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). CONCLUSION 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. LEVEL OF EVIDENCE Therapeutic study, level III.

Effect of propranolol on capsular reaction around silicone implants in guinea pigs

“…The effect of propranolol in reducing capsular inflammation and thickness, and in modulating collagen deposition on textured implants observed in this experiment is consistent with findings from previous studies of others fibrosis conditions 19 , which showed that the application of nonselective beta-adrenoceptors antagonists inhibits maturation of collagen, reduces the number of vessels, collagen density, number of mast cells, eosinophils and myofibroblasts compared with control 22,23,25 .…”

“…Besides alteration of cellular activity related to inflammation, catecholamines stimulate vasoconstriction that causes hypoxia at the wound area and the increase of endothelial cell proliferation, vascular endothelial growth factor (VEGF) expression and angiogenesis. Also, catecholamines promote inhibition of eosinophil influx [23][24] .…”

“…Epinephrine or norepinephrine adrenoceptors, stress-released catecholamines,have been implicated in the pathophysiology of delayed wound healing of cutaneous lesions, acting by delaying the migration and activation of macrophages and neutrophils, inhibiting keratinocyte migration and re-epithelialization in vitro and in vivo wound models [22][23] . Besides alteration of cellular activity related to inflammation, catecholamines stimulate vasoconstriction that causes hypoxia at the wound area and the increase of endothelial cell proliferation, vascular endothelial growth factor (VEGF) expression and angiogenesis.…”

“…Recently was shown that early propranolol administration to severely injured patients can improve bone marrow dysfunction 23 . …”

Prospective evaluation of early propranolol after traumatic brain injury

“…We used a relatively low dose of propranolol in this study. Higher doses of propranolol may be indicated, as a recent study established that trauma patients could receive doses up to 2-mg IV early after admission depending on the HR [25]. Future studies should evaluate optimal propranolol dosing, and an American Association for the Surgery of Trauma multi-institutional study is forthcoming.…”