BOSTON – Terlipressin proved noninferior to noradrenaline as a vasopressor for patients with cirrhosis and septic shock in an open-label study that randomized 84 patients.
Terlipressin also seemed to provide advantages over noradrenaline by contributing to greater hemodynamic stability, improved urine output, reduced variceal bleeding, a lower risk of spontaneous bacterial peritonitis, and reduced mortality in the first 48 hours but not at 28 days, Dr. Ashok K. Choudhury and his associates reported.
“Terlipressin is noninferior to noradrenaline as a vasopressor,” he said at the annual meeting of the American Association for the Study of Liver Diseases.
The investigators randomized consecutive, matched adults with cirrhosis and septic shock not responding to fluid resuscitation for 2 hours. They aimed to achieve a mean arterial pressure (MAP) > 65 mm Hg at 6 hours by treating 42 patients with a continuous infusion of terlipressin 1.3-5.2 mcg/min, stepped up every 15 minutes, and 42 patients with noradrenaline 7.5-6 mcg/min, stepped up every 15 minutes. Both groups received standard medical care of intravenous fluids, antibiotics, and ICU care.
The target MAP was reached within 6 hours in 28 patients on terlipressin (67%) and 23 patients on noradrenaline (55%), a difference that was not statistically significant, said Dr. Choudhury of the Institute of Liver and Biliary Sciences, New Delhi. He won a research award from the Association.
Patients in the two groups were matched by age, sex, etiology and severity of cirrhosis, and scores on the Model for End-Stage Liver Disease and the Sequential Organ Failure Assessment.
Spontaneous bacterial peritonitis was the main cause of sepsis at admission, followed by pneumonia, but pneumonia was the main cause of “second hit” pneumonia, he said.
Terlipressin therapy was associated with a lower failure rate at 6 hours, a greater likelihood of MAP maintenance with cessation of vasopressor requirements at 48 hours, and improved urine output at 24 hours, compared with noradrenaline treatment. At 48 hours, 19 of 40 patients on terlipressin (48%) and 11 of 30 patients on noradrenaline (36%) had an MAP > 65 mm Hg.
No patients on terlipressin developed a variceal bleed, compared with seven patients in the noradrenaline group (10%). Overall rates of adverse events did not differ significantly between groups, but were higher in the terlipressin group than in the noradrenaline group.
Better rates of lactate clearance, central venous oxygen saturation, and carbon dioxide gradient in venous-arterial blood gases in the terlipressin group were not statistically different from rates in the noradrenaline group.
Significantly more patients on terlipressin survived the first 48 hours than patients on noradrenaline, but by day 28 of follow-up survival rates did not differ significantly between groups.
On the whole, septic shock in these patients with cirrhosis was associated with a high mortality rate (80%). Twelve percent of patients were responsive to fluids in 2 hours.
Dr. Choudhury reported having no financial disclosures.
On Twitter @sherryboschert
