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REVIEW ARTICLE

Whats new in obstetric anesthesia


Ruth Landau
Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Seattle, Washington,
USA
Introduction
Labor analgesia
Post-cesarean delivery analgesia
Post-preeclampsia outcomes
Conclusions
References
Introduction
For over three decades, one of the highlights of the an-
nual meeting of the Society for Obstetric Anesthesia and
Perinatology has been the Whats New in Obstetric
Anesthesia lecture. This lecture, renamed in honor of
Gerard W. Ostheimer, MD in 1995, reviews the preced-
ing years literature relevant to the practice of obstetric
anesthesia. This article, which is the result of reviewing
over 1400 scientic manuscripts to create the 2008
Ostheimer lecture, focuses on three key areas: recent
advances in labor analgesia, post-cesarean delivery
analgesia and novel developments surrounding the long-
term outcomes of preeclampsia.
Labor analgesia
Since the rst description of intrathecal cocaine to pro-
vide labor analgesia by Oskar Kreis in 1900,
1
advances
in neuraxial pharmacology and technology have pro-
vided opportunities to expand and improve labor
analgesia.
The International Association for the Study of Pain
(IASP) declared 2007-2008 as the Global Year Against
Pain in Women Real Women, Real Pain.
2
Key points
presented in their report relate to: (1) the importance of
treating pain within the pregnant population and the
substantial public health impact if pain is neglected;
(2) the alarmingly high rate of acute or chronic pain
after delivery (70%); and (3) labor pain as a clinical
model for studying acute pain.
In recent years there has been interest in evaluating
pain and pain relief accurately, due to the subjective nat-
ure of the outcome parameters, signicant inter-individ-
ual variability in pain perception and the complexity of
womens overall experience during labor and delivery.
Ohel et al.
3
prospectively tested nulliparous and multi-
parous women at term for the presence of endogenous
analgesia during the peripartum period. Using a dolo-
rimeter, a pressure algometer applied on different points
on the body to determine pressure pain thresholds, the
authors found an increase in pain threshold during ac-
tive labor compared with an evaluation before labor.
They concluded that this threshold increase might have
a protective effect during the intense experience of labor
pain.
Further directions in research may test the hypothesis
that increased pain thresholds and enhanced endoge-
nous opioids in pregnant women before or during labor
may reduce labor analgesic requirements. If conrmed,
this may translate into clinically relevant outcomes such
as the provision of neuraxial analgesia at later stages in
Accepted April 2009
The 2008 Gerard W. Ostheimer Lecture. Given at the Annual Meeting
of the Society for Obstetric Anesthesia and Perinatology, Chicago, IL,
2008.
Correspondence to: Ruth Landau, MD, Virginia and Prentice Bloedel
Professor of Anesthesiology, Director of Obstetric Anesthesia and
Clinical Genetics Research, Department of Anesthesiology and Pain
Medicine, University of Washington Medical Center, 1959 NE Pacic
Street, Suite BB 1415C, Seattle, WA 98195-6540, USA. Tel.: +1 206
543 2187.
E-mail address: rulandau@u.washington.edu
International Journal of Obstetric Anesthesia (2009) 18, 368372
0959-289X/$ - see front matter

c
2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijoa.2009.04.009
www.obstetanesthesia.com
labor, effective labor or post-cesarean analgesia with
reduced doses of analgesic agents, and improved long-
term postpartum outcomes.
Provision of effective and safe labor analgesia re-
mains an ongoing challenge as demonstrated by the
number of studies investigating the selection of local
anesthetic agents, optimal doses, and location for depo-
sition (for example, the epidural or intrathecal space), as
well as the modalities used for their administration.
Lyons et al.
4
postulated that reducing the concentration
of local anesthetic agents with the aim of reducing tox-
icity and motor blockade might not necessarily require
increasing the dose in a linear manner to provide effec-
tive epidural labor analgesia. Using an up-down sequen-
tial allocation method, the authors sought to determine
the minimum local analgesic volume (MLAV) and min-
imum local analgesic dose (MLAD) of an initial bolus of
epidural bupivacaine 0.125% and 0.25%. MLAV of
bupivacaine 0.125% was 13.6 mL (95% CI 12.414.8)
versus 9.2 mL (95% CI 6.911.5) for bupivacaine
0.25% (P = 0.002). Hence, by reducing concentration,
equivalent labor analgesia was achieved with a signi-
cant reduction in dose of bupivacaine. Such reductions
in dose without compromising analgesic efcacy provide
a greater margin of safety and allow ne-tuning of labor
analgesia. These results are important from both a phar-
macologic and a clinical perspective; similar future stud-
ies could determine the optimal volume of bupivacaine
as an epidural top-up for breakthrough pain at later
stages of labor.
