Intravenous Anesthesia

1
Intravenous Anesthesia

• Steven L. Shafer, MD
• Professor of Anesthesia, Stanford University
• Adjunct Professor of Biopharmaceutical Science,
  UCSF
• Staff Anesthesiologist, Palo Alto VA Health Care
  System

2
What is Anesthesia?

• Sensory
• Absence of intraoperative pain
• Cognitive
• Absence of intraoperative awareness
• Absence of recall of intraoperative events
• Motor
• Absence of movement
• Adequate muscular relaxation
• Autonomic
• Absence of hemodynamic response
• Absence of tearing, flushing, sweating

3
What is Balanced Anesthesia?

• Use specific drugs for each component
• Sensory
• N20, opioids, ketamine for analgesia
• Cognitive
• Produce amnesia, and preferably unconsciousness,
  with N2O, .25-.5 MAC of an inhaled agent, or an
  IV hypnotic (propofol, midazolam, diazepam,
  thiopental)
• Motor
• Muscle relaxants as needed
• Autonomic
• If sensory and cognitive components are adequate,
  usually no additional medication will be needed
  for autonomic stability. If some is needed,
  often a beta blocker /- vasodilator is used.

4
What is Balanced Anesthesia?

• Garbage Anesthesia (everything but the kitchen
  sink)
• LOT2 (Little Of This, Little of That)
• Mixed Technique
• The Usual

5
MAC Reduction
Lang et al, Anesthesiology 85, 721-728, 1996
6
Bolus Dose Equivalents

• Fentanyl 100 mg (1.5 mg/kg)
• Remifentanil 35 mg (0.5 mg/kg)
• Alfentanil 500 mg (7 mg/kg)
• Sufentanil 12 mg (0.2 mg/kg)

7
What is the role of N2O?

• Excellent analgesic in sub-MAC doses
• MAC is around 110.
• MACasleep tends to be about 60 of MAC.
• MACasleep for N2O is 68-73
• Well tolerated by most patients.
• At N2O concentrations of 70, there may be no
  need for additional drugs to ensure lack of
  awareness.
• Has the fastest elimination of any hypnotic agent
  used in anesthesia.
• If you want your patients to wake up quickly,
  keep them within N2O of being awake!

8
Simple Combinations

• Morphine
• 10 mg iv 3-5 minutes prior to induction
• Additional 5 mg 45 minutes before the end of the
  procedure, if it lasts longer than 2 hours
• Propofol
• 2-3 mg/kg on induction
• N2O
• 70
• Sevoflurane
• 0.3-0.6
• Relaxant of choice

9
Simple Combinations

• Fentanyl
• 75-150 on induction
• 25-50 mg now and then during the case
• Propofol
• 2-3 mg/kg on induction
• N2O
• 70
• Sevoflurane
• 0.3-0.6
• Relaxant of choice

10
Setting up drug infusions

• Check out your infusion pump as thoroughly as you
  check out your anesthesia machine.
• Is your drug dilution correct?
• Is the syringe adequately held?
• Is the syringe plunger properly held in the
  clamp?
• Are your infusion units correct?
• Is the weight correct (for calculator pumps)?
• Has the dead space been taken out of the line?
• Have the batteries been checked?
• Think of the check out as though you were going
  to infuse sodium nitroprusside.

11
Setting up drug infusions

• Always infuse drug through a t-piece connected at
  the IV catheter site.
• Typical IV tubing contains 5-8 mls of dead space
  between injection ports and catheter.
• Connecting the infusion at the convenient
  injection port may result in patients receiving
  5-8 mls of remifentanil if the IV rate is
  increased or other drugs are flushed through the
  line.
• After an unintentional bolus there will be a
  period of no drug administration while the tubing
  again fills with remifentanil.

