International Short Course Training in
Research Methodology & Biostatistics
Final Presentation
Critical Appraisal
Title of the article
A Single Injection Ultrasound-Assisted Femoral Nerve Block
Provides Side Effect-sparing Analgesia When Compared with
Intrathecal Morphine in Patients Undergoing Total Knee
Arthroplasty
Presenter: Malinee Wongswadiwat
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Course:
Critical appraisal
Module:
How to read clinical journal?
Objective:
To be able to critically appraise the published
medical research article.
Title:
A Single Injection Ultrasound-Assisted
Femoral Nerve Block Provides Side EffectSparing Analgesia When Compared with
Intrathecal Morphine in Patients Undergoing
Total Knee Arthroplasty
Authors:
Brian D. Sites, MD
Michael Beach, MD, PhD
John D. Gallagher, MD
Robert A. Jarrett, MD
Michael B. Sparks, MD
C. Johan F. Lundberg, MD, phD
Journal:
Anesthesia & Analgesia 2004; 99: 1539-43.
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CONTENT
PAGE
SCENARIO
4
RATIONAL AND BACKGROUND
5
SELECTION OF THE ARTICLE
6
SUMMARY OF THE ARTICLE
7
CRITICAL APPRAISAL OF THE SELECTED ARTICLE
12
CONCLUSION
16
ATTACHED SELECTED ARTICLE
17
3
Clinical Scenario
A patient was scheduled for total knee replacement due to severe osteoarthritis. I was
assigned to the operating room on that day as an anesthesiologist. Patient had been
visited the day before operation and she was very concern about postoperative pain.
Patient did agree with spinal anesthesia technique. Therefore I planed to add
morphine in the spinal anesthesia solution which is one of the standard techniques to
provide better pain control postoperatively. However, with this technique the bladder
catheterization is required for 24 hrs after operation to prevent urinary retention.
One orthopedic surgeon who took responsible for this patient came in and announced
that “Do not use spinal morphine” “I don’t want my patient to have bladder
catheterization” His reason was, he had bad experience in three different cases
previously related to urinary tract infection. He blamed it was the source of septic
joint. Although other orthopedic surgeons did not concern like this surgeon.
However, the bladder catheterization after spinal morphine has been accepted by
orthopedic surgeon internationally. Many questions pop up in my mind.
How many infection rates come from bladder catheterization?
If patient has urinary tract infection from bladder catheterization, how many
prosthetic infections causing by this procedure?
Are there other techniques that provide good postoperative pain control equally
or even better than spinal morphine and do not require bladder catheterization?
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Rationale and background
Total knee replacement (TKR) is considered severe pain postoperatively. Meanwhile,
early ambulation and rehabilitation are required to improve outcome. Good
postoperative pain control is one of the impact factors to control. There are many
techniques to control pain such as patient controlled analgesia, spinal morphine and
femoral nerve block. In our hospital, we apply all these options which depend on
anesthetic technique and options that patient agree.
Spinal anesthesia is the most common technique that we use. Adding
morphine in the spinal anesthetic solution is the easy way and also provide good pain
control for 18-24 hrs and reduce extra morphine requirement for more than 50%.
However, there are some side effects such as itchy, nausea, vomiting and urinary
retention. After I searched for the incidence of urinary retention, one article revealed
that the incidence was 20-40% in the first 24 hrs and decreased to 10% after. Another
study revealed that urinary tract infection developed 1.6 % and 1.7% in whom bladder
catheterization was preoperatively inserted and intermittent as necessary respectively.
One study shown 2.1% (3 patients) prosthesis infection in their study and only one
patient bladder catheterization was inserted.
The orthopedic surgeon is very concern about infection rate therefore even
minute factor that might causing infection is needed to be concerned.
Femoral nerve block with local anesthetic is another technique for reducing
pain when added with anesthetic technique even general or spinal anesthesia.
However, I question about the result of pain control compare with spinal morphine
technique. With this technique the incidence of urinary retention is very low thus we
do not require urinary catheterization.
If femoral nerve block gives equal or better result without urinary
catheterization, we would prefer this technique.
