rct · 2018-02-05 · •may be by chance the first rct picked a population with baseline svo2 of...
TRANSCRIPT
![Page 1: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/1.jpg)
RCT����������
����2018/01/09���������ICU
���
![Page 2: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/2.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 3: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/3.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 4: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/4.jpg)
�������������
↓
�/��� ����
![Page 5: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/5.jpg)
�����������
![Page 6: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/6.jpg)
=O�N�J�-1
FIL5U&3�:/�,A )@L5U#%�"�,A
��� 'H
IK +B.
S>���T
IK +B ���
• P9 ���SCD4MP9T
• 82 ���S����"?3�<
Q &3:/�G;�
(�����T
• P9�<QU�%!$���• ?3�<QU?3E6�*A7�0R�����
![Page 7: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/7.jpg)
=O�N�J�-1
FIL5U&3�:/�,A )@L5U#%�"�,A
��� 'H
IK +B.
S>���T
IK +B ���
• P9 ���SCD4MP9T
• 82 ���S����"?3�<
Q &3:/�G;�
(�����T
• P9�<QU�%!$���• ?3�<QU?3E6�*A7�0R�����
![Page 8: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/8.jpg)
���
Intervention
���
Outcome
• Intervention, Outcome�����• I�O�� ����
![Page 9: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/9.jpg)
• Intervention • Comparison
Patients
PatientPatientPatientPatient ����
Patient ����Patient ����
Patient ����Patient ����PatientPatient
Outcome Outcome
����
![Page 10: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/10.jpg)
• Intervention • Comparison
Patients
PatientPatientPatient
Patient ����Patient ����Patient ����
Patient ����Patient ����
PatientPatient
Outcome ? Outcome
RCT����
![Page 11: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/11.jpg)
#%�"-?PMU
HKN5X&2�;/�,C )BN5X#%�"�,C
��� 'J
KL�+D.
V@��W
KL�+D����
• Q: ���VEF3OQ:W
• 91 ���V����"A2�>
R�&2;/�I=�
(�����W
• Q:�>RX�%!$���• A2�>RXA2G6�*C8�0T��� �
'J�7S�<4����
![Page 12: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/12.jpg)
• Intervention • Comparison
Patients
PatientPatientPatient
Patient ���Patient ���Patient ���
Patient ���Patient ���
PatientPatient
Outcome ? Outcome
RCT������
������
����
![Page 13: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/13.jpg)
RCT�������
DGI4P'2�9/�-? *>I4P$&�#�-?
!��� (F
GH ,@.
N<���O
GH ,@ ���
• K8!���NAB3JK8O
• 71!���N�� �#=2�;
L '29/�E:�
)����O
• K8�;LP�&"%���• =2�;LP=2C5�+?6�0M�����
![Page 14: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/14.jpg)
N Engl J Med 2017;377:465-75.
�����
�����
![Page 15: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/15.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 16: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/16.jpg)
CONSORT (/�• 1996*�#6CONSORT(/�D7
Consolidated Standards of Reporting Trials: >+@I'%�F��<$&3
• 2001*-?↓↓ )� @I;1��C"
↓CONSORT2010�D7• C"�'% .2�B��� • �2=ERCT�54�,����• 25H8 ��������������• 9: .2A�������0!G &3
![Page 17: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/17.jpg)
�
�
�
�
�
�
�
![Page 18: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/18.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 19: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/19.jpg)
![Page 20: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/20.jpg)
����Introduction
�����
•���������rationale ����•���������hypothesis �
• Clinical Question↓
• Research Question�PICO �� ���↓
• Intervention vs. Comparison �� ����
![Page 21: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/21.jpg)
��RQFINER����
• Feasible �����• Interesting ����• Novel������• Ethical ���• Relevant�����
![Page 22: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/22.jpg)
������� ���OK ?• Feasible �����• Interesting ����• Novel������• Ethical����• Relevant���!
![Page 23: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/23.jpg)
• RCTs are one of the possible experiments.
��
Premise��
Hypothesis��
Outcome
![Page 24: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/24.jpg)
• RCTs are one of the possible experiments.
�����
���
��
Premise�
Hypothesis�
Outcome
![Page 25: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/25.jpg)
• RCTs are one of the possible experiments.
