General Anesthetics Tutorial See schedule for appropriate time to study this material

1
General AnestheticsTutorialSee schedule for
appropriatetime to study this material

• Robert Koerker, Ph.D
• Tel [phone] (work) or 434-0949 (home)
• Office 290N WH
• E-mail robert.koerker_at_wright.edu

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Learning Resources

• Required Textbook
• Principles of Pharmacology
• The Pathophysiologic Basis of Drug Therapy
• David E. Golan et. al. , 2008
• Chapter 15, pp. 239-258
• Practice Exam Questions are at end of notes
• Answers will be put on line

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Learning Objectives
Review on own

• Part I - General Concepts
• Define a general anesthetic (GA) and
  differentiate from a local anesthetic
• (LA)
• Describe 4 major objectives of anesthesia
• Learn components of balanced anesthesia
• Recognize stages and planes of ether
  anesthesia
• Understand neuro-pharmacological basis for
  stages of anesthesia
• Define induction, maintenance and recovery phases
  of GA
• Summarize physical properties physiological
  factors associated with GA agents
• Review theories of mechanism of action of GA
• Discuss effects of GA on physiological systems

4
Learning Objectives (continued)
Review on own

• Part II - Specific classes of GA Agents
• Briefly compare and contrast individual agents
  within each of the
• following classes
• Volatile liquids
• Gases
• Dissociative anesthetics
• Neuroleptanalgesics
• Preanesthetic induction agents
• Barbiturates
• Etomidate
• Propofol
• Malignant hyperthermia (Halothane)

5
Clinical Use of GA

• More than 28 million patients receive GA or LA
  during surgery/year in U.S.
• Will increase to 40 million in next 3 decades
• Patients over 65 y.o. undergoing non-cardiac
  surgery will double in next 3 decades

6
Definitions

• Anesthesia - loss of sensation
• General anesthesia loss of sensation associated
  with loss of consciousness
• Local anesthesia localized loss of sensation
  without loss of consciousness
• All anesthetics produce reversible actions
  manifest by depression of excitable tissues such
  as nerves, smooth muscle, myocardium

7
Levels of Consciousness
1
3
2
8
Four Major Objectives of Anesthesia

• Hypnosis (amnesia) -Loss of consciousness
• Analgesia Loss of pain
• Hyporeflexia Decreased spinal reflexes
• Neuromuscular Blockade Adequate muscle
  relaxation

9
Balanced Anesthesia (See Golan, p. 255)

• Preanesthetic Medications
• Sedatives
• Analgesics
• anticholinergic muscarinic blockers (atropine) to
  dry secretions reduce reflexes
• Anesthetic Agents
• single agents or combinations
• Adjunctive Agents
• neuromuscular blocking drugs

10
Stages of Anesthesia (See Golan, Fig 15-1, p. 241)
Fig. 15-1
11
Guedels Stages Planes of Ether Anesthesia
12
Stage I Analgesia

• Minimal CNS depression
• Some amnesia along with analgesia
• Respiration and pupils normal
• No eye movement or loss of reflexes
• Sensory transmission of nociceptive (painful)
  stimuli in spinothalamic tract are interrupted
  due to depression of substantia gelatinosa in
  dorsal horn of spinal cord

13
Stage II Excitement (disinhibition)

• Due to inhibition of inhibitory neurons (e.g.
  Golgi type II cells) release paradoxical
  facilitation of catecholamines.
• Respiration very irregular, coughing
• Pupils dilated
• Eye movements marked
• Loss of eyelid (blink) reflex

14
Stage III Surgical Anesthesia

• Divided into 4 planes based on progressive
  depression of ARAS (ascending reticular
  activating system)
• Plane 1
• Respiration normal and regular
• Pupils normal
• Diminishing eye movements to fixed stare
• Loss of swallowing, conjunctival and pharyngeal
  reflexes
• Plane 2
• Slight depression of respiratory movements
• Loss of laryngeal corneal reflexes
• Adequate for tonsillectomy

15
Stage III Surgical (continued)

• Plane 3
• Marked decrease in depth of inspiration
• Suppression of spinal reflexes contributes to
  muscle relaxation produced by some agents.
• Patient needs to be on mechanical respirator or
  regularly respired by anesthetist.
• Preferred level for most surgeries

• Plane 4
• Depth of expiration decreases
• Pupils dilate and wont respond to light
• Loss of carinal reflex
• Can rapidly progress to Stage IV unless action
  is
• taken to decrease depth of anesthesia stress.

