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June 14, 2018 N Engl J Med 2018; 378:2263-2274 DOI:10.1056/NEJMoa1801601 2018/7/3 ICU Journal Club

2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

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Page 1: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

June 14, 2018 N Engl J Med 2018; 378:2263-2274DOI:10.1056/NEJMoa1801601

2018/7/3 �� ICU Journal Club�� ��

Page 2: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Introduction

Page 3: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Introduction•-�B&65C71*ADE+!��8�+8+!�� B.�C8#'2"�$8�4��H��A8-�B 4/�:,GF?;>

Ann Surg 1961; 154: 803-10Surgery 2003; 133: 49-55

Intensive Care Med 1994; 20: 203-9Br J Anaesth 2004; 93: 121-8

•)0�-A9<E�%�@/�!��-��A-�I-�G=?7L��B/�

→�(83-6kgB�3��

World J Surg 2004; 28: 1046-51Ann Surg 2003; 238: 641-8

World J Surg 2004; 28: 1046-51Lancet 2002; 359: 1812-8

World J Surg 2013; 37: 1193-202

Clin Nutr 2012; 31: 783-800

Page 4: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Introduction

• 46� �0��8)7/"���8�5("�!��8�&)7 Ann Surg 2003; 238: 641-8

Lancet 2002; 359: 1812-8Anesthesiology 2005; 103: 25-32

•��.3"� ���%;D>D<=8-$7

•?CABD=8�,� ���3"enhanced recovery after surgeryEERAS�F2����.#7

�ERASG�� �8�'7��2�$�8��(*:9@B9D

Clin Nutr 2012; 31: 783-800Acta Anaesthesiol Scand 2016; 60: 289-334Lon don: National Institute for Health and Care Excellence, 2017

Clin Nutr 2012; 31: 783-800Acta Anaesthesiol Scand 2016; 60: 289-334JAMA Surg 2017; 152: 292-8

21��1�+-

Page 5: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Introduction

• 505."+�&8/2@&�/?;&��9�,�(�9BFEHD:���Clin Nutr 2012; 31: 783-800Lon don: National Institute for Health and Care Excellence, 2017

JAMA Surg 2017; 152: 292-8Anesth Analg 2012; 114: 640-51

•�,�(�:.�%�9GDCA-=.!#A�<#�$%.#���A�1'36

• 505*(�>. ��1).��!��2) .�%�3) .���)�4)A��47@

1)Chest 1999; 115: 1371-72)Nat Rev Nephrol 2010; 6: 107-15

3)Proc Natl Acad Sci U S A 2005; 102: 3429-344)Anesth Analg 2001; 93: 405-9

Page 6: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Introduction•�'$�=��1;��4+�6��8��0<2,;

•�8%�5$�7�-

• RELIEF")��@?>.*,��6�!�&�

�'$� VS ���5$�ALiberal)

�'$��37+Liberal�9:8���.�/(�65,� �.*,

�#

Page 7: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Methods

Page 8: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial design

RELIEF�'REstrictive versus LIbEral Fluid Therapy in Major

Abdominal Surgery •������&�./,-��#��� �'•���" �+�(*��•!��%�)Liberal�+� •���3000�•�$2013�5�-2016�9�

Page 9: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Patient selection

•���)#!�����,�-•���� �• ���2����•����3���• �*' +(&"*$*%�����

Page 10: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Inclusion Criteria

• 70���• ��#��1��>32<�BA8.@• ���1��>32<�BA8.@• !�% +�$?EOGLO9 ���C38.@• &%�FNDHIO>200 μmol/L (>2.8 mg/dL)• BMI ≥35 kg/m2

• &DMJKO<30 g/L• ���(*�Panaerobic threshold ; ATQ

<12 mL/kg/min����35�

�',�;/6-:A0R7��C=54�"1�)

Page 11: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Inclusion Criteria

•��'2&��'7/-4+-0;"!*�– ASA-PS 3 or 4– �� ���– BMI 30–35 kg/m2

– ��)$#(������– �56.93: <100 g/L– ���-8,12:150–199 μmol/L (>1.7 mg/dL)– ���� �<anaerobic threshold ; AT= 12–14 mL/kg/min�

���$%��

Page 12: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Exclusion Criteria

•���+• ASA-PS 5•/�N�,D@L��&)�•#K?>I�)�+•"5+•TPQV�+W�*�G.��,0= F>8��K F:�+X('2�$���+8TUR-P87�SURO��+8%)��+8��!341+FE

�-6�H;A8EM<YB��G9CIJL� I5�

Page 13: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Randomization•��+�"�'WHODAS,12&�0�

•���'�����>ICU/HDU/��?* ��• 2<69=3=*'!��#�ALiberal�B@A@+:<48�/�)

��(.-$�,�� WHO$���%��7591;WHODAS2.0

Page 14: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatments

• ERAS:<96;5 -.•$��(��!"5��-.• �2��0��"��2��+��,4.•./-*ARB1ACE-I3��5 -.•$�2*����*�)�'*ERAS8=7*�"*#�����5%&-.

