Effects of intermittent intravenous saline infusions
in patients with medication—refractory postural tachycardia
&Rachel L. Parker
Joseph T. Perrault
&Beverly L. Karabin
Received: 31 October 2016 /Accepted: 24 January 2017
#Springer Science+Business Media New York 2017
Background The postural tachycardia syndrome (POTS) is a
heterogeneous group of disorders that results in symptoms of
orthostatic intolerance. Excess blood pooling has been ob-
served to cause low effective circulating volume in the central
vasculature. Consequently, acute volume loading with IV sa-
line has emerged as a potential strategy for clinical interven-
tion. We evaluated the impact of acute volume loading on both
the signs and symptoms of patients suffering from POTS.
Methods Fifty-seven subjects screened from our population
of POTS patients and assenting to participation were admin-
istered the two surveys by telephone. Subjects completed each
survey twice, before, and after initiating IV hydration therapy.
The Orthostatic Hypotension Questionnaire (OHQ) was used
to assess change in clinical symptomatology, while the short
form 36 health survey (SF-36) was employed to assess the
impact of IV saline infusion on quality of life.
Results Fifty-seven patients were included in the analysis.
The average number of medications trialed before referral
for IV hydration was 3.6 ± 1.7 medications. Saline infusions
occurred with mean frequency of 11.3 ± 8.5 days and at a
mean volume of 1.5 ± 0.6 l per infusion. The mean change
of the OHQ was 3.1 ± 0.3 (95% CI 2.6–3.7; P< 0.001), with
significant improvement in allthecompositescores.The
mean change in the SF-36 form was 19.1 ± 2.7 (95% CI
−24.6 to −13.6; P<0.001).
Conclusions Intermittent IV infusions of saline dramatically
reduce symptoms and improve quality of life in patients suf-
fering from POTS. Further work should explore its efficacy as
a bridge study for patients of high symptomatic severity.
Keywords POTS .Refractory POTS .IV hydration
The postural tachycardia syndrome (POTS) is a heteroge-
neous group of disorders that results in symptoms of ortho-
static intolerance. In its most common forms, excess blood
pooling has been observed to cause low effective circulating
volume in the central vasculature . Consequently, acute
volume loading with IV saline has emerged as a potential
strategy for clinical intervention . Despite its growing pop-
ularity, empiric evidence supporting its usage is small. Citing
this paucity of evidence, the most recent consensus guidelines
have recommended against long-term use of intravenous hy-
dration and reserve it for rescue therapy only . A recent
Rachel L. Parker
Joseph T. Perrault
Beverly L. Karabin
University of Toledo, Toledo, OH, USA
University of Toledo Medical Center, 3000 Arlington Ave,
Tol edo , OH 4 3164, U SA
J Interv Card Electrophysiol
investigation, in 2014, showed improvement in resting cardiac
output but failed to demonstrate any improvement in exercise
tolerance among POTS patients . Prior investigations were
more supportive. A 1997 study in Circulation suggested that
acute volume loading with IV saline is more efficacious than
pharmacologic intervention . The key to reconciling these
two results may lie in the distinction between subjective and
objective measures. While concurring with the result from
Jacob et al., a later study reported that IV saline’ssuperiority
in offering symptomatic improvement was distinct from its
comparatively weaker performance on observed cardiovascu-
lar parameters . Similarly, a prospective study of POTS
patients found that those patients who showed symptomatic
improvement after any treatment regimen tended to do so
without improvement in the heart rate response during tilt
table testing .
These results are not necessarily contradictory. As sug-
gested by a recent 5-year retrospective study by Moak et al.
, the dramatic subjective improvement seen after acute vol-
ume loading may increase patient compliance with behavioral
interventions (such as reconditioning) needed to realize long-
term objective improvements. However, these findings are of
uncertain generalizability, given the known changes in auto-
nomic function over the human lifespan .
Examining their validity in adult populations is a research
priority. We evaluated the impact of acute volume loading on
both the signs and symptoms of patients suffering from POTS
to properly rationalize its role in treatment. To the best of our
knowledge, this is the first study in an adult population to
evaluate the response to IV saline infusion in a clinical setting.
This prospective observational study was approved the
University of Toledo Medical Center (UTMC) Institutional
All patients with POTS seen in the Syncope and
Autonomic Disorders clinic between January 1, 2010, and
February 1, 2016, were screened for possible inclusion.
