Introduction to Principles Anesthesia in Emergency and Critical Care

1. Anesthesia
By Ame M. (BSc, MSc in EMCCN)

2. Outline
• Introduction
• Types of anesthesia
• Advantage and disadvantages of both types
• Common anesthetic agents
• Stages of anesthesia
• Perioperative anesthetic care

3. Course Objectives
• Upon completion of this course, the graduate
student will be able to:
– Identify basics of anesthesia
– Identify stages of anesthesia
– Identify types of anesthesia
– Identify the basic principles of anesthesia
management
– Identify common induction agents
– Identify components of Anesthesia Preoperative
Evaluation

4. Introduction
• Anesthesia from Greek "without sensation"
– is a state of controlled, temporary loss of
sensation or awareness that is induced for medical
purposes.
– may include:
• analgesia (relief from or prevention of pain),
• paralysis (muscle relaxation),
• amnesia (loss of memory), or
• unconsciousness.
• A patient under the effects of anesthetic drugs is
referred to as being anesthetized.

5. The History of Anesthesia
• The first successful anesthetic took place
at Massachusetts General Hospital in 1846 by a
dentist, Dr. William T Morton.
• Before Anesthesia
– Surgery uncommon
– Aseptic technique unknown
– Surgical pain relief
• alcohol,
• hashish,
• opium
• physical methods (ice, ischemia)
• unconsciousness (blow to head, strangulation)
• simple restraint most common

6. Type of Anesthesia
• Local Anesthesia loss of sensory perception over a
small area of the body
• Regional Anesthesia loss of sensation over a specific
region of the body (e.g. lower trunk)
• General Anesthesia loss of sensory perception of the
entire body. Can be:
– Inhalational
• Gasses or Vapors
• Volatile liquids
• Usually Halogenated
– Parenteral

7. Desirable components of anesthesia
1. Immobility in response to noxious stimulus
2. Anxiolysis
3. Amnesia
4. Analgesia
5. Unconsiousness
6. Muscle relaxation
7. Loss of autonomic reflexes

8. Phases of Anesthesia
1. Induction putting the patient to sleep
2. Maintenance keeping the patient
asleep (without awareness)
3. Emergence waking the patient up (recovery)

9. Basics of Anesthesiology
Medical Gas Systems
• Oxygen
– stored as a compressed gas at room temp or refrigerated as a
liquid.
– The pressure in an oxygen cylinder is directly proportional to
the volume of oxygen in the cylinder.
• Nitrous oxide
– stored as a liquid at room temperature
– In contrast to oxygen, the cylinder pressure for nitrous oxide
does not indicate the amount of gas remaining in the
cylinder;
– 750 psi as long as any liquid nitrous oxide is present
– when cylinder pressure begins to fall, only about 400 liters of
nitrous oxide remains.
– The cylinder must be weight to determine residual volume of
nitrous oxide.

10. Characteristics of Medical Gas E-
Cylinders
Cylinder Color Form Capacity(L) Pressure(psi)
Oxygen Green Gas 660 1900-2200
Nitrous Oxide Blue Liquid 1,590 745
Carbon Dioxide Gray Liquid 1,590 838
Air Yellow Gas 625 1,800
Nitrogen Black Gas 650 1800-2200
Helium Brown Gas 496 1600-2000

11. Stages of General Anesthesia
• Stage 1 (amnesia)
– begins with induction of anesthesia and ends with the loss
of consciousness (loss of eyelid reflex).
– Pain perception threshold during this stage is not lowered.
• Stage 2 (delirium/excitement) is ch’zed by uninhibited
excitation.
– Agitation, delirium, irregular respiration and breath holding.
– Pupils are dilated and eyes are divergent.
– Responses to noxious stimuli can occur during this stage
may include vomiting, laryngospasm, HTN, tachycardia, and
uncontrolled mov’t.

12. Stages of General Anesthesia
• Stage 3 (surgical anesthesia)
– is characterized by central gaze, constricted pupils,
& regular respirations.
– Target depth of anesthesia is sufficient when
painful stimulation does not elicit somatic reflexes
or deleterious autonomic responses.
• Stage 4 (impending death/overdose)
– is characterized by onset of apnea, dilated and
nonreactive pupils, and hypotension.

13. Pharmacokinetics of inhaled anesthetics
A. Anesthetic conc: The fraction of a gas in a mixture is equal to
the volume of that gas divided by the total volume of the
mixture.
B. Partial pressure: The partial pressure of a component gas in a
mixture is equal to the fraction it contributes toward total
pressure.
C. Minimum alveolar conc (MAC): The minimum alveolar conc of
inhalation agent is the minimum conc necessary to prevent
mov’t in 50% of pts in response to a surgical skin incision.
D. Alveolar uptake
E. Second gas effect
F. Elimination
G. Diffusion hypoxia results from dilution of alveolar oxygen conc.
by the large amount of nitrous oxide leaving the pulm capillary
blood at the conclusion of nitrous oxide administration.

14. Pharmacokinetics of inhaled
anesthetics
• Alveolar uptake: The rate of alveolar uptake is determined by:
1. Inspired concentration
2. Alveolar ventilation
3. Anesthetic breathing system:
- The rate of rise of the alveolar partial pressure of an
inhaled anesthetic is influenced by:
a. the volume of the system,
b. solubility of the inhaled anesthetics into the
components of the system, and
c. gas inflow from the anesthetic machine.
4. Uptake of the inhaled anesthetic

15. Pharmacokinetics of inhaled
anesthetics
• Uptake of the inhaled anesthetic is determined
by:
– Solubility
– Cardiac output
– Alveolar to venous partial pressure difference

16. Pharmacokinetics of intravenous
anesthetics
A. Volume of distribution
B. Plasma concentration curve
1. Distribution (alpha) phase: corresponds to the initial
distribution of drug from the circulation to tissues.
2. Elimination (beta) phase: The second phase is
characterized by a gradual decline in the plasma
conc. of drug and reflects its elimination from the
central vascular compartment by renal and hepatic
mechanisms
C. Elimination half-time

17. Pharmacokinetics of intravenous anesthetics
D. Redistribution: Following systemic absorption of drugs,
the highly perfused tissues (brain, heart, kidneys, liver)
receive a proportionally larger amount of the total dose;
the transfer of drugs to inactive tissue sites (ie, skeletal
muscle) is known as redistribution.
E. Physical characteristics of the drug
1. Highly lipid-soluble iv drugs are taken up rapidly by tissues.
2. With water-soluble agents, molecular size is an important
determinant of diffusibility across plasma membranes.
3. Degree of ionization: The degree of ionization is determined
by the pH of the biophase and the pKa of the drug.
- Only nonionized (basic) molecules diffuse across the
biological membranes.

