SMF/LAB ANESTESIOLOGI & TERAPI INTENSIF RS SAIFUL ANWAR/FK UNIBRAW MALANG

 Nitrous Ethyl

oxide, Chloroform and Ether.

chloride, ethylene, cyclopropane and Enflurane

Methoxyflurane Nitrous

oxide, Halothane, Isoflurane, Desflurane, and Sevoflurane.

 The

course of general anesthesia 1) Induction 2) Maintenance 3) Emergence in the induction of pediatric patients

Useful Adults

prefer rapid induction with intravenous agents.

 Pharmacokinetics

Relationship between a drugs dose, tissue concentration, and elapsed time

(how a body affects a drug)

Pharmacodynamics

(how a drug affects a body)

The study of drug action, including toxic responses MAC (Minimum alveolar concentration)
Clinical

pharmacology of individual agents

Nitrous oxide, Halothane, Isoflurane, Desflurane, Sevoflurane

Mechanism of action of inhalation anesthetics remains unknown Depends on attainment of a therapeutic tissue concentration in the central nervous system There many steps, between the administration of an anesthetic from a vaporizer and its deposition in the brain

Fresh gas flow rate (FGF rate)

Volume of the breathing system (breathing circuit volume) Any absorption by the machine or breathing circuit (circuit absorption)

 Uptake Ventilation

Concentration

 Uptake

1) FA/FI <1.0 2) Uptake Alveolar concentration FA/FI 3) Gas concentration Partial pressure Alveolar partial pressure Anesthetic partial pressure in blood Brain tissue concentration 4) Uptake of Anesthetic agent Induction

 Anesthetic

uptake factors

1) Solubility in the blood 2) Alveolar blood flow 3) Difference in partial pressure between alveolar gas and venous blood

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Solubility in the blood

1) Solubility : Insoluble agents(N2O) < soluble agents(halothane) FA : Insoluble agents(N2O) > soluble agents(halothane) Induction speed : Insoluble > soluble agents

2) Partition coefficients() Relative solubility of an anesthetic in air, blood, and tissues

3) Blood/gas partition coefficient Solubility in Blood Uptake Alveolar partial pr induction speed

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Alveolar blood flow

1) In the absence of pulmonary shunting : ABF = CO CO Uptake Alveolar partial pr induction speed 2) Insoluble agent Alveolar blood flow 3) Soluble agent Low CO Alveolar concentration overdosage

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Difference in partial pressure between alveolar gas and venous blood

1) No tissue uptake Alveolar to venous partial pr difference = 0 2) Factors affecting tissue uptake Tissue solubility of the agent( tissue/blood partition coefficient) Tissue blood flow Difference in partial pressure between arterial blood and the tissue

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4 group of tissue by solubility and blood flow

1) Vessel-rich group ex) brain, heart, liver, kidney, endocrine organ 2) Muscle group ex) skin, muscle 3) Fat group

4) Vessel-poor group ex) bone, ligament, teeth, hair, cartilage

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 Ventilation

Constantly replacing anesthetics taken up by pul bloodstream FA/FI for soluble agent

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Concentration
1) Concentration effect Concentrating effect Augmented inflow effect 2) Second gas effect

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(Anesthetic gas 50% uptake)

Anesthe tic gas : 20 Gas : 10 Anesth etic gas : 80 Gas : 40

O2 :80

O2 :80

O2 :20

O2 :20

10/90=11%

40/60=66%

Concentrating effect
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1% of second gas second O2 gas : 19% O2 : 19(31.7 %)

1% of second gas (1.7%) 1% of O2 :19%

N2O: 40(66.7 %) N2O : 80% gas

N20 : 40%

O2 : 7.6% N2O : 32%

0.4% of second -

Second gas effect

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Alveolar partial pr > Arterial partial pr Alveolar-arterial difference 1) Venous admixture 2) Alveolar dead space

3) Nonuniform alveolar gas distribution

4) Ventilation/perfusion mismatch (ex: atelectasis, emphysema, neumonia)

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Recovery from anesthesia - Anesthetic concentration in brain tissue

Anesthetics can be eliminated by 1) biotransformation 2) transcutaneous

3) exhalation

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 Induction and Recovery

Rebreathing High Fresh gas flows Low Anesthetic-circuit volume Low absorption by the Anesthetic-circuit Decreased Solubility High CBF(Cerebral Blood Flow) - Increased Ventilation

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Diffusion hypoxia
1) Directly affect oxygenation by displacing O2 2) diluting alveolar CO2 respiratory drive prevent : 100% O2

5~10min

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Pharmacodynamics
the study of drug action, including toxic responses how a drug affects a body

General anesthesia
reversible loss of consciousness analgesia of the entire body amnesia muscle relaxation

