莫麗慧，鐘麗花

(海南省婦幼保健院，海南 ?？?570206

米力農(nóng)治療嬰幼兒重癥肺炎合并心力衰竭的臨床療效分析

莫麗慧，鐘麗花

(海南省婦幼保健院，海南 ?？?570206

目的 觀察米力農(nóng)治療嬰幼兒重癥肺炎合并心力衰竭的臨床療效。方法 選擇2013年1月至2015年12月在海南省婦幼保健院就診的120例重癥肺炎合并心力衰竭患兒，隨機(jī)分為試驗(yàn)組80例和對照組40例，兩組均給予常規(guī)治療，在此基礎(chǔ)上試驗(yàn)組給予米力農(nóng)靜脈滴注，對照組給予多巴胺及多巴酚丁胺靜脈滴注，均24h持續(xù)給藥3d，觀察兩組臨床癥狀及體征改善所需時(shí)間、心功能及血流動力學(xué)變化情況。結(jié)果 試驗(yàn)組和對照組總有效率為95.00%和75.00%，組間比較差異有統(tǒng)計(jì)學(xué)意義(χ2=10.379,P<0.05)，試驗(yàn)組精神癥狀好轉(zhuǎn)時(shí)間、心率正常時(shí)間、濕啰音消失時(shí)間、肝臟回縮時(shí)間、氧飽和度改善時(shí)間短于對照組，差異均有統(tǒng)計(jì)學(xué)意義(t值分別為5.362、4.231、4.813、3.977、5.264、4.753，均P<0.05)。試驗(yàn)組治療后左室射血分?jǐn)?shù)(LVEF)、左室短軸(LVSF)、左室收縮末徑(LVSD)、左室舒張末徑(LVDD)、房室瓣EA峰比值(E/A)、左室心臟指數(shù)(LV-CI)和右室心臟指數(shù)(RV-CI)均較治療前均有改善(t值分別為4.558、5.196、4.973、8.114、6.063、7.064、6.128，均P<0.05)；而對照組僅LVEF、LVSF、LVDD較治療前均有改善(t值分別為6.031、7.224、4.097，均P<0.05)。以治療前檢查結(jié)果為協(xié)變量，療后組間協(xié)方差分析表明試驗(yàn)組心功能指標(biāo)LVEF、LVSF、LVSD、LVDD、E/A、LV-CI和RV-CI等改善情況均優(yōu)于對照組，差異有統(tǒng)計(jì)學(xué)意義(F=3.831、5.618、4.052、5.531、5.203、4.076、6.317，均P<0.05)。試驗(yàn)組有1例出現(xiàn)收縮壓下降最低值到85mmHg，減慢輸注速度后癥狀緩解；對照組1例呼吸急促，最高頻率達(dá)25次/min，吸氧后消失；兩組不良反應(yīng)發(fā)生率分別為1.25%(1/80)和2.50%(1/40)，組間比較差異無統(tǒng)計(jì)學(xué)意義(χ2=0.883，P=0.687)。結(jié)論 米力農(nóng)治療嬰幼兒重癥肺炎合并心力衰竭療效顯著，為嬰幼兒重癥肺炎合并心力衰竭的治療提供了一條極有效的途徑。

重癥肺炎；心力衰竭；嬰幼兒；米力農(nóng)

小兒重癥肺炎是引起兒童死亡的主要原因之一，據(jù)統(tǒng)計(jì)，我國每年約有30萬嬰幼兒死于肺炎，為5歲以下兒童死亡的首要原因[1]。正性肌力藥物兼有擴(kuò)張外周血管和改善心室舒張功能的效應(yīng)，能克服傳統(tǒng)藥物使用中心率加快、心肌耗氧量增高、β-受體下調(diào)導(dǎo)致藥效降低等缺點(diǎn)而在臨床廣泛應(yīng)用[2]。目前最常用的藥物是米力農(nóng)，部分研究已經(jīng)證實(shí)米力農(nóng)在重癥肺炎合并心力衰竭患兒的臨床療效[3]，但相關(guān)研究樣本量偏少，而且評價(jià)方法多為主觀性指標(biāo)，證據(jù)力度較低。為進(jìn)一步評價(jià)米力農(nóng)靜脈滴注對嬰幼兒重癥肺炎合并心力衰竭的治療效果，本研究納入部分患兒進(jìn)行對比分析，現(xiàn)報(bào)道如下。

1資料和方法

1.1一般資料

以2013年1月至2015年12月在海南省婦幼保健院兒科病房收治的重癥肺炎合并心力衰竭患兒例為研究對象，除外先天性心臟病、心律失常、擴(kuò)張性心肌病等引起的心力衰竭。符合入選標(biāo)準(zhǔn)的患兒120例，按2:1的比例隨機(jī)分為試驗(yàn)組80例和對照組40例。