Recent studies have examined the motor blocking
effects of local anesthetic agents and the subsequent
impact on mode of delivery. Beilin et al.
5
studied low
concentrations of epidural local anesthetics (0.0625%)
for maintenance of labor analgesia and determined that
bupivacaine was optimal relative to ropivacaine and lev-
obupivacaine in providing effective and cost-efcient
analgesia with minor and inconsequential degrees of mo-
tor blockade. Van de Velde et al.
6
performed a large ran-
domized clinical trial to determine the potency hierarchy
of intrathecal bupivacaine, ropivacaine and levobupiva-
caine at clinically relevant doses combined with opioids.
In this full dose-response study dening the ED95 of all
three local anesthetics for intrathecal labor analgesia,
there appeared to be little or no benet to the substitution
of racemic bupivacaine with ropivacaine or levobupiva-
caine in combination with sufentanil when performing
a combined-spinal epidural (CSE) technique.
Finally, past studies have shown that CSE and low-
dose infusions with patient controlled epidural analgesia
(PCEA) are exceptional tools for improving patient sat-
isfaction with labor analgesia. Women appear to prefer
the option of controlling their pain with a push button.
However, there is no consensus on the optimal program
for PCEA labor analgesia. One of the more interesting
recent concepts relates to the paradigm that large bo-
luses of diluted epidural solutions, rather than a contin-
uous infusion of the same amount of local anesthetics,
may provide better spread of the infusate and therefore
better sensory blockade. Recent studies using various
PCEA pump prototypes with computerized algo-
rithms
79
appear to conrm that these innovative drug
delivery methods achieve better analgesia and patient
satisfaction throughout labor with overall lower
amounts of local anesthetic agent. Sia et al.
10
demon-
strated that high-tech PCEA pumps with automated
mandatory boluses compared with basal continuous
infusions of local anesthetic agents and opioids (ropiva-
caine 0.1% with fentanyl 2 lg/mL; automated 5 mL
boluses 1/h versus a basal infusion of 5 mL/h with
additional 5 mL PCEA boluses) following an initial
spinal analgesic dose resulted in a reduction in total
local anesthetic consumption. Whether these prototype
pumps and sophisticated drug-delivery systems nd
their way into routine clinical practice and further
improve maternal labor analgesia remains to be
determined.
Post-cesarean delivery analgesia
The growing increase in rates of cesarean delivery
11
and
evidence that severe acute postoperative pain may result
in chronic, incapacitating pain after surgery,
12
remind
obstetric anesthesiologists that post-cesarean analgesia
must be optimized to improve short- and long-term
outcomes.
Several studies have examined novel ways to provide
optimal analgesia following neuraxial anesthesia for
cesarean delivery. Carvalho et al.
13,14
conducted two
studies looking at the effects of an extended-release epi-
dural morphine (EREM) formulation for post-cesarean
analgesia. In their second randomized clinical trial, they
compared EREM 10 mg with epidural morphine 4 mg in
a setting reecting current postoperative obstetric multi-
modal analgesia protocols.
14
The authors found a signif-
icant morphine-sparing effect between 24 and 48 h after
delivery, with superior functional activity in the EREM
group. The incidence of side effects and respiratory
depression were similar in the two groups. Despite the
initial excitement generated by liposomal drug delivery,
EREM might not be the panacea for post-cesarean anal-
gesia and requires more research to dene its benets.
Whether EREM justies using the CSE technique to
allow its delivery in the epidural space rather than
performing single-shot spinals for elective cesarean
deliveries is unknown. Lastly, the concern of inadvertent
administration of EREM in the subarachnoid space
remains to be resolved.
Another novel strategy to optimize post-cesarean
analgesia is the intra-wound infusion of non-steroidal
anti-inammatory drugs (NSAIDs). Lavandhomme
et al.
15
tested the hypothesis that diclofenac has periph-
R. Landau 369
eral analgesic properties, in addition to systemic effects,
that could reduce local expression of mediators that
sensitize nociceptors. In their clinical trial, women
scheduled for cesarean delivery under spinal anesthesia
were randomized to one of three groups: (1) intra-
wound infusion of diclofenac (300 mg/48 h) with an
elastomeric pump connected to a multi-hole 20-gauge
catheter (Pain Buster; I-Flow Corporation, Lake For-
est, CA) inserted supercial to the fascia; (2) intra-
wound infusion of ropivacaine 0.2% (5 mL/h for 48 h)
with i.v. diclofenac (4 75 mg over 48 h); or (3) intra-
wound saline infusion with i.v. diclofenac (4 75 mg
over 48 h). Continuous intra-wound infusion of diclo-
fenac resulted in greater opioid-sparing and better post-
operative analgesia than the same dose administered as
an intermittent i.v. bolus, and produced similar analge-
sia to the ropivacaine infusion with i.v. diclofenac. There
was no apparent benet of either solution beyond 24 h,
and the study was underpowered to detect long-term
benets. Nonetheless, the overall rate of persistent pain
at six months post-cesarean was 14%. These ndings are
consistent with other studies suggesting that 7 to 15% of
women suffer moderate to severe chronic pain after
cesarean deliveries with impaired daily activities.
