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Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU (Part II)

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Rahul S. Nanchal, MD, MS, FCCM; Constantine J. Karvellas, MD, MS, FRCPC, FCCM; Ram M. Subramanian, MBA, MD, FCCM
Published: 6/20/2023

Nanchal R, et al. Crit Care Med. 2023;51657-676.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU (Part II)

Citation: Nanchal R, et al. Crit Care Med. 2023;51657-676.

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OBJECTIVE:
Develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU

DESIGN:
The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development.

INTERVENTIONS:
In part 2 of this guideline, the panel was divided into four subgroups: neurology, peritransplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements.

MEASUREMENTS AND MAIN RESULTS:
We report 28 recommendations (from 31 PICO questions) on the management of ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and five had insufficient evidence so we were unable to issue a recommendation.
 
CONCLUSIONS:
Multidisciplinary, international experts formulated evidence-based recommendations for the management of ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Guideline Type: Clinical

Category: Quality and Patient Safety, GI and Nutrition,

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We suggest not using invasive intracranial pressure (ICP) monitoring for critically ill ALF patients with advanced-grade encephalopathy.
Patient Population: ALF
Quality of Evidence: Very low

We suggest, when available, using plasma exchange in critically ill ALF patients who develop hyperammonemia.
Patient Population: ALF patients who develop hyperammonemia
Quality of Evidence: Low

We suggest using hypertonic saline in critically ill ALF patients who are at risk of developing intracranial hypertension.
Patient Population: ALF patients who are at risk of developing intracranial hypertension.
Quality of Evidence: Low

We suggest not routinely using induced moderate hypothermia (< 34°C) for critically ill ALF patients who are at risk of developing intracranial hypertension.
Patient Population: ALF patients who are at risk of developing intracranial hypertension
Quality of Evidence: Very low

We suggest using nonabsorbable disaccharides in critically ill ACLF patients with overt hepatic encephalopathy.
Patient Population: ACLF patients with overt hepatic encephalopathy
Quality of Evidence: Low

We suggest using enteral polyethylene glycol (PEG) as an alternative to lactulose in critically ill ACLF patients with overt hepatic encephalopathy.
Patient Population: ACLF patients with overt hepatic encephalopathy
Quality of Evidence: Low

We suggest using oral rifaximin as adjunctive therapy in critically ill patients ACLF patients with overt hepatic encephalopathy.
Patient population: ACLF patients with overt hepatic encephalopathy
Quality of Evidence: Low

We suggest using LOLA in critically ill ACLF patients with overt hepatic encephalopathy.
Patient population: ACLF patients with overt hepatic encephalopathy
Quality of Evidence: Very low

We suggest not routinely using IV flumazenil, probiotics, zinc supplementation, glycerol phenylbutyrate (GPB), or acarbose as adjunctive therapies in critically ill ACLF patients with overt hepatic encephalopathy.
Patient population: ACLF patients with overt hepatic encephalopathy
Quality of Evidence: Very low

We recommend using antibiotic prophylaxis in critically ill ACLF patients with any type of upper gastrointestinal bleeding (UGIB).
Patient population: ACLF patients with UGIB
Quality of Evidence: Moderate

We recommend using albumin in critically ill ACLF patients with SBP.
Patient population: ACLF patients with SBP
Quality of Evidence: Moderate

We suggest using systemic antifungal prophylaxis in critically ill liver transplant recipients with risk factors for invasive fungal infections.
Patient population: Liver transplant recipients with risk factors for invasive fungal infections
Quality of Evidence: Very low

We suggest not using antifungal prophylaxis in critically ill liver transplant recipients at low risk for invasive fungal infections.
Patient population: Liver transplant recipients at low risk for invasive fungal infections
Quality of Evidence: Very low

We suggest using appropriate antibiotics as soon as possible after recognition and within 1 hour of shock onset in critically ill ACLF patients with SBP and septic shock.
Patient population: ACLF patients with SBP and septic shock
Quality of Evidence: Low

We suggest not performing large volume paracentesis (LVP) in critically ill ACLF patients with SBP.
Patient population: ACLF patients with SBP
Quality of Evidence: Very low

We suggest not using selective bowel decontamination (SBD) for critically ill liver transplant recipients.
Patient population: Liver transplant recipients
Quality of Evidence: Low