Inclusion criteria was a diagnosis with POTS, made or con-
firmed by the UTMC Syncope and Autonomic Disorders clin-
ic, failure of at least one pharmacologic intervention to control
symptoms, and referral for IV hydration therapy. Diagnosis
was made as per the recent consensus guidelines for POTS
which states the following: symptoms of orthostatic intoler-
ance associated with a heart rate increase of 30 beat per minute
(bpm) that occurs within the first 10 min of standing or upright
tilt test in the absence of other secondary causes of orthostatic
intolerance [1,3]. Those who met all inclusion criteria were
contacted by phone and offered the opportunity to participate
in the study. Attempts to contact each potential participant
were made until they were reached or three calls were placed.
Patients declining participation or who could not be reached
after three attempts were excluded from the study.
Each subject underwent a comprehensive chart review to
extract baseline demographic data, comorbidities, and objec-
tive correlates of disease severity, as well as attempted proce-
dural, pharmacologic, and behavioral interventions to amelio-
rate the disease.
Subjects assenting to participation were administered the
Orthostatic Hypotension Questionnaire (OHQ) by telephone.
This tool, validated for clinical use in the longitudinal mea-
surement of the symptomatic severity of orthostatic hypoten-
sion , is routinely employed in our clinic. Patients’re-
sponses were compared before and after initiating IV hydra-
tion therapy. The questionnaire consists of ten composite
scores, six items evaluate symptoms and four assess the im-
pact of symptoms on daily activities. Each item is scored on a
Likert scale from zero to ten with zero indicating the absence
of the symptom in question and ten implicating the worst
expression of said symptom or impact on quality of life.
We also assessed quality of life using the short form 36
health survey (SF-36). The questionnaire contains 36 items
that yield eight category scales divided into two major com-
ponents: mental health and physical health. The scale ranges
from 0 to 100, with lower scores indicating higher disability
and lower quality of life. This questionnaire has been validat-
ed and used to assess quality of life in several medical condi-
tions . In 2002, Benrud-Larson et al. showed that the di-
minished quality of life suffered by POTS patients is compa-
rable to those with chronic obstructive pulmonary disease and
congestive heart failure .
4 Statistical analysis
All data extracted underwent descriptive statistical analysis
using the SPSS 21.0 software (SPSS Inc.). Each patient’sse-
rial response on the OHQ and SF-36 was analyzed for statis-
tical significance using a Student’sttest in a paired sample
Atwo-tailedPvalue of <0.05 was considered to be statis-
Of the 382 patients with POTS who were screened, 72 patients
were prescribed the IV saline infusions and 57 assented to
participation in this retrospective study (Diagram 1).
J Interv Card Electrophysiol
The population of the study was prominently young fe-
males (96.5%) with a mean age of 35.0 ± 12.9 years and no
significant comorbidities. Three had diabetes mellitus, 10 had
hypertension, 4 had other cardiovascular diseases, and none
had kidney impairment. These demographics reflect those
commonly described in patients with POTS .
The fifty-seven patients included in our study had a follow-
up time ranging from 3 to 12 months. The average number of
medications trialed before referral to IV hydration was 3.6 ±
The baseline characteristics of these patients are summa-
rized in Table 1.
6 Therapy protocol
Patients received IV hydration with normal saline through
peripheral IV starts (42 [73.7%]), peripherally inserted central
catheter (PICC) line inserted by certified nurse or interven-
tional radiologist (12 [21.1%]), or subcutaneously implanted
ports (3 [5.3%]). The initial treatment consisted of 1 l of IV
normal saline infused over 1–2 h every week. Therapy was
then titrated up (2 l per week) or down (1 l every 2–4weeks)
depending on the patient’s response and desire.
1.5 ± 0.6 l were received per infusion with a mean frequen-
cy of 11.3 ± 8.5 days.
The average OHQ score before initiating IV hydration therapy
was 6.6 ± 1.5. Dizziness and fatigue were reported as the most
disabling symptoms, with scores of 7.3 ± 2.5 and 8.2 ± 1.6,
The mean change of the OHQ was 3.1 ±0.3 (95% CI 2.6–
3.7; P< 0.001), with significant improvement in all the com-
posite scores, Fig. 1.
Figure 2shows the mean SF-36 for each category at base-
line and after the intervention. As illustrated, IV saline infu-
sion leads to significant improvement in quality of life with
mean difference of 19.1 ± 2.7 (95% CI −24.6 to −13.6;
P< 0.001). This significant improvement was valued across
all the domains appraised by the SF-36.
Most patients reported an immediate improvement in
symptoms that lasted for 3.3 ± 2.2 days.
Four patients reported no improvement in symptoms or
quality of life to our intervention. This subgroup was entirely
Caucasian with a mean age of 19. Three of them had POTS
secondary tohypermobility syndrome. Mean OHQ and SR-36
before intervention were 6.6 and 47.3, respectively.
Hypermobility and young age were the only factors found to
predict poor response to IV hydration, P= 0.015 and P=
0.009, respectively. However, given our small total sample,
it is unclear that this finding is generalizable.
