Anaesthesia 2020, 75, 109–121 doi:10.1111/anae.

14841

Review Article

Prevention of hypotension after spinal anaesthesia for

caesarean section: a systematic review and network
meta-analysis of randomised controlled trials
J. P. Fitzgerald,1 K. A. Fedoruk,2,3 S. M. Jadin,1 B. Carvalho4 and S. H. Halpern2,5

1 Fellow, 2 Staff Anesthesiologist, 3 Assistant Professor, 5 Professor, Department of Anesthesia, Sunnybrook Health
Sciences Centre and the University of Toronto, ON, Canada
4 Professor, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine,
Stanford, CA, USA

Summary
Spinal anaesthesia for caesarean section commonly causes maternal hypotension. This systematic review and
network meta-analysis compared methods to prevent hypotension in women receiving spinal anaesthesia for
caesarean section. We selected randomised controlled trials that compared an intervention to prevent
hypotension with another intervention or inactive control by searching MEDLINE and Embase, Web of Science
to December 2018. There was no language restriction. Two reviewers extracted data on trial characteristics,
methods and outcomes. We assessed risk of bias for individual trials (Cochrane tool) and quality of evidence
(GRADE checklist). We assessed 109 trials (8561 women) and 12 different methods that resulted in 30 direct
comparisons. Methods ranked by OR (95%CI) from most effective to least effective were: metaraminol 0.11
(0.04–0.26); norepinephrine 0.13 (0.06–0.28); phenylephrine 0.18 (0.11–0.29); leg compression 0.25 (0.14–
0.43); ephedrine 0.28 (0.18–0.43); colloid given before induction of anaesthesia 0.38 (0.24–0.61); angiotensin 2,
0.12 (0.02–0.75); colloid given after induction of anaesthesia 0.52 (0.30–0.90); mephentermine 0.09 (0.01–1.30);
crystalloid given after induction of anaesthesia 0.78 (0.46–1.31); and crystalloid given before induction of
anaesthesia 1.16 (0.76–1.79). Phenylephrine caused maternal bradycardia compared with control, OR (95%CI)
0.23 (0.07–0.79). Ephedrine lowered umbilical artery pH more than phenylephrine, standardised mean
difference (95%CI) 0.78 (0.47–1.49). We conclude that vasopressors should be given to healthy women to
prevent hypotension during caesarean section with spinal anaesthesia.

.................................................................................................................................................................
Correspondence to: S. H. Halpern
Email: Stephen.halpern@sunnybrook.ca
Accepted: 12 August 2019
Keywords: anaesthesia, spinal; caesarean section; hypotension; prevention

Introduction severe cases fetal bradycardia and cardiovascular collapse

Spinal anaesthesia is commonly used for elective caesarean [1]. Reduced systemic vascular resistance causes
section as it is easier and quicker than epidural anaesthesia hypotension, exacerbated in the parturient by inferior vena
and it exposes the fetus to fewer drugs than general cava compression, which is partially compensated by
anaesthesia, while the mother can be awake when her baby increased stroke volume and heart rate [2]. The best method
is delivered. to prevent hypotension during caesarean section is
The main disadvantage of spinal anaesthesia is controversial. A new consensus practice statement
maternal hypotension; thus can affect 90% of women and recommends prophylactic vasopressors for all caesarean
causes dizziness, nausea and vomiting, fetal acidosis and in sections [3]. However, the statement did not fully explore

