•hypnotic

Inhibitory at CABA synapse

Decreased cetebral

metabolic rate and blood

flow,decreased CPP,

blood llow,decreased decreased CO.decreased

BP.decreased reflex

tachycardia,decreased

respiration

Class Benzodiazepines - anxiolytic Imidazoledenvatrve • Ultra short-acting

dissociative hypnotic barbiturate

Action Inhibitory at GABA

synapse

Decreased cerebral

metabolic rate and

May acton NMDA (antagonistically). Inhibitory at GABA synapse

opiate,and other receptors

Increased HR.increased BP.

increased SVR,increased coronary Minimal cardiac depression

flow,increased myocardial 02

uptake

CNS and respiratory depression,

bronchial smooth muscle relaxation

Decreases

concentration of GABA chloride

required to activate

receptor

CNS depression

Minimal cardiac or

respiratory depression

Snds to the

Produces anbannety and skeletal

muscle relaxant effects rotiophore site of

GABA-A receptor

ICP.decreased SVR,

decreased BP.and

decreasedSY

Indications Used for sedation,amnesia,and

anxrolysis

Induction Procedural

Maintenance

Total intravenous

anesthesia (TIVA)

Induction when sympathetic

Control of convulsive states, stimulation required (e.g.major

obstetric patients

Induction Induction

Poor cardiac function, induebon

severe valve lesions,

uncontrolled

hypertension

trauma,hypovolemia).IM induction Electroconvulsive

in children'

uncooperative adults therapy (ECt) +

fee.when thereis lack of IV

access),severe asthma because

sympathomimetic

'As of 2011. Thiopental has been discontinued from production for North America

A17 Anesthesia Toronto Notes 2023

Table 8. Intravenous Induction Agents

Thiopental (sodium

thiopental, sodium

thiopentone)’

Ketamine (Ketalar ,

Ketaject )

Benzodiazepines (midazolam Etomidate

(Versed ).diazepam (Valium 5),

lorazepam (Ativan ))

Methohexital

(Brevital )

Propofol

(Diprivan )

Caution Patients who cannot

toleratesudden

decreased BP (e.g.

futed cardiac output

or shock)

Allergy to barbiturates

Uncontrolled hypotension,

shock,cardiac failure

Porphyria,liver disease,

status asthmalicus,

myxedema

IV induction:3-5 mg/kg

Unconsciousabout 30 s

Lasts 5 min

Accumulation with

repeal dosing - not for

maintenance

tut

- 5-10 h

Postoperative sedation

lasts hours

Marked respiratory depression Postoperative nausea Contraindicated in

acute intermittent

porphyria

Ketamine allergy

1CA medication (interaction causes

HTH and dysrhythmias)

History of psychosis

Patients who cannot tolerate HTN

(e.g.CHF.increased ICP.aneurysm)

IV induction1-2 mgfkg

Dissociation in 15 s,analgesia,

amnesia,and unconsciousness in

4S 60 s

Unconsciouslor 10-15 min,

analgesia for 40 min,amnesia

for 1-2 h

lvj*

«3 h

and vomiting

Venous irritation

Dosing IV induction:1.5-2.5

mg/kg (less with

opioids)

Unconscious'

1mm

lasts 4- 6 min

l1> "55 min

Oecreascd

postoperative

sedation,recovery

time. M/V

Onset <5minilgiven IV

Ouralion of action long but variable/

somewhat unpredictable

IV induction 0.3 mg/kg IV induction1to

Onset 30- 60 s

lasts 4 3 min

1.5 mg/kg ol a 1%

solution;doses

must be titrated

to clfed

Special

Considerations due to vasodilation

Reduce burning at IV

site by mixing with

lidocaine

-300decreased BP Combining with rocuronium

causes precipitates to form

High incidence of emergence

reactions (vivid dreaming,out-ofbody sensation,illusions)

