Guidelines GI and Nutrition Quality and Patient Safety

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

PUBLISHED: 02/14/2020

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

Citation: Nanchal R, Subramanian R, Karvellas CJ, et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and renal considerations. Crit Care Med. 2020 Mar;48(3):e173-e191.

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Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are conditions frequently encountered in the ICU and are associated with high mortality. The purpose of these guidelines was to develop evidence-based recommendations addressing common clinical questions surrounding the unique manifestations of liver failure in the critically ill patient.

Often, clinical care must be adapted to individual clinical circumstances and patient/family preferences. These guidelines are meant to supplement and not replace an individual clinician’s cognitive decision-making. The primary goal of these guidelines is to aid best practice and not represent standard of care.

METHODS
Co-chair and vice-chairs were appointed by the Society of Critical Care Medicine (SCCM). Twenty-five other panel members were chosen in accordance with their clinical and/or methodological expertise. Corresponding with individual expertise, the panel was then divided into nine subgroups; the recommendations of five of those subgroups (cardiovascular, hematology, pulmonary, renal, and endocrine) are presented in this document. Each panel member followed all conflict of interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual. The panel proposed, discussed, and finally developed 30 Population Intervention Comparator Outcome questions which they deemed most important 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. We then used the Evidence-to-Decision framework to facilitate transition from evidence to final recommendations. We classified each recommendation as strong or conditional as per GRADE methodology. We accepted a recommendation if 80% consensus was achieved among at least 75% of panel members. We developed best practice statements as ungraded strong recommendations in adherence with strict conditions.

RESULTS
We report 29 recommendations on the management acute or ACLF in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best practice statements, and in two instances, a recommendation was not issued because due to insufficient evidence. We discuss the abbreviated rationale for the six strong recommendations. The full recommendations and complete rationales can be found in the main article published in critical care medicine.

Guideline Type: Clinical

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We recommend against using hydroxyethyl starch for initial fluid resuscitation of patients with ALF or ACLF.
Quality of Evidence: Moderate

Strong Cardiovascular

We suggest against using gelatin solutions for initial fluid resuscitation of patients with ALF or ACLF.
Quality of Evidence: Low

Conditional Cardiovascular

We suggest using albumin for resuscitation of patients with ALF or ACLF over other fluids, especially when serum albumin is low (<3 mg/dL).
Quality of Evidence: Low

Conditional Cardiovascular

We suggest targeting a MAP of 65 mm Hg in patients with ALF or ACLF, with concomitant assessment of perfusion.
Quality of evidence: Moderate

Remarks

Some patients will have adequate perfusion at a lower MAP, and others will have improvement of perfusion at a higher MAP.

Conditional Cardiovascular

We suggest placing an arterial catheter for blood pressure monitoring in patients with ALF or ACLF and shock.
Quality of Evidence: Low

Conditional Cardiovascular

We suggest using invasive hemodynamic monitoring to guide therapy in patients with ALF or ACLF and clinically impaired perfusion.
Quality of Evidence: Low

Conditional Cardiovascular

We recommend using norepinephrine as a first-line vasopressor in patients with ALF or ACLF who remain hypotensive despite fluid resuscitation, or those with profound hypotension and tissue hypoperfusion even if fluid resuscitation is ongoing.
Quality of Evidence: Moderate

Strong Cardiovascular

We suggest adding low-dose vasopressin to norepinephrine in patients with ALF or ACLF who remain hypotensive despite fluid resuscitation to increase blood pressure.
Quality of Evidence: Low

Conditional Cardiovascular

We suggest using viscoelastic testing (TEG/ROTEM) over measuring INR, platelet, and fibrinogen in critically ill patients with ALF or ACLF.
Quality of Evidence: Low

Conditional Hematology

We suggest using a transfusion threshold of 7 mg/dL, over other thresholds, for critically ill patients with ALF or ACLF.
Quality of Evidence: Low

Conditional Hematology

We suggest using LMWH or vitamin K antagonists, over no anticoagulation, in patients with portal venous thrombosis or pulmonary embolus.
Quality of Evidence: Very Low

Conditional Hematology

We suggest using LMWH over pneumatic compression stockings for venous thromboembolism prophylaxis in hospitalized patients with ACLF.
Quality of Evidence: Low

Remarks

There is insufficient evidence to allow a recommendation for patients with ALF.

Conditional Hematology

We recommend viscoelastic testing (TEG/ROTEM), over measuring INR, platelet, fibrinogen, in critically ill patients with ALF or ACLF undergoing procedures.
Quality of Evidence: Moderate

Strong Hematology

We recommend against using Eltrombopag in ACLF patients with thrombocytopenia prior to surgery/invasive procedures.
Quality of Evidence: Low

Remarks

There is insufficient evidence to issue a recommendation for or against prothrombin complex concentrates
(PCCs).

