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Online Data Supplement

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients

Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care

Practitioners

Raghavan Murugan, MD, MS, FRCP, FCCM, Marlies Ostermann, MD, PhD, Zhiyong Peng, MD,

PhD, Koichi Kitamura, MD, Shigeki Fujitani, MD, PhD, Stefano Romagnoli, MD, PhD, Luca Di

Lullo, MD, PhD Nattachai Srisawat, MD, MS, Subhash Todi, MD, MRCP, Nagarajan

Ramakrishnan, MD, MMM, FCCM, FISCCM, Eric Hoste MD, PhD, Chethan Puttarajappa, MD, MS

Sean M. Bagshaw, MD, MSc, Steven Weisbord, MD, MSc, John A. Kellum, MD, MCCM, Paul M.

Palevsky, MD, Rinaldo Bellomo, MD, PhD, Claudio Ronco, MD, PhD

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Table of Contents

Online Data Supplement.........................................................................................................1

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners............................1

eMethods 1: Survey Questions................................................................................................3

eMethods 2: Survey Administration........................................................................................4

eMethods 3: Survey Instrument..............................................................................................5

eMethods 4: Thematic Analysis of Comments........................................................................17

eTable 1: Characteristics of Practitioners who Did and Did Not Complete the Survey............18

eTable 2: Practitioner Countries.............................................................................................22

eTable 3: Distribution of Practitioners by Country.................................................................23

eTable 4: Survey Response by Practitioner Type....................................................................25

eTable 5: Net Ultrafiltration Rates by Country.......................................................................27

eTable 6: Hemodynamic Management and Perceived Barriers to Net Ultrafiltration by Practitioner Type...................................................................................................................29

eTable 7: Perceptions Related to Timing, Protocol Use and Willingness to Enroll Patients in a Clinical Trial of Protocol-Based UFNET......................................................................................30

eTable 8: Perceptions Related to Timing, Protocol Use and Willingness to Enroll Patients in a Clinical Trial of Protocol-Based Net Ultrafiltration by Practitioner Type..................................32

eTable 9: Thematic Analysis of Comments by Practitioner Type.............................................33

eTable 10: Example Comments Amenable to Research and Quality Improvement Interventions.........................................................................................................................34

eFigure 1: Evaluation of Net Fluid Balance During CRRT by Practitioner Type.........................44

eFigure 2: Early, Protocol-based Net Ultrafiltration and Willingness to Enroll in a Clinical Trial..............................................................................................................................................45

eFigure 3: Word Cloud of Comments.....................................................................................46

eReference............................................................................................................................47

2

eMethods 1: Survey Questions

The survey instrument (eMethods 3) consisted of 25 questions. Four questions related to practitioner specialty (i.e., intensivist/nephrologist/advanced practice provider/ICU nurse/dialysis nurse), country and years of practice, as well as type of hospital. One question related to the use of maximum dose of loop diuretic in a patient with oliguric acute kidney injury and fluid overload before determining diuretic resistance.

Two questions related to the most commonly used criteria for initiation and prescription of net ultrafiltration (UFNET). Two questions related to the use of intermittent hemodialysis (IHD) as the first modality for UFNET including estimation of relative frequency of use as well as the typical UFNET prescription per session in the prior month. A similar set of two questions were asked about the use of “slow” forms of hemodialysis such as sustained low-efficiency dialysis (SLED), prolonged intermittent renal replacement therapy (PIRRT) or extended daily dialysis (EDD). One question regarding assessment of prescribed-to-delivered dosing of UFNET using various intermittent forms of hemodialysis.

A set of six questions were asked about the use of continuous renal replacement therapy (CRRT) including estimated percentage of time CRRT was used as the first modality; typical UFNET

prescription for initial and maximal fluid removal rate in hemodynamically stable patients; typical UFNET rate for hemodynamically unstable patients; whether the net volume of fluid removed was achieved by varying the ultrafiltration rate or the replacement fluid rate; and the frequency of assessment of net fluid balance during CRRT.

Two questions related to the proportion of patients developing hemodynamic instability during UFNET using IHD, CRRT or both and practices related to management of hemodynamic instability. One question was asked on perceived barriers to UFNET using IHD, CRRT or both. Finally, two questions were asked whether early and a protocol-based UFNET strategy outlining the rate, volume, and duration of fluid removal based on severity of fluid overload and hemodynamic status of the patient be beneficial. One question on whether the practitioner had equipoise to enroll a patient with oliguric acute kidney and fluid overload in a clinical trial of protocol-based UFNET strategy. Finally, one open ended optional question to capture any missed information from this survey that practitioners thought might be important.

3

eMethods 2: Survey Administration

The default survey language was English and only 1 question was asked in each webpage for a total of 25 questions. All survey questions were set as compulsory fields (except questions 5, 6, 7 and 25) to ensure survey completion. We used adaptive questioning (branched logic) within the instrument to exclude questions 5, 6 and 7 if the responder was a ICU or dialysis nurse as these questions pertained to physicians and nurse practitioners who typically prescribe diuretics and make decision on initiation and prescription of UFNET. Question 25 was an optional free text field to add additional comments by practitioners.

A question number and a progress bar were present on the screen for all questions. A back button feature enabled respondents to change their responses except for questions that used branched logic. Respondents could save their responses and continue later using the same link, if the survey was incomplete. However, respondents were not allowed to change the responses or take the survey again once the survey was completed and submitted or deleted. All responses in progress were recorded up to 1 week after the respondents last activity. All mandatory questions were highlighted and a check for completeness was done before the questionnaire was submitted by respondents.

All items had non-response option such as “not applicable” or “I don’t know” or “I do not prescribe/make decision” and selection of one of the options were enforced. While the duration of the survey was recorded, we did not exclude respondents based on time of completion. The median duration for those who completed the survey was 605 (IQR, 439 – 888) seconds and for those who did not complete the survey was 109 (IQR, 39 – 275) seconds.

The survey was set as an “Open Access” that allowed anyone with the access to the weblink to take the survey without the need for a password. However, respondents were not allowed to take this survey more than once. This was accomplished by placing a cookie on their browser when they submitted a response that prevented subsequent duplicate responses. However, no IP addresses from the respondents were recorded. A tag was also added to the survey to prevent search engines from indexing the survey.

The survey was disseminated to 56,840 members belonging to nine of the fourteen societies. However, many practitioners were members of multiple societies and received the survey more than once. Some societies (American Association of Critical Care Nurses, European Society of Intensive Care Medicine, Chinese Society of Critical Care Medicine, Italian Society of Nephrology) also posted the survey on their webpage and we were unable to obtain the members to whom survey was disseminated from three societies (National Kidney Foundation, Thailand Society of Critical Care Medicine and UK CLRN).

Society No. of members to whom survey was disseminated

Australia and New Zealand Intensive Care Society 814British Association of Critical Care Nurses 2,000Chinese Society of Critical Care Medicine 4,773

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Canadian Critical Care Society 243European Society of Intensive Care Medicine 16,360Indian Society of Critical Care Medicine 9,000Italian Society of Intensive Care 4,649Japanese Society of Critical Care Medicine 9,573Society of Critical Care Medicine 9,428Total 56,840

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eMethods 3: Survey Instrument

6

eMethods 4: Thematic Analysis of Comments

Thematic Analysis

We performed thematic analysis of the free-text comments [1] from practitioners for question 25. Chinese and Japanese language comments were translated into English before analysis by two investigators (ZP and KK) who were fluent in English. Two investigators (RM and MO), who are also fluent in English, performed the thematic analysis. Using an inductive approach, RM and MO coded the comments and generated initial themes independently. Subsequently, these two investigators discussed and converged upon the final themes. Lexical analysis of comments was performed by removing punctuation, using non-conjunctive terms and after changing all letters into lowercase. Term frequencies were then visualized using a word cloud (www.wordclouds.com) (eFigure 3).