��
��
Premise��
Hypothesis��
Outcome
![Page 26: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/26.jpg)
Many other trials, in our opinion,failed either because ,,,,
• Wrong premises
• Premises that were too vague and generic.If too generic, the heterogeneity of thepopulation is an unavoidable consequence.
![Page 27: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/27.jpg)
����� vs. �����• The trialists spent a lot of effort in improving their internal validity, by increasing the numberof rules and caveats to avoid possible biases in the conduct of the trials.
• This obviously makes the results valid only for the restricted patient population enrolled in the study and the generalization of the results(the external validity) is problematic.
![Page 28: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/28.jpg)
EGDT: 2001 → 2015
N Engl J Med 2001;345:1368-77.
![Page 29: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/29.jpg)
![Page 30: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/30.jpg)
�� Hypothesis
• Severe sepsis, septic shock
↓ ��CVP�ABP�SvO2
•���������� �����
![Page 31: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/31.jpg)
Outcome
N Engl J Med 2001;345:1368-77.
○
×××
![Page 32: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/32.jpg)
?
![Page 33: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/33.jpg)
Premise 1, 2 ○
• May be by chance the first RCT picked a population with baseline SvO2 of 48 %.
• The baseline SvO2 in the remaining trialswas already higher than 70 %, suggesting that oxygen imbalance was not the primary problem in the majority of the patients.
![Page 34: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/34.jpg)
?
![Page 35: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/35.jpg)
Premise 3 Too generic and wrong
![Page 36: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/36.jpg)
The pendulum effect• )�/����4��%�2�.0�!$����
• Single center→Multi center�&#��(���-+• EGDT65�.0����• %-�.0�������3�*,�'"����1)���� ��7����
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 37: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/37.jpg)
• Truly negative trials are valuable because they prevent the use of interventions that are either costly but nonbeneficial or even harmful (e.g.,intensive insulin therapy and hydroxyethyl starch).
• Understanding an evidence base requires the ability to distinguish among these reasons so as to differentiate trials that are truly negative from those that may be falsely negative.
![Page 38: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/38.jpg)
• Studies published between January 2007 and May 2013
• Single center���������
![Page 39: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/39.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 40: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/40.jpg)
![Page 41: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/41.jpg)
'- ���
•'- ����&(.�$#,0%�����/�������
•'-+�������*%���.)�� eligibility criteria ��/���!"�
![Page 42: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/42.jpg)
����Participant�
•���������eligibility criteria�
• ���������������
![Page 43: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/43.jpg)
Was the right group of patients not identified?• ���" �� ���$�AMI�����%• �! ������������ICU�� �#�
Why have so many RCTs “failed?”
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 44: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/44.jpg)
• General ICU� ������sepsis�ALI� ������������
![Page 45: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/45.jpg)
High Exclusion Rates Lead to Limited Clinical Applicability
With such tight exclusion criteria limiting enrollment,,,,
• How can the patient population that is actually studied really be representative of the entire population initially considered eligible?
• How can the results be applicable to the general ICU population?
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 46: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/46.jpg)
TRICC study• Just 13% of 6451
patients screened were randomized.
![Page 47: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/47.jpg)
VAAST study• 802 (12.9%) of the 6229
patients screened underwent randomization
![Page 48: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/48.jpg)
����������
• 1679 (84%) of 2011 patients were randomized.
N Engl J Med 2010;362:779-89.
![Page 49: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/49.jpg)
�� Intervention!
•����������������•����������������� �
![Page 50: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/50.jpg)
Were the interventions ineffective?�� �������� ��������
��
truly negative�������� ���������OK
Why have so many RCTs “failed?”
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 51: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/51.jpg)
Was it a question of severity?• 2*"!/�1�)+�( U shape���5)+�3�������� or ���4�� ���6
Is the timing of interventions correct?�%',*�&',*)+�(�0��-$��
�#�. ��
����7%',*8&',* Shock 2007; 28:636–643ARDS7%',*≑&',* Chest 2010; 137:81–87
Why have so many RCTs “failed?”
