title: Early propranolol administration to severely injured patients can improve bone marrow dysfunction.
abstract: BACKGROUND
  Bone marrow (BM) dysfunction is common in severely injured trauma patients, resulting from elevated catecholamines and plasma granulocyte colony-stimulating factor (G-CSF) as well as prolonged mobilization of hematopoietic progenitor cells (HPCs). We have previously shown that propranolol (β-blocker [BB]) reduces HPC mobilization in a rodent model of injury and hemorrhagic shock. We hypothesize that BB would prevent BM dysfunction in humans following severe injury.
  
  
  METHODS
  Forty-five severely injured trauma patients were studied in a prospective, randomized pilot trial. Twenty-five patients received BB, and 20 served as untreated controls. The dose of propranolol was adjusted to decrease the heart rate by 10% to 20% from baseline. Blood was analyzed for the presence of HPC (blast-forming unit erythroid cells [BFU-E] and colony-forming unit erythroid cells) and G-CSF. Demographic data, Injury Severity Score (ISS), hemoglobin, reticulocyte number, and outcome data were obtained.
  
  
  RESULTS
  The mean age of the study population was 33 years; 87% were male, with a mean ISS of 29. There is a significant increase in BFU-E in peripheral blood immediately following traumatic injury, and this mobilization persists for 30 days. The use of BB significantly decreases BFU-E and colony-forming unit erythroid cells at all time points. G-CSF is significantly elevated in both groups on admission; the use of BB decreases G-CSF levels by 51% as compared with 37% for controls. The average hemoglobin is nearly 1 g higher on the day of discharge with propranolol treatment (BB, 9.9 ± 0.4 g/dL vs. no BB, 9.1 ± 0.6 g/dL).
  
  
  CONCLUSIONS
  Following severe trauma, early treatment with propranolol following resuscitation is safe. The use of propranolol blunts early tachycardia, reduces HPC mobilization, and results in a faster return to baseline of the G-CSF peak seen after injury. There is also a trend toward faster recovery and resolution of anemia. Propranolol may be the first therapeutic agent to show improved BM function after severe injury.
  
  
  METHODS
  Therapeutic study, level III.
authors: From the Division of Trauma, Department of Surgery, Rutgers-New Jersey Medical School, Newark, New Jersey.
authors: Letitia E
authors: LE
authors: Bible
authors: Latha V
authors: LV
authors: Pasupuleti
authors: Walter D
authors: WD
authors: Alzate
authors: Amy V
authors: AV
authors: Gore
authors: Kim J
authors: KJ
authors: Song
authors: Ziad C
authors: ZC
authors: Sifri
authors: David H
authors: DH
authors: Livingston
authors: Alicia M
authors: AM
authors: Mohr
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D011433:Propranolol / Q000627:therapeutic use*; D011446:Prospective Studies; D014947:Wounds and Injuries / Q000503:physiopathology*
chemical_list: D011433:Propranolol