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Selection for the article
This article “A single injection ultrasound-assisted femoral nerve block provides
side effect-sparing analgesia when compared with intrathecal morphine in
patients undergoing total knee arthroplasty” was searched by assessing “medline”
the electronic journal database provided by National Library of Medicine. The
website is http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed or
pubmed.com
With the key word “femoral nerve block AND total knee replacement” .There was
52 articles in the list but no even one compare the two techniques. I typed the key
word “femoral nerve block AND total knee replacement AND spinal opioid. I
found 4 articles and only one of these articles attracting me. They compared two
techniques that could provide postoperative analgesia for knee replacement that match
with my question.
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SUMMARY OF THE ARTICLE
TITLE
A single injection ultrasound – assisted femoral nerve block provides side effectsparing analgesia when compared with intrathecal morphine in patient undergoing
total knee arthroplasty
OBJECTIVE
They hypothesized that addition of femoral nerve block with intrathecal bupivacaine
would provide superior analgesia when compare to adding morphine in bupivacaine
for intrathecal and also fewer side effects.
STUDY DESIGN
Randomized controlled trial
STUDY SETTING
Dartmouth medical school, Dartmouth Hitchcock Medical center, Lebanon, New
Hampshire, USA
METHODOLOGY
This study was reviewed and approved by the Dartmouth college committee for
protection of human subjects.
Population: 41 patients, ASA physical status 1-3, single total knee arthroplasty were
enrolled in this study.
Exclusion criteria:
Age under 18 yrs
Pregnancy
Had history of chronic obstructive lung disease, allergy to the study drugs,
chronic pain syndrome unrelated to their knee pathology, chronic opioid use,
contraindications to spinal block and regional anesthesia.
Exclusion after randomization: failed femoral nerve block or spinal block.
Randomization:
Patients were randomized in one of two treatment group on the day of surgery.
Computer generated assignment.
Block randomization, group of 6
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STUDY PROTOCOL
41 patients
Spinal block with 15 mg IT
bupivacaine
+
0.25 mg of morphine
Femoral nerve block: 40 ml of 0.5%
ropivacaine+ 0.075mg clonidine+
5mcg of adrenaline
Spinal block with 15 mg IT
bupivacaine
PACU care
All patients were provided
 PCA morphine
 Extra IV morphine supplement until achieve satisfactory analgesia
(VAS<3) by nurse in PACU
 Ketolorac on schedule basis q6h continue to ward
 Age<55yrs: 30 mg
 Age >55yrs: 15 mg
Data collection by research nurse
Collection at 1, 2, 4,6,12 and 24 h
postoperatively
Systolic blood pressure
Oxygen saturation
Morphine consumption
Others medications
Nausea/vomiting / itching scale
VAS score: at rest, at movement
Cold test for FNB group
Satisfaction score at 1 week after discharge
Nausea, vomiting, itching scale
1=none 2=mild 3=moderate 4=severe
Satisfactory scale
1=unsatisfactory, 2=satisfactory
3=very good 4= outstanding
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Note: femoral nerve block instruction
They used ultrasound guide for only landmark and after skin was marked nerve
stimulator was used as a standard technique.
SAMPLE SIZE CALCULATION
The researcher used a standard deviation of 22 mg of morphine estimated from
previous study at their institution with 250 mcg of intrathecal morphine.
To obtain a power of 80% where delta=20 mg of morphine use and alpha = 0.05 each
study group required an enrollment of 20 patients.
Primary outcome measurement
 Amount of IV morphine used in the first 24 hr.
 VAS score at the difference time intervals.
Secondary outcome measurement
 The incidence of postoperative side effects such as nausea, vomiting, pruritus
and sedation.
 The use of medication for treatment of side effect.
 Satisfaction of patients in their anesthetic experiences.
Statistical analysis
 Univariate analysis was accomplished using unadjusted Pearson x2 for
categorical variable.
 Student’s t-test for continuous variable
 95% CI of differences were reported for continuous variable
 Relative risks were report for binary variables.
