Inhalational ANAESTHETIC Agents Dr. Med. Khaled Radaideh Department of Anesthesiology - Jordan University of Science and Technology Irbid-Jordan Dr. Med. Khaled Radaideh July 18

INHALATIONAL ANAESTHETIC AGENT Objectives 1. Introduction 2. Pathway O2-Brain 3.MAC (Definition and Values and factors effecting MAC) 4. Factors determining how quickly the inhalational agent reaches the alveoli reaches and the brain from the alveoli 5. Nitrous Oxide (N2O) 5.1. physical properties, Pharmacology and side effects) 5.2. What is diffusion hypoxia? 5.3. Second gas effect Dr. Med. Khaled Radaideh July 18

INHALATIONAL ANAESTHETIC AGENT Objectives 6. Halothane 6.1. properties 6.2. Metabolism 6.3. Dosage, Administration an Supply 6.4. Indications and contraindications 6.5. Effect on Organ Systems 6.6. Advantages and Disadvantages Dr. Med. Khaled Radaideh July 18

INHALATIONAL ANAESTHETIC AGENT Objectives 7. Isoflurane and Sevoflurane 7.1. properties 7.2.Effect on Organ Systems 7.3. Advantages and Disadvantages 7.4. Indications and contraindications Dr. Med. Khaled Radaideh July 18

INHALATIONAL ANAESTHETIC AGENT Introduction IV anesthesia : induce anesthesia Inhalation anesthesia : maintain anesthesia IV anesthesia : mg/KG or microgram/Kg Inhalation anesthesia : Percentage of the volume % EXAMPLE: 2 L/min. O2 + 4 L/min N2O  Conc. Of N2O = 4/(2+4) = 66% Dr. Med. Khaled Radaideh July 18

Pathway O2-Brain Oxygen is bubbled in volatile Anesth. agnet Mixture vapor Anesthetic machine Lungs Diffuse across alveolar capillary membrane blood Brain Dr. Med. Khaled Radaideh July 18

MAC Definition Minimal alveolar concentration (MAC): Is defined as the conc. At 1 atmosphere of anesthetic in the alveoli that s required to produce immobility in 50% of adults patient subjected to a surgical incision MAC is important to compare the potencies of various inhalational anesthetic agents 1.2 -1.3 MAC prevent movement in 95% of patients Dr. Med. Khaled Radaideh July 18

MAC Value N2O = 105% Halothane = 0.75% Isoflurane = 1.16% Enflurane = 1.68% Sevoflurane = 2% Desflurane = 6% N2O alone is unable to produce adequate anesthesia ( require high conc. ) Dr. Med. Khaled Radaideh July 18

Factors that alter anesthetic requirements (MAC): * Hyperthermia * Chronic drug abuse (ethanol) * Acute use of amphetamines * hyperthyroidism * Increasing Age * hypothermia * Other anesthetic (opioids) * Acute drug intoxication (ethanol) * Pregnancy * Hypothyroidism * Other drugs ( clonidine ,reserpine) Dr. Med. Khaled Radaideh July 18

No Effect on MAC Gender Duration of anesthesia Carbon dioxide tension (21-95 mmHg) Metabolic Acid base status Hypertension Hyperkalemia Dr. Med. Khaled Radaideh July 18

1-Increasing the delivered concentrations of anesthetic Factors determining how quickly the inhalational agent reaches the alveoli? 1-Increasing the delivered concentrations of anesthetic 2- The gas flow rate through the anesthetic machine 3-Increasing minute ventilation MV = Respiratory Rate × Tidal volume Dr. Med. Khaled Radaideh July 18

1- The rate of blood flow to the brain Factors determining how quickly the inhalational agent reaches the brain from the alveoli in order to establish anesthesia? 1- The rate of blood flow to the brain 2- The solubility of the inhalational agent in the brain 3- The difference in the arterial and venous concentration of the inhalational agent Dr. Med. Khaled Radaideh July 18

NHALATIONAL ANAESTHETIC AGENT Nitrous Oxide (N2O) Dr. Med. Khaled Radaideh July 18

Physical property: laughing Not flammable Odorless Colorless Tasteless Nitrous Oxide (N2O) Physical property: laughing Not flammable Odorless Colorless Tasteless Dr. Med. Khaled Radaideh July 18

Pharmacology: Good Analgesic Weak anesthetic Excreted via lungs Nitrous Oxide (N2O) Pharmacology: Good Analgesic Weak anesthetic Excreted via lungs MAC = 105% Lower water solubility Not Metabolized in the body Dr. Med. Khaled Radaideh July 18

Diffusion Hypoxia.(Fink effect) Nitrous Oxide (N2O) Side Effects: Diffusion Hypoxia.(Fink effect) Effects on closed gas spaces.(nitrous oxide can diffuse 20 times faster into closed spaces than it can be removed, resulting in expansion of pneumothorax, bowel gas, or air embolism or in an increase in pressure within noncompliant cavities such as the cranium or middle ear. CVS depression Toxicity Teratogenic Dr. Med. Khaled Radaideh July 18