12
50 Effect Site Decrement Time
13
20 Effect Site Decrement Time
14
80 Effect Site Decrement Time
15
Continuous Infusions Propofol

• 2-3 mg/kg bolus on induction
• Relaxant of choice
• Titrate propofol infusion from 75-140 mg/kg/min
  during case
• In last 45 minutes, stay from 50-100 mg/kg/min
• N2O 70
• Crack open vaporizor as needed for BP control

16
Propofol Induction
100
90
80
Dose as fraction of dose in a 20 year old
70
60
50
20
40
60
80
Age
17
Propofol/opioid vs Isoflurane/opioid
18
Propofol/opioid vs Isoflurane/opioid
19
Continuous InfusionsFentanyl

• Initial Bolus 150 mg
• Infusion 1 2 mg/min for 6 hours
• Infusion 2 1 mg/min
• End 90 minutes prior to anticipated
  extubation

20
Continuous InfusionsAlfentanil

• Initial Bolus 1000 mg
• Infusion 50 mg/min
• End 45 minutes prior to anticipated
  extubation

21
Continuous InfusionsSufentanil

• Initial Bolus 16 mg
• Infusion 1 1 mg/min for 6 hours
• Infusion 2 0.5 mg/min
• End 30 minutes prior to anticipated
  extubation

22
Observations

• Of these, sufentanil works the best, fentanyl
  works the poorest
• Fentanyl accumulates the most, which can be a
  problem with continuous infusions
• Must remain vigilant for signs of light
  anesthesia
• Change in heart rate is often the first sign.
• If the patient is light, give a 2-3 cc bolus of
  propofol

23
Remifentanil vs. other opioids
100
remifentanil

• Rapid rise to steady state

80
60
alfentanil
Percent of steady-state
effect site opioid concentration
40
sufentanil
20
fentanyl
0
0
10
20
30
40
50
60
Minutes since beginning of continuous infusion
Shafer SL, ASA Refresher Course, Chapter 19, 1996
24
Remifentanil vs. other opioids
100
10
Percent of peak plasma opioid concentration
fentanyl
1
sufentanil
alfentanil
remifentanil
0.1
0
120
240
360
480
600
Minutes since bolus injection
Minto et al, Anesthesiology, in press
25
Remifentanil vs. other opioids
100
sufentanil
80
fentanyl
60
Percent of peak effect site opioid concentration
40
alfentanil
20
remifentanil
0
0
2
4
6
8
10
Minutes since bolus injection
Minto et al, Anesthesiology, in press
26
Remifentanil vs. other opioids

• Recovery from remifentanil is unlike that seen
  with any other opioid
• The time to a given decrease in effect site
  concentration is constant over time
• no accumulation

60
fentanyl
40
20 decrease
alfentanil
20
sufentanil
0
remifentanil
120
fentanyl
90
alfentanil
Minutes required for a given percent decrease in
effect site concentration
60
50 decrease
sufentanil
30
remifentanil
0
300
fentanyl
240
alfentanil
180
80 decrease
120
sufentanil
60
remifentanil
0
0
120
240
360
480
600
Minutes since beginning of infusion
Shafer SL, ASA Refresher Course, Chapter 19, 1996
27
20 effect sitedecrement curves
60
fentanyl
40
Minutes required
alfentanil
20
sufentanil
remifentanil
0
0
120
240
360
480
600
Minutes since beginning of infusion
Shafer SL, ASA Refresher Course, Chapter 19, 1996
28
50 effect sitedecrement curves
Minutes required
Minutes since beginning of infusion
Shafer SL, ASA Refresher Course, Chapter 19, 1996
29
80 effect sitedecrement curves
Minutes required
Minutes since beginning of infusion
Shafer SL, ASA Refresher Course, Chapter 19, 1996
30
Remifentanil/Propofol Induction
g/ml)
m
Target Propofol
Concentration (
0
5
10
15
20
25
30
35
40
Remifentanil Concentration (ng/ml)
Ssuccess (no response to skin incision)
Ffailure (response to skin incision)
Fragen et al, data on file with Glaxo
Pharmaceuticals
31
25
1.0 mg/kg/min
20
15
Remifentanil concentration (ng/ml)
0.5 mg/kg/min
10
Rigidity
Apnea
5
Ventilatory Depression
1.0 mg/kg
0
0
2
4
6
8
10
Minutes
32
Induction TechniqueRemifentanil 1.0 mg/kg/min
25

