Volatile Anesthetics for the Anesthesia Boards

halothane

Effects on CNS

Do not cause retrograde amnesia or prolonged impairment of intellectual function. Cerebral metabolic oxygen requirement are decreased parallel with drug induced decreases in cerebral activity. Drug induced increases in cerebral blood flow may increase intra cranial pressure in patients with space occupying lesion. Volatile anesthetics produce an imprecision in the control of thermoregulatory responses at the level of the anterior hypothalamus. It produces shivering like activity during emergence. (1)

Effects on circulation

Halothane sensitizes the heart to catecholamines It is liable to cause cardiac arrhythmias, occasionally fatal, particularly if hypercapnia has been allowed to develop. Arrhythmias are very common in children anesthetized with halothane. Halothane depresses cardiac index and myocardial contractility in patients with congenital heart disease. (2) Halothane causes reduction in heart rate and hypotension during anesthesia. It has no effect in bronchomotor tone. (3) 1.0 MAC enflurane, halothane and isoflurane mildly disrupt coronary blood flow (CBF) autoregulation, increasing CBF out of proportion to myocardial demands. These anesthetics do not affect maximal CBF or coronary vascular reserve. (4) Volatile anesthetics alter tissue excitability by decreasing the extent of gap junction-mediated cell-cell coupling and by altering the activity of the channels that underlie action potential. The magnitude of the effect of halothane on channel open time isleast for Cx40-like channels and greatest for heteromeric channels. (5)

Effects on neuromuscular function

It is a potent trigger to malignant hyperthermia It relaxes uterine smooth muscles and this may increase blood loss during delivery or termination of pregnancy. Halothane should not be used in patients with neuromuscular disease like Duchenne muscular dystrophy. These patients show evidence of muscle damage with increased serum creatinine kinase concentration and myoglobinuria.

Effects on renal function

Halothane anesthesia does not affect early post operative renal functions. (6)

Effects on hepatic function

Repeated exposure of halothane can result in severe liver injury.This halothane hepatitis is the result from the metabolism of halothane to triflouroacetic acid via oxidative reactions in the liver. Halothane has more deleterious effect on liver blood flow , interferes with liver cell ability to absorb and excrete indocyanine green (ICG). (7)

Effects on hematologic and immune systems

A study on the effect of halothane on division of cultured, murine bone-marrow cells showed that halothane caused a dose-dependent depression of growth rate ranging from a minimal effect at 0.5% to almost total inhibition at 2.0%. Halothane exposure results in increased number of IgG secreting cells as well as the circulating 7S serum agglutinins. (8)

Minimum alveolar concentration and pressures

Oil: gas partition coefficient = 224 Blood: gas partition coefficient = 2.3 MAC = 0.75 vol % Vapor Pressure  244 mmHg (at 20 Deg C)

                           288 mm Hg (at 24 Deg C)

Trace concentrations, O.R. pollution, personnel hazards

Halothane should be used with caution in patients with Phaechromocytoma, Renal failure, Pre existing liver disease, Myasthenia gravis

Advantages

Pleasant odor Slower induction and recovery

References:

Farber NE, Poterack KA, Kampine JP, Schmeling WT. The effects of halothane, isoflurane and enflurane on the thermoregulatory responses in the neuraxis of cats. Anesthesiology 1994 Apr;80(4): 879-91.  Rivenes SM, Lewin MB, Stayer SA, Bent ST, SchoeniqHM, McKenzie ED, Fraser CD, Andropoulos DB. Cardiovascular effects of sevoflurane, isoflurane, halothane and fentanyl-midazolam in children with congenital heart disease: an echocardiographic study of myocardial contractility and hemodynamics. Anesthesiology 2001 Feb;94(2):223-9. Van den Berg AA, Honjol NM. effects of heart arte, blood pressure and bronchomotor tone of halothane, enflurane and isoflurane in young fit patients. Middle East J Anesthesiol 1993 Oct;12(3): 271-86.  Hickey Robert F, Sybert Peter E, Verrier Edward D, Cason Brian A. Effects of Halothane, Enflurane and Isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart. Anesthesiology Jan 1988; 6(1).  Ding Sheng He, Janis M Burt. Mechanism and selectivity of the effects of halothane on gap junction channel function. Circulation Research. 2000;86:e104-e109.  Saricaoqlu, Akinci SB, Oc B, Kanbak M, Akbulut B, Celebioqlu B. The effects of halothane, isoflurane, sevoflurane and propofol infusion on renal function after coronary artery bypass surgery. Middle East J Anesthesiol 2006 Jun;18(5):955-64.  Gelman Simon, Fowler Kathryn, Smithg Lloyd R. Liver circulation and function during isoflurane and halothane anesthesia. Anesthesiology December 1984; 61(6).  Puing NR, Elena GA, Barragan J, Comba JO, Amerio N. Halothane associated enhancement of the secondary immune response to sheep erythrocytes in mice: cell transfer studies. Acta Anaesthesiol Scand. 1993 Oct;37(7):647-51. 