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eTable 1: Characteristics of Practitioners who Did and Did Not Complete the Survey

Characteristic

No. (%)Completed

Survey(N=1,569)

Did Not Complete Survey

(N=998)P Value

ContinentAfrica 8 (0.5) 4 (0.4)

<0.001

Asia 453 (28.9) 126 (12.6)Europe 485 (30.9) 194 (19.4)North America 535 (34.1) 239 (23.9)Oceania 45 (2.9) 6 (0.6)South America 43 (2.7) 4 (0.4)

PractitionerIntensivist 1086 (69.2) 338 (33.9) <0.001Nephrologist 32 (2.0) 16 (1.6) 0.43Intensivist & Nephrologist 55 (3.5) 21 (2.1) 0.04Advanced Practice Provider 41 (2.6) 25 (2.5) 0.86ICU Nurse 346 (22.0) 236 (23.6) 0.34Dialysis Nurse 9 (0.6) 8 (0.8) 0.48

Years of practice, median (IQR) 13.2 (7.2 – 22.0) 10.1 (4.6 -20.0) <0.001

Hospital TypeUniversity-based 903 (57.5) 307 (30.8)

0.72Community-based 385 (24.5) 133 (13.3)Government 194 (12.4) 70 (7.0)Other 87 (5.5) 38 (3.8)

Maximum dose of loop diuretic prescribed (furosemide equivalent), mgs/day

<100 185 (15.3) 45 (4.5)

0.25

100 – 250 535 (44.2) 122 (12.2)251 – 500 217 (18.0) 51 (5.1)501 – 750 51 (4.2) 13 (1.3)751 – 1000 103 (8.5) 22 (2.2)>1000 49 (4.0) 7 (7.0)

Criteria used for initiation of UFNET

Persistent oliguria/anuria (urine output <0.5mL/kg/hour for 12 hours) 515 (42.4) 103 (10.3)

0.03Severe hypoxemia (PaO2/FiO2 ratio <150) 152 (12.5) 26 (2.6)

Pulmonary edema with or without hypoxemia 194 (16.0) 35 (3.5)

Cumulative fluid balance (>1000 mL) 54 (4.4) 10 (1.0)

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http://www.wordclouds.com/

Characteristic

No. (%)Completed

Survey(N=1,569)


(N=998)P Value

Fluid overload >10% of body weight 60 (5.0) 11 (1.1)Ongoing need for fluids in the presence of oliguria 106 (8.7) 15 (1.5)

Criteria used for prescription of UFNET

24-hour fluid balance 156 (12.8) 39 (3.9)

0.002

Cumulative fluid balance 230 (18.9) 30 (3.0)Weight gain 69 (5.7) 3 (0.3)Radiographic features of fluid overload 31 (2.5) 3 (0.3)Hemodynamic status (HR, BP, CVP, PPV, dose of vasopressors) 634 (52.2) 103 (10.3)

Volume of anticipated fluid use in the next 24 hours 23 (1.9) 4 (0.4)

Arterial lactate 8 (0.7) 1 (0.1)

IHD use, median (IQR)Percent use last month 10.0 (2.0 – 30.0) 10.0 (4.0 – 30.0) 0.57Typical prescription, liters per session 2.0 (2.0 – 3.0) 2.1 (1.9 – 3.0) 0.99

Slow forms of IHD use, median (IQR)Percent use last month 6.0 (0 – 34.0) 5.0 (0 – 21.0) 0.35Typical prescription, liters per session 2.0 (1.1 – 3.0) 2.0 (0.6 – 3.0) 0.43

Percent of assessment of prescription-to-delivered UFNET, median (IQR) 70.0 (25.0 – 100.0) 48.0 (5.0 – 95.5) 0.01

CRRT use, median (IQR)Percent use in the last month 71.0 (25.0 – 96.0) 50.0 (8.0 – 81.0) 0.003Initial UFNET rate for hemodynamically stable patient, mL per hour 125.0 (100.0 – 200.0) 149.0 (103.0 – 203.0) 0.60

Maximal UFNET rate for hemodynamically stable patient, mL per hour

299.0 (200.0 – 365.0) 207.0 (199.0 – 397.0) 0.06

UFNET rate for hemodynamically unstable patient, mL per hour 80.0 (49.0 – 111.0) 100.0 (51.0 – 152.0) 0.13

Method used to achieve UFNET using CRRT, No. (%)

By varying ultrafiltration rate only 613 (43.8) 12 (1.2)

0.51By varying replacement fluid rate only 80 (5.7) 2 (0.2)By varying both ultrafiltration and replacement fluid rate 553 (39.5) 19 (1.9)

How frequently did you check net fluid

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Characteristic

No. (%)Completed

Survey(N=1,569)


(N=998)P Value

balance during CRRT? No. (%)1 hour 441 (31.5) 12 (1.2) 0.022 hours 130 (9.3) 5 (0.5)4 hours 178 (12.7) 5 (0.5)6 hours 127 (9.1) 4 (0.4)8 hours 135 (9.6) 2 (0.2)12 hours 140 (10.0) 4 (0.4)24 hours 136 (9.7) 1 (0.1)

Percentage of patients developing new hemodynamic instability during UFNET, median (IQR)

20.0 (10.0 – 35.0) 19.5 (9.5 – 30.0) 0.29

Interventions performed for hemodynamic instability

Decrease the rate of fluid removal 1,103 (70.3) 17 (1.7) <0.001Completely stop fluid removal 562 (35.8) 7 (0.7) <0.001Make no changes to fluid removal rate 52 (3.3) 1 (0.1) <0.001Administer a fluid bolus 496 (31.6) 9 (0.9) <0.001Start or increase the dose of a vasopressor 808 (51.5) 10 (1.0) <0.001

Switch to alternative modality 83 (5.3) 0 <0.001Administer albumin or mannitol bolus 319 (20.3) 2 (0.2) <0.001

Perceived barriers to UFNET

Patient intolerance (e.g., hypotension) 1,184 (75.4) 12 (1.2) <0.001Under prescription 241 (15.3) 3 (0.3) <0.001Frequent interruptions (e.g., trip to CT scan, operating room, filter clotting, catheter malfunction)

690 (44.0) 8 (0.8) <0.001

Inability to titrate fluid removal 124 (7.9) 2 (0.2) <0.001Unavailability of adequately trained nursing staff 202 (12.8) 3 (0.3) <0.001

Unavailability of dialysis machines 192 (12.2) 1 (0.1) <0.001Cost associated with treatment 154 (9.8) 1 (0.1) <0.001

I believe early fluid removal is beneficialStrongly agree 544 (34.7) 3 (0.3) 0.31Agree 620 (39.5) 5 (0.5)Somewhat agree 248 (15.8) 3 (0.3)Neither agree nor disagree 104 (6.6) 1 (0.1)Somewhat disagree 32 (2.0) 0Disagree 15 (1.0) 1 (0.1)Strongly disagree 6 (0.4) 0

