Treatment of fulminant hepatic failure with intravenous prostaglandin E1

Abstract

Fulminant hepatic failure (FHF) is a severe, lifethreatening disorder. Previous studies have suggested that intravenous prostaglandin treatment may improve survival in FHF. The present study was performed to further investigate the possible benefit of intravenous prostaglandin E 1 (PGE 1 ) for patients with FHF. A total of 18 patients, all excluded as candidates for hepatic transplantation, were studied. Thirteen of 18 participated in a randomized, double-blind, placebo-controlled trial. PGE 1 was administered by continuous infusion at a dose of 10 to 40 g/h as tolerated. After 48 hours of blinded treatment, 3 of 7 patients randomized to placebo were converted to open-label PGE 1 for lack of biochemical and/or clinical improvement. Mean values for alanine transaminase, aspartate transaminase, total bilirubin, prothrombin time, factor V percent, factor VII percent, hepatic encephalopathy score, days from onset of symptoms to initiation of treatment, and cause of FHF were similar between treatment groups. Ten of 18 patients (55%) enrolled in this trial survived. However, survival was not different between PGE 1 -(60%) and placebo (50%) treated patients. The greatest predictor of survival was the number of days from onset of symptoms to hospitalization, which was significantly (P ‫؍‬ .002) shorter for survivors (3.3 v 12.4 days), regardless of PGE 1 treatment. Six of 8 patients (75%) who began PGE 1 therapy and 4 of 5 placebo-treated patients (80%) hospitalized within 10 days of onset of symptoms survived. By contrast, all 5 patients who were hospitalized and subsequently began PGE 1 treatment 10 days or longer after the onset of symptoms died. We conclude that early recognition and hospitalization is the most important factor in reduction of mortality from FHF. It is unclear whether PGE 1 treatment is beneficial when administered during this period. However, it is apparent that PGE 1 was not effective for treatment of FHF if treatment started more than 10 days after onset of this clinical syndrome.

AASLD position paper: The management of acute liver failure

“…While prostacyclin and other prostaglandins have appeared promising in some reports, 66,67 others have not supported their efficacy in ALF. 68 NAC may improve systemic circulation parameters in patients with ALF, 69 but this was not observed in all studies. 70 NAC has been shown to improve liver blood flow and function in patients with septic shock.…”

Etiology and management of fulminant hepatic failure

“…Preliminary reports of increased survival of patients treated with prostaglandin-E1 in uncontrolled studies were very encouraging, but no clear benefit supporting the use of this agent has been found in subsequent controlled trials [38].…”

Tissue Hypoperfusion, Hypercoagulopathy, and Kidney and Liver Dysfunction after Ingestion of a Naphazoline-Containing Antiseptic

“…Although no prior report has described the use of intravenous alprostadil for the treatment of α 2 -adrenergic receptor agonist overdose, we selected this agent because prostaglandin E1 has several other benefits, including hepatic and renal cytoprotection [16–18], facilitation of liver regeneration [19], and prevention of further formation of microthrombi [20]. Prostaglandin E1 has also been found to be useful in treating patients with contrast-induced nephropathy [16, 21] and fulminant hepatitis [22, 23]. …”