 

 

 

 

 

Isoflurane

Effects on CNS

Isoflurane causes an increase in cerebral blood flow at deeper levels of anaesthesia, (1·5%), and this may give rise to an increase in cerebral spinal fluid pressure. Where appropriate, this can be prevented or reversed by hyper-ventilating the patient before or during anaesthesia. Isoflurane must be used with caution in patients with increased intracranial pressure Several incidence of postoperative convulsive disorder have been reported after isoflurane anesthesia. If seizures occured after anesthesia, volatile anesthesia itself may not be the cause. (1) 2% isoflurane given immediately after hypoxic ischemia, reduce brain infarct volume in short term as well as brain atrophy and neurobehavioural effects in the long term. (2)

Effects on circulation

Isoflurane is a powerful systemic and coronary arterial dilator. The phenomenon of "coronary steal" means that isoflurane should be used with caution in patients with coronary artery disease. In particular, patients with subendocardial ischaemia might be anticipated to be more susceptible. Isoflurane preserve cardiac index in patients with congenital heart disease. (3) Most appropriate isoflurane dose level is 1.5% v/v yielding stable mean arterial pressure (MAP) and heart rate (HR) with minute to minute variability in MAP and HR of <11%. (4)

Effects on respiration

Isoflurane is a profound respiratory depressant, this effect being accentuated by narcotic premedication or concurrent use of other respiratory depressants. No change in respiratory rate occurs with isoflurane at increasing alveolar concentration whereas at each level of anesthesia, inspiratory time is significantly reduced. (5)

Effects on GI function

Salivation and tracheo-bronchial secretions may be stimulated in children but pharyngeal and laryngeal reflexes are quickly diminished. Gastrointestinal motility is 50% reduced 120 min after the isoflurane anesthesia. (6)

Effects on neuromuscular function

Isoflurane produces sufficient muscle relaxation for some intra- abdominal operations. Isoflurane is compatible with all commonly used muscle relaxants, the effects of which may be markedly potentiated by isoflurane. The effect is most notable in non-depolarising agents, thus lower doses should be used in the presence of isoflurane. The effect of non-depolarising muscle relaxants can be counteracted by administering neostigmine as this has no effect on the relaxant properties of isoflurane. Interaction of rocuronium and volatile anesthetics results in augmentation of the neuromuscular block but does not significantly affect duration of or recovery from the block. (7) 0.95% isoflurane and 1.70% sevoflurane augments and prolongs the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree. (8)

Effects on hepatic function

Isoflurane causes frequent increase in the level of liver enzymes like Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), glutamyl transpeptidase (GTP). (9) Repeat anaesthesia with isoflurane within a short period of time should be approached with caution since the risk of hepatotoxicity is not fully understood. Caution should be exercised when administering isoflurane to patients with pre-existing liver disease.

Other system

Repeated exposure to isoflurane at anaesthetic concentrations has no effect on fertility, pregnancy or delivery. The viability of the offspring was unaffected.

Biotransformation; reaction with CO2 absorbants; toxicity

Isoflurane has been reported to interact with dry carbon dioxide adsorbents during closed circuit anaesthesia, to form carbon monoxide. Inhalation of carbon monoxide may lead to formation of significant levels of carboxyhaemoglobin in exposed patients.