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Stage IV Medullary Depression

• Cardio-respiratory collapse due to depression of
  respiratory and vasomotor centers of medulla.
  Fortunately, neurons are relatively insensitive
  to depressant effects of GA.
• Observed only at toxic doses
• Fixed, dilated pupils signs of pending coma or
  death

17
Properties of Inhaled GA
(Katzung, Table 25-1, p 403, Similar to Golan,
Table 15-1, p. 242)








18
Induction, Maintenance Recovery Phases

• Induction Phase (Guedel Stages I II)
• Time to reach plane 3 of stage III. The
  shorter, the better.
• Induction is shortened by hyperventilating (with
  ventilation-limited (diffusion-) GAs (eg.
  halothane with high B/G part. coef.), decreasing
  cardiac output (allows pp to ), in children
  (high resp. rate)or patients in shock ( CO
  vent. ppalv,) or with thyrotoxicosis (high
  resp. rate).
• Induction is lengthened by hyperventilating
  (with perfusion-limited GAs (eg. N2 O with low
  B/G part. coef.), by hypoventilation (with
  ventilation-limited GAs , e.g Halothane), with
  increased cardiac output, with chronic
  obstructive pulmonary disease, and with
  right-to-left shunt. (physiological shunt that
  causes blood to bypass the alveoli) (See Table
  15-4, Golan, p 252)
• Maintenance Phase
• Period of equilibrium when GAin alveoli GA
  in blood GA in brain
• ?p.p. or min. vent.? deeper anesthesia
• ?p.p. or min. vent.?lighter anesthesia
• Allows moment-to-moment control
• Recovery Phase Reverse of induction
• Time after stopping GA until patient wakes up
  (See Golan, p. 252)

19
Fig. 15-11
20
Ostwald Solubility Coefficient

• The more soluble a GA is in the blood, the higher
  will be the coefficient, and the longer will be
  the induction and recovery periods.

21
Comparison of N2O with Halothane(Katzung, Fig.
25-3, p. 404)

• Why is induction slower with the more soluble
  anesthetic, halothane, than with N2O, which has a
  very low bloodgas partition coefficient and is
  thus not very soluble in the blood?

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Figure Legend

• Solubility of the two agents in blood is
  represented by the relative size of the blood
  compartment (more solublelarger compartment.
• Relative partial pressures (PP) of agent
  indicated by the degree of filling of each
  compartment.
• For a given concentration or PP of the 2 gasses
  in the inspired air, it will take longer for the
  blood PP of the more soluble gas (halothane) to
  rise to the same PP as in the alveoli.
• Since concentration of agent in brain can rise no
  faster than concentration (PP) in blood, the
  onset of anesthesia will be slower with halothane
  than with N2O.

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(Golan, Fig. 15-8, p. 249)
Fig 15-8
24
Three Phases of Distribution of GA
Pulmonary, Circulatory, Tissue

• A. Pulmonary Phase
• Related to partial pressure and solubility of GA
  in blood
• 2. GA with high blood solubility must fill a
  larger blood reservoir so take longer to reach
  equilibrium

25
Arterial Blood Concentration vs. Time(Katzung,
Fig. 25-4, p. 404, similar to Golan, Fig. 15-7,
p. 249)
B/G 0.47
B/G 2.3
B/G 12

• Tension of 3 GA in arterial blood as function of
  time after beginning inhalation. Nitrous oxide is
  relatively insoluble (BG coefficient0.47)
  methoxyflurane is much more soluble (coefficient
  12)