1.2治療方法

兩組患兒均給予常規(guī)基礎(chǔ)治療(吸氧、鎮(zhèn)靜、抗感染等)，試驗(yàn)組米力農(nóng)的具體用法是：首先給予負(fù)荷量分鐘緩慢靜注，以后0.5μg·kg-1·min-1維持至24h；對照組使用多巴胺聯(lián)合多巴酚丁胺3～5μg·kg-1·min-1，兩組均連用3d或各項(xiàng)指標(biāo)得到改善時(shí)停用[4]。

1.3評價(jià)指標(biāo)

①療效評價(jià)，治愈：臨床癥狀及體征消失，實(shí)驗(yàn)室檢測恢復(fù)正常；顯效：臨床癥狀及體征明顯好轉(zhuǎn)實(shí)驗(yàn)室檢測基本恢復(fù)正常；無效：病情無變化或加重；②臨床癥狀及體征，包括患兒的精神癥狀、心率、呼吸頻率、肺部濕啰音消失時(shí)間和肝臟回縮(右肋緣下≤2cm)時(shí)間；③心功能指標(biāo)，應(yīng)用彩色多普勒超聲心動圖對患兒用藥前及用藥后的進(jìn)行檢測，測量指標(biāo)包括左室舒張末徑(left ventricular end-diastolic diameter, LVDD)、左室收縮末徑(left ventricular end-systolicdiameter, LVSD)、左室短軸縮短率(left ventricular shortening fraction, LVSF)、 左 室 射 血 分 數(shù) (left ventricular ejection fraction, LVEF) 、房 室 瓣 EA峰 比 值(Atrioventricular valve EA peak ratios, E/A) 左室心臟指數(shù)(LV-CI)、右室心臟指數(shù)(RV-CI)。

1.4統(tǒng)計(jì)學(xué)方法

以SPSS 19.0軟件進(jìn)行數(shù)據(jù)分析，計(jì)量資料以均值±標(biāo)準(zhǔn)差描述，組間比較采用獨(dú)立樣本t檢驗(yàn)，計(jì)數(shù)資料以百分率描述，組間比較采用χ2檢驗(yàn)；心功能比較以治療前為協(xié)變量，療后數(shù)據(jù)進(jìn)行協(xié)方差分析，以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2結(jié)果

2.1一般情況

兩組年齡、性別、病程、心功能等資料組間比較差異均無統(tǒng)計(jì)學(xué)意義(均P>0.05)，見表1。

兩組患兒均順利接受治療，期間無一例出現(xiàn)心源性休克、惡性心律失常和死亡。兩組治療有效率分別為95.00%和75.00%，組間比較差異有統(tǒng)計(jì)學(xué)意義(χ2=10.379，P<0.05)，見表2。

2.2臨床癥狀及體征療效比較

試驗(yàn)組精神癥狀好轉(zhuǎn)時(shí)間、心率正常時(shí)間、濕啰音消失時(shí)間、肝臟回縮時(shí)間、氧飽和度改善時(shí)間(停止吸氧時(shí)間)均少于對照組，組間比較差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05)，見表3。

項(xiàng)目試驗(yàn)組(n=80)對照組(n=40)t/χ2P年齡(月)16.32±3.3118.26±3.842.9670.082體重(kg)5.29±0.386.64±0.511.8290.296性別(男/女)46/3418/221.6720.354病程(d)3(2～5)4(3～5)1.1630.371心功能LVEF(%)52.21±4.5851.88±4.251.0170.582LVSF(%)27.94±3.4127.95±3.490.7930.661LVDD(mm)31.79±4.6132.06±4.501.3030.449LVSD(mm)39.28±4.1438.65±4.821.0060.431E/A(HV)0.83±0.150.81±0.181.0430.506LV-CI[L·min-1·(m2)-1]7.23±2.486.84±1.710.7840.661RV-CI[L·min-1·(m2)-1]17.08±4.2716.63±5.111.8270.249

表2 兩組治療效果比較(n)
Table2Comparisonoftreatmenteffectbetweentwogroups(n)

組別治愈顯效無效總有效率(%)試驗(yàn)組4729495.00對照組18121075.00

項(xiàng)目試驗(yàn)組(n=80)對照組(n=40)tP精神癥狀好轉(zhuǎn)時(shí)間2.41±2.063.98±1.845.3620.017心率正常時(shí)間5.91±2.936.17±2.244.2310.044呼吸正常時(shí)間4.43±3.315.80±3.724.8130.040濕啰音消失時(shí)間7.24±2.278.82±3.383.9770.048肝臟回縮時(shí)間6.82±1.757.71±2.055.2640.004氧飽和度改善時(shí)間3.42±1.384.05±1.674.7530.012

