Controversies: Vasopressor
Choice for Postspinal Hypotension
During Cesarean Delivery
Alison Macarthur, MD*
Mount Sinai Hospital
Toronto, Ontario, Canada
The use of spinal anesthesia for cesarean delivery has increased with
the introduction of small-gauge, noncutting spinal needles. Most women
in Canada, the United States, Australia, and Europe requiring elective
cesarean delivery receive some variation of a spinal anesthetic technique
owing to the perceived advantages of a clear end point in locating the
subarachnoid space, fast onset of local anesthetic effect, and reduced risk
of local anesthetic toxicity. To successfully administer spinal anesthesia
for cesarean delivery, however, requires consistent attention to details to
minimize side effects, the predominant one being maternal hypotension.
Maternal hypotension is an unwanted consequence of the physiologic onset of spinal blockade, and causes both maternal and fetal effects.
Maternal symptoms include nausea, vomiting, and a sense of impending doom from inadequate cerebral perfusion. Inadequate treatment
of hypotension can ultimately end with the loss of consciousness and
cardiovascular collapse. The fetus is indirectly affected by the development of hypotension, because of its dependency on maternal uterine
artery pressure for adequate uterine blood flow. With a persistent
reduction in uterine blood flow, fetal acidosis will occur; uterine blood
flow reductions of 65% led to acidosis in 10 minutes in the fetal lamb
model.1 Although anesthesiologists do not allow hypotension to persist,
successful treatment can occasionally take longer than desired.
The incidence of maternal hypotension is reported to be 50% to
80% depending upon the definition of hypotension used, the position of
FROM THE *DEPARTMENT OF ANESTHESIOLOGY AND PAIN MANAGEMENT, UNIVERSITY HEALTH NETWORK; AND THE
wDEPARTMENT OF ANESTHESIOLOGY
REPRINTS: DR ALISON MACARTHUR, DEPARTMENT OF ANESTHESIA, ROOM 1514, MOUNT SINAI HOSPITAL, TORONTO,
ONTARIO, CANADA, M5G 1X5, E-MAIL: ALISON.MACARTHUR@UHN.ON.CA
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Vasopressor Therapy
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Ephedrine
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treatment group, with a BE of 5.2 compared with 2.7 for the control
group.
The last issue to address is what is the relative importance of
ephedrines contribution to UA pH changes compared with other
variables. A retrospective study of all elective cesarean deliveries
performed under hyperbaric bupivacaine spinal anesthesia identified
12 explanatory variables and assessed their contribution towards
the prediction of final UA pH.25 The explanatory variables included
patient demographics (age, weight, height, neonatal birth weight),
anesthesia-related information (block height, use of prehydration,
vasopressor used, maximum decrease in systolic pressure, and
length of hypotension) and relevant obstetric information (induction
to delivery time, skin incision to delivery time, uterine incision to
delivery time). Each variable was evaluated in a multivariate linear
regression model, a statistical technique that allows for evaluation of
each variables effect adjusting for the other variables effect on the
outcome, UA pH. The final predictive model concluded that the
important variables to predict the UA pH were whether ephedrine was
used, the length of uterine incision to delivery time, the maximum
decrease in systolic pressure in mm Hg, and the duration of hypotension
in minutes. An interaction term was identified in the model, between
ephedrine use and duration of hypotension, indicating that the women
receiving ephedrine had a further deleterious effect depending upon
the duration of hypotension.
The final mathematical model to predict UA pH in this population
of healthy women under spinal anesthesia was:
UA pH = 7.413 to 0.042 (if ephedrine used) 0.014 duration
of hypotension in minutes (if ephedrine used) 0.001 maximum
decrease in systolic arterial pressure in mm Hg 0.0002 uterine
incision to delivery time+ 0.0002 duration of hypotension in
minutes.
