Total Intravenous
Anesthesia
อ.นพ.ธีรวัฒน์ ชลาชีวะ
ภาควิชาวิสัญญีวิทยา
โรงพยาบาลรามาธิบดี
Beneficial of TIVA
• Decrease global warming from N2O
• Decrease pollution from volatile agents in OR
• Decrease risk in patients or operation :
– Suspected MH
– Air embolism
– Brain surgery
• More suitable during operation that difficult or impossible
to use inhalational anesthesia effectively
– Laryngoscope, bronchoscopy
– Thoracic surgery
– Gastroscopy or colonoscopy
• Decrease risk of PONV
• Ambulatory surgery
• Anesthesia in outside OR
Balanced Anesthesia
Unconscious - IV anesthetic agents
Hypnosis
- Inhalation agents
Amnesia
Reflex
suppression
Analgesia
- Opioid
Immobility
- Muscle
Muscle
relaxants
relaxation
Is the Patient Anesthethetized?
How do you gauge the depth of
anesthesia when using TIVA?
• Same skills are used as when administering
volatile drugs.
Pharmacokinetics and TIVA
• Use of mathematics to describe
How the body “handles” particular
drug
Open, three-compartment model
Organ perfusion
Tissue Group
Vessel-rich
Composition
CO (%)
Body
Mass(%)
10
75
Brain, heart, liver,
endocrine glands
Muscle
Muscle, skin
50
19
Fat
Fat
20
6
Vessel-poor
Bone, ligament,
cartilage
20
0
Open, three-compartment model
Context Sensitive Half Time
• Time plasma concentrations take to
reduce by 50% after discontinuing
infusion.
• Short CSHT drugs are desired for TIVA.
Open, three-compartment model
ke0: Describing drug delivery to the effect site
the pharmacokinetic rate constant which describes
the rate of equilibration between the plasma
concentration and effect site.
Effector Site Delay
Effective Blood Concentration
• Potency of
– Volatile drugs : MAC (anesthetic required to
prevent gross, purposeful movement in 50%
of patients in response to a noxious stimulus)
– Propofol : ED50
• propofol and N2O was 4.5 mcg/ml and the ED95
was 4.7 mcg ml.
• propofol was 6.0 mcg/ml and the ED95 was 6.2
mcg/ml.
Development of delivery
systems
AIM
1st
maintenance of optimum &
stable anesthetic condition
iv. bolus injection : single,
intermittent administration, iv. drip
2nd
Infusion pump
Syringe pump
3rd
TCI
TIVA-TCI : Target Controlled
Infusion
เป็ นเทคนิคที่นาเอาข้อมูลความสัมพันธ์ของอัตราการไหลของยาและ
ระดับยาในกระแสเลือดมาคานวณโดยเครื่ องคอมพิวเตอร์เพื่อควบคุมระดับ
ยาในแต่ละ Compartment ให้เป็ นไปตามต้องการ
• TCI
TIVA-TCI : Drugs suitable for
Hypnosis
 Propofol
 Dexmedetomidine
(Etomidate not suitable
due to suppressant of
adrenal steroidogenesis)
Analgesics
Alfentanil
Remifentanil
? fentanyl not for long infusion
(Morphine not suitable )
l
Propofol
• เป็ นยาในกลุ่ม alkylphenol ซึ่งเป็ นไขมันในอุณหภูมิหอ้ ง
• ประกอบด้วย 1%propofol, 10%soybean oil as longchain triglycerides, 2.25%glycerol and
1.2%purified egg phosphatide มี 0.005%
disodium edetate เพื่อ ป้ องกัน bacterial growth
• Metabolism
– Rapid metabolism in liver by conjugation and
glucorodination
– Renal excretion
– Extrahepatic metabolism ; lung, small intestine,
kidneys
• CNS
– Decrease CMRO2, CBF, ICP
– Anticonvulsion
– Myoclonic, hiccup
• CVS
– Venous dilatation, decrease PVR &CO -->
hypotension
– Greater CVS than thiopental
• Respiration
– may be transient apnea
– decrease TV, rate
Pharmacodynamic variability
• Age
– increased sensitivity of the elderly to the effects of
propofol. ke0, hence plasma effect site equilibration
has been reported not to be changed by age.