18. Local Anesthetics
• MOA of local anesthetics
– prevent increases in neural membrane permeability to
sodium ions,
– slowing the rate of depolarization so that threshold potential
is never reached and
– prevent action potential propagation
– Mostly bind to sodium channels in the inactivated state,
– preventing subsequent channel activation and the large
transient sodium influx associated with membrane
depolarization.
– Rapidly firing nerves are more sensitive and, therefore, are
blocked first.
• Rate of systemic absorption of local anesthetics (from high to
low): intravenous > tracheal > intercostal > caudal > paracervical
> epidural > brachial plexus > sciatic/femoral > subcutaneous.

19. LA Adjuvants
• Epinephrine
• Phenylephrine
• Sodium bicarbonate

20. Toxicity and effects of Local Anesthetics
• Allergic reactions
– Ester-type local anesthetics
• Local hypersensitivity rxns: local erythema, urticaria, edema, or
dermatitis.
– Local toxicity
– Transient radicular irritation (TRI) or transient neurologic
symptoms (TNS)
• dysesthesia, burning pain, low back pain, and aching in the lower
extremities and buttocks.
• usually appear within 24 hrs after complete recovery from SA
and resolve within 7 days.
• Can occur after unintentional subarachnoid injection of large
volumes or high conc. of LA.
• Increased incidence when the lithotomy position is used during
surgery
• An increase incidence of neurotoxicity associated with the
subarachnoid administration of 5% lidocaine has been reported.

21. Toxicity and effects of Local
Anesthetics
• Cauda equina syndrome: Occurs when diffuse injury to
the lumbosacral plexus
– produces varying degrees of sensory anesthesia, bowel and
bladder sphincter dysfunction, and paraplegia.
– Initially reported due to 5% lidocaine and 0.5% tetracaine
given via a microcatheter.
– increased risk:
• large doses of LA are placed in the subarachnoid space
• during and following a continuous SA,
• repeated spinal doses
– Chloroprocaine has been associated with neurotoxicity.
• The cause may be the low pH of chloroprocaine (pH 3.0).

22. Toxicity and effects of Local Anesthetics
• System toxicity
– Cardiovascular toxicity
• LA depress myocardial automaticity and reduce the duration of the
refractory period (prolong PR interval and widening QRS).
• Myocardial contractility and conduction velocity are depressed at
higher conc.
• Smooth muscle relaxation causes some degree of vasodilation (with the
exception of cocaine).
• Cardiac dysrhythmia or circulatory collapse is often a presenting sign of
LA overdose during GA.
• IV bupivacaine has produced severe cardiotoxic reactions, including:
– hypotension, AV block, and dysrhythmias such as ventricular fibrillation.
– Pregnancy, hypoxemia, and respiratory acidosis are predisposing risk factors.
• Ropivacaine lacks significant cardiac toxicity because it dissociates more
rapidly from sodium channels.
• Levobupivacaine has less cardiotoxic effects then bupivacaine.
• Cocaine: only LA that causes vasoconstriction at all doses.

23. Toxicity and effects of Local Anesthetics
• Respiratory effects
– Lidocaine depresses the hypoxic drive (response to low PaO2).
– Apnea can result from phrenic and intercostal nerve paralysis or
depression of the medullary respiratory center following direct
exposure to LA agents (e.g., post retrobulbar apnea syndrome).
• Central nervous system toxicity
– Early symptoms: circumoral numbness, tongue paresthesia, and
dizziness.
– Sensory complaints: tinnitus and blurred vision.
– Excitatory signs (e.g., restlessness, agitation, nervousness, paranoia)
often precede CNS depression (slurred speech, drowsiness,
unconsciousness).
– Tonic-clonic Sz may result from selective blockade of inhibitory
pathways.
– Respiratory arrest often follows seizure activity.
– CNS toxicity is exacerbated by hypercarbia, hypoxia, and acidosis.

24. Toxicity and effects of Local Anesthetics
• Musculoskeletal effects
– LA are myotoxic when injected directly into skeletal muscle.
• Other adverse effects
– Horner syndrome can result from blockade of B fibers in the
T1-T4 nerve roots.
– Clinical signs include: ptosis, miosis, anhydrosis, nasal
congestion, vasodilation, and increased skin temperature.
– Methemoglobinemia after large doses of prilocaine,
benzocaine and EMLA cream.
– Decreased coagulation
• Lidocaine has been demonstrated to:
– prevent thrombosis,
– decrease platelet aggregation and
– enhance fibrinolysis of whole blood

25. Common Local Anesthetics
• Procaine
• Lidocaine
• Tetracaine
• Bupivacaine
• Ropivacaine
• Chloroprocaine
• Mepivacaine
• Prilocaine
• Etidocaine

26. Neuromuscular Blocking Agents
(NMBA)
• also referred to as ‘paralysing agents’.
• in effect, NM BA in some way block or inhibit the
process of nerve stimulation at the NM junction.
• DO NOT provide any sedative effects.
• Divided into two types:
– Depolarizing muscle relaxants (DMR) and
• Suxamethonium
– Non-depolarizing muscle relaxants (NDMR)
• Curare Type: Vecuronium, Pancuronium, Atracurium
Cisatracurium, Rocuronium

27. Neuromuscular Blocking Agents (NMBA)
• Depolarizing muscle relaxants(DMR) - Suxamethonium
– is the only depolarizing muscle relaxant and is made up of two
joined Ach molecules.
– mimics the action of Ach by depolarizing the postsynaptic
membrane at the NM junction.
– Unlike Ach, not destroyed by acetyl cholinesterase, so their
action is sustained.
– Paralysis is achieved as the drug blocks the repolarization of
the motor end plate.
– Produce immediate muscle spasm (or muscle fasciculation's)
– This lasts briefly, then the muscles go flaccid and the pt is
paralyzed.
– Because of their short time to onset (0.5 sec) and short half-
life (about five minutes), DMR are the DOC in ED for RSI unless
contraindicated.

