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Articles
Anaesthesia-relatedmaternalmortalityinlow-income
andmiddle-incomecountries:asystematicreviewand
meta-analysis
SohaSobhy*,JavierZamora*,KuhanDharmarajah,DavidArroyo-Manzano,MatthewWilson,RamesanNavaratnarajah,ArriCoomarasamy,
KhalidSKhan,ShakilaThangaratinam
Summary
Background The risk factors contributing to maternal mortality from anaesthesia in low-income and middle-income LancetGlobHealth2016;
countries and the burden of the problem have not been comprehensively studied up to now. We aimed to obtain precise 4:e320–27
estimates of anaesthesia-attributed deaths in pregnant women exposed to anaesthesia and to identify the factors linked SeeCommentpagee290
to adverse outcomes in pregnant women exposed to anaesthesia in low-income and middle-income countries. *Jointfirstauthors
Women’sHealthResearchUnit
(SSobhyMBBS,
Methods In this systematic review and meta-analysis, we searched major electronic databases from inception until
Oct 1, 2015, for studies reporting risks of maternal death from anaesthesia in low-income and middle-income ProfJZamoraPhD,
ProfKSKhanMSc,
countries. Studies were included if they assessed maternal and perinatal outcomes in pregnant women exposed to ProfSThangaratinamPhD),
anaesthesia for an obstetric procedure in countries categorised as low-income or middle-income by the World Bank. MultidisciplinaryEvidence
We excluded studies in high-income countries, those involving non-pregnant women, case reports, and studies SynthesisHub(mEsh)
(ProfJZamora,ProfKSKhan,
published before 1990 to ensure that the estimates reflect the current burden of the condition. Two independent ProfSThangaratinam),Barts
reviewersundertookqualityassessmentanddataextraction.Wecomputedoddsratiosforriskfactorsandanaesthesia- andTheLondonSchoolof
related complications, and pooled them using a random effects model. This study is registered with PROSPERO, MedicineandDentistry,Queen
MaryUniversityofLondon,
number CRD42015015805. London,UK;Clinical
BiostatisticsUnit,Hospital
Findings 44 studies (632556 pregnancies) reported risks of death from anaesthesia in women who had an obstetric RamonyCajal(IRYCIS,
surgical procedure; 95 (32149636 pregnancies and 36144 deaths) provided rates of anaesthesia-attributed deaths as a CIBERESP),Madrid,Spain
proportion of maternal deaths. The risk of death from anaesthesia in women undergoing obstetric procedures was (ProfJZamora,
1·2 per 1000 women undergoing obstetric procedures (95% CI 0·8–1·7, I²=83%). Anaesthesia accounted for 2·8% DArroyo-ManzanoMSc);
NorthwickParkHospital,
(2·4–3·4, I²=75%) of all maternal deaths, 3·5% (2·9–4·3, I²=79%) of direct maternal deaths (ie, those that resulted Harrow,Middlesex,UK
from obstetric complications), and 13·8% (9·0–20·7, I²=84%) of deaths after caesarean section. Exposure to general (KDharmarajahMRCOG);School
anaesthesia increased the odds of maternal (odds ratio [OR] 3·3, 95% CI 1·2–9·0, I²=58%), and perinatal deaths (2·3, ofHealthandRelatedResearch,
UniversityofSheffield,
1·2–4·1, I²=73%) compared with neuraxial anaesthesia. The rate of any maternal death was 9·8 per 1000 anaesthetics Sheffield,UK(MWilsonMD);
(5·2–15·7, I²=92%) when managed by non-physician anaesthetists compared with 5·2 per 1000 (0·9–12·6, I²=95%) BartsHealthNHSTrust,
when managed by physician anaesthetists. Whitechapel,London,UK
(RNavaratnarajahMRCOG);and
SchoolofClinicaland
Interpretation The current international priority on strengthening health systems should address the risk factors ExperimentalMedicine,College
such as general anaesthesia and rural setting for improving anaesthetic care in pregnant women. ofMedicalandDentalSciences,
UniversityofBirmingham,
Funding Ammalife Charity and ELLY Appeal, Bart’s Charity. Birmingham,UK
(ProfACoomarasamyMD)
Correspondenceto:
Copyright © Sobhy et al. Open Access article distributed under the terms of CC BY. ProfKhalidSKhan,Women’s
HealthResearchUnit,
MultidisciplinaryEvidence
Introduction estimates are available of maternal deaths from obstetric SynthesisHub(mEsh),Bartsand
A quarter of a million women die every year during or anaesthesia, or of overall maternal mortality attributable
after pregnancy and childbirth, and 99% of these are from to anaesthesia, in low-income and middle-income TheLondonSchoolofMedicine
1 andDentistry,QueenMary
low-income and middle-income countries. Anaesthetic countries. Factors that contribute to maternal and UniversityofLondon,
interventions are an integral part of emergency obstetric perinatal mortality in women exposed to anaesthesia in LondonE12AD,UK
care. However,thereisapaucityofphysiciananaesthetists low-income and middle-income countries need to be k.s.khan@qmul.ac.uk
in many of the poorest countries, with an estimated ratio identified.
