Liver Disease:
Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-9. RCT found addition of albumin to cefotaxime vs. antibiotic alone in above population preserved renal function and reduced mortality. Study does not provide information on volume resuscitation in the antibiotic-alone group, however, making it less clear whether albumin has additional benefit beyond what could be achieved with aggressive crystalloids.
PMID: 10432325
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Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009; 137(3):856-64. This RCT of 173 patients is commonly cited as the basis for administering NAC in acute liver failure in patients without acetaminophen exposure. Overall survival did not differ, but 3-week transplant-free survival was improved in the NAC group (40% vs 27%, p = .04).
PMID: 19524577
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García-Pagán JC, Caca K, Bureau C, et al. for the Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010;362:2370-9. In a prospective study of 63 patients with acute variceal bleeding, TIPS placement within 72 hours led to a reduction in mortality and rebleeding rate.
PMID: 20573925
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Nadim MK, Durand F, Kellum JA, et al. Management of the critically ill patient with cirrhosis: A multidisciplinary perspective. J Hepatol. 2016; 64:717-35. This multi-society and multidisciplinary consensus statement promotes the emerging concept of acute on chronic liver failure (ACLF) and provides a series of graded recommendations on general and organ-specific management issues in the critically ill patient with cirrhosis. It relies heavily on expert opinion, which reflects the complexity of the ACLF population and paucity of available data.
PMID: 26519602
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Gastrointestinal bleeding:
Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013; 368:11-21. A large multi-center trial that found a hemoglobin goal of of 7 mg/dL during acute upper gastrointestinal bleed resulted in a lower risk of re-bleeding, adverse events, and a decreased hazard ratio for death at 6 weeks when compared with a 9 mg/dL target. Patients with rapid exsanguination were excluded. The mortality benefit appears greatest in patients with Child-Pugh class A or B cirrhosis.
PMID: 23281973
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Krag M, Marker S, Perner A et al. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med. 2018; 379:2199-2208. This multicenter blinded trial randomized ~3300 ICU patients at risk for gastrointestinal bleeding to 40 mg of intravenous pantoprazole or placebo daily during the ICU stay. There was no difference in 90 day mortality. Significant bleeding was uncommon, affecting 2.5% of the PPI group and 4.2% for placebo. There was no significant difference in incidence of C. difficile infection or pneumonia.
PMID: 30354950
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Young PJ, Bagshaw SM, Forbes AB, et al. Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: The PEPTIC randomized clinical trial. JAMA. 2020; 323:616-626. Large RCT of almost 27,000 patients comparing PPI vs H2RB for stress ulcer prophylaxis found an overall low risk of bleeding but lower in the PPI group (1.3% vs 1.8% for H-2 blocker) without an increase in C.difficile colitis. The difference in 90-day all-cause mortality, the primary outcome, did not differ significantly (18.3% PPI vs 17.5% H-2 blocker). Of note, only 64% in the H2RB group and 82% in the PPI group received their assigned treatment alone.
PMID: 31950977
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