• Hypnotic and relaxant 30-90 seconds prior to
  starting remifentanil infusion.
• Intubate 90-120 seconds after starting
  remifentanil infusion.
• Decrease infusion rate after intubation.

1.0
m
g/kg/min
20
15
Remifentanil concentration (ng/ml)
Intubate

10
Rigidity
Relaxant

Apnea
5
Hypnotic

Ventilatory Depression
0
-2
0
2
4
6
8
10
Minutes
33
Induction TechniqueRemifentanil 1.0 mg/kg bolus

• Hypnotic and relaxant just before remifentanil
  bolus.
• Intubate 60-90 seconds after remifentanil bolus.
• Suitable for rapid sequence.

25
20
15
Remifentanil concentration (ng/ml)
Intubate

10
Rigidity
Relaxant
Apnea

5
Hypnotic

Ventilatory Depression
1.0
m
g/kg
0
-2
0
2
4
6
8
10
Minutes
34
Induction TechniqueRemifentanil 0.5 mg/kg/min

• Start remifentanil infusion.
• Give hypnotic 30-90 seconds after starting
  infusion, followed by relaxant
• Slower, gentler technique.

25
20
15
Remifentanil concentration (ng/ml)
0.5
m
g/kg/min
Intubate
10

Rigidity
Relaxant

Apnea
5
Hypnotic

Ventilatory Depression
0
-2
0
2
4
6
8
10
Minutes
35
Maintenance Infusion Rates

• 1.0 mg/kg/min
• Profound analgesia
• 0.5 mg/kg/min
• Paralysis required
• 0.25 mg/kg/min
• Ventilation required
• gt 50 MAC reduction
• 0.1 mg/kg/min
• May be satisfactoryfor spontaneous ventilation

36
Potential RiskInfusion interruption

• Reports of nearly catastrophic events associated
  with abrupt termination of remifentanil
  infusions.
• Few other drugs in anesthesia where so little
  time exists between infusion interruption and
  severe complications.
• Need to have an alternative plan ready
• Propofol bolus
• Turn on / turn up inhalational anesthetic
• Fentanyl bolus
• Need to have next syringe made up and ready to
  go.
• Spending 2 minutes changing syringe might be too
  long during light anesthetics

37
Propofol/Alfentanil Interaction
400

• Adapted from Vuyk et al, Anesthesiology 838-22,
  1995
• Characterizes the concentrations for
• intubation
• maintenance
• on emergence
• Concentrations are 50 response level

Intubation
300
Maintenance
200
Alfentanil Concentration (ng/ml)
Emergence
100
0
0
2
4
6
8
10
Propofol Concentration (mg/ml)
38
Opioid/Hypnotic Interactions

• Vuyk, et al Pharmacodynamic Interaction of
  Propofol and Alfentanil
• Anesthesiology 838-22, 1995
• Stanski and Shafer Quantifying Anesthetic Drug
  Interaction Implications for Drug Dosing
• Anesthesiology 831-5, 1995

39
Optimal Propofol/Alfentanil

• Infusion rates for propofol and alfentanil
• Propofol levels during maintenance and at
  emergence from anesthesia
• Alfentanil concentrations during maintenance and
  at emergence
• Time from ending the infusion to awakening from
  anesthesia
• The percent decrease in concentration required
  for emergence from anesthesia