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Characteristic

No. (%)Completed

Survey(N=1,569)


(N=998)P Value

I believe a protocol-based fluid removal strategy would be beneficial

Strongly agree 448 (28.5) 3 (0.3)

0.28

Agree 516 (32.9) 4 (0.4)Somewhat agree 314 (20) 1 (0.1)Neither agree nor disagree 149 (9.5) 2 (0.2)Somewhat disagree 74 (4.7) 0Disagree 48 (3.1) 0Strongly disagree 20 (1.3) 1 (0.1)

I would enroll my patient in a clinical trial comparing protocol-based versus usual care

Strongly agree 428 (27.4) 1 (0.1)

0.99

Agree 573 (36.7) 2 (0.2)Somewhat agree 221 (14.2) 1 (0.1)Neither agree nor disagree 238 (15.3) 1 (0.1)Somewhat disagree 37 (2.4) 0Disagree 46 (2.9) 0Strongly disagree 17 (1.1) 0

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eTable 2: Practitioner Countries

Africa Asia Europe North America Oceania South

AmericaEgypt Bahrain Austria Canada Australia Argentina

Nigeria China Belgium Costa Rica New Zealand ArubaSouth Africa Hongkong Bulgaria Cuba Bolivia

Sudan India Croatia Dominican Republic Brazil

Uganda Indonesia Czech Republic El Salvador ChileIran Denmark Guatemala Colombia

Japan Estonia Mexico EcuadorJordan Finland Nicaragua ParaguayKorea France United States Peru

Malaysia Germany TrinidadOman Greece Venezuela

Pakistan HungaryPalestine Iceland

Qatar IrelandRussia Italy

Saudi Arabia LatviaSingapore Lithuania

Taiwan MaltaThailand NetherlandsTurkey Norway

United Arab Emirates PolandVietnam Portugal

RomaniaSerbia

SlovakiaSlovenia

SpainSweden

SwitzerlandUnited Kingdom

Ukraine

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eTable 3: Distribution of Practitioners by Country

No. CountryNo. of Practitioners (%)

(N=1,569)

1. Argentina 10 (0.6)2. Aruba 1 (0.1)3. Australia 39 (2.5)4. Austria 3 (0.2)5. Bahrain 1 (0.1)6. Belgium 16 (1.0)7. Bolivia 1 (0.1)8. Brazil 14 (1.0)9. Bulgaria 4 (0.2)10. Canada 46 (2.9)11. Chile 3 (0.2)12. China 158 (10.1)13. Colombia 5 (0.3)14. Costa Rica 1 (0.1)15. Croatia 1 (0.1)16. Cuba 2 (0.1)17. Czech Republic 1 (0.1)18. Denmark 15 (1.0)19. Dominican Republic 1 (0.1)20. Ecuador 2 (0.1)21. Egypt 2 (0.1)22. El Salvador 1 (0.1)23. Estonia 3 (0.2)24. Finland 2 (0.1)25. France 22 (1.4)26. Germany 17 (1.1)27. Greece 24 (1.5)28. Guatemala 1 (0.1)29. Hong Kong 1 (0.1)30. Hungary 2 (0.1)31. Iceland 2 (0.1)32. India 51 (3.2)33. Indonesia 5 (0.3)34. Iran 3 (0.2)35. Ireland 4 (0.2)36. Italy 78 (5.0)37. Japan 161 (10.3)38. Jordan 1 (0.1)39. Kingdom of Saudi Arabia 19 (1.2)40. Korea 1 (0.1)41. Latvia 2 (0.1)42. Lithuania 2 (0.1)

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No. CountryNo. of Practitioners (%)

(N=1,569)

43. Malaysia 4 (0.2)44. Malta 1 (0.1)45. Mexico 16 (1.0)46. Netherlands 8 (0.5)47. New Zealand 6 (0.4)48. Nicaragua 2 (0.1)49. Nigeria 1 (0.1)50. Norway 5 (0.3)51. Oman 1 (0.1)52. Pakistan 6 (0.4)53. Palestine 1 (0.1)54. Paraguay 1 (0.1)55. Peru 4 (0.2)56. Poland 10 (0.6)57. Portugal 21 (1.3)58. Qatar 2 (0.1)59. Romania 6 (0.4)60. Russia 9 (0.6)61. Serbia 4 (0.2)62. Singapore 2 (0.1)63. Slovakia 2 (0.1)64. Slovenia 1 (0.1)65. South Africa 2 (0.1)66. Spain 31 (2.0)67. Sudan 2 (0.1)68. Sweden 9 (0.6)69. Switzerland 7 (0.4)70. Taiwan 1 (0.1)71. Thailand 7 (0.4)72. Trinidad 1 (0.1)73. Turkey 15 (1.0)74. Uganda 1 (0.1)75. Ukraine 1 (0.1)76. United Arab Emirates 3 (0.2)77. United Kingdom 181 (11.5)78. United States 465 (29.6)79. Venezuela 1 (0.1)80. Vietnam 1 (0.1)

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eTable 4: Survey Response by Practitioner Type

No. (%)

Characteristic All(n=1,569)

Physician (n=1,173)

Nurse & Nurse Practitioner

(n=396)

P value

ContinentAfrica 8 (0.5) 8 (0.5) 0

<0.001

Asia 453 (28.8) 433 (37.0) 20 (5.0)Europe 485 (30.9) 388 (33.1) 97 (24.5)North America 535 (34.1) 266 (22.7) 269 (68.0)Oceania 45 (2.9) 35 (3.0) 10 (2.5)South America 43 (2.7) 43 (3.7) 0

Years of practice, median (IQR)

13.2 (7.2 – 22.0) 15.0 (8.2 – 22.1) 9.7 (5.0 – 20.4) <0.001

Hospital typeUniversity-based 903 (57.5) 665 (56.7) 238 (60.1)

0.18Community-based 385 (24.5) 282 (24.0) 103 (26.0)Government 194 (12.4) 155 (13.2) 39 (9.8)

IHD, median (IQR)Percent use last month

10.0 (2.0 – 30.0) 10.0 (2.0 – 30.0) 10.0 (1.0 – 30.0) 0.06

Typical prescription, liters per session 2.0 (2.0 – 3.0) 2.0 (2.0 – 3.0) 2.0 (1.9 – 2.5) 0.08

Slow forms of IHD, median (IQR)

Percent use last month

6.0 (0 – 34.0) 10.0 (0 – 40.0) 1.0 (0 – 20.0) <0.001

Typical prescription, liters per session 2.0 (1.1 – 3.0) 2.0 (1.0 – 3.0) 2.3 (1.4 – 3.0) 0.51

Percent of assessment of prescribed to delivered dose, median (IQR)

70.0 (25.0 – 100.0) 69.0 (29.0 – 95.5) 72.5 (10.0 – 100) 0.86

CRRT, median (IQR)Percent use last month

71.0 (25.0 – 96.0) 79.5 (30.0 – 99.0) 60.0 (15.0 – 90.0) <0.001

Initial UFNET rate for hemodynamically stable patient, mL per hour

125.0 (100.0 – 200.0)

149.0 (100.0 – 200.0) 100.0 (99.0 – 200.0) <0.001

Maximal UFNET rate 299.0 (200.0 – 300.0 (200.0 – 297.0 (200.0 – 0.08

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No. (%)


Physician (n=1,173)

