[中圖分類號] R614.27;R749.42 [文獻(xiàn)標(biāo)志碼] A
Effect of different administration methods of esketamine on postoperative depression in patients undergoing heart valve replacementLI Zongxiao,MA Xin,MA Wenru,NIU Zejun(Department of Anesthesiology, The Affiliated Hospital of Qingdao University,Qingdao 266oo3,China)
[ABSTRACT]ObjectiveTo investigate the impact of singleorcontinuous administrationof subanesthetic doses of esketamineduringanesthesiaonpostoperativedepressioninpatientsundergoingheartvalvereplacement.MethodsAtotalof 256 patientswhounderwentheartvalvereplacementinourhospitalfromAugust2023toAugust2O24 wereenrolled,andaccording to theuseof esketamineduringsurgery,the patients weredivided intocontrol group(groupC),single-dose group(groupS-S),and continuous-dosegroup(groupC-S).Generalinformationwascolectedandcomparedbetweenthethre groups,aswellas17item HamiltonDepressionRatingScale(HAMD-17)scoreandtheconstituentratioofpatientswithdepressd moodondy1beforesur geryandondays3,7,and 30aftersurgery,Visual Analog Scale(VAS)painscoreand Self-Rating Scaleof Slep(SRSS)score on day3aftersurgeryandtheincidencerateofadversereactions withinlweek aftersurgeryResultsGroupC-Shadasignificantly lower VAS score than group C on day 3 after surgery F=4.617,Plt;0.05) . The three groups showed a significant change in HAMD-17 score from before surgery to different time points after surgery ( Fintragroup=4.497-18.254,Plt;0.05) ; in group C, HAMD-17 score on day 3 after surgery was significantly higher than that on day 1 before surgery ( Plt;0.01 ),while in group C-S, HAMD-17 score on day 7 after surgery was significantly higher than that on day 1 before surgery ( ?Plt;0.05 ); for all three groups, HAMD-17 score at 1 month after surgery was significantly lower than that on day 1 before surgery ( Plt;0.05) . There were significant diffe-rences in HAMD-17 score between the three groups on days 3 and 7 after surgery (Fintergroup=7.218,7.809,Plt;0.05) : groups C-S and S-S had a significantly lower HAMD-17 score than group Con day 3 after surgery ( ?Plt;0.05 ),while group C-S had a significantly lower HAMD-17 score than group C on day 7 after surgery ( Plt;0.05 .For group C,the constituent ratio of patients who deve-loped depressed mood on day 3after surgery was significantly higher than that on day1before surgery(Wald χ2= 33.704, Plt;0.01 ),and there was no significant change in the constituent ratio of patients who developed depressed mood after surgeryin the other two groups ΔPgt;0.05 .Conclusion Continuous intrao-perative application of subanesthetic doses of esketamine can improve depressive symptoms within a short period of time after surgeryand alleviate postoperative pain in patients undergoing heart valvereplacement,withoutincreasingtheincidencerateofadversereactions.Thisaproachcanhelptopromotethepostoperativ recoveryof patientsundergoingheartvalvereplacement.