26
Ventilation-Limited vs. Perfusion-Limited
Anesthetics (see Golan, p. 248)

• Blood/Gas partition coefficient distinguishes
  ventilation- from perfusion-limited anesthetics.
• Ventilation (diffusion) -limited anesthetics
  (e.g. diethyl ether, enflurane, isoflurane,
  halothane)
• Have slow, rate limiting equilibration of
  alveolar with inspired partial pressures.
• Results in slow induction and slow recovery.
• Can speed up induction by increasing rate of rise
  of alveolar partial pressures (increasing
  ventilation rate).
• Perfusion-limited anesthetics (e.g. nitrous
  oxide, desflurane, sevoflurane)
• Induction and recovery occur quickly.
• Agents that are less soluble in blood, induce
  anesthesia faster.

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Ventilation Rate and Arterial Anesthetic
Tension(Katzung, Fig. 25-5, p. 405, similar to
Golan, Fig. 15-9, p.250)
99
perfusion limited
9
As ventilation rate increases, higher tension is
achieved more rapidly.
90
65
ventillation limited
20
45

• Increased ventilation (8 vs. 2 L/min) has a much
  greater effect on equilibration of halothane
  (ventilation limited) than on nitrous oxide
  (perfusion limited).

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Phases of Distribution of GA

• B. Circulatory Phase
• 75 of cardiac output/min. goes to organs
  representing 10 of body mass (brain, liver,
  kidneys, heart, lungs). This vessel rich grp.
  (VRG) of highly perfused organs has low capacity
  and high flow)
• 25 of cardiac output/min. goes to organs
  representing 90 of body mass (muscle, skin,
  fat).
• The muscle grp. (MG muscle skin) has high
  capacity and moderate flow.
• The fat grp. (FG) has very high capacity and low
  flow
• The vessel poor group (VPG bone, cartilage,
  ligaments) has negligible flow and capacity,
  therefore ignored in calculations.

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Distribution of GAs among Major Tissue
Compartments Golan Figure 15-4
p. 245
30
Equilibration of Tissue Groups with Inspired
Partial Pressure (Golan, Fig 15-6, p. 248)
Perfusion Limited Ventilation Limited
Fig.15-6
Alv
VRG
Alv
MG
VRG
MG
Fat
Fat
Rate of equilibration in VRG is limited by its
approach to rising alveolar pressure
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Phases of Distribution of GA

• C. Tissue Phase
• To achieve maintenance anesthesia, the brain
• must be perfused with a stable conc. of GA.
• Most lean tissues have a tissue/blood
  coefficient of about 1.0.
• Transfer of anesthetic in both the lungs and
  tissues is limited by perfusion, rather than
  diffusion. (See Golan, p. 248)
• Some GAs with very high lipid solubility, will
  tend to concentrate in body fat
• Potency of GA is directly related to its lipid
  solubility. More potent GAs require lower
  concentrations to produce anesthesia.

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Meyer-Overton Rule (See Golan Box 15-2, p. 243)
(High Potency)

• Potency of anesthetic increases as its solubility
  in oil increases.
• Molecules with larger oil/gas partition
  coefficients (?) are more potent general
  anesthetics.
• As ? (oil/gas) increases, MAC (ED50) decreases.

(Low Potency)
(Golan, Fig. 15-3, p.244)
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MAC Minimal Alveolar Concentration( Golan,
p.240)

• MAC median effective anesthetic dose (ED50)
• MAC is inversely related to anesthetic potency
• (The higher the potency, the lower the MAC)

Anesthetic MAC Potency
halothane 0.75 most potent
isoflurane 1.20
enflurane 1.60
nitrous oxide 105.00 least potent
MAC can only be achieved at gt 1 atm. pressure
34
Therapeutic and Analgesic Indices(See Golan, p.
241)