28. Adverse S/E of succinylcholine
• Cardiac
– Tachycardia and HTN in adults;
– bradycardia, junctional rhythm and sinus arrest in children
after 1st dose and after 2nd dose in adults (with short dose
interval).
• Hyperkalemia
• Increased intragastric pressure
• Increased ICP, increased CBF, and increased IOP
• Malignant hyperthermia
• Trismus
• Myalgia and Myoglobinuria
• Prolonged blockade
– liver disease, starvation, carcinomas, hypothyroidism, burn
patients, cardiac failure, uremia

29. Neuromuscular Blocking Agents (NMBA)
• Non-depolarizing muscle relaxants(NDMR)
– reversible competitive antagonism of Ach.
– work by flooding the nicotinic receptors by competing
with Ach(or acting as an antagonist).
– this result in non-depolarization of the motor end plate,
the muscles stay flaccid, and paralysis is achieved.
– have an adv over the depolarizing agents in that their
action can be reversed with the drug Neostigmine.
– have various times of onset and duration.
– some can take a full 3–5 minutes to begin working.
– for this reason they are not useful in the ED for RSI, but
are used more often for ongoing paralysis of the pt (e.g.
in OR for Surgery)

30. Neuromuscular Blocking Agents
(NMBA)
• Non-depolarizing muscle relaxants(NDMR)
– relax skeletal muscle
– facilitate intubation
– insure immobility
– Reversed by neostigmine or glycopyrrolate

31. Anticholinesterases
• MOA: inactivate acetylcholinesterase by reversibly
binding to the enzyme increasing the amount of
Ach available to compete w/nondepolarizing
agent.
• In excess doses, paradoxically potentiate a NDNM
blockade and prolong the depolarization blockade
of succinylcholine.
• increases Ach at both nicotinic and muscarinic
receptors.
• Muscarinic S/E can be blocked by admin of
atropine or glycopyrrolate.

32. Anticholinesterases
• Cholinergic receptors
A. Nicotinic receptors (2 subtypes)
1. NM: found at the NMJ in skeletal muscle.
2. NN: found in autonomic ganglia (sympathetic and
parasympathetic), the adrenal medulla, and the CNS.
B. Muscarinic receptors (5 subtypes; all found within the
CNS)
1. M1: located in autonomic ganglia and various secretory
glands.
2. M2: found mainly in the heart and brainstem.
3. M3: found in smooth muscle, exocrine glands, and
cerebral cortex.
4. M4: found in the neostriatum.
5. M5: found in the substantianigra.

33. Anticholinesterases
Muscarinic S/E of Cholinesterase Inhibitors
Organ System Muscarinic Side Effect
Cardiovascular Decreased heart rate, dysrhythmias
Pulmonary Bronchospasm, increased bronchial
secretions
Cerebral Diffuse excitation (physostigmine only)
Gastrointestinal Intestinal spasm, increased salivation
Genitourinary Increased bladder tone
Ophthalmologic Pupillary constriction

34. Anticholinesterases
• Common Anticholinesterases are:
– Edrophonium
– Neostigmine
– Pyridostigmine
– Physostigmine

35. Anticholinergics
• MOA: competitively inhibits the action of Ach at
muscarinic receptors with little or no effect at nicotinic
receptors.
• Used as reversal for NM blockers
• Central anticholinergic syndrome
– Scopolamine and atropine can enter the CNS and produce
symptoms of restlessness and confusion that may progress to
somnolence and unconsciousness.
– Other systemic manifestations include dry mouth, tachycardia,
atropine flush, atropine fever, and impaired vision.
– Physostigmine, anticholinesterase, reverses central
anticholinergic toxicity.
• Glycopyrrolate does not easily cross the BBB, and thus
does not cause a central anticholinergic syndrome.

36. Anticholinergics
• Effects include:
– Tachycardia
– Bronchodilation
– Sedation
– Antisialagogue
– Amnesia
• Common Anticholinergics are:
– Atropine
– Scopolamine
– Glycopyrrolate

37. Benzodiazepines
• MOA:
– selectively attach to alpha subunits to enhance the
chloride channel gating function of the inhibitory
neurotransmitter GABA.
– receptors mostly occur on postsynaptic nerve endings in
the CNS.
– undergo hepatic metabolism via oxidation and glucuronide
conjugation.
• Systemic effects
– CNS effects
• Amnestic, anticonvulsant, hypnotic, muscle-relaxant, and
sedative effects in a dose-dependent manner
• Reduced cerebral oxygen consumption, CBF and ICP.

38. Benzodiazepines
• Cardiovascular effects
– Mild systemic vasodilation and reduction in CO; HR
usually unchanged.
• Pronounced effect in hypovolemic pts, those w/poor
cardiac reserve, or if administered w/opioids.
• Midazolam reduces BP and SVR more than diazepam
• Respiratory effects
– Mild dose-dependent decrease in RR and tidal
volume.
– Increased resp depression with opioids and pulm ds.

39. Benzodiazepines
• Miscellaneous effects
– Reduces MAC by up to 30%.
• Pain during IV/IM injection and thrombophlebitis occurs
with diazepam
• Crosses the placenta and may lead to neonatal depression
• Erythromycin inhibits midazolam metabolism;
• Cimetidine reduces metabolism of diazepam.
• Heparin displaces diazepam from protein-binding sites and
increases the free drug conc.
• Reversal
– Flumazenil is a competitive antagonist of benzodiazepines.

40. Benzodiazepines
• Midazolam (Lorazepam)
– Used to produce anxiolysis, amnesia sedation prior to
induction of GA w/another agent.
– Sedative doses achieved w/in 2 min, w/30 min
duration of action (short duration).
– Effects are reversed with flumazenil.
• Common Benzodiazepines are:
– Diazepam (Valium)
– Lorazepam (Ativan)
– Midazolam (Versed)

41. Opioids
• Classification of opioids receptors
A. Mu receptor
– Mu-1: the main action at this receptor is analgesia, but also
responsible for miosis, N/V, urinary retention, and pruritus.
– Mu-2:respiratory depression, euphoria, sedation,
bradycardia, ileus and physical dependence are elicited by
binding at this receptor.
B. Delta: modulation of mu receptor, physical dependence
C. Kappa: Analgesia, sedation, dysphoria, and
psychomimetic effects are produced by this receptor.
Binding to the kappa receptor inhibits release of
vasopressin and thus promotes diuresis.
D. Sigma: Dysphoria, hypertonia, tachycardia, tachypnea,
and mydriasis are the principal effects of this receptor.

