Albumina Guias 2024. Chest.

1
[ Critical Care Guideline and Consensus Statement ] 56

2 57
3 58
4 59
5 60
6
7
Q1
Use of Intravenous Albumin 61
62
8 A Guideline From the International Collaboration for Transfusion 63
9 64
10
Medicine Guidelines 65
11 66
12 Q57 Jeannie Callum, MD; Nikolaos J. Skubas, MD; Aarti Bathla, MPharm, MPH; Homa Keshavarz, PhD; Edward G. Clark, MD; 67
13 Q2 Bram Rochwerg, MD; Dean Fergusson, PhD; Sesmu Arbous, MD; Seth R. Bauer, PharmD; Louise China, MD; 68
14 Mark Fung, MD; Rachel Jug, MD; Michael Neill; Cary Paine, MD; Katerina Pavenski, MD; Prakesh S. Shah, MD; 69
15 Susan Robinson, MD; Hua Shan, MD; Zbigniew M. Szczepiorkowski, MD, PhD; Thierry Thevenot, MD; Bovey Wu; 70
16 71
Simon Stanworth, MD, PhD; and Nadine Shehata, MD; on behalf of the International Collaboration for Transfusion
17 * 72
Medicine Guidelines Intravenous Albumin Guideline Group
18 73
19 74
20 75
21 BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve 76
22 hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The 77
23 International Collaboration for Transfusion Medicine Guidelines developed guidelines for 78
24 the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, 79
25 undergoing kidney replacement therapy, or experiencing complications of cirrhosis. 80
26 81
METHODS: Cochairs oversaw the guideline development process and the panel included re-
27 82
searchers, clinicians, methodologists, and a patient representative. The evidence informing
28 83
this guideline arises from a systematic review of randomized clinical trials and systematic
29 84
30
reviews, in which multiple databases were searched (inception through November 23, 2022).
85
31 The panel reviewed the data and formulated the guideline recommendations using Grading 86
32 of Recommendations Assessment, Development and Evaluation methodology. The guidelines 87
33 were revised after public consultation. 88
34 RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three 89
35 recommendations), pediatric critical care (one recommendation), neonatal critical care (two 90
36 91
recommendations), cardiovascular surgery (two recommendations), kidney replacement
37 92
therapy (one recommendation), and complications of cirrhosis (five recommendations). Of
38 93
the 14 recommendations, two recommendations had moderate certainty of evidence, five
39 94
40
recommendations had low certainty of evidence, and seven recommendations had very low
95
41 certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin 96
42 for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bac- 97
43 terial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide 98
44 variety of clinical situations where albumin commonly is transfused. 99
45 CONCLUSIONS: Currently, few evidence-based indications support the routine use of albumin 100
46 101
in clinical practice to improve patient outcomes. These guidelines provide clinicians with
47 102
actionable recommendations on the use of albumin. CHEST 2024; -(-):---
48 103
49 KEY WORDS: guideline; intensive care; IV albumin; kidney replacement therapy; liver disease; 104
50 Q6 sepsis 105
51 106
52 107
53 ABBREVIATIONS: GRADE = Grading of Recommendations Assess- AFFILIATIONS: From the Department of Pathology and Molecular 108
Q4
54 ment, Development and Evaluation; ICTMG = International Collab- Medicine (J. C.), Queen’s University and Kingston Health Sciences 109
oration for Transfusion Medicine Guidelines; MD = mean difference; Centre, Kingston, the Division of Nephrology (E. G. C.), Department Q3
55 110
RCT = randomized controlled trial; RR = relative risk of Medicine, University of Ottawa, Ottawa Hospital Research Institute
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PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

111 Summary of Recommendations 1. In critically ill adult patients (excluding patients 166
112 with thermal injuries and acute respiratory distress 167
Q7 Intravenous albumin is a human-derived blood product
113 Q9 168
manufactured from donated human plasma. It is used syndrome), intravenous albumin is not suggested for
114 169
broadly in hospitalized patients, as well as in outpatients first-line volume replacement or to increase serum
115 170
with complications of cirrhosis. Intravenous albumin albumin levels (Conditional Recommendation,
116 171
has been studied in numerous, large, well-designed, Moderate Certainty of Evidence of Effect).
117 172
118 randomized controlled clinical trials in multiple patient 173
2. In critically ill adult patients with thermal
119 populations; the data show few applications of albumin 174
injuries or acute respiratory distress syndrome,
120 that improve patient outcomes. Albumin is more 175
intravenous albumin is not suggested for volume
121 expensive to manufacture and to provide to patients, 176
replacement or to increase serum albumin level
122
Q8 when compared to crystalloids. The International 177
(Conditional Recommendation, Very Low Certainty of
123 Collaboration for Transfusion Medicine Guidelines 178
124
Evidence of Effect). 179
undertook this guideline development process to
125 3. In critically ill adult patients, intravenous 180
provide clinicians with actionable recommendations for
126 181
appropriate use of intravenous albumin. albumin in conjunction with diuretics is not
127 182
suggested for removal of extravascular fluid
128 183
(Conditional Recommendation, Very Low Certainty of
129 184
Evidence of Effect).
130 185
131 (D. F.), Ottawa, the Department of Medicine and Department of 186
Health Research Methods (B. R.), Evidence and Impact, Faculty of 4. In pediatric patients with infection and
132 Health Sciences, McMaster University, Hamilton; the Department of hypoperfusion, intravenous albumin is not 187
133 Laboratory Medicine and Pathobiology (K. P.), the Institute of Health 188
Policy, Management, and Evaluation (P. S. S.), the Department of
recommended to reduce mortality (Strong
134 189
Medicine (N. S.), University of Toronto, the Department of Pediatrics Recommendation, Low Certainty of Evidence of Effect).
135 (P. S. S.), the Transfusion Medicine Laboratory (N. S.), Mount Sinai 190
136 Hospital, Toronto, ON; the Canadian Blood Services (A. B. and H. K.), 5. In preterm neonates (£ 36 weeks) with low serum 191
137 Canada; the Department of Cardiothoracic Anesthesiology (N. J. S.), 192
Anesthesiology Institute, Cleveland Clinic Lerner College of Medicine
albumin levels and respiratory distress, intravenous
138 of Case Western Reserve University; the Department of Pharmacy (S. albumin is not suggested to improve respiratory 193
139 R. B.), Cleveland Clinic, Cleveland, the University of Cincinnati Col- 194
function (Conditional Recommendation, Very Low
140 lege of Medicine (R. J.), Cincinnati, OH; the Department of Pathology 195
and Laboratory Medicine (M. F.), University of Vermont Medical Certainty of Evidence of Effect).
141 Center, Burlington, VT; the Department of Pathology (H. S.), Stanford 196
142 University School of Medicine, Palo Alto; the Department of Internal 6. In preterm neonates (£ 32 weeks or £ 1,500 g) 197
143 Medicine (B. W.), Graduate Medical Education, Loma Linda Univer- 198
sity, Loma Linda, CA; the Department of Pathology and Laboratory
with or without hypoperfusion, intravenous
144 Medicine (Z. M. S.), Dartmouth-Hitchcock Medical Center, Lebanon, albumin is not suggested for volume replacement 199
145 NH; the Division of Nephrology (C. P.), Department of Medicine, (Conditional Recommendation, Very Low Certainty of 200
146 University of Washington, Seattle, WA; the Department of Critical 201
Care (S. A.), Leiden University Medical Center, Leiden, The Evidence of Effect).
147 Netherlands; the Department of Hepatology and ILDH (L. C.), The 202
148 Royal Free NHS Trust and University College London, Department of 7. In patients undergoing kidney replacement 203
149 Clinical Haematology (S. R.), Guy’s and St Thomas’ NHS Foundation therapy, intravenous albumin is not suggested for 204
Trust, London, NHS Blood and Transplant (S. S.), the Radcliffe
150 Department of Medicine (S. S.), University of Oxford; the John Rad- prevention or treatment of intradialytic 205
151 cliffe Hospital (S. S.), Oxford University Hospitals NHS Foundation hypotension or for improving ultrafiltration 206
152 Trust, Oxford, England; the Service d’Hépatologie (T. T.), Centre 207
Hospitalier Régional et Universitaire de Besançon, Besançon, France; (Conditional Recommendation, Very Low Certainty of
153 and Patient representative (M. N.). 208
154 *Collaborators from the International Collaboration for Transfusion 209
155 Medicine Guidelines Intravenous Albumin Guideline Group are listed 8. In adult patients undergoing cardiovascular 210
in the Acknowledgments.
156 surgery, intravenous albumin is not suggested for 211
DISCLAIMER: American College of Chest Physician guidelines are
157 priming the cardiovascular bypass circuit or volume 212
intended for general information only, are not medical advice, and do
158 not replace professional medical care and physician advice, which al- replacement (Conditional Recommendation, Moderate 213
159 ways should be sought for any medical condition. The complete 214
disclaimer for this guideline can be accessed at https://www.chestnet. Certainty of Evidence of Effect).
160 215
org/Guidelines-and-Resources.
161
Q5 CORRESPONDENCE TO: Jeannie Callum, MD; email: jlc17@queensu.ca
9. In pediatric patients undergoing cardiovascular 216
162 Copyright Ó 2024 The Author(s). Published by Elsevier Inc under li- surgery, intravenous albumin is not suggested for 217
163 cense from the American College of Chest Physicians. This is an open priming the cardiovascular bypass circuit or volume 218
access article under the CC BY-NC-ND license (http://
164 replacement (Conditional Recommendation, Very Low 219
creativecommons.org/licenses/by-nc-nd/4.0/).
165 220
DOI: https://doi.org/10.1016/j.chest.2024.02.049 Certainty of Evidence of Effect).
2 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