• Anesthetics have steep dose-response curves and
  low therapeutic indices
• T.I. LD50 /MAC (median effective anesthetic
  concentration. Similar to ED50)
• No antagonists available to correct overdoses,
  but can closely regulate partial pressure in CNS
  by regulating partial pressure of inspired gas.
• Consequently, special training needed to safely
  administer anesthetics.
• Analgesic Index MAC/AP50 (partial pressure
  causing analgesia in 50 of patients) High A.I.
  implies analgesia is induced at partial pressure
  significantly lower than that required for
  surgical anesthesia (e.g. N2 O)

35
Isofluorane- D-Quantal R Curves for Various
Endpoints(Golan, Fig. 15-2, p. 242)
Fig. 15-2
36
GA Elimination

• Major route exhalation
• Exhalation of GA with low bloodgas partition
  coefficients (e.g. nitrous oxide or desflurane)
  is so rapid, back diffusion from blood to
  alveoli, displaces air from alveoli, leading to
  diffusion hypoxia. Prevent by ventilating with
  O2 after terminating GA. (See Golan, p. 253)
• Recovery is the reverse of induction.
• Halogenated GAs may undergo microsomal liver
  metabolism to potentially toxic free halogen
  radicals before being excreted.

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Pharmacodynamics(See Golan, pp. 256 257 )
May not be a unitary mechanism of action , but
each class of GA may have its own mechanism of
action. Read p 257 Golan on effects of GAs on
ion channels to learn about proteins that may
alter neuronal excitability when acted on
by general anesthetics.



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Effects of GAs on Physiological Systems

• Central Nervous System and
• Synaptic Transmission
• GAs depress excitable tissue.
• GAs depress frequency of EEG.
• GAs decrease metabolic rate of brain
• GAs may decrease cerebral vascular resistance and
  thus increase cerebral blood flow which may
  increase intracranial pressure. Minimize this by
  keeping patient well ventilated and PCO2 low.
• Analgesia is due to CNS action on areas of
  integration and interpretation of peripheral
  receptor input
• Peripheral receptors for pain, touch etc. are not
  markedly depressed.
• Poly-synaptic reflexes (e.g. RAS, crossed
  extensor) are depressed much more than are
  mono-synaptic reflexes.
• .

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B. Effects of GA on Respiratory System

• Tonic stimulation by the Reticular Activating
  Center (RAS) to respiratory center is lost.
  Therefore, respiratory center loses its drive to
  increase ventilation during hypoxia.
• Respiratory Center is depressed.
• Sensitivity to changes in CO2 is reduced.
  Consequently, partial pressure of CO2 in arterial
  blood increases.
• Amplitude of respiration is depressed resulting
  in decreased tidal volume.
• Rate of respiration may be increased by some
  agents but insufficient to compensate for
  decreased tidal volume minute ventilation.
• Mucociliary function in airways is depressed
  leading to pooling of mucus, atelectasis, and
  respiratory infections.
• Inhaled GAs can be used to treat status
  asthmaticus
• due to bronchodilator action.

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C. Effects of GA on Cardiovascular System (CV)

• GAs cause CV changes by depressing the
  integrative functions of the CNS resulting in
• 1) enhanced vagal tone and bradcardia.
• 2) alternatively, the stress of surgery, the
  buildup of CO2,
• or the lack of O2 may activate the
  sympathoadrenal
• system predisposing to dysrhythmias.
• 3) depressed baroreceptor reflexes.
• Direct effects on heart may lead to decreased
  cardiac output or bradycardia.
• Halogenated GAs sensitize the myocardium to
  cardiac arrhythmias, especially in presence of
  elevated levels of catecholamines.
  (catecholamine sensitization)

41
Cardiac Arrhythmias Wolff-Parkinson-White
Syndrome
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D. Effects of GA on Renal System

• GAs usually decrease urinary output due to
• Decreased BP
• Vasoconstriction within kidney
• Central stimulation of anti-diuretic hormone
• Halogen radical metabolites of some GAs may be
  directly nephrotoxic (e.g. Sevoflurane)