[KEY WORDs]Anesthesia,cardiac procedures;Antidepressive agents;Esketamine;Depression; Pain,postoperative
手術(shù)對患者來說屬于巨大應(yīng)激事件,圍術(shù)期的緊張、疼痛及手術(shù)造成的創(chuàng)傷都會誘發(fā)或加重心理應(yīng)激反應(yīng),部分患者在手術(shù)后會出現(xiàn)以情緒低落、思維遲緩、意志活動減弱為主要表現(xiàn)的抑郁情緒,這可能對手術(shù)的治療效果和疾病預(yù)后產(chǎn)生不良影響[1-2]。既往研究顯示,非心臟手術(shù)后約有 24% 患者會發(fā)生不同程度的抑郁,這不僅延長了患者康復(fù)和住院時(shí)間,還降低了術(shù)后生活質(zhì)量3;而心臟手術(shù)由于風(fēng)險(xiǎn)更高且手術(shù)創(chuàng)傷較大,患者的心理負(fù)擔(dān)更重,圍術(shù)期出現(xiàn)抑郁情緒的情況更加普遍。一項(xiàng)研究顯示冠狀動脈旁路移植術(shù)后3個(gè)月內(nèi)約有 37% 的患者會出現(xiàn)抑郁情緒[4-5]。因此,探索如何預(yù)防或緩解術(shù)后抑郁對于改善心臟手術(shù)患者預(yù)后具有重要意義。艾司氯胺酮是氯胺酮的S-對映異構(gòu)體,靜脈注射能夠發(fā)揮快速抗抑郁作用[],目前被廣泛用于成人難治性抑郁癥的治療[7-8]。一些臨床研究發(fā)現(xiàn),在非心臟手術(shù)中應(yīng)用亞麻醉劑量的艾司氯胺酮對緩解患者術(shù)后的抑郁情緒似乎具有積極作用[9-10],且不會增加患者術(shù)后不良反應(yīng)發(fā)生率[11」,是目前預(yù)防術(shù)后抑郁的潛在措施?,F(xiàn)有研究中艾司氯胺酮作為麻醉輔助藥物的給藥方式各不相同,但目前尚無研究報(bào)道艾司氯胺酮對心臟瓣膜術(shù)患者術(shù)后抑郁情緒的影響。因此,本研究探討了手術(shù)期間單次給予或持續(xù)給予亞麻醉劑量艾司氯胺酮對心臟瓣膜置換術(shù)患者術(shù)后抑郁的影響,現(xiàn)將結(jié)果報(bào)告如下。
1資料與方法
1.1 一般資料
選擇2023年8月—2024年8月于我院接受開胸心臟瓣膜置換術(shù)的患者256例?;颊呒{入標(biāo)準(zhǔn):① 開胸體外循環(huán)下行二尖瓣或主動脈瓣置換術(shù)者;② 年齡 ?18 周歲者; ③ 臨床資料完整者。排除標(biāo)準(zhǔn): ① 術(shù)前被診斷為抑郁等精神心理疾病者; ② 術(shù)前長期使用精神活性藥物者; ③ 住院期間未完成相應(yīng)抑郁測試者; ④ 住院期間死亡者; ⑤ 住院期間行二次手術(shù)治療者。根據(jù)患者麻醉過程中是否使用艾司氯胺酮及給藥方式對患者進(jìn)行分組,將術(shù)中未使用艾司氯胺酮的患者設(shè)為對照組(C組),僅在麻醉誘導(dǎo)時(shí)接受單次艾司氯胺酮靜脈注射 (0.3~0.5mg/kg) 的患者設(shè)為單次劑量組(S-S組),整個(gè)麻醉過程中持續(xù)給予艾司氯胺酮(麻醉誘導(dǎo)時(shí) 0.5mg/kg 靜脈注射,術(shù)中 0.3mg/(kg?h) 持續(xù)靜脈輸注至手術(shù)結(jié)束)的患者設(shè)為持續(xù)劑量組(C-S組),所有納入患者在麻醉誘導(dǎo)和麻醉維持階段的用藥方案均相似。