42. Opioids
• Systemic effects
• CNS effects
– Sedation and analgesia dose-dependent; euphoria.
– Amnesia with large doses (not reliable).
– Reduces MAC.
– Decreases CBF and metabolic rate.
– Toxicity
• Dysphoria and agitation may occur (higher with
meperidine).
• Seizures may be produced by meperidine
• ICP may increase if ventilation and PaCO2 are not
controlled.

43. Opioids
• Cardiovascular effects
– Minimal contractility effects, except meperidine (direct
myocardial depressant)
– Bradycardia
• Respiratory effects
– Respiratory depression
– Cough suppression: dose-dependent decrease in cough
reflex.
• Pupillary constriction: miosis.
• Muscle rigidity: generalized hypertonus of skeletal
muscle- may prevent ventilation
– Benzodiazepine pretreatment may help in preventing
rigidity.

44. Opioids
• Gastrointestinal effects
– Nausea/vomiting
– Decrease gastric motility; increase tone and secretions of GIT
– Biliary colic: spasm of sphincter of Oddi (less w/meperidine).
• Urinary retention: voiding difficult (reversed w/atropine)
• Endocrine: may block stress response to surgery at high
doses
• Placenta: can cross the placenta causing neonatal
depression
• Histamine release: Morphine and meperidine
– local itching, redness or hives near the site of injection and
may cause a decrease in SVR, hypotension, and tachycardia.
• Tolerance

45. Opioids
• Commonly used IV Opioids are:
– Meperidine
– Morphine
– Fentanyl
– Sufenta
– Alfentanil
– Remifentanil

46. Opioid Antagonist
• 1. Naloxone (Narcan)
– Pure opioids antagonists: administration results in
displacement of opioids agonists from opioids receptors.
– Peak effects seen in 1-2 minutes; duration approximately 30
minutes.
• Side effects
– Pain: may lead to abrupt onset of pain.
• Sudden antagonism can activate the symp NS, resulting in
cardiovascular stimulation.
• Dosage
– Bolus: Adult: 0.04 mg IV in titrated bolus Q2-3 min until the
desired effect; Pedi: 1-4 mcg/kg titrated.
– Continuous infusion: 5 mcg/kg/hr IV, will prevent resp
depression w/o altering the analgesia produced by neuraxial
opioids.

47. Intravenous Induction Agents
1. Sodium Thiopental (Pentothal) and other
barbiturates.
– MOA: depresses the reticular activating system,
reflecting the ability of barbiturates to decrease the rate
of dissociation of the inhibitory neurotransmitter GABA
from its receptors.
– Short DOA (5-10 min) following IV bolus reflects high
lipid solubility and redistribution from the brain to
inactive tissues.
– Protein binding parallels lipid solubility, decreased
protein binding increases drug sensitivity.
– increased sensitivity to thiopental in neonates (Protein
binding in NN is about half of in adults)

48. Intravenous Induction Agents
• Barbiturate Effects on Organ Systems
• Cardiovascular
– Induction doses cause a decrease in BP (peripheral
vasodilation) and tachycardia (a central vagolytic effect).
• Respiratory
– barbiturate depression on; the medullary ventilatory
center decreases the ventilatory response to hypercapnia
and hypoxia.
– Laryngospasm and hiccuping are more common after
methohexital than after thiopental.
• Cerebral
– constrict cerebral vasculature, decreasing CBF and ICP.
– cause a decline in cerebral oxygen consumption and
slowing of the EEG

49. Intravenous Induction Agents
• Barbiturate Effects on Organ Systems
• Renal
– Barbiturates decrease renal blood flow and GFR in
proportion to the fall in BP.
• Hepatic: Hepatic blood flow is decreased.
• Adverse effects
– Barbiturates are Contra Indicated in pts w/acute
intermittent porphyria, variegate porphyria, and hereditary
coprophyria (hereditary metabolism abnormality)
– Venous irritation and tissue damage (reflects possible
barbiturate crystal formation);
– severe pain and possible gangrene (intra-arterial injection)
– Myoclonus and hiccuping.

50. Intravenous Induction Agents
2. Etomidate
• MOA: depresses the reticular activating system
and mimics the inhibitory effects of GABA.
• Effects on organ systems
– Cardiovascular: minimal depressant cardiovascular
changes
– Respiratory: less affected with etomidate than
thiopental
– Cerebral: decreases the cerebral metabolic rate,
CBF, and ICP (may activate seizure foci).

51. Intravenous Induction Agents
2. Etomidate
• Endocrine:
– Induction doses transiently inhibit enzymes involved in
cortisol and aldosterone synthesis.
– Long term infusions lead to adrenocortical suppression.
• Drug interactions:
– Fentanyl increases the plasma level and prolongs the
elimination half-life of etomidate.
• Adverse effects
– Myoclonic mov’ts on induction, opioids levels are decreased.
– High incidence of N/V.
– Venous irritation
– Adrenal suppression.

52. Intravenous Induction Agents
3. Propofol
• MOA: increases the inhibitory neurotransmission
mediated by gamma-aminobutyric acid (GABA)
• highly lipid solubility.
• Short DOA results from a very short initial
distribution half-life (2-8 minutes).
• Elimination – primarily hepatic
• Recovery from propofol is more rapid and
accompanied by less hangover than other
induction agents.

53. Intravenous Induction Agents
3. Propofol
• Effects on organ systems
– Cardiovascular:
• decrease in arterial BP
• Hypotension is more pronounced than with thiopental.
• Propofol markedly impairs the normal arterial baroreflex
response to hypotension.
– Respiratory:
• profound resp depression.
• depression of upper airway reflexes exceeds that of thiopental.
– Cerebral
• decreases CBF and ICP.
• Propofol has antiemetic, antipruritic, and anticonvulsant
properties.

54. Intravenous Induction Agents
3. Propofol
• Other effects
– Venous irritation: Pain may be reduced by prior
administration of opioids or lidocaine.
– Propofol is an emulsion and should be used with
caution if lipid disorder present.
– Propofol is preservative free.
– Very low incidence of anaphylaxis.
– Allergic reactions may reflect pt sensitivity to the
solvent.
– Occasional myoclonic mov’t.
– Subhypnotic doses (10-15 mg) can help treat N/V.