of one physician anaesthetist per million women. There Individual studies have provided varied and imprecise
is also a lack of infrastructure, drugs, and equipment. results, with up to a fifth of all direct maternal deaths
6
The need for safe, affordable surgery and anaesthesia attributed to anaesthesia-related procedures. Systematic
in low-income and middle-income countries is reviews report estimates of complications in all
recognised, with perioperative death as a global safety individuals exposed to anaesthesia, not specifically in
4 7
indicator. In high-income countries, very few maternal pregnant women. We undertook a systematic review to
deaths are attributed to anaesthesia. 5However, no robust obtain precise estimates of anaesthesia-attributed deaths
www.thelancet.com/lancetgh Vol 4 May 2016 e320 Articles
Researchincontext
Evidencebeforethisstudy anaesthesiatooverallmaternalmortality,particularlyindeaths
Existingsystematicreviewsonglobalcausesofmaternaldeath relatedtocaesareansection(13·8%).Weidentifiedtherisk
havenotpreviouslyassessedtheroleofobstetricanaesthesia. factorsformaternaldeathsrelatedtoanaestheticexposure
Arecentsystematicreviewofanaesthesia-relatedmortalityin suchasgeneralanaesthesiaandruralsetting.Weprovided
low-incomeandmiddle-incomecountriesfocusedonriskstothe estimatesofdeathrelatedtoanaesthesiaaccordingtothetype
generalpopulation,andnotspecificallytopregnantwomen, ofanaestheticpractitionerinlow-incomeandmiddle-income
whoareathighrisk.Individualobservationalstudiesvaryintheircountries.Abouttwo-thirdsofreporteddeathsfrom
estimatesforanaesthesia-relatedmaternaldeathsinlow-income anaesthesiawereduetopreventablecomplicationsrelatedto
andmiddle-incomecountriesandrelevantriskfactors. airwaymanagementandpulmonaryaspiration.
Addedvalueofthisstudy Implicationsofalltheavailableevidence
Wehaveprovidedrobustestimatesofriskofanaesthesia- Ongoingandfutureeffortstoimprovethesafetyofobstetric
attributedmaternaldeathinpregnantwomenwhohave anaesthesiainlow-incomeandmiddle-incomecountries
obstetricproceduresinlow-incomeandmiddle-income shouldtargettheriskfactorsidentifiedinourreviewtoimprove
countriesoverall,andinvariousgeographicregionsgroupedby training,infrastructure,andprovisionofresources.
incomestatus.Wehavehighlightedthecontributionof
in pregnant women exposed to anaesthesia and to countries, those including non-pregnant women, case
identify the factors linked to adverse outcomes in reports, and studies published before 1990 to ensure that
pregnant women exposed to anaesthesia in low-income the estimates reflect the current burden of the condition.
