不同剂量甲泼尼龙治疗脓毒性休克失代偿期患儿的临床疗效及对下丘脑-垂体-肾上腺轴的影响
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摘要
目的:探讨不同应激剂量甲泼尼龙(MP)治疗脓毒性休克(SS)失代偿期患儿的临床疗效,分析其对下丘脑-垂体-肾上腺轴(HPA轴)的影响。方法:收集SS失代偿期研究对象81例,随机编入3个治疗组:(1) MP 20 mg·kg-1·d-1治疗组(大剂量组);(2) MP 5 mg·kg-1·d-1治疗组(中剂量组);(3) MP 2 mg·kg-1·d-1治疗组(小剂量组)。疗程均为1周减停。观察3组临床疗效、用药后副作用和转归,监测入院时、第3天、第8天的血清皮质醇、促肾上腺皮质激素(ACTH)变化,并与正常儿童组进行比较分析。结果:中、大剂量组在退热时间、休克纠正时间、血管活性药使用时间等指标上,较小剂量组有明显减少(P <0. 05);但3组死亡率无统计学差异(P> 0. 05)。在平均住院时间上,小、中剂量组较大剂量组显著缩短(P <0. 05);大剂量组的二重感染例数比小、中剂量组显著增多(P <0. 05);在最大血糖波动幅度(LAGE)上,中、大剂量组较小剂量组显著增大(P<0. 05)。入院时,3组的血清皮质醇、ACTH水平较正常儿童组显著升高,3组间差异无统计学意义(P> 0. 05),各组内死亡患儿的水平显著高于存活患儿(P <0. 05)。第3天,3组的血清皮质醇、ACTH均下降,以中、大剂量组的为甚,两组间差异无统计学意义,与小剂量组均有统计学差异(P <0. 05);各组内死亡患儿的水平显著低于存活患儿(P <0. 05)。第8天,3组存活患儿的血清皮质醇、ACTH水平与正常儿童组无统计学差异(P> 0. 05)。结论:SS失代偿期患儿应用小剂量的MP可抑制炎症、缩短平均住院日,有利于减少血糖波动幅度,平缓降低血清皮质醇、ACTH水平。血清皮质醇、ACTH水平过高或降低过快都提示死亡风险。
AIM:To investigate the therapeutic effects of different dosages of methylprednisolone(MP) on the children with septic shock(SS) in decompensation stage,and analyse the changes of hypothalamic-pituitary-adrenal(HPA) axis.METHODS:Eighty-one children with SS in decompensation stage were randomly divided into three groups according to the MP initial dosages:the high-dosage group(20 mg · kg-1· d-1),the middle-dosage group(5 mg·kg-1·d-1) and the low-dosage group(2 mg·kg-1·d-1).The MP dosages were reduced gradually after a week.The therapeutic effects of thethree groups were recorded.The serum cortisol,adrenocorticotropic hormone(ACTH) were analyzed on day 1,3,8 in hospital and compared with those of 27 healthy controls.RESULTS:The fever clearance time,SS correct time and the time of vasoactive drug used in the middle-dosage group and the high-dosage group were obviously decreased compared with the low-dosage group(P < 0.05).The mortality of the three groups were not statistically significant(P > 0.05).The length of stay in the low-dosage group and the middle-dosage group were statistically shorter than that in the high-dosage group(P < 0.05).The double infect in the highdosage group was statistically more than that in the middle-dosage group and the low-dosage group(P <0.05).Large amplitude of glycemic excursions(LAGE) of the high-dosage group and the middledosage group were obviously wider than that of the low-dosage group(P < 0.05).At the first day of admission,the three groups with SS in decompensation stage had statistical increase of serum cortisol and ACTH as compared with the healthy control group,but there were not significant differences among the three groups(P > 0.05),the serum cortisol and ACTH in the death children were significantly higher than the survival children in the three groups(P < 0.05).At the third day of admission,serum cortisol and ACTH in the middle-dosage group and the high-dosage group were obviously decreased as compared with those of the low-dosage group(P< 0.05),the serum cortisol and ACTH in the death children were significantly lower than the survival children in the three groups(P < 0.05).At the eighth day of admission,the serum cortisol and ACTH of the three groups were no statistical differences compared with those of the healthy control group(P > 0.05).CONCLUSION:The low-dosage of MP can be used to guide the therapy of children with SS in decompensation stage,which is conductive to control inflammation,shorten the length of stay,and reduce LAGE,decrease serum cortisol and ACTH slowly.High or rapid decreasing serum cortisol and ACTH levels are indicators of mortality risk.
