Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome
The New England journal of medicine. 2021;384(9):818-828
BACKGROUND The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. METHODS We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons. RESULTS A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group. CONCLUSIONS In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.).
Individualized hemodilution in acute brain infarct using a 20% albumin solution and physiological saline solution Dutch
Nederlands Tijdschrift voor Geneeskunde. 1992;136((49):):2422-8.
OBJECTIVE To determine the effect of normovolaemic haemodilution in patients after a cerebrovascular accident. DESIGN Prospective, randomized clinical trial. SETTING St Lucas Hospital, Amsterdam. METHOD Normovolaemic haemodilution was achieved by means of bloodletting and administration of a 20% solution of albumin plus crystalline infusion fluids under haemodynamic and rheological monitoring during the acute phase of the cerebral infarction. All patients were subjected to general intensive care and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy was guided by a pulmonary wedge pressure of 12 mm Hg (SD 3) and a haematocrit (Ht) of 0.32 l/l (SD 0.02). The control group only received individually dosed rehydration with crystalline infusion fluids. Endpoints of the study after 3 months were mortality and dependence/independence concerning everyday functioning. RESULTS The results in the total haemodilution group and the control group did not differ significantly. However, in the subgroup with normal Ht (< 0.45 l/l; n = 201) there was a significant reduction (p < 0.05) of the mortality after 3 months (27% and 16%, respectively) and an increase of independence at home (35% and 48%, respectively) due to a reduction of the viscosity by means of haemodilution with albumin (a specific viscosity effect in the normovolaemic group). In the control group with raised Ht (dehydration; Ht > or = 0.45 l/l; n = 50) there was a significant decrease (p < 0.005) of the mortality after 3 months (27% and 8%, respectively) and an increase of independence at home (35% and 59%, respectively) compared with the control group with normal Ht without signs of dehydration (Ht < 0.045 l/l; n = 102), due to rehydration exclusively with crystalline infusion fluids (a specific rehydration effect in the dehydrated group). CONCLUSION In cerebrovascular accident patients haemodilution should be adjusted individually; in normovolaemic patients haemodilution should be carried out with an albumin solution; the higher the Ht, the more rehydration with crystalline infusion fluids is to be carried out.