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 52: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/52.jpg)
�����1Outcome2
•���$���!)��*����+��#'�����,�/(�������,������� �
•-0.� ��������"��%&�
![Page 53: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/53.jpg)
G-;VSample sizeW
•�����JAG-;�D�����•*RN@�*B6E�Q>�
�*RN@
• I→?1*B�:→F1*B�=�0<��• N@�$ &("�5;�D���• 5;�7�����α!')�U��+�4T
→=�CS�*RN@�������3 ��p.�P9���28H,/�KL%# (�MO�
![Page 54: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/54.jpg)
Were the end points wrong?
• )�: 3'&�*0$7��9=:,�� ����;
• ��%"<��� !1��#��5.(�-+��9
• ��/<�4�8��
Was the power inadequate?
• �������62����
Why have so many RCTs “failed?”
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 55: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/55.jpg)
•����� ������
![Page 56: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/56.jpg)
• 2������������
![Page 57: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/57.jpg)
34��� ������������
![Page 58: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/58.jpg)
47���������� �����������
![Page 59: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/59.jpg)
(��10!(Allocation concealment) •���� (�2-�&)�,����+*4-"��'%��5�#/� ��.����� (�2-�10� �������
� �������$3
![Page 60: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/60.jpg)
�����
•����allocation ����������•���� � : ����������,�������
![Page 61: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/61.jpg)
• +9����&�$�(:)3
• ��������&�$� �ABAB AABB BABA ,,,,,,������ !:)3
:=�#3 +;�<����>��������.���
concealment�0, 72
• /'����&�$���������.���
58�"1*-�/%'�/������'
�����'�46
![Page 62: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/62.jpg)
• �!��$!#� 2�+�-( �2�+�������
[< �2�+��
)/�BI�CK���
�$�!�#�>U�P�60��!��$G�EW
:F��2�+��D� �� �9T
��!��$,_AM��"����QZ�=?
• &>S!#� 2�+�>U�71�@���X\83�;%�
• *�.!#� 5],��LJ^�4R!#� 5]Y'�VN^��
�!#� 5�HO
![Page 63: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/63.jpg)
���Implementation�
•�� ���������•�����������enrollment�•�������� ����assign�
![Page 64: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/64.jpg)
• 9��������
![Page 65: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/65.jpg)
Proper use of envelopes• Envelopes must be made opaque through use of a
cardboard or aluminium foil insert
• Envelopes must be numbered, opened sequentially
• Reporting the use of sequentially numbered opaque sealed envelopes (SNOSE) is accepted to be the minimum standard
![Page 66: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/66.jpg)
0/&:Blinding;�masking )1
•�����&����*(�$ �,�5�����������������:'%2��#+.2�������4"2��;�
•87�*(��#�9!-�36�
Unblinded RCTs can be a problem because there is a risk that patients will receive different treatment according to the physician’s own beliefs.
Crit Care Med 2010; 38[Suppl.]:S534–S538
![Page 67: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/67.jpg)
$(�#�!-Statistical method.•�&���#� ����%, *�"���$(�#�!�
•������'��)�'����+�#'���!�
![Page 68: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/68.jpg)
���
•!)+Registration,•!) ��&*!)��• �����+Protocol,•�$��-��� ��������•'(��#+Funding,•'(��#�����#+%���"#��,-'(��#���
![Page 69: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/69.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 70: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/70.jpg)
•����Critical Care����RCT
JAMA. 2017;317(13):1321-1328.
![Page 71: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/71.jpg)
?; Premise
•%��'&�#)$!�*( A��97GP�3����
•BQR ./•QI2>�,���5�OJ��M1�C6 ����5�C��4L8��
•DH�:0��-F���������S• MENDS study��"�(*#N=��)'� &K A��28<@+E�C��
![Page 72: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/72.jpg)
�" Hypothesis
���������!��
↓↓ DEX�����#$� ��↓
•���������28���� %
• 28����ventilater-free days %
![Page 73: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/73.jpg)
8$3 Investigator-initiatedChief investigator
• Yu Kawazoe (2003��) �)�-/�� #"�→'���
• Kyohei Miyamoto92006��:�)�-/�� #"�
Collaborater
• Takeshi Morimoto ���.� 2�+� �#!
• Hitoshi Yamamura �7�/� "�→��� �#!