Nurse & Nurse Practitioner

(n=396)

P value

for hemodynamically stable patient, mL per hour

365.0) 399.5) 351.0)

UFNET rate for hemodynamically unstable patient, mL per hour

80.0 (49.0 – 111.0) 92.0 (49.0 – 120.0) 52.0 (25.0 – 102.0) <0.001

Method used to achieve UFNET using CRRT, No. (%)

By varying ultrafiltration rate only

613 (43.8) 411 (39.5) 202 (56.1)

<0.001

By varying replacement fluid rate only

80 (5.7) 72 (6.9) 8 (2.2)

By varying both ultrafiltration and replacement fluid rate

553 (39.5) 461 (44.3) 92 (25.5)

How frequently did you check net fluid balance during CRRT? No. (%)

1 hour 441 (31.5) 200 (19.2) 241 (66.9)

<0.001

2 hours 130 (9.3) 114 (11.0) 16 (4.4)4 hours 178 (12.7) 158 (15.2) 20 (5.6)6 hours 127 (9.1) 115 (11.1) 12 (3.3)8 hours 135 (9.6) 119 (11.4) 16 (4.4)12 hours 140 (10.0) 128 (12.3) 12 (3.3)24 hours 136 (9.7) 125 (12.0) 11 (3.1)

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eTable 5: Net Ultrafiltration Rates by Country

Country No. of observations

Median (IQR) Hemodynamically

Stable PatientsHemodynamically Unstable Patients

InitialUFNET Rate

(mL/h)

MaximalUFNET Rate

(mL/h)

TypicalUFNET Rate

(mL/h)Argentina 2 574.5 (149.0 – 1000.0) 600.5 (201.0 – 1000.0) 553.5 (152.0 – 955.0)Australia 37 193.0 (100.0 – 201.0) 301.0 (251.0 – 400.0) 97.0 (51.0 – 150.0) Austria 3 151.0 (100.0 – 200.0) 400.0 (100.0 – 400.0) 100.0 (25.0 – 100.0)Bahrain 1 203.0 (203.0 – 203.0) 300.0 (300.0 – 300.0) 77.0 (77.0 – 77.0)Belgium 13 107.0 (100.0 – 198.0) 452.0 (300.0 – 712.0) 51.0 (27.5 – 115.0)Bolivia 1 505.0 (505.0 – 505.0) 700.0 (700.0 – 700.0) 205.0 (205.0 – 205.0)Brazil 11 147.0 (51.0 – 200.0) 297.0 (200.0 – 400.0) 87.0 (48.0 – 108.0)Bulgaria 4 177.0 (126.5 – 227.0) 326.0 (206.5 – 351.5) 99.5 (96.0 – 209.5)Canada 43 100.0 (70.0 – 200.0) 200.0 (251.0 – 349.0) 51.0 (25.0 – 100.0)Chile 2 155.5 (111.0 – 200.0) 302.5 (300.0 – 305.0) 126.0 (100.0 – 152.0)China 146 219.0 (198.5 – 310.0) 391.0 (260.0 – 502.0) 169.0 (102.0 – 243.0)Colombia 3 306.0 (152.0 – 415.0) 205.0 (200.0 – 925.0) 215.0 (100.0 – 317.0)Costa Rica 1 102.0 (102.0 – 102.0) 401.0 (401.0 – 401.0) 147.0 (147.0 – 147.0)Croatia 1 179.0 (179.0 – 179.0) 301.0 (301.0 – 301.0) 50.0 (50.0 – 50.0)Cuba 2 266.5 (150.0 – 383.0) 280.0 (250.0 – 310.0) 276.5 (50.0 – 503.0) Czech Republic 1 153.0 (153.0 – 153.0) 314.0 (314.0 – 314.0) 110.0 (110.0 – 110.0)Denmark 15 152.0 (100.0 – 203.0) 302.0 (300.0 – 397.0) 100.0 (76.0 – 192.0)Ecuador 1 518.0 (518.0 – 518.0) 737.0 (737.0 – 737.0) 441.0 (441.0 – 441.0)Egypt 1 204.0 (204.0 – 204.0) 502.0 (502.0 – 502.0) 106.0 (106.0 – 106.0)El Salvador 1 329.0 (329.0 – 329.0) 501.0 (501.0 – 501.0) 201.0 (201.0 – 201.0)Estonia 3 151.0 (100.0 – 200.0) 400.0 (300.0 – 500.0) 151.0 (50.0 – 500.0) Finland 1 103.0 (103.0 – 103.0) 200.0 (200.0 – 200.0) 49.0 (49.0 – 49.0)France 20 193.5 (125.5 – 223.0) 300.5 (250.5 – 372.5) 71.0 (49.0 – 116.0)Germany 15 101.0 (94.0 – 201.0) 251.0 (225.0 – 392.0) 65.0 (0 – 100.0)Greece 22 155.0 (101.0 – 200.0) 300.0 (250.0 – 351.0) 100.0 (68.0 – 120.0)Hong Kong 1 148.0 (148.0 – 148.0) 251.0 (251.0 – 251.0) 51.0 (51.0 – 51.0)Hungary 2 110.0 (100.0 – 120.0) 231.0 (161.0 – 301.0) 64.5 (49.0 – 80.0)Iceland 2 150.0 (100.0 – 200.0) 353.0 (200.0 – 506.0) 75.5 (51.0 – 100.0)India 31 174.0 (100.0 – 300.0) 227.0 (197.0 – 377.5) 100.0 (52.0 – 173.0)Indonesia 4 302.0 (112.0 – 496.0) 357.0 (151.5 – 552.0) 80.5 (64.5 – 91.5)Iran 1 200.0 (200.0 – 200.0) 300.0 (300.0 – 300.0) 200.0 (200.0 – 200.0)Ireland 4 125.5 (100.0 – 164.0) 203. 5 (200.0 – 230.5) 50.0 (36.0 – 90.5)Italy 74 146.5 (100.0 – 200.0) 221.0 (197.0 – 300.0) 98.0 (51.0 – 101.0)Japan 147 100.0 (52.0 – 101.0) 200.0 (151.0 – 300.0) 40.0 (0 – 52.0)Kingdom of Saudi Arabia 18 151.0 (100.0 – 201.0) 293.0 (200.0 – 301.0) 62.5 (51.0 – 100.0)

Korea 1 200.0 (200.0 – 200.0) 355.0 (355.0 – 355.0) 100.0 (100.0 – 100.0)Lithuania 2 150.0 (100.0 – 200.0) 199.5 (151.0 – 248.0) 90.0 (0 – 180.0)Malaysia 4 149.0 (74.5 – 250.0) 280.5 (176.0 – 430.5) 91.0 (56.0 – 125.5)

26

Country No. of observations

Median (IQR) Hemodynamically

Stable PatientsHemodynamically Unstable Patients

InitialUFNET Rate

(mL/h)

MaximalUFNET Rate

(mL/h)

