ajog.
org
Spinal anesthesia-induced hypotension: is it
more than just a pesky nuisance?
Cynthia A. Wong, MD
pinal anesthesia (using cocaine) was first described by
S August Bier in 1899 in Germany, and the first cesarean
delivery with spinal anesthesia was likely performed in North
American in 19011 or 1902.2 However, early after its intro-
duction to surgical anesthesia, hypotension was recognized as
a significant clinical problem.3 The “danger” of spinal anes-
thesia was summarized by Franken4 in a 1934 observational
study of 2088 spinal anesthetics performed for cesarean de-
livery—he reported 1 death for every 139 procedures, which
even in 1934 was considered unacceptably high. The use of
spinal anesthesia in obstetrics likely peaked in the United
States in the 1950s when it was used for both vaginal and
cesarean delivery anesthesia.5 By the early 1960s, methods of
continuous epidural anesthesia were being introduced, and
spinal anesthesia in obstetrics fell out of favor because of its
high incidence of adverse maternal effects, including hypo-
tension, inability to prolong anesthesia and analgesia, and
postdural puncture (“spinal”) headache.2,5 However, starting
in the early 1990s, spinal anesthesia experienced a resurgence
in obstetrical anesthesia practice. New small-bore, disposable,
pencil-point spinal needles significantly decreased the inci-
dence of spinal headache, new drugs were available, and cli-
nicians had a better appreciation of the hemodynamic
consequences of spinal anesthesia. Maternal death was re-
ported in both general6 and epidural7 anesthesia, and by the
late 1990s, it was well recognized that general anesthesia was
associated with a higher anesthesia-related maternal mortality
rate than neuraxial (spinal or epidural) anesthesia.6
Anesthesiologists have long recognized that uteroplacental
perfusion is not autoregulated and is therefore directly
dependent on maternal blood pressure. Because of the
resurgence of spinal anesthesia in the past several decades,
there has been an explosion of research on the prevention and
treatment of spinal anesthesia-induced hypotension. In the
current issue of the American Journal of Obstetrics & Gyne-
cology, Knigin et al8 reported the results of a single-center,
retrospective observational study (data are from 2007 to
2017) in which they investigated factors associated with
From the Department of Anesthesia, University of Iowa Carver College of
Medicine, Iowa City, IA.
Received Aug. 20, 2020; accepted Aug. 26, 2020.
The author reports no conflict of interest.
Corresponding author: Cynthia A. Wong, MD. cynthia-wong@uiowa.edu
0002-9378/free
ª 2020 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2020.08.105
Related article, page 747.
Editorials
neonatal acidosis (defined as umbilical artery pH of 7.1 or
base deficit of 12 mEq/L) in women undergoing planned
cesarean delivery with spinal anesthesia. Sustained hypoten-
sion and a prolonged anesthesia-to-delivery interval were
both associated with fetal acidosis (overall incidence, 2.6%).
The finding of an association between hypotension and
fetal acidosis is not new or surprising. Crawford recognized as
early as 1966 that spinal anesthesia was associated with a
greater degree of fetal acidosis than general anesthesia.9
Depending on the definition of hypotension (and how one
defines “baseline”), the incidence of hypotension in women
undergoing cesarean delivery with spinal anesthesia reaches
100%.10 Helpfully, the advent of noninvasive cardiac output
monitoring in the past 2 decades has allowed more nuanced
assessment of the cardiovascular changes associated with
midthoracic spinal anesthesia. It is now well understood that
the primary mechanism of hypotension is a profound
decrease in systemic vascular resistance owing to dilation of
the arteriolar resistance vessels.11 A compensatory increase in
cardiac output and heart rate is the result.
Along with a better understanding of the hemodynamic
changes associated with spinal anesthesia, the last 2 decades
has brought a sea change in the prevention and treatment of
spinal hypotension. Historically, ephedrine, an indirect-
acting drug with both alpha- and beta-adrenergic agonist
effects, was the vasopressor of choice. Initial studies per-
formed in the 1970s in instrumented gravid ewes suggested
that ephedrine maintained uterine blood flow, whereas
direct alpha-adrenergic agonists decreased flow.12 Subse-
quently however, randomized controlled trials (RCTs) in
humans comparing ephedrine with phenylephrine (a direct-
acting alpha-adrenergic agonist) showed that neonates
whose mothers received phenylephrine had higher umbilical
artery pH and lower base deficit than neonates whose
mothers received ephedrine, although both drugs success-
fully treated hypotension.13 Further study showed that
ephedrine crosses the placenta at a higher rate and un-
dergoes less early metabolism or redistribution in the fetus
than phenylephrine.14 Associated increases in umbilical ar-
tery lactate and pCO2 suggest that the mechanism of fetal
acidosis associated with ephedrine may be because of
ephedrine stimulation of fetal metabolism.
Spinal anesthesia-induced hypotension in the setting of
cesarean delivery has been variably defined, but most studies
have used the definition of a 20% or 30% decrease in baseline
systolic blood pressure or systolic blood pressure of <100
mm Hg,15 and anesthesiologists have used these thresholds to
determine when to treat hypotension. However, further study
has suggested that maternal and neonatal outcomes are better
if maternal blood pressure is maintained close to the baseline.
