doi: 10.1161/01.CIR.101.4.398
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
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