收集患者的性別、年齡、身高、體質(zhì)量、體質(zhì)量指數(shù)(BMI、受教育程度、既往全身麻醉手術(shù)次數(shù)、術(shù)前美國麻醉醫(yī)師學(xué)會(ASA)分級、術(shù)前左心室射血分?jǐn)?shù)(LEVF)、術(shù)前查爾森合并癥指數(shù)、手術(shù)時(shí)長、體外循環(huán)時(shí)長、術(shù)中失血量,以及術(shù)中舒芬太尼、咪達(dá)唑侖、丙泊酚、右美托咪定等麻醉藥品消耗量等資料;收集手術(shù)前1d及術(shù)后第3、7、30天的漢密爾頓17項(xiàng)(HAMD-17)抑郁量表得分;收集患者術(shù)后第3天時(shí)的疼痛視覺模擬評分(VAS)得分和睡眠狀況自評量表(SRSS)得分;收集患者術(shù)后1周內(nèi)惡心、嘔吐、幻覺、噩夢等不良反應(yīng)發(fā)生情況。
1.2 統(tǒng)計(jì)學(xué)處理
使用SPSS27.0軟件對數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。符合正態(tài)分布的計(jì)量資料以 x±s 表示,多組多時(shí)間點(diǎn)的比較采用重復(fù)測量設(shè)計(jì)的方差分析,多組同一時(shí)間點(diǎn)比較使用單因素方差分析,進(jìn)一步組間兩兩比較使用 t 檢驗(yàn);不符合正態(tài)分布的計(jì)量資料以M(P25,P75) 表示,多組間比較用Kruskal-waills H 檢驗(yàn)。計(jì)數(shù)資料以例(率)表示,組間比較采用 χ2 檢驗(yàn),多組多時(shí)間點(diǎn)比較采用廣義估計(jì)方程,進(jìn)一步兩兩比較采用Pearson x2 檢驗(yàn)。以 Plt;0.05 為差異有統(tǒng)計(jì)學(xué)意義。
2結(jié)果
2.1 三組患者一般資料比較
所有患者中,65例患者在麻醉誘導(dǎo)及麻醉維持中接受了艾司氯胺酮持續(xù)靜脈輸注,27例患者僅在麻醉誘導(dǎo)時(shí)接受了單次艾司氯胺酮靜脈注射,164例患者麻醉過程中未使用艾司氯胺酮。三組患者術(shù)后第3天時(shí)VAS得分存在顯著差異( F=4.617 ,Plt;0.05) ,其中C-S組患者術(shù)后第3天時(shí)VAS得分顯著低于C組( ?Plt;0.05) ;三組患者其他指標(biāo)差異無顯著性 (Pgt;0.05) 。見表1。
2.2三組患者術(shù)前及術(shù)后的HAMD-17抑郁量表得分比較
重復(fù)測量設(shè)計(jì)的方差分析結(jié)果顯示,時(shí)間、組別、時(shí)間與組別交互作用均對患者術(shù)后HAMD-17抑郁量表得分存在明顯影響 。單獨(dú)效應(yīng)結(jié)果顯示,三組患者的術(shù)前與術(shù)后各時(shí)間點(diǎn)間HAMD-17抑郁量表得分均存在顯著差異( C???=4.497~ 18.254,Plt;0.05) ;其中三組患者術(shù)后第30天時(shí)HAMD-17抑郁量表得分均低于術(shù)前1d和術(shù)后第3天( ?Plt;0.05 ;C組患者術(shù)后第3天時(shí)HAMD-17抑郁量表得分顯著高于術(shù)前1d,隨后HAMD-17抑郁量表得分逐漸下降( ?Plt;0.01 ; C?S 與S-S組患者HAMD-17抑郁量表得分同樣從術(shù)后第3天開始逐漸下降 (Plt;0.05) ,且C-S組術(shù)后第7天時(shí)的得分顯著低于術(shù)前 1d(Plt;0.05) 。單獨(dú)效應(yīng)結(jié)果顯示,三組患者術(shù)后第3、7天時(shí)HAMD-17抑郁量表得分均有顯著差異 (FzH|iH=7.218,7.809,Plt;0.05) ,其中C-S、S-S組患者術(shù)后第3天時(shí)HAMD-17抑郁量表得分顯著低于C組患者 (Plt;0.05) ,同時(shí)C-S組患者術(shù)后第7天時(shí)HAMD-17抑郁量表得分顯著低于C組患者 (Plt;0.05) 。見表2。