During the study period, the overwhelming majority of
subjects saw sufficient symptomatic improvement to discon-
tinue IV saline infusion altogether. Of the 50 patients who
successfully weaned from saline infusion during the study
period, all had done so in less than 6 months, and 44% did
so in less than 3 months. There was no clear demographic,
behavioral, or treatment characteristic common to this group
Table 1 Characteristics of patients in our study (N=57)
Females, N(%) 55 (96.5%)
Age in years (mean ± SD) 35.0 ± 12.9
White 55 (96.5%)
Other, N(%) 2 (3.5%)
Cause of orthostatic intolerance, N(%)
Idiopathic 41 (71.9%)
Hypermobility 14 (24.6%)
Hyperadrenergic 2 (3.5%)
Previous medication failed, N(%)
Beta-blockers 35 (61.4%)
Midodrine 28 (49.1%)
SSRIs and SNRIs 25 (43.9%)
Desmopressin 24 (42.1%)
Fludrocortisone 17 (29.8%)
Bupropion 14 (24.6%)
Pyridostigmine 14 (24.6%)
Octreotide 10 (17.5%)
Dextroamphetamine/amphetamine 9 (15.8%)
Other 9 (15.8%)
Northera 8 (14.0%)
Epoetin alfa 4 (7.4%)
Ivabradine 2 (3.5%)
Nnumber, SD standard deviation, SSRI selective serotonin reuptake in-
hibitor, SNRI serotonin–norepinephrine reuptake inhibitor
72 patients with
POTS prescribed IV
53 Patients responded
symptoms and quality of
4 Patients with no
symptoms or quality of
life and subsequenty
stopped the therapy
15 Patients lost to follow
up or declined participation
in the study
Diagram 1 Outline of t he study
J Interv Card Electrophysiol
of high-responders. Eventually, four would suffer relapse, re-
quiring transition back to saline infusion therapy. However,
even in these cases, relapsed subjects showed dramatically
reduced need for intervention, with average frequency of in-
fusion lowering from 9.25 ± 4.65 to 20.13 ± 7.88 days.
Among subjects that successfully weaned from saline infusion
for any length of time, some return to therapy during episodes
of acute exacerbation or for limited periods of annual peak
symptomology. There was no clear demographic, behavioral,
or treatment characteristic that allowed discrimination be-
tween those who would could be weaned from therapy and
those who remained on therapy for at least one year’s time.
There were no hospitalizations attributable to IV saline in-
fusion during the period studied. One patient discontinued the
therapy due to development of hypertension. There were no
reported cases of deep vein thrombosis or soft tissue infection.
Despite the apparent gulf in complication rate, these results are
in line with the major trends seen in comparable studies. As
compared with our own study population, where 73.7% of
subjects received therapy via peripheral IV starts, this same
modality of represented only 25.6% of the subjects studied
by Moak . Significantly, the entirety of their reported
complications was among subjects employing peripherally
inserted central catheter (PICC) lines or infusion ports. Risks
associated with IV saline infusion may be more particular to
the modality of administration than intrinsic to the therapeutic
In line with other recent publications, this study offers support
for the safety and efficacy of medium-term IV saline infusion
in the treatment of POTS. The principle distinction between
the recently published work of Moak et al.  and this work is
the population under study. There are a number of behavioral
and physiologic changes with age which might predispose to
worsening of the disease.
Unambiguously, a recent systematic review on sedentary
behavior found a positive correlation between age and total
sedentary time in 70% of all studies reviewed .
Deconditioning after prolonged bed rest is associated with a
decline in stroke volume . Exercise is a first-line interven-
tion in POTS, with even short-term regimens demonstrating
Over all score
Walking long time
Walking short time
Standing long time
Standing short time
Daily activity scale
Head/ Neck discomfor
Composite score from zero to ten, lower scores indicating less severe symptoms
After intervention Before intervention
Fig. 1 Difference in OHQ before
and after IV hydration therapy
PF RP BP GH Physical
VT SF RE MH Mental
PF: Physical function, RP: Role-physical, BP: Bodily pain, GH: General health, VT: Vitality,
SF: Social function, RE: Roleemotional, MH: Mental health
Before intervention After intervention
Fig. 2 SF-36 point score before and after the intervention, lower score indicating lower quality of life
J Interv Card Electrophysiol
up to 8% augmentation of stroke volume . This combina-
tion of physiological and behavioral changes over the life
cycle would be expected to render persistent adult cases of
POTS more refractory to treatment than their juvenile coun-
terparts. Our results were supportive of such a finding; our
subjects having failed a mean of [3.6 ± 1.7] medications as
opposed to the 3.1 trials reported by Moak .