We recommend using broad spectrum antibiotic agents for the initial management of SBP in critically ill ACLF patients.
Patient population: ACLF patients
Quality of Evidence: Low

We suggest not using midodrine or terlipressin empirically for critically ill ACLF patients with SBP.
Patient population: ACLF patients with SBP
Quality of Evidence: Very low

We recommend using proton pump inhibitors (PPIs) in critically ill ACLF patients with portal hypertensive bleeding.
Patient population: ACLF patients with portal hypertensive bleeding
Quality of Evidence: Low

We recommend using octreotide or somatostatin analog (SSA) for the treatment of portal hypertensive bleeding in critically ill patients with ACLF.
Patient population: ACLF patients with portal hypertensive bleeding
Quality of Evidence: Moderate

We suggest using transjugular intrahepatic portosystemic shunt (TIPS) for recurrent variceal bleeding after medical and endoscopic intervention over continued endoscopic therapy in critically ill ACLF patients.
Patient population: ACLF patients with variceal bleeding
Quality of Evidence: Low

We suggest using systemic corticosteroids for deceased liver graft donors.
Patient population: Deceased liver graft donors
Quality of Evidence: Very low

We suggest either using goal-directed fluid management for the deceased organ donor or standard fluid management strategies.
Patient population: Deceased organ donor
Quality of Evidence: Very low

We suggest using either extracorporeal liver support or standard medical therapy in critically ill ALF or ACLF patients.
Patient population: ALF or ACLF patients
Quality of Evidence: Very low

We suggest using balanced (or normochloremic) crystalloid solution over normal (hyperchloremic) saline for peri-transplant fluid replacement in liver transplant recipients.
Patient population: Liver transplant recipients
Quality of Evidence: Low

We suggest using albumin over crystalloid for intraoperative volume replacement during LT.
Patient population: Liver transplant recipients
Quality of Evidence: Low

There was insufficient evidence to issue a recommendation on using lactulose, rifaximin, flumazenil, branch-chain amino acids, carnitine, zinc, probiotics, and L-ornithine L-aspartate (LOLA) in critically ill ALF patients with hyperammonemia.
Patient Population: ALF patients with hyperammonemia

We recommend performing esophagogastroduodenoscopy no later than 12 hours of presentation in critically ill ACLF patients with portal hypertensive bleeding (known or suspected).
Patient Population: ACLF patients with portal hypertensive bleeding

We recommend performing LVP with measurement of intra-abdominal pressure in critically ill ACLF patients with tense ascites and intra-abdominal hypertension or hemodynamic, renal or respiratory compromise.
Patient Population: ACLF patients with tense ascites and intra-abdominal hypertension or hemodynamic, renal or respiratory compromise

There was insufficient evidence to issue a recommendation on using the donor risk index (DRI) in selection of liver allograft.
Patient Population: Organ donors and recipients

There was insufficient evidence to issue a recommendation on peri-transplant fluid restriction accompanied by vasopressor use in liver transplant recipients.
Patient Population: Liver transplant recipients

There was insufficient evidence to issue a recommendation for the choice of intraoperative monitoring in LT recipients.
Patient Population: Liver transplant recipients

There was insufficient evidence to issue recommendation on early extubation of liver transplant recipients.
Patient Population: Liver transplant recipients

Rahul S. Nanchal, MD, MS, FCCM
Rahul S. Nanchal, MD, MS, FCCM
Rahul S. Nanchal, MD, MS, FCCM, is director of the medical ICU at the Medical College of Wisconsin in Delafield, Wisconsin, USA. He served as cochair for the committee that developed the guidelines for management of liver failure in adults in the ICU.
Constantine J. Karvellas, MD, MS, FRCPC, FCCM
Constantine J. Karvellas, MD, MS, FRCPC, FCCM
Constantine J. Karvellas, MD, MS, FRCPC, FCCM, is a professor of medicine at the University of Alberta in Edmonton, Alberta, Canada. He served as co-vice-chair for the committee that developed the guidelines for management of liver failure in adults in the ICU.
Ram M. Subramanian, MBA, MD, FCCM
Ram M. Subramanian, MBA, MD, FCCM
Ram M. Subramanian, MBA, MD, FCCM, is a professor of medicine and surgery at Emory University in Atlanta, Georgia, USA. He served as cochair for the committee that developed the guidelines for management of liver failure in adults in the ICU.

A complete list of the guidelines authors and contributors is available within the published manuscript.