Minimum alveolar concentration and pressures

MAC = 1.15 vol %

Vapor pressure

238 mm Hg 31.7 kPa (at 20 deg C)

295 mm Hg 48.9 kPa (at 25 deg C)

367 mm Hg 48.9 kPa (at 30 deg C)

450 mm Hg 60.0 kPa (at 35 deg C)

 

Blood gas partition coefficient = 1.4

Oil: gas partition coefficient = 98

Trace concentrations, O.R. pollution, personnel hazards

Isoflurane causes postoperative cognitive dysfunction (POCD) Isoflurane induce apoptsis and accumulation and aggregation of amyloid beta protein Adverse effects of isoflurane are hypotension, respiratory depression and arrhythmias It has pungent odor (not suitable for children) Broncho-irritant

Advantages

Stable cardiac rhythm Rapid onset/ recovery Minimal metabolism- low tox potential Excellent muscle relaxant

References:

J Kurata, T Adachi, S Nakao, M Murakawa, T Shichino, M Shibata. Sevoflurane, enflurane and isoflurane have no persistent effects on central nervous system in cats. British Journal of Anesthesia. 1996;76:721-725.  ZhouY, Lekic T, Fathali N, Ostrowski RP, Martin RD, Tang J, Zhang JH. Isoflurane posttreatment reduced neonatal hypoxic-ischemic brain injury in rats by the sphingosine-1-phosphate/ Phosphatidylinositol-3-kinase/Akt pathway. Stroke.2010;41:1521-1527.  Rivenes SM, Lewin MB, Stayer SA, Bent ST, SchoeniqHM, McKenzie ED, Fraser CD, Andropoulos DB. Cardiovascular effects of sevoflurane, isoflurane, halothane and fentanyl-midazolam in children with congenital heart disease: an echocardiographic study of myocardial contractility and hemodynamics. Anesthesiology 2001 Feb;94(2):223-9.  Christakis Constantinides, Richard Mean and Ben J Janssen. Effects of isoflurane anesthesia on cardiovascular function of the C57BL/6 Mouse. ILAR J 2011;52:e21-e31.  Murat I, Chaussain M, Hamza J, Saint-Maurice C. The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children. Anesthesia 1987 Jul;42(7):711-8.  Torjman MC, Joseph JI, Munsick C, Morishita M, Grunwald Z. Effects of isoflurane on gastrointestinal motility after brief exposure in rats. Int J Pharm 2005 Apr 27;294(1-2): 65-71.  Wulf H, Ledowski T, Linstedt U, Proppe D, Sitzlack D. Neuromuscular blocking effects of rocuronium during desflurane, isoflurane and sevoflurane anaesthesia. Can J Anaesth 1998 Jun;45(6):526-32.  LEH Vanlinthout LHDJ Booij, Van Egmond, EN Robertson. effect of isoflurane and sevoflurane on the magnitude an dtime course of neuromuscular block produced by vecuronium, pancuronium and atracurium. British Journal of Anesthesia. 1996;76:389-395.  Tomoki Nishiyama, Takeshi Yokoyama, Kazou Hanaoka. liver function after sevoflurane or isoflurane anesthesia in neurosurgical patients. Can J Anaesth 1998;45(8): 753-756. 

 

 

 

 

Sevoflurane

Effects on CNS

Sevoflurane raises intracranial pressure Sevoflurane had minimal effect on intracranial pressure (ICP) and preserved CO2, responsiveness in patients with normal ICP. Rare cases of seizures have been reported in association with sevoflurane use. Sevoflurane suppresses the background central nervous system electrical activities in a dose dependent manner, leaving the reactive capabilities facilitated at deep anesthesia. (1)

Effects on circulation

During the maintenance of anaesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. Excessive decrease in blood pressure may be related to depth of anaesthesia and in such instances may be corrected by decreasing the inspired concentration of sevoflurane. Sevoflurane has not been associated with untoward cardiovascular changes in volunteers and patients undergoing elective surgery and may have less potent effects on the vascular smooth muscle. (2) Autonomic nerve activity is attenuated by sevoflurane. Parasympathetic input to the heart by respiration is suppressed following apperance of isoelectric EEG. (3) Sevoflurane uptake is higher in patients with higher cardiac output. (4)