and middle-income countries. We defined anaesthesia-attributed complications as
those that occurred directly as a result of anaesthesia (as
Methods established by the primary study authors), and
Searchstrategyandselectioncriteria anaesthesia-related outcomes as those that were directly
In this systematic review and meta-analysis, we used a or indirectly associated with anaesthesia. Maternal
prospective protocol (PROSPERO CRD42015015805) in 8 mortality was defined as the death of a woman during
line with current recommendations, and reported as per pregnancy or at any time until 42 days after delivery,
9
the PRISMA guidelines. irrespective of the duration and site of the pregnancy, as
We searched MEDLINE, Embase, Scopus, the defined by WHO. This definition included deaths from
Cumulative Index to Nursing and Allied Health any cause related to or aggravated by pregnancy and its
Literature (CINAHL), Web of Science, and the WHO management, but not from accidental or incidental
11
Library and Global Index Medicus from inception until causes. Direct maternal deaths were those that resulted
Oct 1, 2015. We used MeSH headings, text words, and from obstetric complications; indirect maternal deaths
word variants for “pregnancy” and combined them with from disorders aggravated by physiological effects of
terms for low-resource countries such as “low-income” pregnancy, by pre-existing disease, or by diseases that
11
or “middle-income” or “developing country”. We developed during pregnancy. We grouped direct and
combined these with terms related to anaesthesia and indirect maternal deaths together as overall maternal
surgery such as “an(a)esthesia” or “an(a)esthetist” death.
or “nurse an(a)esthetist” or “c(a)esarean section” Perinatal death included any fetal death that occurred
SeeOnlineforappendixppendix p 1). There were no language restrictions. after 28 completed weeks of gestation, stillbirths, and
Additionally, we searched the reference lists of the earlyneonataldeathsupto1weekafterbirth. Weclassed
included studies and relevant reviews for eligible studies.Apgar scores as low if they were less than or equal to 7 at
We selected studies in two stages. In the first stage, we 1 and 5 min. We accepted the primary study authors’
screened the titles and abstracts of all citations for definitions for maternal and fetal complications such as
potentially relevant papers. In the second, we assessed post-partum haemorrhage, cardiac arrest, and admission
the full texts of the retrieved papers. Two independent to the intensive care unit.
reviewers (SS, KD) selected the papers against
prespecified inclusion criteria. Any discrepancies were Studyqualityassessmentanddataextraction
resolved after discussion with a third reviewer (ST). Two independent reviewers (SS and KD) undertook
Studies were included if they assessed maternal and study quality assessment and data extraction, and any
perinatal outcomes in pregnant women exposed to discrepancies were resolved with input from the third
anaesthesia for an obstetric procedure in countries reviewer (ST). For studies of rates of anaesthesia-
categorised as low-income and middle-income countries attributed maternal death, we assessed the following
by the World Bank. 1We excluded studies in high-income criteria: representativeness of the population, sample
e321 www.thelancet.com/lancetgh Vol 4 May 2016 Articles
selection, outcome assessment, adequacy of sample size, middle, or upper middle), setting (urban or rural), and year
and ascertainment of the cause of maternal death to of publication (before and after 2000). We assessed the
anaesthesia. 13,We deemed a study to be adequate for effectsofstudyquality(loworhigh)anddesign(prospective
representativenessifitincludedinstitutionsfromvarious or retrospective) on the maternal mortality rates. We used
settings such as rural and urban hospitals in a region or multilevelrandomeffectslogisticmodels,andincludedthe
country, and to be inadequate if it included only one above factors. The meta-regressions were run as separate
hospital or unit. We classed sample selection as adequate univariate analyses. We did sensitivity analysis by limiting
if all deliveries or maternal deaths were included, and as our findings to only direct maternal deaths. We also
inadequate if a particular group of women were excluded. assessed the proportion of all maternal deaths during or
We deemed outcome assessment to be adequate when a after caesarean section attributed to anaesthesia.