NOVEMBER 2020 American Journal of Obstetrics & Gynecology 621
Editorials
In a RCT using phenylephrine, the management strategy of
treating blood pressure whenever it dropped below baseline
was compared to the strategy of treating blood pressure
whenever it dropped below 80% of baseline. Umbilical artery
pH was higher, and the incidence of maternal nausea and
vomiting was lower in women whose blood pressure was
maintained near baseline.16 This study, along with others,
supports the practice of preventing hypotension with pro-
phylactic phenylephrine administration rather than waiting
for the inevitable hypotension to occur and then treating it.17
Intravenous fluid loading before the induction of spinal
anesthesia (“preload”) has been traditionally done to “fill the
tank” made functionally empty by sympathetic blockade and
acute vasodilation. Studies in the past several decades have
demonstrated the flaw in this practice—the intravascular
dwell time of crystalloid administered to a euvolemic patient
(before the induction of anesthesia) is measured in minutes,18
and preloading has been shown to be minimally effective.
However, fluid administration is not without merit. In a trial
in which patients were randomized to receive a phenylephrine
infusion only or a phenylephrine infusion with a rapid fluid
bolus initiated at the induction of spinal anesthesia (termed
“coloading”), the incidence of hypotension was virtually zero
in the phenylephrine with fluid coload group compared with
a 28% incidence of hypotension in patients in the
phenylephrine-only group.19 Thus, in any study of spinal
hypotension, fluid management should be standardized or at
least reported (timing, volume, and rate of administration).
Where do we currently stand with blood pressure man-
agement? International consensus guidelines published in
2018 suggest that a vasopressor with potent alpha-adrenergic
agonist activity should be used prophylactically to prevent
hypotension with the aim of maintaining systolic blood
pressure 90% of baseline.15 This is most easily accom-
plished with a titrated infusion (rather than bolus adminis-
tration) of vasopressor and rapid intravenous administration
of crystalloid (approximately 1 L) at the time of induction of
anesthesia accompanied by frequent (every 1 minute) blood
pressure measurements. Notably, no component of this
management regime was used in the study by Knigin et al,8
alone or in combination. It is interesting to note that in pa-
tients whose hypotension was treated with phenylephrine,
there was no association with neonatal acidosis (95% confi-
dence interval of odds ratio included 1).8
In addition to the unsurprising finding that the extent and
duration of predelivery maternal hypotension were associated
with neonatal acidosis, Knigin et al8 reported that the
anesthesia-delivery time interval was independently associ-
ated with acidosis. This association has also been reported by
others.20 Although investigators have suggested that this in-
terval is potentially modifiable and shortening the interval
may result in less neonatal acidosis, the question still remains
as to the etiology of this association and whether prolonged
(even mild) hypotension played a role in the study results.8
There are hard stops on the degree to which this interval is
modifiable, and the intervals described in the Knigin et al8
622 American Journal of Obstetrics & Gynecology NOVEMBER 2020
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study were not long (median anesthesia-to-delivery interval,
15 minutes; 90th percentile, 24 minutes). To my knowledge,
no study has investigated this association in the setting of
optimal blood pressure management (as described earlier).
Other questions regarding the management of spinal hy-
potension are currently being investigated. Almost all studies
to date have included healthy, nonlaboring women undergoing
planned cesarean delivery. We need to have a better under-
standing of whether the hemodynamic management goals
differ for patients with comorbidities, including those with
reduced placental reserve or those undergoing intrapartum
delivery.21 Historically, systolic blood pressure has been used
because it was easier to measure, but organ perfusion depends
on mean arterial blood pressure, begging the question of
whether we should focus blood pressure management on
mean or on systolic blood pressure. Recently, norepinephrine
has been proposed as an ideal vasopressor, as it may be asso-
ciated with less maternal bradycardia than phenylephrine.22
Should the results of the Knigin et al8 study change our
current preference for neuraxial anesthesia for cesarean de-
livery? The answer is definitively “no,” although anesthesiol-
ogists should pay meticulous attention to blood pressure
management. The findings of Knigin et al8 bear confirmation
in the modern era of blood pressure management. Small
studies suggest that the incidence of neonatal acidosis is very
low if blood pressure is maintained near the baseline.16
Accepting that spinal hypotension causes lower umbilical ar-
tery pH, we also need to ask whether these differences are
worth fussing about in the context of other risks and benefits
of alternative anesthetic techniques. Some cases of spinal hy-
potension are evitable unless we aim to maintain blood pres-
sure higher than the baseline. The association between
neonatal metabolic acidemia and longer-term complications
(eg, neonatal encephalopathy, cerebral palsy) is weak.23 The
finding in the Knigin et al8 study and others20 that secondary
neonatal outcomes (eg, low Apgar scores, transient tachypnea
of the newborn, respiratory distress syndrome, intensive care
unit admission) are not associated with hypotension suggests
that a low incidence of isolated fetal acidosis may be low on our
list of concerns. Our normal practice should be to induce
spinal anesthesia and perform the necessary preparation (eg,
urinary catheter insertion, skin decontamination, draping,
time-out) efficiently and safely. We should not waste time, but
neither should we rush and leave out important steps unless
future research identifies a modifiable step that results in
improved neonatal outcome without increased risk to the
mother. Until these questions are answered and new findings
suggest otherwise, we should not change current management.
ACKNOWLEDGMENTS
The author thanks Alexander J. Butwick, MBBS, FRCA, MS, for his
reading of the manuscript and suggestions. -
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