55. Intravenous Induction Agents
4. Ketamine
• MOA:
– Ketamine blocks polysynaptic reflexes in the spinal
cord, inhibiting excitatory neurotransmitter effects.
– functionally dissociates the thalamus from the
limbic cortex, producing a state of dissociative
anesthesia.
– A dissociative anesthetic that produces a cataleptic
state that includes intense analgesia, amnesia, eyes
open, involuntary limb mov’t, unresponsive to
commands or pain.
– Metabolized in the liver

56. Intravenous Induction Agents
4. Ketamine
Effects on organ systems
• Cardiovascular
– Can be used in shock states (hypotensive) or patients at
risk for bronchospasm.
– Ketamine increases arterial BP, HR, and CO.
• Respiratory:
– Ventilation is minimally affected with normal doses of
ketamine.
– Ketamine is a potent bronchodilator.
– Can be used in patients at risk for bronchospasm
• Cerebral:
– Ketamine increases cerebral oxygen consumption, CBF,
and ICP.

57. Intravenous Induction Agents
4. Ketamine
• Drug interactions:
– NDMR are potentiated by ketamine.
– The combination of ketamine & theophylline may
predispose pts to Sz.
• Adverse effects
– Increased salivation (reduced by preRx w/anticholinergic).
– Emergence delirium: char’zed by visual, auditory,
proprioceptive and confusional illusions (reduced by
benzodiazepine (midazolam) premedication).
– Myoclonic mov’ts.
– Increased ICP.
– Eyes: nystagmus, pupillary dilation, salivation, diplopia,
blepharospasm, and increased IOP.

58. Comparative Pharmacologic Effects and Doses of IV Induction Agents
Propofol Thiopental Etomidate Ketamine
Induction Dose
(mg/kg IV) 1.5-2.5 3-5 0.2-0.6 1-2 (4-8 mg IM)
Anesthesia
Maintenance 50-300 µg/kg/min
30-200
µg/kg/min 10-20 µg/kg/min
0.5-1 mg/kg IV prn
15-90 µg/kg/min IV
Sedation 25-100 µg/kg/min 0.5-1.5 mg/kg 5-8 µg/kg/min
0.2-0.8 mg/kg IV
2-4 mg/kg IM
Systemic BP Decreased Decreased NC or Dec Increased
Heart Rate NC or Dec Increased NC or Dec Increased
SVR Decreased Decreased NC or Dec Increased
CBF Decreased Decreased Decreased Increased
ICP Decreased Decreaseed Decreased Increased
Resp Depression Yes Yes Yes No
Analgesia No No No Yes
Emergence Delirium No No No Yes
Nausea/Vomiting Decreased NC Increased NC
Adrenocortical
Suppression No No Yes No
NC = no change; Dec = decreased

59. Inhaled Anesthetics
1. Sevoflurane
• Advantages
– Well tolerated (non-irritant, sweet odor), even at
high conc., making this the agent of choice for
inhalational induction.
– Rapid induction and recovery
– Does not sensitize the myocardium to
catecholamines as much as halothane.
– Does not result in carbon monoxide production
w/dry soda lime.

60. 1. Sevoflurane
• Disadvantages
– Less potent than similar halogenated agents.
– Interacts w/CO2 absorbers; (soda lime & more w/barium
lime) and produce a vinyl ether which is toxic to the brain,
liver, and kidneys.
– Thus in the presence of soda lime, fresh gas flow rates
should not be less than 2 L/min, and use of barium lime is
contraindicated.
– Risk of renal toxicity:
• About 5% is metabolized and elevation of serum fluoride
levels has led to concerns about the risk of renal toxicity.
– Should be avoided in the presence of renal failure (in theory)
– Postop agitation may be more common in children than
seen w/halothane.

61. Inhaled Anesthetics
2. Desflurane
• Advantages
– Rapid onset and offset of effects
– Stable in the presence of CO2 absorbers.
– Pharmacodynamics effects are similar to those of
isoflurane.
– No increase in CBF and ICP if IPPV started at
induction.

62. 2. Desflurane
• Disadvantages
– Requires a special vaporizer which is electrically
heated and thermostatically controlled.
– Low potency.
– Pungency makes it unsuitable for inhalational
induction
– Irritation of the airways in awake pts causes
coughing, salivation, bronchospasm (poor induction
agent)
– Symp NS stimulation with tachycardia and HTN
(Rapidly increasing the inhaled conc or exceeding
1.25MAC)

63. Inhaled Anesthetics
3. Isoflurane
• Advantages
– Suitable for virtually all types of surgery.
• Disadvantages
– May have coronary steal effect.
– Pungent odor makes unsuitable for inhalational
induction.

64. Inhaled Anesthetics
4. Enflurane
• Advantages
– Non-pungent odor (sweet etheral odor) and non-
irritant;
– however, rarely used for inhalational induction.

65. 4. Enflurane
• Disadvantages
– Cause tonic clonic muscle activity and an epileptiform
EEG trace and should not be used in seizure pts.
– Increases CBF and ICP more than isoflurane.
– Sensitizes myocardium to catecholamines and decrease
arterial BP by decreasing SVR and having –ve inotropic
effect.
– Causes resp depression than isoflurane or halothane
– 2.4% metabolized, resulting in increased blood fluoride
levels.
– Should not be used for longer than 9.6 MAC hours to
avoid fluoride-induced renal toxicity.
– May cause hepatic necrosis (vary rare).

66. Inhaled Anesthetics
5. Halothane
• Advantages
– Potent inhalational agent.
– Sweet, nonirritating odor suitable for inhalational induction.
– Bronchodilator.
• Disadvantages
– Requires preservative, 0.01% thymol, the accumulation of
which can interfere w/vaporizer function.
– Risk of halothane hepatitis (dysfunction).
– Sensitizes myocardium to catecholamines more than other
agents.
– Causes vagal stimulation, which can result in marked
bradycardia.
– Potent trigger for malignant hyperthermia.
– Relaxes uterine muscle.

67. Inhaled Anesthetics
5. Halothane
• Recommendations
– Avoid repeat exposure within 6 months.
– Hx of unexplained jaundice or pyrexia after a
previous halothane anesthetic is a contraindication
to repeat exposure.
– Use caution w/epinephrine. Avoid conc >1:100,000.