221 10. In patients with cirrhosis and ascites undergoing correct low serum albumin levels or to mobilize 276
222 Q10 large volume paracentesis (> 5 liters), intravenous extravascular fluid. 277
223 278
albumin is suggested to prevent paracentesis-induced
224 Hypoalbuminemia is common in acute and chronic 279
circulatory dysfunction (Conditional Recommendation,
225 illness. Hospitalized patients with hypoalbuminemia 280
Very Low Certainty of Evidence of Effect).
226 have been described as having greater morbidity 281
227 11. In patients with cirrhosis and spontaneous compared with patients with preserved albumin levels, 282
228 bacterial peritonitis, intravenous albumin is suggested promoting the use of IV albumin.1,2 In the 283
229 to reduce mortality (Conditional Recommendation, postoperative period, serum albumin levels decreases 284
230 285
Low Certainty of Evidence of Effect). precipitously by 10 to 15 g/L3; hypoalbuminemia is
231 286
thought to be the result of suppressed synthesis by
232 12. In patients with cirrhosis and extraperitoneal 287
inflammatory cytokines4 and transcapillary loss.5 In
233 infections, intravenous albumin is not suggested to 288
234
addition to its use in patients with hypoalbuminemia, 289
reduce mortality or kidney failure (Conditional
235 edema, or both, albumin also is used for the 290
Recommendation, Low Certainty of Evidence of Effect).
236 prevention and treatment of hypovolemia, particular 291
237 13. In hospitalized patients with decompensated after administration of large volumes of IV crystalloid 292
238 cirrhosis with hypoalbuminemia (< 30 g/L), repeated solutions.6 293
239 intravenous albumin to increase albumin levels > 30 294
Practice audits describing the use of albumin show
240 g/L is not suggested to reduce infection, kidney 295
241 Q11 dysfunction or death (Conditional Recommendation, highly variable practice among regions.7,8 Albumin is 296
242 manufactured from large volumes of plasma and is 297
Low Certainty of Evidence of Effect).
243 expensive (approximately $130/25 g [United States 298
244 14. In outpatients with cirrhosis and uncomplicated dollars]; warehouse acquisition cost of albumin), with Q13 299
245 ascites despite diuretic therapy, intravenous albumin the acquisition cost likely a fraction of the total health 300
246 is not routinely suggested to reduce complications care expenditure.9 Albumin also can be associated 301
247 associated with cirrhosis (Conditional with adverse consequences, including fluid 302
248Q12 Recommendation, Low Certainty of Evidence of Effect). overload, 10,11
hypotension, hemodilution requiring 303
12
249 304
RBC transfusion,13 anaphylaxis,14 and peripheral
250 Background 15 305
gangrene from dilution of natural anticoagulants.
251 306
Albumin is administered in a wide spectrum of clinical Because potential benefits and risks are associated
252 307
scenarios including complications of cirrhosis, with its use, a multidisciplinary, international
253 308
254
intradialytic hypotension, volume resuscitation, and guideline panel was convened to develop evidence- 309
255 priming of cardiopulmonary bypass circuit. Iso-oncotic based recommendations for the use of albumin in 310
256 albumin often is used to maintain intravascular volume patient populations where it is prescribed commonly. 311
257 in patients with hypovolemia, assuming that crystalloid These guidelines are designed to assist clinicians in 312
258 resuscitation will be ineffective given its shorter their decisions on the use of albumin for its most 313
259 intravascular half-life. Hyperoncotic albumin is used to common uses. 314
260 315
261 316
262 therapeutic apheresis was excluded because recent guidelines were 317
263
Methods 318
published.16
Guidelines Focus
264 319
These recommendations apply to patients receiving albumin in critical
265 Guidelines Development Process 320
care settings with hypovolemia, sepsis, hypoalbuminemia, thermal
266 injuries, and ARDS; cirrhosis; intradialytic hypotension; and Panel Composition: This guidelines development process was funded 321
267 cardiovascular surgery. These settings were included based on by the Ontario Regional Blood Coordinating Network (Ontario, 322
268 common uses of albumin, the systematic review of the published Canada) and the International Collaboration for Transfusion 323
randomized controlled trials (RCTs), and with input from the panel. Medicine Guidelines (ICTMG; funded by Canadian Blood
269 324
We included studies that compared the use of albumin with that of Services). Neither entity had any input on recommendations or
270 325
other resuscitation fluids, other pharmaceutical treatments, or guidelines content. An international panel of neonatal, pediatric,
271 standard of care. and adult specialists with expertise in the use of albumin developed 326
272 the recommendations. This panel included 20 members with 327
273 expertise in intensive care, hepatology, gastroenterology, 328
Target Population nephrology, hematology, pathology, neonatology, transfusion
274 329
These guidelines provide actionable recommendations for the most medicine, cardiothoracic anesthesiology, internal medicine, and
275 330
common indications for the use of albumin. The use of albumin for methodology and a patient representative. A framework and related
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331 clinical questions were developed according to the United States Grading of the Evidence: Recommendations were formulated on the 386
332 Preventative Services Task Force Criteria. Disclosures were basis of the Grading of Recommendations, Assessment, Development 387
333 ascertained yearly from all members. and Evaluation (GRADE; GRADEpro GDT).19 The evidence certainty Q16
388
was graded as high, moderate, low, or very low certainty based on
334 Systematic Review of the Evidence: A systematic search for articles 389
GRADE criteria.20 The panel ranked clinical outcomes (electronic
335 published between inception and November 23, 2022, in survey) relevant for the development of recommendations according 390
336 MEDLINE, EMBASE, Cochrane, the National Health Service 391
to GRADE criteria. Outcomes were ranked on a nine-part Likert scale
Economic Evaluation Database Cochrane Database of Systematic for all relevant clinical outcomes identified by panel members (1-3 ¼
337 392
Reviews, Cochrane Central Register of Controlled Trials, Ovid low importance, 4-6 ¼ important but not critical, and 7-9 ¼ critical)
338 MEDLINE, Ovid MEDLINE epub ahead of print and in-process, 393
(e-Appendix 5). Recommendation strength was evaluated as strong or
339 and other nonindexed citations was completed with the assistance 394
conditional. A strong recommendation was made according to
340 of an information specialist. The Preferred Reporting Items for GRADE if the panel was “confident that the desirable effects 395
341 Systematic Reviews and Meta-analyses flow diagram for this outweighed the undesirable effects.” A conditional recommendation 396
review is presented in e-Appendix 1. The guideline development
342 was made if the panel concluded that the “desirable effects probably 397
group conducted two systematic reviews: one for patients with outweigh the undesirable effects,” but the trade-offs were not well
343 critical illness or cirrhosis or requiring kidney replacement 398
defined and the recommendation may not be applicable to all
344 therapy (International Prospective Register of Systematic Reviews 399
patients.21 The terms recommend and suggest were used to reflect
345 Identifier: CRD42019145152) and the other for patients
strong and conditional recommendations, respectively. 400
346 undergoing cardiovascular surgery (International Prospective 401
Register of Systematic Reviews Identifier: CRD42020171876). Virtual conferences and electronic correspondence were used to discuss
347 402
Manually searched references of primary articles, relevant the clinical questions and to formulate recommendations. Electronic
348 reviews, and additional articles identified by panel members were surveys were sent to all members to assess agreement with 403
349 included. The search strategy is detailed in e-Appendix 2. Study recommendations. Disagreements were resolved by discussion. If 404
350 inclusion criteria were: (1) original peer-reviewed published RCTs disagreements could not be resolved, a recommendation was accepted 405
351 comparing albumin with an alternative strategy, (2) systematic if most members (50% or more of the panel) agreed. Members 406
reviews and meta-analyses reporting on RCTs, or both, (3) recorded their disclosures, but none were excluded from voting
352 407
including at least one of the following outcomes of interest: (e-Appendix 6). The final guidance document was disseminated widely
353 mortality, multisystem organ failure, need for kidney replacement for public consultation to numerous medical societies (e-Appendix 7). 408
354 therapy or kidney failure, need for vasoactive medications, need The reviewers from these societies were sent a survey consisting of 409
355 for mechanical ventilation, hypotension, hemodynamic metrics, open-ended and closed-ended questions to determine agreement with 410
Q14
356 length of stay (hospital and intensive care), quality of life, health each recommendation and to identify facilitators and barriers to 411
care use, and albumin levels; and (4) published in English. guideline implementation. Comments from reviewers subsequently
357 412
were discussed by panel members and addressed.
358 InsightScope screened publications for eligibility and extracted 413
359 characteristics, outcomes, and risk of bias for all indications, with the The recommendations in this guidance document will be reviewed every 3 414
exception of studies published between November 2018 and years. If a study is published that may impact the recommendations
360 415
November 2022 and the systematic review for cardiovascular surgery. critically before that time, a comment will be added on the ICTMG
361 Quality and risk-of-bias assessment were conducted using the website. Recommendations are intended for critical care physicians, 416
362 established criteria,17,18 presented in detail for all systematic reviews in nephrologists, hepatologists, gastroenterologists, anesthesiologists, 417
363 e-Appendix 3. Discrepancies were resolved by a third reviewer. With cardiovascular surgeons, general internists, hospitalists, hematologists, 418
364 the exception of cardiovascular surgery, comprehensive systematic pathologists, pharmacists, laboratory technologists, and transfusion 419
reviews were available for all other settings that were used to develop medicine physicians. The ICTMG website (https://www.ictmg.org) will
365 420
recommendations. For cardiovascular surgery, where no systematic be used to post implementation tools (eg, podcasts, order sets). The
366 review had been performed, a systematic review and meta-analysis was guideline process adhered to the 2011 Institute of Medicine (United 421
367
Q15 conducted [Brit J Anaesth (in press); citation to follow]. Evidence States) Committee on Standards for Developing Trustworthy Clinical 422
368 tables for all indications are presented in e-Appendix 4. Practice Guidelines. 423
369 424
370 425
371 Recommendations volume replacement or to increase serum albumin 426
372 Recommendations are outlined in Table 1. level (Conditional Recommendation, Very Low 427
373 Certainty of Evidence of Effect). 428
374
Clinical Setting 1: Critically Ill Adult Patients 429
375
Recommendation 3: In critically ill adult patients, 430
Recommendations: Recommendation 1: In critically
376 intravenous albumin in conjunction with diuretics is 431
ill adult patients (excluding patients with thermal
377 not suggested for removal of extravascular fluid 432
injuries and acute respiratory distress syndrome),
378 (Conditional Recommendation, Very Low Certainty of 433
intravenous albumin is not suggested for first-line
379 Evidence of Effect). 434
volume replacement or to increase serum albumin
380 435
levels (Conditional Recommendation, Moderate
381 Evidence Summary: Sixteen22-37 of 19 systematic 436
Certainty of Evidence of Effect).
382 reviews were retrieved and included. These reports 437
383 Recommendation 2: In critically ill adult patients with included a broad critical care patient population, 438
384 thermal injuries or acute respiratory distress including patients with critical illness, sepsis, thermal 439
385 injuries, and ARDS. Three of the 19 systematic reviews 440
syndrome, intravenous albumin is not suggested for