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the adverse effects of vasopressors, such as bradycardia, neonatal Apgar scores one and five minutes after delivery;
although they are mentioned. A recent meta-analysis and umbilical artery pH.
reported over 180 individual comparisons of methods to One reviewer extracted data, which were
prevent hypotension during caesarean section, some of independently checked by a second reviewer.
which included only one trial with fewer than 40 women [4]. Disagreements were resolved by rechecking the
The ‘best’ method cannot be identified from conventional manuscript and, if necessary, requesting adjudication by a
meta-analyses of incomplete pairwise comparisons. third investigator. Risk of bias was determined
Network meta-analysis uses indirect comparisons of independently by two authors using the Cochrane
treatments to substitute and supplement direct collaboration assessment tool. The following domains were
comparisons of treatments, which can increase the assessed as low, unclear or high risk for bias: randomisation-
precision of the effect estimate and can facilitate ranking of sequence generation; concealment of allocation; blinding
treatment efficacy [5]. of personnel and subjects; reported attrition; selective
Our aim was to determine the relative efficacy of reporting and other bias [9]. The overall risk of bias for each
methods to prevent hypotension during elective trial was considered to be the highest for any of the criteria
caesarean section with spinal anaesthesia. We [10]. Publication bias was assessed by accessing the website
included interventions that increased central blood clinicaltrials.gov and attempting to retrieve unpublished
volume and the prophylactic administration of data. In addition, a contour-enhanced funnel plot was
vasopressor drugs. constructed and assessed for asymmetry of small trial
effects using the Harbord test [11].
Methods We used network commands in Stata 15.1 for all
We registered the protocol for this review and used the analyses [12]. We used random-effects modelling to
Prisma Extension checklist for reporting [6]. Two reviewers calculate odds ratio (95%CI) and standardised mean
independently searched MEDLINE, Embase, Web of differences (95%CI). We used the Tau2 statistic to estimate
Science and the Cochrane Library Study Selection to 10 the true heterogeneity between trials. We incorporated
December 2018 (see also Supporting Information, both direct and indirect treatment effects (95% predicted
Appendix). We searched the bibliographies of relevant intervals). We tested the network for consistency and
systematic reviews [4, 7, 8] and clinical practice guidelines drew a network map. We evaluated inconsistency by
[3] for citations. The final list of eligible trials was determined comparing direct and indirect comparisons in magnitude
by consensus. Disagreements were resolved with a third and direction using the ‘sidesplit’ function in Stata. The
adjudicator. updated subroutine ‘mvmeta’ accounts for correlations
We included randomised controlled trials of pre- between effect sizes from multi-arm studies [12]. We used
operative interventions to prevent hypotension during the GRADE method to determine the uncertainty of each
elective caesarean section under spinal anaesthesia in comparison [13]. Our confidence assessment included
healthy women compared with active or inactive risk of bias, indirectness, inconsistency, imprecision and
intervention. We excluded quasi-randomised trials and up- publication bias. Since only randomised trials were
down-sequential dose-finding studies. There was no included, we started with a ‘high’ rating and downgraded
language restriction. We included the following to ‘moderate’, ‘low’ or ‘very low’, depending on the
interventions: intravenous fluid infusion, categorised as assessment of the above factors. We ranked each of the
colloid or crystalloid and categorised as before or after treatments using the surface under the cumulative ranking
induction of anaesthesia; leg compression; and the curve (SUCRA) and the mean rank of each treatment.
vasopressors phenylephrine, ephedrine, norepinephrine, Finally, we performed a sensitivity analysis, removing trials
metaraminol, angiotensin 2 and mephentermine. We that were at high risk of bias.
defined inactive control for fluid infusion as less than or
equal to 500 ml of crystalloid and no prophylactic drugs. Results
We analysed drugs separately, but we did not categorise by We included 109 out of 1021 retrieved trials, which included
route or dose. 8561 women (Fig. 1 and see also Supporting Information,
The primary outcome was the rate of intra-operative Table S1) [14–123]. Twelve interventions (eleven active
hypotension, as defined by the investigators. Secondary treatments and one inactive control) to prevent intra-
outcomes included: the rates of nausea and vomiting; operative hypotension were studied, with 30 direct
maternal tachycardia; bradycardia; reactive hypertension; comparisons (see also Supporting Information, Table S2).

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Fitzgerald et al. | Hypotension and spinal anaesthesia for caesarean section
Figure 2 is the geometry of the network for prevention of
intra-operative hypotension.
The risk of bias was low or unclear for most
comparisons except for fluid type, crystalloid vs. colloid
and timing of fluid infusion, before vs. after induction of
anaesthesia, many of which were not blinded (Fig. 3 and
see also Supporting Information, Table S3). Six trials listed
as completed on the clinicaltrials.gov website had not
published results; their authors did not reply to our
requests for data. The contour-enhanced funnel plot for
the primary outcome appears to be symmetrical (Fig. 4).
The Harbord test did not support significant small trials
effects (p = 0.56). Direct and indirect calculation of the
effects of interventions were concordant, except for
maternal nausea and possibly umbilical artery pH (see also
Supporting Information, Table S4).
All vasopressors, except mephentermine, reduced the
rate of intra-operative hypotension compared with control,
whereas crystalloid before induction of anaesthesia did not
(Fig. 5 and Tables 1 and 2 and see also Supporting
Information, Table S5–S11). Vasopressors reduced the rate
of intra-operative hypotension more than fluid infusion
before or after induction of anaesthesia. There were no
Figure 1 Flow diagram of included and excluded trials.
© 2019 Association of Anaesthetists
Anaesthesia 2020, 75, 109–121
statistical differences in the rates of hypotension with
phenylephrine, norepinephrine or metaraminol, but
hypotension was more common with ephedrine. The rate
of hypotension after colloid infused following induction of
anaesthesia was less than after crystalloid.
We performed a sensitivity analysis on the primary
outcome by eliminating trials that were at high risk of bias,
as determined by lack of blinding. We included 74 trials
(6163 women). None of these trials included the use of
angiotensin 2, leaving 10 active treatments and one active
control. The results were similar to the main analysis
league table and SUCRA (Supporting Information Tables
S12 and S13).
The odds ratios and ranking of interventions for
preventing nausea and vomiting were similar to those for
hypotension (see also Supporting Information, Table S11).
We downgraded our confidence in the results to ‘low’ for
nausea and vomiting as direct and indirect treatment effects
were different, p = 0.02.
Rates of reactive hypertension were low, particularly
after fluid interventions, with corresponding wide
confidence intervals (see also Supporting Information,
Table S12). Reactive hypertension was reported least for
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Pre-crystalloid Pre-colloid

