CRITICAL APPRAISAL
OF DIAGNOSTIC
ARTICLE
10/5/2009
1
Does End Tidal CO2 Monitoring
During Emergency Department
Procedural Sedation and Analgesia
With Propofol Decrease the
Incidence of Hypoxic Events?
Randomized, Controlled Trial
Annals of Emergency Medicine
Article in Press, 2009
10/5/2009
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Learning Objectives
Introduction
 Discussion of the article
 Critical appraisal of the article
 Important calculations
 Overview on LR

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Introduction
Procedural sedation & analgesia for
management of acute procedural pain &
anxiety in the (ED) is part of core
competency in emergency medicine.
 A.C.E.P & A.S.A recommend continuous
monitoring of PR & rhythm, RR, BP, &
pulse oximetry during moderate and deep
sedation

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Introduction
Use of real-time capnography as adjunct
to current procedural sedation safety and
monitoring practice is under increasing
scrutiny.
 Capnography noninvasively measures the
partial pressure of CO2 in exhaled breath
& is tightly correlated with arterial CO2 in
patients with normal lung function

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Introduction
Minute ventilation is depressed by
sedatives by reducing respiratory rate or
tidal volume.
 Respiratory depression may produce
hypercapnia (RR > VT ) or hypocapnia (VT
> RR )

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Introduction
There is now compelling evidence that
capnography identifies respiratory
depression well before the onset of
hypoxia.
 This modality should allow physicians to
intervene to improve ventilatory status.

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Importance
Although pulse oximetry, PR, and BP
monitoring are considered routine practice
during ED procedural sedation &
analgesia, capnography is not.
 If the addition of capnography helps
physicians reduces hypoxia, then perhaps
it should also be routine.

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Goal of Study

determine whether physician use of realtime capnography is associated with a
15% decrease in the incidence of hypoxia
compared with standard monitoring alone
during ED procedural sedation with
propofol
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Materials & Methods
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Study Design

prospective, randomized controlled trial
conducted from November 2006 to
February 2008.
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Setting & Selection of Participants
Study was conducted at Albert Einstein
Medical Center, a 600-bed teaching
hospital located in Philadelphia, with an
annual ED census of 75,000 patients.
 Enrolled consecutive (24 hours a day, 7
days a week) adults >18 years & selected
for propofol sedation in accordance with
their usual practice

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Setting & Selection of Participants

Exclusion critiria:
* severe chronic obstructive pulmonary disease;
* chronic oxygen requirements;
* hemodynamic instability;
* respiratory distress;
* pregnancy;
*Inability to provide informed consent;
* allergy to propofol, morphine, or fentanyl (or other components of its
formulation);
* or if, in judgment of the attending emergency physician, procedural
sedation could compromise patient safety. Informed consent was
obtained from each subject.
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Setting & Selection of Participants
Pts randomly assigned to study group
(standard monitoring and capnography) or
control group (standard monitoring and
blinded capnography) by research
associates using computer-generated
randomization list.
 Research associates & treating physicians
were blinded to the randomization choice
until after enrollment.

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Setting & Selection of Participants

Inaddition to standard electronic
monitoring, they attached a Capnostream
20 monitor, using a nasal-oral CO2
cannula capable of delivering compressed
gasses, with an oral sampling port to
accommodate mouth breathers
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Setting & Selection of Participants
Capnostream 20 monitor displays oximetry
and CO2 waveform and calculates
ETCO2.
 All patients had capnography;
 for the blinded (control) group, the monitor
screen was adjusted to permit
visualization only by the research
associate.

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Setting & Selection of Participants



All patients received supplemental oxygen at 3
L/minute by nasal cannula.
If the treating physician wished to deliver
additional oxygen during the sedation, a
nonrebreather mask connected to wall oxygen at
15 L/minute was placed over the cannula.
All patients received 0.5 g/kg of fentanyl or 0.05
mg/kg of morphine for analgesia no fewer than
30 minutes before administration of propofol for
sedation.
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Setting & Selection of Participants

They started with propofol 1 mg/kg,
administering additional boluses of 0.5 mg/kg
until desired level of sedation was achieved.