Effects on respiration

Sevoflurane causes respiratory depression which increase as anesthesia is deepened Sevoflurane is a suitable agent for induction under spontaneous respiration with higher concentrations in pediatric anesthesia. (5) Sevoflurane produce more profound respiratory depression at high MAC. (6)

Effects on GI function

Deep sedatioj with inhaled sevoflurane for pediatric outpatient gastrointestinal endoscopy is as safe as conventional sedation technique, potentially less expensive, increases endoscopy unit productivity and eliminates the inconvenience associated with obtaining intravenous access in children. (7)

Effects on neuromuscular function

Use of sevoflurane can cause malignant hyperthermia. The syndrome may include non-specific features such as muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and unstable blood pressure. Treatment includes discontinuation of triggering agents (e.g. Sevoflurane), administration of intravenous dantrolene sodium, and application of supportive therapy. Renal failure may appear later, and urine flow should be monitored and sustained if possible. Use of sevoflurane has been associated with very rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in children during the postoperative period. The condition has been described in patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy.

Effects on renal function

Sevoflurane should be used with caution in patients with renal insufficiency No significant renal effects are seen with low flow or high flow sevoflurane. (8)

Effects on hepatic function

Sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. Use of sevoflurane in patients with severe hepatic dysfunction has not been investigated. Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from post marketing experiences. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction. Sevoflurane at concentrations less than 2.0 MAC preserves hepatic arterial blood flow, total hepatic O2 delivery and the O2 delivery to consumption ratio. (9)

Effects on hematologic and immune systems

Transient increases in serum inorganic fluoride levels may occur during and alter Sevoflurane anaesthesia. Generally, concentrations of inorganic fluoride peak within 2 hours of the end of sevoflurane anaesthesia and return within 48 hours to pro-operative levels.

Biotransformation; reaction with CO2 absorbants; toxicity

Sevoflurane produces low levels of Compound A (pentafluoroisopropenyl fluoromethyl ether (PIFE)) and trace amounts of Compound B (pentafluoromethoxy isopropyl fluoromethyl ether (PMFE)), when in direct contact with CO2 absorbents. Levels of Compound A Increase with:- increase in canister temperature; increase in anaesthetic concentration; decrease in gas flow rate and increase more with the use of Baralyme rather than Soda lime. The exothermic reaction that occurs with sevoflurane and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Rare cases of extreme heat, smoke and/or spontaneous fire in the anesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent canister.

Minimum alveolar concentration and pressures

MAC = 2.1 vol %

MAC of sevoflurane decrease with age and with the addition of nitrous oxide

Vapor pressure

157 mm Hg 22.9 kPa (at 20 deg C)

197 mm Hg 26.3 kPa (at 25 deg C)

317 mm Hg 42.3 kPa (at 36 deg C)

 

Blood gas partition coefficient = 0.68

Oil: gas partition coefficient = 47

 

Trace concentrations, O.R. pollution, personnel hazards

Frequent adverse effects of sevoflurane are nausea and vomiting Other adverse effects are:

in adults, hypotension; in elderly, hypotension and bradycardia; in children, agitation and increased cough.

 

Less frequent adverse events associated with sevoflurane administration were; agitation, somnolence, chills, bradycardia, dizziness, increased salivation, respiratory disorder, hypertension, tachycardia, laryngismus, fever, headache, hypothermia, increased SGOT.

 

Occasionally reported adverse effects associated with the administration of sevoflurane administration include : arrhythmias, increased LDH, increased SGPT, hypoxia, apnoea, leukocytosis, ventricular extrasystoles, supraventricular extrasystoles, asthma, confusion, increased creatinine, urinary retention, glycosuria, atrial fibrillation, complete AV block, bigeminy, leucopenia. Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions have also been reported. As with all potent inhaled anaesthetics, sevoflurane may cause dose-dependent cardiorespiratory depression.

