Desflurane why different ?
AHMED TURKISTANIMD.FCCM
ASST.PROFFESSORKKUH
DESFLURANEDESFLURANE
• PharmacokineticsPharmacokinetics• Cardiovascular effectsCardiovascular effects• Pulmonary effectsPulmonary effects• CNS effectsCNS effects• Clinical use Clinical use • Update Update
Desflurane ChemistryDesflurane Chemistry
OO
Fluorine atom replaces chlorine atom on the Fluorine atom replaces chlorine atom on the alpha ethyl carbon of isofluranealpha ethyl carbon of isoflurane
IsofluraneIsoflurane
FF
FF
FF
FFClCl
HH
CC CC CCOOHH FF
DesfluraneDesflurane
HH
FF
FF
FF
FFFF
HH
CC CC CC FF
BrFBrF33
Eger EI II. Desflurane (SupraneEger EI II. Desflurane (Suprane®®). A Compendium and Reference. 1993.). A Compendium and Reference. 1993.
MAC, MAC Awake, and MAC-BARMAC, MAC Awake, and MAC-BAR
In OIn O22 In 60% NIn 60% N22O O MAC-AwakeMAC-Awake -BAR-BAR
DesfluraneDesflurane 6.00%6.00% 2.83%2.83% 2.42%2.42% 1.45 1.45 SevofluraneSevoflurane 1.71%1.71% 0.66%0.66% 0.61%0.61% 2.24 2.24 HalothaneHalothane 0.77%0.77% 0.29%0.29% 0.41%0.41% 1.3 1.3 IsofluraneIsoflurane 1.15%1.15% 0.50%0.50% 0.39%0.39% 1.3 1.3 Nitrous oxideNitrous oxide 104%104% -- 67%67% --
Barash et al. Clinical Anesthesia. 1992; Daniel et al. Anesthesiology. Barash et al. Clinical Anesthesia. 1992; Daniel et al. Anesthesiology. 1998; Jones et al. Anesth Analg. 1990; Katoh et al. Anesthesiology. 1998; Jones et al. Anesth Analg. 1990; Katoh et al. Anesthesiology. 1999; Katoh et al. Br J Anaesth. 1992; Roizen et al. Anesthesiology. 1999; Katoh et al. Br J Anaesth. 1992; Roizen et al. Anesthesiology.
1981; Stoelting et al. Anesthesiology. 1970. 1981; Stoelting et al. Anesthesiology. 1970.
Boiling Points and Vapor PressuresBoiling Points and Vapor Pressures
Boiling PointBoiling Point Vapor PressureVapor Pressure (°C)(°C) (mm Hg at 20°C)(mm Hg at 20°C)
DesfluraneDesflurane 23.523.5 664 664 HalothaneHalothane 50.250.2 241241IsofluraneIsoflurane 48.548.5 238238SevofluraneSevoflurane 58.558.5 160160
Barash et al. Clinical Anesthesia. 1992.Barash et al. Clinical Anesthesia. 1992.
Distinguishing Characteristics of Distinguishing Characteristics of DesfluraneDesflurane
SolubilitySolubility
PotencyPotency
Vapor pressureVapor pressure
The chemical structure of desflurane results in The chemical structure of desflurane results in several distinguishing characteristics compared several distinguishing characteristics compared
to other potent inhaled anesthetic agents:to other potent inhaled anesthetic agents:
Eger EI II. Desflurane (SupraneEger EI II. Desflurane (Suprane®®). A Compendium and Reference. 1993.). A Compendium and Reference. 1993.
Solubility in BloodSolubility in Blood
1960196000
11
22
33
Halothane, 2.54Halothane, 2.54
Isoflurane, 1.46Isoflurane, 1.46
Desflurane, 0.42Desflurane, 0.42
Blood:Gas Blood:Gas Partition Partition
CoefficientCoefficient
Year of Introduction Into PracticeYear of Introduction Into Practice2000200019801980
Sevoflurane, 0.69Sevoflurane, 0.69
Eger EI II. Desflurane (SupraneEger EI II. Desflurane (Suprane®®). A Compendium and Reference. 1993.). A Compendium and Reference. 1993.
Human Tissue:Blood Partition CoefficientsHuman Tissue:Blood Partition Coefficients
DesfluraneDesflurane SevofluraneSevoflurane IsofluraneIsoflurane HalothaneHalothane NN22OO
FatFat 2727 4848 4545 5151 2.32.3
BrainBrain 1.31.3 1.71.7 1.61.6 1.91.9 1.11.1
HeartHeart 1.31.3 1.81.8 1.61.6 1.81.8 ––
LiverLiver 1.31.3 1.81.8 1.81.8 2.12.1 0.80.8
KidneyKidney 1.01.0 1.21.2 1.01.0 1.21.2 ––
MuscleMuscle 2.02.0 3.13.1 2.92.9 3.43.4 1.21.2
Eger EI II. Desflurane (SupraneEger EI II. Desflurane (Suprane®®). A Compendium and Reference. 1993.). A Compendium and Reference. 1993.Eger EI II. In: Miller RD, ed. Anesthesia. 5th ed. 2000.Eger EI II. In: Miller RD, ed. Anesthesia. 5th ed. 2000.
Implications of Low SolubilityImplications of Low Solubility
• More rapid wash-inMore rapid wash-in
• Greater anesthetic control and precisionGreater anesthetic control and precision
• More rapid emergence from anesthesiaMore rapid emergence from anesthesia
• Potentially greater economy through more rapid Potentially greater economy through more rapid recoveryrecovery
Eger EI II. Desflurane (SupraneEger EI II. Desflurane (Suprane®®). A Compendium and Reference. 1993.). A Compendium and Reference. 1993.
