1. WAS
February
27,
2016
Best Papers of 2015
Alana M. Flexman, MD FRCPC
Clinical Assistant Professor
Department of Anesthesiology and Perioperative Care
Vancouver General Hospital
University of British Columbia
Whistler Anesthesiology Summit
February 27, 2016
2. WAS
February
27,
2016
Disclosures
• Research
grants:
² Canadian
Anesthesiologists’
Society
² Hospira,
Inc
² Masimo,
Inc
• Honoraria
² Hospira,
Inc
3. WAS
February
27,
2016
Paper
selecGon
• Clinical
Focus
• General
Appeal
• Past
12
months
• 5
papers
selected
Objec&ve:
To
review
influen&al
publica&ons
from
the
past
year
4. WAS
February
27,
2016
Survey says…
Premedication with lorazepam results in
which of the following:
A. Improved patient satisfaction
B. Similar time to extubation
C. Reduced intraoperative hypotension
D. Slower recovery of early cognition
5. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
6. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
To assess the efficacy of preoperative
sedation in influencing a patient’s
perioperative experience
7. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
N=1062 randomized
Elective surgery, GA
N=354
Lorazepam
2.5 mg
N=354
No Premed
N=354
Placebo
Primary Outcome: Patient Satisfaction (EVAN-G)
Secondary Outcomes: PQRS, cooperation, anxiety, pain,
well-being, quality of sleep & recover, time to extubation
8. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
Lorazepam No
premed
Placebo P-
Value
Overall
satisfaction
72 73 71 0.38
Time to
extubation
17 min 12 min 13 min <0.001
Amnesia 24% 6% 6% <0.001
Anxiety in
OR (VAS)
35 38 44 0.001*
Pain
satisfaction
68 66 53 0.01
9. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
10. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
• Sedation with lorazepam did NOT improve
self-reported patient experience the day of
surgery
• But reduced anxiety on arrival to OR
• Sedation was associated with 4 min
prolongation of extubation time and lower
rate of early cognitive recovery
11. WAS
February
27,
2016
Szamburski
et
al
Szamburski
et
al,
JAMA
2015;
313:
916-‐925.
Rou&ne
premedica&on
with
lorazepam
12. WAS
February
27,
2016
Survey says…
In the management of acute STEMI,
providing supplemental oxygen to normoxic
patients results in:
A. Worse patient outcomes
B. No effect on patient outcomes
C. Improved patient outcomes
13. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
14. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
• AMA: : no clear recommendation
• 90% receive supplemental oxygen
Beasley
et
al,
J
R
Soc
Med
2007;100:130-‐133.
15. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
Compare supplemental oxygen therapy with
no oxygen therapy in normoxic patients with
STEMI to determine its effect on myocardial
infarct size
16. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
Primary
Outcome:
Myocardial
injury
(peak
cTnI
&
CK)
Secondary
Outcomes:
ST-‐segment
resoluGon,
mortality,
major
adverse
cardiac
events,
infarct
size
at
6
months
N=470 enrolled, 441 completed
STEMI, SpO2 >94%
Supplemental O2
8 L/min
N=218
No O2 unless SpO2
<94%
N=223
17. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
• 7% of No Oxygen group required O2
• SpO2 higher in Supplemental O2 group
• Baseline characteristics, hemodynamics
and procedures similar
18. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
Outcome Oxygen No Oxygen P-value
Mean peak TnI 57.4 48.0 0.18
Mean peak CK 1948 1543 0.01
Mean infarct size 14.6 10.2 0.06
ST resolution 62% 70% 0.10
Recurrent MI 5.5% 0.9% 0.006
Death 1.8% 4.5% 0.11
Major arrhythmias 40% 31% 0.05
19. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
20. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
• Routine oxygen therapy not
associated with reduction in
symptoms or infarct size
• Routine high-flow oxygen
may be accompanied by
harm
21. WAS
February
27,
2016
Stub et al
Stub
et
al,
CirculaGon
2015;131:2143-‐2150.
Supplemental
O2
in
normoxia
for
STEMI?
(cardiac
ischemia?)
22. WAS
February
27,
2016
Survey says…
Jorgenson
et
al,
JAMA
2014;312(3):269-‐277.
Which of the following is most
effective in reducing intravascular
catheter-associated infections?
A. Chlorhexidine-alcohol
B. Iodine
C. Iodine-alcohol
D. Skin scrubbing before insertion
23. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
24. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
1) To compare the efficacy of chlorhexidine-
alcohol vs providone iodine-alcohol to
prevent short-term catheter-related
infections
2) To determine the effect of skin scrubbing
with antiseptic detergent on catheter
colonisation
25. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
N=2349 enrolled
ICU requiring CVL or arterial line >48h
Iodine-
alcohol &
scrubbing
N=1286
catheters
Iodine-
alcohol & no
scrubbing
N=1326
catheters
Chlorhex-
alcohol &
scrubbing
N=1270
catheters
Chlorhex-
alcohol & no
scrubbing
N=1277
catheters
Primary
Outcome:
Incidence
of
catheter-‐related
infecGons
Secondary
Outcomes:
Incidence
of
catheter
colonisaGon
26. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
• Groups similar with respect to:
• Demographics
• History of immune deficiency/disease
• Metastatic cancer
• Indication for admission
• Type of line inserted
• Operator experience
28. WAS
February
27,
2016
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
NNT 78 catheters in place for a
mean of 8 days to prevent 1
infection
29. WAS
February
27,
2016
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
Less catheter-related blood
infections with chlorhexidine
30. WAS
February
27,
2016
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
No benefit to scrubbing
31. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
• No difference in ICU length of stay or
mortality between the preps
• No difference in incidence of colonisation
with scrubbing
• Higher rate of severe skin reactions with
chlorhexidine-alcohol (3% vs 1%, p=0.0017)
32. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
1 infection=€19583($39346.89)
Chlorhexidine for 78catheters=€227($456.14)
33. WAS
February
27,
2016
Mimoz et al
Mimoz
et
al,
Lancet
2015;386:2069-‐2077.
