老年患者靶控输注瑞芬太尼、丙泊酚的临床研究
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摘要
目的
国际老龄化趋势日渐明显,手术人群中老年患者的比例逐渐增多。本研究旨在比较不同靶控输注血浆浓度的瑞芬太尼对老年患者靶控输注丙泊酚意识消失的血浆半数有效浓度的影响,以及探求插管时抑制老年患者插管反应时的丙泊酚半数有效血浆浓度,探讨靶控输注瑞芬太尼复合丙泊酚在老年麻醉诱导中的合理配伍模式。
方法
选择ASAⅠ-Ⅱ级、年龄在60-80岁、拟在全麻气管插管下行择期手术的老年患者为研究对象。第一部分共90例病人,根据瑞芬太尼的靶控浓度随机分为;1ng/ml组(A组=22);2ng/ml组(B组=25);3ng/ml(C组=22);4ng/ml组(D组=21)。采用Dixon改良序贯法测定丙泊酚意识消失的血浆半数有效浓度。各组第一例病人丙泊酚血浆靶控浓度设为2.5μg /ml,第一步浓度梯度为0.5μg/ml,出现≥3个阴阳反应的交替波形后,第二步浓度梯度减小为0.2μg /ml,直到再次出现≥6个阴阳反应的交替波形。通过计算各组第二步各阴阳反应交替中点的均值获得各组的丙泊酚意识消失的血浆半数有效浓度。第二部分共15例老年患者,与第一部分同样采用Dixon改良序贯法测定丙泊酚抑制老年患者插管发反应的血浆半数有效浓度,所有老年患者瑞芬太尼的血浆靶控浓度均设为3ng/ml,第一例患者丙泊酚血浆靶控浓度浓度为2.5μg /ml,此后患者的丙泊酚浓度依据上一例病人的反应增减。计算方法同第一部分,可获得抑制插管反应的丙泊酚半数有效血浆浓度。
结果
第一部分四组老年患者的丙泊酚意识消失的血浆半数有效浓度分别为2.50、2.24、2.16、1.90μg /ml ,A组与其它三组之间比较有统计学差异(P<0.05),D组与B、C组比较有统计学意义(P<0.05)。国人60-80岁年龄段老年患者丙泊酚抑制插管反应的半数有效血浆浓度为2.32μg /ml。
结论
不同靶控输注血浆浓度的瑞芬太尼对老年患者靶控输注丙泊酚意识消失的血浆半数有效浓度的影响不同,随着瑞芬太尼的血浆靶控浓度增大,老年患者意识消失的异丙酚靶控血浆半数有效浓度逐渐降低。在瑞芬太尼复合丙泊酚靶控输注抑制气管插管反应时,丙泊酚的血浆靶控浓度应根据老年患者的具体情况作调整,注意对循环系统的影响。对于高龄和危重病人丙泊酚和瑞芬太尼的靶控浓度的选择还有待于进一步的研究。
Objective
With the ageing of the population in our country,the elderly patients who need operation become more and more. The aim of this study was to compare effects of different target controlled plasma concentrations of remifentanil on the effective plasma concentration of propofol by TCI for loss of consciousness(LOC) in 50% of elderly patients aged 60-80yr,and to determine the effective plasma concentration of propofol by TCI combining remifentanil to prevent response to tracheal intubtion(TI) in 50% of elderly patients of that population. We try to find better combined for these two anesthetic agents in elderly patients,wish to provide some information for clinical anaesthesia.
Methods
105 ASAⅠ-Ⅱpatients, aged 60-80yr, scheduled for elective surgery requiring trachel intubation were recruited. In the first part of the study enrolling 90 patients,they were randomly divided into four groups according to target controlled plasma concentrations of remifentanil:GroupA(1ng/ml)、GroupB(2ng/ml)、GroupC(3ng/ml)andGroupD(4ng/ml).The EC50 of propofol were determined with a modified Dixon,s up-and-down method in two stages.The test space in the first stage was 0.5μg /ml,and the first patient in each group received an intial plasma concentration of propofol of 2.5μg /ml.After 3 or more negative-positive up-and-down crossovers,the intial test space was reduced to 0.2μg /ml. There were 6 or more negative-positive up-and-down crossovers in the second stage .The EC50 of propofol were obtained by calculating the mean values for crossover midpoints in the second stage of each group.There were 15 patients,aged 60-80yr, in the second part of the study.Same to the first part,EC50 of propofol were determined with a modified Dixon,s up-and-down method.The initial test space in the first stage was 0.5μg /ml,and was reduced to 0.2μg /ml in the second stage.The first patient in the second part received an initial plasma concentration of propofol of 2.5μg /ml.The plasma concentration of the next patient was set at the designed concentration according to the up-and-down sequence and the first patient..Then EC50 of propofol to prevent response to tracheal intubtion(TI) were calculated as the first part.