Nitrous Oxide (N2O) Diffusion hypoxia What is diffusion hypoxia? Diffusion hypoxia is a decrease in PO2 usually observed as the patient is emerging from an inhalational anesthetic where nitrous oxide (N2O) was a component. The rapid outpouring of insoluble N2O can displace alveolar oxygen, resulting in hypoxia. All patients should receive supplemental O2 at the end of an anesthetic and during the immediate recovery period. Dr. Med. Khaled Radaideh July 18

Nitrous Oxide (N2O) Second gas effect Second gas effect: The ability of the large volume uptake of one gas (first gas) to accelerate the rate of rise of the alveolar partial pressure of a concurrently administered companion gas (second gas) is known as the second gas effect. Dr. Med. Khaled Radaideh July 18

Halothane Dr. Med. Khaled Radaideh July 18

Halothane: (2-bromo-2-chloro-1,1,1-trifloroethane) Synthesized in 1951. * Volatile liquid easily vaporized, stable, and nonflammable * Most potent inhalational anesthetic MAC of 0.75% Colorless liquid , pleasant smell , decomposed by light. So should be stored in container away from light and heat (decomposes to toxic gases of bromine, chlorine and fluorine if not properly stabilized) It has low blood/gas solubility coeffient of 2.5 and thus induction of anasthesia is relatively rapid. Dr. Med. Khaled Radaideh July 18

HALOTHANE Metabolism 20% metabolized in liver by oxidative pathways. Major metabolites : bromin, chlorine, Trifloroacetic acid, Trifloroacetylethanl amide. Dr. Med. Khaled Radaideh July 18

HALOTHANE Dosage and Administration and supply The induction dose varies from patient to patient. The maintenance dose varies from 0.5 to 1.5%. Halothane may be administered with either oxygen or a mixture of oxygen and nitrous oxide. How is Halothane Supplied Halothane is supplied in amber colored 250 mL glass bottles, stabilized with thymol 0.01% (w/w). Store in cool, dry place and protect from undue exposure to light. Dr. Med. Khaled Radaideh July 18

HALOTHANE Indications and Contraindications Halothane is indicated for the induction and maintenance of general anesthesia. Contraindications Halothane is not recommended for obstetrical anesthesia except when uterine relaxation is required. Dr. Med. Khaled Radaideh July 18

HALOTHANE Effect on systems Respiratory system: Halothane anesthesia progressively depresses respiration. Its cause inhibition of salivary & bronchial secretion. Its may cause tachypnea & reduce in tidal volume and alveolar ventilation . Its cause decrease in mucocillary function which lead to sputum retention. It causes bronchodilation. Hypoxia, acidosis, or apnea may develop during deep anesthesia. Dr. Med. Khaled Radaideh July 18

HALOTHANE Effect on systems Cardiovascular system: Halothane anesthesia reduces the blood pressure, and cause bradycardia.(atropin may reverse bradycardia.). It cause myocardial relaxation & Hypotention. Its also causes dilation of the vessels of the skin and skeletal muscles Halothane maybe advantages In pts with CAD , bcz of decrease of oxygen demand. Arrhythemias are very commone .(especially with epinephrine). To minimize effects : Avoid hypoxemia and hypercapnia Avoid conc. Of adrenaline higher than 1 in 10000 Dr. Med. Khaled Radaideh July 18

HALOTHANE Effect on systems Gastro intestinal tract: Inhibition of gastrointestinal motility. Cause sever post. Operative nausea & vomiting Uterus: Halothane relaxes uterine muscle, may cause postpartum hemorrhage . Concentration of less than 0.5 % associated with increase blood loss during therapeutic abortion. Skeletal muscle: Its cause skeletal muscle relaxation . Postoperatively , shivering is common , this increase oxygen requirement>>> which cause hypoxemia Dr. Med. Khaled Radaideh July 18

HALOTHANE Effect on systems Hepatic dysfunction: Two type of dysfunction: 1- Type I hepatotoxicity ,mild, associated with derangement in liver function test , this result from metabolic of Halothane in liver. results from reductive (anaerobic) biotransformation of halothane rather than the normal oxidative pathway. 2- Type II hepatotoxicity: fulminate (uncommon); sever jaundice ,fever,progressing to fulminating hepatic necrosis, Its increased by repeated exposure of the drugs. high mortality 30-70% (1 in 35,000) Given this risk, halothane is not recommended for use in adults. Dr. Med. Khaled Radaideh July 18