2.3心功能指標(biāo)變化

試驗(yàn)組治療后LVEF、LVSF、LVSD、LVDD、E/A、LV-CI和RV-CI較治療前均好轉(zhuǎn)(t值分別為4.558、5.196、4.973、8.114、6.063、7.064、6.128，均P<0.05)，而對照組僅LVEF、LVSF、LVDD較治療前改善(t值分別為6.031、7.224、4.097，均P<0.05)；以治療前檢查結(jié)果為協(xié)變量，療后組間協(xié)方差分析表明試驗(yàn)組心功能指標(biāo)改善情況均優(yōu)于對照組，差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05)，見表4。

項(xiàng)目試驗(yàn)組(n=80)對照組(n=40)FPLVEF(%)56.32±4.17★55.64±5.24★3.8310.042LVSF(%)36.63±5.30★33.25±4.18★5.6180.247LVDD(mm)39.31±4.48★36.09±3.84★4.0520.037LVSD(mm)37.34±5.51★35.71±4.485.5310.024E/A(HV)1.32±0.15★0.96±0.125.2030.017LV-CI[L·min-1·(m2)-1]8.41±3.04★7.43±2.884.0760.038RV-CI[L·min-1·(m2)-1]18.46±3.88★16.97±2.246.3170.007

注：★與治療前相比，P<0.05。

2.4不良反應(yīng)

兩組患兒用藥后均未出現(xiàn)血小板減少、嚴(yán)重心律失常等不良反應(yīng)，肝、腎功能和心電圖也無異常改變，試驗(yàn)組有1例出現(xiàn)收縮壓下降最低值到85mmHg，減慢輸注速度后癥狀緩解，對照組1例呼吸急促，最高頻率達(dá)35次/min，吸氧后消失，兩組不良反應(yīng)發(fā)生率分別為1.25%(1/80)和2.50%(1/40)，組間比較差異無統(tǒng)計(jì)學(xué)意義(χ2=0.883，P=0.687)。

3討論

3.1重癥肺炎合并心力衰竭的病理機(jī)制

心力衰竭是指由于心功能減退超越代償能力，以致不能泵出足夠的氧合血滿足全身組織代謝需要的一種臨床綜合癥[5]。如果心力衰竭不能夠在第一時(shí)間做出正確的診斷和及時(shí)的救治，極短時(shí)間內(nèi)就可進(jìn)展為心源性休克，最終導(dǎo)致機(jī)體各個臟器功能的衰竭，危及患兒生命。心力衰竭是兒科常見急癥之一，嬰幼兒期較兒童期更多見，其中肺炎是嬰幼兒時(shí)期發(fā)生急性心力衰竭的常見原因。如果肺炎合并心力衰竭，即可將其劃入重癥肺炎范疇，預(yù)后的危險(xiǎn)性較普通肺炎明顯增加[6]。

嬰幼兒重癥肺炎合并心力衰竭的機(jī)制目前尚未完全明確，學(xué)界認(rèn)為除病原體的直接侵襲損害外，更重要的原因是病原體及其產(chǎn)生的蛋白質(zhì)或脂質(zhì)產(chǎn)物啟動了自身免疫系統(tǒng)調(diào)控的一系列生物連鎖反應(yīng)，可能涉及補(bǔ)體系統(tǒng)、炎癥因子釋放和凝血系統(tǒng)的激活，病理表現(xiàn)主要有微循環(huán)障礙和微血栓形成[7]。肺部炎癥導(dǎo)致機(jī)體通氣和換氣過程產(chǎn)生障礙，持續(xù)的低氧血癥和高碳酸血癥使機(jī)體出現(xiàn)酸中毒，進(jìn)而干擾血管平滑肌細(xì)胞膜上鈉、鉀離子的轉(zhuǎn)運(yùn)，使肺小動脈發(fā)生痙攣，肺動脈壓力的升高，進(jìn)一步導(dǎo)致右心血液回流障礙，體循環(huán)游血、心輸出量下降最終導(dǎo)致心力衰竭[8]?；純褐饕呐R床表現(xiàn)除有較明顯得紫紺、鼻翼扇動、呼吸困難、三凹征、煩躁、肺濕啰音外，更主要表現(xiàn)為心率增加，呼吸增快，肝腫大右助下或者進(jìn)行性增大。