Inspired and Alveolar Anesthetic Inspired and Alveolar Anesthetic ConcentrationsConcentrations
NN22OODesfluraneDesflurane
IsofluraneIsoflurane
HalothaneHalothane
11
0.80.8
0.60.6
0.40.4
0.20.2
0000 1010 2020 3030
Minutes of AdministrationMinutes of Administration
FFAA/F/FII
SevofluraneSevoflurane
Yasuda et al.Yasuda et al.Anesth Analg. 1991.Anesth Analg. 1991.
Elimination of Inhaled AgentsElimination of Inhaled Agents
0.40.4
0.20.2
00
00
FFAA/F/FA0A0
Minutes of WashoutMinutes of Washout44 88 1212
HalothaneHalothane
IsofluraneIsoflurane
SevofluraneSevoflurane
DesfluraneDesflurane
Long-Term EliminationLong-Term Elimination
1010-4-4
1010-5-5
1010-6-6
1010-7-7
00 11 22 33 44 55Days of EliminationDays of Elimination
HalothaneHalothaneIsofluraneIsoflurane
SevofluraneSevoflurane
DesfluraneDesflurane
FFAA/F/FA0A0
Yasuda et al.Yasuda et al.Anesth Analg. 1991.Anesth Analg. 1991.
Terminal DecrementTerminal Decrement
Bailey JM. Anesth Analg. 1997;85:681.Bailey JM. Anesth Analg. 1997;85:681.
Duration of Anesthetic Duration of Anesthetic Administration (min)Administration (min)
100100
6060
2020
00
4040
8080
00 5050 100100 150150 200200 250250 300300 350350
90%90%DecrementDecrement
TimeTime(min)(min)
EnfluraneEnflurane
IsofluraneIsoflurane
SevofluraneSevoflurane
DesfluraneDesflurane
Metabolic PathwayMetabolic Pathway
IsofluraneIsoflurane DesfluraneDesfluraneF
F
F
F
F
H
H
Cl
C O C C
F
F
F
F
F
H
OH
Cl
C O C C
[O]
F
F
F
F
F
H
O
C OH + HO C C
H2O
[O]
2 HF + CO2 HCl
+
F
F
F
F
F
H
H
F
C O C C
F
F
F
F
F
H
OH
F
C O C C
[O]
F
F
F
F
F
H
O
C OH + HO C C
H2O
[O]
2 HF + CO2 HF
+
Metabolism of Inhaled AgentsMetabolism of Inhaled Agents
% of Uptake Recovered% of Uptake Recoveredas Urinary Metabolitesas Urinary Metabolites
Desflurane 0.02
Isoflurane 0.2
Sevoflurane 5
Halothane 15 - 20
Cascorbi et al. Anesthesiology. 1970; Holaday et al. Anesthesiology. 1975;Cascorbi et al. Anesthesiology. 1970; Holaday et al. Anesthesiology. 1975;Kharasch et al. Anesthesiology. 1995; Rehder et al. Anesthesiology. 1967;Kharasch et al. Anesthesiology. 1995; Rehder et al. Anesthesiology. 1967;
Sutton et al. Anesth Analg. 1991.Sutton et al. Anesth Analg. 1991.
Emergence and Extubation: Desflurane vs Isoflurane, Propofol, and Emergence and Extubation: Desflurane vs Isoflurane, Propofol, and SevofluraneSevoflurane
DesfluraneDesflurane Sevoflurane IsofluraneSevoflurane Isoflurane PropofolPropofol
Beaussier et alBeaussier et al11
EmergenceEmergence (min) (min) 12*12* 24 24 Extubation (min)Extubation (min) 16*16* 3333
Juvin et alJuvin et al22
Emergence (min)Emergence (min) 5.6*5.6* 11.511.5 11.911.9Extubation (min)Extubation (min) 6.9*6.9* 13.113.1 9.99.9
Nathanson et alNathanson et al33
Emergence (min)Emergence (min) 4.8*4.8* 7.87.8Extubation (min)Extubation (min) 5.1*5.1* 8.28.2
* P* P.05 vs other groups.05 vs other groups1. Can J Anaesth. 1998;45:429.1. Can J Anaesth. 1998;45:429.2. Anesth Analg. 1997;85:647.2. Anesth Analg. 1997;85:647.3. Anesth Analg. 1995;81:1186.3. Anesth Analg. 1995;81:1186.
Orientation: Desflurane vs Isoflurane, Orientation: Desflurane vs Isoflurane, Propofol, and SevofluranePropofol, and Sevoflurane
DesfluraneDesflurane SevofluraneSevoflurane IsofluraneIsofluranePropofolPropofol
Beaussier et alBeaussier et al11
State name (min)State name (min)22*22* 4343
Juvin et alJuvin et al22
State name (min)State name (min)10.7*10.7* 18.318.3 16.816.8State birthday (min)State birthday (min) 11.4*11.4* 18.418.4 19.419.4
Nathanson et alNathanson et al33
State name (min)State name (min)9.29.2 11.211.2State birthday (min)State birthday (min) 9.39.3 11.211.2
* P* P.05 vs other groups.05 vs other groups1. Can J Anaesth. 1998;45:429.1. Can J Anaesth. 1998;45:429.2. Anesth Analg. 1997;85:647.2. Anesth Analg. 1997;85:647.3. Anesth Analg. 1995;81:1186.3. Anesth Analg. 1995;81:1186.