 Logistic regression, ordinal regression and standard regression technique were
used as appropriated based on the response to explore predictors of
satisfaction, morphine used and morbidity such as nausea.
 P-value of < 0.05 was used to indicate statistical significance.
RESULTS






Forty-one patients were enrolled.
One patient was removed after randomization because of failed to success
femoral nerve block secondary to patient anxiety.
Demographics revealed no significant difference in sedative, analgesic,
antipruritus, pain and antiemetic or antipruritic medications intraoperatively.
The incidences of nausea, vomiting, and pruritus were significantly more
frequent in the intrathecal morphine postoperatively. (table3)
The use of antiemetic, antipruritic medication was also more frequent in the
intrathecal morphine group. ( table3)
Satisfaction survey revealed 20% of the patients in the ITM group rated
“unsatisfactory” due to severe vomiting compared with none in FNB
group.(table 4)
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Demographics in this study
revealed no differences in an
important characteristic of
patients between groups.
Primary outcome of this study was amount of accumulate morphine at 24 hrs. This
table showed very little magnitude of difference which was no significant between
groups.
24.2-21.4 = 2.8 mg
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CONCLUSION:


Patient experienced equal postoperative analgesia, whereas the femoral nerve
block group sustained fewer side effects including nausea, vomiting, and
itching.
Patients receiving IT morphine were overall less satisfied because of side
effect.
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CRITICAL APPRAISAL OF THE SELECTED ARTICLE
GENERAL STEPS FOR SELECTED ARTICLE
Title
The title was interesting and clearly stated and hit to the point of my question. The
patient group in this article specific to the same operation (Total knee replacement)
that I required the answer. They compared two techniques which generally used in
anesthetic technique.
Authors
The author and colleagues were staffs from medical school and medical center. They
work in anesthesiology department especially the first author was the director of
regional anesthesia .They also had their colleagues from orthopedic department that
were an expert in that operation. There were eight published article related to regional
anesthesia for the first author in Pubmed search.
Abstract
The abstract contained the relevant information about the study design, intervention,
outcome measurements, result and conclusion
Generalizability
This study was conducted quite similar to my practice. So the rational and the result
might be applicable to my practice.
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APPRAISAL OF THE SELECTED ARTICLE
PART 1: Are the results valid?
1. Were patients randomized to treatment groups?
Yes. The computer generated assignment was used for randomization patients into
2 groups of treatment. They also stated their randomization was blocked into
groups of six to minimize any time effect.
The population of each group has been done to be equal all the time with
block randomization. However, the disadvantage of block randomization is
imbalance in prognostic factors.
With the population of 20 each, they should random with block of four instead
of six.
2. Was randomization concealed?
Lack of information indicated that the randomization was concealed.
3. Was follow up rate adequate?
Yes. Forty one patients were enrolled. They stated that one patient was excluded
from the study after randomization because of failed femoral nerve block. All
forty patients in both groups were continued and assessed until the end of study.
4. Were patients analyzed under the groups to which they were originally
randomized?
Yes, there was no contamination or co-intervention between groups.
5. Were patients blinded to group allocation?
No. Femoral nerve block group is the procedure at the groin and especially using
ultrasound and nerve stimulator. Nerve stimulator makes muscle twitching which
difficult to blind the patients. Also sensory distribution of femoral nerve was
tested by cold temperature before performing spinal block in this group.
6. Were clinicians blind to group allocation?
No. although both groups received spinal block procedure but in the femoral nerve
block group, another procedure had to be done before spinal procedure. They did
not mention about sham femoral block in intrathecal morphine group.
7. Were the assessors blinded to group allocation?
Yes. They did mention about placing dry sterile gauze at every patients’ groin,
regardless of group assignment. I assumed that the researcher aim to blind
assessors which was the only one category left to blind. The data were collected
by research nurse at 1, 2, 4, 6, 12, 24 hrs postoperative.
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8. Were the groups similar at the start of trial?
Yes. According to demographics data, there were no significant between 2 groups
of population.
PART 2: What are the results?
1. How large was the treatment effect?
The difference of the primary outcome of this study was only 2.3 mg of morphine.