Norepinephrine

Angiotensin Metaraminol

Co-colloid
Co-
crystalloid

Ephedrine Control

Leg compression
Phenylephrine
Mephentermine
Figure 2 Network diagram for primary outcome. Each intervention is represented by a blue circle proportional in diameter to
the number of women who received the intervention. Connecting lines indicate direct comparisons of interventions, their width
proportional to the number of pairwise comparisons and their colour represents the risk of bias: green, low; yellow, unclear; red,
high.

mephentermine and most for metaraminol. There were no
significant differences in rates of reactive hypertension
between ephedrine, phenylephrine and norepinephrine.
Similarly, rates of maternal bradycardia and tachycardia
were accompanied by wide confidence intervals (see also
Supporting Information, Tables S13 and S14). The rate of
bradycardia after phenylephrine was higher than after
Risk of bias
Randomisaon
Allocaon
Parcipant blinding
Assessor blinding
Arion selecve
ephedrine, mephentermine, norepinephrine and fluid. The
rates of tachycardia after fluid infusion before anaesthesia
and after ephedrine were greater than after metaraminol
and phenylephrine.
Low rates of abnormal neonatal Apgar scores one
minute and five minutes after delivery precluded ranking of
interventions (Table 2). Indirect and direct results were
inconsistent for umbilical artery pH, for which the range of
values was narrow and known to have no direct correlation
with neonatal outcome when in the normal range. Umbilical
artery pH was significantly higher after vasopressors than
after fluid infusion, except after ephedrine, following which
umbilical artery pH was significantly lower than after

Reporng other
mephentermine, phenylephrine, metaraminol or
Bias
angiotensin 2 (see also Supporting Information, Table S15).
0 20 40 60 80 100 120
Low risk Unclear risk High risk Discussion
Figure 3 The proportions of trials with different risks of bias Our network meta-analysis showed that maternal
in each methodological domain: green, low; yellow, hypotension, nausea and vomiting were less common after
unclear; red, high. vasopressors than control, fluid infusion or leg compression.

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.5

Standard error

1.5

2
–5 0 5
Effect estimate

Figure 4 A funnel plot of the relative rate of intra-operative hypotension for intervention vs. control (or second intervention),
adjusted so that the pooled effect for each comparison is zero. Each black dot represents a study. The shaded zones represent
the effect sizes: p < 0.01 = light grey, 0.01 > p < 0.05 = midgrey, 0.05 > p < 0.1 = dark grey, p > 0.1 = white.

Our findings are consistent with a recent international
consensus statement on the management of hypotension
during caesarean section, which recommended alpha-
agonist drugs (but cautioned maternal bradycardia with
phenylephrine), drugs with mixed alpha- and beta-agonist
activity, left uterine displacement, colloid infusion before
and crystalloid infusion after induction of anaesthesia [3].
We suggest that intravenous fluid is a secondary
intervention.
We believe that the women in the trials we included
were similar to one another for characteristics that might
interact with the interventions and outcomes (see also
Supporting Information, Table S1), that is, the ‘transitivity’
requirement for network meta-analysis was met. All the
women and their pregnancies were at low risk of morbidity
and all had spinal anaesthesia for planned caesarean
section. The exclusion of studies that were not randomised
controlled trials reduced most risks of bias and the

Treatment effect Mean with 95%CI and 95%PrI

Mephentermine 0.09 (0.01-1.30) (0.00-1.64)