confidential inquiry, verbal autopsy, or professional panel We assessed for publication bias and the effects of small
established the cause of death and inadequate when studies using funnel plots, and Begg’s 18and Egger’s
19 20
there was no special effort or use of registry data from tests. All analyses were done with Stata (version 13).
only one source. An adequate sample size included data
for at least 10000 births. We regarded studies that Roleofthefundingsource
accounted for the cause of death in at least 95% of The funder of the study had no role in the study design,
maternal deaths to be adequate for ascertainment of data collection, data analysis, data interpretation, or
cause of death. A study was classed as hig13quality if writing of the report. The corresponding author had full
three of the above five criteria were met. access to all the data in the study and had final
For comparative studies, we used the Newcastle-Ottawa responsibility for the decision to submit for publication.
scaletoestablishtheriskofbiasinselection,comparability
of cohorts, and outcome assessment. Studies that scored Results
four stars for selection, two stars for comparability, and From 11782 citations, we included 140 studies. 44 studies
three stars for ascertainment of the outcome were (632556 pregnancies) provided data for risk of death from
regarded to have a low risk of bias. Studies with two or anaesthesia in women undergoing obstetric surgical
three stars for selection, one for comparability, and two procedures, and 95 studies (32149636 pregnancies,
for outcome ascertainment were considered to have a 36144 deaths) reported anaesthesia-attributed maternal
medium risk of bias. We deemed any study with a score mortality as a proportion of maternal deaths. 25 studies
of one for selection or outcome ascertainment, or zero for
15
any of the three domains, to have a high risk of bias. 11782citationsidentified
To compute corresponding proportions for individual 11722citationsidentifiedfromelectronicdatabases
studies, we extracted data for the number of women 60citationsidentifiedthroughreferencesand
othersources
exposed to anaesthesia, total and direct maternal deaths,
anddeathsduringoraftercaesareansection.Weobtained
information about the number of events (anaesthesia- 11312articlesexcluded
1450duplicates
related maternal death and pregnancy complications) in 9862withexclusioncriteria
women exposed and unexposed to risk factors such as
type of anaesthesia (neuraxial or general), setting (urban 470citationsincludedforfulltextreview
or rural), and practitioner (physician or non-physician).
Dataanalysis 330studiesexcluded
We computed odds ratios for various risk factors and 103notprimarystudies
anaesthesia-related complications in individual studies, 10systematicreviews
16 93narrativereviews,
and pooled them using a random effects model. We commentary
used Peto odds ratios when the numbers of events were 74inappropriateexposuresns
too few. We assessed heterogeneity with the I² statistic. 75inappropriateoutcomes
6articlesnotavailable
When comparative data were not available, we reported
the proportion of complications for each risk factor
separately, and provided summary estimates.
140studiesincluded
Summary rates of risk of death from anaesthesia in 25studies*(4149pregnancies)of
pregnancy were reported as deaths per 1000 women 44studies*(632556pregnancies)ofcomplications
undergoing obstetric procedures. We also reported anaesthesia-attributeddeathinpregnantwomen
undergoingsurgicalprocedure
anaesthesia-attributeddeathsasaproportionofallmaternal 95studies*(32149636pregnancies)ofratesof
deaths (direct and indirect). We did subgroup analysis and anaesthesia-attributedmaternalmortality
meta-regression for the following factors that were
prespecified before the analysis: geographical location Figure1:Studyselection
(World Bank classification), country income (low, lower *Somestudieshavebeenusedinmorethanonecategory.
www.thelancet.com/lancetgh Vol 4 May 2016 e322 Articles
The risk of maternal death directly attributed to
A
Representativenessofpopulation 49 46 anaesthesia after obstetric procedures was reported in
44 studies from 15 low-income and middle-income
Sampleselection 85 7 3 countries, which were grouped into the following
regions: sub-Saharan Africa (n=38 studies), south Asia
Outcomesassessment 13 23 59 (n=4), and east Asia and the Pacific (n=2). Most studies
Samplesize>1000 74 17 4 were facility based (42 of 44) and in nearly three-quarters
of studies (31 of 44), women were managed in an urban
<5%ofmaternaldeathsunaccounted 59 23 13
setting. Of the 95 studies (31 countries) that reported
Overallriskofbias 65 30 anaesthesia-attributed mortality as a proportion of all
0 20 40 60 80 100 maternal deaths, 52 provided facility-based data, and
29 provided countrywide data. In 45 studies, women
Proportionofstudies(%)
Lowriskofbias Highriskofbias Unclearriskofbias weremanagedinanurbansetting(appendixp3andp20).
