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重组人生长激素与普萘洛尔联合使用可降低重度烧伤儿童的高代谢和炎症反应。

Combination of recombinant human growth hormone and propranolol decreases hypermetabolism and inflammation in severely burned children.

作者信息

Jeschke Marc G, Finnerty Celeste C, Kulp Gabriela A, Przkora Rene, Mlcak Ronald P, Herndon David N

机构信息

Shriners Hospitals for Children and the Department of Surgery, University Texas Medical Branch, Galveston, TX, USA.

出版信息

Pediatr Crit Care Med. 2008 Mar;9(2):209-16. doi: 10.1097/PCC.0b013e318166d414.

Abstract

OBJECTIVE

Recombinant human growth hormone (rhGH) is a salutary modulator of posttraumatic metabolic responses. However, rhGH administration is associated with deleterious side effects, such as hyperglycemia, increased free fatty acids, and triglycerides, which limit its use. Administration of beta-blocker attenuates cardiac work and resting energy expenditure after severe thermal injury and improves fat metabolism and insulin sensitivity. Therefore, the combination of rhGH plus propranolol appears ideal. The aim of the present study was to determine whether rhGH plus propranolol improves hypermetabolism and the inflammatory and acute phase response after severe burn without causing adverse side effects.

DESIGN

Prospective randomized control trial.

SETTING

Shriners Hospitals for Children.

PATIENTS

Fifteen pediatric patients with burns > 40% total body surface area, 0.1-16 yrs of age, admitted within 7 days after burn. Fifteen children were matched for burn size, age, gender, inhalation injury, and infection and served as controls.

INTERVENTIONS

Patients in the experimental group received rhGH (0.2 mg/kg/day) and propranolol (to decrease heart rate by 15%) for > or = 15 days.

MEASUREMENTS AND MAIN RESULTS

Outcome measurements included resting energy expenditure, body composition, acute phase proteins, and cytokines. Both cohorts were similar in age, burn size, gender, and accompanying injuries. Percent predicted resting energy expenditure significantly decreased in patients receiving rhGH/propranolol (Delta -5% +/- 8%) compared with controls (Delta +35% +/- 20%) (p < .05). rhGH/propranolol administration significantly decreased serum C-reactive protein, cortisone, aspartate aminotransferase, alanine aminotransferase, free fatty acids, interleukin-6, interleukin-8, and macrophage inflammatory protein-1beta when compared with controls, while growth hormone/propranolol increased serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, growth hormone, prealbumin, and interleukin-7 when compared with placebo (p < .05).

CONCLUSIONS

rhGH in combination with propranolol attenuates hypermetabolism and inflammation without the adverse side effects found with rhGH therapy alone.

摘要

目的

重组人生长激素(rhGH)是创伤后代谢反应的有益调节剂。然而,使用rhGH会伴有有害的副作用,如高血糖、游离脂肪酸增加和甘油三酯升高,这限制了其应用。β受体阻滞剂的使用可减轻严重热损伤后的心脏做功和静息能量消耗,并改善脂肪代谢和胰岛素敏感性。因此,rhGH与普萘洛尔联合使用似乎较为理想。本研究的目的是确定rhGH加普萘洛尔能否改善严重烧伤后的高代谢以及炎症和急性期反应,且不引起不良副作用。

设计

前瞻性随机对照试验。

地点

施莱宁儿童医院。

患者

15名烧伤面积超过体表面积40%、年龄在0.1至16岁之间、烧伤后7天内入院的儿科患者。另外15名儿童在烧伤面积、年龄、性别、吸入性损伤和感染方面与之匹配,作为对照组。

干预措施

实验组患者接受rhGH(0.2毫克/千克/天)和普萘洛尔(使心率降低15%),持续≥15天。

测量指标及主要结果

测量指标包括静息能量消耗、身体成分、急性期蛋白和细胞因子。两组在年龄、烧伤面积、性别和伴随损伤方面相似。与对照组(变化+35%±20%)相比,接受rhGH/普萘洛尔治疗的患者预计静息能量消耗百分比显著降低(变化-5%±8%)(p<0.05)。与对照组相比,rhGH/普萘洛尔治疗显著降低了血清C反应蛋白、皮质醇、天冬氨酸转氨酶、丙氨酸转氨酶、游离脂肪酸、白细胞介素-6、白细胞介素-8和巨噬细胞炎性蛋白-1β,而与安慰剂相比,生长激素/普萘洛尔增加了血清胰岛素样生长因子-I、胰岛素样生长因子结合蛋白-3、生长激素、前白蛋白和白细胞介素-7(p< .05)。

结论

rhGH与普萘洛尔联合使用可减轻高代谢和炎症,且无单独使用rhGH治疗时出现的不良副作用。

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