Inhalation anesthetic drugs
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Inhalation anesthetic drugs

Inhalation anesthetic drugs


Inhalation anesthetic drugs

Uptake and distributionProperties of ideal inhalational anesthetic agentsShould have pleasant odor , non irritate , rapid and pleasant induction of anesthesiaLow blood/gas partition coefficient  rapid induction and recovery Stable in storage , not interact with anesthetic apparatus Neither flammable nor explosive


Inhalation anesthetic drugs

Properties of ideal inhalational anesthetic agents Analgesia and muscle relaxant  Minimal depression of cardiovascular and respiratory systems Nontoxic , not be metabolized in body Completely insert and eliminated Completelyand rapid in unchanged from the lung


Inhalation anesthetic drugs

  • Inhaled Anesthetic Agents

  • Nitrous oxide first described 179 and clinical use by Wells 1844

  • 1846 William Morton first successful public demonstration of diethyl ether for GA (flammable , copious airway secretion and severe PONV)

  • 1847 Chloroform (hepatotoxic , severer SVdepression)


Inhalation anesthetic drugs

 1929 Cyclopropane (highly flammable)

 1934 Trichloroethylene (react with) soda lime to form toxic gas phosgene

  • 1954 Fluroxene (Flammable, PONV)

  • 1956 Halothane

  • 1959 Methoxyflurane (free fluoride ions :nephrotoxic)

  • 1972 enflurane

  • 1981 Isoflurane

  • 1993 Desflurane

  • 1995 Sevoflurane


Inhalation anesthetic drugs

Minimal alveolar concentration : MAC

  • เป็นค่า alveolar concentration ของยาดมสลบที่ 1 atm ที่ร้อยละ 50 ของผู้ป่วยไม่ตอบสนองต่อ surgical stimuli

  • เป็นตัวเปรียบเทียบถึง potency ของยาดมสลบแต่ละตัว

  • MAC incubate =1.3 MAC

  • MAC awake =0.5 MAC

  • MAC ไม่เปลี่ยนแปลงตามเพศ เชื้อชาติ ระยะเวลาของการให้ยาดมสลบ


Inhalation anesthetic drugs

  • Factors : increase MAC

  • Yong

  • Chronic alcoholic

  • Acute amphetamine , cocaine , ephedrine intake

  • Hypernatremia

  • Hyperthermia


Inhalation anesthetic drugs

Factors : decrease MAC

 Aging

  • Acute alcohool intake chronic amphetamine intake

  • Hypothermia

  • Anemia (HCT<10) , Hypoxemia (Pao2<40)

  • Shock or induced hypotension

  • Hyponatremia , Hypercalcemia , Metabolic acidosis

  • Pregnancy

  • Drugs : opioids , berbiturate , ketamine , LA , BZP , sympatholytics


Inhalation anesthetic drugs

Inhalational anesthetic agents

  • Anesthetic gas:มีสถานะเป็น gas ที่อุณหภูมิห้องมี 3 ชนิดคือ nitrous oxide (N2O), Cyclopropane (C3H6)ethylene C2H4

  • Volatile anesthetics : มีสถานะเป็นของเหวที่อุณหภูมิห้องและสามารถระเหยเป็นไอง่ายจึงนิยมเรียกว่ายาสลบชนิดไอระเหย

    -Ether เรียกชื่อตาม diethyl ether เป็นยาตัวแรกที่ค้นพบได้แก่ divinyl ether , fluroxene , methoxyflurane , enflurane, isoflurane , sevoflurane , desflurane

    -Halogenated hydrocacarbon ได้แก่ chloroform , trichlorethylene , halathane


Inhalation anesthetic drugs

Anesthetic gas : N2O

  • Physical properties

    - ไม่มีสี ไม่มีกลิ่น not irritate airway

    - ไม่ติดไฟแต่ช่วยให้ไฟติดได้

    - MW 44 , Sp. Gravity 1.5

    - Bl/gas partition coefficient ต่ำมากคือ 0.47 แต่มี MAC สูงคือ 105

    -Stable in soda lime , eliminated unchanged by lung

    -Storage in compressed tank in liquid ดังนั้น สามารถวัดปริมาตรโดยการชั่งน้ำหนักถัง


Inhalation anesthetic drugs

Effect on organ systems

  • Minimal effect to CV and respiratory system

  • good analgesia

  • not trigger MH, no muscle relaxant effect

  • Minimal decrease renal and hepatic blood flow

  • Increase incidence of PONV จากการกระตุ้น CRTA และ vomiting center ใน medulla

  • prolong use : bone marrow suppression  megaloblastic anemia , pernicious anemia and peripheral neuropathies

