1、比较不同浓度舒芬太尼效应室靶控输注在老年冠心病人中的应用袁治国 吕黄伟 王俊科中国医科大学附属第一医院麻醉科 沈阳，110001摘要目的 比较在老年冠心病人全麻诱导及气管插管过程中应用不同浓度舒芬太尼效应室靶控输注对血流动力学的影响。方法 选取择期行CABG的病人 60例，ASA 分级 II级。按舒芬太尼效应室靶浓度（Ce）不同将病人随机分为：L 组（0.5ng/ml） ；M 组（0.6ng/ml）和 H组（0.7ng/ml） 。每组各 20例。分别在麻醉诱导前（T1） 、诱导后(T2)、气管插管后 1min(T3)、3min(T4)记录HR、 SBP、DBP、CO 、CI、SI 、SVR。结
2、果 L组 BP和 HR在 T3和T4时较 T1时均明显增高，而 H组在 T2时 BP和 HR明显降低（P0.05）.Conclusion This study suggests that target controlled infusion of sufentanil at effect-site concentration (Ce0.6ng/ml) may be safely applied in elderly patients with coronary heart disease during induction and intubation, which is maybe more
3、beneficial to maintaining the hemodynamic stability【Key Words】: sufentanil, effect site concentration, cardiovascular homeostasis, elderly patients, coronary heart disease The peri-intubation period is one of the high stress moments of general anesthesia. Induction and endotracheal intubation may in
4、duce clinically relevant cardiovascular response, especially in elderly patients suffering from coronary heart disease, whose compensation capability for hemodynamics was limited and compromised due to the existed pathological changes of coronary artery. Various pharmacological strategies have been
5、proposed to maintain hemodynamic stability in response to intubaiton. Opioids, such as fentanyl, remifentanil and sufentanil, etc, are widely applied to control the cardiovascular response during peri-intubation period. More data have shown that a linear relationship exists between the increasing do
6、se of opioids applied and reduction of intubation response in cardiovascular system1,2.Sufentanil is an highly selective -opioid receptor agonist that provides intense analgesia with its unique pharmakokinetic and pharmacodynamic profile and has been shown to be effective in preventing sympathetic r
7、esponse and maintaining the cardiovascular system stability in cardiac surgery. Moreover, the use of a target-controlled infusion at effect site concentration showed to be more effective in maintaining cardiovascular stability as compared with traditional weight-adjusted infusion. Therefore we condu
8、cted a randomized, double blind study to compare the effectiveness and safety of sufentanil at different effect site concentrations in maintaining cardiovascular homeostasis during peri-intubation period in elderly patients with coronary heart diseaseMaterials and methodsSixty patients, ASA physical
9、 status II, aged 72.26.5 years(mean SD) and weighting 64.711.3kg(mean SD), scheduled for elective CABG were prospectively enrolled in the study.Patients fasted for 8h before surgery and received scopolamine (0.3mg,im) and morphine (10mg,im) 30 min before entering operation room. After arrival in the
10、 operating theater one 18-gauge intravenous cannulas were placed on the forearm, and 10 ml/kg Ringers lactate solution was infused. Standard monitoring was used throughout the study, including noninvasive arterial blood pressure, electrocardiography, heart rate(lead II and V), and pulse oximetry. In
11、 all patients the BIS was also monitored using an EEG monitor ( BIS XP for monitor A2000; Aspect medical systems Inc., Natick, MA, USA). Invasive arterial blood pressure ( left radial artery) and central venous pressure (right jugular vein) monitoring were also introduced under local anesthesia. Non
12、invasive Impedance Cardiography monitoring (Bioz, the ICG Cardiodynamics，USA), recoding CO,CI,SI and SVR, were also used before induction. All patients were induced with Midazolam (0.05mg/kg, IV), Vecuronium (0.1mg/kg,IV),Etomidate (0.2mg/kg), and a target-controlled infusion of sufentanil (Bovill m
13、odel, Fresenuius Vial system, infusion technology, Rchestra, USA ) at different effect site concentration (Ce). All the patients were randomly divided in each of three groups according to the effect site concentration: L group(Ce=0.5ng/ml)；M group (Ce=0.6ng/ml) and H group (Ce=0.7ng/ml) (n=20 each).