Metaraminol 0.11 (0.04-0.26) (0.03-0.42)
Angiotensin 0.12 (0.02-0.75) (0.01-1.00)
Norepinephrine 0.13 (0.06-0.28) (0.04-0.47)
Phenylephrine 0.18 (0.11-0.29) (0.06-0.57)
Leg Compression 0.25 (0.14-0.43) (0.08-0.79)
Ephedrine 0.28 (0.18-0.43) (0.09-0.85)
Pre-colloid 0.38 (0.24-0.61) (0.12-1.18)
Co-colloid 0.52 (0.30-0.90) (0.16-1.66)
Co-crystalloid 0.78 (0.46-1.31) (0.24-2.46)
Pre-crystalloid 1.16 (0.76-1.79) (0.38-3.54)

0.01 1 23

Figure 5 A forest plot of the odds ratio for hypotension during elective caesarean section in healthy women, interventions vs
control. The 95% confidence interval is shown in black and 95% predicted interval is shown in red.

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symmetry of the funnel plot and Harbord test did not

Table 1 Pairwise odds ratios (95%CI) for prevention of hypotension during elective caesarean section under spinal anaesthesia: OR > 1 favour rows, OR < 1 favour

Metaraminol
suggest small trial effects, one cause of which is publication
bias, although there may be more data forthcoming from
trials in the planning stage or not yet published.

Norepinephrine
The inconsistency between direct and indirect
comparisons for rates of intra-operative nausea and

1.2 (0.4–3.5)
vomiting may have been due to differences in the way trials
reported this outcome or variation in confounding factors,
such as the use of sodium citrate, which may increase the

3.0 (1.4–6.2)
3.6 (1.5–8.8)
Pre-colloid
rate of nausea [124], or prophylactic anti-emetics that
reduce the rate [125]. Other factors that may have
contributed to inconsistency include the dose of
11.0 (4.6–26.1) intrathecally injected local anaesthetic or adjuvants, the
Pre-crystalloid

9.0 (4.5–18.0)
3.1 (2.3–4.1)

surgical approach or other local practices that may have

influenced the risk of intra-operative nausea but were
unrelated to maternal hypotension. The inconsistency in the
network for umbilical pH may have been due to the very
Angiotensin 2
0.1 (0.0–0.6)
0.3 (0.05–1.9)

narrow range of values for this outcome. Few trials reported

0.9 (0.1–6.3)
1.2 (0.2–8.1)

the number of neonates with a cord pH of less than 7.2. In all

trials, the rate of abnormal umbilical artery cord gases was
extremely low. The lower umbilical artery pH after
4.9 (1.9–12.4)
0.4 (0.3–0.7)

4.0 (1.8–8.8)
4.3 (0.7–26.3)

ephedrine is of uncertain clinical significance in neonates

1.4 (0.9–2.1)
Co-colloid
columns. Treatments were significantly different (p < 0.05) if the 95%CI did not include 1 (bold).

with high Apgar scores [126].

A recent Cochrane review suggested that crystalloids
alone may be inadequate to prevent hypotension during
0.5 (0.3–0.9)

0.2 (0.2–0.3)

2.2 (1.1–4.4)
2.6 (1.1–6.1)
2.3 (0.4–13.5)

0.7 (0.5–1.1)
Ephedrine

caesarean section and that vasopressors appear more

effective than fluids alone [4]. The review did not find leg
compression effective although we found it more effective
than fluid infusion but less effective than vasopressors.
Leg compression

The trials in our systematic review limited some of our

0.5 (0.3–0.9)

0.2 (0.1–0.3)
2.0 (0.3–12.7)
0.9 (0.5–1.5)

0.6 (0.4–1.1)
1.9 (0.8–4.3)
2.3 (0.9–6.1)

results. Lack of blinding in trials of fluid infusion and leg

compression increased the risk of bias. The protocol for
many of the trials that compared vasopressors included
Mephentermine

infusion of fluid, which could have affected indirect

0.7 (0.0–17.9)

0.7 (0.0–10.5)
0.8 (0.0–13.3)

calculation of the effects of vasopressor in the network

0.4 (0.0–5.4)
0.3 (0.0–4.6)
0.2 (0.0–2.5)

0.1 (0.0–1.1)
0.2 (0.0–3.4)

meta-analysis. However, we were unable to detect a

difference in the effects of vasopressors between trials that
did or did not infuse fluid. Lack of trials limited the precision
Phenylephrine