AIM:To investigate the therapeutic effects of different dosages of methylprednisolone(MP) on the children with septic shock(SS) in decompensation stage,and analyse the changes of hypothalamic-pituitary-adrenal(HPA) axis.METHODS:Eighty-one children with SS in decompensation stage were randomly divided into three groups according to the MP initial dosages:the high-dosage group(20 mg · kg-1· d-1),the middle-dosage group(5 mg·kg-1·d-1) and the low-dosage group(2 mg·kg-1·d-1).The MP dosages were reduced gradually after a week.The therapeutic effects of thethree groups were recorded.The serum cortisol,adrenocorticotropic hormone(ACTH) were analyzed on day 1,3,8 in hospital and compared with those of 27 healthy controls.RESULTS:The fever clearance time,SS correct time and the time of vasoactive drug used in the middle-dosage group and the high-dosage group were obviously decreased compared with the low-dosage group(P < 0.05).The mortality of the three groups were not statistically significant(P > 0.05).The length of stay in the low-dosage group and the middle-dosage group were statistically shorter than that in the high-dosage group(P < 0.05).The double infect in the highdosage group was statistically more than that in the middle-dosage group and the low-dosage group(P <0.05).Large amplitude of glycemic excursions(LAGE) of the high-dosage group and the middledosage group were obviously wider than that of the low-dosage group(P < 0.05).At the first day of admission,the three groups with SS in decompensation stage had statistical increase of serum cortisol and ACTH as compared with the healthy control group,but there were not significant differences among the three groups(P > 0.05),the serum cortisol and ACTH in the death children were significantly higher than the survival children in the three groups(P < 0.05).At the third day of admission,serum cortisol and ACTH in the middle-dosage group and the high-dosage group were obviously decreased as compared with those of the low-dosage group(P< 0.05),the serum cortisol and ACTH in the death children were significantly lower than the survival children in the three groups(P < 0.05).At the eighth day of admission,the serum cortisol and ACTH of the three groups were no statistical differences compared with those of the healthy control group(P > 0.05).CONCLUSION:The low-dosage of MP can be used to guide the therapy of children with SS in decompensation stage,which is conductive to control inflammation,shorten the length of stay,and reduce LAGE,decrease serum cortisol and ACTH slowly.High or rapid decreasing serum cortisol and ACTH levels are indicators of mortality risk.
引文
[1]De Oliveira CF,Troster EJ,Carcillo JA,et al.Abeneficial role of central venous oxygen saturation-targeted septic shock management in children:Follow the pediatric story,not only the adult story[J].Pedia Crit Care Med,2014,15(4):380-382.
[2]张颖,袁杉,汪阳.脓毒性休克患者血清C-反应蛋白、降钙素原和NT-pro-BNP水平及预后意义[J].空军医学杂志,2018,34(1):52-56.
[3]张继燕,肖政辉.脓毒症相关性肾上腺功能障碍的发病机制[J].中国小儿急救医学,2015,22(11):791-794.
[4]Langer M,Modi BP,Agus M.Adrenal insufficiency in the critically ill neonate and child[J].Curr Opin Pedia,2006,18(4):448-453.
[5]Rhodes A,Evans LE,Alhazzani W,et al.Surviving sepsis campaign:international guidelines for management of sepsis and septic shock:2016[J].Inten Care Med,2017,43(3):304-377.
[6]中华医学会儿科学分会急救学组,中华医学会急诊医学分会儿科组.感染性休克(脓毒性休克)诊疗推荐方案[J].中国小儿急救医学,2006,13(4):313-315.
[7]崔娜,刘大为,王郝,等.严重感染患者下丘脑-垂体-靶腺轴功能的早期改变[J].中国危重病急救医学,2007,19(6):332-335.
[8]Annane D,Sebille V,Troche G,et al.A3-level prognostic classification in septic shock based on cortisol leve1s and cortisol response to corticotropin[J].JAMA,2000,283(8):1038-1045.
[9]Rivers B,Nguyen S,Havstad S,et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock[J].N Engl J Med,2001,345(19):1368-1377.
[10]Boonen E,Vervenne H,Meersseman P.Reduced cortisol metabolism during critical illness[J].N Engl J Med,2013,368(16):1477-1488.
[11]Yarema TC,Yost S.Low-dose corticosteroids to treat septic shock:a critical literature review[J].Crit Care Nurse,2011,31(6):16-26.
[12]Bornstein SR,Briegel J.A new role for glucocorticoids in septic shock:balancing the immune response[J].Am J Respir Crit Care Med,2003,167(4):485-486.