• Chlorhexidine-alcohol combination should
now be standard of skin preparation
before major intravascular catheter
insertion
• Scrubbing of the skin with detergent
should not be standard
34. WAS
February
27,
2016
Pollack
et
al
Pollack
et
al,
NEJM
2015;
373:
511-‐20.
Chlorhexidine-‐
alcohol
✔
35. WAS
February
27,
2016
Survey says…
Which of the following is NOT associated with
increased perioperative mortality:
A. Age > 65 years
B. Case start after 4:00pm
C. ASA physical status > 3
D. Male gender
E. Age <1 year
36. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
37. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
• Predictors of postoperative mortality
across broad surgical populations unclear
• National Anesthesia Clinical Outcomes
Registry (NACOR)
38. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
To identify factors associated with
perioperative mortality using the
NACOR dataset
39. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
Entire NACOR Dataset
18 487 093
Outcome eligible
2 948 842 cases
Missing data
17383 cases
Obstetric
65318 cases
Final Dataset
2 866 141
cases
No outcome
15 538 251 cases
40. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
Predictor
variables:
PracGce/facility
type
PaGent
factors
(age,
sex,
ASA)
Emergency/elecGve
Procedure
factors
(type)
Anesthesia
factors
(type)
Case
start
Gme
and
duraGon
Primary
Outcome:
Death
within
48
hours
of
inducGon
41. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
Predictor
variables:
PracGce/facility
type
PaGent
factors
(age,
sex,
ASA)
Emergency/elecGve
Procedure
factors
(type)
Anesthesia
factors
(type)
Case
start
Gme
and
duraGon
Primary
Outcome:
Death
within
48
hours
of
inducGon
Multivariate regression
42. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
Predictor
variables:
PracGce/facility
type
PaGent
factors
(age,
sex,
ASA)
Emergency/elecGve
Procedure
factors
(type)
Anesthesia
factors
(type)
Case
start
Gme
and
duraGon
Primary
Outcome:
Death
within
48
hours
of
inducGon
Sensitivity analysesMultivariate regression
43. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
Variables independently associated with mortality
Increasing ASA
Emergency case
Age < 1 year
Age > 65 years
Cases beginning between 4:00pm and 6:59am
44. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
45. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
46. WAS
February
27,
2016
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
• Confirmed association with known
predictors of outcome (e.g. ASA
class, age)
• Increased mortality in cases starting
after 4pm
• Potentially modifiable risk factor NEW
47. WAS
February
27,
2016
Minimize
surgery
aIer
4:00pm?
✔
Whitlock et al
Whitlock
et
al,
Anesthesiology
2015;123:1312-‐1321.
48. WAS
February
27,
2016
Survey says…
In patients with atrial fibrillation, bridging
warfarin with LMW heparin around surgery:
A. Reduces the risk of stroke
B. Increases the risk of bleeding
C. Reduces the risk of DVT/PE
D. Reduces the risk of death
49. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
50. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
51. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
N=1884 randomized
Afib on Warfarin
Bridging
(Dalteparin)
No bridging
(Placebo)
Primary Efficacy Outcome: Arterial thromboembolism
Primary Safety Outcome: Major bleeding
52. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
Patients:
• Mean CHADS2 score: 2.3
• 34% on ASA
• 3.7% on Clopidogrel
• 31% CHF or LV dysfunction
53. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
Outcome
No
Bridging
Bridging
P-‐value
Arterial
thromboembolism
0.4%
0.3%
0.73
(0.01
Non-‐Inf)
Major
Bleeding
1.3%
3.2%
0.005
Death
0.5%
0.4%
0.88
Myocardial
Infarc&on
0.8%
1.6%
0.10
DVT/PE
0%
0.1%
0.25
Minor
Bleeding
12%
20.9%
<0.001
54. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
• Discontinuing warfarin without bridging was
non-inferior to bridging in preventing arterial
thromboembolism
• Bridging led to increased major and minor
bleeding
• No difference in MI, VTE, death
• Net benefit in avoiding bridging
55. WAS
February
27,
2016
DoukeGs
et
al
DoukeGs
et
al,
NEJM
2015;373:823-‐33.
Rou&ne
bridging
for
atrial
fibrilla&on
56. WAS
February
27,
2016
References
1. Maurice-Szamburski A, Auquier P, Viarre-Oreal V, Cuvillon P, Carles M, Ripart
J, et al. Effect of sedative premedication on patient experience after
general anesthesia: a randomized clinical trial. JAMA. 2015 Mar 3;313(9):
916-25.
2. Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air
Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation.
2015 Jun 16;131(24):2143-50.
3. Mimoz O, Lucet JC, Kerforne T, Pascal J, Souweine B, Goudet V, et al. Skin
antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol,
with and without skin scrubbing, for prevention of intravascular-catheter-
related infection (CLEAN): an open-label, multicentre, randomised,
controlled, two-by-two factorial trial. Lancet. 2015 Nov 21;386(10008):
2069-77.
4. Whitlock EL, Feiner JR, Chen LL. Perioperative Mortality, 2010 to 2014: A
Retrospective Cohort Study Using the National Anesthesia Clinical
Outcomes Registry. Anesthesiology. 2015 Dec;123(6):1312-21.
5. Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, et al.
Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.
N Engl J Med. 2015 Aug 27;373(9):823-33.