Stanski and Shafer Anesthesiology 831-5, 1995
40
Propofol/Opioid Technique
Stanski and Shafer Anesthesiology 831-5, 1995
Shafer SL, ASA Refresher Course, Chapter 19, 1996
41
Propofol/OpioidTime to Awakening
Alfentanil Technique
Remifentanil Technique
20
15
10
5
0
600

120
240
360
480
600
0
120
240
360
480
Time (Minutes)
Time (Minutes)
Shafer SL, ASA Refresher Course, Chapter 19, 1996
42
Propofol/OpioidInfusion rates
Alfentanil Technique
Remifentanil Technique
400
300
Remifentanil (ng/kg/min)
Alfentanil (ng/kg/min)
200
Propofol (mg/kg/min)
Propofol (mg/kg/min)
100
0
600

120
240
360
480
600
0
120
240
360
480
Time (Minutes)
Time (Minutes)
Shafer SL, ASA Refresher Course, Chapter 19, 1996
43
Propofol/OpioidPropofol Levels (mg/ml)
Alfentanil Technique
Remifentanil Technique
6
4
Maintenance
Maintenance
2
Emergence
Emergence
0
600

120
240
360
480
600
0
120
240
360
480
Time (Minutes)
Time (Minutes)
Shafer SL, ASA Refresher Course, Chapter 19, 1996
44
Propofol/OpioidPercent Decrease on Emergence
Alfentanil Technique
Remifentanil Technique
100
75
Remifentanil
Propofol
50
Propofol
25
Alfentanil
0
600

120
240
360
480
600
0
120
240
360
480
Time (Minutes)
Time (Minutes)
Shafer SL, ASA Refresher Course, Chapter 19, 1996
45
Propofol/Remifentanil TIVA

• Remifentanil
• 0.25 mg/kg/min
• Propofol
• 80 mg/kg/min
• Requires controlled ventilation

Shafer SL, ASA Refresher Course, Chapter 19, 1996

• Little tolerance for interruption of
  remifentanil or propofol infusion

46
Easy Propofol - Remifentanil

• Add 1 mg of remifentanil to your 50 cc propofol
  syringe
• Remifentanil concentration will be 20 mg/ml
• Approach gives a bit less remi than in prior
  slide
• Use with 70 N2O, or increase propofol dose to
  100-120 mg/kg/min

47
Easy Propofol - Ketamine

• Add 50 mg of ketamine to your 50 cc propofol
  syringe
• The ketamine takes the place of the nitrous oxide
• Propofol effectively blunts the psychotomimetic
  effects to ketamine

48
The ASPECT Data Base

• Aspect Medical System
• Inventor of the Bispectral Index
• mysteriously called the BIS
• Validating Bispectral Index as a measure of
  anesthetic depth
• Movement in response to noxious stimulation - in
  gt 300 patients undergoing surgery
• Recall, Sedation, Eyelash reflex - in gt100
  volunteers

49
The ASPECT Data Base

• Patient trials (movement)
• Thiopental
• Propofol
• Fentanyl/Alfentanil/Sufentanil
• Isoflurane
• Nitrous Oxide
• Volunteer trials (recall, sedation, eyelash)
• Propofol
• Isoflurane
• Alfentanil
• Midazolam

50
Recall vs. Heart Rate and Blood Pressure
51
RecallBIS vs Blood Pressure
52
RecallBispectral Index vs Concentration
53
MovementHeart Rate vs Blood Pressure
54
MovementD Heart Rate vs D Blood Pressure
55
MovementBlood Pressure vs Concentration
56
SedationBispectral Index vs Concentration
1.0


0.8












0.6








Probability of Deep Sedation
0.4













0.2























0



























































































10





























0






















































8


























20
































































































6




























































40














































































































































4












































































60






















































































Effect Site Concentration






















































BIS
2
80
0
100
57
Bottom line on awareness

• Give enough drug.
• Dont completely paralyze patients unless
  absolutely necessary.
• Look for changes in heart rate.
• Respond to light anesthesia with a bolus of
  hypnotic.
• Give enough drug!