SPECIAL ARTICLES

Executive Summary: Guidelines for the

Management of Adult Acute and Acute-on-
Chronic Liver Failure in the ICU: Neurology,
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Peri-Transplant Medicine, Infectious Disease,

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and Gastroenterology Considerations

Rahul Nanchal, MD, MS, FCCM (Co-Chair)1
KEY WORDS: acute liver failure; acute on chronic liver failure; clinical practice Ram Subramanian, MD, FCCM (Co-Chair)2
guidelines; Grading Recommendations, Assessment, Development, and Evaluation Waleed Alhazzani, MBBS, MSc, FRCPC
(Methods Chair, Vice Co-Chair)3

A
Joanna C. Dionne, MD, MS, BN3
cute liver failure (ALF) and acute on chronic liver failure (ACLF) William J. Peppard, PharmD, BCPS, FCCM4
are conditions frequently encountered in the ICU and are associated Kai Singbartl, MD, MPH, EDIC, FCCM5
with high mortality. We previously published recommendations for Jonathon Truwit, MD, MBA6
the management of the critically ill patient with liver disease focused on car- Ali H. Al-Khafaji, MD, MPH, FCCM7

diovascular, hematological, pulmonary, renal, and endocrine/nutrition issues Alley J. Killian, PharmD, BCPS2

(1). In continuation of this document, we developed evidence-based recom- Mustafa Alquraini, MBBS, SBEM,
ABEM, MMed, CCM8
mendations addressing infectious disease, peri-transplant, gastrointestinal Khalil Alshammari, MBBS8
and neurologic issues that present unique challenges in this population of Fayez Alshamsi, MBBS8
patients. Emilie Belley-Cote, MD3
Clinical care is very often adapted to individual clinical circumstances Rodrigo Cartin-Ceba, MD, MS9
and patient/family preferences. These guidelines are meant to supplement Steven M. Hollenberg, MD, FACC, FCCM,
FAHA, FCCP10
and not replace an individual clinician’s cognitive decision-making. The
Dragos M. Galusca, MD, FASA, FCCP11
primary goal of these guidelines is to aid best practice and not represent
David T. Huang, MD, MPH, FCCM7
standard of care.
Robert C. Hyzy, MD, MCCM12
Mats Junek, BSc(H), MD3
METHODS Prem Kandiah, MD2
Gagan Kumar, MD, MA, MS13
Co-chair and vice-chairs were appointed by the Society of Critical Care
Rebecca L. Morgan, PhD, MPH14
Medicine (SCCM). Twenty-five other panel members were chosen in accord-
Peter E. Morris, MD15
ance with their clinical and/or methodological expertise. Corresponding with Jody C. Olson, MD16
individual expertise, the panel was then divided into nine subgroups; the rec- Rita Sieracki, MLS6
ommendations of five of those subgroups (cardiovascular, hematology, pulmo- Randolph Steadman, MD17
nary, renal, and endocrine) are presented in this document. Each panel member Beth Taylor, DCN, RDN-AP, CNSC, FCCM18
followed all conflict-of-interest procedures as documented in the American Constantine J. Karvellas, MD, MS,
College of Critical Care Medicine/SCCM Standard Operating Procedures FRCPC, FCCM (Vice Co-Chair)19

Manual. The panel proposed, discussed, and finally developed 32 Population

Intervention Comparator Outcome questions which they deemed most im-
portant to the patient and the end-users of this guideline. We used Grading
Recommendations, Assessment, Development, and Evaluation (GRADE)
approach to prioritize outcomes, assess quality of evidence, and determine the
strength of outcomes (2). We then used the Evidence-to-Decision framework Copyright © 2023 by the Society of
to facilitate transition from evidence to final recommendations. We classified Critical Care Medicine.
each recommendation as strong or conditional as per GRADE methodology. DOI: 10.1097/CCM.0000000000005825

Critical Care Medicine www.ccmjournal.org     653

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 Nanchal et al

We accepted a recommendation if 80% consensus was Recommendation: We recommend using antibiotic

achieved among at least 75% of panel members. We prophylaxis in critically ill ACLF patients with any type
developed best practice statements as ungraded strong of UGIB. (Strong Recommendation, moderate quality
recommendations in adherence with strict conditions. of evidence).
Rationale: In patients with ACLF, UGIB is a major
RESULTS risk factor for the subsequent development of bacte-
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rial infections with 45% to 66% of patients developing