Studies compared the odds of adverse maternal and
B fetal outcomes for risk factors such as the type of
Selection 11 12 2 anaesthesia (25 studies, 414069 pregnancies), setting (one
Comparability 4 1 20 study, 8070 pregnancies), and anaesthesia provider (one
study, 8070 pregnancies). Rates of any maternal death in
Ascertainmentofoutcome 14 11 anaesthesia administered by a non-physician were
assessed in eight studies (27714 pregnancies), and by a
0 20 40 60 80 100
Proportionofstudies(%) physician anaesthetist in six studies (20313 pregnancies).
Both high-risk and low-risk women were studied, and
Lowriskofbias Mediumriskofbias Highriskofbias
caesarean section was the most common surgical
Figure2:Riskofbiasassessment procedure. Studies ascertained the cause of maternal
(A)Studiesofanaesthesia-attributedmaternalmortalityrates.(B)Studiesevaluatinganaesthesia-relatedrideaths and exposure to anaesthesia from theatre records,
factorsandmaternalandfetalcomplications.
patient notes, facility and countrywide maternal death
reviews, and verbal autopsies.
Number Number Numberof Maternal 95%CI I2 Meta- 65 (68%) of 95 included studies of anaesthesia-
of of women deathsper regression attributed maternal mortality had low risk of bias. About
studies deaths undergoing 1000women pvalue
surgical undergoing half had high risk of bias for representativeness of the
population and setting, and 90% had adequate sample
procedures surgery
Overall 44 264 632556 1·2 0·82–1·7 83% .. selection,andaquarterhadhighriskofbiasforoutcomes
reporting (figure 2A). Three-quarters of all studies had
WorldBank
regions adequate sample size and about two-thirds adequately
accounted for maternal deaths (figure 2A).
SouthAsia 4 16 37132 0·34 0·13–0·90 71% 0·004
Sub-Saharan 38 237 567431 1·5 1·1–2·2 85% Four-fifths of studies of risk factors for complications
Africa in women exposed to obstetric anaesthesia had high risk
EastAsiaand 2 11 27993 0·40 0·22–0·71 .. of bias (figure 2B). Nearly half of the included studies
Pacific had low risk of bias for study selection; a fifth of studies
Year
had low or medium risk of bias for comparability of the
<2000 17 55 49232 1·2 0·76–1·7 50% 0·74 cohorts, and more than half of studies had low risk of
≥2000 27 209 583324 1·2 0·74–2·1 86% bias for ascertainment of the outcome (figure 2B).
Setting In women undergoing an obstetric procedure, the risk
Urban 31 85 72203 1·5 1·0–2·3 67% 0·02 ofdeathattributedtoanaesthesiawas1·2per1000women
Rural 1 1 69 14·5 0·00–42·7 .. (95% CI 0·82–1·7, I²=83%), with the highest rates in
Both 12 178 560284 0·67 0·37–1·2 89% sub-Saharan Africa (1·5 per 1000 women, 1·1–2·2,
Countryincome I²=85%; table 1). The appendix provides estimates for
Low 13 53 33431 1·5 0·84–2·8 63% 0·003 individual countries (appendix p 14). Caesarean section
Lowermiddle 27 90 80295 1·4 0·92–2·2 72% wasthesurgicalproceduredonein37studies,comprising
97% (611291/632556) of the included women. Seven
Uppermiddle 4 121 518830 0·23 0·20–0·28 24%
studies either reported other obstetric procedures (eg,
Table1:Mortalityratesfromanaesthesiainwomenundergoingobstetricsurgicalproceduresin cervical cerclage, laparotomy for ectopic pregnancy,
low-incomeandmiddle-incomecountries
dilatation and curettage, and removal of retained
placenta), or failed to specify the type of obstetric surgery.