Recovery Score: Desflurane vs Recovery Score: Desflurane vs Isoflurane, Propofol, and SevofluraneIsoflurane, Propofol, and Sevoflurane
DesfluraneDesflurane SevofluraneSevoflurane IsofluraneIsoflurane PropofolPropofol
Beaussier et alBeaussier et al11
Steward scoreSteward score 28*28* 5757of 6 (min)of 6 (min)
Song et alSong et al22
Aldrete scoreAldrete score 10.010.0†† 11.711.7 15.715.7of 10 (min)of 10 (min)
* P=.003 vs isoflurane* P=.003 vs isoflurane†† P<.05 vs propofolP<.05 vs propofol 1. Can J Anaesth. 1998;45:429.1. Can J Anaesth. 1998;45:429.
2. Anesth Analg. 1998;86:267.2. Anesth Analg. 1998;86:267.
Summary: Anesthetic Recovery Summary: Anesthetic Recovery With DesfluraneWith Desflurane
• Emergence, extubation, and orientation occur sooner Emergence, extubation, and orientation occur sooner with desflurane than with isoflurane,with desflurane than with isoflurane,1,21,2 sevoflurane, sevoflurane,33 or or propofolpropofol22
• Duration of desflurane anesthesia has minimal effect Duration of desflurane anesthesia has minimal effect on recovery timeon recovery time44
• Faster emergence and orientation with desflurane can Faster emergence and orientation with desflurane can lead to faster PACU and hospital dischargelead to faster PACU and hospital discharge5,65,6
1. Beaussier et al; 2. Juvin et al; 3. Nathanson et al;1. Beaussier et al; 2. Juvin et al; 3. Nathanson et al;4. Tsai et al; 5. Loan et al; 6. Song et al.4. Tsai et al; 5. Loan et al; 6. Song et al.
Minimal Effect of Anesthetic Duration on Recovery With Minimal Effect of Anesthetic Duration on Recovery With DesfluraneDesflurane
Duration of Anesthesia (min)Duration of Anesthesia (min)
< 100< 100 100-150100-150 > 150> 150
Minutes to:Minutes to:
Spontaneous movementSpontaneous movement 5.6 5.6 7.0 7.0 4.4 4.4
Response to commandsResponse to commands 8.2 8.2 8.7 8.7 6.2 6.2
Orientation to age, name,Orientation to age, name, 11.4 11.4 12.0 12.0 9.0 9.0and body partsand body parts
ExtubationExtubation 8.2 8.2 7.8 7.8 6.2 6.2
Tsai et al. Br J Anesth. 1992;69:255.Tsai et al. Br J Anesth. 1992;69:255.No significant differencesNo significant differences
Orientation With Desflurane vs Orientation With Desflurane vs Sevoflurane: Effect of Anesthetic DurationSevoflurane: Effect of Anesthetic Duration
00
2020
4040
22 44 66 88 22 44 66 88
Time to OrientationTime to OrientationTime to ResponseTime to Responseto Commandto Command
Hours of AnesthesiaHours of Anesthesia
Minutes Minutes AfterAfter
1.25 MAC1.25 MACAnesthesiaAnesthesia DesfluraneDesflurane
SevofluraneSevoflurane
SevofluraneSevoflurane
DesfluraneDesflurane
Eger et al. Anesth Analg. 1998;86:414.Eger et al. Anesth Analg. 1998;86:414.
Fast-Track Eligibility: Desflurane vs Fast-Track Eligibility: Desflurane vs Sevoflurane and PropofolSevoflurane and Propofol
26%*
75%
90%
0
20
40
60
80
100
Desflurane Sevoflurane Propofol
Patients Fast-Track Eligible on Arrival in PACU
Song et al. Anesth Analg. 1998;86:267.Song et al. Anesth Analg. 1998;86:267.* P<.05 vs other 2 groups* P<.05 vs other 2 groups
%
Fast-Track Eligibility After Ambulatory Fast-Track Eligibility After Ambulatory Laparoscopic SurgeryLaparoscopic Surgery
* P<.05 vs other groups* P<.05 vs other groupsN=40 per groupN=40 per group Song et al. Anesth AnalgSong et al. Anesth Analg.. 1998;86:267. 1998;86:267.
9.811.3
14.7
10
11.7
15.7
0
2
4
6
8
10
12
14
16
Minutes
Orientation Aldrete Score of 10
Desflurane
Sevoflurane
Propofol
****
1. Hargasser et al; 2. Avramov et al; 3. Bennett et al; 4. Eger et al; 1. Hargasser et al; 2. Avramov et al; 3. Bennett et al; 4. Eger et al; 5. Yasuda et al; 6. Juvin et al; 7. Weiskopf et al.5. Yasuda et al; 6. Juvin et al; 7. Weiskopf et al.
Desflurane: Advantages in Fast-Track Desflurane: Advantages in Fast-Track AnesthesiaAnesthesia
• Precise control of agent concentrationPrecise control of agent concentration1,2,31,2,3
• Rapid elimination and recovery Rapid elimination and recovery regardless of anesthetic duration or flow regardless of anesthetic duration or flow ratesrates4,5,64,5,6
• Safe to use with fresh gas low flow ratesSafe to use with fresh gas low flow rates44
• Inexpensive at low flowsInexpensive at low flows44
• Best used at 1 MAC or lower to minimize Best used at 1 MAC or lower to minimize cardiorespiratory effectscardiorespiratory effects77
Lubarsky DA. J Clin AnesthLubarsky DA. J Clin Anesth.. 1996;8:70S. 1996;8:70S.