– These properties suggest that induction in elderly
patients should be achieved with lower plasma
concentrations than in younger adults, however it
should also be titrated more slowly to avoid side
effects.
Pharmacodynamic variability
• Systemic disease
– It has often been assumed
– patients with significant disease would require
less anaesthetic
• increased central nervous system sensitivity to the
drug
• increased free fraction of drug secondary to
reduced plasma protein binding (subtle
pharmacokinetic changes)
ในกรณี ไม่ใช้เครื่ อง TCI
การนาสลบ
ขนาดยานาสลบโดยปกติใช้ 1-2.5 มก./ กก. โดย
- ในผู้ใหญ่ ไม่ ได้ รับยา opioid หรือ benzodiazepine เป็ นยา premedication ใช้ 2.25-2.5 มก./ กก.
- คนแก่ อายุมากกว่ า 60 ปี ไม่ ได้ รับยา opioid หรือ benzodiazepine เป็ นยา premedication ใช้ 1.75
มก./ กก.
- เด็กไม่ ได้ รับยา opioid หรือ benzodiazepine เป็ นยา premedication ใช้ 2-3 มก./ กก.
การป้ องกัน hypotension ในผู้ป่วยทีป่ ่ วยเรื้อรัง หรือผู้ป่วยทีม่ ารับการผ่ าตัดหัวใจ ควรค่ อยๆให้
propofol 10-30 มก. จนกระทัง่ ผู้ป่วยสลบและควรให้ สารนา้ นาไปก่ อนให้ เพียงพอ
ในกรณี ไม่ใช้เครื่ อง TCI
Maintenance dose
- ในกรณีฉีดยาเป็ นครั้งคราว(intermittent bolus) ให้ 10-40 มก. ทุกๆ 2-3 นาที
- ในกรณีหยดยาอย่ างต่ อเนื่อง(continuous infusion) หลังให้ ยานาสลบ หยดยา 140 มคก./กก./นาที
เป็ นเวลา 10 นาที ต่ อด้ วย 100 มคก./กก./นาที โดยให้ ร่วมกับ fentanyl 0.02 มคก./กก./นาที หรือ
alfentanil 0.25 มคก./กก./นาที
TIVA-MCI : manually-controlled
infusion
“ are used to designate manual adjustment of
infusion rates for anaesthesia syringe pumps”
Initial infusion rate 10 min
Subsequence adjustment
so as to maintain
a stable level of anesthesia
Less
Pain
With
N2O
Without
N2O
Start
8
10
12
>10 mins.
5
7
9
>2 hrs.
3
5
7
Not easy to control
Time-consuming calculation
No compensate for interrupted infusion
Delayed emergence !!!
Require skill & experience
Propofol infusion rate (mg/kg/hr)
13
10 นาทีแรก
11
10 นาทีแรก
9
10 นาที-2 ชม
10 นาทีแรก
10 นาที-2 ชม
7
5
> 2 ชม
10 นาที-2 ชม
3 หัตถการที่ไม่ ปวด
> 2 ชม
> 2 ชม
ผ่าตัดในช่ องท้ อง
Opioid + N2O
ผ่าตัดในช่ องท้ อง
Opioid
หยุดยาก่ อนเวลาทีต่ ้ องการให้ ผู้ป่วยตืน่
ระยะเวลาของการสลบ
15 นาที
30 นาที
1 ชม.
2 ชม.
3 ชม.
4 ชม.
5 ชม.
6 ชม.
ควรหยุดยาก่ อนให้ ตนื่
5 (3-8) นาที
7.5 (4-12) นาที
10 (4-15) นาที
12.5 (5-20) นาที
15 (6-23) นาที
20 (8-33) นาที
25 (9-43) นาที
30 (20-47) นาที
TCI –propofol concentration
Cet 2-3 µg/ml loss of
eyelash reflex
Cet 4-8 µg/ml for
anesthetic procedure
Intubation, LMA
CP50 2.7 – 3.4
µg/ml loss of
response to verbal
or tactile stimuli*
Target = ?
Target concn based on
•Level of stimulation
•Drug interaction
•Desired clinical endpoint
•Decrement time
•Intraindividual variability
* : Vuyk J et al. Anesthesiology 1992; 77: 3.