• Akihiro Fuke �7�/� %1��,����
• Atsunori Hashimoto ���.� "�
• Makoto Ito ��-/1��,���� 86
• Nobuaki Shime 5�,���� "�
• Kohei Kato &��.� "�
• Kenji Yamauchi �(�
• Hiroyuki Koami 4�
�ESICM�������* https://www.esicm.org/ictv-presidents-session-desire-trial-results/
February 2013 ; January 201603�
![Page 74: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/74.jpg)
Inclusion
• 20#��!-' +0�)��)1
•���� 24"/�������(&0NIV�1��.�*���� +
•��,$���%�%�'����
![Page 75: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/75.jpg)
Exclusion
•+��(,�(Child-Pugh�-B or C)•���&!���+�����(NYHA �)•)"��� �� ��•'%#��+�*$,�•��� ��• Dexmedetomidine����� ��• Attending physician's decision
![Page 76: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/76.jpg)
![Page 77: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/77.jpg)
',#�!���
Attending physician�eligible ")�•',���',&*��%(
• Internet Data and Information Center for Medical Research (INDICE)�+-�����$
�INDICEUMIN��� ����������“electronic data capturing system”
![Page 78: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/78.jpg)
![Page 79: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/79.jpg)
• ��������"(����� �@→46:�����)
• ' "A8*;)�=>79.13�COPD
• �46:�ID��������/• (?�+ �0<�8*;)�-$��!• ,:ID�����"�2#5&��%
![Page 80: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/80.jpg)
• "#%�(��)*� ���+����������)*��� ,����'�
• �����$!�)*&�
![Page 81: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/81.jpg)
���
•�$��JSICM������%��•����������•"#�&���"#�&��� ���%��•�!�JSICM������%��
![Page 82: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/82.jpg)
Primary Outcome0!Co - Primary Outcome• 28&)�*• 28&Ventilator Free Days (����.�)47+ &%�28&8-�"��(25
2015/5/2�Ventilator Free Days��'(Outcome data�������/1)• �"���(2���→)��#3���
�$,�5&�)�→�"���(2�5&�VFD�0&� ���26&$,�28&�)��6�4&$,�6&�)��4�-���VFD2&5
![Page 83: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/83.jpg)
Sample size28����%!• �" 80% ��" 60%�MENDS study ��-84% vs. 59% ↓ α 5% β 20%
• �"172�'!↓ 15%#$�
• �"200��'!
����� ����(25�'!����25×,�&×2�.400 *�)�3�����+
![Page 84: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/84.jpg)
$� �
28����(#• ��% 80%→80% ��% 60%→72%
↓ α 5% β 20%
• �%172 *#
↓ 15%�&'�
• �%200 �*#
����!"����+25 *#����25×/�)×2�0400 -�,�3�����.
![Page 85: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/85.jpg)
Masking, Blinding
Open label•'- �)* �"���!#�+����•�����/�-35)*-4�"���!#�+����
→)*�/���������&������%2 ($1���limitation�,��.0
![Page 86: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/86.jpg)
The main statistical analysis for efficacyComparison between groups of 28-day mortalityMeasure: Death until 28 days after the initiation of mechanical ventilation. Patients who were alive at 28 days were censored at 28 days. Aim: Comparison of the occurrence of the events between groupsTest: Log-rank test, Cox proportional hazard model Significance: Two-sided p values of less than 0.05 were considered statistically significant. Confidence interval: 95%confidence interval (CI) of the hazard ratio were calculated. Expression: The number of the occurrence of the events, Cumulative incidence, and hazard ratio.
![Page 87: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/87.jpg)
Negative !
![Page 88: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/88.jpg)
The secondary statistical analysis for efficacy28-day mortality Measure: Death during 28 days Aim: Comparison of the occurrence of the events between groups Test: Chi-square test or Fisher exact testSignificance: Two-sided p values of less than 0.05 wereconsidered statistically significant.Confidence interval: NA.Expression: The number of the occurrence of the events, the ratio of the occurrence of the events.
![Page 89: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/89.jpg)
Data and safety monitoring board (DSMB) and interim analysis• Dr. Sadao Kawasaki (Department of Emergency
Medicine Minami Wakayama Medical Center, Japan) →���
• Dr. Takahiro Ashikawa (Department of emergency medicine, Minami Wakayama Medical Center, Japan) →���
• Dr. Yasuhiro Iwasaki (Department of Emergency and Critical Care Medicine, Wakayama Medical University, Japan) →���
![Page 90: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/90.jpg)
The DSMB will independently perform����•�$ ����1����)%�•'+"#����&
• Emergent reporting system�������������*�����(!