Results
In the first part of the study,The EC50 of propofol was 2.50μg /ml in the groupA,2.24μg /ml in the groupB,2.16μg /ml in the groupC and 1.90μg /ml in the groupD.Comparing groupA,the EC50 of propofol was decreased significantly(P<0.05) in groupB、C、D.GroupD was decreased significantly(P<0.05)compared with groupB、C.In the second part of the study,to patients aged 60-80yr,EC50 of propofol by TCI combining remifentanil to prevent response to tracheal intubtion(TI) in 50% of elderly patients was 2.32μg /ml.
Conclusion
The effects of different target controlled plasma concentrations of remifentanil on the EC50 of propofol were different in elderly patients.With the concentrations of remifentanil increased,the EC50 of propofol decreased in elderly patients. To patients 60-80yr,the plasma concentration of propofol combining remifentanil to prevent response to TI should be adjusted according to status of individual patient,and influence on hemodynamics should be cautioned.Further studies are needed to seek proper concentration of propofol and remifentanil in patients of advanced age and with critical cardiovascular or pulmonary disease.
国际老龄化趋势日渐明显,手术人群中老年患者的比例逐渐增多。本研究旨在比较不同靶控输注血浆浓度的瑞芬太尼对老年患者靶控输注丙泊酚意识消失的血浆半数有效浓度的影响,以及探求插管时抑制老年患者插管反应时的丙泊酚半数有效血浆浓度,探讨靶控输注瑞芬太尼复合丙泊酚在老年麻醉诱导中的合理配伍模式。
方法
选择ASAⅠ-Ⅱ级、年龄在60-80岁、拟在全麻气管插管下行择期手术的老年患者为研究对象。第一部分共90例病人,根据瑞芬太尼的靶控浓度随机分为;1ng/ml组(A组=22);2ng/ml组(B组=25);3ng/ml(C组=22);4ng/ml组(D组=21)。采用Dixon改良序贯法测定丙泊酚意识消失的血浆半数有效浓度。各组第一例病人丙泊酚血浆靶控浓度设为2.5μg /ml,第一步浓度梯度为0.5μg/ml,出现≥3个阴阳反应的交替波形后,第二步浓度梯度减小为0.2μg /ml,直到再次出现≥6个阴阳反应的交替波形。通过计算各组第二步各阴阳反应交替中点的均值获得各组的丙泊酚意识消失的血浆半数有效浓度。第二部分共15例老年患者,与第一部分同样采用Dixon改良序贯法测定丙泊酚抑制老年患者插管发反应的血浆半数有效浓度,所有老年患者瑞芬太尼的血浆靶控浓度均设为3ng/ml,第一例患者丙泊酚血浆靶控浓度浓度为2.5μg /ml,此后患者的丙泊酚浓度依据上一例病人的反应增减。计算方法同第一部分,可获得抑制插管反应的丙泊酚半数有效血浆浓度。
结果
第一部分四组老年患者的丙泊酚意识消失的血浆半数有效浓度分别为2.50、2.24、2.16、1.90μg /ml ,A组与其它三组之间比较有统计学差异(P<0.05),D组与B、C组比较有统计学意义(P<0.05)。国人60-80岁年龄段老年患者丙泊酚抑制插管反应的半数有效血浆浓度为2.32μg /ml。
结论
不同靶控输注血浆浓度的瑞芬太尼对老年患者靶控输注丙泊酚意识消失的血浆半数有效浓度的影响不同,随着瑞芬太尼的血浆靶控浓度增大,老年患者意识消失的异丙酚靶控血浆半数有效浓度逐渐降低。在瑞芬太尼复合丙泊酚靶控输注抑制气管插管反应时,丙泊酚的血浆靶控浓度应根据老年患者的具体情况作调整,注意对循环系统的影响。对于高龄和危重病人丙泊酚和瑞芬太尼的靶控浓度的选择还有待于进一步的研究。
Objective
With the ageing of the population in our country,the elderly patients who need operation become more and more. The aim of this study was to compare effects of different target controlled plasma concentrations of remifentanil on the effective plasma concentration of propofol by TCI for loss of consciousness(LOC) in 50% of elderly patients aged 60-80yr,and to determine the effective plasma concentration of propofol by TCI combining remifentanil to prevent response to tracheal intubtion(TI) in 50% of elderly patients of that population. We try to find better combined for these two anesthetic agents in elderly patients,wish to provide some information for clinical anaesthesia.