General anesthesia agent

inert elements ( ex: xenon ) simple inorganic compounds ( ex: nitrous oxide) halogenated hydrocarbons ( ex: halothane ) complex organic structures (ex: barbiturate )

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Alveolar concentration that prevents movement in 50% of patients in response to a standardized stimulation
MAC is useful measure brain partial pressure agents potency experimental evaluation The MAC value for different anesthetics are roughly additive The same MAC CNS depression Myocardial depression

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Point on dose-response curve ED50,( median effective dose) 1.3 MAC of any of the volatile anesthetics prevent movement in about 95% patients surgical incision ED95 MAC Awake = 0.3 ~ 0.4 MAC One of the most striking is the 6% decrease in MAC per decade of age, regardless of volatile anesthetic Unaffected by species, sex, or duration of anesthesia
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inorganic anesthetic gas , , O2 , gas ,

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In vitro- stimulate the sympathetic nervous system in vitro, direct depression of myocardial contractility In vivo- Stimulation of catecholamine ABP, CO, HR Unchanged or slightly N2O Myocardial depression unmasked Coronary artery diseases Severe hypovolemia BP myocardial ischemia Constriction pulmonary vascular smooth muscle pulmonary vascular resistance Rt. Ventricular end-diastolic pr. Endogenous catecholamine level epinephrine induced arrhythmia
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CNS stimulation, pulmonary stretch receptor activation respiratory rate(tachypnea) & tidal volume : net effect -> minimal change in minute ventilation and resting arterial CO2 level
Hypoxic drive

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Cerebral blood flow & Cerebral blood volume Intracranial pressure mild CMOR2(Cerebral oxygen consumption) Levels of nitrous oxide below MAC provide analgesia in dental surgery and other minor procedures

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Neuromuscular not provide significant muscle relaxation not a triggering agent of malignant hyperthermia Renal Renal vascular resistance renal blood flow : glomerular filtration rate(GFR) & urinary output Hepatic Hepatic blood flow Gastrointestinal Activation of the chemoreceptor trigger zone and the vomiting center in the medulla Postoperative nausea & vomiting
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Eliminated by exhalation : almost diffuses out through skin : small amount biotransformation : than less 0.01% Vit B12 cobalt Vit B12 dependent enzyme Myelin methionine synthetase DNA thymidylate synthetase

Prolonged exposure of anesthetic level Bone marrow depression(ex: megaloblastic anemia ) Neurological deficiencies (ex:peripheral neuropathies and pernicious anemia)

Teratogenic effect
Polymorphonuclear leukocytes chemotaxis motility decrease immunological response change
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Air embolism Pneumothorax Acute intestinal obstruction Intracranial air ( ex: dural closure or pneumoencephalus tension pneumocephalus Pulmonary HTN patient

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MAC = 105 vol% combination with the more potent volatile agent Neuromuscular blockade (but effect : N2O< volatile agents) Requirements of other agents Second gas effect

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Halogenated alkane Nonexplosive Nonflammable Least expensive volatile anesthetics

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Dose-dependent reduction of arterial blood pressure Myocardial depression (2.0MAC : BP 50%) Coronary artery vasodilator But Systemic arterial pressure coronary blood flow Hypotension Vagal stimulation , HR But this reflex, sinoatrial node conduction slowing Junctional rhythm and bradycardia In infant : HR & myocardial contratility CO Sensitize the heart to the arrhythmogenic effects to epinephrine : epinephrine 1.5g/kg is dangerous

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Rapid, shallow breathing Not enough to counter TV alveolar ventilation, resting PaCO2 * Cause of ventilatory effect central mechanism (medullary depression) peripheral mechanism (intercostal muscle dysfunction) : pre-existing lung disease : surgical stimulation

Hypoxic drive
A potent bronchodilators ( Airway reflex , bronchial smooth muscle decrease ) Mucociliary function postoperative hypoxia & atelectasis
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Cerebral vessels dilating cerebral vascular resistance , CBF Autoregulation (Arterial blood pressure increases, CBF also increases) Intracranial pressure

Prevent: Hyperventilation

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Neuromuscular Skeletal muscle relaxation Non-depolarizing neuromuscular-blocking agents (NMBA) effect Malignant hyperthermia Renal Renal blood flow, GFR(glomelular filtration rate), urinary output ( Arterial blood pressure & cardiac output ) GFR < Renal blood flow Filtration fraction Prevent : Preoperative hydration

Hepatic CO hepatic blood flow Hepatic artery vasospasm The metabolism and clearance of Fentanyl, phenytoin, verapamil

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Be oxidized in the liver by a cytochrome P450 (2EI) trifluoroacetic acid : Inhibited by pretreatment with disulfiram

viral hepatitis, impaired hepatic perfusion, hepatocyte hypoxia, sepsis, hemolysis, benign postoperative intrahepatic cholestasis, drug induced hepatitis postoperative hepatic dysfunction Halothane hepatitis is extremely rare (1/35000 )