Patients closely monitored from the initiation of
sedation until they were back to their baseline
alertness and ready for discharge.
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Data Collection and Processing
Data were collected by trained research
associates, physicians who had
participated in previous sedation studies &
had no duties other than patient
enrollment and data recording.
 They were trained in procedural sedation
& analgesia, study protocol and its
definitions, all monitoring devices, and
signs of respiratory depression.

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Data Collection and Processing


They recorded age, sex, medical history, Rx,
allergies, types of procedures performed, vital
signs, & sedation and procedure times on a
standardized data collection instrument.
The patient’s level of alertness was assessed at
baseline, 90 s after preprocedure drug
administration, & before discharge, using a
modified Ramsay scale
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Data Collection and Processing



Before the study, physicians & nurses trained in
identification of respiratory depression with
capnography
Treating physicians were instructed to perform
procedural sedation and analgesia according to
standard protocol
Any intervention for an adverse event should be
based on their judgment and clinical expertise
with or without capnography, depending on
randomization arm.
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Data Collection and Processing
Capnostream 20 records data
electronically every 5 seconds during
course of each sedation,
 Research associates used electronic
marking and time stamping to record
specific events such as drug
administration, beginning and end of
procedure, and point of readiness for
discharge

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Data Collection and Processing


They noted time and nature of any intervention
for respiratory depression or hypoxia, such as
verbal or physical stimulation, airway
realignment, use of additional oxygen, and the
use of airway adjuncts, assisted ventilation, or
intubation.
Research associates manually recorded other
sedation-associated adverse events, including
hypotension, bradycardia, arrhythmia, vomiting,
prolonged ED stay, or admission
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Outcome Measures
Electronic data from each sedation were
downloaded from the monitor into a
Microsoft Excel 2000 database & were
checked for any discrepancies, with
handwritten notations taken by the
research associates.
 printed time evaluation graph of the
patient’s sedation was then produced

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Outcome Measures
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Outcome Measures



Before study blinding was broken, 3
investigators evaluated each graph to code the
presence or absence of hypoxia & respiratory
depression.
Hypoxia was defined a priori as an SpO2 level of
less than 93% for 15 seconds or greater.
Respiratory depression was defined a priori as
an ETCO2 level of 50 mm Hg or greater, an
absolute increase or decrease from baseline of
10% or greater, or a loss of waveform for 15
seconds or greater
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Outcome Measures
Grafs disqualified if they had greater than
35% data loss, unless all 3 evaluators
agreed that there was unequivocal
evidence of hypoxia or respiratory
depression.
 Lost data were typically due to patient
movement (ie, dislodgement of the
cannula) or blood pressure cuff
insufflation.

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Primary Data Analysis



Data analyzed descriptively & using χ2, with
P<.05 considered significant. All analyses were
with SPSS version 10.
Previous research has reported rates of hypoxia
during ED propofol sedation ranging from 15%
to 30%.
To identify a 15% decrease in hypoxia from a
20% presumed baseline, they calculated that
they would need 72 pts in each arm (assuming a
1-tailed analysis, a power of 80%, and an α of
5%).
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RESULTS
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Characteristics of Study Subjects
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Characteristics of Study Subjects
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Main Results
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Main Results
majority of patients who developed respiratory depression had an
ETCO2 change greater than 10% from baseline
loss of waveform was most likely to lead to hypoxia.
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Main Results
• With capnography there were more physician interventions to
improve respiratory status, 24 of 68 (35%) versus 14 of 64 (22%;
difference 13%; 95% CI –2% to 27%)
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Limitations
They had a higher-than-expected
disqualification rate, leaving slightly less
than calculated 72 patients per group for
analysis.
 However, they found a significant
difference in their main outcome, and thus
the study was not underpowered

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Limitations
The observed rate of hypoxia (32.5%) was
higher than that observed in most other
studies of propofol for ED procedural
sedation.
 A rate of hypoxia more consistent with
previous studies may have produced a
smaller, nonsignificant difference between
groups

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Limitations

possibly that the continuous electronic
data collection using the Capnostream 20
influenced the rate of hypoxia because it
would detect episodes that might
otherwise be missed through recording
only at spaced intervals or through human
inattention or error.
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Limitations
unlikely that any device error contributed
to the higher-than-expected rates of
hypoxia and respiratory depression
 It is possible that, if the clinicians had used
greater amounts of supplemental oxygen,
there would have been less overall
hypoxia

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Limitations
They chose a priori an SpO2 of 93% as
baseline level for hypoxia because they
believe that most physicians will pay close
attention and potentially intervene at this
level.
 A lower threshold would have resulted in
less overall hypoxia.