68. Inhaled Anesthetics
6. Nitrous oxide
• Advantages
– Powerful analgesic properties.
– Decreases the MAC and accelerates the uptake of
these agents.
– safe in pts w/MH susceptibility.
– Rapid induction and recovery
– No effect on smooth muscle.

69. 6. Nitrous oxide
• Disadvantages
– Decreases myocardial contractility (offset by stimulating
effect on the SNS, increasing SVR).
– Also increases PVR in pts w/preexisting pulm HTN.
– 35X more soluble than nitrogen in blood, thus causing a
rapid increase in the size of air-filled spaces.
– Also leads to diffusion hypoxia when N2O is stopped.
– Supports combustion and can contribute to fires.
– Increases risk of postop N/V.
– May increase ICP by increasing CBF.
– Inhibits methionine synthetase (prolonged exposure may
lead to megaloblastic bone marrow changes).
– Long-term use can lead to peripheral neuropathy.
– Possible teratogenic effect.

70. Effects of Inhaled Anesthetics on Organ Systems
Sevoflurane Isoflurane/
Desflurane
Halothane Enflurane Nitrous
Oxide
CO 0 0 -* --* 0
HR 0 + 0 ++* 0
BP -- --* -* --* 0
SV -- -* -* --* -
Contractility -- --* ---* --* -*
SVR - -- 0 - 0
PVR 0 0 0 0 +
ICP + + ++ ++ +
CBF + + ++ + +
Seizures - - - + -
Hepatic BF - - -- -- -
RR + + ++ ++ +
TV - - - - -
PaCO2 + + + ++ 0
*=Dose Dependent; 0=No Change; - =Decrease; +=Increase; ?=Uncertain

71. Anesthesia Preoperative Evaluation
• The overall goal Anesthesia Preoperative
Evaluation is to:
– reduce perioperative morbidity and mortality and
– alleviate pt anxiety.
• Has the following components:
– Anesthesia preoperative hx and P/E
– Preoperative laboratory evaluation
– Pediatric preoperative evaluation

72. Anesthesia preop hx & P/E
A. Note:
– the date and time of the interview,
– the planned procedure, and
– a description of any extraordinary circumstances
regarding the anesthesia.
B. Current medications and allergies:
– hx of steroids,
– hs of chemotherapy and herb and
– hx of dietary supplements
C. Cigarette, alcohol, and illicit drug hx, including most
recent use.

73. Anesthesia preop hx & P/E
D. Anesthetic hx, including specific details of any problems.
E. Prior surgical procedures and hospitalizations.
F. Family hx, esp. anesthetic problems.
- Birth and development hx (pediatric).
G. Obstetrical history: LMP (females).
H. Medical hx; evaluation, current Rx, and degree of control
I. Review of systems, including general, cardiac, pulm,
neurologic, liver, renal, gastrointestinal, endocrine,
hematologic, psychiatric.
J. Hx of airway problems (difficult intubation or airway ds,
symptoms of temporomandibular joint ds, loose teeth,
etc.).

74. Anesthesia preop hx & P/E
K. Last oral intake.
L. Physical exam, including:
- airway evaluation,
- current vital signs,
- height and body weight,
- baseline mental status,
- evaluation of heart and lungs,
- vascular access.

75. Anesthesia preop hx & P/E
M. Overall impression of the complexity of the
patient’s medical condition, with assignment of
ASA Physical Status Class.
N. Anesthetic plan (general, regional, spinal, MAC).
- The anesthetic plan is based on:
- the patient's medical status,
- the planned operation, and
- the patient’s wishes.
O. Documentation that risks and benefits were
explained to the patient.

76. Preoperative Laboratory Evaluation
A. Hemoglobin: menstruating females, children <6 mo or
w/suspected SCD, hx of anemia, blood dyscrasia or
malignancy, congenital heart ds, chronic ds states, age
>50 yrs (65 yrs for males) pts likely to experience large
blood loss.
B. WBC count: suspected infection or immunosuppression.
C. Platelet count: hx of abnormal bleeding or bruising,
liver ds, blood dyscrasias, chemotherapy, hypersplenism
D. Coagulation studies: hx of abnormal bleeding,
anticoagulant drug therapy, liver ds, malabsorption,
poor nutrition, vascular procedure.

77. Preoperative laboratory evaluation
E. Electrolytes, blood glucose, BUN/Creatinine: renal ds,
adrenal or thyroid disorders, DM, diuretic therapy,
chemotherapy.
F. Liver function tests: pts w/liver ds, hx of or exposure to
hepatitis, hx of alcohol or drug abuse, drug therapy
w/agents that may affect liver function.
G. Pregnancy test: pts for whom pregnancy might
complicate the surgery, pts of uncertain status by hx
and/or exam.
H. Electrocardiogram: age ≥50, HTN, current or past
significant cardiac ds or circulatory ds, DM in a person
age ≥40.

78. Preoperative laboratory evaluation
I. Chest x-ray: asthma or COPD w/change of
symptoms or acute episode w/in the past 6 months,
cardiothoracic procedures.
J. Urinalysis: GU procedures; surgeon may request to
rule out infection before certain surgical procedures.
K. Cervical spine flexion/extension X-rays: pts
w/rheumatoid arthritis or Down’s syndrome.
- Routine screening in asymptomatic pts is generally
not required.
L. Preoperative pulmonary function tests (PFTs)

79. Preoperative laboratory evaluation
• Preoperative pulmonary function tests (PFTs)
– There is no evidence to suggest that PFTs are useful for
purposes of risk ass’t or modification in pts w/cigarette
smoking or adequately treated bronchospastic ds.
• Candidates for preoperative PFTs
A. Pts considered for pneumonectomy.
B. Pts w/moderate to severe pulm ds scheduled for
major abdominal or thoracic surgery.
C. Pts w/dyspnea at rest.
D. Pts w/chest wall and spinal deformities.
E. Morbidity obese pts.
F. Pts w/airway obstructive lesions.

80. Preoperative Airway Evaluation
• Preoperative Airway evaluation: assessed by:
– historical interview (i.e., hx of difficult intubation,
sleep apnea) and P/E and
– occasionally with radiographs, PFTs, and direct
fiber-optic examination.
**The physical exam is the most important method of
detecting and anticipating airway difficulties.

