Alan I. Leibowitz

Results of a protocol for the management of patients with fulminant liver failure

Objective:To assess the safety and efficacy of a protocol to support management of intracerebral pressure in patients with fulminant liver failure (FLF). Design and Setting:A prospective series was conducted between May 2004 and September 2006 at Banner Good Samaritan Medical Center, a 650-bed teaching hospital in Phoenix, Arizona. Patients:We recruited consecutive patients with FLF and stage 3 or 4 encephalopathy. Interventions:We placed an intracranial pressure monitor in each patient and employed a protocol to support decisions regarding hemostatic management and prevention and treatment of intracranial hypertension (IHTN). Treatment modalities included hypothermia, hypocarbia, intravenous pentobarbital, intravenous mannitol and vasopressor titration for maintenance of cerebral perfusion pressure. The main outcome measure was survival in transplant candidates. Measurements and Main Results:Twenty-two patients entered the study and 21 (95%) had at least one episode of IHTN. Eighty-two discrete episodes of IHTN occurred, and 78 of these (95%) resolved with treatment. Overall survival was 55%. Eleven of 18 (61%) of transplant candidates survived with good neurologic outcome. No patient died from isolated cerebral edema. Three patients had intracranial hemorrhages related to the intracranial pressure monitor. Conclusions:Protocol-driven management of intracranial pressure in FLF can result in good clinical outcomes in most transplant candidates, even if IHTN occurs. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Explain the most common cause of death in fulminant liver failure. Describe the protocol for management of patients with fulminant liver failure. Use this information in a clinical setting. Dr. Raschke has disclosed that he was a consultant/advisor for Cardinal Health and attended and spoke at several paid meetings and conferences in regards to intravenous heparin. The remaining authors have not disclosed any potential conflicts of interest. The authors have disclosed that the U.S. Food and Drug Administration has not approved pentobarbital for the treatment of intracranial hypertension discussed in this article. Please consult the products labeling information for approved indications and usage. All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationship with, or financial interests in, any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web Site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Fibroblast interferon treatment of a patient with chronic active hepatitis: Increased number of circulating T lymphocytes and elimination of rosette-inhibitory factor

A 23 year old woman with chronic active hepatitis documented by liver biopsy demonstrated persistent hepatitis B surface antigen, hepatitis B virus specific DNA polymerase hepatitis B core antigen (HBcAg), for approximately one year. The number of circulating T lymphocytes that rosetted with sheep erythrocytes was decreased, and a rosette-inhibitory factor was present in her peripheral blood. Interferon treatment (1 X 10(6) U/day intramuscularly for 82 days) resulted in a decrease of HBsAg and disappearance of HBcAg, (HBeAg) and specific DNA polymerase. In addition, the number of T lymphocytes increased to normal, and the rosette-inhibitory factor disappeared from the circulation. These findings suggest that the effect of interferon in chronic active hepatitis is mediated in part through its action on the immune system.

Purified human fibroblast interferon in vivo: skin reactions and effect on bone marrow precursor cells.

Human interferon from normal diploid fibroblasts, purified by sequential chromatography on concanavalin A-agarose and phenyl-sepharose, was administered parenterally in 4 subjects. Fever, marked skin hypersensitivity reactions and suppression of marrow stem cells (estimated by the count of myeloid colony-forming cells), side-effects common for less purified fibroblast and leukocyte interferons, were absent. Purified fibroblast interferon retained antiviral and immunomodulatory activity, evidenced by reduction of the blastogenic response of peripheral lymphocytes and decrease of hepatitis B virus markers in a patient with chronic hepatitis B infection treated with this substance.

Influence of carbon tetrachloride on circulating endotoxin after exogenous administration of endotoxin in rats.

Abstract To ascertain the influence of carbon tetrachloride on the ability of the liver to remove circulating endotoxin, groups of rats were injected ip with endotoxin obtained from Escherichia coli 026 and also received carbon tetrachloride orally. The serum concentrations of endotoxin at different time intervals were measured by an immunoradiometric assay specific for the endotoxin used. It was shown that carbon tetrachloride delayed the removal of endotoxin by the liver. The effect was dependent on the dose of carbon tetrachloride given and was seen as early as 1 hr after the endotoxin injection.