$�

Page 15: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatments

•-�82+H0�F%&(#I82'�G��?C•�!36��"M1<L• Goal-directed(GD)RUNOH�$M.4ZCVP9��3WTPY97/SQVXY

• 5���sBP≦90mmHgM�,�F�)Z�*G�@D� >BC

• HDU9ICUEK-�24�5JEI�@(#

-�

-�

•-�G6�+M�?D:DK9,�;��ALJE� AL=FM��

Page 16: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatments

•���balanced salt solution�����• Hb70 g/L������� �����������������������

�����

Page 17: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Liberal������(4 ��� !�#&���

$�#���**'.+035,24OK

���1006��%��&�100kg# "��

GD/1+-�� "�)��

Page 18: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Active ������������

�OK

Page 19: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Restrictive���100��������100kg����

GD�������� ���

Page 20: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

���

Active�� �����������

OK

Page 21: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatments

���100��� ���100kg����

Page 22: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

375ml��

375ml/h4���1500ml

60ml/h������ �����

750ml

600ml/h4���2400ml

112ml/h���24�������

2690ml��

<3000ml >5400ml

�����1875ml �����3150ml

����75kg���4������

Page 23: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatments

•�!9#���8�06,(���,��)�9 �-�&7�:,�38FKCAJ*"�

• ITT'�,PP'�,sensitivity'�;$42•(���9�69%�@?:,�#��, +8�5.$=<2

•��8:,IGDLC/2EKLBHLC>��/2

19�

Page 24: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Blinding and Data quality

•+(��,ECA2?�' ,��FGIL:<7B8/DQSM�>�6A�56.4

• Primary OutcomeA&�2?��FGIL;,DQSM�>�6A�=3T�)��U

• Secondary Outcome;��•��ORKS;,PRHN9���%A$1,JSG:���7��A�"14

• 1632�:� /PRHN�0@4-7,��9�*#�A!54

Page 25: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Measurments and Patient follow-up•��&*"3��1�1+96;<•�/�5QoR-155�!*��• 1 � ��� Hb Hct 12���� CRP��• 3 � QoR-155��• 30 �.7:85�'��& ��,��5,4

Primary Outcome2&$0Secondary Outcome#�%)*!-!"��&(

• 30 �.QoR-15,WHODAS5���• 3,6,12"��.WHODAS5��

Page 26: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

WHODAS

���� ���� WHO�����������WHODAS2.0

Page 27: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

QoR-15

$�=��/:0H.

*�J�4B3;/:0H.

��/;I9,H.

E,#"/;IH.

'D��;LRSPKXNTW/;IH.

�)��D!&�>MQXOJ-2FIH.

�2J.G6+��/:0H.

�(:LWOVXU/E,;�5H.

����C41?��/:0H.

�%/,,;�5H.

Moderate < A

Severe< A

�4AJ�5H@7?-8��

��:�GJ�5H

Page 28: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Outcomes

hPrimary Outcomei8�1�NB�QJ/�LMFVKO• WHODAS 24-��(=25%��RB�EU)H6G%���3NB�EUO�4

hSecondary Outcomei• ��6��D30!�R(�.D�9 70�0f 70D�8=��'D��=`eYD5,gD7*�>�(6d24"@�gDCRP$C�D<7DICU+�&@D A&@D���ICU �D��R;D90!�R6�#1)R2/.DYbW\^c�(8�1!D3!g

��6��S6��Y_X]`WN:f[Zea1-3N�IJQVTP?0g

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Statistical Analysis

• Modified ITT��*�"#��• 13-0��(������#��*�)(!�"%�*��

•�*�'��$��'��*/+24•�*�'��!��&� % �%.4,*��

Page 30: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Statistical Analysis

•��1(�*"��$'�1�265%)��• Type 1 error 0.05)��•���90%�96?8�0.8�log-rank test��• 2650�, �@��/$"-� �1 �850�A ��

• :4=?(!*� � (1#)2��$2800�,5>;<537+�0.%&

Page 31: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Statistical Analysis

•+�� �?2016�6�30�=��40'�<#"46.�>#"!=91:*)