43
E. Effects of GA on Liver Function

• All inhalation GAs decrease hepatic blood flow by
  15-45
• May be secondary to ? CO2 or ? O2 or release of
  catecholamines
• Patients with defect in hepatic cell membrane are
  at increased risk of severe liver damage if
  exposed multiple times to a free radical
  metabolite of Halothane (Mechanism for Halothane
  hepatitis discovered in 1995)
• Autoimmune response causes massive hepatic
  necrosis (1/35,000 patients)
• Most common with repeat exposure over short time
  frame, in women and in obese patients

44
F. Effect of GA on Uterus

• Halogenated hydrocarbon GAs relax uterine smooth
  muscle
• Beneficial for intrauterine fetal manipulation
  during delivery

45
Selected Characteristics of Individual GAs
46
Part II - Diethyl ether (ether) (see Golan, p.
254)

• Ether, a volatile liquid, was 1st demonstrated to
  be an effective anesthetic in 1846 by William
  Morton, a year 2 medical student at Mass. General
  Hospital.
• Beneficial Effects
• Excellent analgesia and muscle relaxation
• Stimulates respiration down to plane 3 of stage 3
  before depressing respiration at higher levels
• Maintains circulation
• Produces bronchodilation
• Large safety margin
• Still used in third world countries
• Adverse Effects
• No longer used for surgery in U.S. because it is
  explosive, flammable and irritating to mucous
  membranes
• Prolonged and stormy induction and recovery with
  coughing and breath holding
• Causes post-operative nausea and vomiting

47
Halothane (Fluothane) beneficial effects(see
Golan, p.220)

• Most commonly used anesthetic for children in
  U.S. because of low incidence of adverse effects.
  Sevoflurane is gaining popularity for use in
  children.
• Standard against which other GA are compared
• Potent, non-flammable inhalation GA
• When combined with 50 N2O, MAC is reduced from
  0.75 to 0.30
• Smooth induction and recovery
• Causes bronchodilation
• Secondary Rx for status asthmaticus
• Causes uterine relaxation which is helpful in
  manipulating and positioning fetus for delivery
  BUT may lead to ?blood loss after caesarean
  section or therapeutic abortion

48
Halothane- adverse effects

• Respiratory Depression
• Profound myocardial depression
• Causes hypotension by decreasing cardiac output
• Sensitizes heart to ventricular arrhythmias
• Slowed conductive tissues allow escape and
  re-entry (W-P-W)
• Poor analgesia
• Hepatotoxicity has almost eliminated its use in
  adults in U.S., however, is still most
  appropriate GA for patient with ischemic heart
  disease and for children (see Golan, p. 254)
• Can produce malignant hyperthermia
• (See Golan, p. 254 and subsequent slides)

49
Malignant Hyperthermia (see Golan, p.254)

• Susceptibility-inherited autosomal dominant
  characteristic linked to chromosome 19 which
  effects ryanodine receptor in sarcoplasmic
• reticulum Ca channel.
• Observed after use of halothane, isoflurane,
  sevoflurane or succinylcholine alone or after
  combination of anesthetic and succinylcholine.
• Warning signs
• Myopathy or neuropathy
• Muscle spasms and pain
• Elevated serum creatinine phosphokinase
• Risk absent lt 3 yo, peak at 20 yo
• Predominantly in muscular males
• Prodromal sign muscle hypertonus in masseter
  muscle in response to succinylcholine (Difficult
  to intubate patient)

50
Malignant Hyperthermia (continued)

• Body temperature rises 1F. every 5-10 minutes
• Sinus tachycardia, myoglobinemia, hyperkalemia,
  metabolic acidosis
• ?liver enzymes (SGOT, Lactic dehydrogenase,
  phosphate, aldolase)
• Results in ? myoplasmic calcium due to increased
  release or
• inhibited uptake by sarcoplasmic reticulum
• Disruption of mitochondrial respiration initiates
  ?glycolysis
• lactate production???pH which causes changes in
  actomyosin
• Halothane incriminated more than other GAs

