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192]

Review Article

Anaesthesia for non-obstetric surgery during

pregnancy

Address for correspondence: Madhusudan Upadya, PJ Saneesh1

Dr. Madhusudan Upadya, Department of Anaesthesia, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India,
Department of Anaesthesia, 1
Department of Anaesthesia, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman
Kasturba Medical
College Hospital, Attavar,
Mangalore - 575 001, ABSTRACT
Karnataka, India.
E-mail: madhusudan.upadya@
Non-obstetric surgery during pregnancy posts additional concerns to anaesthesiologists. The
manipal.edu
chief goals are to preserve maternal safety, maintain the pregnant state and achieve the best
possible foetal outcome. The choice of anaesthetic technique and the selection of appropriate
anaesthetic drugs should be guided by indication for surgery, nature, and site of the surgical
Access this article online procedure. Anaesthesiologist must consider the effects of the disease process itself and inhibit
Website: www.ijaweb.org uterine contractions and avoid preterm labour and delivery. Foetal safety requires avoidance of
potentially dangerous drugs and assurance of continuation of adequate uteroplacental perfusion.
DOI: 10.4103/0019-5049.179445
Until date, no anaesthetic drug has been shown to be clearly dangerous to the human foetus.
Quick response code
The decision on proceeding with surgery should be made by multidisciplinary team involving
anaesthesiologists, obstetricians,surgeons and perinatologists. This review describes the general
anaesthetic principles, concerns regarding anaesthetic drugs and outlines some specific conditions
of non-obstetric surgeries.

Key words: Anaesthesia, foetal development, non-obstetric surgery, pregnancy, teratogenicity

INTRODUCTION appropriate changes in the management plans by the

anaesthesiologist or intensivist. In the largest single
Anaesthesia for non-obstetric procedures is frequently series exploring incidental surgeries during pregnancy,
needed for maternal procedures like cervical encirclage, trimester-wise breakup is reported to be 42%, 35% and
as well as foetal procedures like ex utero intrapartum 23% during the first, second and third, respectively.[5]
treatment, at varying times during pregnancy and
even for in vitro fertilisation procedures or assisted PRINCIPLES OF ANAESTHETIC MANAGEMENT
reproductive techniques. When pregnant patients
require surgery the ‘two-in-one package’, comprising To ensure maternal safety and to maintain the pregnant
of the patient herself and the unborn foetus in utero, state, in-depth understanding of the physiological
presents substantial anaesthetic challenges. Currently, changes and pharmacological adaptations to pregnancy
surgical mortality is not significantly greater in is required. Avoidance of potentially dangerous
women who are pregnant compared to those that are
drugs at critical times during foetal development and
not.[1] In addition to preserving maternal safety, our
maintenance of adequate uteroplacental perfusion
goals extend to maintaining the pregnant state and
are imperative for foetal safety. More importantly,
achieving the best possible foetal outcome.
This is an open access article distributed under the terms of the Creative
The estimated incidence of pregnant women requiring Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
non-obstetric surgery is around 1–2%.[2] Appendicitis, author is credited and the new creations are licensed under the identical terms.
ovarian disorders (torsion or neoplasm) and trauma
For reprints contact: reprints@medknow.com
constitute the most common non-obstetric conditions
requiring surgery during pregnancy. Obstetric How to cite this article: Upadya M, Saneesh PJ. Anaesthesia
patients presenting for neurosurgery[3] or admitted in for non-obstetric surgery during pregnancy. Indian J Anaesth
intensive care unit[4] for various indications require 2016;60:234-41.