Crankshaw DP et al. Anaesth Intensive Care 1994; 22: 481.
Smith C et al. Anesthesiology 1994; 81: 820.
TCI for induction & Intubation
•MO 5-10mg
•Midazolam1-2mg
Propofol TCI
•Cet 2-3 µg/ml
loss of response
Check ventilation
↓Cet 2-3 µg/ml
wait for
next painful stimuli
↑Cet 4-6 µg/ml
for skin incision
Muscle relaxant
Ventilate 1.0-1.5 min
 Cet 4-8 µg/ml
for intubation
Ventilate 1.0-1.5 min
TTPE
Propofol in different lipids
• The standard propofol formulation
contains 10%soybean oil as long-chain
triglycerides.
– Pain on injection 14.7%
• Long- and medium-chain trigycerides
reduced incidence of pain on injection to
2.7%.
Propofol-related infusion syndrome
High dose infusion >5 mg/kg/hr for > 48 hrs
Abrupt onset of profound bradycardia,
metabolic acidosis lipemic plasma,
symptoms
renal failure, fatty liver,
rhabdomyolysis or myoglobinuria
Risk factors : poor oxygen delivery, sepsis
serious cerebral injury
Monitor : acidosis, K+, renal function
Thank you for your attention
THIOBARBITURATE(THIOPENTAL)
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Preparation
2.5% pale yellow solution pH 10 - 11
bacteriostatic
Mechanism of action
Interacts with GABA receptor-->membrane
hyperpolarization
• Terminal of action
• Redistribution-->ultrashort acting
• Metabolism --- liver
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Excretion--renal excretion of water-soluble
Dose
3-5 mg/kg IV depending on age, ASA :
Onset = 60 seconds
Recovery = 5-10 mins
• Pharmacologic actions
• CNS
– Decrease ICP, CMRO2, CBF
– Anticonvulsant 50-100 mg IV
– Cerebral protection
• Create electrical silence ;15-40 mg/kg then 2-4
mg/kg/hr
• CVS
– Venous dilatation--> CO, ABP
– Baroreceptor reflex
– Increase HR
• CO may decrease markedly
– Hypovolemia
– Beta blocker
– Previous heart disease
• Respiratory
–
–
–
–
Depression medullary center--> RR, TV
Apnea
Upper airway obstruction
Airway reflex
• Bronchospasm
• Laryngospasm
Side Effects
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Thrombophlebitis
Intraarterial injection-->spasm
Allergic reaction( histamine release )
Hypotension
Subcutaneous injection-->necrosis
Contraindication *PORPHYRIA*
BENZODIAZEPINES
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Minor tranquilizer
Antianxiety, sedation
Amnesia
Control convulsion
Relax skeletal muscle
DIAZEPAM (Valium)
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Highly lipid soluble
Insoluble in water
Mechanism of action
Modifies GABA receptor activity
Metabolism--> hepatic
Excretion--> renal
Indication
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–
–
–
Premedication : 0.05-0.1 mg/kg
Induction of anesthesia :0.3-0.5 mg/kg
Intravenous sedation : 1-2 mg p.r.n. IV
Treatment of seizure
MIDAZOLAM (Dormicum)
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pH<4-->Water soluble
Physiologic pH--> lipid soluble
Mechanism of action
Modifies GABA receptor activity
t 1/2 = 1 - 4 hr.
Metabolism--> hepatic
Excretion--> renal
Indication
– Premedication : 0.07-0.15 mg/kg
– induction of anesthesia : 0.15-0.3 mg/kg
– intravenous sedation : 0.5-1 mg repeat to effect
BENZODIAZEPINES
• CNS
–
–
–
–
Decrease CMRO2, CBF
HR increase due to drug induce vagolysis
Anxiolysis, amnesia (dose related)
Anticonvulsant properties
• CVS
– Slight decrease SVR, BP
• Respiratory
–
–
–
–
Dose related respiratory depression
Respiratory response to CO2 decrease
Lower incidence of apnea
Careful titration
FLUMAZENIL (Anexate)
• Central acting benzodiazepine antagonist
• Dose 0.25 - 0.5 mg.
• Onset in 30 - 60 sec.
