As a clinical pharmacist, you should evaluate the use of terlipressin for hepatorenal syndrome. Terlipressin (Glypressin, Haemoxamine) will be the first FDA-approved medication for hepatorenal syndrome with acute kidney injury (HRS-AKI). HRS-AKI typically occurs in patients with cirrhosis and ascites who develop splanchnic vasodilation. This causes decreased perfusion to the kidneys. The best treatment is a liver transplant, but many patients don’t qualify for or live long enough to get a transplant.
Focus on short-term management using vasoconstrictors PLUS albumin to improve perfusion and reverse AKI. Until now, the vasoconstrictors for treating HRS-AKI in the US were norepinephrine for ICU patients, or octreotide (Sandostatin) plus midodrine.
Terlipressin is a new vasoconstrictor. Think of it like vasopressin, but longer-acting and more selective. It’s been used abroad for decades, but only studied more recently in the US. Using terlipressin to treat HRS-AKI leads to improved kidney function versus placebo, primarily by reducing serum creatinine. But when comparing terlipressin to norepinephrine for HRS-AKI, limited data suggest no difference in mortality or reversing kidney injury. And using either terlipressin or norepinephrine seems to reverse kidney injury better than octreotide plus midodrine.
Terlipressin has the advantage of Q6H IV push dosing, and is NOT required to be given in an ICU or through a central line. But the starting dose for terlipressin is very cost, norepinephrine is often very cheap and much less expensive than terlipressin For now, lean toward norepinephrine as the vasoconstrictor to add to albumin. Titrate norepinephrine to raise the mean arterial pressure by at least 10 mm Hg, or urine output over 200 mL/4 hours. Save terlipressin for when norepinephrine isn’t an option, such as a drug shortage or in a patient outside the ICU.
Be aware, some evidence suggests terlipressin has serious respiratory risks, such as pulmonary edema. Don’t give terlipressin to patients with ischemia or oxygen saturation below 90%. And use continuous pulse oximetry to monitor patients receiving it.
REFERENCES
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Wong F, Pappas SC, Curry MP, Reddy KR, Rubin RA, Porayko MK, Gonzalez SA, Mumtaz K, Lim N, Simonetto DA, Sharma P, Sanyal AJ, Mayo MJ, Frederick RT, Escalante S, Jamil K; CONFIRM Study Investigators. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 2021 Mar 4;384(9):818-828. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2008290
Pitre T, Kiflen M, Helmeczi W, Dionne JC, Rewa O, Bagshaw SM, Needham-Nethercott N, Alhazzani W, Zeraatkar D, Rochwerg B. The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis. Crit Care Med. 2022 Oct 1;50(10):1419-1429. Available at: https://journals.lww.com/ccmjournal/Abstract/2022/10000/The_Comparative_Effectiveness_of_Vasoactive.1.aspx
Belcher JM, Parada XV, Simonetto DA, Juncos LA, Karakala N, Wadei HM, Sharma P, Regner KR, Nadim MK, Garcia-Tsao G, Velez JCQ, Parikh SM, Chung RT, Allegretti AS; HRS-HARMONY Study Investigators. Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward. Am J Kidney Dis. 2022 May;79(5):737-745. Available at: https://www.ajkd.org/article/S0272-6386(21)00890-8/fulltext