• 2578�GSVMR�Y��=PIUW2&F86�(1443�Z46�,;0Primary Outcome2300�<0��CDA/1 .�"�!85X786•5>6@0JVQTJHLG3000�=�B46

• 380���>��A43?.�2�E�(2;E<��• �80%• OKWN�0.75

•�->$%;?533�>events2#"Y .�"�!82%Z[�80%0OKWN�0.78

Page 32: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Statistical Analysis

• Primary Outcome1��AKaplan-Meier method8��• 2�"1$5��1� '!)73.1=:@<�ACox proportional hazards model. • 9>?;'!)6/&,+��2%���0�#*%

Schoenfeld residuals testing0�-(�����8�,+

•��5$��3.1�"1��4��0�,+

Page 33: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Statistical Analysis

• V%�8��2?6ACMDO<-/5?0;FQSN;�";�110��8.?=- ��,�@��37 ��:PHE�@��3-ExactRGHKBJE���8&:$�36

• 30��9�+�:��36�T�'���(U:�*2?6LSI@�/7-2!;�+�(9'2:)4>ACMDO@Wilcoxon-Breslow-Gehan��8�#36

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Statistical Analysis• A40P]_fakSE*,@�����5���O)JL

• �H�$WQPMNFY� S'Qob�"JE�H�$WR� S����)[JL

• ;#R?C[cqfornKYLWE�NRsecondary outcomeQ��<)HB/IZL• Holm-Bonferroni+[/FE&�0)RLWg\jmrp^e`lr.0.049[/FN>�JL

• ��E�D��E�%%=R��s�tE3727 9R(-EGXT1*!�:6R�/ULS��/[�Vdhbnri<)[8ML

Page 35: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Results

Page 36: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

7��47��

����

Page 37: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

���2013.5-2016.9

������

FigS1

Page 38: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

FigS1

Page 39: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

����

Page 40: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

����

Page 41: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

����

Page 42: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

����

Page 43: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Trial Treatment

�����200ml������

���PACU������� ��

���� ������

��

PACU

�24���

Day1 PACU�

����� �

������

Page 44: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

��

PACU

�24�����

� ���������������� ��������

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��#�������$�

�!������ ��

���%

���� ��$Liberal� �����!�

�$���% Liberal� ��"����

Page 48: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

��������� ��

Liberal�� ��

SSI�����

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Liberal 81.9%

Restrictive 82.3%

Primary Outcome

�1��������������" �������!�!��� �������

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�������Liberal��� ��������

Prespecified Subgroups��� ���� ��

�� � ������Liberal��� ��������

Fig2

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Table S8 : �������

��������� ���

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Table S9 :�����������

�������������

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Secondary Outcomes

SSI�� ������

������������

AKI��� ������

Table3

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Cr � �) �

Stage 1 1.5���8��90.3 mg/dl��8��

0.5 ml/kg/hr16�*��$%

Stage 2 2���8Cr8�� 0.5 ml/kg/hr112�*��$%

Stage 3 3���8Cr8��9 �8Cr14.0 mg/dl��

0.3 ml/kg/hr124�*��$%.9��112�*��$%

9&���#�8�'2017/6/6 ICU���A-��!B ;<�"

Stage159���/<.Stage2@3�59���701�>3=6���/<AKICKDIGO�,5�(

�) �?+�24:.Stage2@3?�>34���/<

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Adverse events

�39*�4���70���:Liberal 4+"��:�' 4�,&

MildE�!-%�4.=B@A+����8;5?6�)>.2/7,

ModerateE����8�)>.21SevereE����>� 0+����C#���<�(��D>�$51=

TableS13

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Sensitivity Analyses

Page 60: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Discussion

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Discussion��D"#

•)���NJID46�%D�*'.�)C76?5-��0$A Liberal$H�,;=�1"#H(652�DB6���H+�;=

•�)1��D2�DB6���C�EB8>=-��0$ 81.9% vs Liberal$ 82.3% Hazard� 1.05 ; 95%�3/0.88-1.24 ; PQ0.61

• ��&��D �E5-��0$@��C�8>=

-��0$ 8.6% vs Liberal$ 5.0% Hazard� 1.71 ; 95%�3/1.29-2.27 ; P<0.001

•KOLMPJH!�A;=-��0H<FA5��&��9 �<F:A9G8>=

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Discussion•�����'"#-��)��(+ '��$.-

Ann Surg 2003; 238: 641-8

Acta Anaesthesiol Scand 2009; 53: 843-51

Restrictive /1.75L/day Balanced 1.75-2.75L/dayliberal 02.75L/day

�� � 24��*%

Restrictive 1.7L 1.9LBalanced 3.0L 3.0L

•��(��%)