 

 

Convulsions may occur extremely rarely following sevoflurane administration, particularly in children. There have been very rare reports of pulmonary oedema.

 

Advantages

Fast induction/ recovery High potency (least soluble) Non irritating vapor

References:

Osawa M, Shingu K, Murakawa M, Adachi T, Kurata J, Seo N, Murayama T, Nakao S, Mori K. Effects of sevoflurane on central nervous system electrical activity in cats. Anesth Analg. 1994 Jul;79(1):52-7.  Ebert TJ. Cardiovascular and autonomic effects of sevoflurane. Acta Anaesthesiol Belg. 1996;47(1):15-21.  Itsuo Nakatsuka, Ryoichi Ochai, Junzo Takeda. Changes in heart rate variability in sevoflurane and nitrous oxide anesthesia: effects of respiration and depth of anesthesia. Journal of Clinical Anesthesia. May 2002;14(3):196-200.  JFA Hendrickx, AAJ Van Zundert, AM De Wulf. Sevoflurane pharmacokinetics: effect of cardiac output. British Journal of Anesthesia. 1998;81:495-501 Mori N, Suzuki M. Sevoflurane in pediatric anesthesia: effects on respiration and circulation during induction and recovery. Pediatr Anaesth. 1996;6(2):95-102.   M Yamakage,K Tamiyamd,  Dai Horikawa, K Sato, A Namikimd. Effects of halothane and sevoflurane on the pediatric respiratory pattern. Pediatric Anesthesia. January 1994;4(1):53-56. Montes RG, Bohn RA. Deep sedation with inhaled sevoflurane for pediatric outpatient gastrointestinal endoscopy. J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):41-6.  Bito Hiromichi, Ikeuchi Yukako, Ikeda Kazuyuki. Effects of low flow sevoflurane anesthesia on renal function: comparison with high flow sevoflurane anesthesia and low flow isoflurane anesthesia. Anesthesiology 1997;86(6):1231-1237.  Frink Edward J, Morgan Scott EBS, Coetzee Andre, Conzen Peter F, Brown Burnell R. The effects of sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology January 1992;76(1). 

 

 

 

Desflurane

Effects on CNS

Desflurane causes dose dependent decrease in cerebrovascular resistance and cerebral metabolic rate of oxygen consumption (CMRO2). (1) It is a cerebral arteriolar dilator Desflurane cause cerebral vasodilation and may result in change in intracranial pressure in vulnerable patients, however if adequate hyperventilation and depth of anesthesia are maintained, it is safe to use desflurane. (1) With desflurane anesthesia, there is increase in activity in the midbrain at surgical end tidal anesthetic concentration. (2)

Effects on circulation

Use of desflurane causes tachycardia Increase in desflurane concentration increase the sympathetic and renin angiotensin system activity and cause transient increase in arterial blood pressure and heart rate. It also causes a transient increase in plasma AVP concentration. (3) 6% desflurane significantly prolongs QTc interval in children with normal QTc interval undergoing inguinal herniorraphy. (4)

Effects on respiration

It causes airway irritability and laryngospasm at concentration greater than 10 vol %. Desflurane causes respiratory depression at concentration higher than 1 MAC due to decrease in tidal volume. So, it should be avoided at high concentration in infants and chuildren with spontaneous ventilation. (5) There is dose dependent decrease in tidal volume and increase in respiratory rate, arterial carbon dioxide tension, dead space/tidal ventilation ratio, and intrapulmonary shunt fraction. (6) Desflurane does not affect respiratory resistance at 1 MAC, but at 1.5 MAC it causes significant increase in both total and airway resistance with return to baseline values after discontinuation. (7)

Effects on GI function

Desflurane maintain the esophageal barrier pressure (BrP = Lower esophageal sphincter pressure - gastric pressure). Hence, it can be used in patients with high risk of regurgitation. (8)

Effects on neuromuscular function

In susceptible individuals, desflurane may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The clinical syndrome is signaled by hypercapnea, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia: acute hypoxia, hypercapnia, and hypovolemia.