Methods
105 ASAⅠ-Ⅱpatients, aged 60-80yr, scheduled for elective surgery requiring trachel intubation were recruited. In the first part of the study enrolling 90 patients,they were randomly divided into four groups according to target controlled plasma concentrations of remifentanil:GroupA(1ng/ml)、GroupB(2ng/ml)、GroupC(3ng/ml)andGroupD(4ng/ml).The EC50 of propofol were determined with a modified Dixon,s up-and-down method in two stages.The test space in the first stage was 0.5μg /ml,and the first patient in each group received an intial plasma concentration of propofol of 2.5μg /ml.After 3 or more negative-positive up-and-down crossovers,the intial test space was reduced to 0.2μg /ml. There were 6 or more negative-positive up-and-down crossovers in the second stage .The EC50 of propofol were obtained by calculating the mean values for crossover midpoints in the second stage of each group.There were 15 patients,aged 60-80yr, in the second part of the study.Same to the first part,EC50 of propofol were determined with a modified Dixon,s up-and-down method.The initial test space in the first stage was 0.5μg /ml,and was reduced to 0.2μg /ml in the second stage.The first patient in the second part received an initial plasma concentration of propofol of 2.5μg /ml.The plasma concentration of the next patient was set at the designed concentration according to the up-and-down sequence and the first patient..Then EC50 of propofol to prevent response to tracheal intubtion(TI) were calculated as the first part.
Results
In the first part of the study,The EC50 of propofol was 2.50μg /ml in the groupA,2.24μg /ml in the groupB,2.16μg /ml in the groupC and 1.90μg /ml in the groupD.Comparing groupA,the EC50 of propofol was decreased significantly(P<0.05) in groupB、C、D.GroupD was decreased significantly(P<0.05)compared with groupB、C.In the second part of the study,to patients aged 60-80yr,EC50 of propofol by TCI combining remifentanil to prevent response to tracheal intubtion(TI) in 50% of elderly patients was 2.32μg /ml.
Conclusion
The effects of different target controlled plasma concentrations of remifentanil on the EC50 of propofol were different in elderly patients.With the concentrations of remifentanil increased,the EC50 of propofol decreased in elderly patients. To patients 60-80yr,the plasma concentration of propofol combining remifentanil to prevent response to TI should be adjusted according to status of individual patient,and influence on hemodynamics should be cautioned.Further studies are needed to seek proper concentration of propofol and remifentanil in patients of advanced age and with critical cardiovascular or pulmonary disease.
引文
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1 Mertens M J,Engbers F H M,Burm A C L,et al,Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia, Br J Anaesth2003;90:132-141.
2 陈宇珂,张兴安,张延武,智能化静脉麻醉靶控系统的研制.中国医学装备2005;2:22-23.
3 张加强,邢玉英,杜文力,瑞芬太尼靶控输注时靶浓度和实测血药浓度的差异一靶控输注系统的性能评价,中华麻醉学杂志2005;25:645-648.
4 Minto C F, Schnider F W, Egan T D .et al,Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil-I model. Anesthesiolgy 1997; 86(1):10-23.
5 De.Castrov,Godetc,Mencia,et al.Target-controlled infusion for remifentanil in vascular patients hemodynamics and decrease remifentanil requirement. Anesth Analg 2003; 96(1):33-38.
6 张利萍,张昭,张芝翠等,全麻病人注射瑞芬太尼的药代动力学,中华麻醉学杂志 2006;26:43-45.
7GlassPS,HowellS.A.review.of.the.pharmacokinetics.and.pharmacodynamics.of.remifentanil, Anesth.Analg1999;89:7-14.
8Pitson,Wilmer,Bodenham,etal,Pharmacokinetics.of.remifentanil.and.its.major.metobolite,remifentanil.acid.in.ICU.patients.with.renal.impairment.BJAnesthesia2004;92:493-503.