51
Malignant Hyperthermia (continued)

• Treatment
• Stop anesthetic
• Quickly cool body
• Use sodium bicarbonate to correct acidosis
• Administer O2
• Correct hyperkalemia with insulin and glucose
• Specific antidote procaine or procainamide
• iv mannitol is used to clear myoglobin from
  kidneys.
• Dantrolene, a central acting muscle relaxant
  that blocks calcium release from sarcoplasmic
  reticulum, is used to relieve muscle hypertonus.
• (Read Golan p. 254. This drug effect has been
  has been asked on the USMLE )

52
Isoflurane (Forane) beneficial effects(see
Golan, p. 254)

• Pre-eminent GA for adults in U.S. even though
  costs 25X more than halothane.
• Non-flammable
• Better muscle relaxant than enflurane
• Less respiratory depression than enflurane
• Less depression of cardiac output (CO) than
  enflurane or halothane
• Little or no sensitization toward arrhythmias
• Less likelihood of metabolic acidosis due to
  skeletal muscle vasodilation but may cause
  hypotension.
• May cause coronary steal and worsen angina in
  patients with ischemic heart disease

53
Coronary Steal (See Golan, p. 373
54
Isoflurane-beneficial effects (cont.)

• Less likely than halothane to increase cerebral
  blood flow at normal CO2
• Preserves cerebral auto-regulation during
  intracranial surgery
• Induction and recovery comparable to enflurane
• Pungent vapors may cause breath holding and
  coughing during induction
• Dilates bronchiolar smooth muscle, therefore may
  be used for status asthmaticus (Safer than
  halothane)
• Does not induce EEG changes as seen with
  enflurane
• Less likely than halothane or enflurane to
  produce hepatic or renal toxicity
• Relaxes uterine smooth muscle similar to
  halothane and enflurane

55
Desflurane (Suprane) see Golan, p. 254)

• Beneficial Effects
• Popular in U.S.
• Good for outpatient surgery due to rapid
  induction
• (similar to N2O) and recovery (5-7 min)
• Rapid induction due to blood/gas partition
  coefficient of 0.45
• Patients are street ready in 3.3 hours (rapid
  recovery)
• Completely eliminated by ventilation
• No evidence of nephro- or hepato-toxicity
• Adverse Effects
• Causes respiratory irritation, coughing, breath
  holding and even laryngospasm (like ether)
• Requires i.v. inducing agent
• Causes increased BP and HR due to central
  sympathetic stimulation
• Concern for patients with hypertension or heart
  disease

56
Nitrous Oxide (N2O) (see Golan, p. 254) Do not
confuse with nitric oxide (NO) which is
endothelium derived relaxing factor

• Beneficial Effect
• An anesthetic gas
• Rapid induction and recovery due to low blood
  solubility
• Excellent analgesic and amnesic
• No respiratory depression if given with 20 O2
• No CV depression if given with 20 O2
• Increases cerebral blood flow lt other gases
• Used at gt50 concentration in combination with
  volatile liquid GAs
• Allows reducing dose of halogenated GA thus
  minimizing undesirable features

57
Nitrous oxide

• Adverse Effects
• Does not fulfill all objectives of GA
• Not capable of producing surgical anesthesia
  (Stage III) in un-premedicated patient
• Poor muscle-relaxing potential, does not cause
  hyporeflexia
• Because it is so weak (MAC 105), danger of
  hypoxia if given in high concentration
• Must be given with O2 at flow rate of 6-7
  liters/min.
• Should not be used at concentrations gt 70,
  even with high-flow techniques
• Accumulates in body during anesthesia
• Due to low solubility in blood, N2O displaces
  nitrogen and expands into air pockets thus
  increasing pressure in bowel, middle ear,
  pneumothorax and pneumocephalus

58
Nitrous oxide - Adverse Effects (cont)

• May cause diffusion hypoxia at termination of
  anesthesia
• Due to low blood solubility, rapid outflow of
  N2O from
• blood into alveoli can dilute available O2 in
  alveoli
• causing diffusion hypoxia.
• Prolonged use may cause bone marrow depression
  neurologic deficits in patients with Vitamin B12
  deficiency.