Pretreat with glycopyrrolate to

decrease salivation

Antagonist;flumazenil (Anexate -) Adrenal suppression

competibve inhibitor,0.2 mg IV over after first dose,cannot

15 s,repeat with 0.1mg/min (max of 2 repeat dose or use as

mg),tw of 60 min

Midazolam also hasamnestic

infusion

Myoclonic movements

(antegrade)effectand decreased risk during induction

of thrombophlebitis

*As of 2011, Thiopental hasbeen discontinued from production lor North America

Volatile Inhalational Agents

• e,g. sevofluratio, dcslluranc, isoflurano, enflurane, halothanc, and nitrous oxide

Table 9. Volatile Inhalational Agents

See landmark Anesthesiolsgy trials table for more

informationonMYtUO trial,which details the

impact of votat leanesthetits vs.total intravenous

anesthesia inpatents undergoing CABG.

Sevoflurane Desflurane’ Isoflurane" Enflurane Halothane Nitrous oxide

(N20)’

”

MAC 2.0 6.0 1.2 1.7 0.8 104

(% gas into)

CNS Increased ICP Increased ICP Decreased cerebral

metabolic rate

IncreasedICP

Respiratory depression (severely decreased TV.increased RR).decreased response to respiratory CO;

reflexes,bronchodilation

ECG seizure-like

activity

IncreasedICP

Increased ICP and

cerebral blood flow

Rcsp

Stable HR.

decreased

theoretical chance ol contractility

coronary steal* *

Decreased BP.CO.

HR.and conduction

Sensitizes myocardium paediatric patients

lo epinephrine-induced with existing heart

disease

Can cause

decreased HR in

CVS less decrease Tachycardia with Decreased BP and

of contractility, rapid increase in CO.increased HR.

stable HR concentration

arrhythmias

MSK Muscle relaxation,potentiationol other muscle relaxants.uterine relaxation

'Airway irritant: desflurane can provokebreath holding, laryngospasm. and salivation, so itis not used lor inhalationalinduction

"Coronary steal:isoflurane causes small vessel dilation which may compromise blood flow to areas ot Uie heart with fixed perfusion (e.g.stents.

atherosclerosis)

'"Properties and Adverse Effects of NrrO

Due to its high MAC.NzO is combined with other anesthetic gases to attain surgical anesthesia.A MAC of 104% is possible in a pressuiized chamber

only

Second Gas Effect

Expansion ol closed spaces:closedspaces such as a pneumothorax,the middle ear.bowel lumen,and ETT cuff will markedly enlarge if NzO is

administered

Diffusion hypoxia:during anesthesia,the washout of NrO front body stores kilo alveoli can dilute Uie alveolar (O2),creating a hypoxic mixture il the

original IQuJis low

Minimum Alveolar Concentration

• minimum alveolar concentration (MAC) is the alveolar concentration of a volatile anesthetic at one

atmosphere (atm) of pressure that will prevent movement in 50% of patients in response to a surgical

stimulus (e.g. abdominal incision)

• potency of inhalational agents is compared using MAC

• MAC of halogenated volatile anesthetics decreases by approximately 6% per additional decade of age

in adults

• 1.2-1.3 times MAC will often ablate response to stimuli in the general population

• MAC values are roughly additive when mixing N’O with another volatile agent; however,this only

applies to movement, not other effects such as BP changes (e.g. 0.5 MAC of a potent agent + 0.5 MAC

of N 20 = 1 MAC of potent agent)

• MAC-intubation:the MAC of anesthetic that will inhibit movement and coughing during

endotracheal intubation; generally 1.3 MAC

• MAC-block adrenergic response (MAC-BAR):the MAC necessary to blunt the sympathetic response to

noxious stimuli; generally 1.5 MAC

• M AC-awake: the MAC of a given volatile anesthetic at which a patient will open their eyes to

command; generally 0.3-0.5 of the usual MAC

Factors increasing MAC:chronic

alcohol use.hyperthyroidism,

hyperthermia,acute amphetamine use,

cannabinoids. young age

Factors decreasing MAC:acute

alcohol intoxication,hypothermia,

sedating drugs,advanced age.chronic

amphetamine use. drugs (opioids,

benzodiazepines),a 2 adrenergic

agonists,nitrous oxide,IV anesthetics,

shock r1

c. J

+

A18 Anesthesia Toronto Notes 2023

Muscle Relaxants and Reversing Agents

Prejunctional

motor nerve ending

Vesicles with ACh

Lower [K-]

