Transcript Slide 1

Israeli Family Physicians: what to know?
Throwing the Mother Out with the Bathwater—
Misuse of randomized controlled trials
Michael C. Klein
Centre Community Child Health Research
BC Research Institute for Children’s and
Women’s Health
Emeritus Professor of Family Practice and
Pediatrics
University of British Columbia
Variation surfaces—BC Women’s Hospital
1993-----
25 docs 75% or more
Family Physicians Nullip SVD Episiotomy
Rates
Apr 95-Mar 96: mean rate=19.2
Apr 96-Mar 97: mean rate=14.9
April 98-Mar 99
60
50 53
40
30
20
Std. Dev = 21.78
10
N = 96.00
.
60
.
70
.
80
.
90
0
0
0
0
0
0.0
10
.
50
0
5
0
.
30
0
4
.
40
.
20
0.0
4
6
0
0
Mean = 13.1
7
.
10
8
Episiotomy Rate (%)
2 remaining
Variation surfaces Vancouver CQI
1993
Does Epidural Analgesia
Increase the Likelihood of
Cesarean Section?
 How
many think it does?
 How
many think it does not?
Epidural Cxion
A natural experiment at nearby community
hospital
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In early 1990s Community Hospital had Cxion rate of
about 8%, while Women’s about 20%
We Created matched cohort of healthy women
Odds of having a Cxion at the tertiary care centre vs
community 3.4 (CI 2.1—5.4)
Why?
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More advanced cervical dilation on arrival (opportunity for
doulas)
Use of epidural analgesia—largest effect: Epidural rate of 15.4%
community, 67.2% tertiary
Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates:
The role of pain management. J Fam Pract 2001; 50(3):217-223
A natural experiment at nearby
community hospital
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Differences between the hospitals:
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Increased ambulation at the community (12% vs 5%)
Fewer numbers of caregivers for each woman at
community
More oxytocin augmentation at community
(32.3 vs 24.9%)
Less offering of epidural at community (qualitative)
16.7% vs 42.3%
Strong Head of OB at community who worked
collaboratively with strong nursing and FP leadership,
and together developed a coherent philosophy of care
A natural experiment at nearby
community hospital
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But when controlled for epidural, the Cxion rate at the
two hospital was the same, about 12%
In other words, women with an epidural in each facility
had a similarly high Cxion rate and women not receiving
an epidural had a similarly low Cxion rate
Only real difference was: community hospital used
epidural less often, and in so doing had a low Cxion rate
When Head of OB retired and nursing leadership also
changed, the epidural and Cxion rate at the community
hospital rapidly reached usual levels for BC
Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates: The
role of pain management. J Fam Pract 2001; 50(3):217-223
Meanwhile Departmental CQI
evolved into research