234 © 2016 Indian Journal of Anaesthesia | Published by Wolters Kluwer ‑ Medknow

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Upadya and Saneesh: Non-obstetric surgery during pregnancy

the anaesthesiologist must consider the effects of the Table 1: The key anaesthetic concerns for non‑obstetric
disease process itself, inhibit uterine contractions and surgery during pregnancy
avoid preterm labour and delivery. The key anaesthetic Anaesthetic concern Brief description
Maternal safety Physiological changes of pregnancy
concerns may be summarised as given in Table 1.
Conditions compelling surgery
during pregnancy
Maternal safety Foetal safety Placental transfer of drugs
According to American College of Obstetricians and Issue of teratogenicity
Gynecologists’ Committee on Obstetric Practice, Timing of exposure
regardless of trimester, pregnant woman should not Duration/dosage of exposure
be denied indicated surgery. The choice of anaesthetic FDA pregnancy category
Individual anaesthetic drugs
technique(s), and the selection of appropriate drugs of
Maternal factors leading to foetal
anaesthesia should be guided by maternal indications compromise
for surgery and the location of the surgical procedure. Maternal hypoxia
Resuscitation, if required, should be vigorously Maternal hyper/hypocarbia
performed following the standard advanced life Changes in uterine blood flow
Avoidance and/or treatment of Identification
support or advanced trauma life support protocols,
preterm labour and delivery Management
with the addition of left lateral tilt to avoid supine FDA – Food and Drug Administration
hypotension.
Placental transfer of drugs
Rapid-sequence intravenous induction and intubation, The placental drug transfer depends on various
with effective cricoid pressure, should be preceded by factors. High lipid solubility allows the rapid transfer,
meticulous pre-oxygenation with 100% oxygen for but may result in trapping of the drug in the placenta.
5 min. However, in cases of failed intubation, laryngeal Protein binding has a variable effect depending on the
mask airway has been used to ventilate successfully particular drug and protein interaction.
and safely in the reverse Trendelenburg’s position for
brief periods. As changes in maternal position can The drugs crossing placenta may be categorised into
have profound haemodynamic effects, positioning three types. In type 1 (e.g., thiopental), complete
during anaesthesia should be carried out slowly. transfer occurs with equilibrating concentrations in
maternal and foetal blood. In type 2 (e.g., ketamine),
The effects of light general anaesthesia and its the drug reaches a higher concentration in
associated catecholamine surge with resulting foetal blood compared to maternal blood. In
impaired uteroplacental perfusion are considerably type 3 (e.g., succinylcholine), only minimal amount
more dangerous to foetus. Positive pressure ventilation reaches the foetal blood.
should be used with care and end-tidal carbon dioxide
levels should be maintained within the limits. Since The mechanism of placental drug transfer may be
there is a good correlation between end-tidal CO2 (i) simple diffusion e.g., paracetamol, midazolam;
(ETCO2) and PaCO2 in pregnancy, ETCO2 can be used (ii) facilitated diffusion e.g., glucocorticoids,
to guide ventilation in pregnant patients.[6] Patients cephalosporins; (iii) active transport e.g., dopamine,
should be extubated fully awake as the risk of aspiration norepinephrine; or (iv) pinocytosis. Table 2 depicts
persists until protective airway reflexes have returned. the commonly used drugs and their placental transfer
characteristics.
Foetal safety
Depending on the dose administered, the timing of Issue of teratogenicity
exposure with respect to development, and the route A teratogen is defined as a substance that causes
of administration of any drug given during pregnancy an increase in the incidence of a particular defect
can potentially jeopardise the development of the in a foetus that cannot be attributed to chance. The
foetus. Until date, no anaesthetic drug has been proven teratogen must be given in a sufficient dose for a
to be clearly hazardous to the human foetus. It may substantial period of time at a critical developmental
be noted that no animal model perfectly simulates point to produce the defect.
human gestation and a randomised trial on pregnant
patients in this regard would be definitely unethical. When considering the possible teratogenicity of
Hence, definitive evidence seems elusive. various anaesthetic agents, several important points

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Table 2: The placental transfer characteristics of commonly used drugs