3-may other anesthetic cause 4-1 case per 6000-35,000 patients Type 2 hepatotoxicity Type 1 hepatotoxicity (Subclinical) 1-immune mediated 2-fever, jaundice, and grossly elevated serum transaminase levels(massive centrilobular liver necrosis that leads to fulminant liver failure) 3-may other anesthetic cause 4-1 case per 6000-35,000 patients 5-(50-80)% 1-reductive (anaerobic) biotransformation 2-a)mild transient increases in serum transaminase and glutathione S-transferase 3-only halothane 4-25-30% 5-mortality rate rare Dr. Med. Khaled Radaideh July 18

Recommendation for Halothane anasthesia: 1- A careful anasthetic history . 2- repeated exposure of halothane within 3 months should be avoided. 3- History of unexplained jaundice or pyrexia after previous exposure of halothane. Dr. Med. Khaled Radaideh July 18

Main advantages of halothane: Rapid smooth induction . Minimal stimulation of salivary & bronchial secretion. Brochiodilatation. Muscle relaxant . Relatively rapid recovery. Dr. Med. Khaled Radaideh July 18

Main disadvantages are: Poor analgesia. Arrhythmias. Post operatively shivering. Possibility of liver toxicity. Dr. Med. Khaled Radaideh July 18

Potent cardiovascular depressant Enflurane MAC =1.68% Potent cardiovascular depressant Dr. Med. Khaled Radaideh July 18

Isoflurane Properties isomer of enflurane. Carcinogenic (not approved) colorless, volatile, liquid, pungent odor. stable. No preservative . Non-flammable. Dr. Med. Khaled Radaideh July 18

Isoflurane Properties Least soluble of the modern inhalational agent  equilibrate more rapidly Induction rapid theoretically (pungency??) pungency  cough, breath holding. Alveolare concentration equilibirate more rapidly with inspired concentration. Dr. Med. Khaled Radaideh July 18

Isoflurane effects on systems:- Respiratory: dose dependent depression of vetilation. CVS: myocardial depressant (vitro Vs Clinical), coronary vasodilatation (coronary steal syndrome). uterus: relaxation of uterine muscles (same). Decrease in tidal volume but increase in ventilatory rate (if opioids drugs are absent) Dr. Med. Khaled Radaideh July 18

coronary steal syndrome is a phenomenon where an alteration of circulation patterns lead to a reduction in the blood directed to the coronary circulation.  It is caused when there is narrowing of the coronary arteries and a coronary vasodilator is used – "stealing" blood away from those parts of the heart. This happens as a result of the narrowed coronary arteries being always maximally dilated to compensate for the decreased upstream blood supply. Thus, dilating the resistance vessels in the coronary circulation causes blood to be shunted away from the coronary vessels supplying the ischemic zones, creating more ischemia. Dr. Med. Khaled Radaideh July 18

Dr. Med. Khaled Radaideh July 18

Isoflurane effects on systems:- CNS: low concentration Vs High concentration. Low : no change on the flow. High : increase blood flow by vasodilatation of the cerebral arteries. Muscles: relaxation (dose-dependent). Dr. Med. Khaled Radaideh July 18

Advantages and Disadvantages Isoflurane Advantages and Disadvantages Advantages Rapid induction and recovery. Little risk of hepatic or renal toxicity. Cardiovascular stability. Muscle relaxation. Disadvantages Pungent odor. Coronary vasodilatation *(in compare with halothane why ?) Dr. Med. Khaled Radaideh July 18

Sevoflurane Properties New drug. Non flammable. Pleasant smell. MAC 2%. Stable. Low blood/gas partition coefficient  faster equilibrium. non irritant so the fastest for induction. Dr. Med. Khaled Radaideh July 18

Advantages and Disadvantages Sevoflurane Advantages and Disadvantages Advantages 1. Well tolerated (non-irritant, sweet odor), even at high concentrations, making this the agent of choice for inhalational induction. 2. Rapid induction and recovery (low blood:gas coefficient) 3. Does not sensitize the myocardium to catecholamines as much as halothane. 4. Does not result in carbon monoxide production with dry soda lime. Dr. Med. Khaled Radaideh July 18

Advantages and Disadvantages Sevoflurane Advantages and Disadvantages Disadvantages 1. Less potent than similar halogenated agents. 2. Interacts with CO2 absorbers. In the presence of soda lime (and more with barium lime) compound A (a vinyl ether) is produced which is toxic to the brain, liver, and kidneys. 3. About 5% is metabolized and elevation of serum fluoride levels has led to concerns about the risk of renal toxicity. 4. Postoperative agitation may be more common in children than seen with halothane. Dr. Med. Khaled Radaideh July 18

Sevoflurane effects on systems Respiratory: non-irritant, depression. CVS: same as isoflurane (slightly lower effect) CNS: same as halothane and isoflurane. Muscle relaxation: same as isoflurane. Dr. Med. Khaled Radaideh July 18

Desflurane MAC =6 % Dr. Med. Khaled Radaideh July 18

Dr. Med. Khaled Radaideh July 18

Dr. Med. Khaled Radaideh July 18

Dr. Med. Khaled Radaideh July 18

Thank you Dr. Med. Khaled Radaideh July 18