Although this formula seems overwhelming, its applicability can be
seen using a case of extreme pathophysiology: a woman for elective
cesarean delivery under spinal anesthesia has a significant reduction of
systolic arterial pressure of 40 mm Hg, who then receives ephedrine and
has a hypotensive episode of 5 minutes and then experiences a longer
than usual uterine incision to delivery time of 32 seconds. In this case,
the above formula predicts the resulting UA pH to be 7.25. This
demonstrates that there is a large reserve for protecting the fetus from
acidosis.2628
Ephedrine, with its longer duration of action, still has a role in
obstetric anesthesia to prevent or treat spinal-induced hypotension
when given in an appropriate dose. The optimal method to administer
ephedrine, whether combined with other vasopressor therapy or
nonmedication therapy, awaits future study.
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Phenylephrine
Concerns With Using a-1-agonist Agents
Standard obstetric anesthesia textbooks up until the 1990s condemned the use of a-1-agonists in the treatment or prevention of
maternal hypotension. These recommendations were based on sheep
studies, which detailed drastic reductions in uterine blood flow after the
administration of methoxamine, metaraminol, or phenylephrine.29
However, in the 1990s clinical researchers reported on the effectiveness
of phenylephrine in treating spinal anesthesia-induced hypotension.30
The incentive to evaluate this vasopressor arose from the failure of
ephedrine when used in the recommended 5 to 10 mg IV bolus doses,
and a desire to reduce the tachycardia elicited by ephedrine that was
undesirable in some parturients.
Between 1991 and 2001, 7 studies compared ephedrine with
phenylephrine among women undergoing elective cesarean delivery
under spinal anesthesia.3137 These studies were summarized by Lee
et al38 in a quantitative review. The summary concluded that ephedrine
and phenylephrine were not different in preventing or treating
hypotension (refer to Table 1). The only difference identified in the
studies was that women given phenylephrine had neonates with higher
umbilical arterial pH values, by 0.03 pH units. Umbilical arterial base
excess was greatest amongst neonates born to mothers receiving
phenylephrine (weighted mean difference = 1.41; 95% confidence
interval, 0.812.02).
This unexpected finding of improved neonatal parameters with
phenylephrine may be explained by the lack of fetal metabolic effect as
compared with ephedrine. Although UA resistance may be increased
with phenylephrine, the oxygen consumption by the fetus is not, and
therefore the net oxygen balance is more favorable than ephedrine.
Phenylephrine has been incorporated into the clinical practice of North
American obstetric anesthesiologists as the evidence grows that it is not
more harmful than ephedrine.
Table 1.
Relative Risk
1.09 (95% CI, 0.71-1.69)
1.00 (95% CI, 0.95-1.05)
1.00 (95% CI, 0.96-1.06)
WMD
0.03 (95% CI, 0.02-0.04)
0.78 (95% CI, 0.16-3.92)
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blood pressure was kept within the assigned groups range. The primary
outcome was the difference in UA pH between the 3 groups, and
secondary outcomes of the incidence of hypotension, reactive hypertension, nausea, and vomiting. Despite an almost 2-fold increase in the
mean phenylephrine dose administered, women in the 100% baseline
group had fewer episodes of nausea or vomiting (4% vs. 16%, 40%) and
their neonatal mean umbilical arterial pH was higher (7.32 0.04 vs.
7.30 0.03 for both other groups). The unpleasant symptoms of
hypotension are better controlled with tight control of blood pressure
using aggressive vasopressor administration. Maximizing uterine artery
perfusion after the sympathectomy of spinal anesthesia may be more
important in maintaining uterine blood flow and fetal well being than
previously understood.
Our concern with a-1-agonists vasoconstrictive effects on the
uterine artery has distracted us from their effects across different
vascular beds. In an elegant study of pregnant and nonpregnant sheep,
Magness et al41 demonstrated that the pregnant uterine artery was less
responsive to a-1-agonist stimulation than the nonpregnant uterine
artery. Figure 3 illustrates the relative changes in pregnant and
nonpregnant uterine vascular resistance, SVR, mean arterial pressure,
Figure 3. Relationship between the percent change in uterine vascular resistance (*) and blood
flow (D) with mean arterial pressure (&) and SVR (^) during systemic infusions of phenylephrine
in nonpregnant sheep.
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Conclusions
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