DrugDrug Cost ($)Cost ($) PACU Cost ($) PACU Cost ($)
IsofluraneIsoflurane 1818 198198
DesfluraneDesflurane 2222 178178
SevofluraneSevoflurane 2323 175175
PropofolPropofol 4040 174174
Drug Cost Is Much Less Than PACU CostDrug Cost Is Much Less Than PACU Cost((1996 Data from Duke University Medical Center)1996 Data from Duke University Medical Center)
DESFLURANEDESFLURANE
• CARDIOVASCULAR EFFECTSCARDIOVASCULAR EFFECTS
Cahalan et al. Anesth Analg. 1991;73:157; Malan et al. Anesthesiology. 1995;83:918; Stevens et al. Anesthesiology. 1971;35:8; Weiskopf et al. Anesth Analg. 1991;73:143.
Systemic Vascular ResistanceSystemic Vascular Resistance
1400
1200
1000
800
600
400
SVR(dyne •s • cm-5)
MAC1.00 2.0
Isoflurane-O2
Sevoflurane-O2
Desflurane-O2
Desflurane-N2O
Heart RateHeart Rate
Cahalan et al. Anesth Analg. 1991;73:157; Malan et al. Anesthesiology. 1995;83:918; Stevens et al. Anesthesiology. 1971;35:8; Weiskopf et al. Anesth Analg. 1991;73:143.
95
85
75
65
60
70
80
90
0 1.0 2.0
Heart Rate (bpm)
MAC
Isoflurane-O2
Sevoflurane-O2
Desflurane-O2
Desflurane-N2O
Transient Sympathetic Stimulation Transient Sympathetic Stimulation With Isoflurane and DesfluraneWith Isoflurane and Desflurane
*
*
*
* * *
Isoflurane
Desflurane
Time (min)
Heart Rate(bpm)
130
120
110
100
90
80
70
60BA 0 5 10 15 20 25 30 35
Weiskopf et al. Anesthesiology. 1994;80:1035.* P<.05 vs isoflurane* P<.05 vs isoflurane
Average Response to Vaporizer Change Average Response to Vaporizer Change From 0.5 to 1.0 MAC: Desflurane vs From 0.5 to 1.0 MAC: Desflurane vs
IsofluraneIsoflurane
Ebert, Muzi. Anesthesiology. Ebert, Muzi. Anesthesiology. 1993;79:444.1993;79:444.* P<.05 vs 0.5 MAC steady state for same agent* P<.05 vs 0.5 MAC steady state for same agent
IsofluraneDesflurane
IsofluraneDesflurane
IsofluraneDesflurane
Sympathetic Nerve Activity (total activity)
Heart Rate (bpm)
Mean Arterial Pressure (mm Hg)
40
200
70
5090
80
7060
0.5 2.5 4.5 7.5 9.5 11.5Steady state
Minutes After Vaporizer Change(0.5 to 1.0 MAC)
* *
* * * *
* * * *
* * * * *
* * * * * *
Average Response to Vaporizer Change Average Response to Vaporizer Change From 0.5 to 1.0 MAC: Desflurane vs From 0.5 to 1.0 MAC: Desflurane vs
IsofluraneIsoflurane
Ebert, Muzi. Anesthesiology. Ebert, Muzi. Anesthesiology. 1993;79:444.1993;79:444.* P<.05 vs 0.5 MAC steady state for same agent* P<.05 vs 0.5 MAC steady state for same agent
IsofluraneDesflurane
IsofluraneDesflurane
IsofluraneDesflurane
Sympathetic Nerve Activity (total activity)
Heart Rate (bpm)
Mean Arterial Pressure (mm Hg)
40
200
70
5090
80
7060
0.5 2.5 4.5 7.5 9.5 11.5Steady state
Minutes After Vaporizer Change(0.5 to 1.0 MAC)
* *
* * * *
* * * *
* * * * *
* * * * * *
Group Responses to Vaporizer Change From Group Responses to Vaporizer Change From 1.0 to 1.5 MAC: Desflurane vs Isoflurane1.0 to 1.5 MAC: Desflurane vs Isoflurane
Ebert, Muzi. Anesthesiology. Ebert, Muzi. Anesthesiology. 1993;79:444.1993;79:444.
* P<.05 vs 1.0 MAC steady state for same agent* P<.05 vs 1.0 MAC steady state for same agent† † Different group responseDifferent group response
Isoflurane
Desflurane
Isoflurane
Desflurane
Isoflurane
Desflurane
Sympathetic Nerve Activity (total activity)
Heart Rate (bpm)
Mean Arterial Pressure (mm Hg)
40
20
0110
7050
80
60
400.5 2.5 4.5 7.5 9.5 11.5
Steady state
Minutes After Vaporizer Change(1.0 to 1.5 MAC)
**
** * *
*
*
**
†
*
*
*
*
*
*
90†* * * * *
* * * *
†*
*
*
*
*
* *
*
Changes Associated With 1.0 to 1.5 Changes Associated With 1.0 to 1.5 MAC Step Change in Dialed MAC Step Change in Dialed
ConcentrationConcentrationDesfluraneDesflurane• BP and HR transiently increase, followed by BP BP and HR transiently increase, followed by BP
decrease to below control and HR decrease todecrease to below control and HR decrease toabove controlabove control
• SNA: increases transiently with desflurane > 1 MAC, SNA: increases transiently with desflurane > 1 MAC, followed by return to control valuefollowed by return to control value
IsofluraneIsoflurane• BP decreases, HR remains unchanged with BP decreases, HR remains unchanged with
isoflurane > 1 MACisoflurane > 1 MAC• SNA: unchangedSNA: unchanged
Ebert, Muzi. Anesthesiology. Ebert, Muzi. Anesthesiology. 1993;79:444.1993;79:444.