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Intracranial mass lesion Intracranial hypertension Hypovolemic pt. Severe cardiac disease ( ex: aortic stenosis ) Pheochromocytoma

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- adrenergic blocking agent (propranolol), Ca++ channel blocking agent (verapamil) Myocardial depression Tricyclic antidepressants, MAO inhibitor fluctuations in blood pressure & arrhythmias ( but not absolute contraindication) Aminophylline Severe ventricular arrhythmias

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Nonflammable volatile anesthetic Pungent ethereal oder Chemical isomer of enflurane but different physiochemical property

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Minimal cardiac depression but carotid baroreflex HR CO stable -adrenergic stimulation skeletal muscle blood flow systemic vascular resistance arterial blood pressure Dilates coronary arteries

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Respiratory depression, Tachypnea ( less pronounced) minute ventilation( more pronounced)

Good bronchodilator

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>1.0 MAC : CBF & intracranial pressure but Isoflurane < Halothane Reversed by hyperventilation

Cerebral metabolic oxygen requirement

2.0 MAC electrically silent electroencephalogram(EEG) : EEG suppression cerebral ischemia brain protection

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Neuromuscular Relax skeletal muscles Renal Renal blood flow , glomerular filtration rate , urinary output Hepatic Total hepatic flow Hepatic oxygen supply : better maintained than with Halothane

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Serum fluoride fluid levels may rise But no nephrotoxicity

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No unique contraindication

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Safe dose of Epinephrine: up to 4.5 g/kg NMBAs effect

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High vapor pressure special vapor Low solubility in blood and body tissues Ultrashort duration Very rapid wash in and wash out of anesthetic Moderate potency

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Similar to isoflurane Dose systemic vascular resistance arterial blood pressure CO unchanged or mild(1~2 MAC) Heart rate, central venous pressure, pulmonary artery pressure: moderate Cardiovascular disease desflurane concentration rapid heart rate, BP, catecholamine level worrisome Attenuated by fentanyl, esmolol, clonidine coronary blood flow unchanged
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TV RR Alveolar ventilation resting PaCO 2 Ventilatory response

Pungency and airway irritation during induction salivation, breath-holding, coughing, laryngospasm

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Similar to Isoflurane Directly vasodilates the cerebral vasculature ICP CBF ,

Cerebral metabolic rate of oxygen(CMRO2) cerebral vasoconstriction & CBF

Cerebral oxygen consumption During periods of desflurane-induced hypotension, CBF is adequate to maintain aerobic metabolism

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Neuromuscular dose-dependent of TOF Renal No evidence of any nephrotoxic effects Hepatic No evidence of hepatic injury

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Minimal metabolism Insignificant percutaneous loss CO poisoning(by carbon dioxide absorbent) : disposing of dried out absorbent or use of calcium hydroxide minimize the risk

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Severe hypovolemia Malignant hyperthermia Intracranial hypertension

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Potentiates nondepolarizing neuromuscular blocking agents Safe dose of Epinephrine : Up to 4~5 g/kg Associated with delirium in some pediatric patients

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Nonpungency & rapid increase in alveolar anesthetic concentration Smooth & rapid inhalation induction Rapid emergence than Isoflurane Faster emergence Greater incidence of delirium in some pediatric patients * treated with 1.0~2.0 g/kg of fentanyl

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Cardiovascular Depresses myocardial contractility. Systemic vascular resistance & arterial blood pr. Prolong the QT interval

Respiratory Depresses respiration Reverse bronchospasm

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CBF, ICP slight

>1.5 MAC impair autoregulation of CBF CBF during hemorrhagic hypotension Cerebral metabolic oxygen requirement

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Neuromuscular Produce adequate muscle relaxation & intubation of children Renal RBF slight Hepatic Portal vein blood flow but hepatic artery blood flow Maintain total hepatic blood flow & oxygen delivery

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Liver microsomal enzyme P-450(2E1) Inorganic fluoride : nephrotoxicity but clinically associated with significant renal dysfunction By Alkali ( Barium hydroxide lime or soda lime ) Sevoflurane Nephrotoxic end product ( Compound A, fluorometal-2, 2-difluoro-1-vinylether ) Compound A production will increase by Respiratory gas temperature Low-flow anesthesia Dry barium hydroxide absorbent (Baralyme) Sevoflurane concentration Anesthetic of long duration Hydrogen fluoride acid burn on respiratory mucosa
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Severe hypovolemia
Malignant hyperthermia Intracranial hypertension

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Potentiates NMBAs Catecholamine-induced arrhythmia is not affected

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