59
Sevoflurane (Ultane) Beneficial Effects(see
Golan, p. 254)

• Closest to ideal inhalation anesthetic
• Pleasant odor provides useful alternative to
  halothane in children
• Popular for outpatient anesthesia due to rapid
  smooth induction and rapid recovery
• Does not produce tachycardia
• Therefore, preferable in patients with
  myocardial ischemia
• Most effective bronchodilator among inhalation GAs

60
Sevoflurane Adverse Effects

• Chemically unstable
• Forms toxic products if soda lime is used to
  absorb CO2 in anesthesia circuits
• Need to use a dedicated anesthesia machine that
  has a different CO2 adsorbant
• Potential for producing nephrotoxicity not
  proven
• 3 metabolized by cytochrome P450 to organic
  fluoride

61
Dissociative Anesthetics(see Golan, p.255)

• Class of drugs that dissociate consciousness from
  perception of sensation
• Patient is awake responsive but has catatonia,
  amnesia, and selective analgesia
• Acts on limbic system and cortex rather than RAS
• Prototype Ketamine
• Related to phencyclidine (PCP)
• street drug angel dust
• May cause unpleasant sensations and dreams when
  awakening

62
Ketamine Beneficial Effects

• Produces good analgesia and amnesia
• Used in musculotendon, orthopedic and cutaneous
  cases such as burn debridement
• Airway reflexes maintained
• No significant respiratory depression
• Abolishes bronchospasm
• Increases CO, HR BP due to sympathetic
  stimulation even though depresses myocardium

63
Ketamine Adverse Effects

• Emergence delirium can be controlled with
  barbiturates (thiopental), benzodiazepines
  (diazepam), or psycho-sedatives (droperidol)
• Not used in thoracic or abdominal surgery due to
  poor visceral analgesia
• Contraindicated in neurosurgical procedures due
  to increased cerebral blood flow, O2 consumption,
  and intracranial pressure

64
Neuroleptanalgesia

• Causes patient to become indifferent to
  surrounding environment along with reduced motor
  activity
• Patient is sedated, sleepy, but remains
  responsive to voice instructions.
• Prototype Innovar
• Fixed-dose combination of 2 drugs
• Fentanyl - a short acting (30-60 min), potent
  opioid analgesic
• Droperidol a long acting (3-6 hours)
  psycho-sedative
• Sufentanil is sometimes substituted for
  fentanyl. It is 10X more potent than fentanyl.
• Both fentanyl and sufentanil have shorter time
  to peak analgesia shorter recovery times than
  morphine.

65
Innovar Beneficial Effects

• Will enhance the effects of other CNS depressants
• Neurolept anesthesia (deeper CNS depression) is
  produced by administering N2O along with Innovar

66
Innovar - Adverse Effects

• Fentanyl component of Innovar may cause cardiac
  slowing and hypotension
• Fentanyl may cause severe respiratory depression
• Innovar may increase CSF pressure if pCO2
  increases due to ? ventilation
• Innovar may cause nausea, vomiting and
  extrapyramidal muscle movements
• Droperidol (a psychosedative) may cause
• a potentially fatal ventricular tachycardia
• known as torsade de pointes (TdP) by
• prolonging the QTc interval.

