朱妍,伍力學,林兆奮
右美托咪啶在不同年齡機械通氣患者鎮(zhèn)靜中的應用效果
朱妍,伍力學,林兆奮
目的探討右美托咪啶對不同年齡段重癥監(jiān)護室(ICU)機械通氣患者的鎮(zhèn)靜有效性和安全性。方法選擇不同年齡段[25~50歲(A組)、51~80歲(B組)]入住ICU的機械通氣患者各157例。給予右美托咪啶直至獲得目標鎮(zhèn)靜(Ramsay評分3~4分)。期間連續(xù)監(jiān)測無創(chuàng)血壓(SBP、DBP、MAP)、心率(HR)、氧飽和度(SpO2)、呼吸頻率(RR)和吸入氧濃度(FiO2)變化,于用藥前(T1)及用藥后10min(T2)、30min(T3)、120min(T4)、拔管時(T5)、拔管后30min(T6)記錄上述各參數(shù)。觀察并記錄用藥后不良反應(高血壓、低血壓、心動過速、心動過緩及譫妄等)的發(fā)生情況。結果A、B兩組患者使用右美托咪啶后SBP、DBP、MAP、HR均降低(P<0.05),以B組下降更為明顯,但仍維持于可接受范圍(MAP >80mmHg,HR>60次/min);兩組RR均減低(P<0.05),但FiO2未受影響(P>0.05);SpO2始終未降低,使用右美托咪啶30min后甚至較前上升(P<0.05)。兩組拔管前后血壓、SpO2、RR穩(wěn)定(P>0.05),B組患者HR稍減慢(P<0.05);B組發(fā)生不良反應的概率明顯高于A組(P<0.05)。結論右美托咪啶用于不同年齡組機械通氣及拔管患者均無明顯呼吸抑制,血流動力學穩(wěn)定,是理想的鎮(zhèn)靜藥物選擇。但對于年老患者使用時需加強監(jiān)護,尤其早期使用負荷劑量時,應防止低血壓及心動過緩等不良反應的發(fā)生并及時處理。
右美托咪啶;呼吸,人工;重癥監(jiān)護病房;深度鎮(zhèn)靜
鎮(zhèn)靜鎮(zhèn)痛是重癥監(jiān)護病房尤其是機械通氣(MV)患者的基本治療措施,理想和適度的鎮(zhèn)靜鎮(zhèn)痛可減輕患者的應激反應,縮短機械通氣和住ICU時間,而不恰當?shù)逆?zhèn)靜鎮(zhèn)痛卻適得其反。理想的鎮(zhèn)靜鎮(zhèn)痛藥物在提供充分鎮(zhèn)靜和鎮(zhèn)痛的同時,還應具有起效快、停藥后恢復快、體內蓄積和不良反應少等優(yōu)點。右美托咪啶是一種非阿片類、非苯二氮類的新型α2受體激動劑,已廣泛應用于ICU的鎮(zhèn)痛鎮(zhèn)靜治療[1-2]。本研究擬通過對右美托咪啶在不同年齡段重癥監(jiān)護病房機械通氣患者的鎮(zhèn)靜作用及相關不良反應的比較,評價其鎮(zhèn)靜效果及安全性。
1.1 一般資料 上海8個三級醫(yī)院綜合ICU 2012年7月-2013年5月接受機械通氣治療的成年患者314例,男164例,女150例,年齡56.5±26.7歲,體重63.1±19.8kg,身高166.0±15.8cm,既往無精神疾病史及長期使用鎮(zhèn)靜鎮(zhèn)痛藥物史。其中術后患者142例,外傷52例,重癥肺炎64例,心肺復蘇后45例,急性重癥胰腺炎8例,急性丙烯酰胺中毒1例,重度燒傷1例,感染性心內膜炎1例。
1.2 入選及排除標準 入選標準:年齡25~80歲,體重波動程度<標準體重的15%。排除標準:左心室射血分數(shù)<0.30,房室傳導阻滯,嚴重的心動過緩、心律失常,合并嚴重并發(fā)癥(如胰島素依賴型糖尿病),肝衰竭,腎衰竭,妊娠和哺乳期婦女。本研究符合醫(yī)學倫理學標準,并經(jīng)醫(yī)院倫理委員會批準,所有治療均獲得患者或家屬的知情同意。
1.3 分組及治療方法 根據(jù)年齡將納入患者分成A組(25~50歲,共157例)及B組(51~80歲,共157例)。兩組性別、體重、身高等一般資料比較差異無統(tǒng)計學意義(P>0.05),具有可比性。隨機將A、B兩組中各46例患者列入脫機拔管觀察。機械通氣患者入住ICU后,給予鹽酸右美托咪啶[200ml(200μg)/支,江蘇恒瑞醫(yī)藥股份有限公司]負荷量0.5μg/kg,靜脈泵注20min,根據(jù)不同鎮(zhèn)靜程度維持劑量為0.2~0.7μg/(kg.h)。依據(jù)RASS鎮(zhèn)靜評估結果調整藥物劑量,維持恰當?shù)逆?zhèn)靜深度,直至獲得滿意的目標鎮(zhèn)靜(Ramsay評分3~4 分)。每日上午停止泵入所有鎮(zhèn)靜、鎮(zhèn)痛藥,至完全喚醒后進行疼痛視覺模擬評分(VAS評分)。同時采用自主呼吸試驗(SBT)進行脫機篩查,觀察患者自主呼吸參數(shù),評價脫機指數(shù),達到脫機條件者脫離呼吸機,不能脫機者繼續(xù)予鎮(zhèn)靜鎮(zhèn)痛治療。撤機標準:引起本次呼衰的病因已被控制或去除;在吸入氧濃度(FiO2)≤0.4、吸氣末正壓(PEEP)≤5cmH2O(1cmH2O=0.098kPa)的支持水平下,PaO2>60mmHg;潮氣量>5ml/kg,呼吸頻率(RR)<35次/min,每分通氣量(MV)<10L/min,脈搏氧飽和度(SpO2)>0.90;血流動力學穩(wěn)定,血壓、心率等正常;停用血管活性藥和鎮(zhèn)靜藥。撤機成功標準:撤機48h內患者主觀感覺舒適,循環(huán)穩(wěn)定,血氣分析顯示無呼吸性酸中毒,不需再插管。撤機失敗標準:在自主呼吸試驗中出現(xiàn)明顯胸悶、出汗和發(fā)紺,心率(HR)增快>20次/min或RR>35次/ min或血壓升高>20mmHg;血氣分析顯示PCO2上升>10mmHg,48h內需再插管。