• Duration 1 hr.
• Liver metabolized
• Side effects
• dizziness, anxiety, nausea, vomiting,
agitation
KETAMINE
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Preparation
Water soluble, racemic mixture
Mechanism of action
Act on NMDA receptor
Act on opioid and cholinergic receptor
Causes dissociation
Metabolism-- hepatic
Norketamine--1/5 potency of ketamine
Excretion--renal
• Indications
– induction of anesthesia
– sole anesthesia
– premedication
• DOSE
– 1-2 mg/kg IV induction
– 3-5 mg/kg IM induction
– 0.2-0.8 mg/kg IV sedation-->5-20 mcg/kg/min
– 15-45 mcg/kg/min with O2/N2O maintenance
• CNS
– Increase CMRO2, CBF, ICP
– Amnesia, analgesia
• CVS
– Increase MAP, CO, HR
– If cathecholamine depletion or autonomic
– block--> depress myocardium
• Respiration
– Bronchodilation--sym mediated
– Relative preservation of laryngeal reflexs
PROPOFOL (Dripivan)
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2,6 di-isopropylphenol; 1% solution in
egg white lecithin emulsion
Mechanism
May be at GABA receptor
Metabilism--liver
Excretion--renal
• CNS
– Decrease CMRO2, CBF, ICP
– Anticonvulsion
– Myoclonic, hiccup
• CVS
– Venous dilatation, decrease PVR &cardiac
– depression--> hypotension
– Greater CVS than thiopental
• Respiration
– may be transient apnea
– decrease TV, rate
• Indication
– Induction of anesthesia
– Sole anesthetic for short procedure
– Treatment of seizures
• Dose
– 2-2.5 mg/kg IV induction
– 100-200 mcg/kg/min maintenance
– 25-100 mcg/kg/min sedation
ETOMIDATE
• Mechanism
– May act at GABA receptor at reticular
activating system
• Metabolism--hepatic
• Excretion--renal
• Dose
– 0.2-0.4 mg/kg IV induction
– onset 30-60 sec.
– Recovery = 5 mins
• CNS
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–
–
–
–
–
may increase EEG activity in those with
epilepsy
Myoclonic movement (pretreat c opioid )
CBF, ICP, CMRO2 decrease
CPP maintained
Enhance SSEP response
• CVS-- STABLE
• Respiration
– Transient apnea
– Decrease rate and TV
• Disadvantage ; Adrenocortical suppression
OPIOIDS
• Agonist
• Partial agonist
• Agonist -antagonist
• Antagonist
• Agonist
Morphine
Codeine
Pethidine
Sufentanyl
Fentanyl
Alfentanyl
• Partial agonist
• Agonist - antagonist
Buprenorphine
Pentazocine,
Nalbuphine,
Nalorphine
•
Antagonist
Naloxone
• Benefits
– Good analgesia (dull pain)
– Sedation, euphoria
– Antitussive
• Indications
– Premedication
– Supplement anesthesia
– Sole anesthesia
– Analgesia
• Acute postoperative pain
• Cancer pain
Side effects
• Nausea and vomiting
• Pruritus
• Visceral smooth
muscle
– Constipation
– Biliary spasm
– Ureteral spasm
• CVS
– Hypotension
– Bradycardia
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RR and response
to PaCO2
Chest wall rigidity
Urinary retension
Histamine release
MORPHINE
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Supraspinal analgesia
Increase pain threshold
Sedation, euphoria
Pruritus, urinary difficulty
Histamine release
Spasm of sphincter of oddi
Anti - tussive
Dose related resp. depression
PETHIDINE
• Potency 1/10 of MOSO4
• Equianalgesic dose : same effect of resp.
depression
• Shorter duration of action
• Atropine - like effects :
HR,bronchodilatation, mydriasis
• Active metabolites Norpethidine
• CNS excitement, agitation seizures
FENTANYL
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Potency = 100 times MOSO4
Rapid onset, short duration
No histamine release
Bradycardia
Truncal rigidity
NALOXONE
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Pure opioid antagonis
Dose 1 - 4 mcg/kg
Duration 30 - 45 min
Caution > close observe for
– recurrent sedation/depression
– increase sympathetic outflow
– reverse analgesia + resp. depression