TypicalUFNET Rate

(mL/h)Malta 1 155.0 (155.0 – 155.0) 232.0 (232.0 – 232.0) 126.0 (126.0 – 126.0)Mexico 12 136.0 (100.0 – 200.0) 228.0 (162.5 – 300.0) 100.0 (51.0 – 151.0) Netherlands 7 51.0 (50.0 – 92.0) 249.0 (190.0 – 300.0) 10.0 (0 – 51.0)New Zealand 5 120.0 (100.0 – 150.0) 300.0 (200.0 – 303.0.) 89.0 (80.0 – 96.0)Norway 5 149.0 (100.0 – 152.0) 300.0 (252.0 – 311.0) 100.0 (52.0 – 100.0)Oman 1 249.0 (249.0 – 249.0) 501.0 (501.0 – 501.0) 100.0 (100.0 – 100.0)Pakistan 3 200.0 (61.0 – 600.0) 300.0 (101.0 – 601.0) 100.0 (25.0 – 600.0.)Poland 10 174.5 (107.0 – 200.0) 276.5 (200.0 – 400.0) 125.0 (94.0 – 151.0)Portugal 19 152.5 (100.5 – 200.5) 251.0 (200.0 – 302.0) 100.0 (51.0 – 149.0)Romania 6 173.0 (100.0 – 300.0) 401.0 (4000 – 503.0) 103.0 (100.0 – 258.0)Russia 8 129.5 (103.0 – 200.0) 301.0 (99.5 – 451.5) 75.5 (51.0 – 150.5)Serbia 4 151.0 (51.0 – 300.0) 280.0 (251.5 – 654.0) 28.0 (0 – 102.5)Singapore 2 75.0 (50.0 – 100.0) 325.5 (150.0 – 501.0) 125.5 (50.0 – 201.0)Slovakia 2 160.0 (120.0 – 200.0) 225.5 (151.0 – 300.0) 90.0 (80.0 – 100.0)South Africa 1 301.0 (301.0 – 301.0) 501.0 (501.0 – 501.0) 297.0 (297.0 – 297.0)Spain 28 151.0 (103.0 – 197.0) 253.0 (200.0 – 313.0) 100.0 (59.0 – 107.0)Sudan 1 300.0 (300.0 – 300.0) 500.0 (500.0 – 500.0) 200.0 (200.0 – 200.0)Sweden 9 124.0 (100.0 – 177.0) 399.0 (275.5 – 500.0) 103.0 (100.0 – 151.0)Switzerland 6 100.0 (51.0 – 101.0) 225.0 (200.0 – 351.0) 50.0 (5.0 – 101.0)Taiwan 1 200.0 (200.0 – 200.0) 200.0 (200.0 – 200.0) 200.0 (200.0 – 200.0)Thailand 6 153.0 (54.0 – 210.0) 324.5 (194.0 – 487.0) 45.0 (11.0 – 54.0)Trinidad 1 100.0 (100.0 – 100.0) 200.0 (200.0 – 200.0) 0 (0 – 0)Turkey 14 148.0 (100.0 – 200.0) 200.0 (187.5 – 253.0) 77.5 (51.0 – 100.0)Ukraine 1 - - 103.0 (103.0 – 103.0)United Arab Emirates 2 134.5 (119.0 – 150.0) 227.0 (152.0 – 302.0) 100.0 (100.0 – 100.0)

United Kingdom 175 122.0 (100.0 – 200.0) 300.0 (246.0 – 400.0) 80.0 (49.0 – 101.0)United States 384 100.0 (78.0 – 200.0) 285.0 (200.0 – 341.0) 51.0 (25.0 – 100.0)Vietnam 1 156.0 (156.0 – 156.0) 301.0 (301.0 – 301.0) 68.0 (68.0 – 68.0)

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eTable 6: Hemodynamic Management and Perceived Barriers to Net Ultrafiltration by

Practitioner Type

No. (%)


Physician (n=1,173)

Nurse & Nurse Practitioners

(n=396)

P value

Percentage of patients developing new hemodynamic instability during UFNET median (IQR)

20.0 (10.0 – 35.0) 20.0 (10.0 – 33.0) 20.0 (10.0 – 40.0) 0.32

Interventions performed for hemodynamic instability

Decrease the rate of fluid removal 1,103 (70.3) 806 (68.7) 297 (75.0) 0.01

Completely stop fluid removal 562 (35.8) 392 (33.4) 170 (42.9) 0.001

Make no changes to fluid removal rate 53 (3.4) 41 (3.5) 12 (3.0) 0.65

Administer a fluid bolus 496 (31.6) 353 (30.1) 143 (36.1) 0.03Start or increase the dose of a vasopressor 808 (51.5) 558 (47.5) 250 (63.1) <0.001

Switch to alternative modality 83 (5.3) 67 (5.7) 16 (4.0) 0.19

Administer albumin or mannitol bolus 319 (20.3) 198 (16.9) 121 (30.6) <0.001

Perceived barriers to UFNET

Patient intolerance (e.g., hypotension) 1,184 (75.4) 862 (73.4) 322 (81.3) 0.002

Under prescription 241 (15.3) 177 (15.1) 64 (16.1) 0.60Frequent interruptions (e.g., trip to CT scan, operating room, filter clotting, catheter malfunction)

690 (44.0) 474 (40.4) 216 (54.5) <0.001

Inability to titrate fluid removal 124 (7.9) 91 (7.7) 33 (8.3) 0.71

Unavailability of adequately trained nursing staff

202 (12.8) 140 (11.9) 62 (15.6) 0.04

Unavailability of dialysis machines 192 (12.2) 168 (14.3) 24 (6.1) <0.001

Cost associated with treatment 154 (9.8) 142 (12.1) 12 (3.0) <0.001

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eTable 7: Perceptions Related to Timing, Protocol Use and Willingness to Enroll Patients in a Clinical Trial of Protocol-Based UFNET

Characteristic

No (%)

Africa(N=8)

Asia(N=453)

Europe(N=485)

North America(N=535)

Oceania(N=45)

South America(N=43)

All(N=1,569)

I believe early fluid removal is beneficial a

Strongly agree 5 (62.5) 177 (39.1) 159 (32.8) 172 (32.1) 12 (26.7) 19 (44.2) 544 (34.7)Agree 2 (25.0) 177 (39.1) 195 (40.2) 215 (40.2) 18 (40.0) 13 (30.2) 620 (39.5)Somewhat agree 0 61 (13.5) 86 (17.7) 87 (16.3) 8 (17.8) 6 (13.9) 248 (15.8)Neither agree nor disagree 0 20 (4.4) 34 (7.0) 44 (8.2) 4 (8.9) 2 (4.6) 104 (6.6)Somewhat disagree 1 (12.5) 11 (2.4) 8 (1.6) 9 (1.7) 2 (4.4) 1 (2.3) 32 (2.0)Disagree 0 6 (1.3) 3 (0.6) 4 (0.7) 1 (2.2) 1 (2.3) 15 (1.0)Strongly disagree 0 1 (0.2) 8 (1.6) 4 (0.7) 0 1 (2.3) 6 (0.4)

I believe a protocol-based fluid removal strategy would be beneficial b

Strongly agree 4 (50.0) 167 (36.7) 123 (25.4) 130 (24.3) 4 (8.9) 20 (46.5) 448 (28.5)Agree 3 (37.5) 160 (35.3) 148 (30.5) 183 (34.2) 6 (13.4) 16 (37.2) 516 (32.9)Somewhat agree 0 69 (15.2) 103 (21.2) 122 (22.8) 18 (40) 2 (4.6) 314 (20.0)Neither agree nor disagree 0 28 (6.2) 52 (10.7) 62 (11.6) 5 (11.1) 2 (4.6) 149 (9.5)Somewhat disagree 1 (12.5) 17 (3.7) 28 (5.8) 23 (4.3) 3 (6.7) 2 (4.6) 74 (4.7)Disagree 0 8 (1.8) 22 (4.5) 11 (2.1) 7 (15.6) 0 48 (3.1)Strongly disagree 0 4 (0.9) 9 (1.9) 4 (0.7) 2 (4.4) 1 (2.3) 20 (1.3)