441 TABLE 1 ] The 14 Recommendations From the Panel, Ordered by Strength of the Recommendations 496
Q52
442 497
Moderate Certainty of Evidence Q58
443 Recommendation 1: In critically ill adult patients (excluding patients with thermal injuries and acute respiratory distress 498
444 syndrome), intravenous albumin is not suggested for first-line volume replacement or to increase serum albumin levels 499
445 (Conditional Recommendation, Moderate Certainty of Evidence of Effect). 500
446 Recommendation 8: In adult patients undergoing cardiovascular surgery, intravenous albumin is not suggested for 501
priming the cardiovascular bypass circuit or for volume replacement (Conditional Recommendation, Moderate Certainty of
447 502
448 503
Low Certainty of Evidence
449 504
Recommendation 4: In pediatric patients with infection and hypoperfusion, intravenous albumin is not recommended to
450 reduce mortality (Strong Recommendation, Low Certainty of Evidence of Effect). 505
451 Recommendation 11: In patients with cirrhosis and spontaneous bacterial peritonitis, intravenous albumin is suggested to 506
452 reduce mortality (Conditional Recommendation, Low Certainty of Evidence of Effect). 507
453 Recommendation 12: In patients with cirrhosis and extraperitoneal infections, intravenous albumin is not suggested to 508
reduce mortality or kidney failure (Conditional Recommendation, Low Certainty of Evidence of Effect).
454 509
Recommendation 13: In hospitalized patients with decompensated cirrhosis with hypoalbuminemia (< 30 g/L), repeated
455 intravenous albumin to increase albumin levels > 30 g/L is not suggested to reduce infection, kidney dysfunction or death 510
Q53
456 (Conditional Recommendation, Low Certainty of Evidence of Effect). 511

457 Recommendation 14: In outpatients with cirrhosis and uncomplicated ascites despite diuretic therapy, intravenous 512
albumin is not routinely suggested "suggested routinely" per journal style?–> to reduce complications associated with Q54
458 513
cirrhosis (Conditional Recommendation, Low Certainty of Evidence of Effect).
459 514
460 Very low Certainty of Evidence 515
Recommendation 2: In critically ill adult patients with thermal injuries or acute respiratory distress syndrome, intravenous
461 516
albumin is not suggested for volume replacement or to increase serum albumin level (Conditional Recommendation, Very
462 Low Certainty of Evidence of Effect). 517
463 Recommendation 3: In critically ill adult patients, intravenous albumin in conjunction with diuretics is not suggested for 518
464 removal of extravascular fluid (Conditional Recommendation, Very Low Certainty of Evidence of Effect). 519
465 Recommendation 5: In preterm neonates (# 36 wk) with respiratory distress and low serum albumin levels, 520
intravenous albumin is not suggested to improve respiratory function (Conditional Recommendation, Very Low
466 521
Certainty of Evidence of Effect).
467 Recommendation 6: In preterm neonates (# 32 wk or # 1,500 g) with or without hypoperfusion, intravenous albumin 522
468 is not suggested for volume replacement (Conditional Recommendation, Very Low Certainty of Evidence of Effect). 523
469 Recommendation 7: In patients undergoing kidney replacement therapy, intravenous albumin is not suggested for the 524
470 prevention or treatment of intradialytic hypotension or for improving ultrafiltration (Conditional Recommendation, Very 525
Low Certainty of Evidence of Effect).
471 526
Recommendation 9: In pediatric patients undergoing cardiovascular surgery, intravenous albumin is not suggested for
472 priming the cardiovascular bypass circuit or for volume replacement (Conditional Recommendation, Very Low Certainty 527
473 of Evidence of Effect). 528
Q55
474 Recommendation 10: In patients with cirrhosis and ascites undergoing large volume paracentesis (> 5 liters), 529
475 intravenous albumin is suggested to prevent paracentesis-induced circulatory dysfunction (Conditional 530
Recommendation, Very Low Certainty of Evidence of Effect).
476 531
477 532
478 40 533
were excluded because they assessed the impact of differences in mortality or other outcomes were found.
479 534
albumin only on fluid balance,33 gelatin vs colloids,38 or A systematic review from 2018 conducted by the
480 22 535
all colloids compared with crystalloids (without reporting Cochrane collaboration found no difference in
481 536
482
albumin vs other fluids).39 mortality in patients in the ICU (20 studies; n ¼ 13,047) Q17537
Q18
483 A systematic review from 201934 identified 55 RCTs when patients managed with crystalloids were compared 538
484 comparing crystalloid with colloids in critical care. Data with those managed with albumin at the end of follow-up 539
485 on mortality were available for 26,329 patients from 46 (RR, 0.98; 95% CI, 0.92-1.06), at 30 days (RR, 0.99, 95% CI, 540
486 studies. No mortality benefit was found when crystalloid 0.93-1.06), or at 90 days (RR, 0.98; 95% CI, 0.92-1.04) or 541
487 was compared with albumin (relative risk [RR] 1.02; who needed kidney replacement therapy (RR, 1.11; 542
Q19
488 95% CI, 0.96-1.27). The largest randomized trial is the 543
95% CI, 0.96-1.10). Crystalloids were less effective than
489
colloids in hemodynamic resuscitation end points (eg, Saline versus Albumin Fluid Evaluation trial published in 544
490 545
mean arterial pressure) but this did not translate into 2004,13 which enrolled 6,997 patients receiving critical
491 546
improvements in patient outcomes. After this systematic care (including a mix of medical and surgical patients) and
492 547
493 review, one RCT was identified that examined 360 compared 4% albumin with 0.9% normal saline. No 548
494 patients with sepsis with an underlying diagnosis of differences were found in outcomes, including 28-day 549
495 cancer (albumin was compared with Ringer’s lactate); no mortality (RR, 0.99; 95% CI, 0.91-1.09). 550
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551 A 2015 systematic review evaluated the administration evaluated the impact of albumin, as compared with 606
552 of albumin in critical care patients with traumatic injury; crystalloid, in patients with ARDS.32 Three RCTs (n ¼ 607
553 608
the review included five trials comparing albumin with 204) were included; no difference in mortality was found
554 609
crystalloid and found a higher mortality in albumin- (RR, 0.89; 95% CI, 0.62-1.28). Similarly, a 2014
555 610
treated patients (RR, 1.35; 95% CI, 1.03-1.77).23 This systematic review that included two small RCTs (n ¼
556 611
systematic review was dominated by the Saline versus 70) found no difference in ventilator-free days or
557 612
558
Albumin Fluid Evaluation trial (57% of patients).13 The mortality when albumin with diuretics, as compared 613
559 Saline versus Albumin Fluid Evaluation trial subgroup with diuretics alone, were used to improve respiratory 614
560 analysis found that patients with traumatic brain injury status in critically ill patients.33 615
561
Q20 showed a higher mortality rate (RR, 1.62; 95% CI, 1.12- 616
A 2014 systematic review evaluated the impact of
562 2.34), but those without traumatic brain injury did not 617
albumin with furosemide, compared with furosemide
563 (RR, 1.00; 95% CI, 0.56-1.79).13 Hence, it is uncertain 618
564
alone, to facilitate fluid removal in patients with 619
whether albumin may be unsafe only in patients with
565 hypoalbuminemia and hypervolemia.36 The systematic 620
traumatic brain injury as compared with the wider
566 review identified 10 studies (n ¼ 343). Although urine 621
trauma population.
567 output was higher at 6 h in the patients receiving 622
568 A 2020 systematic review and sequential network albumin-furosemide, no difference was found in urine 623
569 analysis of RCTs in the setting of sepsis35 included 23 output at 24 h. One RCT of 49 patients with edema 624
570 randomized trials (n ¼ 14,659); the vast majority of the receiving critical care was identified subsequent to this 625
571 trials used a physiologic target for volume resuscitation systematic review that compared albumin and 626
572 627
or at the discretion of the clinician, rather than a furosemide with furosemide alone; no difference in
573 628
target albumin level. The review found albumin not to urine output at 8 h was found.42
574 629
be superior to crystalloids for mortality or acute kidney
575 Rationale for Recommendations: A substantial amount 630
injury. A 2014 systematic review24 included 16
576 of evidence from RCTs in critically ill adult patients 631
577
randomized trials (n ¼ 4,190) comparing crystalloid or 632
across a wide range of patient subgroups provides little
578 albumin and found no difference in mortality (RR, 0.94; 633
supportive evidence for the use of albumin as fluid
579 95% CI, 0.87-1.01). Two network meta-analyses have 634
replacement to reduce mortality, the need for kidney
580 been performed and reported no mortality benefit from 635
replacement therapy, or other outcomes considered
581 albumin.28,29 The largest randomized trial in sepsis was 636
important or critical for decision-making by the panel.
582 the Albumin Italian Outcome Sepsis trial,41 which 637
583
Given the wide CIs for the estimates from the systematic 638
randomized 1,818 patients with sepsis at 100 sites to
584 reviews, all recommendations were considered 639
20% albumin (targeting plasma albumin level of $ 30 g/L)
585 conditional because of the residual uncertainty. 640
vs crystalloid. The Albumin Italian Outcome Sepsis trial
586 641
did not observe improvements in mortality at 28 days In systematic reviews evaluating the role of albumin in
587 642
(RR, 1.00; 95% CI, 0.87-1.14) or other important patients with sepsis, the use of albumin has not been
588 643
outcomes. found to be associated with improved outcomes,
589 644
590 although a benefit has not been excluded because of the 645
Three systematic reviews found no impact of albumin in
591 wide CI in the most recent systematic review.35 The 646
critically ill adults on the need for kidney replacement
592 Surviving Sepsis Campaign guidelines published in 647
therapy, including two network meta-analyses30,35 and
593 202143 recommend albumin in addition to crystalloids 648
the 2018 Cochrane review.22 A systematic review
594 when patients require large volumes of crystalloids 649
evaluated the impact of albumin on patient outcomes
595 (weak recommendation, moderate-quality evidence). 650
596
after thermal injuries.31 The report identified four RCTs 651
Specific formulations of albumin (4%-5% or 20%-25%),
597 and found no impact on the incidence of kidney failure 652
volumes or doses, serum albumin targets, or a
598 or mortality (RR, 1.41; 95% CI, 0.27-7.38). 653
combination thereof were not described. The guidelines Q21
599 654
A 2022 systematic review evaluating the impact of state, “The lack of proven benefit and higher cost of
600 655
albumin and diuretics, as compared with diuretics alone, albumin compared to crystalloid contributed to our
601 656
602
in mechanically ventilated patients (three trials; n ¼ strong recommendation for the use of crystalloids as 657
603 129); albumin reduced hypotensive episodes, but did not first-line fluid for resuscitation in sepsis and septic 658
604 shorten the duration of mechanical ventilation or shock.”43 More studies will be needed to evaluate the 659
605 improve the mortality rate.37 A 2014 systematic review role and timing of albumin as a rescue fluid in patients 660