2.3三組患者抑郁情緒及持續(xù)性抑郁情緒發(fā)生情 況比較
廣義估計(jì)方程結(jié)果顯示,時(shí)間對發(fā)生抑郁情緒患者構(gòu)成比存在明顯影響 (Waldχ2=21.158,Plt; 0.01),組別、時(shí)間與組別交互作用對發(fā)生抑郁情緒患者構(gòu)成比無明顯影響 (Pgt;0.05) 。單獨(dú)效應(yīng)結(jié)果顯示,C組術(shù)后第3天時(shí)發(fā)生抑郁情緒患者構(gòu)成比高于術(shù)前 ,但其他兩組手術(shù)前后發(fā)生抑郁情緒患者構(gòu)成比無顯著差異(Pgt;0.05) 。見表3。共18例患者術(shù)后存在持續(xù)抑郁情緒,C、C-S、S-S組發(fā)生持續(xù)性抑郁情患者構(gòu)成比分別為 8.5%.4.6%.3.7% ,但發(fā)生持續(xù)性抑郁情緒患者構(gòu)成比無顯著差異( ΔPgt;0.5) 。
3討論
艾司氯胺酮被廣泛應(yīng)用于重度抑郁癥的治療,研究發(fā)現(xiàn)單次小劑量艾司氯胺酮靜脈注射能夠顯著減輕重度抑郁癥患者用藥后2周內(nèi)的抑郁癥狀[12]在全身麻醉中使用小劑量[負(fù)荷量 0.5~1mg/kg 維持量 0.5~3mg/(kg?h)] 艾司氯胺酮被證實(shí)能夠減輕患者術(shù)后疼痛,提高術(shù)后身體舒適度,并改善術(shù)后情緒狀態(tài),并且不會增加術(shù)后不良事件的發(fā)生風(fēng)險(xiǎn)[13-14]。同時(shí),初步臨床研究發(fā)現(xiàn)非心臟手術(shù)中應(yīng)用亞麻醉劑量的艾司氯胺酮可減輕患者術(shù)后早期抑郁情緒[15-16],然而艾司氯胺酮對心臟手術(shù)患者術(shù)后抑郁的影響目前尚無研究報(bào)道。因此,本研究探討了艾司氯胺酮對心臟瓣膜置換術(shù)患者術(shù)后抑郁情緒的影響。
本研究主要發(fā)現(xiàn)術(shù)中持續(xù)靜脈注射亞麻醉劑量的艾司氯胺酮可降低心臟瓣膜置換術(shù)患者術(shù)后第3、7天時(shí)的HAMD-17抑郁量表得分,而麻醉誘導(dǎo)時(shí)單次靜脈注射艾司氯胺酮也能降低患者術(shù)后第3天時(shí)的HAMD-17抑郁量表得分。HAMD-17抑郁量表是臨床上評估抑郁狀態(tài)最常用的量表,得分越高反映患者的抑郁癥狀越重。本研究結(jié)果與既往臨床研究當(dāng)中艾司氯胺酮可以降低患者術(shù)后短期內(nèi)HAMD-17 抑郁量表得分的結(jié)果相似[10,15-16],而術(shù)中持續(xù)靜脈用藥的抗抑郁效果可能在術(shù)后的持續(xù)時(shí)間更長。抑郁情緒的發(fā)生與中樞神經(jīng)系統(tǒng)炎癥關(guān)系密切[4,17],手術(shù)創(chuàng)傷引起的全身無菌性炎癥會破壞血腦屏障,使促炎因子進(jìn)入中樞神經(jīng)系統(tǒng)并激活小膠質(zhì)細(xì)胞,進(jìn)而引起中樞神經(jīng)系統(tǒng)炎癥[18],這是發(fā)生術(shù)后抑郁的可能機(jī)制之一。