We report 28 recommendations (from 31 Population infections within the first 7 days of the bleeding ep-
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Intervention Comparison Outcome questions) on the isode. Administration of prophylactic antibiotics

management ALF and ACLF in the ICU related to four (typically third generation cephalosporins) in ACLF
groups (neurology, infectious diseases, gastroenterology, patients with UGIB substantially reduces the occur-
and peri-transplant). Overall, five were strong recom- rence rate of infections and rebleeding as well as
mendations, 21 were conditional recommendations, two improves survival (3).
were best-practice statements, and we were unable to Question: In critically ill ACLF patients with spon-
issue a recommendation for five questions due to insuf- taneous bacterial peritonitis (SBP), should we recom-
ficient evidence. A summary of main recommendations mend using albumin versus no albumin?
is presented in Table 1, and we discuss the abbreviated Recommendation: We recommend using albumin
rationale for the five strong recommendations. The full in critically ill ACLF patients with SBP. (Strong recom-
recommendations and complete rationales can be found mendation, moderate quality of evidence).
in the main article published in critical care medicine. Rationale: SBP is the most common infection-related
Question: In critically ill ACLF patients with upper complication in cirrhotic patients with ascites. Once
gastrointestinal bleeding (UGIB), should we recom- SBP develops, the inherent vasodilated and immune-
mend using antibiotic prophylaxis versus no antibiotic dysfunctional state of cirrhotic patients places them at
prophylaxis? high risk of developing shock, acute kidney injury, and

TABLE 1.
Summary of Main Recommendations
Strength of
Recommendation Recommendation Quality of Evidence

We recommend performing esophagogastroduodenoscopy no later Best practice statement Best practice statement
than 12 hr of presentation in critically ill ACLF patients with portal
hypertensive bleeding (known or suspected)
We recommend performing large volume paracentesis with meas- Best practice statement Best practice statement
urement of intra-abdominal pressure in critically ill ACLF patients
with tense ascites and intra-abdominal hypertension or hemody-
namic, renal or respiratory compromise
We recommend using antibiotic prophylaxis in critically ill ACLF Strong Moderate
patients with any type of upper gastrointestinal bleeding
We recommend using albumin in critically ill ACLF patients with Strong Moderate
SBP
We recommend using octreotide or somatostatin analog for the Strong Moderate
treatment of portal hypertensive bleeding in critically ill ACLF
patients
We recommend using proton pump inhibitors in critically ill ACLF Strong Low
patients with portal hypertensive bleeding
We recommend using broad spectrum antibiotic agents for the Strong Low
initial management of SBP in critically ill ACLF patients
ACLF = acute on chronic liver failure, SBP = spontaneous bacterial peritonitis.

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 Special Articles

other organ failures. Evidence suggests that use of al- portal hypertensive bleeding reduces the risk of rebleed-
bumin in SBP substantially reduces the risk of mortality ing rate but does not impact mortality (9). Furthermore,
and development of acute kidney injury (4). Further, extrapolating from the indirect evidence of the nonvari-
because effective arterial circulating volume character- ceal cohorts, short-term physiologic benefits as well as
izes cirrhosis, albumin should be administered at diag- the consistent demonstration of reduction in rebleeding
nosis of SBP even without the obvious need of volume across the studies, we issued a strong recommendation.
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resuscitation to prevent progression to ACLF. Question: In critically ill ACLF patients with portal
Question: In critically ill ACLF patients with SBP, hypertensive bleeding should we recommend using
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should we recommend using broad spectrum antibiot- octreotide or somatostatin analogs (SSAs) versus no
ics versus narrow spectrum antibiotics for the initial octreotide and no SSA?
management? Recommendation: We recommend using octreotide
Recommendation: We recommend using broad or SSA in the treatment of portal hypertensive bleed-
spectrum antibiotic agents for the initial management ing in critically ill ACLF patients. (Strong recommen-
of SBP in critically ill ACLF patients. (Strong recom- dation, moderate quality of evidence).
mendation, low quality of evidence). Rationale: In patients with ACLF, acute variceal bleed-
Rationale: SBP is a common life-threatening com- ing is associated with mortality rates greater than 10%
plication in cirrhosis (5). Delayed administration of per episode. Besides endoscopic variceal banding or scle-
appropriate antimicrobial therapy is associated with rotherapy, pharmacological agents that may be used for
increased mortality. Third generation cephalosporins the treatment of acute variceal bleeding are terlipressin
are generally accepted agents of choice for empirical and its analogs (not available in North America) or SSAs
treatment of community-acquired SBP. However, there (i.e., octreotide). The use of SSA compared with placebo
is a trend of increased Gram-positive and multidrug is associated with reductions in mortality and may be as-
resistance pathogen, including methicillin-resistant sociated with reductions in rebleeding risk (10).
Staphylococcus aureus (MRSA), vancomycin-resistant
enterococci (VRE), and extended-spectrum beta-lacta- 1 Division of Pulmonary and Critical Care Medicine, Medical
mase (ESBL) in multiple geographic areas that mandate College of Wisconsin, Milwaukee, WI.
careful consideration of the initial treatment agent for 2 Emory University Hospital, Atlanta, GA.
SBP in settings with high drug resistance patterns (6, 3 Department of Medicine, McMaster University, Hamilton,
ON, Canada.
7). Thus, use of third generation cephalosporin as the
4 Froedtert and the Medical College of Wisconsin, Milwaukee,
initial empirical treatment should be limited to low- WI.
risk community acquired SBP patients in the setting of 5 Mayo Clinic, Phoenix, AZ.
low prevalence of drug resistance. Active agents against 6 Medical College of Wisconsin, Milwaukee, WI.
ESBL-producing pathogen should be considered for 7 University of Pittsburgh Medical Center, Pittsburgh, PA.
the empirical treatment of healthcare associated SBP. 8 GUIDE Group, McMaster University, Hamilton, ON, Canada.
In high-risk critically ill patients and nosocomial infec- 9 Mayo Clinic, Rochester, MN.
tions, tailored approach according to the antimicrobial 10 Hackensack University Medical Center, Hackensack, NJ.
prevalence pattern covering resistant pathogens (ESBL, 11 Henry Ford Health System, Detroit, MI.
MRSA, ± VRE) is best suited for the empirical therapy. 12 University of Michigan Hospitals, Ann Arbor, MI.
Question: In critically ill ACLF patients with portal 13 Northeast Georgia Medical Center, Gainesville, GA.
hypertensive bleeding should we recommend using 14 Health Research Methods, Evidence, and Impact, McMaster
proton pump inhibitors (PPIs) versus no PPIs? University, Hamilton, ON, Canada.
Recommendation: We recommend using PPIs in crit- 15 University of Kentucky College of Medicine, Lexington, KY.
ically ill ACLF patients with portal hypertensive bleed- 16 Kansas University Medical Center, Kansas City, KS.
ing. (Strong recommendation, low quality of evidence). 17 University of California Los Angeles Medical Center, Los
Angeles, CA.
Rationale: In nonvariceal UGIB, PPIs have consist-
18 Barnes Jewish Hospital, St. Louis, MO.
ently been shown to reduce rates of rebleeding, need
19 Department of Critical Care Medicine and Division of
for surgical or repeat endoscopic intervention (8). Gastroenterology (Liver Unit), University of Alberta, Edmonton,
Evidence suggests that use of PPIs in patients with AB, Canada.

