title: Failed rescue therapy with rapamycin after paraquat intoxication.
abstract: BACKGROUND
  Ingestion of large quantities of paraquat leads to irreversible, often fatal pulmonary fibrosis. Case presentation. A 50-year-old man (body weight of 78.6 kg) ingested 500 mL Gramoxone containing 200 g/L of paraquat in a suicide attempt. The patient did not seek medical attention until 15 h after ingestion. Initial treatment consisted of the administration of intravenous methylprednisolone, 250 mg once daily. Seventy-two hours after ingestion the patient was transferred to our tertiary care center. Paraquat concentration was 0.2 mg/L in the serum and urinary concentration was 4.42 mg/L. Antioxidative therapy including the administration of acetylcysteine and an anti-inflammatory therapy employing methylprednisolone (1 g/day) was started. Extended daily dialysis was initiated. As the high plasma concentration of paraquat indicated a 100% predicted mortality, we expanded treatment strategies by using the antiproliferative agent rapamycin. A dose of 8 mg/day was started 72 h after the intoxication. Maximum rapamycin concentrations amounted to 12.9 microg/L. Despite these efforts, the patient died on day 18 after intoxication from respiratory failure caused by severe pulmonary fibrosis.
  
  
  CONCLUSIONS
  Despite theoretical considerations suggesting the use of rapamycin in paraquat poisoning, the substance failed to halt the progression of pulmonary fibrosis in this case.
authors.affiliation: Department of Internal Medicine, Medical School Hannover, Hannover, Germany.
authors.forename: Johan Matthes
authors.initials: JM
authors.lastname: Lorenzen
authors.forename: Eva
authors.initials: E
authors.lastname: Schonenberger
authors.forename: Carsten
authors.initials: C
authors.lastname: Hafer
authors.forename: Marius
authors.initials: M
authors.lastname: Hoeper
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D003956:Dialysis; D017809:Fatal Outcome; D006540:Herbicides / Q000506:poisoning*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D010102:Oxygen Inhalation Therapy; D010269:Paraquat / Q000506:poisoning*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000517:prevention & control; D020123:Sirolimus / Q000627:therapeutic use*; D013405:Suicide; D058570:TOR Serine-Threonine Kinases; D017211:Treatment Failure
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006540:Herbicides; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D010269:Paraquat; D020123:Sirolimus; D008775:Methylprednisolone