I would enroll my patient in a clinical trial comparing protocol-based versus usual care c

Strongly agree 3 (37.5) 139 (31.0) 127 (26.2) 130 (24.4) 5 (11.4) 24 (55.8) 428 (27.4)Agree 3 (37.5) 144 (32.1) 195 (40.3) 199 (37.3) 21 (47.7) 11 (25.6) 573 (36.7)Somewhat agree 0 83 (18.5) 72 (14.9) 59 (11.1) 6 (13.6) 1 (2.3) 221 (14.2)

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Characteristic

No (%)

Africa(N=8)

Asia(N=453)

Europe(N=485)

North America(N=535)

Oceania(N=45)

South America(N=43)

All(N=1,569)

Neither agree nor disagree 2 (25.0) 56 (12.5) 61 (12.6) 110 (20.6) 5 (11.4) 4 (9.3) 238 (15.3)Somewhat disagree 0 12 (2.7) 11 (2.3) 8 (1.5) 4 (9.1) 2 (4.6) 37 (2.4)Disagree 0 11 (2.5) 15 (3.1) 17 (3.2) 2 (4.5) 1 (2.3) 46 (2.9)Strongly disagree 0 3 (0.7) 3 (0.6) 10 (1.9) 1 (2.3) 2 (4.6) 17 (1.1)

a P value=0.15; b P value<0.001; c P value=0.003

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eTable 8: Perceptions Related to Timing, Protocol Use and Willingness to Enroll Patients in a

Clinical Trial of Protocol-Based Net Ultrafiltration by Practitioner Type

No. (%)


Physician (n=1,173)

Nurse & Nurse Practitioners

(n=396)

P value

I believe early fluid removal is beneficial

Strongly agree 544 (34.7) 409 (34.9) 135 (34.1)

0.02

Agree 620 (39.5) 440 (37.5) 180 (45.4)Somewhat agree 248 (15.8) 198 (16.9) 50 (12.6)Neither agree nor disagree

104 (6.6) 80 (6.8) 24 (6.1)

Somewhat disagree 32 (2.0) 30 (2.6) 2 (0.5)Disagree 15 (1.0) 11 (0.9) 4 (1.0)Strongly disagree 6 (0.4) 5 (0.4) 1 (0.2)

I believe a protocol-based fluid removal strategy would be beneficial

Strongly agree 448 (28.5) 328 (28) 120 (30.3)

0.39

Agree 516 (32.9) 382 (32.6) 134 (33.8)Somewhat agree 314 (20.0) 232 (19.8) 82 (20.7)Neither agree nor disagree 149 (9.5) 121 (10.3) 28 (7.1)


I would enroll my patient in a clinical trial comparing protocol-based versus usual care

Strongly agree 428 (27.4) 340 (29.0) 88 (22.7)

<0.001

Agree 573 (36.7) 446 (38.0) 127 (32.8)Somewhat agree 221 (14.2) 180 (15.3) 41 (10.6)Neither agree nor disagree 238 (15.3) 126 (10.7) 112 (29.0)


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eTable 9: Thematic Analysis of Comments by Practitioner Type

No. (%)

Theme or SubthemeAll

Comments(N=458)

Physician Comments

(N=355)

Nurse Comments

(N=103)Tools to facilitate UFNET

Functional hemodynamic monitoring 40 (8.7) 39 (11.0) 1 (1.0)

Biomarker 10 (2.2) 9 (2.5) 1 (1.0)Use of protocol 7 (1.5) 6 (1.7) 1 (1.0)Use of precision medicine 25 (5.5) 17 (4.8) 8 (7.8)Use of vasopressors 16 (3.5) 13 (3.7) 3 (2.9)Prescription-related factors 45 (9.8) 37 (10.4) 8 (7.8)

Organizational factorsResources 19 (4.1) 11 (3.1) 8 (7.8)Practice characteristics 10 (2.2) 9 (2.5) 1 (1.0)Practice variation 20 (4.4) 13 (12.6) 7 (2.0)

Clinician-related factorsEducation/Training 20 (4.4) 7 (2.0) 13 (12.6)Experience 6 (1.3) 3 (0.8) 3 (2.9)Communication 2 (0.4) 2 (0.5) 0

Patient-related factorsUnderlying cause of FO 11 (2.4) 9 (2.5) 2 (1.9)Assessment of fluid overload 27 (5.9) 25 (7.0) 2 (1.9)Comorbidities 28 (6.1) 23 (6.5) 5 (4.8)Intravascular volume assessment 17 (3.7) 16 (4.5) 1 (1.0)

Fluid management 26 (5.7) 22 (6.2) 4 (3.9)Monitoring 10 (2.2) 8 (2.2) 2 (1.9)Oliguria treatment 10 (2.2) 10 (2.8) 0Complication management 4 (1.1) 1 (1.0)

RRT related factorsAnticoagulation 10 (2.2) 8 (2.2) 2 (1.9)Treatment interruption 10 (2.2) 3 (0.8) 7 (6.8)Timing of initiation of UFNET 28 (6.1) 18 (5.1) 10 (9.7)Modality 14 (3.1) 12 (3.4) 2 (1.9)

Miscellaneous 43 (9.4) 38 (10.7) 5 (4.8)

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eTable 10: Example Comments Amenable to Research and Quality Improvement Interventions

Theme Comments Amenable to Research Comments Amenable to Quality Improvement

Vasopressor use during net ultrafiltration

“Is it fluid first or wean vasopressors first. Always the question of the day” – ICU nurse

“After the initial start and fluid removal, I have seen that we actually titrate down vasopressors and inotropes with fluid removal” – ICU nurse

“Fluid removal from patients with volume overload but still needs vasopressor, harmful or beneficial?” – Intensivist

“Earlier use of vasopressors in sepsis” – Intensivist

“Deciding how much pressor willing to tolerate to allow for fluid removal. Goal is to return to euvolemia NOT liberate from pressors. Pressor liberation will follow patient recovery.” – Intensivist and Nephrologist

“Avoiding excess fluid administration even if vasopressor dosage must be increased” – Intensivist

Practice variation “Clear guidance for recommended UF rates would be extremely beneficial, there is nothing that I have seen in my time within critical care to guide nurses on fluid removal rates. I feel it is very variable between nurses, for example, one nurse may be happy with removing 350-400 mL/hr with a patient on 0.19 mcgs of noradrenaline and a slightly elevated but static lactate with this increase in UF, whereas another nurse may not be comfortable” – ICU nurse

“Find two doctors who agree on the fluid status and you have group think, because there are no good grounds for saying anything other than diagnosing fluid overload using standard

“The management of dialysis therapies is highly consultant specific, with each senior medical lead prescribing according to beliefs and current practices so there is high variability in prescribing practices” – Advanced Practice Provider

“Physicians that do not agree on ultrafiltration orders (net vs. set rates) can delay or adversely affect treatment” – ICU nurse

“As a senior nurse within the ICU and having done 32 years of ICU and renal replacement therapy for our