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 Nanchal et al

Conflicts of interest were reviewed and adjudicated by the co- failure in the ICU: Cardiovascular, endocrine, hematologic,
chairs and co-vice chairs of the guidelines. In the event an in- pulmonary, and renal considerations. Crit Care Med 2020;
dividual disclosed a conflict or potential conflict by submitted 48:e173–e191
form or verbally during the process of guidelines, those indi- 2. GRADEpro GDT: GRADEpro Guideline Development Tool
viduals abstained from voting on related questions. The task- [Software]. 2015. Available at: gradepro.org. Accessed August
force followed all procedures as documented in the American 8, 2021
College of Critical Care Medicine/Society of Critical Care 3. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, et al:
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Medicine (SCCM) Standard Operating Procedures Manual. Meta-analysis: Antibiotic prophylaxis for cirrhotic patients with
Drs. Singbartl, Nanchal, Killian, Olson, Karvellas, Subramanian, upper gastrointestinal bleeding - an updated Cochrane review.
and Truwit disclosed authorship on several related articles with Aliment Pharmacol Ther 2011; 34:509–518
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potential intellectual conflicts explored and adjudicated. Dr.

4. Salerno F, Navickis RJ, Wilkes MM: Albumin infusion improves
Dionne described volunteer service for Canadian Association
outcomes of patients with spontaneous bacterial peritonitis: A
of Gastroenterology, American College of Gastroenterology,
meta-analysis of randomized trials. Clin Gastroenterol Hepatol
American Gastroenterological Association, and European
2013; 11:123–130.e1
Society of Intensive Care Medicine. Dr. Hyzy described
volunteer service for American Thoracic Society, Quality 5. Jalan R, Fernandez J, Wiest R, et al: Bacterial infections in
Improvement and Implementation Committee, and the SCCM cirrhosis: A position statement based on the EASL Special
Finance Committee as well as service as an expert witness in Conference 2013. J Hepatol 2014; 60:1310–1324
a previous medical case involving this subject matter. Taylor 6. Friedrich K, Nussle S, Rehlen T, et al: Microbiology and re-
advised of service as an author on the SCCM/American sistance in first episodes of spontaneous bacterial peritonitis:
Society for Parenteral and Enteral Nutrition (ASPEN) nutri- Implications for management and prognosis. J Gastroenterol
tion guidelines and service on the ASPEN research commit- Hepatol 2016; 31:1191–1195
tee. Dr. Huang disclosed service on the American College of 7. Fiore M, Maraolo AE, Gentile I, et al: Nosocomial sponta-
Emergency Physicians sepsis task force. Dr. Karvellas dis- neous bacterial peritonitis antibiotic treatment in the era of
closed service on an acute liver failure study group. Dr. Hyzy multi-drug resistance pathogens: A systematic review. World J
and Dr. Olson disclosed being expert witnesses. The remaining Gastroenterol 2017; 23:4654–4660
authors have disclosed that they do not have any potential con- 8. Leontiadis GI, Sharma VK, Howden CW: Proton pump inhibi-
flicts of interest. tors in acute non-variceal upper gastrointestinal bleeding. J
For information regarding this article, E-mail: rnanchal@mcw.edu Gastroenterol Hepatol 2006; 21:1763–1765
9. Lin L, Cui B, Deng Y, et al: The efficacy of proton pump inhib-
itor in cirrhotics with variceal bleeding: A systemic review and
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