早期给予严重创伤患者普萘洛尔可改善骨髓功能障碍。
Early propranolol administration to severely injured patients can improve bone marrow dysfunction.
机构信息
From the Division of Trauma, Department of Surgery, Rutgers-New Jersey Medical School, Newark, New Jersey.
出版信息
J Trauma Acute Care Surg. 2014 Jul;77(1):54-60; discussion 59-60. doi: 10.1097/TA.0000000000000264.
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.
背景
骨髓（BM）功能障碍在严重创伤患者中很常见，这是由于儿茶酚胺和血浆粒细胞集落刺激因子（G-CSF）升高以及造血祖细胞（HPC）的长期动员所致。我们之前已经表明，普萘洛尔（β受体阻滞剂[BB]）可减少啮齿动物创伤和失血性休克模型中的 HPC 动员。我们假设 BB 会防止严重创伤后人体的 BM 功能障碍。
方法
在一项前瞻性、随机试验中研究了 45 名严重创伤的患者。25 名患者接受了 BB 治疗，20 名患者作为未治疗的对照组。普萘洛尔的剂量调整为使心率从基线降低 10%至 20%。分析血液中 HPC（红系爆式形成单位细胞[BFU-E]和红系集落形成单位细胞）和 G-CSF 的存在。获得人口统计学数据、损伤严重程度评分（ISS）、血红蛋白、网织红细胞计数和结果数据。
结果
研究人群的平均年龄为 33 岁；87%为男性，平均 ISS 为 29。创伤后外周血中 BFU-E 立即显著增加，这种动员持续 30 天。BB 的使用在所有时间点均显著减少 BFU-E 和红系集落形成单位细胞。两组入院时 G-CSF 均显著升高；与对照组的 37%相比，BB 降低 G-CSF 水平 51%。接受普萘洛尔治疗的患者在出院当天的平均血红蛋白水平高出 1g（BB，9.9±0.4g/dL 与无 BB，9.1±0.6g/dL）。
结论
在严重创伤后，复苏后早期使用普萘洛尔进行治疗是安全的。普萘洛尔的使用可减轻早期心动过速，减少 HPC 动员，并导致损伤后 G-CSF 峰值更快恢复至基线。贫血的恢复和缓解也呈上升趋势。普萘洛尔可能是第一个显示严重创伤后骨髓功能改善的治疗药物。
证据水平
治疗性研究，III 级。
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