1.4 觀察指標 期間以HP多功能監(jiān)測系統(tǒng)連續(xù)監(jiān)測無創(chuàng)血壓、HR、SpO2、RR及FiO2變化,分別于用藥前(T1)及用藥后10min(T2)、30min(T3)、120min(T4)、拔管時(T5)、拔管后30min(T6)記錄上述各參數(shù)。
1.5 統(tǒng)計學處理 采用SPSS 11.5軟件進行統(tǒng)計分析。計量資料以表示,組間比較采用獨立樣本及配對t檢驗,計數(shù)資料以率表示,組間比較采用χ2檢驗。P<0.05為差異有統(tǒng)計學意義。
2.1 應用右美托咪啶后兩組循環(huán)及呼吸指標比較應用右美托咪啶后兩組患者SBP、DBP、平均動脈壓(MAP)、HR均降低(P<0.05),其中僅2例MAP<60mmHg,其余均維持于可接受范圍(MAP>65mmHg,HR>60次/min);用藥前A組SBP明顯低于B組(P<0.05),但MAP及HR差異無統(tǒng)計學意義(P>0.05),用藥120min后A組MAP及HR明顯高于B 組(P<0.05)。應用右美托咪啶后兩組患者RR均減低(P<0.05),但在正常范圍,且不影響FiO2(P>0.05);A組RR始終快于B組(P<0.05),但兩組間SpO2差異無統(tǒng)計學意義(P>0.05)。A組FiO2始終低于B組。SpO2始終未降低,應用右美托咪啶后30min甚至較前上升(P<0.05,表1)。
2.2 拔管前后兩組循環(huán)及呼吸指標比較 將右美托咪啶用于機械通氣患者拔管時鎮(zhèn)靜,A組患者拔管前后SBP、DBP、MAP、HR、SpO2、RR之間均無明顯差異(P>0.05),B組患者拔管后SBP和DBP升高、HR減慢,與拔管前比較差異有統(tǒng)計學意義(P<0.05)。與A組比較,B組SBP、DBP明顯升高,HR明顯降低,差異有統(tǒng)計學意義(P<0.05,表2)。
2.3 兩組不良反應發(fā)生率比較 B組高血壓、低血壓、心動過速、心動過緩、低血壓+心動過速、低血壓+心動過緩、高血壓+心動過緩、高血壓+心動過速、譫妄等藥物不良反應發(fā)生率分別為8.3%(13/157)、15.9%(25/157)、5.7%(9/157)、7.0%(11/157)、1.9%(3/157)、3.2%(5/157)、0.6%(1/157)、4.5%(7/157)、7.0%(11/157),均明顯高于A組[分別為0.6%(1/157)、3.2%(5/157)、0(0/157)、1.3%(2/157)、0(0/157)、0(0/157)、0(0/157)、0(0/157)、0(0/157)],差異有統(tǒng)計學意義(P<0.05)。
表1 右美托咪啶對兩組機械通氣患者循環(huán)及呼吸指標的影響(±s,n=157)Tab.1 Effect of dexmedetomidine on each indicator of mechanically ventilated patients between two groups (±s,n=157)
表1 右美托咪啶對兩組機械通氣患者循環(huán)及呼吸指標的影響(±s,n=157)Tab.1 Effect of dexmedetomidine on each indicator of mechanically ventilated patients between two groups (±s,n=157)
SBP. Systolic blood pressure; DBP. Diastolic blood pressure; MAP. Mean artery pressure; HR. Heart rate; SO2. Oxygen saturation; RR. Respiratory rate; FiO2. Fraction of inspiration oxygen. (1)P<0.05 compared with T1; (2)P<0.05 compared with T4; (3)P<0.05 compared with group B
