Ms. Boyle
Clinical question: Which risk factors predict new-onset respiratory failure during terlipressin use for the treatment of patients with rapidly deteriorating kidney function attributed to type 1 hepatorenal syndrome (HRS-AKI)?
Background: Terlipressin, a synthetic vasopressin analog, has long been an international standard of care for HRS-AKI under the European Clinical Practice Guidelines. The agent offers two attractive advantages to norepinephrine, another vasoconstrictive agent employed for the treatment of HRS-AKI, in that terlipressin administration does not require central venous access or intensive care unit admission. The results of the CONFIRM trial demonstrated terlipressin’s superiority in improving kidney function compared to placebo and were instrumental in terlipressin’s approval for use in the U.S. in September 2022. However, the trial re-demonstrated the increased incidence of respiratory failure associated with terlipressin use seen in earlier, smaller trials. This post-hoc analysis of CONFIRM sought to identify risk factors for terlipressin-associated respiratory failure.
Study design: Post-hoc analysis of the randomized, double-blind, placebo-controlled CONFIRM trial
Setting: 70 centers across the U.S. and Canada
Synopsis: Acute on chronic liver failure (ACLF) grade is defined as the number of organ system failures under the Chronic Liver Failure-Sequential Organ Failure Assessment scoring system.
Significantly more patients developed respiratory failure under terlipressin treatment compared to placebo. Univariate logistic regression analysis revealed ACLF scores to be a predictor of respiratory failure. Patients with baseline ACLF grade 3 were significantly more likely to develop respiratory failure on terlipressin compared with those with ACLF grades 1–2 (30% for ACLF grade 3 versus 9.4% for grade 1–2, P=0.002). Patients with baseline ACLF grade 3 were also more likely to experience death attributed to respiratory failure on terlipressin as compared to those receiving placebo (22.5% versus 0%, P=0.05).
Multivariate logistic regression analysis identified baseline international normalized ratio, mean arterial pressure, and oxygen saturation as additional risk factors associated with the development of respiratory failure following terlipressin. Of note, the volume of albumin administration as a continuous variable was not found to be a predictor of respiratory failure in the terlipressin arm. No significant predictors of respiratory failure were identified among patients with HRS-AKI receiving a placebo.
Hospitalists can employ the ACLF scoring system to identify the subgroup of patients with HRS-AKI in whom the risks of terlipressin therapy may outweigh the benefits. For those patients with ACLF grade 3 in whom terlipressin is administered, hospitalists may wish to consider intensifying monitoring for respiratory compromise and have a lower threshold to discontinue therapeutic trials of terlipressin.
Bottom line: In contrast to patients with baseline ACLF grades 1–2, patients with ACLF grade 3 failed to achieve greater rates of hepatorenal syndrome reversal with terlipressin compared to placebo. Patients with baseline ACLF grade 3 were found to be at increased risk of respiratory failure and associated mortality following terlipressin therapy.
Citation: Wong F, Pappas SC, et al. Terlipressin use and respiratory failure in patients with hepatorenal syndrome type 1 and severe acute-on-chronic liver failure. Aliment Pharmacol Ther. 2022;56(8):1284-93.
Ms. Boyle helped launch the first APP hospitalist service at Stanford Hospital where she works in inpatient transplant nephrology.