Restrictive 1.0-2.7LBalanced 2.8-5.4L

•��(��%)

��(��(�����(��)��&�!,.-

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Discussion/=:4

• ERASAD@CBE#"�?%.</5?�

•��8�$�6"�9�(4,<•�7+�����9�����;�& ���7!�2<5->=3-<

)Ann Surg 2003; 238: 641-8 Lancet 2002; 359: 1812-8

*Anesthesiology 2005; 103: 25-32•��8�06��E�'"�8��?�13-<

Clin Nutr 2012; 31: 783-800Acta Anaesthesiol Scand 2016; 60: 289334

Proc Nutr Soc 2010; 69: 488-98Acta Anaesthesiol Scand 2009; 53: 843-51London: National Institute for Health and Care Excellence, 2017

Nat Rev Nephrol 2010; 6: 107-15

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Ann Surg 2003; 238: 641-8

:#";53�B�*"C3�H�2>9&)P%)�6�E�� H�.?G

:LJIO;NOKM9-�'$�9��/07

:�4;1999�11�Q2001�8�:�1;&)P%)�,H�=@ASA-PS 1-3E���'172�:Primary Outcome;�,30��FAD�� <!�>@�'�:Secondary Outcome;��9(��9�+

8

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0�3$

Restricted Regimen Standard Regimen

(.�;4� ��G? 6%HAES500ml��

3rd space loss ��G? &9

1!7KE7ml/kg/hr<3!7KE5ml/kg/hr<3!7�83ml/kg/hr

,:9I1� 5%XVO*500ml 0�:#H�@D&9500ml��

/ HAESM /6F�6��<BC? /6

+500mlKE���

/500mlKE&91000-15000ml��< /500ml��EJHAESM��

3/J /1500mlM2=D>L-�<YZUP\TU�M�"H?B

0�3$

Restricted Regimen Standard Regimen

0� `5%XVO*1000ml��`V]a_�$F�6MHAESE1�`�5��

%�b+� �?B

1kg����bW^R[V'

1000-2000mlIP\QS^NV��AI�J�)���

Methods

Ann Surg 2003; 238: 641-8

HAESb Hydroxyethyl starch 6% in normal saline

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����

Ann Surg 2003; 238: 641-8

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��� Day1

���R�median 2740 mL [range, 1100–8050] S�median 5388 mL [range, 2700–11083]

P<0.0005

Day 1R�median 500 mL [range, 0–5000] S�median 1500 mL [range, 0–6000]

P�0.003

Ann Surg 2003; 238: 641-8���

��

����

Day1

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Day2 R��1kg��S��3.5kg�

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Per-protocol��

��

Ann Surg 2003; 238: 641-8

ITT��

28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002

���� �����������

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��

Ann Surg 2003; 238: 641-8

R

R

R S

S

R

R S

S

R SR S

R S

R S

R S

R SR S

SS

S

SS

R S

SS

SS

Major Complications

Minor Complications

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�� ����� ����������������

Ann Surg 2003; 238: 641-8

�� ����

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Anesthesiology 2005; 103:25–32

;$#<61�&\RPG)CLiberalD1�&\LPG)I�0@:)(4�+�E��[��!I�,AH

;PMKZ<WZNV�:��>:-�'%�.8

;�/<2�#)(4�+I ?BASA-PS 1-3E���'152�;Primary Outcome<��GBF��!=" @B�'�;Secondary Outcome<����:�7�5:�+3��E�3��[STQLXOQ���[�+3��EJYRUZ���[SpO2��:1*I ?B�'�

9

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Primary Outcome ��0i�:•�K�&w�K[mB\'^poVl_]j�Ki9D�Td9D\'^po

•�KQMwC�%�@A,V( 7EV��KuvsV?L�j!Fq�Ge_gXNn��0ekg^gX

•@>�B2wrtvl_]jCTdI%•;,w<K�8�6i Hh�ZV38���i3-V4E/��V�1�TO�i2c��q+a`•�J�&0w"�P�VS�V3-V4E/��gfi0.\WnV��Td9D$\10���•#E0w9D�&VU/��*VS=VS��V4E/)�/��iYb2R5��q+a`

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Primary Outcome ��7d�@•�;,�yCK-MBf`epurqvTd�'YST��f`eQ1�5•!���bA0GyH�74w kYsWYXVD#�Y*-2GY3Wxb6"Kw�#�YTP�2GYAB2Gx

•�%Dy12N�aL�•EJ<U�y&`c6"KlMgY24(T��$>•����:R7�?y��87d��:RYCS�=�9a"KZiYPF/200)3YPAWP18mmHg)3h_^e��OI"K]c[