There is no clear consensus in medical literature as to the
role and efficacy of intermittent intravenous fluid loading in
POTS patients. While contemporary treatment protocols for
intravenous hydration space interventions in days to weeks,
responsiveness to crystalloid bolus is usually understood over
a much shorter time frame. Studying healthy volunteers,
Grothwohl reported a complete reversal of the peak expansion
in plasma volume in only 8 h . In critically ill postopera-
tive patients, hemodynamic benefits were reversed in 2 h .
While a comprehensive mechanism for this disparity in time
course is as yet unarticulated, suggestive evidence has begun to
emerge in understanding factors controlling blood pressure
. In normal human physiology, responsiveness to sympa-
thetic neural activity seems to vary inversely with CVP [19,
20]. This relationship serves as a compensatory homeostatic
mechanism during hypovolemia. The particular defects of
POTS may compromise this function. An experimental model
using nitroprusside-induced hypotension found that in compar-
ison to controls, these patients could increase the frequency but
not amplitude of sympathetic neural activity . This has
been interpreted in light of extant evidence as attributable to
sympathetic denervation. Though even these results are incon-
sistent , and other defects seem responsible for some symp-
tomatic complaints in this patient population , saline infu-
sion may be effective insofar as it decreases reliance on path-
ologically influenced system. Further complicating this pic-
ture, our study joins a sizable preceding body of work that
failed to identify clinically significant hemodynamic changes
to correlate with the subjects’self-reported improvements.
The present results nonetheless present a powerful role for
saline infusion as a bridge therapy in the treatment of POTS.
Deconditioning creates a vicious cycle of symptomatic worsen-
ing in this patient population and represents a major challenge in
treatment. For instance, one exercise-based regimen reported
both an excellent response rate of 71% disease remission and
that a full 23.6% of all enrollees withdrew from therapy as they
found the required exercise too difficult . It stands to reason
that bridge therapies which alleviate acute symptomatic com-
plaints might facilitate increased compliance. This effect has
already been observed in a major study of adolescent POTS
patients . Researchers found no instrument ideal for tracking
compliance during the present study. However, the sustained
independence from saline infusion in the majority of our sub-
jects, all of whom were treatment refractory upon enrollment,
suggests a similar dynamic wherein short-term symptom relief
facilitates long-term disease control. In the context of both acute
exacerbations and medication-refractory initial presentations, IV
saline infusion seems an effective method for breaking the pos-
itive feedback between deconditioning and symptom severity.
The first major study of this kind was published in 2015
. Both that study and this one are single center using self-
reported scales as a primary outcome. Results were of a con-
sistent magnitude and statistical robustness. Their findings
might also be considered complimentary. While the former
employed a non-specific quality of life questionnaire, with
implicitly presumed attribution to improvement in disease
state, our study added a validated instrument for tracking dis-
ease severity and consequent improvement in quality of life.
study. The relatively young age of the subjects [mean age of
35.0 ± 12.9] without significant comorbidities may have led to
a more favorable outcome and reduced complications.
Moreover, compliance to other medical therapy and exercise
programs was not accounted for, which could have altered the
course of the disease. This may also have allowed the develop-
ment of psychological dependence to saline infusion to go
As a non-blinded non-controlled observational study, pla-
cebo effect cannot be excluded. A blinded study protocol
comparing sham and actual saline infusions is justified clarify
this point. Nonetheless, these results provided a preliminary
evidence for the efficacy of IV hydration therapy and thereby
provide justification for larger better controlled studies. As a
whole, our sample was highly responsive to IV fluid loading,
with improvement reported in 93.0% of subjects. It is worth
examining whether this represents a particular subset of the
disease by etiology or presentation, and which medications
might be synergistic with IV fluid loading. The present study,
like other existing literature, suggests a wide variability in the
duration of intravenous hydration therapy. With increasing
clinical experience, the contours of a regimen for timing and
method of discontinuation IV therapy should emerge. While
increased compliance with behavioral interventions such as
reconditioning has been informally observed, it is unclear
whether these or some alternative mechanism are the driver
of the long-term improvements observed.
This study examined the validity of IV infusion as a
second-line therapy without regard to defining the efficacy
of any first-line treatment program. For the first-line therapy,
patients should be treated in accordance with our previously
published recommendations [1,3].
In, conclusion, intermittent IV infusions of saline dra-
matically reduce symptoms in patients suffering from
postural tachycardia syndrome. Paired with its relative
safety and low cost, this quality makes it an ideal can-
didate for bridge therapy to allow the implementation of
long-term interventions in highly symptomatic patients.
Further studies will be necessary to better refine this
J Interv Card Electrophysiol
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
Source of funding None.
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