Drug Properties Placental transfer Remarks
Induction agents
Thiopental Highly lipid soluble, weak acid +++ Quickly cleared by neonate after delivery
Propofol[7] Lipid soluble +++ Transient depression of Apgar score and
neurobehavioral effects in neonate
Ketamine Weak base ++++ F/M ratio 1.26 occurs within 2 min of intravenous bolus
Inhalation agents
Volatile anaesthetics[8,9] Highly lipid soluble; low +++ Greater sedative effect on neonate if dose‑delivery
molecular weight interval is prolonged
Nitrous oxide[10] ++ Possible diffusion hypoxia in neonate
Opioids
Morphine Less lipid soluble; but low ++
protein‑binding
Fentanyl Lipid soluble +++
Pethidine Only 50% plasma protein bound ++ Prolonged neonatal depression due to increased half‑life
of meperidine and its metabolite ‑ normeperidine
Remifentanil[11] + No adverse fetal effects as rapidly metabolised by fetus
Naloxone +++ Though short‑term safety of naloxone is well
documented, it should be used only in cases of
absolute or relative maternal opioid overdose
Benzodiazepine Highly lipid soluble ++ More neonatal depression; midazolam ‑ less placental
transfer than diazepam
NM blockers Large molecules; poorly lipid ‑ No significant clinical effects on foetus
soluble; highly ionised
Anticholinergics
Atropine Lipid soluble; tertiary amine ++
Glycopyrrolate Fully ionised; quaternary ‑
ammonium compound
Neostigmine Quaternary ammonium +++ May cause foetal bradycardia; hence it is better to add
compound; but a small molecule atropine to neostigmine in incidental surgery during
pregnancy
Local anaesthetics
Lignocaine Less lipid soluble; low protein ++ Can accumulate in the foetus due to ‘ion trapping’ if the
binding foetus becomes acidotic
Bupivacaine; ropivacaine Highly lipid soluble; but high ++
protein binding
F/M – Foetal/maternal; NM – Neuromuscular

must be kept in mind. First, the background incidence Food and drug administration pregnancy risk
of congenital anomalies in humans is approximately categories
3%. Second, physiologic derangements such as The Food and Drug Administration (FDA) final rule
hypoxaemia, hypercarbia, stress and hypotension may requires the removal of the pregnancy categories A,
be teratogenic themselves. These problems can occur B, C, D and X from all human prescription drug and
during anaesthesia and surgery and sometimes exist biological product labelling.[14] The new regulation
pre-operatively. requires that the labeling includes a summary of the
risks of using a drug during pregnancy and lactation,
As early as 1960s, Tuchmann-Duplessis[12] observed a discussion of the data supporting that summary, and
that major congenital malformations were most relevant information to help health care providers
likely to occur from exposures between 2 weeks make prescribing decisions and counsel women about
and 2 months of gestation. During the first 15 days the use of drugs during pregnancy and lactation.
of human gestation, the embryo is typically
aborted or preserved fully intact (an all-or-nothing FDA appeals healthcare professionals to continue
phenomenon). Among the multitude of case–control to follow the existing recommendations in
studies, rather than excess birth defects, most have current drug labels regarding the use of analgesics
shown a small increase in the risk of miscarriage or during pregnancy. Current drug labels state that
preterm delivery.[1,5,13] pregnant women should not use non-steroidal anti-