3.2重癥肺炎合并心力衰竭的治療現(xiàn)況

對于嬰幼兒重癥肺炎合并心力衰竭的治療，多數(shù)學(xué)者主張?jiān)诳垢腥?、吸氧、?zhèn)靜的基礎(chǔ)上抗心力衰竭治療。米力農(nóng)屬于第二代磷酸二酯酶抑制劑，由受體旁道途徑起效，通過選擇性增加細(xì)胞內(nèi)環(huán)磷酸腺苷的含量，促進(jìn)鈣離子內(nèi)流，使心肌細(xì)胞質(zhì)的鈣離子濃度增高，從而發(fā)揮具有正性肌力作用，增加心肌排血量[9]。米力農(nóng)半衰期短，80%的藥物在24h后經(jīng)腎臟以原型排出，停藥后2h血流動力學(xué)和心功能指標(biāo)恢即可復(fù)至用藥前水平，因此適合嬰幼兒使用。它的不良反應(yīng)包括頭痛、低血壓、室性心律失常、肢體無力、血小板計(jì)數(shù)減少等，從而限制了其在兒科臨床中的使用，但也有學(xué)者認(rèn)為嬰幼兒極少發(fā)生不良反應(yīng)[10-11]，本研究結(jié)果再次表明，米力農(nóng)并不會增加不良反應(yīng)發(fā)生率，安全性與多巴胺和多巴酚丁胺同樣可靠。

綜上所述，米力農(nóng)靜脈給藥能有效治療重癥肺炎合并心力衰竭，不良反應(yīng)輕微，為嬰幼兒重癥肺炎合并心力衰竭的治療提供了一條極有效的途徑。

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[專業(yè)責(zé)任編輯：侯 偉]

Clinical efficacy of milrinone on infants with severe pneumonia combined with heart failure

MO Li-hui, ZHONG Li-hua

(Hainan Maternal and Child Health Care Hospital, Hainan Haikou 570206, China)

Objective To evaluate the efficacy of milrinone on infants with severe pneumonia combined with heart failure. Methods Altogether 120 infants suffering from severe pneumonia combined with heart failure visiting Hainan Maternal and Child Health Care Hospital from January 2013 to December 2015 were selected and randomly divided into experimental group (n=80) and control group (n=40). Both groups were given conventional treatment, and on this basis experimental group was given milrinone intravenous infusion and control group

dopamine and dobutamine intravenous infusion. Both were administrated continuously for 24h with duration of 3 days. Time for clinical symptom and sign improvement, heart function and hemodynamic changes in two groups were observed. Results Total effective rates in experimental group and control group were 95.00% and 75.00%, respectively, and difference between groups was statistically significant (χ2=10.379,P<0.05). Time for psychiatric symptom improvement, heart rate becoming normal, wet rales disappear, liver retraction, oxygen saturation improvement in experimental group were shorter than those in control group, and differences were statistically significant (tvalue was 5.362, 4.231, 4.813, 3.977, 5.264 and 4.753, respectively, allP<0.05). Left ventricular ejection fraction (LVEF), left ventricular short axis (LVSA), left ventricular end systolic diameter (LVSD), left ventricular end diastolic diameter (LVDD), atrioventricular valve EA peak ratio (E/A), cardiac index of left ventricular (LV-CI), cardiac index of right ventricular (RV-CI) in experimental group were all improved after treatment (tvalue was 4.558, 5.196, 4.973, 8.114, 6.063, 7.064 and 6.128, respectively, allP<0.05), while only LVEF, LVSA and LVDD were improved after treatment in control group (tvalue was 6.031, 7.224 and 4.097, respectively, allP<0.05). Taken examine results before treatment as covariant component, inter group covariance analysis after treatment showed that cardiac function indexes including LVEF, LVSA, LVSD, LVDD, E/A, LV-CI and RV-CI in experimental group were improved better than those in control group with statistical significance (Fvalue was 3.831, 5.618, 4.052, 5.531, 5.203, 4.076 and 6.317, respectively, allP<0.05). One patient in experimental group complained of decrease of systolic blood pressure to lowest value of 85mmHg with symptom relieved after slower infusion. One patient in control group complained of polypnea, with highest respiratory rate reaching 25 times per min and symptom disappeared after oxygen inhalation. Adverse reaction rates in two groups were 1.25% (1/80) and 2.50% (1/40), respectively, and difference had no statistical significance (χ2=0.883,P=0.687). Conclusion Milrinone has significant effect in treating infants with severe pneumonia combined with heart failure. It provides effective way for treatment of patients with neonatal severe pneumonia combined with heart failure.

severe pneumonia; heart failure; infants; milrinone

2016-06-23

莫麗慧(1967-)，女，主管藥師，主要從事臨床藥學(xué)研究工作。

鐘麗花，副主任醫(yī)師。

10.3969/j.issn.1673-5293.2017.07.022

R725.6

A

1673-5293(2017)07-0820-03