81. Preoperative Airway Evaluation
• Physical exam
A. Mouth
– Opening: note symmetry and extent of opening (3
finger breadths optimal).
– Dentition: ascertain the presence of loose,
cracked, or missing teeth; dental prostheses; and
co-existing dental abnormalities.
– Macroglossia: will increase difficultly of
intubation.

82. Preoperative Airway Evaluation
B. Neck/Chin
• Anterior mandibular space (thyromental distance): the
distance b/n the hyoid bone and the inside of the
mentum (mental prominence) or b/n the notch of the
thyroid cartilage to the mentum.
• An inadequate mandibular space is associated with a
hyomental distance of <3 cm or a thyromental distance of
<6 cm.
• Cervical spine mobility (atlanto-occipital joint
extension): 35 degrees of extension is normal; limited
neck extension (<30 degrees associated with increased
difficulty of intubation.
• Evaluate for presence of a healed or patent tracheostomy
stoma; prior surgeries or pathology of the head and neck
(laryngeal cancer); presence of a hoarse voice or stridor.

83. Airway Evaluation
Airway classification
A. Mallampati Classification (Size of Tongue Vs
Pharynx)
– Class I: Soft palate, anterior and posterior tonsillar
pillars and uvula visible
– Class II: Tonsillar pillars and base of uvula hidden
by base of tongue
– Class III: Only soft palate visible
– Class IV: Soft palate not visible

84. Airway Evaluation
Airway classification
B. Laryngoscopic view grades
– Grade 1: full view of the entire glottic opening.
– Grade 2: posterior portion of the glottic opening is
visible.
– Grade 3: only the epiglottis is visible.
– Grade 4: only soft palate is visible.

85. Predictors of difficult intubation
A. Anatomic variations:
- Micrognathia (small jaw),
- large tongue,
- Arched palate,
- Short neck,
- Prominent upper incisors,
- Buckteeth,
- Decreased jaw movement,
- Receding mandible or anterior larynx,

86. Predictors of difficult intubation
B. Medical conditions associated with difficult
intubations:
– Arthritis
– Tumors
– Infections
– Trauma
– Down’s Syndrome
– Scleroderma
– Obesity

87. ASA Physical Status Classification
• has been shown to generally correlate with the
perioperative mortality rate (MR given below).
• ASA 1: a normal healthy pt (0.06-0.08%).
• ASA 2: a pt w/mild systemic ds (mild diabetes, controlled
HTN, obesity [0.27-0.4%]).
• ASA 3: a pt w/severe systemic ds that limits activity
(angina, COPD, prior MI [1.8-4.3%]).
• ASA 4: a pt with an incapacitating ds that is a constant
threat to life (CHF, renal failure [7.8-23%]).
• ASA 5: a moribund pt not expected to survive 24 hrs
(ruptured aneurysm [9.4-51%]).
• ASA 6: brain-dead pt whose organs are being harvested.
• For emergent operations, add the letter ‘E’ after the
classification.

88. Preoperative Fasting Guidelines
• Recommendations (applies to all ages)
• Ingested Material Minimum Fasting Period (hrs)
• Clear liquids 2
• Breast milk 4
• Infant formula 6
• Non-human milk 6
• Light solid foods 6

89. Preoperative Bacterial Endocarditis
Prophylaxis
1. Antibiotic prophylaxis is recommended for pts
with prosthetic cardiac valves, previous hx of
endocarditis, most congenital malformations,
rheumatic valvular ds, hypertrophic
cardiomyopathy, and mitral valve regurgitation.
2. Prophylactic regimens for dental, oral, respiratory
tract, or esophageal procedures
- Amoxicillin, ampicillin or Clindamycin
3. Prophylactic regimens for GU/GI (excluding
esophageal) procedures
–Amoxicillin + Gentamycin or
–Ampicillin + Gentamycin or
–Vancomycin + Gentamycin

90. Aspiration Pneumonia Prophylaxis
• Nizatidine
• Famotidine
• Ranitidine
• Cimetidine
• Metoclopramide
• Bicitra
• Omeprazole
• Lansoprazole

91. Premedications
• The goals of premedications include:
– anxiety relief, sedation, analgesia, amnesia,
– increase in gastric fluid pH,
– decrease in gastric fluid volume,
– attenuation of SNS reflex responses,
– decrease in anesthetic requirements,
– prevent bronchospasm,
– prophylaxis against allergic reactions, and
– decrease post-op nausea/vomiting.

92. Common Premedications
• Pentobarbital
• Methohexital
• Fentanyl
• Sufentanil
• Morphine
• Meperidine
• Diazepam
• Flurazepam
• Midazolam
• Lorazepam
• Triazolam
• Clonidine
• Dexamethasone
• Droperidol
• Granisetron
• Ondansetron
• Atropine
• Scopolamine
• Glycopyrrolate

93. Postanesthesia Care Unit
• Postoperative Hemodynamic Complications
– Hypotension
– Hypertension
– Cardiac dysrhythmias
• Postoperative Respiratory and Airway
Complications
– the most frequently encountered complications in the
PACU, with the majority related to:
– airway obstruction,
– Hypoxemia
– Hypoventilation
– Laryngospasm and laryngeal edema

94. Postanesthesia Care Unit
• Postoperative Neurologic Complications
– Delayed awakening:
– Emergence delirium (agitation)
• Rx Haloperidol, Benzodiazepines or Physostigmine
• Postoperative Nausea and Vomiting
• Rx
– Ondansetron (5-HT3 antagonist) to prevent
– Avoidance of N2O
– Propofol for induction
– Keterolac vs. opioid for analgesia
– Droperidol, metaclopromide dexamethasone

95. Postanesthesia Care Unit Pain Control
• Moderate-to-severe postoperative pain in the
PACU
– Meperidine 25-150 mg (0.25-0.5 mg/kg in children).
– Morphine 2-4 mg (0.025-0.05 mg/kg in children).
– Fentanyl 12.5-50 mcg IV.
• Nonsteroidal anti-inflammatory drugs are an
effective complement to opioids.
– Ketorolac 30 mg IV followed by 15 mg q6-8h.
• Patient-controlled and continuous epidural
analgesia should be started in the PACU

96. Miscellaneous Postanesthesia
Complications
• Renal dysfunction: oliguria
• Bleeding abnormalities: inadequate surgical
hemostasis or coagulopathies.
• Shivering (hypothermia)
• Rx
– warming measures.
– Small doses of meperidine (12.5-25 mg) IV.