0.7 (0.5–0.9)
0.4 (0.2–0.6)

0.2 (0.1–0.2)
0.5 (0.3–0.8)
2.1 (0.2–29.4)

and possibly the accuracy of treatment effect for

0.7 (0.4–1.3)

1.5 (0.3–9.1)

1.4 (0.7–2.8)
1.7 (0.8–3.9)

mephentermine (one trial), angiotensin 2 (three trials) and

metaraminol (five trials).
Our results cannot be reliably extended to women and
11.4 (0.8–168.9)

8.2 (1.3–50.7)

7.7 (3.5–16.9)
9.4 (3.8–23.6)

pregnancies at high risk of morbidity or women having

5.5 (3.4–8.9)

4.1 (2.3–7.1)
3.6 (2.3–5.6)
1.9 (1.1–3.4)

2.6 (1.6–4.2)
0.9 (0.6–1.3)

epidural anaesthesia or general anaesthesia. We did

Control

include trials that combined spinal injection with epidural

catheter, provided no drug was given through the epidural
6.4 (1.0–39.1)

6.0 (2.8–12.8)
7.3 (3.0–18.1)
Co-crystalloid

8.8 (0.6–130.4)

catheter during surgery, which is different to the inclusion

4.3 (2.7–6.7)

3.2 (1.8–5.6)
2.8 (1.8–4.3)

0.7 (0.5–1.0)
2.0 (1.3–3.1)
0.8 (0.5–1.3)

1.5 (1.0–2.3)

criteria used by the Cochrane review [4].

We did not analyse the effect of fluid dose or drug dose
or route of administration and we did not analyse the effect

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Table 2 The number of trials, number of patients, relative rankings for efficacy, GRADE ranking and heterogeneity (Tau2) for all
outcomes.
Number Number Treatment ranked
Outcome of trials of women according to efficacy GRADE Tau2 (95%CI) Comments
Hypotension 105 8262 Metaraminol High to 0.27 (0.13–0.46) Some of the fluid
Norepinephrine moderate treatments
Mephentermine were not blinded.
Angiotensin 2 Ephedrine was the least
Phenylephrine effective vasopressor.
Leg compression
Ephedrine
Colloid before induction
Colloid after induction
Crystalloid after induction
Control
Crystalloid before induction
Nausea and 72 6186 Metaraminol Moderate 0.42 (0.17–0.77) Network inconsistency,
vomiting Angiotensin 2 to lowa, b p = 0.01. Heterogeneity
Phenylephrine among trials might be
Norepinephrine because nausea and
Leg compression vomiting were recorded
Ephedrine and reported differently.
Colloid before induction
Colloid after induction
Crystalloid after induction
Mephentermine
Control
Crystalloid before induction
Reactive 40 3148 Mephentermine Moderatea 0.04 (0–0.73) Few trials with
hypertension Colloid after induction to low mephentermine
Crystalloid after induction and angiotensin
Colloid before induction 2. Mephentermine
Angiotensin 2 was least likely and
Crystalloid before induction metaraminol was most
Leg compression likely to cause reactive
Control hypertension. There
Norepinephrine were
Phenylephrine no significant differences
Ephedrine between phenylephrine,
Metaraminol ephedrine and
norepinephrine.
Fluids were significantly
less likely to cause
reactive hypertension.
Bradycardia 48 3840 Ephedrine Moderatea 0.04 (0–1.2) Bradycardia was
Control significantly
Norepinephrine more common in
Leg compression patients
Crystalloid after induction receiving phenylephrine
Crystalloid before induction compared with
Mephentermine ephedrine or
Colloid before induction norepinephrine.
Angiotensin 2
Colloid after induction
Metaraminol
Phenylephrine

(continued)

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Table 2 (continued)

Number Number Treatment ranked

Outcome of trials of women according to efficacy GRADE Tau2 (95%CI) Comments
a
Tachycardiac 15 1017 Metaraminol Moderate 0.13 (0–2.3) Metaraminol and
Phenylephrine to low. phenylephrine
Angiotensin 2 significantly better than
Norepinephrine ephedrine or crystalloid
Placebo before induction.
Colloid before induction
Ephedrine
Crystalloid before induction
1 min 66 4224 Insufficient data to Low to very 0 (0–0.20) Only 55 events.
Apgar < 7 meaningfully rank lowa Metaraminol
was significantly better
than
crystalloid
after induction.
5 min 77 5738 Insufficient data to Very lowa 0 (0–0.20) Only 23 events: none of
Apgar < 7 meaningfully rank the treatments
were statistically
different
and ranking
was not meaningful.
Umbilical 58 4646 Mephentermine Lowb, d 0.25 (0.14–0.46) The network was
artery pH Angiotensin 2 inconsistent.
Norepinephrine The pH after
Metaraminol vasopressors
Phenylephrine (except for ephedrine)
Leg compression was
Control significantly higher than
Crystalloid after induction after
Colloid after induction fluid infusion.
Ephedrine
Crystalloid before induction
Colloid before induction
a
Rated down for imprecision.
b
Rated down for inconsistency.
c
Insufficient data to rank some treatments.
d
Rated down for indirectness.

