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Anesthesia Agents III. Methyl Ethyl Ethers. Penthrane (Methoxyflurane) CHCl 2 CF 2 OCH 3 CH 3 metabolically unstable No halogen to protect Lipid soluble and stays there Nonflammable No preservative. Methyl Ethyl Ethers. Penthrane (Methoxyflurane) CHCl 2 CF 2 OCH 3
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Methyl Ethyl Ethers Penthrane (Methoxyflurane) CHCl2CF2OCH3 CH3 metabolically unstable No halogen to protect Lipid soluble and stays there Nonflammable No preservative
Methyl Ethyl Ethers Penthrane (Methoxyflurane) CHCl2CF2OCH3 CH3 metabolically unstable No halogen to protect Lipid soluble and stays there Nonflammable, No preservative
Penthrane Renal toxicity Polyuric dysfunction - High output renal failure Caused by release of Fluoride ion during metabolism, Plasma fluoride > 50 microMols puts patient at risk Boiling Point 105 MAC 0.23 Vapor Pressure 30
Nephrotoxicity Newer agents have much fewer metabolites Plasma levels of metabolites increase with longer cases Desflurane has not been found to cause significant changes in renal function FDA recommends to use Sevoflurane with caution in renal patients
Enflurane (Ethrane) > fluorination when compared with methoxyflurane More stable More volatile Releases more fluoride than halothane and desflurane Pungent, sweet smelling Extended induction and emergence
Enflurane Boiling Point 56.5o C Vapor Pressure 174.5 MAC 1.68
Enflurane Halogenated methyl ethyl ether Pungent, ethereal odor Less potent than halothane, isoflurane, or desflurane
Enflurane Halogenated methyl ethyl ether Isomer of isoflurane Volatile at room temperature Less potent than other volatile agents Clear, nonflammable liquid Synthesized - 1963 Clinical Use - 1972
Advantages Increased doses of epinephrine > halothane or isoflurane < dysrhythmias Minimal analgesia Muscle relaxant Caution in patients with Myasthenia Gravis Risk of seizures in patient with seizure history (> 2 MAC for > 30 minutes and/or extended periods of hypocarbia (< 30 torr))
Disadvantages Extremely rare risk of postop liver dysfunction Mild self-limited hepatic dysfunction unless there is decreased blood flow to liver for extended time Slow onset – slow awakening Increases rate of production of CSF Very rare risk of renal toxicity
Advantages Extremely rate risk of postop liver dysfunction Ability to use more epinephrine with enflurane than with halothane or isoflurane before seeing arrthythmias
Disadvantages Very rare risk of renal toxicity
Isoflurane (Forane) Structural Isomer of Enflurane Frequently used volatile anesthetic today Lowest cost of an agent on the market No noted problems with toxicity Boiling Point 48.5o C Vapor Pressure 239.5 MAC 1.15
Advantage Little blunting of the baroreceptor reflex with maintenance of CO by increase in heart rate Ablility to use more epinephrine with this agent than halothane but less than enflurane
Disadvantage More likely to see a tachycardia
Isoflurane Halogenated methyl ethyl ether Clear, nonflammable liquid Volatile at room temperature Synthesized 1965 Clinical Practice 1981
Properties Molecular weight 184 Boiling Point 48.5 oC Vapor pressure 240 torr @ 20 C Odor Pungent, ethereal Partition Coefficients Blood/gas 1.4 - 1.46 Brain/gas 1.6 Oil/Gas 90.8 MAC Nitrous Oxide 0.5 Oxygen 1.15
Advantage < blunting of the baroreceptor reflex Maintenance of CO Increase in heart rate – aortic baroreceptor response Bronchodilator Epinephrine > halothane < enflurane
Disadvantage Slow induction – emergence Pungent odor Coughing Breath holding Tachycardia Hypotension Extremely potent vasodilator
Desflurane (Suprane) Most volatile of all agents Stable and inert Differs from isoflurane by replacing one fluoride with a chloride Rapid onset and recovery Pungent irritating vapors make it possibly unsuitable for inhalation induction Low solubility Gas at room temperature
Desflurane Pharmacodynamcally, desflurane is almost identical to isoflurane Dose related decreases in BP and CO is similar to somewhat greater than seen with isoflurane Its advantage is chiefly pharmacokinetically With its low blood/gas partitiion coefficient, the drug is very fast-on, fast-off Metabolism is somewhat less than isoflurane
Desflurane Boiling Point 23.5o C Vapor Pressure 669.2 MAC 6.0
Desflurane Tec 6 Vaporizer Electrically powered, heated, pressurized Keeps temperature at 39º C Make sure it’s plugged in so it’s warmed up Battery backup supplies alarms only Vaporizer shuts off with loss of power Can be refilled while being used (only one) Some concern of “false alarms” Very sensitive New vaporizer: Tec 6 Plus Problems of false alarms alleviated