Minimizing the Sympathetic Response to Minimizing the Sympathetic Response to Rapid Increases in Desflurane Rapid Increases in Desflurane
ConcentrationConcentration
• Increased heart rate and blood pressureIncreased heart rate and blood pressure– Transient responseTransient response– Does not occur in all patients, less likely in elderly patientsDoes not occur in all patients, less likely in elderly patients– Treatment may not be needed due to brief durationTreatment may not be needed due to brief duration– Narcotic pretreatment minimizes the responseNarcotic pretreatment minimizes the response
• Recommendations to minimize hemodynamic responseRecommendations to minimize hemodynamic response– Consider IV opioids prior to increasing desflurane concentrationConsider IV opioids prior to increasing desflurane concentration– Initial vaporizer setting: 3% to 6% desfluraneInitial vaporizer setting: 3% to 6% desflurane– Increments: 1% delivered concentrationIncrements: 1% delivered concentration– Consider a short-acting beta blocker such as esmololConsider a short-acting beta blocker such as esmolol
Cardiovascular Effects of Cardiovascular Effects of Desflurane in Adults: SummaryDesflurane in Adults: Summary
• Desflurane decreases arterial pressure, systemic vascular Desflurane decreases arterial pressure, systemic vascular resistance, and myocardial contractility, and increases heart resistance, and myocardial contractility, and increases heart rate; these effects are similar to those seen with isofluranerate; these effects are similar to those seen with isoflurane
• Desflurane may transiently increase blood pressure and heart Desflurane may transiently increase blood pressure and heart rate when concentrations are rapidly increased above 1 MAC; rate when concentrations are rapidly increased above 1 MAC; opioid premedication can minimize these effectsopioid premedication can minimize these effects
• Desflurane may be rapidly titrated, providing faster control of Desflurane may be rapidly titrated, providing faster control of the hemodynamic state compared to isofluranethe hemodynamic state compared to isoflurane
DESFLURANEDESFLURANE
• Pulmonary effectsPulmonary effects
Depression of Ventilation With DesfluraneDepression of Ventilation With Desflurane
• Respiratory depression is comparable to that Respiratory depression is comparable to that with isoflurane, with and without Nwith isoflurane, with and without N22OO
• Ventilatory response to increasing levels of Ventilatory response to increasing levels of PaCOPaCO22 is similar to that produced by isoflurane is similar to that produced by isoflurane or Nor N22O and marginally less than that with O and marginally less than that with halothanehalothane
Fourcade et al. Anesthesiology. 1971;35:26.Fourcade et al. Anesthesiology. 1971;35:26.Lockhart et al. Anesthesiology. 1991;74:484.Lockhart et al. Anesthesiology. 1991;74:484.Munson et al. Anesthesiology. 1966;27:716. Munson et al. Anesthesiology. 1966;27:716.
Adverse Respiratory Events in Adults During Adverse Respiratory Events in Adults During InductionInduction
Data on file, Baxter Healthcare Corporation.Data on file, Baxter Healthcare Corporation.
DesfluraneDesflurane IsofluraneIsoflurane PropofolPropofol(n = 1162)(n = 1162) (n = 415)(n = 415) (n = 266)(n = 266)
CoughingCoughing 10.9*10.9* 0.20.2 4.54.5 SalivationSalivation 4.0*4.0* 0.50.5 1.51.5LaryngospasmLaryngospasm 3.5*3.5* 0.20.2 1.51.5BreathholdingBreathholding 8.5*8.5* 0.00.0 7.17.1BronchospasmBronchospasm 0.30.3 0.50.5 0.40.4SpOSpO22 80%80% 0.80.8 1.21.2 1.51.5SpOSpO22 85%85% 2.22.2 2.22.2 1.91.9SpOSpO22 90%90% 5.95.9 4.34.3 3.03.0
Incidence (%)Incidence (%)
* P<.05 vs isoflurane* P<.05 vs isoflurane
Desflurane Desflurane
CNS effectsCNS effects
Effects of Anesthetics on CBF Effects of Anesthetics on CBF and Cerebral Metabolic Rateand Cerebral Metabolic Rate
Lenz et al. Anesthesiology. 1999;91:1720;Lenz et al. Anesthesiology. 1999;91:1720;Drummond JC, Patel PM. In: Drummond JC, Patel PM. In:
Miller RD. Anesthesia. 2000:695.Miller RD. Anesthesia. 2000:695.
IsofluraneIsoflurane
DesfluraneDesflurane
SevofluraneSevoflurane
YesYes
YesYes
YesYes
Direct Direct Cerebral Cerebral
VasodilationVasodilationCMROCMRO22CBFCBFAgentAgent
Isoflurane in NeurosurgeryIsoflurane in Neurosurgery
• Considered the “gold standard” inhalation agent for Considered the “gold standard” inhalation agent for neurosurgical proceduresneurosurgical procedures
• Preserves myocardial function to a greater extent than Preserves myocardial function to a greater extent than did older inhalation anestheticsdid older inhalation anesthetics
• CSF pressure maintained during controlled ventilationCSF pressure maintained during controlled ventilation
• Ventilation producing hypocapnia attenuates Ventilation producing hypocapnia attenuates increases in CBF and CSF pressure resulting from the increases in CBF and CSF pressure resulting from the use of isoflurane (and other inhalation agents)use of isoflurane (and other inhalation agents)
• Simultaneous initiation of hyperventilation and Simultaneous initiation of hyperventilation and isoflurane during anesthesia induction prevents a isoflurane during anesthesia induction prevents a significant increase in ICPsignificant increase in ICP
Adams et al. Anesthesiology. 1981;54:97.Adams et al. Anesthesiology. 1981;54:97.Frost EAM. Br J Anaesth. 1984;Frost EAM. Br J Anaesth. 1984;56(suppl 1):47S.