of method used to compress the leg. In addition, we did not the range of doses [129]. Further study is needed to
assume equipotent doses were used by the authors of the determine the most effective dose and route of
trials. Currently, there are few reports comparing different administration of drugs that minimise side-effects. We
doses of drugs. A dose-response reduction of hypotension confined our review to drugs for which the mechanism of
has been shown for ephedrine in doses between 5 mg and effect on maternal haemodynamics is known. Other drugs,
30 mg, but there is also an increase in the rate of reactive such as ondansetron, have been studied but their
hypertension [79, 127]. Tanaka et al. found the ED95 for mechanism of haemodynamic action is unclear.
bolus doses of phenylephrine was 120 lg. At this dose, Ondansetron has a proven effect on nausea and vomiting
the rate of hypotension and nausea was 20% and the rate but its effect on haemodynamics is uncertain [130]. Similarly,
of reactive hypertension was 28% [128]. Recently, Xiao prevention of hypotension by glycopyrrolate is uncertain
et al. studied four infusion rates from 0.25 to [131].
1 1
0.625 lg.kg .min . They found a dose-response In conclusion, we found that vasopressors reduced
reduction in the rates of hypotension and reactive episodes of hypotension, nausea and vomiting during
hypertension. There was no difference in the number of scheduled caesarean section in otherwise healthy women
physician interventions needed to treat side-effects whereas crystalloid infusion did not. Metaraminol was the
(hypotension, hypertension, nausea and shivering) through most effective vasopressor and ephedrine was the least

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Fitzgerald et al. | Hypotension and spinal anaesthesia for caesarean section
effective vasopressor. Phenylephrine caused maternal
bradycardia more often than other vasopressors and
ephedrine caused tachycardia more often than other
vasopressors. The clinical condition of neonates was
unaffected by any intervention, but umbilical artery pH was
higher when delivered from mothers treated with
vasopressors. Further study is needed to determine the best
vasopressor doses that reduce episodes of maternal
hypotension and associated side-effects, and the best
preventative strategies in high risk parturients and
neonates.
Acknowledgements
We would like to thank K. Samanian and Dr C. Margarido for
their assistance in translation. We would also like to
acknowledge Dr M. Halpern for his technical assistance. We
registered the protocol for this review with the PROSPERO
International Prospective Register of Systematic Reviews
(CRD42018109818). Funding for this project was provided
by departmental funds. No competing interests declared.
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Supporting Information
Additional supporting information may be found online in
the Supporting Information section at the end of the article.
Table S1. Characteristics of studies.
Table S2. Direct comparisons (Hypotension). All direct
comparisons between treatments shown. The 95%CI and p
value were derived from random effects modelling.
Table S3. Bias for individual studies.
Table S4. Consistency: Comparison of Direct and
Indirect log odds ratio and standard error.
Table S5. Interval plots with OR, 95%CIs and 95%
Predicted Intervals
Table S6–S11. Mean Rank and SUCRA for each
outcome.
Table S12. Sensitivity analysis omitting studies at high
risk for bias. OR and 95%CI, hypotension. OR > 1 favour
row, OR < 1 favours column.
Table S13. Sensitivity analysis, omitting studies at high
risk for bias. SUCRA and mean rank all treatments.
Table S14. Nausea and vomiting. OR and 95%CIs
shown. Bolded comparisons are statistically significant.
Table S15. Reactive hypertension OR and 95%CIs
shown. Bolded comparisons are statistically significant.
Table S16. Maternal bradycardia. OR and 95%CIs
shown. Bolded comparisons are statistically significant.
Table S17. Maternal tachycardia. OR and 95%CIs
shown. Bolded comparisons are statistically significant.
Table S18. Supp umbilical artery pH. Standardised
mean difference and 95%CI shown. Bolded comparisons
are statistically significant.
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