9MichelsenLG,HolfordNH,Luw,etal,The.pharmacokinetics.of.remifentanil.in.patients.undergoing.coronary.artery.bypass.grafting.with.cardiopulmonary.bypass,Anesth.Analg.2001;93:1100-1105.
10 Kee.Warwick D,Khaw. Kims,Ma. Kwok, et al. Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery:a randomized double-blind controlled.trial.Anesthesiology 2006;104:14-20.
11JhaveriR,JushiP,Batenhovstr,etal,Dose.comparison.of.remifentanil.and.alfentanil.for.loss.of.consciousness.Anesthesiology1997;87:253-259.
12Bilgin,Hülya,Basagan.Mogol.Elif,Bekar,Ahmet;etal,A.Comparison.of.Effects.of.Alfentanil.Fentanyl.and.Remifentanil.on.Hemodynamic.and.Respiratory.ParametersDuring.Stereotactic.BraiBiopsy.Neurosurgical.Anesthesiology,2006;18,pp179-184.
13TwerskyRs,JanersonB,WarnerDS,etal,Hemodynamics.and.emergence.profile.of.remifentail.versus.fentanyl.compared.in.alarge.population.of.surgical.patients.JClin.Anesth 2001;13:407-416.
14Lecomte.Patrick;Quatala.Alexendre;LeManach,etal,The.coronary.and.myocardial.effect.of.remifentanil.and.sufentanil.in.Erythrocyte-perfuse.Isolated.Rabbit.Heart,Anesthesia Analgesia.2006;103:9-14.
15KayeAlanD,Blach.Amir,Phelps.James,An.analysis.of.remifentanil.in.the.pulmonary.vascular.bed.of.the.cat.AnesthesiaAnalgesia2006;102:118-123.
16 马浩男,赵军,瑞芬太尼药理学和临床应用进展,河北医药 2006;28:132-134.
17Wallden,Thorn,Wattwil.The.delay.of.gastric.empting.induced.by.remifentanil.is.not.influenced.by.posture.AnesthesiaAnalgesia2004;99:429-434.
18Crawford,Hickey,Zaarour,etal,Development.of.acute.opioid.Tolance.during.infusion.of.remifentanil.for.pediatric.scoliosis.surgery.AnesthesiaAnalgesia2006;12:1662-1667.
19 Celerier,Gonzalez,Maldonada,etal,Opioid-induced hyperalgesia in a murine model of postoperative pain:role of Nitric Oxide generated from the inducible nitric oxide synthase,Anesthesiology2006;104:546-555.
20 Tirault,Perrode,Clevenotet al,The effect of nefopam on morphine overconsumption induced by dose rimefentanil during propofol anesthesia for major abdominal surgery,Anesthesia,Analgesia2006;102:110-117.
21 Lee,LIbbyH.Y,Irwin,Michael,Lui,Siu-Kuen,Introperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide,Anexthesiology2005;102:398-402.
22 Leone,Rousseau,Avidan etal,Target concentrations of remifentanil with propofol to blunt coughing during intubation,cuff inflation,and trachel sunctioning.British Journal of Anesthesia2004;93:660-663.
23 吴滨阳,陈杰,王俊科。不同效应室浓度瑞芬太尼靶控时气管插管诱发病人的心血管反应。中华麻醉学杂志,2005,25:940-941。
24.曹建国,周仁龙,张马忠等。不同瑞芬太尼血浆靶控浓度实施气管插管的条件和心血管反应。临床麻醉学杂志 2005;21:219-221.
25 David S.Hemodynamics and emergence profile of remifentanil versue fentanyl prospectively compared in large population of surgical patients. Anesthesiology2002;46:207-208.
26.耿志宇,宋琳,许辛等,异丙酚复合芬太尼或瑞芬太尼靶控静脉麻醉与静吸复合麻醉的比较。中华麻醉学杂志 2004;24:14-17.
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60 麻醉手术期间液体治疗专家共识(2007 版)3-4.
1 Mertens M J,Engbers F H M,Burm A C L,et al,Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia, Br J Anaesth2003;90:132-141.
2 陈宇珂,张兴安,张延武,智能化静脉麻醉靶控系统的研制.中国医学装备2005;2:22-23.
