Treatment of fulminant hepatic failure with intravenous prostaglandin E1.
Fulminant hepatic failure (FHF) is a severe, life-threatening 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 E1 (PGE1) 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. PGE1 was administered by continuous infusion at a dose of 10 to 40 microg/h as tolerated. After 48 hours of blinded treatment, 3 of 7 patients randomized to placebo were converted to open-label PGE1 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 PGE1-(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 PGE1 treatment. Six of 8 patients (75%) who began PGE1 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 PGE1 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 PGE1 treatment is beneficial when administered during this period. However, it is apparent that PGE1 was not effective for treatment of FHF if treatment started more than 10 days after onset of this clinical syndrome.
Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0711, USA.
R K
RK
Sterling
V A
VA
Luketic
A J
AJ
Sanyal
M L
ML
Shiffman
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000527:Alprostadil / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D000410:Alanine Transaminase; D000527:Alprostadil