661 with sepsis failing front-line crystalloid resuscitation, of adult patients. Among them, a very large trial of 716
662 particularly given the considerably higher cost of children with febrile illness and hypoperfusion found 717
663 718
albumin compared with crystalloids, the risks of excess mortality when either an albumin bolus or a
664 719
albumin, and the lack of benefit shown in RCTs. crystalloid bolus strategy was compared with a no bolus
665 720
strategy. Given the extensive, albeit indirect, literature
666 721
Clinical Setting 2: Critically Ill Pediatric Patients base in adult critical care showing no improvement in
667 722
With Severe Infection mortality or other important outcomes and the above
668 723
669 Recommendation: Recommendation 4: In pediatric large trial in children suggesting excess mortality with a 724
670 patients with infection and hypoperfusion, front-line albumin bolus strategy, pediatric intensivists 725
671 intravenous albumin is not recommended to reduce probably should not use albumin as a first-line treatment 726
672 mortality (Strong Recommendation, Low Certainty of outside of a clinical trial for severe infections in critically 727
673 Evidence of Effect). ill children. Because most children enrolled in these 728
674 RCTs had malaria, it is uncertain if the results are 729
675 Evidence Summary: A single systematic review44 730
applicable to all critically ill children with infections or
676 identified three RCTs that compared albumin with 731
the broader pediatric critical care population. In
677 crystalloid in critically ill children.45-47 All RCTs 732
addition, the increased mortality in the Fluid Expansion
678 enrolled children primarily in African countries with 733
as Supportive Therapy trial may be the result of the
679 either severe malaria or febrile illness with impaired 734
bolus administration, rather than the type of fluid, with
680 perfusion. The first trial enrolled 61 children with severe 735
681
substudies of the Fluid Expansion as Supportive Therapy 736
malaria and found no difference in mortality when
682 trial showing that the bolus of either fluid type was 737
albumin was compared with crystalloid.46 The second
683 associated with higher rates of cardiovascular collapse.49 738
trial enrolled 150 children with severe malaria and found
684 739
an improvement in the mortality with albumin as Clinical Setting 3: Neonates in Critical Care
685 740
compared with crystalloid.47 A mortality difference was
686 Recommendation 5: In preterm neonates (£ 36 weeks) 741
687
not found in a large, well-designed RCT (Fluid 742
with low serum albumin levels and respiratory
688
Q22 Expansion As Supportive Therapy; n ¼ 3,141) that 743
distress, intravenous albumin is not suggested to
689 included children with severe febrile illness with 744
improve respiratory function (Conditional
690 impaired perfusion (60% had malaria).45 This RCT had 745
Recommendation, Very Low Certainty of Evidence of
691 three arms comparing saline bolus, 5% albumin bolus, 746
Effect).
692 and no bolus. The trial was terminated by the 747
693 independent data safety monitoring committee at the Recommendation 6: In preterm neonates (£ 32 weeks 748
694 fifth interim analysis based on data from 2,995 children or £ 1,500 g) with or without hypoperfusion, 749
695 750
and after 3,141 of 3,600 planned patients were enrolled intravenous albumin is not suggested for volume
696 751
because of excess mortality in the patients treated with replacement (Conditional Recommendation, Very Low
697 752
both the albumin bolus (RR, 1.45; 95% CI, 1.10-1.92) Certainty of Evidence of Effect).
698 753
and the saline bolus (RR, 1.44; 95% CI, 1.09-1.90)
699 Evidence Summary: A Cochrane systematic review 754
700
compared with children who received no bolus. No 755
evaluated the use of albumin in preterm neonates (#
701 mortality difference was found when the albumin bolus 756
36 weeks’ gestation at birth) with hypoalbuminemia
702 arm was compared with the crystalloid bolus arm (RR, 757
(two RCTs enrolling 64 preterm neonates).50 Only one
703 1.00; 95% CI, 0.78-1.29) at 48 h. Similar differences in 758
study reported mortality rates and no difference was
704 mortality were observed between groups at 28 days, 759
found. No other important differences in outcomes were
705 again with an excess mortality in the albumin and saline 760
observed. A Cochrane systematic review of RCTs of
706 bolus groups compared with the no bolus group (RR, 761
707Q23
early volume expansion compared normal saline, 762
1.40 [95% CI, 1.08-1.80] and 1.38 [95% CI, 1.07-1.78]).
708 plasma, albumin, plasma substitutes, or blood with no 763
Children treated with both saline and albumin boluses
709 treatment or another fluid treatment in preterm 764
showed higher rates of respiratory and neurologic
710 neonates (# 32 weeks or # 1,500 g).51 Early volume 765
dysfunction and of hyperchloremic acidosis and a
711 expansion was defined as > 10 mL/kg of body weight in 766
greater reduction in hemoglobin levels.48
712 the first 3 days. The studies included variable indications 767
713 Rationale for Recommendations: The systematic for the administration of IV fluids. Eight studies were 768
714 review of the literature for pediatric patients receiving identified, with four studies evaluating albumin with a 769
715 770
critical care found fewer RCTs as compared with studies comparative arm (two vs normal saline, one vs plasma,
chestjournal.org 7

771 and one vs no treatment). The two studies (n ¼ 102 and with albumin vs other fluid, but found no 826
772 n ¼ 63) comparing 5% albumin with normal saline in improvements in other outcomes, including improving 827
773 828
hypotensive infants found no difference in mortality ultrafiltration. Finally, a 2021 randomized crossover
774 829
(RR, 1.02; 95% CI, 0.50-2.06) or any other patient- trial involving 65 hospitalized patients requiring
775 830
important outcomes. The one study (n ¼ 25) comparing hemodialysis with serum albumin levels of < 30 g/L57
776 831
20% albumin with no treatment in normotensive infants found that hypotension, lowest intradialytic systolic BP,
777 832
778
also found no difference in mortality (RR, 0.92; 95% CI, and ultrafiltration rate were improved with 833
779 0.23-3.72). Finally, one trial (n ¼ 20) in hypotensive 25% albumin compared with saline. 834
780 infants compared plasma with albumin and found no 835
Rationale for Recommendation: Intradialytic
781 difference in duration of ventilation (mortality not 836
hypotension and fluid overload are experienced
782 reported). Since the publication of these two Cochrane 837
commonly during kidney replacement therapy.58,59
783 reviews, a single RCT (n ¼ 33) was identified comparing 838
Patients with intradialytic hypotension are at greater risk
784 5% albumin with normal saline (both 10 mL/kg) for 839
785
of morbidity and mortality.60 Given the costs of 840
term infants with dehydration, metabolic acidosis, and
786 albumin, the need for thrice weekly treatment for 841
diarrhea and found no differences in outcomes.52
787 patients receiving maintenance hemodialysis and the 842
788 Rationale for Recommendations: Few RCTs have lack of evidence to support superiority over less costly 843
789 evaluated the impact of albumin compared with other fluid alternatives, alternative fluids, or treatments need 844
790 alternative fluids in preterm or term neonates with to be considered. The annual cost of 25 g of albumin 845
791 either hypoalbuminemia or hypovolemia. Very little given with thrice-weekly maintenance dialysis is 846
792 evidence is available in the literature to guide the use of estimated at $20,000 per patient (United States dollars). 847
793 848
albumin in term neonates. All trials in the two Midodrine (an oral vasopressor) given alone or in
794 849
systematic reviews included small numbers of neonates, combination with use of a high dialysate calcium
795 850
preventing any definitive conclusions. Indirect evidence concentration and lower dialysate temperature has been
796 851
from the adult and pediatric literature, the costs of explored as a therapeutic option to mitigate intradialytic
797 852
798
albumin, and the lack of trials assessing the potential hypotension.61-63 In patients prescribed kidney 853
799 harms of albumin should be considered when including replacement therapy, higher dialysate calcium, lower 854
800 albumin in neonatal fluid protocols. dialysate temperature, individualized ultrafiltration 855
801 rates, or a combination of these strategies may mitigate 856
802 Clinical Setting 4: Patients Undergoing Kidney intradialytic hypotension.64-66 Further studies are 857
803 Replacement Therapy needed to understand the pathophysiology of 858
804 intradialytic hypotension67 to determine if albumin 859
Recommendation: Recommendation 7: In patients
805 prevents intradialytic hypotension or improves 860
undergoing kidney replacement therapy, intravenous
806 861
albumin is not suggested for prevention or treatment ultrafiltration,68 mitigates associated symptoms, or
807 862
of intradialytic hypotension or for improving improves patient-important outcomes.
808 863
809
ultrafiltration (conditional recommendation, very low 864
certainty of evidence of effect). Clinical Setting 5: Patients Undergoing Cardiac or
810 865
Vascular Surgery
811 866
Q24 Evidence Summary: A single Cochrane systematic
812 Recommendations: Recommendation 8: In adult 867
review was identified evaluating the use of albumin,
813 patients undergoing cardiovascular surgery, 868
compared with an alternative strategy, for the treatment
814 intravenous albumin is not suggested for priming the 869
of intradialytic hypotension.53 The review identified a
815 cardiovascular bypass circuit or volume replacement 870
816
single (n ¼ 45) randomized crossover trial of 871
(Conditional Recommendation, Moderate Certainty of
817 5% albumin compared with normal saline and did not 872
818 find a difference in the primary outcome (percentage 873
819 target ultrafiltration achieved) or other clinical Recommendation 9: In pediatric patients undergoing 874
820 outcomes.54 Two small crossover trials identified in this cardiovascular surgery, intravenous albumin is not 875
821 review evaluated 20% albumin as compared with gelatin suggested for priming the cardiovascular bypass 876
822 (n ¼ 10) and a three-arm study compared 20% albumin circuit or volume replacement (Conditional 877
823 with both saline and hydroxyethyl starch (n ¼ 10).55,56 Recommendation, Very Low Certainty of Evidence of 878
824 879
These RCTs suggested that BP was maintained better Effect).
825 880