3 张加强,邢玉英,杜文力,瑞芬太尼靶控输注时靶浓度和实测血药浓度的差异一靶控输注系统的性能评价,中华麻醉学杂志2005;25:645-648.
4 Minto C F, Schnider F W, Egan T D .et al,Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil-I model. Anesthesiolgy 1997; 86(1):10-23.
5 De.Castrov,Godetc,Mencia,et al.Target-controlled infusion for remifentanil in vascular patients hemodynamics and decrease remifentanil requirement. Anesth Analg 2003; 96(1):33-38.
6 张利萍,张昭,张芝翠等,全麻病人注射瑞芬太尼的药代动力学,中华麻醉学杂志 2006;26:43-45.
7GlassPS,HowellS.A.review.of.the.pharmacokinetics.and.pharmacodynamics.of.remifentanil, Anesth.Analg1999;89:7-14.
8Pitson,Wilmer,Bodenham,etal,Pharmacokinetics.of.remifentanil.and.its.major.metobolite,remifentanil.acid.in.ICU.patients.with.renal.impairment.BJAnesthesia2004;92:493-503.
9MichelsenLG,HolfordNH,Luw,etal,The.pharmacokinetics.of.remifentanil.in.patients.undergoing.coronary.artery.bypass.grafting.with.cardiopulmonary.bypass,Anesth.Analg.2001;93:1100-1105.
10 Kee.Warwick D,Khaw. Kims,Ma. Kwok, et al. Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery:a randomized double-blind controlled.trial.Anesthesiology 2006;104:14-20.
11JhaveriR,JushiP,Batenhovstr,etal,Dose.comparison.of.remifentanil.and.alfentanil.for.loss.of.consciousness.Anesthesiology1997;87:253-259.
12Bilgin,Hülya,Basagan.Mogol.Elif,Bekar,Ahmet;etal,A.Comparison.of.Effects.of.Alfentanil.Fentanyl.and.Remifentanil.on.Hemodynamic.and.Respiratory.ParametersDuring.Stereotactic.BraiBiopsy.Neurosurgical.Anesthesiology,2006;18,pp179-184.
13TwerskyRs,JanersonB,WarnerDS,etal,Hemodynamics.and.emergence.profile.of.remifentail.versus.fentanyl.compared.in.alarge.population.of.surgical.patients.JClin.Anesth 2001;13:407-416.
14Lecomte.Patrick;Quatala.Alexendre;LeManach,etal,The.coronary.and.myocardial.effect.of.remifentanil.and.sufentanil.in.Erythrocyte-perfuse.Isolated.Rabbit.Heart,Anesthesia Analgesia.2006;103:9-14.
15KayeAlanD,Blach.Amir,Phelps.James,An.analysis.of.remifentanil.in.the.pulmonary.vascular.bed.of.the.cat.AnesthesiaAnalgesia2006;102:118-123.
16 马浩男,赵军,瑞芬太尼药理学和临床应用进展,河北医药 2006;28:132-134.
17Wallden,Thorn,Wattwil.The.delay.of.gastric.empting.induced.by.remifentanil.is.not.influenced.by.posture.AnesthesiaAnalgesia2004;99:429-434.
18Crawford,Hickey,Zaarour,etal,Development.of.acute.opioid.Tolance.during.infusion.of.remifentanil.for.pediatric.scoliosis.surgery.AnesthesiaAnalgesia2006;12:1662-1667.
19 Celerier,Gonzalez,Maldonada,etal,Opioid-induced hyperalgesia in a murine model of postoperative pain:role of Nitric Oxide generated from the inducible nitric oxide synthase,Anesthesiology2006;104:546-555.
20 Tirault,Perrode,Clevenotet al,The effect of nefopam on morphine overconsumption induced by dose rimefentanil during propofol anesthesia for major abdominal surgery,Anesthesia,Analgesia2006;102:110-117.
21 Lee,LIbbyH.Y,Irwin,Michael,Lui,Siu-Kuen,Introperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide,Anexthesiology2005;102:398-402.
22 Leone,Rousseau,Avidan etal,Target concentrations of remifentanil with propofol to blunt coughing during intubation,cuff inflation,and trachel sunctioning.British Journal of Anesthesia2004;93:660-663.
23 吴滨阳,陈杰,王俊科。不同效应室浓度瑞芬太尼靶控时气管插管诱发病人的心血管反应。中华麻醉学杂志,2005,25:940-941。
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