Strong Hematology

We suggest using a low tidal volume strategy over high tidal volume strategy in patients with ALF or ACLF and ARDS.
Quality of Evidence: Low

Conditional Pulmonary

We suggest against using high PEEP, over low PEEP, in patients with ALF or ACLF and ARDS.
Quality of Evidence: Low

Remarks

Clinicians may cautiously choose high PEEP in moderate to severe ARDS after balancing potential benefit to risk of increasing intracranial pressure (ICP) and reducing venous return.

Conditional Pulmonary

We suggest treating portopulmonary hypertension with agents approved for pulmonary arterial hypertension in patients with mean pulmonary artery pressure greater than 35 mm Hg.
Quality of Evidence: Very Low

Conditional Pulmonary

We recommend supportive care with supplemental oxygen in the treatment of hepatopulmonary syndrome (HPS), pending possible liver transplantation.

Best-Practice-Statement Pulmonary

We recommend placing chest tube with an attempt to pleurodesis for hepatic hydrothorax in patients in whom transjugular intrahepatic portosystemic shunt (TIPS) is not an option or as a palliative intent.

Best-Practice-Statement Pulmonary

We suggest using HFNC over noninvasive ventilation in hypoxic critically ill patients with ALF or ACLF.
Quality of Evidence: Low

Remarks

In patients with hypercarbia, it may be more appropriate to use noninvasive positive pressure ventilation (NIPPV) or invasive mechanical ventilation over HFNC.

Conditional Pulmonary

We suggest using RRT early in patients with ALF and AKI.
Quality of Evidence: Very Low

Remarks

There is insufficient evidence to issue a recommendation for the ACLF population. Early initiation of RRT is defined as initiation of RRT before 1) hyperkalemia (> 6 mmol/L with electrocardiographic abnormalities), 2) fluid overload/pulmonary edema resistant to diuretic administration, 3) severe metabolic acidosis (pH < 7.15), 4) blood urea concentration greater than 35.7 mmol/L, or 5) Kidney Disease Improving Global Outcomes stage 3 AKI.

Conditional Renal

We recommend using vasopressors, over not using vasopressors, in critically ill patients with ACLF who develop hepatorenal syndrome.
Quality of Evidence: Moderate

Remarks

Vasopressors could be any of the following: terlipressin, norepinephrine, or midodrine and octreotide.

Strong Renal

We recommend targeting a serum blood glucose of 110-180 mg/dL in patients with ALF or ACLF.
Quality of Evidence: Moderate

Strong Endocrine-Nutrition

We suggest using stress-dose glucocorticoids in the treatment of septic shock in patients with ALF or ACLF.
Quality of Evidence: Low

Remarks

Stress dose glucocorticoids should be used if adequate fluid resuscitation and vasopressor agents are unable to restore hemodynamic stability.

Conditional Endocrine-Nutrition

We suggest against using a low protein goal in patients with ALF or ACLF, but rather targeting protein goals comparable with critically ill patients without liver failure (1.2-2.0g protein/kg dry or ideal body weight per day).
Quality of Evidence: Very Low

Conditional Endocrine-Nutrition

We suggest not using branched-chain amino acids in critically ill patients hospitalized with ALF or ACLF who are tolerating enteral medications.
Quality of Evidence: Very Low

Conditional Endocrine-Nutrition

We suggest enteral nutrition over parenteral nutrition in critically ill patients hospitalized with ALF or ACLF without contraindication for enteral feeding.
Quality of Evidence: Low

Conditional Endocrine-Nutrition

We recommend screening patients with ALF or ACLF for drug-induced causes of liver failure. Drugs that are proven or highly suspected to be the cause of ALF or ACLF should be discontinued.

Best-Practice-Statement Endocrine-Nutrition

In patients with ALF or ACLF, we recommend adjusting the doses of medications that undergo hepatic metabolism based on the patient’s residual hepatic function and using the best available literature. When available, a clinical pharmacist should be consulted.

Best-Practice-Statement Endocrine-Nutrition

Intraoperative Renal Replacement Therapy During Liver Transplant Surgery
There is insufficient evidence to issue a recommendation.

Remarks

Patients with ongoing emergent indications for RRT such as hyperkalemia or severe acid-base abnormalities should not have RRT discontinued.

Renal

Transjugular Intrahepatic Portosystemic Shunt for Prevention of HRS
There is insufficient evidence to issue a recommendation.

Renal

ACLF = acute on chronic liver failure, AKI = acute kidney injury, ALF = acute liver failure, ARDS = acute respiratory distress syndrome, HFNC = high-flow nasal cannula, INR = international normalized ratio, LMWH = low-molecular-weight heparin, MAP = mean arterial pressure, PEEP = positive end-expiratory pressure, ROTEM = rotational thromboelastometry, RRT = renal replacement therapy, TEG = thromboelastography.

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

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