881 Evidence Summary: A systematic review and meta- dysfunction (Conditional Recommendation, Very Low 936
882 analysis of RCTs in pediatric and adult patients Certainty of Evidence of Effect). 937
883 938
undergoing cardiovascular surgery was performed
884 Recommendation 11: In patients with cirrhosis and 939
(e-Appendix 8). We identified 43 randomized studies
885 spontaneous bacterial peritonitis, intravenous 940
(n ¼ 3,862), comparing albumin with gelatin, starches,
886 albumin is suggested to reduce mortality (Conditional 941
or crystalloid solutions for priming the cardiopulmonary
887 Recommendation, Low Certainty of Evidence of Effect). 942
888
bypass circuit, volume expansion, or both. The vast 943
889 majority of the trials were conducted in patients Recommendation 12: In patients with cirrhosis and 944
890 undergoing on-pump cardiac surgery, with the extraperitoneal infections, intravenous albumin is not 945
891 exception of two RCTs conducted in patients suggested to reduce mortality or kidney failure 946
892 undergoing off-pump cardiac surgery.69,70 (Conditional Recommendation, Low Certainty of 947
893 Evidence of Effect). 948
894
Albumin infusion did not result in a lower mortality rate 949
895 when compared with other fluids (risk difference, 0.00; Recommendation 13: In hospitalized patients with 950
896 95% CI, –0.01 to 0.01; n ¼ 2,711). No differences were decompensated cirrhosis with hypoalbuminemia (< 30 951
897 found for the rates of kidney failure (risk difference, g/L), repeated intravenous albumin to increase 952
898 0.01; 95% CI, –0.01 to 0.03; n ¼ 1,703), blood loss (mean albumin levels > 30 g/L is not suggested to reduce 953
899Q25 difference [MD], –0.04 L; 95% CI, –0.04 to 0.01 L), ICU infection, kidney dysfunction or death (Conditional 954
Q27
900 length of stay (MD, –0.12 days; 95% CI, –0.31 to Recommendation, Low Certainty of Evidence of Effect). 955
901 0.06 days; n ¼ 1,371), hospital length of stay (MD, 956
902 0.02 days; 95% CI, –0.95 to 1.00 days; n ¼ 870), blood Recommendation 14: In outpatients with cirrhosis 957
903 and uncomplicated ascites despite diuretic therapy, 958
component use (MD, 0.03 L; 95% CI, –0.03 to 0.08 L;
904 intravenous albumin is not routinely suggested to 959
n ¼ 1,547), or cardiac index (MD, 0.07 L/min/m2;
905 reduce complications associated with cirrhosis 960
95% CI, –0.10 to 0.25 L/min/m2; n ¼ 499). Fluid balance
906 (Conditional Recommendation, Low Certainty of 961
907
was lower with albumin compared with alternative 962
solutions (MD, –0.55 L; 95% CI, –1.06 to –0.40 L; n ¼ Evidence of Effect). Q28
908 963
909 450). The largest trial enrolled 1,386 patients and 964
Evidence Summary: We identified a 2019 Cochrane
910 compared 4% albumin (20% albumin diluted in Ringer’s 965
systematic review including 27 RCTs (n ¼ 1,592)
911 lactate) with Ringer’s lactate for both the pump prime 966
examining the use of any plasma volume expanders in
912 and for fluid resuscitation71; albumin-treated patients 967
patients with cirrhosis undergoing paracentesis.74 In
913 showed higher rates of bleeding, resternotomy, and 968
914
general, enrolled patients were undergoing large-volume 969
infection.
915 paracentesis (> 5 L), and the most commonly used 970
916 Rationale for Recommendations: Despite the common albumin doses were either 6 to 8 g of albumin per 1 L of 971
917 use of albumin during cardiovascular surgery,72 little fluid removed or a standard dose of 20 to 40 g. 972
918 evidence supports the use of albumin to improve patient Compared with no plasma expander, no statistically 973
919 outcomes. The largest study to date performed in 1,386 significant effect of using hyperoncotic (20%-25%) 974
920 patients at a single center, Albumin in Cardiac albumin on mortality (RR, 0.52; 95% CI, 0.06-4.83), 975
921 Surgery,71 found increased morbidity when albumin was kidney impairment (RR, 0.32; 95% CI, 0.02-5.88), or 976
922 compared with Ringer’s lactate. Albumin in Cardiac 977
recurrence of ascites (RR, 1.3; 95% CI, 0.49-3.42) was
923 978
Surgery was performed predominantly in low-risk found. Compared with hyperoncotic albumin, use of
924 979
cardiac surgery, and therefore, its role in improving other fluids showed uncertain effects on mortality (RR,
925 980
outcomes in high-risk cardiac surgery has yet to be 1.03; 95% CI, 0.82-1.30), kidney impairment (RR, 1.17;
926 981
927
studied (a 590-patient RCT is underway, Albumin in 95% CI, 0.71-1.91), and recurrence of ascites (RR, 1.14; 982
928 Cardiac Surgery Australia; Identifier, 95% CI, 0.96-1.36). Paracentesis-induced circulatory 983
929 ACTRN12619001355167).73 dysfunction was more frequent with nonalbumin plasma 984
930 expanders (RR, 1.98; 95% CI, 1.31-2.99) compared with 985
931
Clinical Setting 6: Patients With Cirrhosis albumin. A 2020 systematic review focused on the 986
932 Recommendations: Recommendation 10: In patients impact of different therapies (albumin, other fluids, 987
933 with cirrhosis and ascites undergoing large volume vasoactive drugs) on the rate of postparacentesis 988
934Q26 paracentesis (> 5 liters), intravenous albumin is circulatory dysfunction and identified nine RCTs (n ¼ 989
935 990
suggested to prevent paracentesis-induced circulatory 620).75 Albumin at a dose of 8 g/L was found to be
chestjournal.org 9

991 superior to other volume expanders for the prevention treated patients (saline, 39.0% vs albumin, 43.5%; P ¼ 1046
992 of postparacentesis circulatory dysfunction (rise in .42, Fisher exact test); longer-term outcomes were not 1047
993 1048
plasma renin activity by $ 50% of baseline). Similar to reported. In the second, smaller trial, albumin was
994 1049
the Cochrane review, uncertainty regarding the role of superior to crystalloid for reversal of hypotension
995 1050
albumin as compared with alternative treatments was without initiation of vasopressors at 3 h (22% vs 62%;
996 1051
noted for the prevention of complications after P < .001), but this improvement in hemodynamics did
997 1052
998
paracentesis. RCTs comparing high-dose albumin (6-8 not reduce the rate of dialysis, length of stay, or 1053
999 g/L of ascitic fluid removed) with low-dose albumin (2-4 mortality at 28 days.83 In the latter trial, patients 1054
1000 g/L of ascitic fluid removed) found no difference in the randomized to albumin vs crystalloid showed higher 1055
1001 rate of paracentesis associated circulatory dysfunction, rates of circulatory overload. 1056
1002 although uncertainty exists regarding the risk to benefit 1057
We identified one RCT, Albumin to Prevent Infection in
1003 profile of the two doses, given the small sample size (two 1058
Chronic Liver Failure (n ¼ 777), that evaluated the role
1004 studies [n ¼ 120]; RR, 1.00; 95% CI, 0.22-4.49).74 1059
1005 of hyperoncotic albumin to target an albumin level of > 1060
1006 Two systematic reviews (in 2013 and 2020) identified 30 g/L (median, 200 g albumin over 14 days) as 1061
1007 five open-label RCTs in patients with spontaneous compared with no albumin in hospitalized patients with 1062
1008 bacterial peritonitis both using variable doses and decompensated cirrhosis and hypoalbuminemia (< 30 1063
1009 duration of hyperoncotic albumin (eg, 0.5-1.0 g/kg every g/L).10 No difference was found in the primary end 1064
1010 3 days for a maximum of 21 days; 1.5 g/kg on day 1 and point (composite of new infections, kidney dysfunction, 1065
1011 1.0 g/kg on day 3).76,77 Albumin reduced the rate of or death between days 3 and 15) between groups (OR, 1066
1012 kidney impairment (OR, 0.21; 95% CI, 0.11-0.42) and 0.98; 95% CI, 0.71-1.33). More severe or life-threatening 1067
1013 1068
mortality (OR, 0.34; 95% CI, 0.19-0.60).77 The largest serious adverse events were reported in the albumin-
1014 1069
randomized trial78 randomized 126 patients to albumin treated patients, primarily a numerical increase in
1015 1070
(plus antibiotics) or antibiotics alone (without an pulmonary edema.
1016 1071
1017
explicit fluid resuscitation for the control arm). Patients 1072
A 2021 systematic review was identified that evaluated
1018 treated with albumin showed lower rates of kidney 1073
albumin in patients with hepatic encephalopathy.84 The
1019 impairment (10% vs 33%; P ¼ .002) and in-hospital 1074
review identified two RCTs (n ¼ 176). Albumin
1020 mortality (10% vs 29%; P ¼ .01). The second largest trial 1075
resulted in a reduction in hepatic encephalopathy (RR,
1021 randomized 118 patients to albumin (plus antibiotics) or 1076
0.60; 95% CI, 0.38-0.95) and mortality (RR, 0.54;
1022 antibiotics alone (without an explicit fluid resuscitation 1077
95% CI, 0.33-0.90). The first open-label trial
1023 for the control arm).79 The primary end point of in- 1078
1024
randomized 120 patient to albumin (1.5 g/kg/d for up 1079
hospital mortality was not different (13% albumin
1025 to 10 days and lactulose) vs lactulose alone.85 Complete 1080
vs 11% antibiotics alone; P ¼ .66).
1026 resolution of hepatic encephalopathy by day 10 was 1081
1027 A 2020 systematic review and meta-analysis of RCTs seen in 75% of the albumin-lactulose group vs 53% of 1082
1028 comparing albumin plus antibiotics with antibiotics the lactulose alone group (P ¼ .03). Mortality was 1083
1029 alone in patients with cirrhosis and extraperitoneal 18% in the albumin-lactulose group vs 32% in the 1084
1030 infections found no effect on mortality or kidney lactulose alone group at day 10 (P ¼ .04). The second 1085
1031 impairment, but observed higher rates of pulmonary masked RCT of albumin (1.5 g/kg on day 1 and 1.0 g/kg 1086
1032 1087
edema with albumin (three studies [n ¼ 406]; OR, 5.17; on day 3) vs normal saline enrolled 56 patients.86 No
1033 1088
95% CI, 1.62-16.47).80 A 2019 systematic review in the difference was found in the rate of resolution of hepatic
1034 1089
same population also found no improvements in encephalopathy at day 4 (albumin, 58% vs saline, 53%;
1035 1090
outcomes when albumin with antibiotics was compared P ¼ .7). The mortality rate was lower in albumin-
1036 1091
1037
with antibiotics alone.81 Subsequent to this 2020 treated patients at 90 days (23% vs 47%) and 1092
1038 systematic review, two randomized trials have been transplant-free survival was improved (P ¼ .02, 1093
1039 published (308 and 100 patients, respectively) Kaplan-Meier estimate). A 2021 systematic review of 1094
1040 comparing albumin with crystalloid in patients with RCTs and cohort studies evaluating the role of albumin 1095
1041 cirrhosis and hypotension resulting from sepsis.82,83 in prevention and treatment suggested that albumin 1096
1042 Both trials included patients with sepsis from all causes, may assist with the resolution or prevention of hepatic 1097
1043 including a small proportion (20%-25%) with encephalopathy and may reduce mortality87; only the 1098
1044 spontaneous bacterial peritonitis. In the larger trial, two RCTs identified in the aforementioned systematic 1099
1045 1100
survival at 7 days was not improved in the albumin- review were identified for the treatment of hepatic