Depolarization and

muscle contraction

t

Post synaptic ACh receptor

muscle membrane

Higher (Na)

4. Change inmembiane permeability 5

5 AChEhydrolyzes ACh

6.Action potential spreads across musclemembrane

( Action potential arrives

2 Release of ACh into cleft

3.ACh binds to ACh leceptor,ion channels open

:

—>

Q

Figure 12. Review of anatomy and physiology of theneuromuscular junction (NMJ)

Muscle Relaxants

•two types of muscle relaxants

1. depolarizing muscle relaxants:SCh

2. non-depolarizing muscle relaxants:rocuronium, mivacurium, vecuronium, cisatracurium,

pancuronium

•block nicotinic cholinergic receptors in NM|

• providesskeletal muscle paralysis, including the diaphragm, but spares involuntary musclessuch as

the heart and smooth muscle

• never use muscle relaxants without adequate preparation and equipment to maintain airway and

ventilation

•muscle relaxation produces the following desired effects:

1. facilitates intubation

2. assists with mechanical ventilation

3. prevents muscle stretch reflex and decreases muscle tone

4. allows access to the surgical field (intracavity surgery)

• nerve stimulator (i.e. train of four) is used intraoperatively to assess the degree of nerve block; no

twitch response seen with complete neuromuscular blockade

Pseudocholinesterase

Pseudocholinesterase is produced

by the liver and metabolizes SCh and

mivacurium. A prolonged duration of

block ade by SCh occurs with:

(a)decreascd quantity of plasma

cholinesterase (e.g. congenital

(hereditary),liver disease,pregnancy,

malignancy,malnutrition, collagen

vascular disease,hypothyroidism)

(b)abnormal quality of plasma

cholinesterase (e.g. normal levels

but impaired activity of enzymes,

genetically inherited)

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A19 Anesthesia Toronto Notes 2023

Table 10. Depolarizing Muscle Relaxants (Non-Competitive): Succinylcholine (SCh)

Mechanism ol Mimics ACh and binds toACh receptors causing prolonged depolarization:Initial fiiscleulalion may be seen, followed by

Action temporary paralysis secondary to blocked ACh receptors by SCh

Intubating M.5

Dosc (mglkg)

Onset

Duration

Metabolism

30-60 s -rapid (fastest olall muscle relaxants)

3-5 min - short (no reversing agent(or SCh)

SCh is hydrolyzed by plasma cholinesterase (i.e.pseudocholinesterase),found only in plasma and notat the NMJ

Assist intubation

Increased risk of aspiration (e.g.full stomach,hiatus hernia,obesity,pregnancy,trauma);need rapid paralystsand airway

control)

Short procedures

Indications

ECT

Laryngospasm

1.SCh also stimulates muscarinic cholinergic autonomic receptors (in addition to nicotinic receptors;maycause bradycardia,

dysrhythmias, sinus arrest,increased secrelions of salivary glands (especially inchildren))

2. Hyperkalemia

Disruption of motor nerve activity causes proliferation ol extrajunctional (outside NMJ) cholinergic receptors

Depolarization ol an increased number olreceptors by SCh may lead lo massive release of potassium out of muscle cells

Patients at risk

3rd degree burns 24 h- 6 mo after injury

Traumatic paralysis or neuromuscular diseases (e.g.muscular dystrophy)

Severe intra-abdominal Infections

Severe dosed head injury

Upper motor neuron lesions

3.Can trigger MH (seeMalignant Hyperthermia. A29)

4.Increased ICPNntraocular pressure/intragastric pressure (no increased risk of aspiration if competent LES)