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tools; euvolemia is hard to diagnose, hypovolemia is routinely over-diagnosed and often undiagnosed.” – Intensivist

patient group the biggest issue I find is the variation in individual consultant/intensivist practice.” – ICU nurse

“There is difference in the understanding of what maintaining a net balance of fluid removal in intensive care units in different institutions.” – ICU nurse

“How often the intensivist’s and nephrologist discuss together before deciding the fluid to be removed and how often the nurses are aware of importance of hourly monitoring and alerting duty doctor about tendency to go in to positive balance.” – Intensivist

“Changes of consultant occasionally leading to extreme changes to fluid balance i.e. replacement of large amounts of fluid and next day aggressively removing fluid. Perhaps a more consistent approach would result in less hemodynamic instability and better fluid management overall.” – ICU nurse

Treatment interruption

“I feel that we very often run our CRRT blood flow rate too slow which I think contributes to frequent clotting of the CRRT set. I worked outpatient HD before becoming a nurse and we experienced increased set clotting when the blood flow rate needed to be run slow due to catheter or fistula problems. I have brought this up to Renal before (they write our CRRT orders) and they don't listen. This increased clotting may influence the fluid removal goal.” – ICU nurse

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“When prescribing large fluid removal rates, the resulting rise in filtration fraction too often goes unnoticed and addressed, leading to earlier filter clogging and all that follows.” – ICU nurse

“Interruption in CRRT is frequent in the ICU due to the machine frequently clotting or having issues all together with initiating treatment. The delay in treatment often occurs due to alarms during the setup/priming of this machine. Multiple machines may be used” – ICU nurse

Timing “Time schedule for fluid resuscitation vs. removal is important. In my opinion, most patients with septic shock need fluid resuscitation for up to 24 hrs after treatment onset; sometimes up to 48 hrs. During this time, fluid removal by RRT is contraindicated. Afterwards, they usually do need any fluid (except for nutrition) and are eligible for fluid removal (even if still on some dose of vasopressors). If fluid removal causes severe hypotension relapse, one should immediately look for an explanation (e.g. bleeding, untreated sepsis focus, right heart failure, severe hypalbuminemia), because it is very uncommon that you cannot achieve a negative balance 48 hrs after treatment onset. These aspects should be considered in a potential clinical trial protocol.” – Intensivist

“Criteria for discontinuation of CRRT” – Intensivist

“We support initiation of RRT early in positive fluid balance state before fluid overload occurs.” – Intensivist

“I want the MD to start CRRT earlier than they do and not as the last line of defense in ARF. I know earlier initiation of CRRT improves outcomes in our sepsis patients and recovery of kidney function.” – ICU nurse

“Unfortunately, in the hospital in which I am employed this method is primarily used as a last resort and the patients usually do not have good outcomes.” – ICU nurse

“RRT whether intermittent HD or CRRT should be initiated early in volume overload when clinically indicated, but the clinical condition including age and comorbidities must be considered in tandem. We are experiencing a surge in poor candidates for L/BiVAD/ECMO patients that are requiring CRRT for volume management and our outcomes have been less than encouraging. In some of these cases, resource utilization needs to be considered and these

35


“Early removal of fluid overload but not aggressive, no problem to make your patient euvolemic over few days” – Intensivist

“Is not important if the patient may be wet or dry but when we can do it.” – Intensivist

“Clinical targets for terminating renal replacement therapy, use of diuretics in between two sessions of intermittent hemodialysis” – Intensivist

advanced therapies may not/should not be considered.” – ICU nurse

Resource “If we are going to have to calculate hourly fluid removal based on intake, the patient in the ICU should be a single assignment. It would be difficult to accomplish this goal with more than one patient.” – ICU nurse

“Most community hospitals do not have CRRT or SLED.” – Intensivist

“I would do a qualitative study looking at nurse or renal technician anxiety first. If you don't factor this in your protocol won’t get delivered” – Intensivist

“Institutional ability for all intensivists to be able to prescribe their own CRRT provides the ability to have much more aggressive institution of these therapies.” – Intensivist

Education “The current education mantra surrounding CRRT taught to nurses surrounds low removal rates for long periods of time. Coverage of adequate fluid removal,

36


including net fluid removal, is not well covered. I find most nurses in my practice do not understand the benefit of volume expanders or fluid volumes for hemodynamic instability, instead they stop fluid removal for many hours at a time. In my unit, CRRT is initiated far too late in the patient’s case, usually waiting until MODs is advanced and potentially irreversible. A large percent of our CRRT patient progress to death.” – ICU nurse

“Continuous RRT education for junior doctors & nurses. Ignorance and disagreements are key barriers in fluid management, in addition to misinterpretation of protocol” – ICU nurse

“Staff need to be educated as to the theory behind UF and dialysis as they will be better to manage complications and the treatment. ICU staff are not always aware of the theory.” – ICU nurse

Precision Medicine “Fluid removal cannot be managed in isolation to the overall clinical scenario. For example, fluid removal with some pressor support might be justified to avoid pulmonary failure and mechanical ventilation especially in high risk patients (elderly, neutropenic, very obese, etc.). On the other hand, an intubated patient with some pulmonary edema and low ventilator settings might wait until vasopressors are off before performing aggressive UF. The main barrier to a protocolized fluid removal strategy is the heterogeneity of ICU patients” – Intensivist

“I feel like so much of our work flow is over protocolized and algorithmic, taking the "art" of nursing away along with our critical thinking. Having a more aggressive fluid removal program is appealing because I know how beneficial it can be. However, I worry that it will be one more "to do" that will be added on to the increasingly tasky requirements in ICU care. Perhaps adding more education on assessing volume status, utilizing the passive leg raise or other noninvasive maneuvers, and also encouraging more physicians to utilize bedside ultrasonography more

37


“Individualized management plan for critically ill patients is pivotal.” – Intensivist

“Cardiorenal syndrome vs post-surgical fluid overload may have different implications for fluid removal and timing of fluid removal with or without vasopressors” – Nephrologist

“Our patients are on a burn/trauma ICU - fluid protocols are tricky with burned patients...each one is unique.” – ICU nurse

“There needs to be patient specific guidelines regarding fluid removal in patients (i.e. more fluid removal and in turn having patient on more vasopressors, or less fluid removal to keep patient off of vasopressors).” – ICU nurse

would be the most helpful.” – ICU nurse

“Protocolized processes help efficiency but stop clinicians from THINKING. I wouldn't use a protocol. I'd pay attention and manage the process.” – Intensivist

“Given AKI in ICU is usually part of a multisystem disease process, I think it is not good medicine to protocolize all patients into the same method and there needs to be senior clinician assessment and input regularly into the patient's treatment (i.e., more than once day).” – Intensivist

Protocol-based treatment

“It is still an area of debate and wide range of variability in practice worldwide so if there is a protocol-based practice think we may achieve better outcome for our patients.” – Intensivist

“Whether a protocol that can improve long-term prognosis can be established” – Intensivist

“Fluid overload is a very complex issue that cannot be addressed by simplistic management protocols. The role of fluid management changes markedly over the course of illness as resuscitation escalates, stabilizes and then de-escalates.” - Nephrologist

“Important to create a plan with ICU team for fluid removal including goals and triggers to stop/reassess. Much that you would consider in a guideline if you don't have one. I guess one question is how prescriptive you can be for all comers.” – Intensivist

Intravascular volume assessment

“Measure of plasma refill rate. This is probably an important factor that we don’t measure accurately in ICU patients” -