1101 encephalopathy.84 In the subsequent large Albumin to Rationale for Recommendations: Approximately one- 1156
1102 Prevent Infection in Chronic Liver Failure trial,10 the third of albumin is used for patients with cirrhosis,8 and 1157
1103 1158
subgroup (n ¼ 149) of patients admitted with hepatic although this practice is exceedingly common, the
1104 1159
encephalopathy randomized to albumin as compared certainty of evidence supporting this therapy in this
1105 1160
with placebo did not show an improvement in the population is insufficient to allow for strong
1106 1161
composite end point of new infections, kidney recommendations. Although the use of albumin for
1107 1162
1108
dysfunction, or death between days 3 and 15 (adjusted large-volume paracentesis is a commonly accepted 1163
1109 OR, 0.91; 95% CI, 0.44-1.86). Subsequent to the two clinical practice and is endorsed by guidelines,92-94 the 1164
1110 systematic reviews, a single RCT was identified that reported trials have important limitations that affect the 1165
1111 randomized 48 outpatients with hepatic certainty in outcomes. These trials included a small 1166
1112 encephalopathy to weekly hyperoncotic albumin for number of patients and that findings for most patient- 1167
1113 5 weeks as compared with saline and found important outcomes (mortality, kidney dysfunction) 1168
1114 improvements in cognitive function with albumin.88 were imprecise, leaving residual uncertainty regarding 1169
1115 true clinical benefits and harms. Albumin, as compared 1170
1116 A 2021 systematic review of RCTs evaluating 1171
with other fluid expanders, may be superior for the
1117 outpatient hyperoncotic albumin for patients with 1172
prevention of paracentesis-induced circulatory
1118 cirrhosis and ascites identified five trials (n ¼ 716).89 1173
dysfunction (rise in serum renin level on the sixth day
1119 The systematic review found no difference in 1174
after paracentesis), but whether this translates to
1120 mortality at 12 to 36 months (RR, 0.88; 95% CI, 0.67- 1175
1121
improvement in patient-important outcomes is less 1176
1.14) or any other outcome, with the exception of
1122 certain. Plasma renin levels are predictive of greater 1177
reducing the need for paracentesis (RR, 0.56; 95% CI,
1123 morbidity in patients with cirrhosis.95-97 The panel 1178
0.48-0.67). Two large randomized trials were included
1124 suggested continuing this commonly accepted practice 1179
in the review.90,91 The first unmasked trial
1125 for patients undergoing large-volume paracentesis, but 1180
randomized 440 patients with cirrhosis and
1126 believed the data supported only a conditional 1181
1127
uncomplicated, persistent ascites despite diuretic 1182
recommendation based on low-quality evidence. Further
1128 therapy to albumin (40 g twice weekly for 2 weeks and 1183
trials are needed urgently to clarify if albumin improves
1129 then 40 g weekly for up to 18 months) or no 1184
patient important outcomes, to elucidate the optimal
1130 albumin.91 Patients randomized to albumin 1185
dosing strategy, to further the understanding of the
1131 experienced longer time to first paracentesis; required 1186
safety profile of the treatment, and to evaluate
1132 fewer paracenteses; were less likely to demonstrate 1187
alternative fluids and therapies. It is unclear if improving
1133 hepatic encephalopathy, hepatorenal syndrome, 1188
1134
laboratory measures of paracentesis-induced circulatory 1189
spontaneous bacterial peritonitis, nonperitonitis
1135 dysfunction will translate into reductions in renal 1190
infections, hyponatremia, or episodes of kidney
1136 failure, hospital admission, or other patient-important 1191
dysfunction; experienced fewer days in hospital; and
1137 outcomes. The panel also highlighted the need to 1192
showed lower all-cause mortality (77% vs 66% survival
1138 personalize the use of albumin, the dose after 1193
at 18 months; hazard ratio, 0.62; 95% CI, 0.40-0.95).
1139 paracentesis, or both, considering the patient’s baseline 1194
1140
The most important limitation of this study is that the 1195
creatinine, volume of ascites removed, and history of
1141 albumin-treated patients underwent weekly health 1196
hypotensive symptoms after prior procedures.
1142 care interactions and the control group did not, 1197
1143 raising the concern that the observed differences may Similarly, the role of albumin for improving outcomes in 1198
1144 have been the result of increased health care exposure. patients with spontaneous bacterial peritonitis is 1199
1145 The second trial randomized 196 outpatients with unclear. The trial data specific to this patient population 1200
1146 cirrhosis and ascites awaiting liver transplantation to are limited.77,78 The two largest RCTs failed to provide 1201
1147 oral midodrine and albumin as compared with an explicit fluid resuscitation protocol for the patients 1202
1148 1203
placebo tablets and a 0.9% saline infusion and found randomized to no albumin, raising the concern for
1149 1204
no difference in patient outcomes.90 The dose of underresuscitation in the control arms of both studies.
1150 1205
albumin given as part of the intervention was lower When similar albumin dosing strategies were used in
1151 1206
(40 g every 15 days). The study improved on the trials examining patients with cirrhosis and
1152 1207
1153
methodology of the first trial by achieving masking to extraperitoneal infections, no benefit was seen and 1208
1154 treatment assignment and ensuring the same health concern for harm was expressed.80 The panel suggested 1209
1155 care exposure in both study groups. the use of albumin for spontaneous bacterial peritonitis 1210
chestjournal.org 11

1211 (conditional recommendation), but raised concerns examined biweekly albumin infusions.90 The latter trial 1266
1212 regarding the dosing protocol used in two of the four enrolled a smaller number of patients and used a lower 1267
1213 1268
trials and the risk of fluid overload (1.5 g/kg on day 1 dose, and therefore may have failed to detect a difference
1214 1269
and 1.0 g/kg on day 3) and the lack of data suggesting in outcomes. The panel reported residual uncertainty
1215 1270
this specific regimen is beneficial compared with regarding the benefit of this treatment and given this,
1216 1271
alternative dosing (eg, lower dose daily for 3 days). The suggested against its routine use until additional RCTs
1217 1272
1218
panel also considered the lack of clarity on whether have been conducted. The use of weekly albumin in this 1273
1219 albumin is necessary for all patients with spontaneous patient population would have considerable impacts on 1274
1220 bacterial peritonitis or whether it could be used patients, would require chronic IV access, would have 1275
1221 selectively (ie, patients at high risk of kidney failure or considerable impacts on outpatient infusion clinics, and 1276
1222 death: serum bilirubin > 4 mg/dL or serum creatinine would require a dependable supply of albumin. 1277
1223 >1 mg/dL). Additional studies are necessary to address Although the unmasked trial reported cost- 1278
1224 dosing, to address the benefit for patients with and effectiveness,91 additional masked trials with cost- 1279
1225 without kidney impairment, and to clarify the risks of effectiveness analyses are necessary to improve precision 1280
1226 1281
adverse events. The panel also noted that not all and generalizability and to inform future guidelines.
1227 1282
physicians currently adhere to the trial dosing
1228 A 2020100 and a 2019101 systematic review on the 1283
strategy,98,99 although it continues to be recommended
1229 treatment of hepatorenal syndrome did not identify any 1284
in current guidelines.92,93 A careful assessment of the
1230 randomized trials examining albumin for these patients 1285
1231
patient’s volume status, cardiovascular status, and 1286
as compared with placebo or no treatment. Rather, all
1232 degree of kidney impairment before transfusion is 1287
trials examining this patient population uniformly have
1233 advised and the dose, frequency, or both being modified 1288
administered albumin in both treatment and control
1234 accordingly. In contrast, the RCTs find no support for 1289
arms and have compared vasoconstrictor agents (eg,
1235 the use of albumin in patients with cirrhosis and 1290
terlipressin, midodrine) with placebo infusions. Hence,
1236 extraperitoneal infections.80 1291
1237
no recommendations regarding the use of albumin for 1292
1238 In the setting of patients admitted with decompensated patients with cirrhosis and hepatorenal syndrome could 1293
Q29
1239 cirrhosis and hypoalbuminemia, this guideline is be made. 1294
1240 informed by an RCT involving 777 patients10 that found 1295
1241 no improvement in patient important outcomes and a 1296
Discussion
1242 concern for increased adverse events. This led the panel 1297
The evidence-base guiding of albumin use largely was
1243 to suggest conditionally against the use of albumin in 1298
1244
instigated by the Cochrane Injuries Group Albumin 1299
this setting.
1245 systematic review in 1998,102 which raised the concern 1300
1246 Although a 2021 systematic review of two small RCTs for harm from albumin. Subsequent to this publication, 1301
1247 suggested a benefit for facilitating resolution of hepatic RCTs comparing albumin with other fluid treatments in 1302
1248 encephalopathy and reducing mortality,84 the subgroup multiple patient populations were completed. These 1303
1249 trials failed to confirm the concerns for higher mortality 1304
of patients in the Albumin to Prevent Infection in
1250 rates in albumin-treated patients. The ICTMG 1305
Chronic Liver Failure study admitted with hepatic
1251 undertook these evidence-based albumin guidelines 1306
encephalopathy did not show improvements in
1252 1307
mortality.10 The panel had uncertainty regarding the because no comprehensive evidence-based guidelines
1253 1308
benefit of albumin in this patient population and few had been published yet. The goal of the guidelines is to
1254 1309
data on the risks of the treatment, and therefore provide clinicians with recommendations and evidence
1255 1310
abstained from making a statement on the role of summaries for common indications for albumin,
1256 1311
1257 albumin in this setting until further adequately powered information on ongoing clinical trials, and areas in need 1312
1258 RCTs are conducted. of additional research. The ICTMG guidelines group 1313
1259 suggested that albumin should not be used routinely for 1314
1260 In nonhospitalized patients with cirrhosis and persistent neonatal, pediatric, and adult patients in critical care; for 1315
1261 ascites despite optimized medical management, the role patients experiencing intradialytic hypotension; for 1316
1262 of weekly or biweekly albumin infusions remains patients undergoing cardiovascular surgery; for admitted 1317
1263 unclear. One unmasked study of weekly albumin patients with cirrhosis for treatment (or correction) of 1318
1264 infusions found improvements in outcomes,91 but this hypoalbuminemia or extraperitoneal infections; or for 1319
1265 was not replicated in a placebo-controlled trial that 1320
outpatients with ascites. The ICTMG guidelines