14、 Endotracheal intubation was performed when each patient BIS maintained stable ranging between 40-50 and then ventilation was assisted with a oxygen-isoflurane mixture and mechanically controlled using a Cato-Drager anesthesia working station set to maintain an end tidal partial pressure of carbon d
15、ioxide randing between 35-40 mmHg and facilitated by vecuronium as muscle relaxant.Heart rate, systolic and diastolic arterial blood pressure (SBP,DBP), and non-invasive cardiovascular hemodynamic variables (including CO, CI, SI and SVR), were all recorded simultaneously at different interval time d
16、uring peri-intubation period: baseline (T1) ,after induction (T2), 1min(T3), 3min(T4)after intubation.Statistical analysisStatistical analysis was performed using SPSS10.0 (SPSS Inc. USA). Changes in HR, BP and hemodynamic variables were analyzed using analysis of variance and t-test. A value of P l
17、ess or equal to 5% was considered statistically significant. Data are presented as mean standard deviation.ResultsThese three groups were similar with respect to age, height, weight and gender and ASA score (table 1). The trachea was always intubated at the first attempt (max time 20s).The changes o
18、f HR,SBP and DBP in each group during peri-intubation period: Statistically significant increase of HR, SBP and DBP were observed at T3 and T4 in L group, and remarkable reduction at T2 in H group（P0.05). Inter-group significance of HR, SBP and DBP existed among these three groups at T2-T4 (P0.05） (
19、table 3).Table 1.Patients demographics. variable L group(n=20)M group(n=20)H group(n=20)Age（years） 72.456.08 71.085.23 72.756.46Hight（cm） 169.338.05 170.116.05 168.458.22Weight（kg） 65.3313.05 67.5613.85 65.4414.01Gender(male/female) 13:7 14:6 15:5ASA（II/III/IV） 14:6:- 13:7:- 15:5:-Table 2.The change
20、s of HR,SBP and DBP in each group during peri-intubation period（xS）group T1 T2 T3 T4L 79.89. 2 74.18.5 91.811. 5*# 86.310.8*#M 77.610.5 70.49.5 73.912.0 73.89.6HR(bpm)H 79.89.5 63.78.7*# 73.610.1 75.58.86L 133.618.7 128.49.8 158.914.6*# 151.111.5*#M 129.510.3 117.613.3 120.911.7 115.38.8SBP(mmHg)H 1
21、30.912.0 100.212.5* 118.814.5 119.510.9L 52.212.7 50.513.5 75.218.2*# 72.314.3*#M 53.310.9 54.911.2 57.09.6 54.212.0DBP(mmHg)H 51.715.1 40.216.8*# 45.610.9*# 52.810.4Compared with T1， *P0.05 compared with M group， #P0.05Table 3.The changes of HR,SBP and DBP in each group during peri-intubation perio
22、d（xS）variable group T1 T2 T3 T4L 3.380.77 2.940.87 3.520.83# 3.450.58#M 3.420.45 2.720.75 2.750.90 2.720.65CO(L/min)H 3.380.82 2.010.68*# 2.270.98*# 2.200.80*#L 2.35 0.17 2.10 0.15 2.16 0.11 2.18 0.21M 2.48 0.21 2.08 0.24 2.15 0.22 2.13 0.18CI(Lmin-1m-2)H 2.37 0.15 1.35 0.19*# 1.70 0.20* 1.98 0.16L
23、32.46.3 28.75.8 29.66.0 28.05.5M 33.26.0 25.45.4 26.26.1 26.85.8SI(ml m-2)H 32.05.8 20.76.8*# 22.85.7* 23.66.7*L 1410.6806.2 1265.6495.0 1375.6580.5 1210.6558.7M 1385.6657.8 1308.8582.2 1210.6656.3 1210.6583.9SVR(dynscm-5)H 1407.6752.9 1110.4616.7*# 1175.6554.1* 1286.6590.4Compared with T1， *P0.05 c
24、ompared with M group， #P0.05Discussion and conclusionsInduction of anesthesia and endotracheal intubation may induce profound alterations of the hemodynamic state of patients, especially those elderly with coronary heart disease, according to both the effects and the techniques of anesthetics admini
25、stered perioperatively. Many pharmacological protocols have been proposed to blunt cardiovascular response during induction and intubaiton, including the use of topical, nebulized local anesthetics, the use of beta-blockers, or other cardiovascular drugs. Opioids administration is the most extensive