67
Induction Agents for Anesthesia

• Agents given prior to GA to aide in induction
• Ultra-short-acting i.v.anesthetics (e.g.,
  thiopental)
• Etomidate a non-barbiturate
• Propofol (Diprivan) an oil at room
  temperature given i.v. as an emulsion

68
Intravenous Anesthetics(Golan, p. 254)

• Allows rapid induction because bypasses
  pulmonary phase observed with inhalation GA.
• Disadvantage loss of moment-to-moment control.
• Must wait for circulatory, renal and metabolic
  systems to lower blood levels

69
Ultra-short-acting Barbiturates

• Intravenous administration produces very rapid
  induction due to high lipid solubility.
• Short duration of action (5-10 min) due to
  redistribution of drug from brain to other
  tissues. (See Golan, Fig. 15-13)
• Subsequent doses have longer duration of action
  due to saturation of peripheral tissues.
• Marked CNS depression ?respiratory depression.
• May cause apnea, cough, laryngeo-
  broncho-spasm.
• Be prepared to intubate and ventilate.
• Poor analgesia and muscle relaxation

70
Redistribution of Thiopental(Golan, Fig. 15-13,
p. 255 )
71
Barbiturates (continued)

• Minimal CV effects
• May decrease cerebral blood flow
• Useful in patients with cerebral edema
• Contraindicated in patients with acute
  intermittent porphyria
• Induces hepatic ALA synthase
• Effects liver microsomes
• Aggravates porphyria (difficulty metabolizing
  porphyrin)
• Only a hypnotic if used alone (does not achieve
  objectives of anesthesia)
• Causes vascular damage if extravasation occurs
  during iv injection

72
Etomidate (a non-barbiturate sedative induction
agent) (See Golan, p 255)

• Induction and recovery similar to barbiturate
• Mild reflex tachycardia transient apnea
• No analgesic or muscle relaxing effect
• May cause nausea, vomiting, injection pain and
  myoclonus
• May cause phlebitis, thrombosis
  thrombophlebitis
• May cause adrenocortical suppression after a
  single injection
• Contraindicated in children lt 10 yo, in pregnancy
  and in delivery

73
Propofol (a pre-anesthetic induction agent)(See
Golan, p 254)

• Used for rapidly inducing anesthesia, for
  sedating during regional anesthesia in patients
  requiring controlled ventilation. Causes less
  severe hangover allows rapid discharge from
  recovery room.
• Used for prolonged sedation in critical care
  unit. Eliminated by rapid metabolism so can be
  used for longer periods than can thiopental.
• Contraindicated to sedate children in ICU
• More negative inotropy than with etomidate or
  thiopental
• May cause apnea if combined with iv narcotics
• May lower coronary blood flow (CBF) and CSF
  pressure

74
Propofol

• Most commonly used parenteral anesthetic in U.S.
• Formulated as 1 emulsion in 10 soybean oil with
  preservatives.
• Administered in small boluses or as infusion
  tailored to patient.
• Must be administered or discarded shortly after
  removal from sterile packaging to avoid bacterial
  contamination.
• Intralipid preparation provides a large caloric
  source, important for critically ill patients who
  may receive prolonged propofol infusions.
• Sedating doses are 20-50 of those required for
  general anesthesia, but even at these doses,
  caregivers should be vigilant and prepared for
  all potential side effects of propofol.
• Highly protein bound. Pharmacokinetics are
  affected by protein levels.
• May have proconvulsant activity when combined
  with other drugs.
• Dose dependent in BP due to vasodilation
  myocardial CF.
• Causes greater respiratory depression than
  thiopental. Patients should be monitored to
  ensure adequate oxygenation and ventilation.

75
Summary of Adjunctive Agents

• Often necessary to use more than 1 GA
  sequentially during a surgical procedure
• Pre-anesthetics used to for analgesia and
  sedation
• Sedatives and antihistamines used to smooth
  induction
• Anti-anxiety medications used prior to surgery
• Narcotics used for preoperative and postoperative
  pain
• Anticholinergics (e.g. atropine or scopolamine)
  used to dry respiratory and GI secretions and
  block vagal reflexes
• Neuromuscular blockers used for skeletal muscle
  relaxation

76
The End

• Contact Dr. Robert Koerker if you have any
  questions
• Tel [phone] (work) 434-0949 (home)
• Office 290N W.H.
• E-mail robert.koerker_at_wright.edu
• Answers to practice exam questions at the end of
  the notes can be found on line