We studied natural variation in
relation to physician epidural rates
 Maternal
outcomes
 Newborn outcomes
 The physician rather than the woman as
the unit of analysis
Nulliparous Maternal Outcomes by
Epidural Cohorts
70
66.5
58.2
60
54.9
Low Epidural
Mid Epidural
High Epidural
50
40
30
35.5 34.2
23.2
25.3
29.8
19.3
20
24.4
20.7
21.9
19.9
14.1
12.2
10
0
OP/OT
Augment
Forc/Vac
SVD
Cxion
Nulliparous Malposition (OP-OT)
Rates by Epidural by Race
40
35.5
35
36.6
34.7
34.2
Low Epidural
Mid Epidural
High Epidural
33.1
30
26.3
25
23.2
20
17
15
10
5
0
All
asi
Cauc
an
Cau
n
o
N
36.6
c
Nulliparous Oxytocin Augmentation Rate
by Epidural Cohorts by Race
35
29.8
30
30.5
28.2
27
25.4
24
25
20
14.8
15
12.2
10.9
10
5
0
All
asi
Cauc
an
Non-
Cauc
Low Epidual
Mid Epidural
High Epidural
Nulliparous Cesarean Rate by
Epidural Cohorts by Race
30
25
19.9
20.6
19
20
15
26.2
24.4
20.1
17
14.1
Low Epidual
Mid Epidural
High Epidural
12.6
10
p values range from <.001 overall to
.034 for caucasians and .049 for noncaucasians
5
0
All
Caucasian
NonCaucas
Epidural study
Nulliparous NCN/SCN Admission Rates
by Epidural by Race
16
1 3 .7
14
1 2 .8
1 2 .4
12
10
Low Epidural
Mid Epidural
High Epidural
9 .1
8 .3
7 .7
8
7 .2
7 .4
6 .8
p values range from .012 overall to
.193 for caucas ians and .064 for
non-caucas ians
6
4
2
0
All
asi
c
u
a
C
an
Cau
Non-
c
Were the physicians who were in
each epidural cohort practicing
differently?
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Not only did they use epidurals less often,
but
Used epidurals later
 Spent more time with their patients in
hospital--even though their patients spent less
time in hospital
 Indeed they practiced differently—more
intimacy and engagement
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Conclusion:
•Physicians who employ epidural
analgesia often (and early) in labor
expose them to higher intervention rates
and more adverse maternal and newborn
outcomes than those who on average
employ epidural analgesia less often and
later in labor.
 But not the fault of the anesthesia establishment
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at BC Women’s or likely elsewhere.
Anesthesia provides an excellent service. They
help us resolve many problems
It is we who ask for help!!!!!!!!!
At least at BC Women’s, there is no evidence that
anesthetists are scavenging for business
There is evidence from rural family practice
(Stuart Iglesias) that epidurals can be introduced
and associated with lowering of Cxion rate
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But that study requires contextual or environmental
analysis
The Tyranny of
Meta-analysis
And the misuse of
Randomized
Controlled Trials
Collateral damage or
Blowby—think Iraq
 Or
throwing the mother (and at
times the baby) out with the
bathwater.
 Or consequences of left-sided
thinking—what about the right
side (think right brain)
David Sackett: understanding
clinical trials. BMJ 309: 1994
 Information
from trials “….should
go far beyond efficacy…to include
measures of harm as well as benefit
and to integrate patient’s views on
the quality of life with and
without treatment, and to include
economic consequences of the
treatment alternatives.”
Cochrane Meta-analysis of Effect of
Epidural Analgesia
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Comparing Epidural to Narcotics
Previously meta-analyses showed a 10%
increase in Cxion rate with epidural analgesia
Current Cochrane does not—why not? Is
Cochrane wrong?
It is not the fault of the RCT as a methodology!!
It is the inclusion in the meta-analysis of studies
that ought not to be there—or the studies need
to be grouped or stratified according to their
settings or approaches so one can know if the
results apply to one’s own setting
Central Concepts in
Applicability of EBM
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Look at both the left and the right
side of the equation
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What about the “inadvertent”
consequences of the approach or
procedure addressed by the trial or
what you are interested in compared to
the big picture consequences for this
and future pregnancies?
4.3 hour increase with
epidural
Sharma only 1 hour increase with
epidural
1.4 hour increase
with epidural
Sharma only 19 min
increase with epidural
52%
38%
Sharma only 33% epidural 15% control
15%
7%
27% 16%
Increase in Perineal trauma as well