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inflammatory drugs (NSAIDs) in their third trimester Maternal factors linked to foetal compromise
of pregnancy because of the risk of premature closure Since autoregulation is absent for the uteroplacental
of the ductus arteriosus in the foetus. FDA evaluated circulation, any reduction in maternal arterial
research studies published in the medical literature pressure can compromise uteroplacental blood flow
and determined they are too limited to make any leading to foetal ischaemia. Therefore, except under
recommendations at this time. unusual circumstances such as severe maternal
cardiac or renal disease, the intravenous fluid
Teratogenicity of common anaesthetic drugs administration can be liberal. Both ephedrine and
N2O inhibits methionine synthetase, an enzyme phenylephrine are currently considered safe and
necessary for DNA synthesis. Teratogenic effects effective vasopressors during pregnancy for control of
are shown in animals after administering high maternal hypotension.[21]
concentrations for prolonged periods.[15] However,
such high required doses are not encountered in Because foetal haemoglobin has a high affinity for
clinical practice. However, some recommend avoiding oxygen, transient decreases in maternal oxygenation
nitrous oxide in pregnant women.[16,17] In modern day are well tolerated by the foetus.[22] However,
practice, it is rarely necessary to use nitrous oxide in a prolonged or significant maternal hypoxaemia leads
pregnant patient, and we have so many alternatives for to uteroplacental vasoconstriction, reduced perfusion
general anaesthesia. and subsequent in foetal hypoxaemia, acidosis, and
death.[23] Maternal hypercarbia also can produce
General anaesthetic drugs inhibit synaptic uterine artery vasoconstriction compromising uterine
transmission and may lead to abnormal synaptic blood flow.[24] It can also directly lead to foetal
connections and inappropriate apoptosis.[18] Many respiratory acidosis. Similarly, hypocapnoea causes
anaesthetic agents have effects on neuronal receptors reduced uterine blood flow and can eventually trigger
which are necessary for neuronal differentiation, foetal acidosis. Uterine hypertension, as occurs
synaptogenesis, and survival during development. In with increased uterine irritability, can also lead to a
humans, the phase of rapid synaptogenesis extends reduction in the uteroplacental blood flow.
from mid-gestation to several years after birth, and
most of the perinatal anaesthetic exposure will be Risk of preterm labour
only for a brief fraction of the susceptible phase. There Many studies have reported an increased incidence
is no definite evidence to show the teratogenicity of of spontaneous abortion, premature labour, and
any volatile anaesthetic. However, it is prudent to use preterm delivery after non-obstetric surgery during
the lowest effective concentrations for the shortest pregnancy. This may be attributed to the surgery
possible time, especially because many of these drugs itself, manipulation of the uterus, or the underlying
do cause significant maternal hypotension. condition of the patient, mainly sepsis. As early as
1977, one study showed that foetal mortality was 8.7%
Benzodiazepine use in pregnancy has been associated when appendicitis occurred without perforation, but
with cleft palate and cardiac anomalies. However, was 35.7% when peritonitis was present.[25] The lowest
many recent controlled studies have countered this risk for preterm labour is reported during the second
association.[19,20] It is usually recommended to avoid trimester and for surgeries that do not manipulate the
benzodiazepine use throughout gestation and most uterus.[26]
especially during the first trimester. However, it may
be appropriate to provide judicious pre-operative When premature labour occurs, tocolytics are
anxiolysis so as to avoid increases in circulating indicated to preserve the pregnancy. Although its
catecholamine levels, which impair uteroplacental efficacy during non-obstetric surgery is debatable,
perfusion. prophylactic tocolytics may be considered in the
third trimester for lower abdominal or pelvic surgery
Most other anaesthetic medications, including for inflammatory conditions. Volatile anaesthetic
barbiturates, propofol, opioids, muscle relaxants, agents may help relaxing the uterus, although high
and local anaesthetics have been widely used during concentrations can cause undesirable hypotension.
pregnancy with a good safety record. Nonetheless, Other alternatives include, but not limited to,
delicate associations cannot be ruled out. β-mimetics (e.g., terbutaline), magnesium sulphate,