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Discussion
Rate of hypoxic events decreased by
using capnography in conjunction with
standard monitoring. (17%)
 Capnographic respiratory depression
occurred before the onset of hypoxia and
was temporally linked to subsequent
hypoxic events.

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Discussion
every patient who developed hypoxia had
a corresponding ETCO2 change.
 the increased sensitivity of the nearcontinuous electronic data capture with the
Capnostream 20 allowed to measure this
effect.

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Discussion
Capnography can provide early warning of
ventilatory abnormalities, alerting
physicians to respiratory depression
before the onset of a hypoxic event.
 Using capnography in this study,
emergency physicians improved pt safety
by decreasing rate of hypoxic events ass.
with procedural sedation & analgesia

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Discussion
a number of patients had respiratory
depression & hypoxia & treating physician
did not intervene, with the episodes
resolving spontaneously.
 If every incidence of respiratory
depression had led to an intervention, it is
possible that there would have been less
hypoxia

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1. Are the results in
the study valid ?
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Primary Guide

Was there an independent, blind
comparison with a reference standard ?

Did the pt sample include an appropriate
spectrum of pts to whom the diagnostic
test will be applied in the clinical practice ?
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Secondary guide

Did the results of the test being evaluated
influence the decision to perform the
reference standard ?

Were the methods for performing the test
described in sufficient detail to permit
replication ?
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What are the results?
Are LR for the test results
presented or data neccessery
for their calculation provided ?
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R.D
+
R.D
totals
10/5/2009
Hypoxia
+
17
a
0
c
17
a+c
Hypoxia
22
b
29
d
51
b+d
totals
39
a+b
29
c+d
68
a+b+c+d
49
Results

Sensitivity = a /a+c
(TP among diseased)
= 17 / 17 = 1 = 100%

Specificity = d /b+d
(TN among non diseased)
= 29 / 51 = 0.57 = 57%
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Results
PPV = a /a+b (TP among all Positives)
= 17 / 39 = 0.44 = 44%
 NPV= d /c+d (TN among all Negatives)
= 29 / 29 = 1 = 100%
 LH+ = (sens) / (1 - spec )
= 100 / 43 = 2.3
 LR- = (1-sens) / (spec)
=0

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Results
Prevalence = (a+c) / (a+b+c+d)
= 17 / 68 = 25 %
 Pre-test odds = prevalence / (1-prevalence)
= 25 / 75 = 0.33
 Post-test odds = pre-test odds * LR
for (+)
= 0.33 X 2.3 = 0.79
for (-)
= 0.0.33 X 0 = 0
 Post-test Probability = post-test odds / (post-test
odds + 1) = 0.43 = 44 %

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Will the results help
me in caring for my
patients ?
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
Will the reproducibility of the test results &
its interpretation be satisfactory in my
setting ?

Are the results applicable to my patients ?

Will the results change my management ?

Will patients be better off as a result of the
test ?
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Definition

(LR) is the likelihood that a given test
result would be expected in a patient with
the target disorder compared to the
likelihood that that same result would be
expected in a patient without the target
disorder
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
LH ratio for a positive result (LR+) tells
you how much the odds of the disease
increase when a test is positive.

LH ratio for a negative result (LR-) tells
you how much the odds of the disease
decrease when a test is negative.
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
Depending on article or source, a single
LR might be presented without reference
to “positive” or “negative”
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 LR
= 1 means the post-test probability is
exactly the same as the pre-test probability
 LR
> 1 increases the probability that the target
disorder is present
 LR
< 1 decreases the probability that the
target disorder is present
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Applications
LR is used to assess how good a diagnostic test
is and to help in selecting an appropriate
diagnostic test(s) or sequence of tests.
 They have advantages over sensitivity and
specificity because:
 they are less likely to change with the
prevalence of the disorder,
 they can be calculated for several levels of the
symptom/sign or test,
 they can be used to combine the results of
multiple diagnostic test
 can be used to calculate post-test probability for
a target disorder

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