Desflurane vs Isoflurane: Desflurane vs Isoflurane: Cerebral Blood Flow (CBF) During Cerebral Blood Flow (CBF) During
CraniotomyCraniotomy
Ornstein et al. Anesthesiology. 1993;Ornstein et al. Anesthesiology. 1993;79:498.
Cerebral Blood Flow(mL/100 g/min)
Desflurane
Isoflurane
Mean + SD
1.5 MAC1.0 MAC
20
15
10
5
0
Desflurane and CSF Pressure:Desflurane and CSF Pressure:Results From 3 StudiesResults From 3 Studies
• Muzzi et al, n=14 (D=7, I=7)Muzzi et al, n=14 (D=7, I=7)– Dose dependent: no change in CSF pressure with Dose dependent: no change in CSF pressure with
either 0.5 MAC desflurane or isoflurane in 50% Neither 0.5 MAC desflurane or isoflurane in 50% N22OO
• Muzzi et al, n=20 (D=12, I=8)Muzzi et al, n=20 (D=12, I=8)– Increase of 7 mm Hg above baseline valuesIncrease of 7 mm Hg above baseline values
with 1.0 MAC desfluranewith 1.0 MAC desflurane
• Ebrahim et al, n = 12Ebrahim et al, n = 12– No increase in CSF pressure above postinduction No increase in CSF pressure above postinduction
baseline values with 1.0 MAC desfluranebaseline values with 1.0 MAC desflurane
Emergence and Recovery in NeurosurgeryEmergence and Recovery in Neurosurgery
14.9
30.6
19.6
34.2
22.1
39.1
0
5
10
15
20
25
30
35
40
Minutes
Open Eyes Squeeze Hand State Name
Desflurane
Isoflurane
30 Patients Undergoing Acoustic Neuroma Procedures30 Patients Undergoing Acoustic Neuroma Procedures
*†
†
* P<.001* P<.001† † P<.005P<.005
Boisson-Bertrand et al. Br J Anaesth. 1998;80(suppl 1):136.Boisson-Bertrand et al. Br J Anaesth. 1998;80(suppl 1):136.
Desflurane Desflurane
•Clinical useClinical use
Desflurane Vaporizer (1)Desflurane Vaporizer (1)
• Tec 6: electrically powered, heated, Tec 6: electrically powered, heated, pressurizedpressurized
• Output concentration: 0% to 18% Output concentration: 0% to 18% (separate safety feature for(separate safety feature forconcentrations > 12%)concentrations > 12%)
• Fresh gas flow range: 0.2 to 10 L/minFresh gas flow range: 0.2 to 10 L/min
• Accuracy: 0.5% absolute or 15% relative, Accuracy: 0.5% absolute or 15% relative, whichever is greater (similar to otherwhichever is greater (similar to otherTec-type vaporizers)Tec-type vaporizers)Weiskopf RB et al. Br J Anaesth. 1994;72:474-479; Yasuda Weiskopf RB et al. Br J Anaesth. 1994;72:474-479; Yasuda N et al. Anesth Analg. 1991;72:316-324; Tec 6 Vaporizer N et al. Anesth Analg. 1991;72:316-324; Tec 6 Vaporizer [product brochure]. Liberty Corner, NJ: Ohmeda [product brochure]. Liberty Corner, NJ: Ohmeda Pharmaceutical Products Division Inc; 1995.Pharmaceutical Products Division Inc; 1995.
Desflurane Vaporizer (2)Desflurane Vaporizer (2)
• CapacityCapacity
– 400 mL working volume400 mL working volume(LCD indicator)(LCD indicator)
– 50 mL reserve (not indicated)50 mL reserve (not indicated)
• Can be refilled with desfluraneCan be refilled with desflurane(at room temperature) while in use(at room temperature) while in use
• Multiple alarm featuresMultiple alarm features(with battery back-up)(with battery back-up)
• Battery back-up supplies alarms Battery back-up supplies alarms only (vaporizer shuts off with loss only (vaporizer shuts off with loss of main power)of main power)
Actual Desflurane Actual Desflurane Concentration at Various Flow Concentration at Various Flow
RatesRates20
16
12
8
4
02 4 6 8 10 12Flow Rate (L/min)
3% in O2
3% in N2O
6% in O2
6% in N2O
12% in O2
12% in N2O
18% in O2
18% in N2O
Nominal DesfluraneConcentration
Actual % Desflurane
Johnston RV Jr et al. Anesth Analg. 1994;79:548-552.Weiskopf RB et al. Br J Anaesth. 1994;72:474-479.Tec 6 Vaporizer [product brochure]. Liberty Corner, NJ: Tec 6 Vaporizer [product brochure]. Liberty Corner, NJ: Ohmeda Ohmeda Pharmaceutical Products Division Inc; 1995. Pharmaceutical Products Division Inc; 1995.
Effect of Fentanyl on MAC of DesfluraneEffect of Fentanyl on MAC of Desflurane
MAC of desflurane with 60% NMAC of desflurane with 60% N22O*O* 31-65 Years31-65 Years
+ 0 mcg/kg fentanyl+ 0 mcg/kg fentanyl 3.7%3.7%
+ 3 mcg/kg fentanyl+ 3 mcg/kg fentanyl 3.0% 3.0%
+ 6 mcg/kg fentanyl+ 6 mcg/kg fentanyl 1.2% 1.2%
+ 9 mcg/kg fentanyl+ 9 mcg/kg fentanyl 0.1% 0.1%
Ages
* Effect on MAC lessens over time* Effect on MAC lessens over time
Ghouri, White. Anesth Analg. 1991;72:377; Ghouri, White. Anesth Analg. 1991;72:377; Sebel PS et al. Anesthesiology. 1992;76:52-59.
