孵化器医院教学课件静脉麻醉进展

静脉麻醉进展新速效短效药Newerrapidandshort-actingdrugs丙泊酚、依托咪酯、雷米芬太尼新药代概念New

pharmocokinetic

concepts多室药代模型应用于临床长时间输注后半衰期效应室新给药系统New

delivery

systems

-

TCI静脉麻醉药的时－量相关半衰期药代学进展－多室模型应用于临床实际Maintenance

infusion

rate

= CT

×V1×(

k10

+

k12e-

k21t

+

k13e-

k31t

)TCI模型麻醉药镇静镇痛肌松苏芬太尼瑞芬太尼MarshArdenGepts

Minto----爱可松-----Szenohradszky丙泊酚依托咪酯TCI两大贡献TCI

自动提供计算的血浆药物浓度

TCI=Intravenous

VaporizerTCI靶浓度滴定药物作用的治疗窗EC50

=

MAC64208100102030Target

Concentration

(µg/ml)TCI-实时血药浓度非实际血药浓度缺乏国人的药代动力学参数临床研究证明用于国人是可靠的丙泊酚Marsh模型系统误差为10%-30%min效应室（生物相）v2v3v1注射k13k31k21k12k1eKeoKeo效应室（生物相）BLOOD

-

EFFECT

DELAY10864200102030Target

Concentration

(µg/ml)实时监测呼气末丙泊酚浓度On-line

monitoring

of

end-tidal

propofol

concentrationReal-time

monitoring

of

propofol

in

expired

air

inhumans

undergoing

total

intravenous

anesthesiaHornuss

C,

Anesthesiol

2007;106:665-74On-line

monitoring

of

end-tidal

propofolconcentration

in

anesthetized

patientsEvan

D

Kharasch, Anesthesiol

2007;106:652-4Shortly

after

the

clinical

introduction

ofpropofol,

the

aroma

noticeableimmediately

upon

opening

the

bottlesuggested

a

sufficiently

high

vaporpressure

to

portend

pulmonary

propofolelimination,

and

hence

the

possibility

ofdetecting

and

quantifying

propofol

inexpired

gas

by

the

mass

spectrometerthen

in

use

in

the

OR.

A

proposal

to

ourOR’s

mass

spectrometer

manufacturer

toinvestigate

this

possibility

was

notreviewed

favorably,

and

the

idea

wassoon

forgotten.Concentration

of

propofol

in

plasma

(ug/ml)药效学进展TCI靶浓度滴定药物作用的治疗窗EC50

=

MAC丙泊酚意识消失国人与白种人差异–

a

multicenter

clinical

trial(EC05

–

EC95)(3.1

-

7.3)(2.86

-

4.80)(1.5

-

4.1)Cp(µg/ml)Et(µg/ml)BIS白人国人白人国人白人国人EC505.23.832.82.2370.957.9(1.29

-

3.18)(88.8

-

52.9)(77.2

-

39.6)Kenny

GNC.

BJA

2003;90(2):127Xu

ZP,

et

al.

Anesth

Analg

2009;

108(2):478-83药效：药物的相互作用药效：不同目标点药物相互作用-EC95281004

6药物B1.0药

0.9物

0.8A

0.70.60.50.40.30.20.10.095%

noresponse

toverbal

command95%

no

movement

at

skin

incision95%

no

hemodynamic

responseat

skin

incisionIdealClinical

AnesthesiaPK-PD

Models响应曲面模型的应用各种比例下(B/(A+B),两种药的同时效应作为一种新药。每一条实线代表一种“新药”的药效学S曲线，由若干条曲线确定一个曲面，这个曲面就是药物相互作用的响应曲面PK-PD

Models意识消失EC50-EC95范围消除伤害刺激EC50-EC95范围两药同时应用，自动根据其相互作用计算和显示各自新的EC50-EC95范围awake,awarenesstoodeepanesthesiaadequateanesthesiaawake,awarenesstoodeepanesthesiaawake,awarenesstoodeepanesthesiaadequate

anesthesiaSmartPilot白色圆点：计算得到的当前的麻醉深度白色箭头：计算得到的15分钟后的麻醉深度SmartPilot

ViewA：MAC

90B：MAC

50C：MAC

awake

（MAC

awake

50）用于吸入麻药的二维图

用于静脉麻药的二维图A：TOL

90B：TOL

50C：TOSS

（TOSS

50）闭环控制麻醉Closed-loop

control

of

anesthesiaClosed-loop

systems自动达到和维持预设的靶目标监测变量-导向-控制-生理学/药理学功能帮助麻醉医生滴定最佳的给药剂量防止给药过量或不足计算机技术/可靠的药理学作用测定麻醉深度监测仍是难题给药指标:吸入-MAC静脉-TCI反馈指标:

BISNarcotrendTOF

-Watch监测：个体差异过量不足残余作用肌肉松弛程度可以精确监测Ｔ４消失表明阻滞程度达75%

Ｔ３和Ｔ２消失阻滞程度分别达到80%和90%最后Ｔ１消失，表明阻滞程度达到100%如４次颤搐反应都存在则表明阻滞程度不足

75%方法与TOF-watch比较验证肌松闭环输注系统监测肌松的准确性30例自身对照每一例病人均同时进行两种肌松监测

验证肌松闭环输注系统麻醉中的有效性和安全性闭环肌松输注系统罗库溴铵输注参数-诱导量为0.6mg/kg，维持输注速度为0.12mg/kg/h，增药速度为2mg/kg/h，反馈条件-计数2系统设定当肌松监测达到反馈条件（计数2)连续3次后开始增药当肌松监测低于反馈条件（计数2）连续2次后则转为维持速度临床满意麻醉－阈值/底线意识-无知晓镇痛-无伤害性刺激引起的不良(应激)反应肌肉-松弛reduction

inincidence

ofawareness

withrecall(high

risk

patientsp<0.05)11

cases2

casesNo

BISn=1,238BISn=1,22782%1%0.5%0%Myles

PS,

et

al.

Bispectral

index

monitoring

to

prevent

awareness

during

anaesthesia:The

B-Aware

randomised

controlled

trial. Lancet

2004;

363:1757–63首次BIS预防知晓多中心研究:B-AwareEkman

A,

Lindholm

ML,

et

al.

Acta

Anaesthesiol

Scand

2004,48:20–6.77%2

casesBisgroupn=

4945Historicalgroupn=

7826应用BIS监测知晓率由

0.18%（历史对照）降至

0.04%Anesthesia

Awarenessandthe

BispectralIndex-

The

B-Unaware

Trial0.200.40.610.8B-UNAwareIncidence

(%)Avidan

MS,

et

al.

N

Engl

J

Med

2008,

358:1097-108ETAG

BISn=974

967ETAG组2例知晓BIS组2例知晓BIS-guided

group

(A)Control

group

(B)61

2

3

4

5

6543

4

421

2

21

1

1

1

1

1

10center

center

center

center

center

center

center

center

center

center

center

center

center7

8

9

10

11

12

13CentersFrequencyawareness

frequency

in

Group

A

awarenessfrequency

in

Group

Bconfirmedawareness4

(0.14%）减少77%15

(0.65%)P=0.002possibleawareness4

(0.14%)6

(0.26%)P=0.485dreaming90

(3.1%)71

(3.1%)P=0.986Zhang

C,

etal.

Bispectral

index

monitoringprevent

awareness

during

total

intravenousanaesthesia:

a

prospective,

randomized,

double-blinded,

multicentre

controlled

trial.CMJ

2011,124:3664-95228

cases

/

13

centers监测伤害性刺激指标评价体动心血管反应内分泌反应心率变异性(HRV)TPI

(Tip

PerfusionIndex)SSI

(Surgery

Stress

Index

)末梢灌注指数(TPI)Masimo脉氧血红蛋白监测仪血管容积波的波形光传感器末梢血管内通过的血容量大小转化为电信号-血管容积波经计算机处理后转化为0-100的指数Analgesia

/

Nociception

Index

(ANI)Mathieu

JEANNE,

MD,

PhDAnesthesia

&

Intensive

CareCic-It

807

InsermUniversity

HospitalLille,

FrancePhysioDoloris:

a

monitoring

device

forAnalgesia

/

Nociception

balanceevaluation

using

Heart

Rate

Variability

analysisExcessAnesthesiaExcessAnesthesiaExcessAnesthesia预防知晓只需简单加深麻醉？病人无必要去耐受深麻醉！加深麻醉深度将导致其他并发症过度镇静与术后死亡率高有关

BIS<45（深麻醉）术后一年死亡率明显增加Sub-study证实死亡率与镇静状态关系的报道来自于针对其他目的前瞻性研究数据的追加分析最初设计目的是评估BIS对知晓发生率的影响B-AwareMyles

PS,

et

al. Lancet

2004,363:1757–63B-UnawareAvidan

MS,etal. NEnglJMed2008,

358:1097-108LindholmEkman

A,Lindholm

ML,

et

al. Acta

AnaesthesiolScand2004,48:20–6The

Effect

of

Bispectral

Index

Monitoring

on

Long-TermSurvival

in

the

B-Aware

Trial4.1-yr随访BIS监测组-低BIS与预后的关系（对照组未记录BIS）BIS

<40

for>5

min与其余BIS监测病人比较

hazard

ratio

for

death1.41(95%

CI:

1.02-1.95;

P

<

0.039)odds

ratios

for

MI1.94

(P

<

0.02)for

stroke

3.23

(P

<

0.01)B-Aware亚研究结论理想BIS组的死亡率和发病率明显较低Leslie

K,

Myles

PS,

et

al.

Anesth

Analg

2010;110:816–22substudy

of

the

B-Aware

trialn

=

4087,

2

yr

follow

upTBIS

<45预测术后1年和2年死亡率hazard

ratio

=1.13

和1.18The

effect

is

very

weak

in

comparison

withASA

IV

=19.3malignancy

status

=9.3age＞80

=2.93Lindholm’s

subsdutyLindholm

et

al.

Anesth

Analg

2009;108:508-12Association

of

perioperative

risk

factors

and

cumulativeduration

of

low

bispectral

index

with

intermediate-termmortality

after

cardiac

surgery

in

the

B-Unaware