most common complication of HRS treatment includes respiratory failure
- related: hepatorenal syndrome HRS
- tags: #literature #pulmonary
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The most concerning cause of death in this patient with hepatorenal syndrome (HRS) type 1 treated with terlipressin and IV albumin is respiratory failure (choice C is correct).
HRS is one of the multiple potential causes of acute kidney injury (AKI) in patients with acute or chronic liver disease and is the end stage of a sequence of reductions in kidney perfusion induced by increasingly severe hepatic injury. The diagnosis of HRS is a diagnosis of exclusion and is a devastating complication associated with high morbidity and mortality. On the basis of the rapid decline of renal function, two forms of HRS have been described. Type 1 HRS, or HRS-AKI, is the more serious of the two types and is defined by a twofold increase in serum creatinine level (reflecting a 50% reduction in creatinine clearance) to a level greater than 2.5 mg/dL (221 μmol/L) during a period of less than 2 weeks, as occurred in this patient. Type 2 HRS, or diuretic-resistant ascites, has a less severe manifestation and is characterized by renal dysfunction that occurs in the setting of ascites resistant to diuretics over a longer time.
The pathophysiological hallmarks of HRS include circulatory dysfunction, characterized by splanchnic vasodilation resulting in a decrease in effective circulating volume. The definitive treatment for HRS is liver transplant; however, this option is not available for all patients with advanced liver disease. In the absence of liver transplant, supportive treatment includes the use of systemic vasoconstrictors in combination with IV albumin. Terlipressin is recommended as the first-line vasoactive drug for the management of HRS in Europe and Asia and in September 2022 was approved by the US Food and Drug Administration.
Because systemic vasodilation is one of the main pathogenic mechanisms of HRS, potent vasoconstrictors that induce an increment of mean arterial pressure in patients with HRS correlate inversely with changes in serum creatinine level. Terlipressin is a vasopressin analogue, which is metabolized into the pharmacologically active metabolite lysine-vasopressin, that acts predominantly on the V1a receptor in vascular smooth muscle. Compared with vasopressin or its direct predecessor, ornipressin, terlipressin has a longer half-life and more predictable therapeutic window, which allows for bolus administration through a peripheral IV catheter rather than a central venous catheter. Other vasopressors, such as norepinephrine, have shown efficacy in the management of HRS, but these agents require continuous infusion and ICU monitoring.
Investigators in the multicenter, randomized, placebo-controlled, double-blind study to confirm the efficacy and safety of terlipressin in subjects with HRS type 1 (the CONFIRM study) investigated terlipressin at a dose of 1 mg IV every 6 h plus albumin vs placebo plus albumin to reverse HRS. The administration of terlipressin in addition to IV albumin was more effective than placebo plus albumin in improving renal function in patients with cirrhosis and HRS type 1. However, terlipressin administration was associated with serious adverse events, including respiratory failure and death from respiratory disorders within 90 days after the first dose of terlipressin. Respiratory failure in patients receiving terlipressin is likely related to the direct cardiovascular and pulmonary effects of terlipressin. Death within 90 days because of respiratory disorders occurred in 11% of patients in the terlipressin group compared with 2% of patients in the placebo group. In contrast, the incidence of shock and cardiac disorders, including cardiac arrhythmias (eg, atrial fibrillation), was no different in the terlipressin group (choices A and B are incorrect).
Reversal of HRS, including HRS reversal with no need for renal replacement therapy through the first 30 days, was higher in patients receiving terlipressin than in those receiving placebo. Terlipressin avoids the need for hemodialysis and the development of severe hyperkalemia associated with renal dysfunction in patients with cirrhosis (choice D is incorrect).
With US Food and Drug Administration approval of terlipressin, the number of patients exposed to this medication is expected to increase. Serious adverse events have been cited as a limiting factor for use of terlipressin. In the CONFIRM trial, GI bleeding (4% vs 0%), sepsis (4% vs 0%), and respiratory failure (10% vs 3%) were seen in higher proportion in the terlipressin group than in the placebo group. Given these risks, careful evaluation of individual characteristics and baseline comorbidities is needed before considering using terlipressin in clinical practice.1