5.Fasciculations.postoperative myalgia - may be minimized if small dose of non depolarizing agent given before SCh

administration

Side Effects

Contraindications

Known hypersensitivity or allergy,positive history of MH.myotonia (m.congenita,m.dystrophica.paramyotonia congenital),

high-risk for hyperkalemic response

Known history of plasma cholinesterase deficiency,myasthenia gravis,myasthenic syndrome, familialperiodic paralysis,open

eye injury

Absolute

Relative

Table 11. Non-Depolarizing Muscle Relaxants (Competitive)

Mechanism of Action Competitive blockade of poslsynaptic ACh receptorspreventing depolarization

Classilicalion Short Intermediate tong

Mivacurium Rocuronium Vecuronium Cisalracurium Pancuronium

Intubating Oosc 0.2 0.61.0 0.1 0.2 0.1

(mg/kg|

Onset (min)

Duration (min)

Metabolism

23 1.5 2-3 3 35

15 -25 30 45 45-60 40-60 90120

Plasma

cholinesterase

Liver (major)

Renal (minor)

0.6-1.0

Liver Hofmann

Elimination

Renal (major)Liver

(minor)

Intubating Dose

(mg/kg|

Indications

0.2 0.1 0.2 0.1

Assist intubation,assist mechanical ventilation in some ICU patients,reduce fasciculations,and postoperative myalgias

secondary to SCh

SideEffects

Histamine Release Ves

Other -

No No No No

- Tachycardia

Cisalracurium is Pancuronium if increased

good for patients HR andBP desired

with renal or hepatic

insufficiency

Considerations Increased duration of Ouick onset of rocuronium

action in renal or liver allows its use in rapid

lailure sequence induction

Reversal Agents

• sugammadex is a selective relaxant binding agent and can be administered immediately alter dose of

NMDR

• neostigmine, pyridostigmine, and edrophonium are acetylcholinesterase inhibitors - these are

competitive inhibitors and therefore can only be administered when there has been some recovery of

blockade (i.e. train of four muscle response to stimulation)

can only reverse the effect of non-depolarizing muscle relaxants

• anticholinergic agents (e.g. atropine, glvcopvrrolate) are simultaneously administered to minimize

muscarinic effect of reversal agents (i.e. bradycardia,salivation, increased peristalsis, and

bronchoconstriction)

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A20 Anesthesia Toronto Notes 2023

Table 12. Reversal Agents for Non-Depolarizing Relaxants

Agent Pyridostigmine Neostigmine Edrophonium Sugammadex

Onset Slow Intermediate Intermediate fast

Mechanism ol ACNE:inhibit emymalic degradation olACh,increase ACh at nicotinic and

muscarinic receptors,displace non-depolariring muscle relaxants

Muscarinic elfecls olreversing agents include unwanted bradycardia, salivation. amount ol agent available to bind to

and increased bowel peristalsis*

0.04 0.08

Glycopyrrolalc

Encapsulates and Inactivates rocuronium

Action and vecuronium »

receptors in NMJ

Dose (mg/kg) 0.1 0.4

Recommended Glycopyrrolalc

Anticholinergic

Ooscol

Anticholinergic

(per mg)

0.5-1 216

Atropine N/A

0.05 mg 0.2mg 0.014 mg N/A

'Atropine and glycopyrrolate are anticholinergic agents administeredto mlnlmire muscarinic ellccts ol reveisal agents

Analgesia

• options include opioids (e.g.morphine, fentanyl, hydromorphone), NSA1DS/COX-2- inhibitors,

acetaminophen, ketamine, gabapentinoids, and local and regional anesthetics (see Table 15, A25)

Maintenance

• general anesthesia is maintained using volatile inhalation agents and/or IV agents(i.e. propofol

infusion)

• analgesia (usually IV opioids)

± muscle relaxants given as needed

See landmark Anesthesiology Trialstablefor more

nformabon on resultsfrom the ENGAGES trial,which

d etalsthe efficacy of using EEG goided anesthetic

administration in patientswith postoperative

detuiom.