This study revealed that the accumulation of IV morphine used in 24 hrs were not
significant differences between groups. Mean and SD of accumulation of
morphine used in ITM and FNB were 21.4 (22.0) and 24.2(10.5) respectively.
They showed the incidence of postoperative side effects for the secondary
outcome, nausea, vomiting, itching, antiemitic medication and antipruritus
medication between ITM and FNB were statistical significant p<0.05. ITM had
higher side effect when compared with FNB group.
According to the incidence of postoperative side effect in table 3, I calculated
NNH as the following table
outcomes
Hypotensive event
Desaturation event
Moderate to severe nausea
Moderate to severe vomiting
Moderate to severe itching
Moderate to severe sedation
ARR
25
20
45
45
65
20
RRR
0.27
0.57
0.6
0.56
0.92
0.8
NNH
4
5
2.2
2.2
1.5
5
I also calculated total of postoperative side effects compared between two groups
as the table below.
Side effects
ARR
RRR
NNH
ITM 102/142
43.6
0.6
2.3
FNB 40/142
Patients’ satisfaction was calculated in NNT as the table below
outcomes
satisfied
ARR
20
NNT
5
2. How precise was the estimate of the treatment?
Overall 95% CI of primary outcome was quite wide (-14-8.5) which means no
significant between group and not precise.
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PART 3: How can I apply the results to my practice?
1. Does the study provide a direct enough answer to my clinical question in
terms of type of patients, intervention and outcome?
YES. Even though, this article was not exactly clear in term of controlling factor
which it interfered the primary outcomes. There were many drugs influence the
primary outcome which they could not conclude about the difference in
techniques. For example, ketorolac was used in every patient and it reduced pain
intensity and they might not get the real pain expression and morphine
consumption. They also added clonidine in the local anesthetic solution for
femoral nerve block. This drug has documented to reduce pain when use with
peripheral nerve. However, these drugs that they added, ketorolac, clonidine were
the standard regimen in some institutes. The only thing that they did not clearly
mention was the extra IV morphine that they used to achieve satisfactory
analgesia without report. They should let patients use only IV PCA to titrate at the
beginning and bring total amount of morphine to be calculated.
2. Were the study patients similar to the patient in my practice?
a. Look for biological differences in the illness under study that may
alter my patient’s treatment response
The disease and operation of my patient were exactly the same.
b. Look for biological differences among patients that may alter their
treatment response.
My patients are in the same age group so this should be the same
biological condition.
c. Look for co-morbid condition that may significant alter my
treatment response.
The drugs that given to patients in both groups were no significant affect
to others condition.
d. Compare the incidence of outcome in untreated patients in your
target population with that of the control group in the study.
There is very severe pain in untreated patient. However this study
compared 2 treatments, ITM and FNB. The incidence of side effects from
ITM was quite high when compared with FNB.
3. Were all clinical relevant outcomes considered?
Yes. They reported the primary outcomes which we usually use. Also they
reported the side effect that occurred in their study. These side effects will
determine our decision if the primary outcomes were not difference.
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4. Are the likely treatment benefits worth the potential harm and cost?
Yes. Side effect from ITM made patients unsatisfied and also need to be treated
with medications which consume some cost. However, FNB take higher cost from
the equipment for nerve stimulation and local anesthetic drug but easy to perform
and less postoperative side effect. These side effects may cause prolong hospital
stay and patients unsatisfied that cost even more. I might be considered if this
study was clearly conducted in research methodology.
CONCLUSION
Overall, this article was not clearly conducted in methodology which made their
results unclear. I think this research should be redoing with more carefully control
other factors that might affect the results.
However, there were strong and weak points in research methodology in the
article.
Strong point
Randomized control trial
Complete follow up rate
Sample size was appropriated to
determine primary outcome
Calculated 95% CI for difference
Weak point
Did not mention about concealment
Patients, clinician were not blinded
The title “ultrasound assisted FNB” did
not reveal how important for using
ultrasound in discussion or conclusion
part.
Many confounding factors those affect
the outcomes.
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