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vasodilators (e.g., GTN) and calcium-channel blockers pregnant patients. Laboratory and other testing should
(e.g., nifedipine). be performed as indicated by the patient’s comorbidities
and the proposed surgery. In addition to standard
DECISION-MAKING ALGORITHM FOR NON- pre-operative procedures, preparation of pregnant
OBSTETRIC SURGERY DURING PREGNANCY women takes into account risks of aspiration, difficult
intubation, thromboembolism, and the well-being of
Elective surgery should be delayed until as late as 6 weeks the foetus. Standard adult fasting guidelines, i.e., 6–8 h
postpartum. This will allow resolution of physiological for solid food, depending on the type of food ingested
changes of pregnancy. An overall miscarriage rate (e.g., fat content) are applicable to these patients.
following surgery is reported as 5.8%, increasing to • Aspiration prophylaxis: The gastric emptying
10.5% during the first trimester.[27] A multidisciplinary has recently been shown to be normal during
team-involving surgeons, anaesthesiologists, pregnancy until the onset of labour. However,
obstetricians and perinatologists should be involved in the risk of aspiration is still higher due to
the decision on proceeding with surgery. The second reduced gastric barrier pressure and lower
trimester is chosen for semi-elective surgery, which oesophageal sphincter tone (a progesterone
cannot be postponed. Urgent surgery should not be effect).[28] The presence of additional risk
delayed because secondary complications may increase for regurgitation and aspiration, including
the risk to the mother and/or foetus. Greater risk of active reflux or obesity should be surveyed.
uterine irritability and preterm labour are encountered Prophylaxis against aspiration pneumonitis
in the advanced stages of pregnancy. This is believed should be administered from 16 weeks
to result from the direct manipulation of the uterus gestation with H2-receptor antagonists and
during surgery or the disease process itself, as there is non-particulate antacids.
no evidence to suggest that any anaesthetic technique, • Antibiotic prophylaxis: The need for antibiotic
agent or dose influences this risk. Conditions associated prophylaxis depends on the specific procedure.
with a particularly high risk include lower abdominal However, attention should be paid in selecting
and pelvic inflammatory conditions, such as acute antibiotics with good safety profile in pregnancy.
appendicitis with peritonitis. Figure 1 summarises the • Prophylactic glucocorticoids: Administration of a
decision-making algorithm in this regard. course of antenatal glucocorticoids 24–48 h before
surgery between 24 and 34 weeks of gestation can
GENERAL PRINCIPLES OF ANAESTHESIA
reduce perinatal morbidity/mortality if preterm
MANAGEMENT
birth occurs. Despite the potential benefits to the
Pre-operative preparation foetus, however, antenatal glucocorticoids are
Pregnant patients who require surgery should be best avoided in the setting of systemic infection
evaluated pre-operatively in the same manner as non- (such as sepsis or a ruptured appendix), because
they may impair the ability of the maternal
immune system to contain the infection.
• Thromboprophylaxis: Pregnancy is a
hypercoagulable state. The 2012 American
College of Chest Physicians clinical practice
guideline on prevention and treatment of
thrombosis recommends mechanical or
pharmacologic thromboprophylaxis for all
pregnant patients undergoing surgery.[29]
• Prophylactic tocolytics: There is no proven
benefit to routine administration of prophylactic
perioperative tocolytic therapy. Minimising
uterine manipulation may reduce the risk
of development of uterine contractions and
preterm labour. Tocolytics are indicated for the
treatment of preterm labour until resolution of
Figure 1: Decision-making algorithm for non-obstetric surgery during the underlying, self-limited condition that may
pregnancy have caused the contractions.
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Conduct of anaesthesia Monitoring for uterine contractions

Pregnant patients beyond 18–20 weeks of gestation When external tocodynamometer can be placed
should be positioned with a 15° left lateral tilt, to reduce outside of the surgical field, uterine contractions may
aortocaval compression and supine hypotension be monitored intraoperatively. If uterine contractions
syndrome. Alternatively, a wedge may be placed are detected, maternal haemodynamics should be
under the right hip. Regional anaesthesia, which improved by giving more intravenous fluids and also
includes peripheral nerve blocks as well as neuraxial consider tocolytic treatment in consultation with
anaesthesia, is an option for some surgical procedures, the perinatologist/obstetrician. Tocometry during
particularly those involving the extremities. Regional post-operative period is useful as post-operative
anaesthesia does reduce the exposure of foetuses to analgesia may mask awareness of mild early
potential teratogens, avoids the potential risk of failed contractions and delay tocolysis.
intubation and aspiration, and provides excellent
post-operative analgesia. Management of neuraxial Recovery from anaesthesia
anaesthesia for non-obstetric surgery in the pregnant Recovery from anaesthesia requires close monitoring,
patient is no different than its management for particularly of the airway and respiratory system,
because most severe anaesthetic complications due
caesarean delivery. The major concern with neuraxial
to hypoventilation or airway obstruction occur during
anaesthesia is maternal hypotension, which may
emergence, extubation, or recovery.
reduce placental perfusion. However, there is no
conclusive evidence demonstrating superior safety Post-operative analgesia
for regional anaesthesia, and general anaesthesia is Provision of adequate analgesia is important in the
frequently required. Thiopentone in late pregnancy post-operative period as well, since the pain has
had no significant effect on intra-uterine pressure. been shown to increase the risk of premature labour.
Ketamine was found to cause uterine contraction (equal Regional nerve or plexus blockade or epidural analgesia
to ergometrine) in early pregnancy. However, ketamine can provide excellent post-operative analgesia and
exerts no effect in late pregnancy.[30] Therefore, reduce the risk of opioid-induced hypoventilation
ketamine’s excellent analgesic property may be when compared with intravenous opioids. Opioids
utilised in late pregnancy. Volatile anaesthetics such as can be used, as needed, to control post-operative
halothane, sevoflurane, desflurane and isoflurane are pain. Paracetamol is the analgesic of choice for the
shown to inhibit the uterine contractility, which may treatment of mild to moderate pain during any stage
prove beneficial in preventing preterm contractions.[31] of pregnancy. NSAIDs should be avoided, especially
During anaesthesia and surgery, foetal well-being is after 32 weeks of gestation, because they may cause
best ensured by careful maintenance of stable maternal premature closure of the foetal ductus arteriosus (if
haemodynamic parameters and oxygenation. Close given for more than 48 h). They are also associated
monitoring of foetal responses for signs of distress is with oligohydramnios with reduced foetal renal
strongly advocated. function. NSAIDs can also inhibit uterine contraction.