研究發(fā)現(xiàn),重度抑郁癥患者前額葉皮質(zhì)、前扣帶皮質(zhì)和島葉等腦區(qū)常出現(xiàn)大量活化小膠質(zhì)細(xì)胞和明顯炎癥反應(yīng)[19-20]。而艾司氯胺酮能夠激活瞬時(shí)受體電位香草酸4通道和α7型煙堿型乙酰膽堿介導(dǎo)的內(nèi)源性膽堿能通路等抗炎信號通路[21-22],通過減輕外周和中樞神經(jīng)系統(tǒng)的炎癥反應(yīng)改善患者術(shù)后情緒。同時(shí),艾司氯胺酮還可以通過調(diào)節(jié)小膠質(zhì)細(xì)胞的自噬通量,減輕小膠質(zhì)細(xì)胞對中樞神經(jīng)系統(tǒng)造成的損傷[23];另外艾司氯胺酮也能夠提升大腦皮質(zhì)當(dāng)中腦源性神經(jīng)營養(yǎng)因子(BDNF)的含量,并增強(qiáng)BDNF/TrkB信號通路的活化,從而發(fā)揮快速抗抑郁作用[24]。
HAMD-17抑郁量表得分 gt;17 分時(shí)提示患者存在中重度抑郁癥狀,本研究將這部分癥狀較重的患者診斷為抑郁情緒,并關(guān)注了艾司氯胺酮對術(shù)后抑郁情緒發(fā)生的影響。研究發(fā)現(xiàn)對照組術(shù)后第3天時(shí)發(fā)生抑郁情緒患者構(gòu)成比高于術(shù)前,而單次注射或持續(xù)輸注艾司氯胺酮的患者術(shù)后抑郁情緒發(fā)生構(gòu)成比與術(shù)前無顯著差異,這提示了艾司氯胺酮可能對預(yù)防術(shù)后中重度抑郁狀態(tài)發(fā)生具有積極作用。但本研究結(jié)果中未觀察到艾司氯胺酮對各組間發(fā)生抑郁情緒及持續(xù)性抑郁情緒患者構(gòu)成比的影響。既往一些非心臟手術(shù)研究還關(guān)注到,術(shù)前就存在輕中度抑郁癥狀的患者術(shù)中持續(xù)靜脈泵人艾司氯胺酮也可改善術(shù)后抑郁癥狀[16]。因此,艾司氯胺酮對圍術(shù)期不同程度抑郁狀態(tài)的預(yù)防或改善效果仍有待進(jìn)一步研究。此外,本研究還觀察到術(shù)中持續(xù)靜注艾司氯胺酮的患者術(shù)后第3天時(shí)VAS得分顯著低于未使用艾司氯胺酮的患者,這提示緩解術(shù)后急性疼痛可能也是其改善術(shù)后負(fù)面情緒的機(jī)制之—[25] 。
本研究存在一些局限性。首先,作為一項(xiàng)單中心研究,納入患者的來源較為單一,使得結(jié)果可能缺乏普適性。其次,本研究只收集了術(shù)后1個(gè)月內(nèi)患者的抑郁量表得分,未觀察持續(xù)性抑郁情緒患者在術(shù)后1個(gè)月后的長期恢復(fù)情況。最后,由于本研究為回顧性研究,未針對性控制研究變量,可能影響了對艾司氯胺酮作用的準(zhǔn)確評估。
綜上所述,本研究結(jié)果提示心臟瓣膜置換術(shù)中持續(xù)應(yīng)用亞麻醉劑量的艾司氯胺酮能夠改善術(shù)后短期內(nèi)的抑郁癥狀,同時(shí)緩解術(shù)后疼痛,且不增加不良反應(yīng)的發(fā)生率,有利于促進(jìn)心臟瓣膜置換術(shù)患者術(shù)后的恢復(fù)。
倫理批準(zhǔn)和知情同意:本研究涉及的所有試驗(yàn)均已通過醫(yī)學(xué)倫理委員會的審核批準(zhǔn)(文件號QYFYW2LL29626)。受試對象或其親屬已經(jīng)簽署知情同意書。
作者聲明:所有作者均參與了研究設(shè)計(jì)、論文的寫作和修改。所有作者均閱讀并同意發(fā)表該論文,且均聲明不存在利益沖突。
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(本文編輯 范睿心 厲建強(qiáng))