Time point SBP(mmHg) DBP(mmHg) MAP(mmHg) HR(/min) SO2(%) RR(/min) FiO2(%) T1 Group A 130.1±16.8(3) 83.1±13.2 97.6±13.7 116.6±25.1 97.3±2.7 25.6±6.6(3) 43.6±10.3(2)(3)Group B 142.4±16.8 82.4±15.3 98.7±17.5 114.0±26.3 97.2±4.0 22.3±6.8(2) 45.1±11.5 T2 Group A 126.9±16.1(1) 81.5±12.5(1) 95.9±14.0(1) 113.8±26.0(1) 98.3±1.9(1) 24.2±6.4(1)(3) 43.6±10.3(3)Group B 133.1±17.5(1) 77.1±16.0(1) 92.8±17.9(1) 112.2±25.4(1) 98.4±2.3(1) 21.6±6.3 45.8±10.7 T3 Group A 123.3±18.4(1)(3) 78.6±14.2(1) 92.5±17.0(1) 107.8±26.3(1) 98.8±1.5(1) 23.4±8.0(1)(3) 43.1±8.7(3)Group B 112.4±15.0(1) 75.5±15.3(1) 89.9±16.2(1) 104.3±24.1(1) 98.6±1.7(1) 19.1±4.5 45.1±11.7 T4 Group A 117±17.4(1)(3) 76.7±14.5(1)(3) 89.6±15.1(1)(3) 101.9±23.7(1)(3) 98.8±1.4(1) 20.9±4.0(1)(3) 42.5±7.1(3)Group B 123.8±20.7(1) 71.7±12.9(1) 84.8±14.3(1) 97.1±21.2(1) 98.7±1.5(1) 18.7±3.9 44.7±10.0
表2 右美托咪啶對拔管前后兩組循環(huán)及呼吸指標的影響(±s,n=46)Tab.2 Effect of dexmedetomidine on parameters of ICU patients before and after extubation(±s,n=46)
表2 右美托咪啶對拔管前后兩組循環(huán)及呼吸指標的影響(±s,n=46)Tab.2 Effect of dexmedetomidine on parameters of ICU patients before and after extubation(±s,n=46)
SBP. Systolic blood pressure; DBP. Diastolic blood pressure; MAP. Mean artery pressure; HR. Heart rate; SO2. Oxygen saturation; RR. Respiratory rate. (1)P<0.05 compared with T6; (2)P<0.05 compared with group A
Group SBP(mmHg) DBP(mmHg) MAP(mmHg) HR(/min) SO2(%) RR(/min) Group A T5 116.7±14.0 81.2±10.6 95.2±14.0 113.9±21.4 98.7±0.4 21.0±3.4 T6 117.0±11.1 82.0±8.6 95.7±11.4 114.0±19.6 98.7±0.4 20.5±3.6 Group B T5 102.8±11.4(1)(2) 75.1±7.9(1)(2) 88.9±9.6 99.4±21.1(1)(2) 98.8±0.6 19.4±2.0 T6 110.3±9.8(2) 77.3±6.3(2) 89.6±8.3 96.5±17.7(2) 98.6±0.8 19.3±2.0
鹽酸右旋美托咪定為咪唑類衍生物,是高效和高選擇性的α2腎上腺素受體激動藥,分別作用于藍斑核、脊髓后角發(fā)揮鎮(zhèn)靜催眠和抗傷害性效應,并通過作用于外周及中樞共同發(fā)揮抗交感活性效應,產生劑量依賴性的鎮(zhèn)靜、催眠和抗焦慮作用[3-5]。右美托咪啶有效劑量小,代謝快,成年人經(jīng)10min靜脈輸注負荷劑量右美托咪啶1μg/kg,給藥分布半衰期為6min,消除半衰期約2h[6]。
右美托咪啶在ICU中已得到廣泛應用。臨床試驗證明,對于進行氣管插管機械通氣的患者,注射右美托咪啶能使患者更安靜,對機械通氣的耐受性更好,但對血壓、心率會產生不同程度的影響[7-9]。單次靜脈注射或快速注射右美托咪啶時,初始激動血管平滑肌上的α2腎上腺素能受體,可導致血管收縮、血壓增高,繼而延髓血管舒縮中樞的α2腎上腺素能受體被激動,交感活性降低,導致血壓降低和心率減慢[10]。本研究對不同年齡組機械通氣患者使用右美托咪啶前后血壓、心率、呼吸的變化進行比較,結果顯示,使用右美托咪啶前B組SBP明顯高于A組(P<0.05),但MAP及HR兩組間差異無統(tǒng)計學意義(P>0.05)。用藥120min后,A組血壓及心率明顯高于B組,提示右美托咪啶對老年患者具有更強的降血壓及減慢心率的效果。