Desflurane Maintenance: Initial Uptake Desflurane Maintenance: Initial Uptake
• IV opioids (eg, fentanyl 1.5-2.0 mcg/kg) may be administeredIV opioids (eg, fentanyl 1.5-2.0 mcg/kg) may be administeredprior to inductionprior to induction
• Induction may be accomplished with an IV agent (eg, propofol or Induction may be accomplished with an IV agent (eg, propofol or thiopental), followed by administration of desflurane via mask, LMA, thiopental), followed by administration of desflurane via mask, LMA, or endotracheal tube for maintenanceor endotracheal tube for maintenance
• Following IV induction, a reasonable initial vaporizer setting is 3% Following IV induction, a reasonable initial vaporizer setting is 3% with a fresh gas flow of 4-6 L/min during initial uptake of desfluranewith a fresh gas flow of 4-6 L/min during initial uptake of desflurane
• The anesthesia clinician should consider the patient’s clinical The anesthesia clinician should consider the patient’s clinical condition and the presence of other agents, such as Ncondition and the presence of other agents, such as N22O and O and
intravenous drugsintravenous drugsSuprane® (desflurane, USP) prescribing information. Baxter Healthcare Corporation, New Providence, NJ.
Desflurane Maintenance:Desflurane Maintenance:Achieving Surgical DepthAchieving Surgical Depth
• Delivered desflurane concentration should be gradually increased in Delivered desflurane concentration should be gradually increased in 1% increments (at 4-6 L/min flow rate) every few breaths until 1% increments (at 4-6 L/min flow rate) every few breaths until desired anesthetic depth is reacheddesired anesthetic depth is reached
• Fresh gas flow rates may be reduced to 1-3 L/min once adequate Fresh gas flow rates may be reduced to 1-3 L/min once adequate anesthetic depth is attained because of the rapid approach of anesthetic depth is attained because of the rapid approach of alveolar to inspired concentrations with desfluranealveolar to inspired concentrations with desflurane
• Desflurane concentrations of less than 6% rarely produce clinical Desflurane concentrations of less than 6% rarely produce clinical manifestations of airway irritation or sympathetic stimulationmanifestations of airway irritation or sympathetic stimulation
• Such effects may be minimized by administering anesthetic Such effects may be minimized by administering anesthetic adjuvants (eg, Nadjuvants (eg, N22O, opioids, or a short-acting beta blocker)O, opioids, or a short-acting beta blocker)
SupraneSuprane®® (desflurane) prescribing information. (desflurane) prescribing information.
Desflurane Maintenance:Desflurane Maintenance:Titrating Anesthetic DepthTitrating Anesthetic Depth
• When altering anesthetic depth, increase or decrease When altering anesthetic depth, increase or decrease desfluranedesflurane concentration in increments of 1% and concentration in increments of 1% and increase the fresh gas flow rate to 4-6 L/min until the increase the fresh gas flow rate to 4-6 L/min until the desired anesthetic depth is reacheddesired anesthetic depth is reached
• Anesthetic depth can be more rapidly titrated with Anesthetic depth can be more rapidly titrated with desflurane than with isoflurane. This allows more desflurane than with isoflurane. This allows more rapid control of elevated blood pressure resulting rapid control of elevated blood pressure resulting from surgical stimulusfrom surgical stimulus
Avramov MN et al. Anesth Analg.1998;87:666-670.Avramov MN et al. Anesth Analg.1998;87:666-670.
Desflurane Maintenance:Desflurane Maintenance:Emergence and the Postoperative PeriodEmergence and the Postoperative Period
Emergence RecommendationsEmergence Recommendations• Perform all airway manipulation and suctioning while patient is Perform all airway manipulation and suctioning while patient is
adequately anesthetizedadequately anesthetized• If patient is intubated, consider extubation while patient is If patient is intubated, consider extubation while patient is
adequately anesthetizedadequately anesthetized• Avoid stimulation during stage II anesthesiaAvoid stimulation during stage II anesthesia• To minimize or attenuate cough during emergence, administer a To minimize or attenuate cough during emergence, administer a
small dose of opioid, propofol, or lidocainesmall dose of opioid, propofol, or lidocaine
Significance of Rapid Awakening Seen With DesfluraneSignificance of Rapid Awakening Seen With Desflurane• Earlier assessment of cognitive function is possibleEarlier assessment of cognitive function is possible• Earlier reversal of muscle relaxants should be consideredEarlier reversal of muscle relaxants should be considered• Earlier assessment of analgesic needs may be necessaryEarlier assessment of analgesic needs may be necessary
Clinically Relevant PropertiesClinically Relevant Properties
• More rapid control of the anesthetic state, especially at More rapid control of the anesthetic state, especially at low flowslow flows
• More rapid return of cognitive functionMore rapid return of cognitive function
• Better quality of recoveryBetter quality of recovery
• Less critical to anticipate end of surgeryLess critical to anticipate end of surgery
• More rapid awakening .Only drug FAST-IN, FAST–More rapid awakening .Only drug FAST-IN, FAST–OUT OUT
• May permit earlier discharge from PACUMay permit earlier discharge from PACU
Avramov et al; Beaussier et al; Bennett et al; Avramov et al; Beaussier et al; Bennett et al; Ghouri et al; Loan et al; Tsai et al; Yasuda et Ghouri et al; Loan et al; Tsai et al; Yasuda et
al.al.
