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Total Intravenous Anesthesia

Total Intravenous Anesthesia. อ.นพ.ธีรวัฒน์ ชลาชีวะ ภาควิชาวิสัญญีวิทยา โรงพยาบาลรามาธิบดี. Beneficial of TIVA. Decrease global warming from N 2 O Decrease pollution from volatile agents in OR Decrease risk in patients or operation : Suspected MH Air embolism Brain surgery

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Total Intravenous Anesthesia

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  1. Total Intravenous Anesthesia อ.นพ.ธีรวัฒน์ ชลาชีวะ ภาควิชาวิสัญญีวิทยา โรงพยาบาลรามาธิบดี

  2. 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 duringoperation 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

  3. Balanced Anesthesia Unconscious Hypnosis Amnesia - IV anesthetic agents - Inhalation agents Reflex suppression Analgesia Immobility Muscle relaxation - Muscle relaxants - Opioid

  4. Is the Patient Anesthethetized?How do you gauge the depth of anesthesia when using TIVA? • Same skills are used as when administering volatile drugs.

  5. Pharmacokinetics and TIVA • Use of mathematics to describe How the body “handles” particular drug

  6. Open, three-compartment model

  7. Tissue Group Composition Body Mass(%) CO (%) Vessel-rich Brain, heart, liver, endocrine glands 10 75 Muscle Muscle, skin 50 19 Fat Fat 20 6 Vessel-poor Bone, ligament, cartilage 20 0 Organ perfusion

  8. Open, three-compartment model

  9. Context Sensitive Half Time • Time plasma concentrations take to reduce by 50% after discontinuing infusion. • Short CSHT drugs are desired for TIVA.

  10. Open, three-compartment model

  11. 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.

  12. Effector Site Delay

  13. 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.

  14. Development of delivery systems maintenance of optimum & stable anesthetic condition AIM 1st iv. bolus injection : single, intermittent administration, iv. drip Infusion pump Syringe pump TCI 2nd 3rd

  15. TIVA-TCI : Target Controlled Infusion • TCIเป็นเทคนิคที่นำเอาข้อมูลความสัมพันธ์ของอัตราการไหลของยาและระดับยาในกระแสเลือดมาคำนวณโดยเครื่องคอมพิวเตอร์เพื่อควบคุมระดับยาในแต่ละ Compartmentให้เป็นไปตามต้องการ

  16. 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 Check wake up time Propofol Cet 1.5-2.0 µg/ml = wake up √ Check wake up time Propofol Cet 1.5-2.0 µg/ml = wake up √

  17. Propofol • เป็นยาในกลุ่ม alkylphenol ซึ่งเป็นไขมันในอุณหภูมิห้อง • ประกอบด้วย 1%propofol, 10%soybean oil as long-chain triglycerides, 2.25%glycerol and 1.2%purified egg phosphatide มี 0.005% disodium edetate เพื่อ ป้องกัน bacterial growth • Metabolism • Rapid metabolism in liver by conjugation and glucorodination • Renal excretion • Extrahepatic metabolism ; lung, small intestine, kidneys

  18. 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

  19. 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 sideeffects.

  20. 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)

  21. ในกรณีไม่ใช้เครื่อง TCI การนำสลบ ขนาดยานำสลบโดยปกติใช้ 1-2.5 มก./ กก.โดย - ในผู้ใหญ่ ไม่ได้รับยา opioid หรือ benzodiazepine เป็นยา premedication ใช้ 2.25-2.5 มก./ กก. - คนแก่อายุมากกว่า 60 ปีไม่ได้รับยา opioid หรือ benzodiazepine เป็นยา premedication ใช้ 1.75 มก./ กก. - เด็กไม่ได้รับยา opioid หรือ benzodiazepine เป็นยา premedication ใช้ 2-3 มก./ กก. การป้องกัน hypotension ในผู้ป่วยที่ป่วยเรื้อรัง หรือผู้ป่วยที่มารับการผ่าตัดหัวใจ ควรค่อยๆให้ propofol 10-30 มก.จนกระทั่งผู้ป่วยสลบและควรให้สารน้ำนำไปก่อนให้เพียงพอ

  22. ในกรณีไม่ใช้เครื่อง TCI Maintenance dose - ในกรณีฉีดยาเป็นครั้งคราว(intermittent bolus) ให้ 10-40 มก. ทุกๆ 2-3 นาที - ในกรณีหยดยาอย่างต่อเนื่อง(continuous infusion) หลังให้ยานำสลบ หยดยา 140 มคก./กก./นาที เป็นเวลา 10 นาที ต่อด้วย 100 มคก./กก./นาทีโดยให้ร่วมกับ fentanyl 0.02 มคก./กก./นาทีหรือ alfentanil 0.25 มคก./กก./นาที

  23. TIVA-MCI: manually-controlled infusion Less Pain With N2O Without N2O Start 8 10 12 >10 mins. 5 7 9 >2 hrs. 3 5 7 “ are used to designate manual adjustment of infusion rates for anaesthesia syringe pumps” “ 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 Not easy to control Time-consuming calculation No compensate for interrupted infusion Delayed emergence !!! Require skill & experience

  24. ระยะเวลาของการสลบ ควรหยุดยาก่อนให้ตื่น 15 นาที 5 (3-8) นาที 30 นาที 7.5 (4-12) นาที 1 ชม. 10 (4-15) นาที 2 ชม. 12.5 (5-20) นาที 3 ชม. 15 (6-23) นาที 4 ชม. 20 (8-33) นาที 5 ชม. 25 (9-43) นาที 6 ชม. 30 (20-47) นาที หยุดยาก่อนเวลาที่ต้องการให้ผู้ป่วยตื่น

  25. TCI –propofol concentration • Target concn based on • Level of stimulation • Drug interaction • Desired clinical endpoint • Decrement time • Intraindividual variability 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* Cet 2-3 µg/ml loss of eyelash reflex Cet 4-8 µg/ml for anesthetic procedure Intubation, LMA Target = ? * : 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.

  26. TCI for induction & Intubation ↓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 • MO 5-10mg • Midazolam1-2mg • Propofol TCI • Cet 2-3 µg/ml • loss of response • Check ventilation

  27. 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%.

  28. 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

  29. Thank you for your attention

  30. THIOBARBITURATE(THIOPENTAL) • 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

  31. Excretion--renal excretion of water-soluble • Dose • 3-5 mg/kg IV depending on age, ASA : • Onset = 60 seconds • Recovery = 5-10 mins

  32. 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

  33. Side Effects • Thrombophlebitis • Intraarterial injection-->spasm • Allergic reaction( histamine release ) • Hypotension • Subcutaneous injection-->necrosis Contraindication *PORPHYRIA*

  34. BENZODIAZEPINES • Minor tranquilizer • Antianxiety, sedation • Amnesia • Control convulsion • Relax skeletal muscle

  35. DIAZEPAM (Valium) • Highly lipid soluble • Insoluble in water • Mechanism of action • Modifies GABA receptor activity • Metabolism--> hepatic • Excretion--> renal • Indication • 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

  36. MIDAZOLAM (Dormicum) • 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

  37. 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

  38. 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

  39. KETAMINE • 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

  40. 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

  41. 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

  42. PROPOFOL (Dripivan) • 2,6 di-isopropylphenol; 1% solution in • egg white lecithin emulsion • Mechanism • May be at GABA receptor • Metabilism--liver • Excretion--renal

  43. 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

  44. 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

  45. 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

  46. CNS • 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

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