1321 TABLE 2 ] Ongoing, Large Randomized Clinical Trials Comparing IV Albumin With Alternative Treatments 1376
1322 1377
Trial Trial Details
1323 1378
Effect of Albumin Administration in Hypoalbuminemic Three hundred sixty patients with community-acquired
1324 1379
Hospitalized Patients With Community-Acquired pneumonia. Will compare the outcomes of patients
1325 1380
Pneumonia (ClinicalTrials.gov Identifier: NCT04071041) treated with albumin (100 mL of 20% every 12 h for 4 d)
1326 compared with standard of care. The primary outcome is 1381
1327 the proportion of patients with clinical stability at day 5 of 1382
1328 hospitalization. 1383
1329 Albumin Replacement Therapy in Septic Shock One thousand six hundred sixty-two patients with septic 1384
1330 (ClinicalTrials.gov Identifier: NCT03869385) shock randomized to 20% albumin or usual care fluids. 1385
The primary outcome is 90-d all-cause mortality.
1331 1386
1332 Albumin in Cardiac Surgery Australian (Postoperative Five hundred ninety patients undergoing high-risk cardiac 1387
20% Albumin vs Standard Care and Acute Kidney Injury surgery (combined procedure or eGFR < 60 mL/min/1.73
1333 1388
After High-Risk Cardiac Surgery; Australian New Zealand m2) and will compare 20% albumin infusion with standard
1334 Clinical Trials Registry Identifier: care. The study fluid will be administered on arrival in the 1389
1335 ACTRN1261900135516703) ICU and continued for 15 h. The primary outcome is the 1390
1336 proportion of patients who demonstrate acute kidney 1391
1337 injury in both groups. 1392
1338 Effects of Long-term Administration of Human Albumin in Four hundred ten outpatients with decompensated cirrhosis 1393
1339 Subjects With Decompensated Cirrhosis and Ascites and ascites will evaluate open-label hyperoncotic albumin 1394
(ClinicalTrials.gov Identifier: NCT03451292) as compared with standard medical management (dose of
1340 1395
1.5 g/kg every 10 d for up to 12 mo). The primary
1341 outcome is the time to liver transplantation or death at 12 1396
1342 mo. 1397
1343 Albumin to Enhance Recovery After Acute Kidney Injury Eight hundred fifty-six critically ill patients with acute kidney 1398
1344 (ClinicalTrials.gov Identifier: NCT04705896) injury requiring kidney replacement therapy will be 1399
1345 randomized to hyperoncotic albumin (25%; 100 mL two 1400
1346 doses) compared with normal saline placebo doses, given 1401
with all kidney replacement therapy treatments in the ICU
1347 1402
for up to 14 d. The primary outcome is organ support-free
1348 days at 28 d after initiation of kidney replacement 1403
1349 therapy. 1404
1350 1405
eGFR ¼ estimated glomerular filtration rate.
1351 1406
1352 1407
1353 1408
conditionally recommended the use of albumin for Association for the Study of the Liver jointly released
1354 1409
patients with cirrhosis undergoing large-volume guidelines for the management of liver failure in critical
1355 1410
paracentesis or with spontaneous bacterial peritonitis. care.103 They recommend the use of albumin for
1356 1411
1357
One of 14 recommendations was a strong hepatorenal syndrome (with terlipressin), large-volume 1412
1358 recommendation based on more definitive clinical trial paracentesis (> 5 L), and spontaneous bacterial peritonitis. 1413
1359 evidence, but most of the recommendations were The American Association for the Study of Liver Disease 1414
1360 conditional based on low- or very low-quality evidence Guidelines from 202192 recommend the use of albumin for 1415
1361 because of the paucity or conflicting RCT evidence, large-volume paracentesis, severe muscle cramps, severe 1416
1362 highlighting the need for ongoing research. The hyponatremia (sodium < 120 mEq/L), spontaneous 1417
1363 implementation of the guidelines will help to reduce the bacterial peritonitis, and hepatorenal syndrome. The 1418
1364 Italian Association for the Study of Liver Disease and the 1419
unnecessary transfusion of albumin and the variability
1365 Italian Society for Transfusion Medicine and 1420
between hospitals.
1366 1421
Immunohematology guidelines update from 2020 include
1367 1422
Guidelines for select patient populations have been the use of albumin for ascites requiring moderate doses of
1368 1423
published in some jurisdictions, particularly in patients diuretics as an outpatient treatment.104 This was an update
1369 1424
1370
with cirrhosis. The British Society for Gastroenterology from their 2016 guidelines that also recommended the use 1425
1371 published guidelines on the management of patients with of albumin in patients requiring large-volume paracentesis, 1426
1372 cirrhosis and ascites.93 They recommend albumin for with spontaneous bacterial peritonitis, or with hepatorenal 1427
1373 patients undergoing large-volume paracentesis or with syndrome.105 Similarly, the European Association for the 1428
1374 spontaneous bacterial peritonitis. The French Society of Study of the Liver 2018 guidelines detailing the 1429
1375 Anesthesiology and Critical Care Medicine and the French management of patients with decompensated cirrhosis 1430
chestjournal.org 13

1431 recommended albumin for patients undergoing large- recommendations, inclusion of a patient representative in 1486
1432 volume paracentesis, with spontaneous bacterial the guideline process, and broad community consultation 1487
1433 1488
peritonitis, with acute kidney injury without known cause, process. The guidelines will be supported by tools
1434 1489
or with hepatorenal syndrome.94 The ICTMG guidelines developed by the ICTMG Dissemination and
1435 1490
are concordant with these guidelines for recommending Implementation Committee to assist hospitals with
1436 1491
albumin for large-volume paracentesis and spontaneous aligning practice with the evidence.
1437 1492
1438
bacterial peritonitis, but report insufficient evidence to 1493
Future research is needed in multiple clinical settings
1439 support its use in other settings. The use of albumin for 1494
including: (1) the role and timing of albumin in patients
1440 hepatorenal syndrome, in conjunction with terlipressin, 1495
with sepsis or other conditions with insufficient response to
1441 was recommended commonly in prior guidelines, likely 1496
crystalloids, (2) the role of albumin in patients undergoing
1442 based on both expert opinion and the fact that randomized 1497
surgery, (3) the role of albumin for intradialytic
1443 trials used albumin in both treatment arms (albumin 1498
hypotension, and (4) the role of albumin in all indications
1444 vs albumin plus terlipressin). We elected to refrain from 1499
1445
for patients with cirrhosis. Research also is needed to 1500
making a recommendation without clinical trial evidence
1446 understand therapeutic targets of albumin resuscitation 1501
to support its use and highlight that this indication needs
1447 (hemodynamic, urinary output, laboratory), the optimal 1502
further study.
1448 formulation, and the dosing strategy. The risk of IV 1503
1449 Guidelines from the Association of the Scientific albumin infusions needs further investigation to allow 1504
1450 Medical Societies in Germany published perioperative clinicians to weigh the risk to benefit profile appropriately. 1505
1451 fluid guidelines for children in 2017.106 They Studies should include patient-important outcomes, rather 1506
1452 than focusing on short-term physiologic outcomes. 1507
recommended that colloids, including albumin, be used
1453 1508
during surgery where crystalloids alone are not
1454 Funding/Support Q30 1509
sufficiently effective and blood products are not
1455 1510
indicated. In 2021, the Surviving Sepsis Campaign Funded by the Ontario Regional Blood Coordinating
1456 1511
1457
guidelines recommended the use of albumin in the fluid Network and the International Collaboration for
1512
1458 resuscitation of severe sepsis and septic shock when Transfusion Medicine Guidelines. The ICTMG receives 1513
1459 patients required large volumes of crystalloids.43 funding from Canadian Blood Services (funded by the Q56 1514
1460 federal government [Health Canada] and the provincial 1515
Five RCTs that will enroll an additional 4,864 patients and territorial ministries of health).
1461 1516
are ongoing and are expected to provide additional
1462 1517
1463
clarity on the role of albumin (Table 2). These trials will 1518
Financial/Nonfinancial Disclosures Q31
1464 add clarity to the ICTMG recommendations for 1519

The authors have reported to CHEST the following: J. C.
1465 intensive care patients with infection, high-risk adult 1520
receives research support from Canadian Blood Services
1466 cardiac surgery, patients with acute kidney injury 1521
and Octapharma and serves on the board of directors of
1467 receiving kidney replacement therapy, and outpatients 1522
1468
the Canadian Hematology Society. N. J. S. is a director of 1523
with decompensated cirrhosis.
1469 the National Board of Echocardiography and receives 1524
1470 These guidelines is limited by the uncertainty in the royalties from Wolters Kluwer. A. B. is an employee of 1525
1471 evidence identified in the literature search for many Canadian Blood Services. H. K. is an employee of 1526
1472 different patient populations and the limitation of the Canadian Blood Services. E. G. C. receives research 1527
1473 search to the English language. The lack of comparative funding (related to albumin) from Department of 1528
1474 dosing strategies leaves uncertainty on the choice between Medicine, The Ottawa Hospital and University of 1529
1475 4% to 5% and 20% to 25% albumin formulations, the dose Ottawa, The Ottawa Hospital Academic Medical 1530
1476 for each indication, the risk of fluid overload, and the Organization, Kidney Foundation of Canada, and 1531
1477 1532
dosing schedules. The guidelines are limited to common Physician Services Incorporated Foundation; is an
1478 1533
uses of albumin and cannot address every possible patient editorial board member of the Canadian Journal of
1479 1534
scenario where albumin has been used in RCTs. The Kidney Health and Disease; and is a member of the
1480 1535
published studies often did not collect or did report Contrast-Associated Acute Kidney Injury guideline panel
1481 1536
1482
adverse reactions from IV albumin, or both, limiting the for the Canadian Association of Radiologists. B. R. is a 1537
1483 conclusions regarding the potential risks of albumin. guideline methodologist for American Thoracic Society, 1538
1484 These guidelines improve on those previously published the Society of Critical Care Medicine, and Canadian 1539
1485 because of the rigorous methodology, broad scope of the Blood Services; is the KT director for Canadian Critical Q32 1540