(414069 pregnancies) assessed the association between Subgroup analysis and meta-regression showed a
anaesthesia-related risk factors and complications in significant difference between regions (p=0·004). The
women undergoing obstetric procedure (figure 1). risks of death from anaesthesia were higher in rural than
e323 www.thelancet.com/lancetgh Vol 4 May 2016 Articles
urban settings (p=0·02), and in low-income and lower- Number Numberof Total Anaesthesia-95%CI I Meta-
middle-income than upper-middle-income countries ofstudies deathsfrom number attributed regression
(p=0·003). There were no differences for year of
anaesthesia of mortality pvalue
publication (p=0·74; table 1). maternal
Anaesthesia was reported as the main cause of death in deaths
2·8% (95% CI 2·4–3·4, I²=75%) of all maternal deaths Overall 95 987 36144 2·8% 2·4–3·4 75%
(direct and indirect), with the highest rates in Middle WorldBank
regions*
East and north Africa (6·2%, 3·9–9·7, I²=86%), and the
lowest in east Asia and Pacific (1·5%, 0·9–2·3, I²=63%; Sub-Saharan 50 675 24873 2·9% 2·3–3·6 61% 0·004
Africa
table2).Theappendixprovides estimates from individual SouthAsia 18 89 4317 2·4% 1·5–3·8 79%
countries (appendix p 14). Anaesthesia was reported as
the cause of death in 3·5 % (95% CI 2·9–4·3, I²=79%) of MiddleEast 10 136 2555 6·2% 3·9–9·7 86%
andnorth
direct maternal deaths (76 studies, 20780 deaths, Africa
26750727 pregnancies), and 13·8% (95% CI 9·0–20·7, EastAsiaand 9 49 3276 1·5% 0·9–2·3 63%
Pacific
I²=84%) of all deaths that occurred during or after
caesarean section (31 studies, 1028 deaths; Europeand 4 14 455 3·0% 1·3–6·7 64%
centralAsia
appendix pp 17–18). LatinAmerica 4 24 668 3·6% 2·4–5·3 0%
Meta-regression showed a significant difference in
the overall anaesthesia-attributed mortality rates by andthe
Caribbean
geographical region (p=0·004) and year of publication Year
(p=0·002). We noted no significant differences by setting,
<2000 28 250 6589 4·1% 3·0–5·5 77% 0·002
study design, income level, or study quality (table 2). >2000 67 737 29555 2·4% 1·9–2·9 72%
Compared with neuraxial anaesthesia, administration
Setting 0·29
of general anaesthesia tripled the odds of maternal death Rural 8 14 894 1·9% 0·9–3·8 38%
(OR 3·3, 95% CI 1·2–9·0, I²=58%), with mortality rates Urban 45 245 7987 3·3% 2·5–4·2 72%
of5·9per1000and1·2per1000forgeneralandneuraxial
Both 42 728 27263 2·5% 1·9–3·4 80%
anaesthesia, respectively. General anaesthesia also Studydesign 0·68
doubled the odds of perinatal death (odds ratio [OR] 2·3,
Prospective 9 35 1819 2·5% 1·1–5·6 77%
95% CI 1·2–4·1, I²=73%) compared with neuraxial Retrospective86 952 34325 2·9% 2·4–3·4 75%
anaesthesia.Therewasanincreaseinothercomplications
Countryincome 0·57
such as post-partum haemorrhage (OR 9·4, 95% CI Low 17 89 3171 2·6% 1·9–3·6 35%
5·1– 17·2, I²=65%), low Apgar score at 1 min (6·3,
2·9–13·6, I²=64%) and at 5 min (3·2, 2·3–4·4, I²=0%) Lowermiddle 38 199 8130 2·6% 1·9–3·6 78%
Uppermiddle 40 699 24843 3·1% 2·4–4·1 78%
with general compared to neuraxial anaesthesia
(figure 3). There were no differences in cardiac arrest Studyquality 0·12
High 65 859 32099 2·6% 2·1–3·2 79%
(OR 3·6, 95% CI 0·6–20·6, I²=71%) between the two
groups. Management in a rural setting was associated Low 30 128 4045 3·6% 2·6–4·8 59%
with an increase in the odds of maternal death (2·1, *Basedon2015WorldBankdata.
