To address developments in the management of cirrhosis, the American Gastroenterological Association (AGA) released a clinical practice update, which includes 12 Best Practice recommendations for the use of IV vasoactive drugs and IV albumin in three areas, including in the management of VH, ascites and SBP, and HRS-AKI. Among the vasoactive substances addressed are terlipressin, norepinephrine, and the combination of octreotide and midodrine. Octreotide represents a somatostatin-type medication, whereas terlipressin is an example of a vasopressin analogue.
Three Best Practice recommendations were made for the management of VH. It has been suggested that vasoactive medications should be started as soon as the diagnosis of VH is suspected or confirmed—even before the use of endoscopy. This is imperative since acute VH has a mortality rate of up to 43% at 6 weeks and the use of IV vasoactive drugs can stop acute hemorrhage in up to 80% of patients. It is also recommended that IV vasoactive therapy be continued for 2 to 5 days following initial endoscopy to induce hemostasis to prevent early rebleeding. Since there is controversy over how long to continue treatment, therapy may be reduced to 2 days only in select patients such as those with Child-Pugh class A or B cirrhosis with no active bleeding observed during endoscopy. For the management of VH, octreotide is the IV vasoactive drug of choice compared with vasopressin due to a better safety profile; use of vasopressin is no longer advised. The article also addresses the limitations of the use of terlipressin for this indication.
Four Best Practice recommendations were made for the management of ascites and SBP. In this condition, IV albumin should be administered at the time of large-volume (>5 L) paracentesis (LVP) to reduce the risk of postparacentesis circulatory dysfunction (PCD). PCD is associated with a marked increase in plasma renin activity and aldosterone levels within 48 hours of LVP. The use of IV albumin is also suggested in patients with SBP to help prevent the development of HRS-AKI. However, the use of IV albumin is not recommended for infections other than SBP because of the increased risk of pulmonary edema. Also, IV albumin should not be used in patients with cirrhosis and uncomplicated ascites, as the standard therapy for cirrhotic ascites is sodium restriction along with diuretic therapy. Additionally, vasoconstrictor use is not advised in the management of uncomplicated ascites, after LVP, or in patients with SBP. Evidence for the use of vasoconstrictors is lacking in these situations.
Lastly, for HRS-AKI, the clinical practice update recommends the use of IV albumin as the volume expander of choice in hospitalized patients with cirrhosis and ascites who develop AKI. The dose of IV albumin is 1 g/kg of body weight daily for 2 consecutive days (maximum of 100 g/day). Vasoactive medications including terlipressin, norepinephrine, or octreotide/midodrine should only be used for the treatment of HRS-AKI, not for other forms of AKI associated with cirrhosis. This is because HRS-AKI is associated with extreme splanchnic vasodilation that results in low effective arterial blood volumes, which trigger the development of renal vasoconstriction and decreased blood flow to the kidneys and a drop in the glomerular filtration rate.
Terlipressin, which is approved in the United States to improve kidney function in adults with HRS and a rapid reduction in kidney function, does not require ICU monitoring and can be given IV via a peripheral line. However, terlipressin use is contraindicated in patients with hypoxemia and those with coronary, peripheral, or mesenteric ischemia. It should be used with caution in those with acute on chronic liver failure (ACLF) grade 3. ACLF grade 3 involves the development of three or more organ failures and is associated with a mortality rate of >90% at 1 year when a liver transplant is not performed. Terlipressin should be avoided in those with a serum creatinine >5 mg/dL, as patients are unlikely to experience benefit. It should also not be administered in patients awaiting a liver transplant with a Model for End-Stage Liver Disease score of >35, which is associated with a 3-month mortality of >50%.
This clinical practice update provides valuable information for pharmacists caring for patients with cirrhosis and represents best practice advice to optimize the care and improve the survival of patients with this potentially fatal condition.
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