Safety Information for DesfluraneSafety Information for Desflurane
• Not recommended for induction in infants Not recommended for induction in infants and childrenand children
• Concentrations above 1 MAC may increase Concentrations above 1 MAC may increase heart rate and blood pressure, if used without heart rate and blood pressure, if used without opioids or premedicationopioids or premedication
• Like other agents, may trigger malignant Like other agents, may trigger malignant hyperthermiahyperthermia
Desflurane Desflurane
updateupdate
The effect of fentanyl on the emergence The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane characteristics after desflurane or sevoflurane
anesthesia in childrenanesthesia in children
• Anesth Analg 2002 May;94(5):1178-81Anesth Analg 2002 May;94(5):1178-81
The concurrent use of fentanyl in a dose of 2.5 microg/kg in children receiving desflurane or sevoflurane results in a low incidence of emergence agitation. Desflurane allows for a more rapid emergence and recovery than sevoflurane.
Tracheal extubation of deeply anesthetized Tracheal extubation of deeply anesthetized pediatric patients: a comparison of desflurane pediatric patients: a comparison of desflurane
and sevofluraneand sevoflurane
• Anesth Analg. 2003 May;96(5):1320-4Anesth Analg. 2003 May;96(5):1320-4 • Valley RD Freid EB, Bailey AG, Kopp VJ, Georges LS, Fletcher J, KeiferValley RD Freid EB, Bailey AG, Kopp VJ, Georges LS, Fletcher J, Keifer
• Deep extubation of children can be performed Deep extubation of children can be performed safely with desflurane or sevoflurane. Airway safely with desflurane or sevoflurane. Airway problems occur more frequently with desflurane. problems occur more frequently with desflurane. Awakening occurs more quickly with desflurane. Awakening occurs more quickly with desflurane. Midazolam premedication has a greater effect on Midazolam premedication has a greater effect on emergence times than does the choice of emergence times than does the choice of inhaled anesthetic. Emergence agitation occurs inhaled anesthetic. Emergence agitation occurs frequently with either technique.frequently with either technique.
The effect of sevoflurane and desflurane on The effect of sevoflurane and desflurane on upper airway reactivity.upper airway reactivity.
• Anesthesiology. 2001 Jun;94(6):963-7Anesthesiology. 2001 Jun;94(6):963-7 • Klock PA Jr, Czeslick EG, Klafta JM, Ovassapian A, Moss J.Klock PA Jr, Czeslick EG, Klafta JM, Ovassapian A, Moss J.
•
CONCLUSIONSCONCLUSIONS:: The assessment of the cough The assessment of the cough response to tracheal stimulation by endotracheal response to tracheal stimulation by endotracheal tube cuff inflation is a reliable and clinically tube cuff inflation is a reliable and clinically meaningful measure of upper airway reactivity. meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is superior to At 1.0 MAC, sevoflurane is superior to desflurane for suppressing moderate and severe desflurane for suppressing moderate and severe responses to this stimulusresponses to this stimulus..
A comparison of airway responses during desflurane A comparison of airway responses during desflurane and sevoflurane administration via a laryngeal mask and sevoflurane administration via a laryngeal mask
airway for maintenance of anesthesia.airway for maintenance of anesthesia.
• Anesth Analg. 2003 Mar;96(3):701-5Anesth Analg. 2003 Mar;96(3):701-5
• IMPLICATIONSIMPLICATIONS: : Although sevoflurane is less pungent Although sevoflurane is less pungent than desflurane at larger concentrations, neither than desflurane at larger concentrations, neither anesthetic seems to irritate the airway when anesthetic seems to irritate the airway when administered at the smaller concentrations often administered at the smaller concentrations often used during maintenance of anesthesia. Both used during maintenance of anesthesia. Both anesthetics may be delivered effectively via a anesthetics may be delivered effectively via a laryngeal mask airway, with minimal evidence of laryngeal mask airway, with minimal evidence of airway irritation.airway irritation.
The recovery of cognitive function after general The recovery of cognitive function after general anesthesia in elderly patients: a comparison of anesthesia in elderly patients: a comparison of
desflurane and sevoflurane.desflurane and sevoflurane.
• Anesth Analg. 2001 Dec;93(6):1489-94Anesth Analg. 2001 Dec;93(6):1489-94 • Chen X, Zhao M, White PF, Li S, Tang J, Wender RH, Chen X, Zhao M, White PF, Li S, Tang J, Wender RH,
Sloninsky A, Naruse R, Kariger R, Webb T, Norel E.Sloninsky A, Naruse R, Kariger R, Webb T, Norel E.
• IMPLICATIONSIMPLICATIONS: : Desflurane was associated with a Desflurane was associated with a faster early recovery than sevoflurane after general faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of anesthesia in elderly patients. However, recovery of cognitive function was similar with both volatile cognitive function was similar with both volatile anesthetics.anesthetics.
Carbon monoxide production from desflurane, Carbon monoxide production from desflurane, enflurane, halothane, isoflurane, and sevoflurane with enflurane, halothane, isoflurane, and sevoflurane with
dry soda lime.dry soda lime.
• Anesthesiology. 2001 Nov;95(5):1205-12Anesthesiology. 2001 Nov;95(5):1205-12• Wissing H, Kuhn I, Warnken U, Dudziak R.Wissing H, Kuhn I, Warnken U, Dudziak R.
• CONCLUSIONS: CONCLUSIONS: The absorbent temperature increased with The absorbent temperature increased with all anesthetics but was highest for sevoflurane. The all anesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane smaller but significant CO formation from sevoflurane was found, which may account for the CO hemoglobin was found, which may account for the CO hemoglobin concentrations reported in infants. With all agents, CO concentrations reported in infants. With all agents, CO formation appears to be self-limited.formation appears to be self-limited.
•