97. Postanesthesia Care Unit Discharge
Criteria
1. All pts should be evaluated by an anesthesiologist
prior to discharge; pts should have been observed
for resp depression for at least 30 min after the last
dose of parenteral narcotic.
2. Patients receiving regional anesthesia should show
signs of resolution of both sensory and motor
blockade prior to discharge.
3. Other minimum discharge criteria include stable
V/S, alert and oriented (or to baseline), able to
maintain adequate oxygen saturation, free of N/V,
absence of bleeding, adequate urine output,
adequate pain control, stabilization or resolution of
any problems, and movement of extremity
following regional anesthesia.

98. Malignant Hyperthermia
• Definition: a fulminant skeletal muscle hypermetabolic
syndrome occurring in genetically susceptible pts after
exposure to an anesthetic triggering agent.
• Triggering agents include halothane, enflurane,
isoflurane, desflurane, sevoflurane, and succinylcholine.
• Etiology: the gene for MH is the genetic coding site for
the calcium release channel of skeletal muscle
sarcoplasmic reticulum.
• The syndrome is caused by a reduction in the reuptake of
calcium by the sarcoplasmic reticulum necessary for
termination of muscle contraction, resulting in a
sustained muscle contraction.
• Mortality: 10% overall; up to 70% without dantrolene
therapy. Early therapy than 5%.

99. Malignant Hyperthermia
Clinical findings
• Signs of onset:
– tachycardia, tachypnea, hypercarbia (increased
end-tidal CO2 is the most sensitive clinical sign).
• Early signs:
– tachycardia, tachypnea, unstable BP, arrhythmias,
cyanosis, mottling, sweating, rapid temperature
increase, and cola-colored urine.

100. Malignant Hyperthermia
Clinical findings
• Late (6-24 hours) signs:
– pyrexia, skeletal muscle swelling, left heart failure, renal
failure, DIC, hepatic failure.
– Muscle rigidity in the presence of NM blockade.
– Masseter spasm after giving succinylcholine is
associated with MH.
– The presence of a large difference b/n mixed venous
and arterial CO2 tensions confirms the dx of MH.
• Laboratory:
– respiratory and metabolic acidosis, hypoxemia,
increased serum levels of K, Ca, and myoglobinuria.

101. MH Treatment Protocol
• Stop triggering anesthetic agent immediately
• Hyperventilate: 100% oxygen, high flows, use new
circuit and soda lime.
• Admin dantrolene 2.5 mg/kg IV; rpt Q5-10 min until
symptoms are controlled or a total dose of up to 10
mg/kg is given.
• Correct metabolic acidosis: admin sodium
bicarbonate, 1-2 mEq/kg IV guided by arterial pH
and pCO2. Follow with ABG.
• Hyperkalemia: correct with bicarb or glucose (25-
gm) & regular insulin (10-20 u).

102. MH Treatment Protocol
• Actively cool patient
– Iced IV NS (not LR) 15 mL/kg Q10 min times three
if needed.
– Lavage stomach, bladder, rectum, peritoneal and
thoracic cavities.
– Surface cooling with ice and hypothermia blanket.
• Maintain urine output >1-2 mL/kg/hr. If
needed, mannitol 0.25 g/kg IV or furosemide
1 mg/kg IV (up to 4 times) and/or hydration.

103. MH Treatment Protocol
• Labs:
– Labs: PT, PTT, platelets, urine myoglobin, ABG, K,
Ca, lactate.
– Consider invasive monitoring: arterial BP and CVP.
• Postoperatively:
– Continue dantrolene 1 mg/kg IV q6h x 72 hrs to
prevent recurrence.
– Observe in ICU until stable 24-48 hrs.
– CCB should not be given when dantrolene is
administered b/c hyperkalemia and myocardial
depression may occur.

104. SUMMARY
• Opioid agonists and
antagonists
– Fentanyl
– Sufentanil
– Remifentanil
– Alfentanil
– Morphine Sulfate
– Meperidine
– Naloxone
• Muscle relaxants
– Rocuronium
– Cis-Atracurium
– Pancuronium bromide
– Atracurium
– Succinylcholine chloride
• Anticholinesterases
and anticholinergics
– Neostigmine
– Glycopyrrolate
– Atropine Sulfate
• Induction agents
– Propofol
– Thiopental
– Ketamine
– Etomidate
Common Anesthetic agents

105. Common Anesthetic agents
• Inhaled agents
– Desflurane
– Sevoflurane
– Isoflurane
– Nitrous Oxide
• Anxiolytics
– Midazolam
• Antiemetics
– Ondansetron
– Dimenhydrinate
– Prochlorperazine
• Vasoactive agents
– Phenylephrine
– Ephedrine sulfate
– Epinephrine
• Local anesthetics
– Bupivacaine
– Lidocaine
• Miscellaneous
– Ketorolac tromethamine
– Diphenhydramine
– Dantrolene

106. Induction Agents
• Barbiturates
– e.g. Thiopentone, Propofol, Etomidate etc.
• Gaseous
– e.g. Nitrous oxide, Halothane, Isoflurane,
Desflurane, Sevoflurane
• Opioids
– (Fentanyl), Sufentanil, Remifentanil
• Benzodiazepines
– Midazolam, Diazepam, Lorazepam

107. Preanesthetic Medications
• Benzodiazepines
– Reduce anxiety
• Midazolam
• Barbiturates
– Sedation
• Pentobarbital
• Antihistamines
– Prevention of allergic
reactions
• Diphenhydramine
• Antiemetics
– Prevent aspiration of
stomach contents
– Reduce postsurgical
nausea and vomiting
• Ondansetrone
• Opioids
– Provide analgesia
• Fentanyl
• Anticholinergics
– Amnesia, prevent
bradycardia, and fluid
secretion
• Scopolamine, Atropine
• Muscle relaxants
– Facilitation of intubation

108. References
1. Handbook Of Anesthesiology: Mark R. Ezekiel; 2008 Edition.
2. Understanding Anesthesia: Karen Raymer A Learner's Handbook, first
EDITION, McMaster University. www.understandinganesthesia.ca
3. Recommendations for Standards of Monitoring During Anaesthesia and
Recovery 4th Edition: The Association of Anaesthetists of Great Britain
and Ireland, 21 Portland Place, London, 2007.

109. THANK YOU !!!