1·2–3·7) compared with an urban setting. 21
No direct comparative data were available for physician Table2:Anaesthesia-attributedmaternalmortalityinlow-incomeandmiddle-incomecountries
versus non-physician providers of anaesthetic care. The
overall risk of any maternal death when non-physicians ventilation difficulties, and hypoxia; 38 (31%) from
provided care was 9·8 per 1000 (95% CI 5·2–15·7, pulmonary aspiration; 34 (27%) from issues related to
I²=92%), and the rates of anaesthesia-attributed maternal staff competency, poor pre-assessment, intraoperative
deaths was 1·8 per 1000 (0·25–4·3, I²=85%). The monitoring,andequipmentfailure.Othercausesincluded
corresponding estimates for physician anaesthetists were cardiac arrest at induction or during the procedure (seven
5·2 per 1000 (0·9–12·6, I²= 95%) for any maternal death, [6%]), high spinal anaesthesia (eight [6%]), and drug
and 1·3 per 1000 (0·16–3·1, I²=79%) for anaesthesia- overdose or adverse reactions (seven [6%]).
attributed maternal deaths, respectively (appendix p 13). With regard to publication bias and small studies
One study reported an increase in the odds of maternal effects, a funnel plot of studies reporting risk of death
deaths (OR 2·7, 95% CI 1·6–4·6) when maternal care was from anaesthesia in women undergoing obstetric
managed by non-physician anaesthetists without formal procedure showed significant asymmetry (Egger’s test
structured training compared to those with training. 21 p=0·001), although Begg’s test failed to confirm this
The underlying causes were reported for 124 maternal effect. There was no asymmetry in a funnel plot of
deaths (24 studies). 56 (45%) of all deaths resulted from studies that reported anaesthesia-attributed mortality as
airway complications such as difficult or failed tracheal a proportion of all maternal deaths (Egger’s and Begg’s
intubation, oesophageal intubation, bronchospasm, tests p>0·05; appendix p 19).
www.thelancet.com/lancetgh Vol 4 May 2016 e324 Articles
Number GeneralanaesthesiaRegionalanaesthesia OR(95%CI) I²
ofstudies
Number Number Number Number
ofevents ofwomen ofevents ofwomen
Maternaldeath 9 138 23256 25 21035 3·3(1·2–9) 58%
Perinataldeath 5 860 4882 181 3459 2·3(1·2–4·1) 73%
Post-partumhaemorrhage 4 183 2923 302 67694 9·4(5·1–17·2)65%
Intensivecareunitadmissionofmother 319 14243 126 286682 34·4(8·9–133·2)5%
Cardiacarrest 4 21 8234 10 15130 3·6(0·62–20·6)71%
LowApgarscoreat5min 7 282 909 62 919 3·2(2·3–4·4) 0%
LowApgarscoreat1min 6 254 303 57 395 6·3(2·9–13·6)64%
0·1 1 10 100
FavoursgeneralFavoursregional
anaesthesia anaesthesia
Figure3:Maternalandfetalcomplicationsinwomenexposedtogeneralversusneuraxialanaesthesiainlow-incomeandmiddle-incomecountries
Discussion higher than current estimates because of scarce data from
Anaesthesia contributes disproportionately to maternal these low-income and middle-income countries with high
mortality in low-income and middle-income countries. maternal mortality and poor health-care resources. We
About one in seven maternal deaths during or after used the 2015 World Bank atlas for classification of a
caesarean section was due to anaesthesia, a very high country’s income status, and adjustment for year of
5
mortality rate compared with developed countries. publication could have resulted in some differences in
Exposure to general anaesthesia, and administration of classification. We noted significant heterogeneity in our
anaesthesia by non-physicians, especially those with no findings despite adjusting for various factors because of
formal training, were major risk factors for maternal variations in the characteristics of population, setting, type
deaths from anaesthesia. We have mapped the safety of of anaesthesia, availability of caesarean section, and
obstetric anaesthesia across various economic regions and provider. Few studies provided detailed reports on the
individual countries. Most studies were from the sub- underlying cause of death from anaesthesia.