Desflurane Fluorinated methyl Ethel ether Closely resembles isoflurane in structure Fluorine substituted for chlorine “Super Forane” High vapor pressure (681 mmHg at 20º C), so it boils at room temperature at high altitudes Special vaporizer required Stored as liquid under pressure Low solubility; thus quick onset & quick emergence
Desflurane Molecular weight 168 Boiling Point 22.8 oC Vapor pressure 669 Odor Ethereal, irritating Partition Coefficients Blood/Gas 0.45 Brain/Gas 1.3 Oil/Gas 18.7 MAC Nitrous Oxide 2.83 – 3.0 Oxygen 6.0
Desflurane Pharmacodynamics almost identical to isoflurane Dose related decreases in BP and CO Greater than seen with isoflurane Factor of rapidity of increasing dose Dose dependent tachycardia
MAC Requirements Decrease with Age Desflurane 100% O2 60% N2O/O2 < 1 year: 10.0 % 7.5 % 25 years: 7.3 % 4.0 % 45 years: 6.0 % 2.8 % 70 years: 5.2 % 1.7 %
Desflurane Good for Fast Track anesthesia Low solubility, so quick induction & emergence Wake up is quick, whether short or long case Dupont, 1999: Emergence was twice as fast with Desflurane than Forane or Sevoflurane in pulmonary surgery With other agents, the longer the case, the longer the time to wake up the patient Early discharge
Desflurane: Cardiac Effects Smaller decreases in B/P, contractility & SVR occur with Desflurane than Isoflurane HR stable at lower concentrations HR & B/P may increase with Desflurane if increase is rapid Due to SNS activity Can be lessened if changes are made slowly
Desflurane: Cardiac Effects Desflurane has only a moderate effect on coronary blood flow Less vasodilation than isoflurane Less coronary steal No increase in ischemia/infarction when compared to Isoflurane
Increased B/P and Heart Rate Rarely occurs when agent <6% After IV induction, a reasonable initial setting: 3% with FGF of 4-6 L/min Gradually by 1% every few breaths until desired depth is reached Can be lessened if narcotic given to patient (EX: Fentanyl 1 – 3 mcg/kg) FGF to 1-3 L/min
Desflurane: Pediatrics With pediatric patients, SB & arrhythmias occur less often than with Halothane Desflurane provides a quicker response when anesthesia is deepened
Study by Parsons, et al Found that Desflurane decreased B/P & SVR Desflurane > 1 MAC may HR & B/P Does not mean patient is “light” Cardiopulmonary effects similar to Forane but may provide better control of systemic arterial pressure during stressful stimuli Able to achieve rapid control of circulatory responses & limit myocardial stress & ischemia Useful in patients with CAD
Pulmonary Effects of Suprane Pungent; May be irritable to airway May lead to coughing, laryngospasm or bronchospasm Not recommended for inhalation induction
Avoiding Airway Irritation Irritation may be minimized by giving an opioid, using N2O (1st), or giving a short-acting beta blocker (occasionally) Rarely occurs when agent < 6% due to less irritant However, occurs less when patient is deep Once IV induction is complete (& LMA placed), turn up agent so deep level is obtained Deep levels lead to bronchodilation and prevention of coughing
Recovery of Cognitive Function Desflurane Quicker wake up Quicker return of neurological function Able to assess neurological function quicker Works well for long cases, the elderly, the obese Currently recommended for the elder, obese, and neurological patient where rapid evaluation of status is necessary (Todd, 2001)
Burst Suppression to Decrease Cerebral Injury Burst suppression decreases CBF & metabolism & should result in decreased emboli to brain Cerebral emboli are a major cause of neurologic injury in cardiac surgery Hundreds to thousands of cerebral microemboli may occur during cardiac surgery Greater numbers are associated with greater postoperative injury Desflurane can successfully be used for burst suppression
Burst Suppression to Decrease Cerebral Injury Desflurane at 9% can produce burst suppression EEG and significantly increase tissue PO2 and pH and decrease PCO2 (Hoffman) Desflurane improves oxygen rich blood flow in the brain during surgery for very sick patients with subarachnoid hemorrhage (Hoffman) B/P supported with Neosynephrine
Juvin, et al, 1997 Less Desflurane needs to be released from tissues & eliminated from body at end of long case due to its low solubility Forane has a higher solubility, thus longer recovery Propofol, a lipid-soluble anesthetic, may have prolonged effects due to increased proportion of fat in elderly