Extubation

• criteria:patient must no longer have intubation requirements

• patency:airsvay must be patent

protection: airsvay reflexes intact

» patient must be oxygenating and ventilating spontaneously

• general guidelines

• ensure patient has normal neuromuscular function (peripheral nerve stimulator monitoring) and

hemodynamic status

ensure patient is breathing spontaneously with adequate rate and tidal volume

allosv ventilation (spontaneous or controlled) with 100% 02 for 3-5 min

• suction secretions from pharynx,deflate cuff, remove ETT on inspiration (vocal cords abducted)

» ensure patient is breathing adequately after extubation

ensure face mask for 02 delivery available

proper positioning of patient during transfer to recovery room (supine, head elevated)

Complications of Extubation

• early extubation: aspiration, laryngospasm

• late extubation: transient vocal cord incompetence, edema (glottic,subglottic), pharyngitis, tracheitis

Laryngospasm

• defined as forceful involuntary spasm of laryngeal muscles caused by stimulation of superior

laryngeal nerve (by oropharyngeal secretions,blood, early extubation)

• causes partial or total airway obstruction

• more likely to occur in semi-conscious patients

• prevention: extubate while patient isstill deeply under anesthesia or fully awake

• treatment:suction, remove oral airway/LMA, apply sustained positive pressure (CHAP) with

anesthetic reservoir bag and partial closure of APL valve BMV with 100% O2, low-dose propofol (0.5-

1.0 mg/kg) optional, low-dose SCh (approximately 0.25 mg/kg), and re-intubate if hypoxia develops

ri

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AL GRAWANY

A2 I Anesthesia Toronto Notes 2023

Regional Anesthesia Benefits of Regional Anesthesia

• Reduced perioperative pulmonary

complications

• Reduced perioperative analgesia

requirements

• Decreased PONV

• Ability to monitor CNS status during

procedure

• Improved perfusion

• Lower incidence of VTE

• Shorter recovery and improved

rehabilitation

• Pain blockade with preserved motor

function

•local anesthetic applied around a peripheral nerve at any point along the length of the nerve (from

spinal cord up to, but not including, the nerve endings) for the purpose of reducing or preventing

impulse transmission

•no CNS depression (unless overdose of LA); patient remains conscious

•regional anesthetic techniques categorized asfollows:

epidural and spinal anesthesia (neuraxial anesthesia)

peripheral nerve blocks

IV regional anesthesia (e.g. Bier block)

Patient Preparation

•sedation and /or anxiolysis may be indicated before block

•monitoring should be as extensive as for CiA Q

Epidural and Spinal Anesthesia Landmarking Epidural/Spinal

Anesthesia

• Spinous processes should be

maximally flexed

• L4 spinous processes found between

Iliac crests

• T7 landmark at the tip of the scapula

•most common for surgeries performed below the level of umbilicus but can be extended to any level

(useful in thoracic, abdominal, and lower extremity surgeries). Typically placed in thoracic or lumbar

spine

Anatomy of Spinal/Epidural Area

•spinal cord extends to L1; dural sac to S2 in adults

• nerve roots (cauda equina ) from 1.2 to S2

• needle inserted below 1.2 should not encounter cord, thus L3- L4, 1.

-1-1.5 interspace commonly used

•structures penetrated (outside to Inside)

• skin

subcutaneous fat

supraspinous ligament

interspinous ligament

* ligamentum flavum (last layer before epidural space)

dura + arachnoid for spinal anesthesia

Classic Presentation of Dural Puncture

Headache

• Onset 6 h 3 d after dural puncture

• Postural component (worse when

sitting)

• Occipital or frontal localization

• ±tinnitus,diplopia

Effectof Anaesthesia type on Postoperative

Mortality and Morbidities:A Matched Analysis of

the NSOIP Database

Br J Anaesth 2017:118:105-111

Purpose: Determine the effects ol PA vs. CA on

postoperative survival and morbidities.

Methods Matched surgical procedures anil type ol

anesthesia using IhellS national Surgical Quality

Improvement database. Primary outcomewas 30 d

postoperative mortality and secondary outcomes

were hospital length of stay and postoperative orgao

system dyshmeioo.