Saharan African region, which also had the highest risk of The asymmetry recorded in the funnel plot was the
deaths from anaesthesia in women undergoing surgery. result of high rates of maternal deaths in small studies
Ours is the first review, to our knowledge, to making them more likely to be published, similar to the
comprehensively assess the risk factors for maternal and effect reported in many non-comparative reviews on
perinatal deaths and complications from anaesthesia in proportions. 23 This asymmetry could have slightly
low-income and middle-income countries, and the overestimated the recorded maternal death rates.
overall risk of maternal death from anaesthesia. Our However, the magnitude of the bias is probably small in
estimates of the risk in low-income and middle-income view of the low weight of these studies in the analysis.
countries are significantly higher than those reported in Pregnant women requiring general anaesthesia need
high-income countries such as the USA, where the case tracheal intubation to ensure the airway is secure from
fatality rate from general and regional anaesthesia given aspiration. Compared with the general surgical
for caesarean section were 6·5 and 3·8 per million population, pregnant women are at increased risk of
22
anaesthetics, respectively. We assessed the extent of the complications from general anaesthesia, with eight times
problem in detail by assessing rates of death in women higher risk of failed intubation and its associated
who had surgery, and as a proportion of any, direct, and hazards. 24,2Our findings support existing data for the
caesarean-section-related maternal deaths. We reported role of airway complications, and pulmonary aspiration
the effects of study quality on mortality estimates. We of gastric contents as major causes of death from
26
looked for variations in anaesthesia-attributed maternal anaesthesia, and the need for specific training.
mortality rates according to economic regions, individual The increased mortality and morbidity that we
countries, setting, year, and anaesthesia provider. identified with general anaesthesia could be due to the
Our findings were limited by the differences in quality following reasons: inadequate training and resources,
and reporting of outcomes in the studies. Studies focused poor general condition of the mother, or concomitant
mainly on assessing the risks associated with type of complications such as post-partum haemorrhage. The
anaesthesia, and less on other factors, which limited our low Apgar scores associated with general anaesthesia
synthesis, and we could only provide rates for these risk exposure could be indicators of neonatal and anaesthetic
factors separately. Fewer studies were published in low- facilities, including limited access to modern, volatile
income countries that are outside sub-Saharan Africa. The anaesthetic agents that minimise fetal respiratory
27
actual rates of anaesthesia-attributed deaths are probably depression. The increased blood loss associated with
e325 www.thelancet.com/lancetgh Vol 4 May 2016 Articles
exposure to general anaesthesia is similar to the findings MW provided expert anaesthetic advice. SS and ST prepared the initial
of the Cochrane review, which reported higher blood loss drafts of the manuscript, with additional input from KSK, AC, MW, and RN.
with general than regional anaesthesia in pregnant All authors contributed to the drafts and final version of the manuscript.
women undergoing caesarean section. 28 Declarationofinterests
In high-income countries such as the USA, no We declare no competing interests.
Acknowledgments
measured differences were recorded in anaesthetic
complications between physician and non-physician This study was funded by Ammalife Charity (Registered UK Charity
29–31 1120236) and ELLY Appeal, Bart’s Charity (Registered UK Charity
anaesthetists. However, compared with the rigorous 212563). We thank Angela Enright, Clinical Professor of Anaesthesia at
additional training provided to non-physician the University of British Columbia, for her input into the report.
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