Effects on renal function

Concentrations of 1-4% desflurane in nitrous oxide /oxygen have been used in patients with chronic renal or hepatic impairment and during renal transplantation surgery. Because of minimal metabolism, a need for dose adjustment in patients with renal and hepatic impairment is not to be expected. Desflurane does not aggravate renal impairment in patients with preexisting renal insufficiency. (9)

Effects on hepatic function

Use of desflurane may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics Better post operative hepatic tests and INR are seen using desflurane in living donors undergoing right hepatectomy. (10)

Effects on hematologic and immune systems

It has the most rapid onset and offset among the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

Biotransformation; reaction with CO2 absorbants; toxicity

Desflurane has been shown to react with the carbon dioxide absorbent in anesthesia circuits to produce detectable levels of carbon monoxide through degradation of the anesthetic agent. The CO2 absorbent, Baralyme, when dried, is most culpable for the production of carbon monoxide from desflurane degradation, although it is also seen with soda lime absorbent as well. Dry conditions in the carbon dioxide absorbent are conducive to this phenomenon, such as those resulting from high fresh gas flows

Minimum alveolar concentration and pressures

MAC = 6 vol %

Vapor pressure

672 mm Hg 88.5 kPa (at 20 deg C)

804 mm Hg 107 kPa (at 24 deg C)

 

Blood gas partition coefficient = 0.42

Oil: gas partition coefficient = 19

 

Trace concentrations, O.R. pollution, personnel hazards

Very pungent Irritating to airways Laryngospasm Expensive Desflurane is a green house gas and contributes to global warming. Adverse effects associated with use of desflurane include arrhythmia, myocardial ischemia, vasodilation; hepatitis; agitation, diziiness; dyspnea, hypoxia;increased creatinine phosphokinase level; myalgia and pruritis

Advantages

Rapid onset/recovery High potency (least soluble) Even less metabolism

References: 

WL Young. Effects of desflurane on the central nervous system. Anesthesia & Analagesia. 1992;75(4):S32-7.  DJA Vaughan, C Thornton, DR Wright, JR Fernandes, P Robbins, C Dore, MD Brunner. Effects of different concentrations of sevoflurane and desflurane on subcortical somatosensory evoked responses in anesthetized, non stimulated patients. Br J Anaesth. 2001;86(1):59-62. Weiskopf RB, Moore MA, Eqer EI, Noorani M, McKay L, Chortkoff B, Hart PS, Damask M. Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans. Anesthesiology 1994 May;80(5):1035-45.  Aypar E, Karaqoz AH, Ozer S, Celiker A, Ocal T. The effects of sevoflurane and desflurane anesthesia on QTc interval and cardiac rhythm in children. Paediatr Anaesth. 2007 Jun;17(6):563-7.  Behforouz N, Dubousset AM, Jamali S, Ecoffey C. Respiratory effects of desflurane anesthesia on spontaneous ventilation in infants and children. Anesth Analg. 1998 Nov;87(5):1052-5.  Warltier DC, Pagel PS. Cardiovascular and respiratory actions of desflurane: is desflurane different from isoflurane? Anesth Analg. 1992 Oct;75(4 Suppl):S17-29.  V. Nyktari, A papaioannou, N. Volakakis, A lappa, P Margaritsanaki, H Askitopoulou. Respiratory depression during anesthesia with isoflurane, sevoflurane and desflurane: a randomized clinical trial. Br J Anaesth 2011.  D Chassard, JP Tournadre, KR Berrada, B Bryssine, P Bouletreau. Effect of halothane, isoflurane anbd desflurane on lower esophageal sphincter tone. British Journal of anesthesia. 1996;77:781-783.  Litz RJ, Hubler M, Lorenz W, Meier VK, Albrecht DM. Renal responses to desflurane and isoflurane in patients with renal insufficiency. Anesthesiology 2002 Nov;97(5):1133-6.  Topark HI, Sahin T, Aslan S, Karahan K, Sanli M, Ersoy MO. Effects of desflurane and isoflurane on hepatic an drenal functions and coagulation profile during donor hepatectomy. Transplant Proc. 2012 Jul-Aug;44(6):1635-9.