Results:therewas np difference in 30 d mortality. RA

wassignificantly associated with increased likelihood

of early discharge (HR1.09; P< 0.001|.There were

lower odds of intraoperative complications (47%).

respiratory corn cations (24%|. DVT (TS%|. and

any one postoperative complication (15%) (OR 0.8S;

P < 0.0011.

Conclusion: RA was associated with significantly

lower odds of several postoperative complications,

decreased hospital length olstay, but not mortality

when compaitd with CA.

Table 13. Epidural vs. Spinal Anesthesia

Epidural Spinal

Deposition Site t A injected in epidural space (space between ligamentum

llavum and dura)

Initial blockade Is at the spinal toolsfollowed by some

degree of spinal cord aneslhesia as LA diffuses into the

subarachnoid space through the dura

Significant blockade requires10-15 min

Slower onset of side effects

IA injected into subarachnoid space in thedural sac

surrounding the spinal cord and nerve toots

Onset Rapid blockade (onsetin 2-5 min)

Effectiveness Effectiveness of blockade can be variable

Difficulty

Patient

Positioning Post- an issue

injection

Specific Gravity/

Spread

Very effective blockade

Easier to perform due fo visual confirmation of CSF flow

Hyperbaric LAsolution - position ol patient important

Technically more difficult;greater failure rate

Position of patient not asimportant:specific gravity not

Epidural injectionsspread throughout the potential space:

specific gravity ol solution does not affect spread

IA solution may be made hyperbaric (of greater specific

gravity than the CSF by mixing with 10% dextrose, thus

increasing spread of LA to the dependent flow) areas of the

subarachnoid space)

Smaller dose ol LA required (usually < toxic IV dose)

None

larger rolume/dosc of LA (usually > toxic IV dose)

Use ol catheter allows for continuous infusion or repeal

injections

Failure of technique

Hypotension

Bradycardia if cardiac sympathetics blocked (only if »T4

block),e.g.“high block"

Epidural orsubarachnoid hematoma

Accidentalsubarachnoid injection can producespinal

anesthesia (and any of the above complications)

Systemic toxicity ol LA (accidental intravenous)

Catheter complications(shearing, kinking, vascular,or

subarachnoid placement)

Infection

Post-dural puncture

Combines the benefits of rapid, reliable,intense blockade olspinal anesthesia together with the flexibility of an epidural

catheter

Dosage

Continuous

Infusion

Complications Failure of technique

Hypotension

Bradycardia if cardiac sympathetics blocked (only if

-14

block),e.g.‘high spinal"

Epidural or subarachnoid hematoma

Post-spinal headache (CSF leak)

transient paresthesias

Spinal cord trauma

Infection

Combined SpinalEpidural +

A22 Anesthesia Toronto Notes 2023

L2 Supraspinous ligament

Interspinousligament

•Ligamentumflavum

/

Lumbar

spinous ]

processes

Safe injection

below12/13 '

•Dura mater

CSF in lumbar cistern

Cauda equina

L3

k

L4/L5 level

-

Tullier'

s line"

’

Iliac crest \

For spinal anaesthesia

a

\

L4

-Epidural space

\

o \ For epidural anaesthesia Spinalcord

— L2

S \ Filum

terminale

Figure14.Sagittal cross-section of the anatomy of neuraxial anesthesia Epidural space v*

*

-

1

Oura mater —

Contraindications to Spinal/Epidural Anesthesia

• absolute contraindications

• lack of resuscitative drugs/equipment

patient refusal

allergy to local anesthetic

infection at puncture site or underlying tissues

coagulopathies/bleeding diathesis

• raised 1CP

• sepsis/bacteremia

• severe hypovolemia

cardiac lesion with fixed outputstates (e.g.severe mitral/aortic stenosis)

• lack of IV access

• relative contraindications

pre-existing neurological disease (e.g. demyelinating lesions)

• previousspinalsurgery;severe spinal deformity

• prolonged surgery

• major blood loss or maneuvers that can compromise reaction

L4

Subarachnoid

spacewith ,

L5

CSF

S2

X

x