  • Teratogenic effect esp, first trimester


Inhalation anesthetic drugs

Contraindication : N2O

  • Air embolism

  • Pneumothorax

  • Acute intestinal obstruction

  • Intracranial air

  • Lung cyst

  • Intraoccular bubbles

  • Tympanic membrane graft


Inhalation anesthetic drugs

Diffusion hypoxia : N2O

  • เมื่อสิ้นสุดการผ่าตัดจะพบว่ามีในตรัสออกไซด์ถูกขับออกมาที่ alveoli จำนวนมากและรวดเร็วจะทำให้ alveolar oxygen ลดลงเป็น dilutional effect นั่นเอง

  • เราสามารถป้องกันได้โดยให้สูดดม 100% ออกซิเจนเป็นเวลานาน 5-10 นาทีหลังหยุดให้ในตรัสออกไซด์ และให้สูดดมออกซิเจนในห้องพักฟื้นด้วย


Inhalation anesthetic drugs

Halothane

  • 2-bromo-2-1,1,1,-trifluoroethane

  • colorless, not pungent odor

  • 0.01% Thymol preservative and amber-colored

  • bottle retard spontaneous oxidative decomposition

  • not expensive

  • Low Bl/gas =2.3

  • 1MAC=0.74


Inhalation anesthetic drugs

Halothane

  • Metabolism : ประมาณ 20 % ถูกทำลายที่ตับโดย oxidative pathway ได้ metabolites เป็น Bromide,Chlorie, trifluoroacetic acid และ trifluoroacetylethnol amide

  • ส่วนน้อยถูกทำลายโดย reductive pathway โดยเฉพาะโดยเฉพาะถ้ามีภาวะ hypoxia หรือได้รับยาพวก enzyme inducing agents เช่น phenobarbitaone จะได้ metabolites เป็น fluoride ion


Inhalation anesthetic drugs

Effect on organ systems : CVS

  • Direct myocardial depression : dosedependent

  • Bradycardia : dose dependent (central vagal stimulation)

  • Decrease blood pressure : dose dependent

  • Decrease myocardial oxygen demand

  • Sensitizes hart t exogenous catecholamine : should avoid using adrenaline > 1.5 microgram/kg


Inhalation anesthetic drugs

  • Effect on organ systems : CNS เพิ่ม CBF และ ICP แต่ลด CMRO2

  • สามารถใช้ได้ในการผ่าตัดสมอง แต่ควรทำ hyperventilation ก่อนให้


Inhalation anesthetic drugs

Effect on organ

Systems: Respiratory system

Nonirritate airway , not pungent order ,less airway secretion

Depress pharyngeal and laryngeal reflexes enough MV so increasing CO2: dose dependent

Impair mucociliary function : dose dependent

Potent bronchodilator


Inhalation anesthetic drugs

Effect on organ systems :GI

 Decrease GI motility

PONV but not severe


Inhalation anesthetic drugs

  • Effect on organ systems : Skeletal muscle

  • Muscle relaxation ,potentiate MR

  • Trigger MH

  • PO shivering


Inhalation anesthetic drugs

Effect on organ systems:Uterus

Uterine muscle relax esp. conc > 0.5% เกิด uterine atony and postpartum hemorrhage ได้ใน C/S or therapeutic abortion


Inhalation anesthetic drugs

Effect on organ systems: Renal and liver

 Decrease GFR ,urine output

Decrease hepatic blood flow

Decrease matabolism of other drugs


Inhalation anesthetic drugs

  • Halothane associated hepatic dysfunction

  • 1:35,000

  • สาเหตุแท้จริงยังไม่ทราบ เชื่อว่าเกิดจาก toxix metabolites จากการทำลาย halothane ผ่านทาง reductive pathway และระบบ immune system

  • Centrilobular necrosis

  • Risk factors

  • - Hypoxemia ,Obesity

  • - repeat halothane exposure (3 month)

  • - enzyme inducting agent

  • - Family history or previous liver dysfunction


Inhalation anesthetic drugs

  • Advantages : Halothane

  • Rapid snooth induction

  • Minimal stimulation of salivary and bronchial secretions

  • Bronchodilatation

  • Muscle relaxation

  • Relatively rapid recovery


Inhalation anesthetic drugs

  • Disadvantages : Halothane

  • Poor analgesia

  • Arrhythmias

  • Postoperative shivering

  • Possibility of liver toxicity especially in repeated administration


Inhalation anesthetic drugs

  • Enfiurane

  • Colorless , not pungent odor , not irritate airway , less secretion

  • Bl/gas = 1.9 MAC = 1.7

  • 2.5% metabolised at liver

  • metabilites : very low inorganic fluoride


Inhalation anesthetic drugs

  • Enflurane : effect on organ systems

  • Depress respiration as halothane , Increase PaCO2 > halothane

  • Depress CV : dose dependent

  • No central vadal stimulation so may cause reflex tachycardia

  • เพิ่ม CBF และ ICP ลด CMRO2

  • In high conc. (>3%) พบ EEG คล้าย tonic clonic seizures esp. in hypocapnia (เลี่ยงการทำ hyperventilation เพื่อลด ICP)