[13]Annane D,Bellissant E,Sebille V,et al.Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve[J].Br J Clin Pharmacol,1998,46(6):589-597.
[14]钱芳.糖皮质激素在临床中的应用[J].青岛医药卫生,2010,42(2):124-125.
[15]Govender Y,Avenant C,Verhoog NJ,et al.The injectab1e-on1y contraceptive medroxyprogesterone acetate,unlike norethisteronc acetate and progesterone,regulates inflammatory genes in endocervical ce11s via the g1ucocorticoid receptor[J].PLo S One,2014,9(5):e96497.
[16]Oppert M,Schindler R,Husung C,et al.Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock[J].Crit Care Med,2005,33(11):2457-2464.
[17]齐宇洁,樊寻梅,周涛,等.不同剂量氢化可的松对早期脓毒性休克大鼠下丘脑-垂体-肾上腺轴的影响[J].实用儿科临床杂志,2007,22(6):421-423.
[18]陈朝彦,罗佐杰,秦映芬,等.血糖变异度与重症监护病房患者预后的相关性[J].中国糖尿病杂志,2014,22(3):243-245.
[19]Sharshar T,Gray F,Lorin de la Grandmaison G,et al.Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock[J].Lancet,2003,362:1799-1805.
[2]张颖,袁杉,汪阳.脓毒性休克患者血清C-反应蛋白、降钙素原和NT-pro-BNP水平及预后意义[J].空军医学杂志,2018,34(1):52-56.
[3]张继燕,肖政辉.脓毒症相关性肾上腺功能障碍的发病机制[J].中国小儿急救医学,2015,22(11):791-794.
[4]Langer M,Modi BP,Agus M.Adrenal insufficiency in the critically ill neonate and child[J].Curr Opin Pedia,2006,18(4):448-453.
[5]Rhodes A,Evans LE,Alhazzani W,et al.Surviving sepsis campaign:international guidelines for management of sepsis and septic shock:2016[J].Inten Care Med,2017,43(3):304-377.
[6]中华医学会儿科学分会急救学组,中华医学会急诊医学分会儿科组.感染性休克(脓毒性休克)诊疗推荐方案[J].中国小儿急救医学,2006,13(4):313-315.
[7]崔娜,刘大为,王郝,等.严重感染患者下丘脑-垂体-靶腺轴功能的早期改变[J].中国危重病急救医学,2007,19(6):332-335.
[8]Annane D,Sebille V,Troche G,et al.A3-level prognostic classification in septic shock based on cortisol leve1s and cortisol response to corticotropin[J].JAMA,2000,283(8):1038-1045.
[9]Rivers B,Nguyen S,Havstad S,et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock[J].N Engl J Med,2001,345(19):1368-1377.
[10]Boonen E,Vervenne H,Meersseman P.Reduced cortisol metabolism during critical illness[J].N Engl J Med,2013,368(16):1477-1488.
[11]Yarema TC,Yost S.Low-dose corticosteroids to treat septic shock:a critical literature review[J].Crit Care Nurse,2011,31(6):16-26.
[12]Bornstein SR,Briegel J.A new role for glucocorticoids in septic shock:balancing the immune response[J].Am J Respir Crit Care Med,2003,167(4):485-486.
[13]Annane D,Bellissant E,Sebille V,et al.Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve[J].Br J Clin Pharmacol,1998,46(6):589-597.
[14]钱芳.糖皮质激素在临床中的应用[J].青岛医药卫生,2010,42(2):124-125.
[15]Govender Y,Avenant C,Verhoog NJ,et al.The injectab1e-on1y contraceptive medroxyprogesterone acetate,unlike norethisteronc acetate and progesterone,regulates inflammatory genes in endocervical ce11s via the g1ucocorticoid receptor[J].PLo S One,2014,9(5):e96497.
[16]Oppert M,Schindler R,Husung C,et al.Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock[J].Crit Care Med,2005,33(11):2457-2464.
[17]齐宇洁,樊寻梅,周涛,等.不同剂量氢化可的松对早期脓毒性休克大鼠下丘脑-垂体-肾上腺轴的影响[J].实用儿科临床杂志,2007,22(6):421-423.
[18]陈朝彦,罗佐杰,秦映芬,等.血糖变异度与重症监护病房患者预后的相关性[J].中国糖尿病杂志,2014,22(3):243-245.
[19]Sharshar T,Gray F,Lorin de la Grandmaison G,et al.Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock[J].Lancet,2003,362:1799-1805.