12,1619
Post-preeclampsia outcomes
Despite numerous studies and advances in identifying the
pathophysiologic mechanisms, preeclampsia remains the
disease of theories involving endothelial dysfunction,
20
metabolic abnormalities
21
and inammatory activa-
tion;
22,23
each of these entities may reect genetic predis-
posing factors.
24,25
However, the search for biological
markers to predict preeclampsia remains ongoing.
2631
Recent epidemiological studies indicate that pre-
eclampsia is not just a pregnancy-related disease that
resolves with delivery. In fact, preeclampsia may be
considered a risk marker for later-life diseases, including
cardiovascular and renal diseases, as most recently sug-
gested.
32
Whether preeclampsia directly contributes to
these diseases or simply unmasks preexisting shared risk
factors is unknown. The two-stage model of defective
placentation and impaired spiral artery remodeling fol-
lowed by maternal systemic manifestations may now be
considered to include a third, later-life stage of long-term
chronic endothelial and metabolic dysfunction.
Studies that have investigated the etiology and pre-
vention of eclampsia have also provided evidence that
seizures may be the result of an underlying hypertensive
encephalopathy.
33
First described in 1996, hypertensive
encephalopathy associated with specic neuroradiologic
imaging has been named posterior reversible encepha-
lopathy syndrome (PRES).
34
PRES is characterized by
headaches, seizures, altered mental status, and visual
disturbances and has been found in patients with pre-
eclampsia, renal failure, and hypercalcemia and those
taking immunosuppressive and chemotherapeutic drugs.
The purported mechanism of PRES includes endothelial
dysfunction, acute increases in blood pressure that may
exceed the upper limit of cerebral autoregulation, and
vasogenic edema. A number of publications have
reported PRES in the peripartum period, some of
which,
35,36
but not all,
3740
noting an association with
preeclampsia. Two cases of PRES have occurred in the
presence of postdural puncture headache, which compli-
cates the recognition and management of the dis-
ease.
36,40
The prompt diagnosis of PRES is critical for
early management of hypertensive encephalopathy and
to prevent subsequent irreversible white matter lesions
of the brain. Dyer et al.
41
emphasized the important role
that anesthesiologists play in the management of these
sick women, particularly in regards to regulating the
hemodynamic and cardiovascular effects of neuraxial
anesthesia during cesarean delivery.
To test the hypothesis that the hypertensive encepha-
lopathy underlying eclampsia causes white matter dam-
age that might impair long-term cognitive function,
Aukes et al.
42
evaluated 30 women formerly diagnosed
with eclampsia, 31 women with preeclampsia, and 30
healthy parous controls. The Cognitive Failures Ques-
tionnaire was used to assess the likelihood of commit-
ting errors during the completion of daily tasks;
women who had experienced eclamptic seizures were
shown to have decient cognitive function including
memory impairment and distractibility. The study indi-
cated the potential importance of preventing eclamptic
seizures and suggested that full clinical recovery after
eclampsia may not be expected.
Finally, a systematic review and meta-analysis of 25
trials (n = 3,488,260 women) by Bellamy et al.
43
to
assess the risk for cardiovascular disease and cancer
later in life, revealed that preeclampsia appears to be
associated with an increased risk for hypertension, fatal
and non-fatal ischemic heart disease (particularly with
the onset of preeclampsia before 37 weeks of gestation),
strokes and venous thromboembolism. Preeclampsia
was not associated with an increased risk for cancer in
this review, although lower breast cancer risks in for-
merly preeclamptic women have been suggested by
others.
44
Conclusions
The literature published in 2007 has generated evidence
highlighting pregnancy, labor and delivery as crucial
events that have the potential to impact womens health
and well-being long after delivery. Obstetric anesthe-
siologists should seize the opportunity to: (1) provide
optimal low-dose labor analgesia, (2) prevent persistent
and disabling post-partum pain by identifying and treat-
ing women prone to severe pain with multimodal post-
cesarean delivery analgesia, and (3) control maternal
370 Whats new in obstetric anesthesia
hypertension in preeclamptic women to prevent the
devastating outcomes associated with hypertensive
encephalopathy, posterior reversible encephalopathy
syndrome, and seizures.
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372 Whats new in obstetric anesthesia

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