•A�+7yCTaA�+lMgj•F��yntmoqv�].��d50%lQ\j

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�� �������3L� *#%�!'(�&�)&+5% dextrose–0.45% NaCl 1L����������1������������ "$10mg����

��

RPG,4ml/kg/hr

LPG,���10ml/kg��2ml/kg/hr

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Methods

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����

Anesthesiology 2005; 103:25–32

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��

Anesthesiology 2005; 103:25–32

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Primary Outcome

P �0.046

������������ �

Anesthesiology 2005; 103:25–32

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���$)*��&�'� ��!"���$���� ��#"

Secondary OutcomeLPG RPG P�

���� Day1 1.93 � 0.52 kgDay3 1.85 � 0.62 kg

Day1 0.51 � 0.67 kgDay3 0.24 � 0.61 kg

P < 0.01

��,.� 4 [3–7] days 3 [2–7] days P < 0.001

���� 6 [4–9] days 4 [3–9] days P < 0.001

���� 9 days (7–24) 8 days (6–21) P < 0.01

451-701�+836:(���$��#";� �(%!<

-9+/2:�SpO2(� %�#"

451-701 +836:

-9+/2: SpO2

Anesthesiology 2005; 103:25–32

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�)'$��!%�� ���$�

•�����"� �• &(�#�$�������•������� �

Anesthesiology 2005; 103:25–32

�Ann Surg 2003; 238: 641-8

Page 80: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Discussion��D"#

•)���NJID46�%D�*'.�)C76?5-��0$A Liberal$H�,;=�1"#H(652�DB6���H+�;=

•�)1��D2�DB6���C�EB8>=-��0$ 81.9% vs Liberal$ 82.3% Hazard� 1.05 ; 95%�3/0.88-1.24 ; PQ0.61

• ��&��D �E5-��0$@��C�8>=

-��0$ 8.6% vs Liberal$ 5.0% Hazard� 1.71 ; 95%�3/1.29-2.27 ; P<0.001

•KOLMPJH!�A;=-��0H<FA5��&��9 �<F:A9G8>=

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Discussion

•�=��>+&�(�F��4C@=9>;-• Liberal;&�=�/+�*�&�AB@��9,C1:F�36

• 1D?9+&�<AC�"/����F' 25C:-ED806•�+�*!9�$)����/.76

GGG� =#��%/��2DC

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Limitations

•(��D#��91A5H4WTQZ]MC�2K�7>�'�95I

•)�24�/FADU\RN[A5H4=D�D,�E��<JB8?>

•)�1-3�E�.� A:B8?>�&96>•TX^O^Y]S4��AE4Liberal%D�91��D�0�!� 938?>

• Secondary OutcomeE"�9�B;4V^PYL]�*A+�A:B6>G4$�9/-?@6I�'�95I

Page 83: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Editorial

Page 84: 2018/7/3 · 2018. 7. 6. · Day2 R 1kg S 3.5kg Per-protocol Ann Surg 2003; 238: 641 -8 ITT 28(33%) 44(51%) 0.013 27(31%) 47(55%) 0.002 Ann Surg 2003; 238: 641 -8 R R R S S R R S S

Editorial• 1990��[G<�Y�BZ'&E�!��a;I4-6kgZ�A��a>\UIR

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• �B?$hW13#7i[��"*W�4�5Y�,XZKW(�=O`_^JYXSR

Ann Surg 2003; 238: 641-8

C928.8�<�Z��)�LG?$acfdegbY�TNWV YXSR

• QZ�G?$@Z %YTIU�HZ/0��LVUMRBr J Anaesth 2004; 93: 121-8JAMA 1993; 270: 2699-707BMJ 1999; 318: 1099-103World J Surg 2004; 28: 1046-51

Ann Surg 1961; 154: 803-10Surgery 2003; 133: 49-55Intensive Care Med 1994; 20: 203-9

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Editorial��5��

• ?B<>����$D ��"�2Liberal�;��•���!��;�+93000�5��• Primary OutcomeD1� 4#�3*�-0&9,2•�"�6%@=?A�2��-0Primary Outcome)8&2&',263(/.

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CCC�"�1Outcome)8&2��-0&.CCC,:715��26�39��

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Editorial•� @� (�OLiberal# 6L -# 3.7L�+��OLiberal# 1.6kg -# 0.3kg

•�@� "�DECAF3?�+��4�>1Lancet 2015; 385: Suppl 2: S11Surgery 2003; 133: 49-55

•��. ��@*�<0�$�%4�76>:9�@�$=�'8;�&IJMI4��80��@��4<5FD2?>:9

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Editorial

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Editorial

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