  • เลี่ยงในผู้ป่วย epilepsy


Inhalation anesthetic drugs

  • Advantages : Enflurane

  • Rapid induction and recovery

  • Little biotransformation

  • Muscle relaxation

  • Low incidence of arrhythmias


Inhalation anesthetic drugs

  • Disadvantages : Enflurane

  • Relatively high cost

  • Seizure activity on EEG


Inhalation anesthetic drugs

  • Isoflurane

  • Isomer of enflurane

  • Colorless , pungent odor

  • Stable in storage , nonflammable

  • Bl/gas = 1.2

  • MAC = 1.2


Inhalation anesthetic drugs

  • Isoflurane : effecton organ systems

  • Depress respiration and bronchodilatation

  • Less myocardium depression than halothane and enflurane

  • Decrease vasodilation coronary steal syndrome in CAHD pt .

  • Muscle relaxation , uterine relaxation, potentate MR

  • 0.2 % metabolised at liver

  • Non toxic to liver


Inhalation anesthetic drugs

  • Advantages : Isoflurane

  • Rapid induction and recovery

  • Minimal biotransformation

  • Cardiovascular stability

  • Muscle relaxation


Inhalation anesthetic drugs

  • Disadvantages : Isoflurane

  • High cost

  • Pungent odor

  • Coronary steal syndrome at high conc


Inhalation anesthetic drugs

Sevoflurane

pleasant odor

Not stable in soda lime แต่สลายตัวไม่มาก

Bl/gas = 0.6

MAC = 2.0

Metabolized in liver ใกล้เคียงกับ isoflurane


Inhalation anesthetic drugs

Sevoflurane : effect on organ systems

  • Depress respiration likes others

  • Minimal depress myocardium

  • No seizure activity , เพิ่ม CBF และICP, ลด CMRO 2

  • muscle relaxation, potentiate MR

  • Gas induction in children


Inhalation anesthetic drugs

Sevoflurane : not stable in sodalime

  • Reaction with soda lime  compound A (renal toxic)

  • ปกติจะเกิดน้อย แต่จะมีขนาดสูงขึ้นถ้า

  • Increase inspired flow temperature

  • Low flow anesthesia (FGF = 2 Lmin)

  • Dry sodalime

  • High concentration of sevoflurane

  • Long duration of sevoflurane administration


Inhalation anesthetic drugs

Advantages : Sevoflurane

  • Rapid induction and recovery

  • Gas induction ดีมาก


Inhalation anesthetic drugs

Disadvantages: Sevoflurane

  • High cost

  • Compound A in soda lime


Inhalation anesthetic drugs

Desflurane

  • Low boiling Point ( 23.50 C ) : requires

  • specific vaporizer

  • กลิ่นไม่หอม แต่ฉุนน้อยกว่า isoflurane

  • Bl/gas 0.42

  • MAC = 6-7

  • Stable in soda lime

  • No preservative


Inhalation anesthetic drugs

Desflurane : effect on organ systems

  • Depress respiration likes others

  • CV effect likes isoflurane but no coronary steal syndrome

  • CNS like other but no seizure activity

  • Muscle relaxation

  • Very low metabolized

  • nontoxic to kidney and liver


Inhalation anesthetic drugs

Advantages : Desflurane

  • The most rapid induction and recovery

  • Rapid adjustment of depth of anesthesia

  • non toxic to kidney and liver


Inhalation anesthetic drugs

Disadvantages : Desflurane

  • High cost

  • Need specialized vaporizer


Clinical use

Clinical use

  • Induction

  • Maintenance


Inhalation anesthetic drugs

Induction

  • Use of volatile anesthetics via face mask is common in pediatrics. But relatively rare in adult.

  • Halothane induction is commonly used in pediatrics, meanwhile, halothane induction in adults was also practice, but not popular


Inhalation anesthetic drugs

Induction

  • Resurgence of interest in mask induction in adult when using sevoflurane, the agent that possess low blood : gas solubility makes for a raid induction and typical time to loss of consciousness averages 1 Minutes when deliver via face mask


Inhalation anesthetic drugs

Maintenance

  • Volatile anesthetic used in clinical anesthesia

    - 1) Minimal concentration as a supplement to thiopentone – N2O-O2 (part of a balanced technique)

    - 2) Greater concentration as the main anesthetic agent


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