Sharma only 9.1% epidural
3.6% control
versus
24%
6%
Why not an
increase in
cesarean as well?
All studies: mixed parity, various
concentrations of agents both study arms
and mostly IM narcotic
12-13%
10-14%
5%
both
arms
Sharma: Dallas Parkland 12% base Cxion rate, low dose oxy augmentation,
Randomization @4-5cms. Clark: Louisville, 70%>4 cms, high dose oxy,
Loughan: London UK Randomization 3-4cms,
Sharma!!!!
Klein Sensitivity Analysis: retaining only those
studies that randomized early at < 4-5 cms
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Wong CA, Scavone BM, Peaceman AM,
McCarthy RJ, Sullivan JT, Diaz NT, et al. The
risk of cesarean delivery with neuraxial
analgesia given early versus late in labor. N
Engl J Med 2005;352: 655-65
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Authors and NEJM editorialist claimed that early
epidurals do not increase the rate of caesarean
deliveries.
The study was not of early epidural analgesia, and the
oxytocin augmentation rate of 75% at first analgesia
makes for lack of generalisability.
The claim that women need not worry that early
epidurals will lead to increased caesareans is false.
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This trial was about two methods of
helping women with pain in early labour.
In the so called epidural arm, an epidural
catheter was placed. On first request for
analgesia, women received intrathecal
fentanyl, and in the narcotic arm,
hydromorphone.
On second request, almost two thirds of
women in both arms were in active labour,
4 cm or more dilated.
In the intrathecal "epidural" arm, they
received low dose epidurals; in the
narcotic arm, hydromophone.
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This trial, as others that have contributed to the
Cochrane meta-analysis showed no increase in
caesareans in the presence of epidural analgesia, but
does not acknowledge that most women were in active
labour at time of second request or when they actually
got an epidural-- when most will do well.
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Wong et al, like Sharma et al, the other major
contributors to the Cochrane meta-analysis showing no
difference, have shown only that when women's pain in
the latent phase is managed with intrathecal, narcotic, or
other pharmacological or non-pharmacological means,
an epidural in the active phase of labour does not
increase the rate of caesarean section.
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And neuraxial analgesia. Mmmmmmmmmmmmmm
Ohel from Israel (Am J Obs and Gyn 2006 vol 194)
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Well conducted RCT of Epidural vs Narcotics
449 nulliparous women at term randomized at
less than 3 cms
Mean point of randomization 2.6 vs 4.6 cms for
epidural vs narcotic
CS 13% vs 11% (LOW!!!!!!!!!!!!!)
But labor supported by nurse midwives fully—
Obstetricians only as consultants
Clearly an intimate style of care
Again it is about environment—yours?
Latest Meta-analyses
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Patient-requested Neuraxial
Analgesia for Labor--Marucci et al
Anesthesiology May 2007
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Review comes up with the same conclusions
based on the same literature
New Cochrane meta-analysis same
All now state that early epidurals are not a
problem
Epidural analgesia, while a superb
technology, and the “best” form of pain
relief has completely transformed
normal birth--leading to a cascade of
interventions.
• 3 of 4 Canadian women receive
one or more major procedures or
interventions in labor (CIHI, 2004)
and epidurals are a major
contributing cause: Epidural Rate
45.4% Canada, 36.3% Vancouver
and rising
Why don’t we acknowledge that Epidural
Analgesia has changed the landscape?
•Subversion by RCTs and EBM?
• Cochrane reviews by
Anesthesiologists?
•Nurse/Doctor’s comfort—we like it!!
•Economics?
•Existence of a dedicated anesthetic
workforce that we created?
•Not the fault of the anesthesia
establishment!!!!! We asked for it
•Women asked for it
•(Think Twilight Sleep)
•but we taught them to ask for it!
From EBM to Research designed
to deliver answers that we want
to receive!
From Evidence-based decisionmaking
To what Philip Hall has called:
•“Decision Based
Evidence Making”
Whose evidence?
• Does the study setting apply to me in my
setting?