1541 Care Society; is the grants and manuscripts chair for and Cerus (not albumin related). Z. M. S. is a consultant 1596
1542 Canadian Critical Care Trials Group, and in a guideline and advisory board member of Grifols, Fresenius Kabi, 1597
1543
group member for multiple guidelines. S. R. B. is the chair and Novartis; receives research funding from Erydel and 1598
1544
of the Clinical Pharmacy and Pharmacology section for Fresenius Kabi; serves on the board of directors for the 1599
1545 1600
the Society of Critical Care Medicine (not albumin use BEST Collaborative and ICCBBA, Inc.; is the AABB Q36
1546 1601
related), is a paid consultant for Wolters Kluwer Committee Chair; is vice chair, treasurer, and committee
1547 1602
1548
(Lexicomp), is a Society of Critical Care Medicine Social chair for ICCBBA, Inc.; is treasurer for BEST 1603
1549 Media Committee member, is a Surviving Sepsis Collaborative; and has a family member (child) who is a 1604
1550 Campaign Research Committee member, and has summer intern with Grifols, Inc. T. T. is a paid consultant 1605
1551 received a research grant from the National Institute of for Inter-View Partners France, AþA, Bayer HealthCare 1606
1552Q33 General Medicine Sciences. M. B. is a consultant, has SAS, BVA, Axess Research, and All Global; has received 1607
1553 received honoraria, or both from Grifols, CSL Behring, honoraria from AbbeVie, Gilead Sciences, Advanz 1608
1554 Martin Pharmaceuticals, Octapharma, Takeda, and Pharma France, and Ipsen Pharma; in the principal 1609
1555 PPTA; is the treasurer for European Association for the investigator of randomized controlled trial ALBCIR-INF 1610 Q37
1556
Study of the Liver (EASL); is a guideline panel member (ClinicalTrials.gov Identifier, NCT01359813) published 1611
1557
for the European Association for the Study of the Liver in 2015; and is a member of the Liver Cirrhosis-related 1612
1558 1613
(EASL), the Italian Association for the Study of the Liver Complications (LCC)-International Special Interest
1559 1614
(AISF), and the Italian Society of Transfusion Medicine Group. B. W. is a resident physician at Loma Linda
1560 1615
1561
and Immunohaematology (SIMTI) (albumin related); University Medical Center. S. S. is chair of the ICTMG 1616
1562 and is involved in peer-reviewed publications (multiple and is an employee of NHSBT, a blood service operator in Q381617
1563 topics including relevant to albumin use). L. C. is a England. However, NHSBT is not a manufacturer of the 1618
1564 guideline group member for the British Society of intervention. N. S. is an employee of Canadian Blood 1619
1565 Gastroenterology (management of ascites in liver Services; receives research funding from the Canadian 1620
1566 cirrhosis), is involved in peer-reviewed publications Institutes for Health Research (TRICS IV RBC 1621
Q39
1567 (multiple topics including relevant to albumin use), transfusion in young cardiac patients; not related to 1622
1568 received lecturer honoraria for the Canadian Liver albumin); is an advisory board member for Fresenius 1623
1569 1624
Conference 2022, is a hepatology consultant for the Royal Kabius and Janssen; has received honoraria from the
1570
Free Hospital London, and is a Liver Committee member International Financial Corporation of the World Bank, 1625
1571 1626
of the British Society of Gastroenterology. M. F. receives Canadian Blood Services, and Ferring; and serves on the
1572 1627
consultant fees from Cerus Corporation and Biocogniv, PKD guideline panel and ICTMG guideline panels
1573 1628
1574
Inc.; has received honoraria from Grifols (none were (FNAIT, HDN, platelet transfusion, RBC specifications). Q40 1629
1575 albumin related); is a board member for Project Santa Fe None declared (D. F., S. A., M. N., C. P., S. R.). See 1630
1576 Foundation and the American Board of Pathology; is the Appendix I for the ICTMG Conflict of Interest Policy. Q41 1631
1577 Histocompatibility and Identity Testing Committee 1632
1578 Chair for College of American Pathologists; is co-team Acknowledgments 1633
1579Q34 leader for the BEST Collaborative; and is the Editorial Author contributions: All authors had access to all the included 1634
1580 Committee co-chair for the ICTMG. R. J. has received evidence base for the guideline, took responsibility for the guideline 1635
statements, had authority over manuscript preparation, and the
1581 fellowship funding from Canadian Blood Services, is an 1636
decision to submit the manuscript for publication. All authors
1582 contributed to study concept and design. All authors contributed to 1637
employee of William Osler Health System and the
1583 analysis and interpretation of the data. J. C., N. J. S., E. G. C., B. R., and 1638
University of Cincinnati Medical Center, and is a panel N. S. contributed to drafting the article. All authors contributed to
1584 1639
member for ICTMG Platelet Utilization guideline critical revision of the article for important intellectual content. All
1585 authors contributed to final approval of the article. H. K. and D. L. 1640
Q42
development group. K. P. serves on the board of directors
1586 contributed administrative, technical, or logistical support. J. C., N. J. 1641
1587
Q35 in North America for ISBT, is a 2023 AABB RBC S., and N. S. contributed to collection and assembly of data.
1642
1588 guideline panel member, and is a member of the National * International Collaboration for Transfusion Medicine Guidelines 1643
Advisory Committee of Blood and Blood Products. P. S. Intravenous Albumin Group Collaborators: Jerome Flores, PharmD, Q43
1589 1644
University Health Network, Toronto; Stéfanie Frappier, University of
1590 S. is director of the Canadian Neonatal Network, director Ottawa, Ottawa; Yvette Hou, Trillium Health Partners; Lilly Jean- 1645
1591 of the Canadian Preterm Birth Network, director of the Pierre, Carleton University; Danny Jomaa, MSc, MBI, School of 1646
Medicine, Queen’s University, Kingston; Monisha Kabir, MSc, Bruyère
1592 International Network to Evaluate Outcomes of 1647
Research Institute, Ottawa; Leo Kadota, MD, Faculty of Medicine,
1593 Neonates, and an external advisory board member for the University of British Columbia; Michelle Lam, CHEO ED SUPPORT 1648
1594 Program, Carleton University; David A. Ripsman, Department of 1649
Canadian Perinatal Surveillance system (none related to Neurology, Faculty of Medicine, University of British Columbia; Ryan
1595 1650
albumin manufacturers). H. S. is a consultant for Terumo Sandarage, Faculty of Medicine, University of British Columbia;
chestjournal.org 15

1651 Emiliyan Staykov, BSc, Michael G. DeGroote School of Medicine, 7. Tarin Remohi MJ, Sanchez Arcos A, Santos Ramos B, Bautista 1706
1652 Hamilton; Angelica Venes, Department of Biochemistry, Microbiology Paloma J, Guerrero Aznar MD. Costs related to inappropriate use 1707
and Immunology, University of Ottawa, Ottawa; and Melissa Wan, of albumin in Spain. Ann Pharmacother. 2000;34(10):1198-1205.
1653 MD, Department of Family Medicine, Queen’s University, Kingston. 1708
8. Buckley MS, Knutson KD, Agarwal SK, et al. Clinical pharmacist-
1654 None of the authors reports any conflicts of interest. led impact on inappropriate albumin use and costs in the critically 1709
1655 * International Collaboration for Transfusion Medicine Guidelines ill. Ann Pharmacother. 2020;54(2):105-112. 1710
1656 Collaborators: Arwa Al Riyami, MD, Sultan Qaboos University 9. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, 1711
Spahn DR. Activity-based costs of blood transfusions in surgical
1657 Hospital, Oman; Shubha Allard, MD, National Health Service Blood & 1712
Transplant, United Kingdom; Melissa Brouwers, PhD, University of patients at four hospitals. Transfusion. 2010;50(4):753-765.
1658 Ottawa, Canada; Jeannie Callum, MD, Sunnybrook Health Sciences 1713
10. China L, Freemantle N, Forrest E, et al. A randomized trial of
1659 Centre and University of Toronto, Canada; James Daly, MBBS, albumin infusions in hospitalized patients with cirrhosis. N Engl J 1714
1660 Australian Red Cross Lifeblood, Australia; Gregory A. Denomme, PhD, Med. 2021;384(9):808-817. 1715
Versiti Blood Centre of Wisconsin, United States; Lise Estcourt, MB
1661 BChir, DLSHTM, DPhil, National Health Services Blood & Transplant, 11. Thevenot T, Bureau C, Oberti F, et al. Effect of albumin in cirrhotic 1716
patients with infection other than spontaneous bacterial peritonitis.
1662 United Kingdom; Dean Fergusson, PhD, MHA, Ottawa Hospital A randomized trial. J Hepatol. 2015;62(4):822-830. 1717
1663 Research Institute, Canada; Mark Fung, MD, PhD, University of 12. Howard G, Downward G, Bowie D. Human serum albumin 1718
Vermont Medical Center, United States; Laura Green, MBBS, MD
1664 (Res), National Health Service Blood & Transplant, United Kingdom; induced hypotension in the postoperative phase of cardiac surgery. 1719
1665 Andreas Greinacher, MD, University of Greifswald; Heather Hume, Anaesth Intensive Care. 2001;29(6):591-594. 1720
1666 MD, University of Montreal, Canada; Rachel Jug, MD, Canadian Blood 13. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and
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1667 Hospital Adult Transfusion Service, United States; Hyungsuk Kim, Med. 2004;350(22):2247-2256. 1722
1668 MD, Seoul National University Hospital, Korea; Vernon Louw, PhD, 14. Shimode N, Yasuoka H, Kinoshita M, et al. Severe anaphylaxis after 1723
1669 Groote Schuur Hospital, University of Cape Town, South Africa; albumin infusion in a patient with ahaptoglobinemia. 1724
Tadashi Matsushita, MD, PhD, Nagoya University Hospital, Japan; Anesthesiology. 2006;105(2):425-426.
1670 Michael Murphy, MD, University of Oxford and National Health 1725
15. Warkentin TE, Ning S, Lim W. Colloid transfusion, natural
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1673 Cynthia So-Osman, MD, PhD, Sanquin and Erasmus Medical Center, 16. Connelly-Smith L, Alquist CR, Aqui NA, et al. Guidelines on the 1728
1674 The Netherlands; Simon Stanworth, PhD, NHS Blood and Transplant use of therapeutic apheresis in clinical practice—evidence-based 1729
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1677 United States; and Erica Wood, MBBS, Monash University, Australia. Collaboration’s tool for assessing risk of bias in randomised trials. 1732
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[ Critical Care Guideline and Consensus Statement ] 56

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

2 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

4 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

456 (Conditional Recommendation, Low Certainty of Evidence of Effect). 511

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

6 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

8 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

10 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

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12 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

1464 add clarity to the ICTMG recommendations for 1519

14 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

16 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

PGL 5.6.0 DTD CHEST6129_proof 27 March 2024 6:58 pm EO: CHEST-D-23-03350

18 Guideline and Consensus Statement [ -#- CHEST - 2024 ]

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