26、ly used method. Sufentanil is well concerned and extensively applied in cardiovascular surgery due to its unique analgesic characteristics and little interference with hemodynamic stability3-5. Casati et al. reported that the use of small bolus dose of sufentanil (0.1 mg/kg) effectively blunt the ca
27、rdiovascular response to intubation6. Target controlled infusion (TCI) system has been developed as a standardised infusion system for the administration of opioids, propofol and other anaesthetics7. Existing systems target the plasma drug concentration, which may be less than ideal because the plas
28、ma is not the site of drug effect. TCI at site effect concentration may be the most accurate and appropriate method to obtain the expected pharmacokinetics and pharmacodynamics8. In our study, we determine to choose target controlled infusion with sufentanil at different site effect concentrations,
29、a better choice of combination with an appropriate infusing technique and proper analgesics, to observe the exact influence on hemodynamic stability in elderly patients with coronary artery disease.The results of our study suggest that target controlled infusion of sufentanyl at effect site concentr
30、ation about Ce0.6ng/ml, might more effectively avoid the increases in blood pressure and heart rate due to the relative insufficient dose of sufentanyl（Ce0.5ng/ml） in L group during induction and endotracheal intubation. Meanwhile, it also avoid the decreases in blood pressure or heart rate observed
31、 in H group resulted from high dose of sufentanyl（Ce 0.7ng/ml）. so we assume that the cardiovascular stability could be well maintained and stress response effectively inhibited during indection and intubation in elderly patients with coronary artery disease. In a conclusion, target controlled infus
32、ion of sufentanil at Ce0.6ng/ml effect site concentration may be safely and reliably applied in elderly patients with coronary heart disease with benefits in maintaining hemodynamics stable during induction and intubation. Referrence9. Savoia G, Loreto M, Gravino E. Sufentanil: an overview of its us
33、e for acute pain management. Minerva Anestesiol,2001,67:206-216. Review.10. Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. Pain Symptom Manage,2005,29: 90-103. Review.11. Chung KS, Sinatra RS, Halevy JD, et al. A comparison of fentanyl, esmolol and their combination for blunting the
34、haemodynamic responses during rapid-sequence induction. Can J Anaesth, 1992, 39:774-779.12. Iannuzzi E, Iannuzzi M, Cirillo V, et al. Peri-intubation cardiovascular response during low dose remifentanil or sufentanil administration in association with propofol TCI. A double blind comparison.Minerva
35、Anestesiol, 2004, 70:109-115.13. Forestier F, Hirschi M, Rouget P, et al. Propofol and sufentanil titration with the bispectral index to provide anesthesia for coronary artery surgery. Anesthesiology, 2003, 99:334-346.14. Casati A, Fanelli G, Albertin A, et al. Small doses of remifentanil or sufenta
36、nil for blunting cardiovascular changes induced by tracheal intubation: a double-blind comparison. Eur J Anaesthesiol, 2001, 18:102-112.15. Guarracino F, Lapolla F, Cariello C,et al. Target controlled infusion: TCI.Minerva Anestesiol, 2005,71:335-337. Review.16. Van Poucke GE, Bravo LJ, Shafer SL, et al. Target controlled infusions: targeting the effect site while limiting peak plasma concentration. IEEE Trans Biomed Eng, 2004, 51:1869-1875.