Basic problems with RCTs
 Results

apply only for the conditions of
the trial (“Murray Enkin’s first law”)
Are conditions my conditions?
• Do the participating
practitioners practice the way
that I practice?

Collateral damage or Blowby (2)
 Example:
Canadian Post-Term trial
of expectant management vs
induction at 41 weeks
 Outside
rarified atmosphere of the RCT,
thinking that placenta degenerates at 41
3/7th weeks unleashes a cascade of
“side effects” NO! EFFECTS--resulting
in increased not decreased cxion rates
and consequences for next pregnancy:
8% vs 44% cxion rate for nulliparous
women at BC Womens

Post-term trial: this and subsequent
pregnancies, increase in:
 induction, EFM, epidurals,
instrumentation, perineal trauma,
Cxions, sense of failure, parenting
problems, postpartum DIC
 Next pregnancy: placental previa and
other problems of placentation,
abruptions, ectopics, infertility,
stillbirths
The Induction Cascade

Induction requires continuous electronic fetal
monitoring because it is considered a “high risk”
procedure.

This is because over-stimulation of the uterus can
occur and that can lead to stress on the fetus.
o
Women receiving continuous electronic fetal
monitoring are kept in bed almost all the time.
o
Immobility leads to abnormal progress of labor,
which in turn leads to labour dysfunction
Induction Cascade 2
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Continuous electronic fetal monitoring leads
to more cesarean sections, likely because
of the immobility and because abnormalities
that are seen on the monitoring tracings are
often misinterpreted as “fetal distress,” and
cesarean is the usual response.
--Labors that are induced are more
painful than labors that occur naturally.
--Hence women are much more
likely to receive an
epidural
analgesic than
women in
spontaneous
labor.
Induction Cascade 3
o
Epidural analgesia gives very
effective pain relief—but “there is
no free lunch!”
--Epidural analgesia causes
posterior pituitary gland to
produce less natural oxytocin
--Epidural analgesia will
greatly prolong the first
stage of labor on
average by 3-4 hours
Induction Cascade 4

If given very early in labor at less than 4
centimeters of cervical dilation (which is the case
in most labors), epidural analgesia causes
abnormal positions of the fetus, such as an
extended neck rather than the usual flexed
position. This leads to more back labors (posterior
labors) and transverse or side positions.

A baby whose head is extended cannot rotate
and cannot easily descend in the birth canal.

Epidural analgesia will increased the length
of the second stage of labor by at least 30
minutes
Induction Cascade 5
o
Epidural analgesia will lead to the
inability of women to push effectively,
thus leading to more use of synthetic
oxytocin and need for assistance in
the delivery by use of vacuum or
forceps.
--The use of these instruments in the
presence of epidural analgesia, and even
without, will lead to more perineal trau
requiring stitching.
--If given early in labor,
epidural analgesia will increase
the cesarean section rate by
more than two times over
women not receiving epidurals
at all or only after 4-5
centimeters of cervical dilation.
Induction Cascade 6 (the Psychological
cascade)

Induction changes everything

The birth process has now been moved from
her process to process managed and
controlled by the caregivers and the system

What takes place is largely driven by protocols
and guidelines. This is true birth control
Induction Cascade 7 (the Psychological cascade)

She now needs management and her fetus is potentially at risk for the
consequences of the interventions that follow logically from the induction.

We watch her more carefully, and we will indeed find things to
worry about. It just goes with the territory.
(Some of those findings will be real and would have occurred anyhow
due conditions present in the mother or the fetus, but others will be
caused by the interventions dictated by her altered state--caused by our
good intentions. [In medicine we have a term for this: iatrogenic disease
or disease cased by doctors (or any caregiver behaving this way)].

Friendly fire or collateral damage can be the result
o
And it is not just that we professionals will feel
differently about the induced woman, but she will feel
differently about herself.
Induction Cascade 8 (the Psychological
cascade)

She will have begun to feel less in control, less confident,
less competent, more dependent

Dependency feeds into the laboring process itself.

Increased maternal anxiety is inevitable and leads to
the production of stress hormones that interfere with
ands slow labor --And this feeds back into the
evolving cascade such that a sense of the joy and
power and the transformative nature of childbirth are
undermined.
Induction Cascade 9 (The Next Birth Cascade)

Now she has a uterine scar
o
When the fertilized egg searches for a place to attach,
it can attach low down at or on the scar.
(Scar made up of a fiber-like material rather
than
the soft , juicy material of normal lining of
uterus).
--Then the attachment of what will
become
the developing placenta
will be weak and
subject to pealing
off as the placenta and
uterus grow
Induction Cascade 10 (The Next Birth Cascade)
Placental abruption occurs, when the placenta detaches itself
in whole or in part, leading to severe bleeding and high
likelihood of loss of the pregnancy. [Note that in Canada
ectopic pregnancy rates increased from 10/1000 to 16/1000
between 1981 and 1990, parallel to the rise in the cesarean
section rates].

