Failed rescue therapy with rapamycin after paraquat intoxication.
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.
Lorenzen
Johan Matthes
JM
Department of Internal Medicine, Medical School Hannover, Hannover, Germany.
Schonenberger
Eva
E
Hafer
Carsten
C
Hoeper
Marius
M
Kielstein
Jan T
JT
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
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