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Intensivist

“Some assessment of the restoration of the integrity of endothelial function. That is, can the patient tolerate the reduction in blood volume by pulling fluid back out of the interstitium or not?” – Intensivist

Prescription of fluid removal

“Some ICUs I have worked at have the prescription for UF as "net" for the hour; others have simply a UF removal rate (so net varies by INs and other OUTs); I think having some sense of how UF is prescribed matters.” – Intensivist

“Emergency patients with pulmonary edema need 1000 ml removal for one hour and then say 200 mL/ hr will do.” – Intensivist

“I would not want to enroll patients in any trial where fluid removal was ongoing in the face of hemodynamic instability associated with all the clinical signs of intravascular depletion and prescription of vasopressors” – Intensivist

“I would be more aggressive with fluid removal if it was evidence based.” – Intensivist

“Renal, lung and heart echography use for initiation, titration and weaning RRT” – Intensivist

“The criteria for fluid removal should be more aggressive if the patient is hemodynamically stable.” – Intensivist

“I feel that more UF is better - we can always give some volume back if the patient gets too dry. Nurses are hesitant to push the UF to make more work for themselves.” – ICU nurse

“Orders aren’t clear regarding CRRT patients. Some order straight fluid removal while others want the fluid adjusted according to intake adjustments. Often partners differ. Since these are paper faxed orders not communicated well in EHR and practices vary nurse to nurse. We don’t do CRRT consistently then sometimes we have three running at one time. It’s hard to do in low volume high risk proficient competencies for these patients. It would be nice to all be trained the same way for standardized patient care and outcomes.” – ICU nurse

“Some ICUs I have worked at have the prescription for UF as "net" for the hour; others have simply a UF removal rate (so net varies by Ins and other Outs); I think having some sense of how UF is prescribed matters” – Intensivist

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Hemodynamic monitoring

“What hemodynamic monitoring should be used before to stop the remove of fluid” – Intensivist

“We should use bed side IVC collapsibility status pulse pressure variability, stroke volume variability index and other clues to fluid status” – Intensivist

“ECHO and lung ultrasound are frequently used in the unit to guide volume removal. We have some 10-20L in a day in selected patient with beneficial outcomes, such as reduced inotropes, extubation, improved renal function etc. especially in the RV failure group” – Intensivist

Practice characteristics

“Although I would be the last to "relinquish" control of RRT to intensivists, I also believe that an ideal CRRT program does "hand over" a fair bit of control of the UF rate to the ICU team and ICU RN. Involvement of ICU teams, especially ICU RN's, will be critical to the success of any protocol seeking to address UFR.” – Nephrologist

Assessment of fluid overload

“How to diagnose and measure fluid overload?” – Intensivist

“I think patient weight/weight change is a better marker of cumulative fluid balance status than the in/out balances that are commonly used.” – Intensivist

“I think that fluid overload is somewhat difficult to diagnose; many patients have too much fluid "on board" without meeting clear criteria of physiological derangements; many intensivists are reluctant to initiate RRT, as they want to try diuretics first; I am very much in favor of initiation RRT (either CRRT or SLED) in accordance with KDIGO criteria of AKI; RRT should in my opinion be initiated when reaching KDIGO grade 3.” – Intensivist

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“Accurate I&Os are important. My hospitals policy is to document net I&O as whatever is ordered/set on the machine each hour, not what is actually removed.” – ICU nurse

Training and experience

“I think a limiting factor in achieving fluid balance targets/adequate fluid removal is often due to inexperience of nursing staff caring for patients receiving intermittent or continuous fluid removal.” – ICU nurse

“Physicians who are not specialized in intensive care, especially physicians are not aware of the harmfulness of excessive fluids but are also pathologically feared for hypovolemia. They do not have the ability to properly evaluate the intravascular volume and the amount of water in the body. It is the most difficult task to make them understand the necessity of water removal” – Intensivist

“Educate doctors on using pre-replacement fluid. The class teaches that when there is dialysate, post-replacement, and pre-fluid the machine runs a lot better!!” – ICU nurse

“The need for CRRT in our ICUs is quite infrequent and we are concerned about nursing maintenance of skills managing CVVH” – ICU nurse

Use of biomarker to guide fluid removal

“Measurement of blood lactate as a marker of tissue oxygen metabolism during water removal with CRRT is important” –

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Intensivist Modality of kidney replacement therapy used for net ultrafiltration

“Use of hemofiltration should be better modality than hemodiafiltration for fluid removal” – Intensivist

“Intermittent dialysis tends to be too aggressive in fluid removal leading to prolonged time on CRRT.” – ICU nurse

“In patients with cerebral edema/high ICP the choice of dialysis modality & fluid removal may be limited by CNS status. This was not included in this survey.” – Intensivist

“Most of the time, there is not a single factor that determines the need for initiating CRRT. In ICU, intermittent HD is hardly ever started as a first therapy. It is worth considering to separate these modalities in the trial. Lumping May not give the desired results.” – Intensivist

“CRRT offers no more benefit than intermittent hemodialysis ran by an experienced dialysis nurse. In my opinion, CRRT is used for improved billing return/revenue. Intermittent hemodialysis is just as effective if not more so than CRRT. I have been a dialysis/ICU nurse for over 30 years, please show me the data that says "slow solute removal" is more effective than intermittent dialysis. That would be a study NOT paid for by the CRRT machine makers!” – ICU nurse

“I think you should ask about availability of various modalities in the ICU/hospital. e.g. we only have CRRT, there is no SCUF/SLED/IHD in our hospital.” – Intensivist

“I feel there is no role for conventional duration IHD in this context as required UF rates are too high” – Intensivist and Nephrologist

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eFigure 1: Evaluation of Net Fluid Balance During CRRT by Practitioner Type

Figure shows the proportion of responses for evaluation of net fluid balance (i.e., the difference

between patient and machine fluid balance) across CRRT treatment hours by physicians and

nurses. P value<0.001. Physicians were less likely to evaluate net fluid balance hourly and more

likely to evaluate beyond the first hour compared with nurses.

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eFigure 2: Early, Protocol-based Net Ultrafiltration and Willingness to Enroll in a Clinical Trial

A

The figure shows the proportion of practitioners who agreed to whether early initiation of net ultrafiltration and use of a protocol be beneficial and willingness to enroll patients in a clinical trial of protocol-based net ultrafiltration compared with usual care. Across continents, there was no variation in agreement towards early fluid removal (P=0.15). However, there was significant variation in protocol-based fluid removal (P<0.001) and willingness to enroll in a clinical trial (P=0.003).

B

Practitioners who agree whether early and protocol-based net ultrafiltration would be beneficial and willing to enroll their patients in a clinical trial of protocol-based net ultrafiltration versus usual care (C). Physicians and nurses agreed that early and protocol-based net ultrafiltration would be beneficial (P=0.10 for both responses). Whereas, physicians were more willing to enroll patients in a clinical trial than nurses (P<0.001).

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eFigure 3: Word Cloud of Comments

Lexical analysis of practitioner comments revealed top five non-conjunctive terms such as

“fluid” (168 words), “patient” (132), “removal” (93), “CRRT” (78), and “treatment” (42).

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eReference

1. Braun V, Clarke V, (2014) What can "thematic analysis" offer health and wellbeing researchers? Int J Qual Stud Health Well-being 9: 26152

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