If the fertilization occurs in the fallopian tube, the result is
ectopic pregnancy--also leads to bleeding and fetal loss.

If the attachment is placed over the inner opening of the
cervix, the result is a “placenta previa,” which can be an
emergency leading to cesarean section and a fetus at risk.

If the attachment “invades” the wall of the uterus it is placenta
accreta. This is a placenta that will not detach at the birth,
with very severe bleeding consequences and likely loss of
the uterus for future childbearing.
Induction Cascade 11 (The Next Birth Cascade)

Adhesions secondary to the first cesarean
surgery can lead later to maternal bowel
obstruction.
o
All these complications are increased once a
woman has had the first cesarean, and if
present, make the woman more likely to have
problems getting pregnant the second time
(infertility) and if she gets pregnant, of having a
stillbirth.
o
Paradox: We started the induction to
prevent stillbirth…………………………
 Post-Term
trial about induction
 Results
in huge number of women
thinking that they are biologically
defective—biological nonsense
 1000
inductions needed to possibly
prevent one stillbirth BUT at what price?
This is the right side of the equation.
Informed consent?
 Contributes
massively to medicalization
of childbirth that has led some to
suggest that Cxion-on-demand is an
answer—a surgical fix for a problem in
caring.

COMMENTARY ON: Lyerly et al: Values, and decision
making surrounding pregnancy. Obstet Gynecol
2007;109(4):979–98 in The Patient-Centered
(R)Evolution
“The risk discussion about induction for post-term
pregnancy care focuses on the perceived risk of NOT
inducing rather than the risk of operative delivery
associated with induction. Furthermore, the risk
discussion about NOT allowing spontaneous labor and
primary vaginal delivery misses a full discussion of the
risk of elective primary cesarean. In intrapartum care,
our risk distortion is that we err on the side of
intervening too much.”--Andrew Kotaska
Other Problematic RCTs
Walking
in Labor—NEJM
(1998:Bloom et al Volume 339:76-9)
Term-Breech
Trial
Misuse Term-Breech Trial
Results

Trial showed at 3 months postpartum that
newborn and mother better off with CS for
prevention of pelvic floor problems
(UI, Fecal Incontinence, Sexual)—
generalized to vertex births.

OBs stopped delivering breeches even
before trial published—why?
But 2 year f/u shows no difference in any
maternal or newborn outcomes—
including pelvic floor
 And pelvic floor outcomes—what does it
say about the resilience and self-healing
properties of pelvic floor for women
experiencing vaginal birth?
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GBS!!!!!!!!!!!
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And think ahead to the collateral damage
caused by our obsession with GBS—at
what price to the mother for a marginal to
no advantage to the baby?
BC Women’s status pre and post case
finding and now screening?
More antibiotics for the mother:
anaphylaxis, changes in bacterial flora,
emergence of resistant strains
Further disruption of what would have been
normal labor- -IV, early admission to
hospital, induction/augmentation if NIL and
the cascade of interventions including CS
GBS!!!!!!!!!!!
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Left sided thinking!
Pediatricians and infectious
disease specialists worry about
the baby
Fair enough, but what about the
mother?
Right side is collateral damage to
the mother
The precautionary principle of nonmaleficence (first do no harm),
requires that potentially harmful
actions or routines in the
“management” of vaginal birth be
eliminated before recommending a
potentially harmful intrusion like
routine epidural analgesia or
Cesarean on demand.
Examples of such practices:
undermining women’s capacity to give birth with
as little intervention as possible
 failure to utilize non-pharmacological
approaches to pain management first
 unsupported labor (think doulas)
 unphysiological positions and purple pushing
 routine episiotomy
All of which lead to complications that make
women feel incapable of giving birth without
massive intervention and promote requests for
early epidurals and even Cxion on demand

The End