Foetal monitoring CLINICAL PEARLS REGARDING NON-OBSTETRIC

Foetal heart monitoring should be interpreted by an SURGERY DURING PREGNANCY
experienced operator with an understanding of the
changes encountered during surgery and anaesthesia. • Based on current evidence, pregnancy testing is
Foetal heart rate (FHR) monitoring is practical from a cost-effective method and should be offered to
18 to 22 weeks, and from 25 weeks, heart rate variability all verbally consenting females of childbearing
(HRV) can be readily observed. Anaesthetic agents potential. This does not substitute for an
reduce both baseline FHR and HRV, so readings must appropriate pregnancy history.
be interpreted in the context of administered drugs. • Regarding fluid resuscitation during
The value of intraoperative FHR monitoring is that it pregnancy, rather than the type of fluid,
detects an early compromise, allowing optimization maintenance of hemodynamic goals take
of maternal haemodynamics and oxygenation with higher priority. Positioning concerns to avoid
appropriate fluid therapy, vasopressors, blood aortocaval compression by the gravid uterus
product administration, hyperventilation or position is an important consideration while managing
adjustment. persistent hypotension.

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• While contemplating on blood transfusion anaesthesia with high end-tidal concentrations

during pregnancy, additional concerns arise of volatile anaesthetic agents, while resulting
due to maternal physiological changes and the hypotension and insufficient uteroplacental blood
risks to foetus due to alloimmunisation and flow are managed with vasopressor. Alternatively,
infective complications. Expected physiological EXIT procedures can be performed using neuraxial
changes in vital signs during pregnancy and anaesthesia with intravenous nitroglycerine to
some pregnancy-related comorbids such as achieve uterine relaxation.[33,34]
pre-eclampsia, thrombocytopaenia, coagulation
changes, etc., make the blood loss estimations a SUMMARY
thorny problem.[32]
• Pregnancy is no longer considered a While dealing with non-obstetric surgery or
contraindication to laparoscopic surgery. some maternal procedures during pregnancy,
Laparoscopic techniques may be preferred when anaesthesiologist is dealing with “two clients in one”
abdominal surgery is undertaken of reduced scenario, where the safety of both is very important
morbidity for the mother, and potentially a and challenging. Anaesthesia management, including
decreased incidence of preterm labour as a post-operative analgesia, should be planned well to
result of reduced manipulation of the uterus. preserve the pregnancy and to ensure the safety of
The advantages include smaller incisions, the mother as well as the foetus. A multidisciplinary
decreased pain, less need for analgesics, and team approach is highly recommended to ensure an
more rapid recovery and mobilisation. adequate standard of care.
• Trauma in itself complicates 6–7% of
pregnancies. The emphasis is on maternal Financial support and sponsorship
resuscitation and in life-threatening Nil.
multi-trauma, caesarean section may be
Conflicts of interest
performed to improve maternal haemodynamics.
There are no conflicts of interest.
• Neuro-anaesthesia may be indicated during
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Indian Journal of Anaesthesia | Vol. 60 | Issue 4 | Apr 2016 241

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