本研究中靜脈注射右美托咪啶后共有9.56%患者血壓下降,經(jīng)根據(jù)中心靜脈壓(CVP)及時補充血容量,選擇合適的血管活性藥和減少劑量等積極處理后均予以糾正。這可能與右美托咪啶可興奮交感神經(jīng)末梢的突觸前α2腎上腺素能受體,但對交感神經(jīng)突觸后受體無阻滯作用,從而抑制去甲腎上腺素釋放,保存交感神經(jīng)對意外性低血壓、低血容量或出血反應的儲備能力,保存血管活性藥物治療的有效性有關[11]。此外,使用右美托咪啶后低血壓發(fā)生率明顯高于高血壓,其機制可能是右美托咪啶通過血腦屏障后發(fā)揮強大的抗交感活性及增強迷走神經(jīng)的作用,從而使血壓下降,而這種作用強于其激動外周血管的α2受體后所致升壓及心率加快的效應[12]。
右美托咪啶產生鎮(zhèn)靜作用時不通過γ-氨基丁酸系統(tǒng),呼吸抑制作用比阿片類藥物更弱[13-14],這一特點在拔除氣管插管后患者的鎮(zhèn)靜治療中具有獨特優(yōu)勢。本研究中,用藥后兩組患者呼吸頻率減低(P<0.05),但不影響FiO2(P>0.05),SpO2始終未降低,甚至在使用右美托咪啶30min后較用藥前上升(P<0.05),可能與適當鎮(zhèn)靜減少人機對抗有關。本研究A組患者呼吸頻率始終快于B組,F(xiàn)iO2始終低于B組(P<0.05),但SpO2之間差異無統(tǒng)計學意義(P>0.05),可能與年輕組應激反應更強烈,機體代償明顯有關。
右美托咪啶能提供良好的可合作鎮(zhèn)靜狀態(tài)且不抑制呼吸,是清醒氣管插管的理想選擇[15-16]。對于需脫機和氣管插管拔管的患者,由于吸痰、拔管等操作的影響及呼吸吞咽反射的恢復,患者的循環(huán)受到明顯影響,特別是對于伴有心、腦血管疾病的患者來說,可能導致嚴重的不良事件發(fā)生。因減少鎮(zhèn)痛鎮(zhèn)靜用藥導致煩躁及心血管刺激反應以致脫機失敗的患者,在使用右美托咪啶鎮(zhèn)靜后可順利脫機拔管,不再發(fā)生煩躁和血流動力學不穩(wěn)定的情況[17]。在此次多中心臨床研究中,同樣發(fā)現(xiàn)右美托咪啶用于拔管時鎮(zhèn)靜,拔管前后MAP、SpO2、呼吸頻率穩(wěn)定(P>0.05),其中A組心率穩(wěn)定,B組心率稍減慢(P<0.05)。目前,大多數(shù)右美托咪啶用于氣管插管拔管的研究為對術后ICU期間脫機拔管患者的觀察,證實在維持輸注右美托咪啶期間就可以拔除氣管導管,拔管后仍可以維持輸注以保證患者的無痛和鎮(zhèn)靜[18]。
右美托咪啶常見的不良反應較少,低血壓和心動過緩是右美托咪啶最主要的不良反應[19]。低血壓往往在并存低血容量時出現(xiàn),可以通過補液、減慢或暫停給藥予以糾正;嚴重的心動過緩少見。本研究證實,ICU機械通氣患者使用右美托咪啶不良反應發(fā)生率較低,且與年齡顯著相關,是否與所合并的基礎疾病有關尚有待研究。右美托咪啶安全范圍廣,在過量使用達到0.5μg/(kg.min)時只產生過度的鎮(zhèn)靜效應,并未出現(xiàn)高血壓或嚴重的心動過緩[20]??傊颐劳羞溧ぽ斪⒁子诳刂?,起效、清除快,在腎功能嚴重受損人群清除不受影響,長時間應用能很好地耐受,且無撤藥反應,安全性能較好[21]。用于重癥監(jiān)護病房機械通氣及拔管患者無呼吸抑制,血流動力學穩(wěn)定,是理想的鎮(zhèn)靜藥物選擇。但對于年老患者需加強監(jiān)護,尤其早期使用負荷劑量時,應防止低血壓及心動過緩等不良反應的發(fā)生并及時處理。
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The clinical value of dexmedetomidine during mechanical ventilation in ICU patients of different ages
ZHU Yan, WU Li-xue, LIN Zhao-fen*
Department of Emergency, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author, E-mail: linzhaofen@sina.com
Objectives To provide basis for the safe use of indigenous dexmedetomidine hydrochloride by observing its sedative effect and safety when it was given to mechanically ventilated patients of different ages.MethodsThree hundred and fourteen mechanically ventilated patients were admitted to our ICU. According to the age, patients were divided into two subgroups: group A (25-50 years old) and group B (51-80 years old), with 157 patients in each group. Dexmedetomidine was given to achieve the target sedation level (Ramsay score 3). The changes in noninvasive blood pressure (SBP, DBP, MAP), heart rate, SpO2, respiratory rate and FiO2were continuously monitored and recorded before treatment (T1), and 10min (T2), 30min (T3) and 120min (T4) after drug administration, on the instant moment of extubation (T5), and 30min after extubation (T6). The adverse reactions such as hypertension, hypotension, bradycardia, tachycardia, delirium were also observed and recorded after treatment.ResultsPatients of both A and B groups showed a lowering of SBP, DBP, MAP and HR after treatment with dexmedetomidine, especially in group B (P<0.05), though they were still maintained at an acceptable range (MAP>80mmHg, HR>60 times/min). Respiratory rate was reduced (P<0.05), without affecting FiO2and PEEP (P>0.05). SpO2was not reduced, and it even rose 30min after administration of dexmedetomidine (P<0.05). In addition, sedation was maintained in patients of both C and D groups during extubation, and their blood pressure, SpO2, respiratory rate were maintained stable before and after extubation (P>0.05), and the heart rate was slightly slower in group B (P<0.05). The probability of occurrence of adverse reactions, such as hypertension, hypotension, tachycardia, bradycardia and delirium was significantly higher in group B than in group A.ConclusionsDexmedetomidine does not depress respiration, and a stable hemodynamics was maintained after extubation in ICU patients undergoing mechanical ventilation, thus it is an ideal sedative drug. But when it is used in elderly patients, proper monitoring should be maintained, especially when a loading dose is used, in order to prevent adverse reactions such as hypotension and bradycardia, and should be corrected in time.
dexmedetomidine; respiration, artificial; intensive care units; deep sedation
R971.1;R605.973
A
0577-7402(2015)09-0758-05
10.11855/j.issn.0577-7402.2015.09.15
2015-02-27;
2015-07-22)
(責任編輯:熊曉然)
朱妍,主治醫(yī)師。主要從事膿毒血癥的臨床診治工作
200003 上海 第二軍醫(yī)大學長征醫(yī)院急救科(朱妍、伍力學、林兆奮)
林兆奮,E-mail: linzhaofen@sina.com