![Page 91: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/91.jpg)
Discussion
• The study may have identified a clinically important benefit of dexmedetomidine—an 8% reduction in 28-day mortality—that did not demonstrate statistical significance.
• Physicians may consider an 8% difference in 28-day mortality to be clinically significant but this study was underpowered to detect this difference.
![Page 92: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/92.jpg)
Funding• Funding/Support: This study was supported in part by a noncontractual research grant to Wakayama Medical University provided by Hospira Japan.
• Role of the Funder/Sponsor: Hospira Japan participated in part of the design of this study;however, it had no role in the conduct of the study;collection, management, analysis, and interpretation of the data; preparation or approval of the manuscript; or decision to submit the manuscript for publication.
![Page 93: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/93.jpg)
��
• No earlier multicenter RCTs have investigated the effects of ANP infusion in patients with cardiac surgery–associated AKI.
��
• We therefore decided to evaluate the effects of ANP on renal function and medical costs in patients with cardiac surgery–associated AKI.
![Page 94: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/94.jpg)
• ��&"&�0+�/�0+�)#����ICU�!$��ICU��-��ICU
• (*���
• 11%.���• May 2012 - March 201511��,���2• '���� 90�������
![Page 95: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/95.jpg)
����
• Double-blind
• ANP 0.02 μg /kg/min (2 mL/h) •��� (5% glucose, 2 mL/h�
• Preoperative level�����
•��������������
![Page 96: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/96.jpg)
���������
•����Study coordinators�INDICE��• INDICE randomization system����
![Page 97: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/97.jpg)
Inclusion
• Age of ≥20 years
• Recent elective cardiac surgery, namely, CABG, valve surgery, thoracic aortic aneurysm surgery, or a combination thereof.
• AKI within 48 hours after cardiac surgery
��������ANP����
Exclusion
• Severe hypotension or cardiogenic shock
• Right ventricular infarction
• Dehydration
• End-stage renal disease
• Administration of nonsteroidal anti-inflammatory drugs,
angiotensin-converting enzyme(ACE) inhibitor, or angiotensin
receptor blocker (ARB) within 24 hours before the operation
• Administration of contrast agent within 3 days before the operation
• Extracorporeal membrane oxygenation.
![Page 98: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/98.jpg)
The primary end point
• Change in renal function over the 90-day follow-up measured by serum levels of creatinine and cystatin C, and creatinine clearance or eGFR.
![Page 99: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/99.jpg)
• ������→ a difference in means of 74.25 � ���
↓↓↓ α 5% β 20%
• ��87���↓ 10%����
• ��97���
����������������
Sample size and power calculation
![Page 100: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/100.jpg)
![Page 101: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/101.jpg)
Reasons why,,,,• approval of ethics committees• difficulty in obtaining consent from patients• decisions by several hospitals to prioritize
patients with ventricular assist devices.
• many surgeons in trial sites insisted on using ANP in patients with high preoperative creatinine levels
→these patients were excluded before assessment for eligibility and were administered ANP during surgery.
![Page 102: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/102.jpg)
• �!���#(+ � �
• ������%'("� )�� “��$&”�������������*
![Page 103: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/103.jpg)
����������
![Page 104: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/104.jpg)
Funding
• This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
![Page 105: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/105.jpg)
•��RCT�• CONSORT����• CONSORT�� Introduction• CONSORT�� Method• RCT�•��
![Page 106: RCT · 2018-02-05 · •May be by chance the first RCT picked a population with baseline SvO2 of 48 %. •The baseline SvO2 inthe remaining trials was already higher than 70 %,](https://reader034.vdocuments.us/reader034/viewer/2022050223/5f685b6d8f6f5f5ecc1b2d4c/html5/thumbnails/106.jpg)
49#�+�7!�� ;
• 1�.*�"�� ;����positive �negative �-)6• �����.*��� ;/:��positive��-)6?
'�+�7!�� ;
• 1�.*�"�� ;����positive ��-)6?• �����.*��� ;/:��positive��-)6?=$�������?>
.*� ;�%8(��3�5&������#�?
,2<���0?